ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ
┠ḟ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ ...... 3 ⮫ᗋヨ㦂୍ぴ⾲ ...... 3 2.7.6.1 ᾏእ⮫ᗋ➨ I ┦ヨ㦂㸦CNTO1275NAP1002 ヨ㦂㸪ཧ⪃㈨ᩱ㸸5.3.1.2.1㸧 ...... 6 2.7.6.2 ➨ III ┦ᅜ㝿ඹྠヨ㦂㸸ᐶゎᑟධヨ㦂㸦CNTO1275CRD3001 ヨ㦂㸪 ホ౯㈨ᩱ㸸5.3.5.1.1㸧 ...... 12 2.7.6.3 ➨ III ┦ᅜ㝿ඹྠヨ㦂㸸ᐶゎᑟධヨ㦂㸦CNTO1275CRD3002 ヨ㦂㸪 ホ౯㈨ᩱ㸸5.3.5.1.2㸧 ...... 84 2.7.6.4 ➨ III ┦ᅜ㝿ඹྠヨ㦂㸸ᐶゎ⥔ᣢヨ㦂㸦CNTO1275CRD3003 ヨ㦂㸪 ホ౯㈨ᩱ㸸5.3.5.1.3-1㸧 ...... 137 2.7.6.5 ᾏእ⮫ᗋ➨ IIa ┦ヨ㦂㸦C0379T07 ヨ㦂㸪ཧ⪃㈨ᩱ㸸5.3.5.1.4㸧 ...... 385 2.7.6.6 ᾏእ⮫ᗋ➨ IIb ┦ヨ㦂㸦C0743T26 ヨ㦂㸪ཧ⪃㈨ᩱ㸸5.3.5.1.5㸧 ...... 393
1 (1) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ
␎ྕ୍ぴ⾲
␎ྕཪࡣ␎⛠ ྡ⛠ཬࡧෆᐜ 5-ASA 5-aminosalicylate㸦5-࣑ࣀࢧࣜࢳࣝ㓟㸧 area under the serum concentration versus time curve from time 0 to infinity with
AUCinf extrapolation of the terminal phase㸦⤊ᮎ┦ࢆእᤄࡋࡓ 0 㛫ࡽ↓㝈㛫 ࡲ࡛ࡢ⾑Ύ୰⃰ᗘ-㛫᭤⥺ୗ㠃✚㸧 area under the concentration versus time curve from time 0 to last quantifiable AUC last time㸦0 㛫ࡽ᭱⤊ᐃ㔞ྍ⬟㛫ࡲ࡛ࡢ⾑Ύ୰⃰ᗘ-㛫᭤⥺ୗ㠃✚㸧 BMI body mass index㸦య᱁ᣦᩘ㸧 CDAI Crohn’s Disease Activity Index CDEIS Crohn’s Disease Endoscopic Index of Severity CI confidence interval㸦ಙ㢗༊㛫㸧 CL total systemic clearance㸦㌟ࢡࣜࣛࣥࢫ㸧
Cmax maximum observed serum concentration㸦᭱㧗⾑Ύ୰⃰ᗘ㸧 CRP C-reactive protein㸦C ᛂᛶࡓࢇⓑ㸧 DMC Data Monitoring Committee㸦ࢹ࣮ࢱࣔࢽࢱࣜࣥࢢጤဨ㸧 DNA deoxyribonucleic acid㸦ࢹ࢜࢟ࢩࣜ࣎᰾㓟㸧 GCP Good Clinical Practice㸦་⸆ရࡢ⮫ᗋヨ㦂ࡢᐇࡢᇶ‽㸧 HBV hepatitis B virus㸦B ᆺ⫢⅖࢘ࣝࢫ㸧 HCV hepatitis C virus㸦C ᆺ⫢⅖࢘ࣝࢫ㸧 HIV human immunodeficiency virus㸦ࣄࢺච࢘ࣝࢫ㸧 IBDQ Inflammatory Bowel Disease Questionnaire JSEQ Jenkins Sleep Evaluation Questionnaire㸦ࢪ࢙ࣥ࢟ࣥࢫ╧╀ホ౯㉁ၥ⚊㸧 IL interleukin㸦ࣥࢱ࣮ࣟ࢟ࣥ㸧 ITT intent to treat IV intravenous㸦㟼⬦ෆ㸧 LIV liquid in vial㸦ᾮయࣂࣝ〇㸧 LOR loss of response㸦response ࡢᾘኻ㸧 MCS Mental Component Summary㸦⢭⚄ⓗഃ㠃ࡢ QOL ࢧ࣐࣮ࣜ㸧 MedDRA Medical Dictionary for Regulatory Activities㸦ICH ᅜ㝿་⸆⏝ㄒ㞟㸧 PCS Physical Component Summary㸦㌟యⓗഃ㠃ࡢ QOL ࢧ࣐࣮ࣜ㸧 PDAI Perianal Disease Activity Index QOL quality of life㸦⏕άࡢ㉁㸧 RNA ribonucleic acid㸦ࣜ࣎᰾㓟㸧 SAE serious adverse event㸦㔜⠜࡞᭷ᐖ㇟㸧 SC subcutaneous㸦⓶ୗ㸧 SD standard deviation㸦ᶆ‽೫ᕪ㸧 SF-36 36-item Short-form Health Survey
T1/2 half-life㸦ᾘኻ༙ῶᮇ㸧 TB tuberculosis 㸦⤖᰾㸧 TEAEs Treatment Emergent Adverse Events TNF tumor necrosis factor㸦⭘⒆ቯṚᅉᏊ㸧 VAS Visual Analog Scale
Vz volume of distribution during the terminal phase㸦⤊ᮎ┦ࡢศᕸᐜ✚㸧 WLQ Work Limitations Questionnaire
2 (2)
࠙ࠬ࠹ࠠࡑࡉ (1) 2.7.6 ޘߩ⹜㛎ߩ߹ߣ
ో⥃ᐥ⹜㛎৻ⷩ
⹜㛎ߩ ⹜㛎⇟ภ ⹜㛎ߩਥ⋡⊛ ⹜㛎࠺ࠩࠗࡦ ⵍ㛎⮎߮ኻᾖ⮎ ⵍ㛎⠪ᢙ ஜᐽⵍ㛎⠪ ᛩਈᦼ㑆 ⹜㛎ߩ 2.7.6 ⒳㘃 [⹜㛎ႎ๔ᦠ ߮ ᛩਈᣇᴺ ߪ ㅴⴕ⁁ᴫ ᷝઃ႐ᚲ] ኻᾖߩ⒳㘃 ᛩਈ⚻〝 ᖚ⠪ߩ⸻ᢿฬ ႎ๔ᦠߩ ⒳㘃 ⮎‛േᘒ CNTO1275NAP1002 ஜᐽⵍ㛎⠪ߦᧄߩᶧࡃࠗࠕ࡞ ╙ I ⋧㧘ᄙᣉ⸳ห㧘 90 mg/mL LIV ⟲㧦 140 ஜᐽⵍ㛎⠪ න࿁ ቢੌ [5.3.1.2.1] 㧔LIV㧕2 㧔90 mg/mL LIV ࡦ࠳ࡓൻ㧘ਗⴕ⟲ Day 1 ߦ㧘ᧄ 90 mg/mL LIV㧔ኻᾖ⮎㧕ࠍ ቢోߥ ߮ 5 mg/mL LIV㧕ࠍ 6 mg/kg ߩ↪㊂ 㑆㧘㕖⋤ᬌ㧘න৻↪ 6 mg/kg ߢන࿁㕒⣂ౝᛩਈ㧔ࡐࡦࡊࠍ ႎ๔ᦠ ߢන࿁㕒⣂ౝᛩਈߒߚߣ߈ߩ⮎‛േ ㊂㧘㒮㧛ᄖ᧪ㅢ㒮⹜ ↪㧕 ᘒࠍᲧセߔࠆޕ 㛎 5 mg/mL LIV ⟲㧦 ኻᾖ⮎㧦ᧄ Day 1 ߦ㧘ᧄ 5 mg/mL LIV㧔ⵍ㛎⮎㧕ࠍ 90 mg/mL LIV 6 mg/kg ߢන࿁㕒⣂ౝᛩਈ㧔ࡐࡦࡊࠍ ↪㧕 ലᕈ CNTO1275CRD3001 1. 1 એߩ᛫ TNF㧔⣲≌უᱫ࿃ ╙ III ⋧㧘ࡦ࠳ࡓ 0 ㅳ⋡ߦ㧘ࡊࡏ㧘ᧄߩ࿕ቯ↪㊂ 769 ਛ╬∝߆ࠄ㊀∝ߩ න࿁ ቢੌ ోᕈ [5.3.5.1.1] ሶ㧕⮎ᴦ≮ߢലᨐਇචಽߪᔋ ൻ㧘ੑ㊀⋤ᬌ㧘ࡊ 㧔130 mg㧕ߪ㊀↪㊂㧔㨪6 mg/kg㧕ߩ 㧔⹜㛎ౣ㐿ᓟ ᵴേᦼࠢࡠࡦ∛ ቢోߥ ኈᕈߩߥਛ╬∝߆ࠄ㊀∝ߩᵴ ࡏኻᾖ㧘ਗⴕ⟲㑆㧘ᄙ ߕࠇ߆ࠍන࿁㕒⣂ౝᛩਈ ߦࡦ࠳ࡓൻ ᖚ⠪ ႎ๔ᦠ േᦼࠢࡠࡦ∛ᖚ⠪ߦ߅ߡ㧘 ᣉ⸳ห⹜㛎 ߐࠇߚⵍ㛎 ᧄߩ㕒⣂ౝᛩਈߦࠃࠆኡ⸃ዉ ኻᾖ⮎㧦ࡊࡏ ⠪㧦741 㧕 ≮ᴺߩ clinical response ߢߩ ലᕈࠍ⹏ଔߔࠆޕ 2. 1 એߩ᛫ TNF ⮎ᴦ≮ߢലᨐ ਇචಽߪᔋኈᕈߩߥਛ╬∝ ߆ࠄ㊀∝ߩᵴേᦼࠢࡠࡦ∛ᖚ ⠪ߦ߅ߡ㧘ᧄߩ㕒⣂ౝᛩਈ ߦࠃࠆኡ⸃ዉ≮ᴺߩోᕈࠍ ⹏ଔߔࠆޕ ലᕈ CNTO1275CRD3002 1. ਛ╬∝߆ࠄ㊀∝ߩᵴേᦼࠢࡠ ╙ III ⋧㧘ࡦ࠳ࡓ 0 ㅳ⋡ߦ㧘ࡊࡏ㧘ᧄߩ࿕ቯ↪㊂ 640 㧔⹜㛎 ਛ╬∝߆ࠄ㊀∝ߩ න࿁ ቢੌ ోᕈ [5.3.5.1.2] ࡦ∛ᖚ⠪ߦ߅ߡ㧘ᧄߩ㕒⣂ ൻ㧘ੑ㊀⋤ᬌ㧘ࡊ 㧔130 mg㧕ߪ㊀↪㊂㧔㨪6 mg/kg㧕ߩ ౣ㐿ᓟߦࡦ ᵴേᦼࠢࡠࡦ∛ ቢోߥ ౝᛩਈߦࠃࠆኡ⸃ዉ≮ᴺߩ ࡏኻᾖ㧘ਗⴕ⟲㑆㧘ᄙ ߕࠇ߆ࠍන࿁㕒⣂ౝᛩਈ ࠳ࡓൻߐࠇߚ ᖚ⠪ ႎ๔ᦠ
clinical response ߢߩലᕈࠍ⹏ ᣉ⸳ห⹜㛎 ⵍ㛎⠪㧦628 ޘߩ⹜㛎ߩ߹ߣ ଔߔࠆޕ ኻᾖ⮎㧦ࡊࡏ 㧕 2. ਛ╬∝߆ࠄ㊀∝ߩᵴേᦼࠢࡠ ࡦ∛ᖚ⠪ߦ߅ߡ㧘ᧄߩ㕒⣂ ౝᛩਈߦࠃࠆኡ⸃ዉ≮ᴺߩ ోᕈࠍ⹏ଔߔࠆޕ
3
࠙ࠬ࠹ࠠࡑࡉ (2) ⹜㛎ߩ ⹜㛎⇟ภ ⹜㛎ߩਥ⋡⊛ ⹜㛎࠺ࠩࠗࡦ ⵍ㛎⮎߮ኻᾖ⮎ ⵍ㛎⠪ᢙ ஜᐽⵍ㛎⠪ ᛩਈᦼ㑆 ⹜㛎ߩ ⒳㘃 [⹜㛎ႎ๔ᦠ ߮ ᛩਈᣇᴺ ߪ ㅴⴕ⁁ᴫ ᷝઃ႐ᚲ] ኻᾖߩ⒳㘃 ᛩਈ⚻〝 ᖚ⠪ߩ⸻ᢿฬ ႎ๔ᦠߩ ⒳㘃 ലᕈ CNTO1275CRD3003 1. ኡ⸃ዉ⹜㛎 ╙ III ⋧㧘ࡦ࠳ࡓ ਥⷐߥኻ⽎㓸࿅㧦 1281 㧔⹜㛎 ਛ╬∝߆ࠄ㊀∝ߩ 44 ㅳ㑆 ታᣉਛ ోᕈ [5.3.5.1.3-1] CNTO1275CRD3001 ߪ ൻ㧘ੑ㊀⋤ᬌ㧘ࡊ ᧄߦࠃࠆኡ⸃ዉ≮ᴺߢ clinical response ౣ㐿ᓟߦࡦ ᵴേᦼࠢࡠࡦ∛ 㐳ᦼ⛮⛯ (㐳ᦼ⛮⛯
CNTO1275CRD3002 ߢ㧘ᧄߩ ࡏኻᾖ㧘ਗⴕ⟲㑆㧘ᄙ ߇ᓧࠄࠇߚⵍ㛎⠪ࠍ㧘એਅߩ 3 ⟲ߦࡦ࠳ ࠳ࡓൻߐࠇߚ ᖚ⠪ ᛩਈ㧦 ᛩਈᦼ) 2.7.6 㕒⣂ౝᛩਈߦࠃࠅ clinical ᣉ⸳ห⹜㛎 ࡓൻ ⵍ㛎⠪㧦1255 272 ㅳ⋡߹ ਛ㑆 response ߇ᓧࠄࠇߚ㧘ਛ╬∝߆ ኻᾖ⮎㧦ࡊࡏ ࡊࡏ⊹ਅᛩਈ 㧕 ߢ ႎ๔ᦠ ࠄ㊀∝ߩᵴേᦼࠢࡠࡦ∛ᖚ⠪ ᧄ 90 mg q12w ⊹ਅᛩਈ ࠍኻ⽎ߦ㧘ᧄߩ⊹ਅᛩਈߦࠃ ߥ߅㧘44 ㅳ⋡ߩో ᧄ 90 mg q8w ⊹ਅᛩਈ ࠆ 2 ߟߩኡ⸃⛽ᜬ≮ᴺߦ߅ߌࠆ ᕈ߮ലᕈ⹏ଔ⚳ੌ clinical remission ࠍ⹏ଔߔࠆޕ ᤨߦ⛮⛯ᛩਈ߇⋉ߢ ߘߩઁߩኻ⽎㓸࿅㧦 2. ਛ╬∝߆ࠄ㊀∝ߩᵴേᦼࠢࡠ ࠆߣ್ᢿߐࠇߚ႐ว ࡊࡏߦࠃࠆኡ⸃ዉ≮ᴺߢ ࡦ∛ᖚ⠪ࠍኻ⽎ߦ㧘ᧄߩ⊹ਅ ߪ㧘㐳ᦼ⛮⛯ᛩਈᦼߣ clinical response ߇ᓧࠄࠇߚⵍ㛎⠪㧦 ᛩਈߦࠃࠆ 2 ߟߩኡ⸃⛽ᜬ≮ᴺ ߒߡᦨ㐳 272 ㅳ⋡߹ߢ ࡊࡏ⊹ਅᛩਈ ߦ߅ߌࠆోᕈࠍ⹏ଔߔࠆޕ ᧄ⹜㛎ࠍ⛮⛯ ᧄߦࠃࠆኡ⸃ዉ≮ᴺߢ clinical response ߇ᓧࠄࠇߥ߆ߞߚⵍ㛎⠪㧦 0 ㅳ⋡ߦᧄ 90 mg ࠍ⊹ਅᛩਈ ψᧄ 90 mg q8w ⊹ਅᛩਈ ࡊࡏߦࠃࠆኡ⸃ዉ≮ᴺߢ clinical response ߇ᓧࠄࠇߥ߆ߞߚⵍ㛎 ⠪㧦 0 ㅳ⋡ߦᧄ 130 mg ࠍ㕒⣂ౝᛩਈ ψᧄ 90 mg q12w ⊹ਅᛩਈ ޘߩ⹜㛎ߩ߹ߣ
4
࠙ࠬ࠹ࠠࡑࡉ (3) ⹜㛎ߩ ⹜㛎⇟ภ ⹜㛎ߩਥ⋡⊛ ⹜㛎࠺ࠩࠗࡦ ⵍ㛎⮎߮ኻᾖ⮎ ⵍ㛎⠪ᢙ ஜᐽⵍ㛎⠪ ᛩਈᦼ㑆 ⹜㛎ߩ ⒳㘃 [⹜㛎ႎ๔ᦠ ߮ ᛩਈᣇᴺ ߪ ㅴⴕ⁁ᴫ ᷝઃ႐ᚲ] ኻᾖߩ⒳㘃 ᛩਈ⚻〝 ᖚ⠪ߩ⸻ᢿฬ ႎ๔ᦠߩ ⒳㘃 ലᕈ C0379T07 1. 5-ࠕࡒࡁࠨ࠴࡞㉄㧔ASA㧕ൻ ╙ IIa ⋧㧘ᄙᣉ⸳ ਥ⸃ᨆኻ⽎㓸࿅㧔㓸࿅ 1㧕㧦5-ASA ൻว 㓸࿅ 1㧦 ਛ╬∝߆ࠄ㊀∝ߩ ᛩਈᦼ㑆 ቢੌ ోᕈ [5.3.5.1.4] ว‛㧘᛫↢‛⾰㧘ࠦ࡞࠴ࠦࠬ࠹ ห㧘ࡦ࠳ࡓൻ⹜㛎 ‛㧘᛫↢‛⾰㧘ࠦ࡞࠴ࠦࠬ࠹ࡠࠗ࠼߮㧛 104 ᵴേᦼࠢࡠࡦ∛ ߪഀࠅઃ ቢోߥ
ࡠࠗ࠼߮㧛ߪ∉⺞▵⮎ߦ ኻᾖ⮎㧦ࡊࡏ ߪ∉⺞▵⮎㧔᛫ TNF ⮎ࠍ㧕ߦࠃࠆ 㓸࿅ 2㧦 ᖚ⠪ ߌࠄࠇߚ ႎ๔ᦠ 2.7.6 ࠃࠆᴦ≮ࠍฃߌߚߦ߽߆߆ࠊࠄ ᴦ≮ࠍฃߌߚߦ߽߆߆ࠊࠄߕലᨐ߇ᓧࠄࠇ 27 㓸࿅߮ ߕᜬ⛯ߔࠆ㧘ਛ╬∝߆ࠄ㊀∝ߩ ߥ߆ߞߚᖚ⠪ࠍ㧘એਅߩ 4 ⟲ߦࡦ࠳ࡓൻ ᛩਈ⟲ߦ ᵴേᦼࠢࡠࡦ∛㨇Crohn̉s · 0㧘1㧘2 ߮ 3 ㅳ⋡ߦࡊࡏࠍ⊹ਅ ࠃࠅ⇣ߥ Disease Activity Index㧔CDAI㧕 ᛩਈߒ㧘8㧘9㧘10 ߮ 11 ㅳ⋡ߦᧄ ࠆޕ ࠬࠦࠕ߇ 220 એ 450 એਅ㨉ᖚ 90 mg ࠍ⊹ਅᛩਈ 㓸࿅ 1㧦 ⠪ࠍኻ⽎ߣߒߡ㧘ࠢࡠࡦ∛ߩ · 0㧘1㧘2 ߮ 3 ㅳ⋡ߦᧄ 90 mg ࠍ⊹ · 11 ㅳ ᓽ߮∝⁁ߩ✭ߦ߅ߌࠆᧄ ਅᛩਈߒ㧘8㧘9㧘10 ߮ 11 ㅳ⋡ߦࡊ 㑆 ߩലᕈࠍ⹏ଔߔࠆޕ ࡏࠍ⊹ਅᛩਈ · 8 ㅳ㑆 2. ࠢࡠࡦ∛ᖚ⠪ࠍኻ⽎ߣߒߡ㧘 · 0 ㅳ⋡ߦࡊࡏࠍ㕒⣂ౝᛩਈߒ㧘8 ᧄߩ⊹ਅᛩਈᤨ߮㕒⣂ౝᛩ ㅳ⋡ߦᧄ 4.5 mg/kg ࠍ㕒⣂ౝᛩਈ 㓸࿅ 2㧦 ਈᤨߩోᕈࠍ⹏ଔߔࠆޕ · 0 ㅳ⋡ߦᧄ 4.5 mg/kg ࠍ㕒⣂ౝᛩਈ · 3 ㅳ㑆 ߒ㧘8 ㅳ⋡ߦࡊࡏࠍ㕒⣂ౝᛩਈ · 1 ᣣ㑆 㧔0 ㅳ ᰴ⸃ᨆኻ⽎㓸࿅㧔㓸࿅ 2㧕㧦☨࿖ߢߩࠢ ⋡㧕 ࡠࡦ∛ߦኻߔࠆᦨᄢᛚ↪㊂߮↪ᴺߩ ࠗࡦࡈࠠࠪࡑࡉᛩਈࠍฃߌߚ߇㧘ലᨐਇ චಽߪലᨐࠍ␜ߒߚ߽ߩߩߘߩᓟലᨐ߇ ᶖᄬߒߚᖚ⠪ࠍ㧘એਅߩ 2 ⟲ߦࡦ࠳ࡓൻ · 0㧘1㧘2 ߮ 3 ㅳ⋡ߦᧄ 90 mg ࠍ⊹ ਅᛩਈ · 0 ㅳ⋡ߦᧄ 4.5 mg/kg ࠍ㕒⣂ౝᛩਈ ലᕈ C0743T26 ࠢࡠࡦ∛ᴦ≮ߦኻߒߡᛚߐࠇߚ ╙ IIb ⋧㧘ᄙᣉ⸳ 0 ㅳ⋡ߦࡦ࠳ࡓൻߐࠇ㧘ኡ⸃ዉ≮ᴺߣ 526 ਛ╬∝߆ࠄ㊀∝ߩ 16 ㅳ㑆 ቢੌ ోᕈ [5.3.5.1.5] ↪ᴺ↪㊂ߩ 1 એߩ᛫ TNF ⮎ᴦ ห㧘ࡦ࠳ࡓൻ㧘ੑ㊀ ߒߡࡊࡏ㧘⧯ߒߊߪᧄ 1㧘3 ߪ ᵴേᦼࠢࡠࡦ∛ ቢోߥ ≮ࠍฃߌߚ߇㧘৻ᰴήലߢߞߚ ⋤ᬌ㧘ࡊࡏኻᾖ㧘 6 mg/kg ߇㕒⣂ౝᛩਈߐࠇߚޕ8 ㅳ⋡ߦ㧘0 ᖚ⠪ ႎ๔ᦠ ߆㧘ೋᦼߦലᨐࠍ␜ߒߚ߽ߩߩߘߩ ਗⴕ⟲㑆㧘↪㊂⸳ቯ⹜ ㅳ⋡ߦኡ⸃ዉ≮ᴺߢᧄߦഀࠅઃߌࠄࠇ ᓟലᨐ߇ᶖᄬߒߚᖚ⠪㧘ߪߎࠇࠄ 㛎 ߚⵍ㛎⠪ࠍ㧘6 ㅳ⋡ߩ clinical response ߦၮ ߩᴦ≮ߦኻߒߡᔋኈᕈ߇ߥ㧘ਛ╬ ኻᾖ⮎㧦ࡊࡏ ߠ߈ౣࡦ࠳ࡓൻߒ㧘ኡ⸃⛽ᜬᦼߩᛩਈߣ ޘߩ⹜㛎ߩ߹ߣ ∝߆ࠄ㊀∝ߩᵴേᦼࠢࡠࡦ∛ᖚ⠪ ߒߡ 8 ㅳ⋡߮ 16 ㅳ⋡ߦᧄ㧔90 mg㧕 ߦ߅ߡ㧘ᧄߦࠃࠆ clinical ߪࡊࡏࠍ⊹ਅᛩਈߒߚޕ response ߩዉߦ߅ߌࠆലᕈ߮ ోᕈࠍ⹏ଔߔࠆޕ
5 ࠙ࠬ࠹ࠠࡑࡉ 2.7.6 ޘߩ⹜㛎ߩ߹ߣ NAP1002 ⹜㛎
2.7.6.1 ᶏᄖ⥃ᐥ╙ I ⋧⹜㛎㧔CNTO1275NAP1002 ⹜㛎㧘ෳ⠨⾗ᢱ㧦5.3.1.2.1㧕
2.7.6.1.1 ⷐ
(1) ᴦ㛎ታᣉ⸘↹ᦠ⇟ภ CNTO1275NAP1002
(2) ᴦ㛎ߩᮡ㗴 ࠙ࠬ࠹ࠠࡑࡉ㧔એਅ㧘ᧄ㧕ߩᶧࡃࠗࠕ࡞ 2 ࠍ㕒⣂ౝන࿁ᛩਈߒߚߣ߈ߩ⮎‛േᘒࠍ Ყセߔࠆ╙ I ⋧㧘ࡦ࠳ࡓൻ㧘㕖⋤ᬌ㧘ਗⴕ⟲㑆Ყセ⹜㛎
(3) ᴦ㛎⺞ᢛකᏧ
(4) ᴦ㛎ታᣉක≮ᯏ㑐 3 ᣉ⸳㧔☨࿖㧕
(5) ᢥ₂㧔ᒁ↪ᢥ₂㧕 ߥߒ
(6) ᴦ㛎ታᣉᦼ㑆 2014 ᐕ 6 ᣣ㨪2014 ᐕ 12 ᣣ㧔࠺࠲ࡌࠬ࿕ቯ㧦20 ᐕᣣ㧕
(7) 㐿⊒ߩ⋧ ╙ I ⋧
(8) ⋡⊛ ਥ⋡⊛ ஜᐽⵍ㛎⠪ߦᧄߩᶧࡃࠗࠕ࡞㧔LIV㧕2 㧔90 mg/mL LIV ߮ 5 mg/mL LIV㧕ࠍ 6 mg/kg ߩ↪㊂ߢන࿁㕒⣂ౝᛩਈߒߚߣ߈ߩ⮎‛േᘒࠍᲧセߔࠆޕ
ᰴ⋡⊛ ஜᐽⵍ㛎⠪ߦᧄ 6 mg/kg ࠍන࿁㕒⣂ౝᛩਈߒߚߣ߈ߩోᕈ㧘ᔋኈᕈ㧘߮∉ේᕈࠍ⹏ଔ ߔࠆޕ
6 㧔1㧕 ࠙ࠬ࠹ࠠࡑࡉ 2.7.6 ޘߩ⹜㛎ߩ߹ߣ NAP1002 ⹜㛎
(9) ᴦ㛎ᣇᴺ ᧄ⹜㛎ߪ㧘ᧄߩ LIV 2 㧔90 mg/mL LIV ߮ 5 mg/mL LIV㧕ࠍ㧘ஜᐽⵍ㛎⠪ߦ 6 mg/kg ߩ ↪㊂ߢන࿁㕒⣂ౝᛩਈߒߚߣ߈ߩ⮎‛േᘒࠍᲧセߔࠆ㧘ᄙᣉ⸳ห㧘ࡦ࠳ࡓൻ㧘ਗⴕ⟲㑆㧘㕖 ⋤ᬌ㧘න৻↪㊂㧘㒮㧛ᄖ᧪ㅢ㒮⹜㛎ߢࠆޕ ᴦ㛎⮎ࠍᛩਈߔࠆ೨ߦ㧘ⵍ㛎⠪ࠍᧄߩ 2 ߟߩ LIV ⟲ߩߕࠇ߆ߦ㧘1㧦1 ߢࡦ࠳ࡓߦഀࠅ ઃߌߚޕ 90 mg/mL LIV ⟲㧦Day 1 ߦ㧘ᧄ 90 mg/mL LIV㧔ኻᾖ⮎㧕ࠍ 6 mg/kg ߩ↪㊂ߢන࿁㕒⣂ౝᛩਈ 㧔ࡐࡦࡊࠍ↪㧕ߒߚ㧔70 㧕ޕ 5 mg/mL LIV ⟲㧦Day 1 ߦ㧘ᧄ 5 mg/mL LIV㧔ⵍ㛎⮎㧕ࠍ 6 mg/kg ߩ↪㊂ߢන࿁㕒⣂ౝᛩਈ 㧔ࡐࡦࡊࠍ↪㧕ߒߚ㧔70 㧕ޕ ߔߴߡߩⵍ㛎⠪ߩᴦ㛎ෳടᦼ㑆ߪ⚂ 20 ㅳ㑆ߢࠅ㧘ߘߩઁߦᴦ㛎⮎ᛩਈ೨ 4 ㅳ㑆એౝߦࠬࠢ ࠾ࡦࠣߩߚ᧪㒮ߒߚޕ ⴊᷡਛ࠙ࠬ࠹ࠠࡑࡉỚᐲ᷹ቯ↪߮᛫࠙ࠬ࠹ࠠࡑࡉ᛫ᬌ↪ߩⴊᶧᬌࠍᴦ㛎ታᣉ⸘↹ ᦠߦⷙቯߒߚᤨὐߦណขߔࠆߎߣߣߒ㧘ోᕈߪᴦ㛎ᦼ㑆ࠍㅢߒߡ⹏ଔߒߚޕ
(10) ⵍ㛎⠪ᢙ㧔⸘↹ᤨ߮⸃ᨆᤨ㧕 ⸘↹ᤨ 140 ⸃ᨆᤨ 140 ߇⊓㍳ߐࠇ㧘ోࠍ⮎‛േᘒ⸃ᨆኻ⽎㓸࿅߮ోᕈ⸃ᨆኻ⽎㓸࿅ߣߒߚޕ
(11) ⸻ᢿ߮ਥߥㆬᛯၮḰ ᧄ⹜㛎ߩኻ⽎ߪ㧘18 ᱦ㧔ߪᴦ㛎߇ታᣉߐࠇࠆ▤ロၞߦ߅ߌࠆหᗧขᓧน⢻ߥᴺቯᐕ㦂㧕એ 55 ᱦએਅߢ㧘㊀߇ 50 kg એ 90 kg એਅ㧘ᩰᜰᢙ㧔BMI㧕߇ 18.5 kg/m2 એ 29.0 kg/m2 એ ਅߩஜᐽߥ↵ᕈߪᅚᕈߣߒߚޕ߹ߚ㧘ⵍ㛎⠪ߪ㕖༛ᾍ⠪߆㧘ᴦ㛎ᦼ㑆ਛ 1 ᣣߚࠅ⚕Ꮞ࠲ࡃࠦ 10 ᧄ㧘ߪ⪲Ꮞ 2 ᧄࠍ߃ࠆ༛ᾍࠍߒߥߎߣߦวᗧߔࠆᔅⷐ߇ࠅ㧘⥃ᐥ⊛ߦ㊀ⷐߥౝ⑼⊛∔ ᖚߪౝ⑼⊛㓚ኂࠍߒߡߥߎߣߣߒߚޕᅚᕈⵍ㛎⠪ߪ㧘ᅧᇚ㧘ᇚ㧘ߪᅧᆼࠍ⸘↹ߒ ߡࠆ⠪ߢߪߥߎߣߣߒ㧘ࠬࠢ࠾ࡦࠣᦼ㑆߮ᴦ㛎⮎ᛩਈᓟᦨૐ 5 ࠞ㑆ࠍᴦ㛎ᦼ㑆 ਛ㧘↢ᱺഥක≮ߩ⋡⊛ߢෆ⚦⢩㧔ෆሶ㧘ෆᲣ⚦⢩㧕ࠍឭଏߢ߈ߥߎߣߣߒߚޕ↵ᕈⵍ㛎⠪ߪ㧘 ᴦ㛎ᦼ㑆ਛ߮ᴦ㛎⮎ᛩਈᓟ 5 ࠞ㑆ߪ♖ሶࠍឭଏߢ߈ߥߎߣߣߒߚޕ
(12) ⵍ㛎⮎㧘↪㊂߮ᛩਈᣇᴺ㧘ࡠ࠶࠻⇟ภ ᧄ 5 mg/mL LIV ߪ㧘30 mL ࠟࠬࡃࠗࠕ࡞㨇26 mL ߦ࠙ࠬ࠹ࠠࡑࡉ㧔ㆮવሶ⚵឵߃㧕 130 mg ࠍ㨉ߦలႯߐࠇߚන࿁ᛩਈ↪㧘ή⩶ᶧߣߒߡଏ⛎ߐࠇ㧘ⵍ㛎⠪ߦ㕒⣂ౝᛩਈ㧔ࡐ ࡦࡊࠍ↪㧕ߐࠇߚޕᧄᶧߪ㧘1 mL ߚࠅ࠙ࠬ࠹ࠠࡑࡉ㧔ㆮવሶ⚵឵߃㧕5 mg ࠍߔࠆ 㧔ࡠ࠶࠻⇟ภ㧦 㧕ޕ
7 㧔2㧕 ࠙ࠬ࠹ࠠࡑࡉ 2.7.6 ޘߩ⹜㛎ߩ߹ߣ NAP1002 ⹜㛎
(13) ኻᾖ⮎㧘↪㊂߮ᛩਈᣇᴺ㧘ࡠ࠶࠻⇟ภ ᧄ 90 mg/mL LIV ߪ㧘2 mL ࠟࠬࡃࠗࠕ࡞ߦలႯߐࠇߚන࿁ᛩਈ↪㧘ή⩶ᶧߣߒߡଏ⛎ߐ ࠇ㧘ⵍ㛎⠪ߦ㕒⣂ౝᛩਈ㧔ࡐࡦࡊࠍ↪㧕ߐࠇߚޕᧄᶧߪ㧘1 mL ߚࠅ࠙ࠬ࠹ࠠࡑࡉ㧔ㆮ વሶ⚵឵߃㧕90 mg ࠍߔࠆ㧔ࡠ࠶࠻⇟ภ㧦 㧕ޕ
(14) ᛩਈᦼ㑆 ߔߴߡߩⵍ㛎⠪ߩᴦ㛎ෳടᦼ㑆ߪ⚂ 20 ㅳ㑆ߢࠅ㧘ߘߩઁߦᴦ㛎⮎ᛩਈ೨ 4 ㅳ㑆એౝߦࠬࠢ ࠾ࡦࠣߩߚ᧪㒮ߒߚޕDay 1 ߩᦺߦᴦ㛎⮎ࠍᛩਈߒ㧘Day 4 ߹ߢ㒮ߒߚᓟ㧘ⵍ㛎⠪ߪ Day 6 ߮ 8 ߦᄖ᧪ㅢ㒮ߔࠆߎߣߣߒߚޕ߹ߚ㧘ߘߩᓟ㧘ోᕈߩㅊ〔⺞ᩏߣ⮎‛േᘒ↪ߩណⴊ ߩߚ㧘ᴦ㛎⮎ᛩਈᓟ 16 ㅳ㑆ߪ㧘1 ㅳ㑆ߪ 2 ㅳ㑆ߦ 1 ࿁ߩᄖ᧪ㅢ㒮߇ᔅⷐߣߐࠇߚޕᄖ᧪ㅢ㒮 ߦࠃࠆᦨ⚳ߩㅊ〔⺞ᩏߪ Day 113 ߦⴕ߁ߎߣߣߒߚޕⵍ㛎⠪ߩోᕈߩᦨ⚳⺞ᩏߪ㧘ᴦ㛎⮎ᛩਈ ߩ 20 ㅳ㑆ᓟ㧔Day 141㧕ߦ㧘ᴦ㛎ታᣉක≮ᯏ㑐ߩᜂᒰ⠪ߦࠃࠆ㔚⏕ߦࠃࠅⴕߞߚޕ
(15) ⹏ଔ㗄⋡ ⮎‛േᘒ ⴊᷡਛ࠙ࠬ࠹ࠠࡑࡉỚᐲߩ᷹ቯ߮᛫࠙ࠬ࠹ࠠࡑࡉ᛫ߩᬌߩߚ㧘ߔߴߡߩⵍ㛎⠪߆ ࠄ㕒⣂ⴊࠍណขߒߚޕ ࠙ࠬ࠹ࠠࡑࡉߩ⮎‛േᘒࡄࡔ࠲ߪ㧘ⴊᷡਛ࠙ࠬ࠹ࠠࡑࡉỚᐲ-ᤨ㑆ߩ࠺࠲ࠍ↪㧘 ࡁࡦࠦࡦࡄ࠻ࡔࡦ࠻⸃ᨆߦࠃࠅ▚ߒߚޕᧄߩන࿁㕒⣂ౝᛩਈᓟߩ⮎‛േᘒࡄࡔ࠲ߣߒ
ߡ㧘ᦨ㜞ⴊᷡਛỚᐲ㧔Cmax㧕㧘⚳ᧃ⋧ࠍᄖᝌߒߚ 0 ᤨ㑆߆ࠄή㒢ᄢᤨ㑆߹ߢߩⴊᷡਛỚᐲ-ᤨ㑆ᦛ
✢ਅ㕙Ⓧ㧔AUCinf㧕㧘0 ᤨ㑆߆ࠄᦨ⚳ቯ㊂น⢻ᤨὐ߹ߢߩⴊᷡਛỚᐲ-ᤨ㑆ᦛ✢ਅ㕙Ⓧ㧔AUClast㧕㧘
ᶖᄬඨᷫᦼ㧔T1/2㧕㧘ోりࠢࠕࡦࠬ㧔CL㧕㧘⚳ᧃ⋧ߩಽᏓኈⓍ㧔Vz㧕╬ࠍ▚ߒߚޕ
∉ේᕈ ߔߴߡߩⵍ㛎⠪ߩⴊᷡᬌࠍ↪ߡ㧘᛫࠙ࠬ࠹ࠠࡑࡉ᛫ࠍ⹏ଔߒߚޕ
ోᕈ ోᕈ߮ᔋኈᕈߦߟߡߪ㧘りᚲ㧘ࡃࠗ࠲࡞ࠨࠗࡦ㧘ࠗࡦࡈࡘ࡚ࠫࡦࠕ࡚ࠢࠪࡦ㧘 ᔃ㔚࿑㧔ࠬࠢ࠾ࡦࠣᤨ㧘ࡌࠬࠗࡦᤨ㧘߮ᦨ⚳᧪㒮ᣣߩߺ㧕㧘⥃ᐥᬌᩏ୯㧔ⴊᶧቇ⊛ᬌ ᩏ㧘ⴊᷡ↢ൻቇᬌᩏ㧘߮ዩᬌᩏ㧕㧘ኂ⽎߮㊀◊ߥኂ⽎㧔SAE㧕ࠍ⹏ଔߒߚޕ߹ߚ㧘 ࠬࠢ࠾ࡦࠣᤨߦ㧘ࡅ࠻∉ਇో࠙ࠗ࡞ࠬ㧔HIV㧕㧘B ဳ⢄Ἳ࠙ࠗ࡞ࠬ㧔HBV㧕߮ C ဳ⢄Ἳ ࠙ࠗ࡞ࠬ㧔HCV㧕ᬌᩏ㧘ਗ߮ߦ QuantiFERON-Tuberculosis㧔TB㧕Gold ߦࠃࠆ⚿ᩭᬌᩏࠍታᣉߒ ߚޕ
8 㧔3㧕 ࠙ࠬ࠹ࠠࡑࡉ 2.7.6 ޘߩ⹜㛎ߩ߹ߣ NAP1002 ⹜㛎
(16) ⛔⸘ᚻᴺ ⵍ㛎⠪ᢙߩ⸳ቯ ᧄ⹜㛎ߢߪᱜᑼߥ⺑ᬌቯߪⴕࠊߥ߆ߞߚߚ㧘ᱜᑼߥⵍ㛎⠪ᢙ߮ᬌജߩ⸳ቯߪⴕࠊߥ߆ ߞߚޕᧄ⹜㛎ߩⵍ㛎⠪ᢙߦߟߡ㧘ஜᐽⵍ㛎⠪ߦන࿁ᛩਈᓟߩ↢‛ቇ⊛ห╬ᕈߩ⸃ᨆࠍⴕߞߚ㓙 ߩᬌജࠍ⹏ଔߒߚޕ
⮎‛േᘒ ዋߥߊߣ߽ 1 ߟߩ⮎‛േᘒࡄࡔ࠲ߩᱜ⏕ߥ▚߇น⢻ߥⴊᷡਛ࠙ࠬ࠹ࠠࡑࡉỚᐲ-ᤨ㑆 ࡊࡠࡈࠔࠗ࡞ࠍߔࠆⵍ㛎⠪ࠍ⮎‛േᘒ⸃ᨆኻ⽎㓸࿅ߣቯ⟵ߒߚޕⴊᷡਛ࠙ࠬ࠹ࠠࡑࡉỚᐲߪ㧘 ⷙቯߐࠇߚណⴊᤨὐߦ߅ߌࠆ⸥ㅀ⛔⸘㊂ࠍ↪ߡᛩਈ⟲ߏߣߦⷐ⚂ߒߚޕ⮎‛േᘒࡄࡔ࠲ߪ㧘 ⮎‛േᘒ⸃ᨆኻ⽎㓸࿅ߦߟߡᛩਈ⟲ߏߣߦⷐ⚂ߒߚޕ᛫࠙ࠬ࠹ࠠࡑࡉ᛫߇ᬌߐࠇߚ႐ว ߪ㧘᛫ᬌߩήߦ⮎‛േᘒࡄࡔ࠲ࠍⷐ⚂ߔࠆߎߣߣߒߚޕ⮎‛േᘒ࠺࠲ߪࠣࡈൻ ߒߡᬌ⸛ߒߚޕᧄߩ LIV 2 㧔90 mg/mL LIV ߮ 5 mg/mL LIV㧕ߩ⮎‛േᘒࠍᲧセߔࠆߚ
ߦ㧘5 mg/mL LIV㧔ⵍ㛎⮎㧕ߣ 90 mg/mL LIV㧔ኻᾖ⮎㧕ߦ߅ߡᓧࠄࠇߚ Cmax ߣ AUC㧔AUCinf
߮ AUClast㧕ߩᐞᐔဋ୯ߩᲧ㧘ਗ߮ߦࡄࡔ࠻࠶ࠢᚻᴺߦࠃࠆ 90%ା㗬㑆㧔CI㧕ࠍ▚ ߒߚޕ
∉ේᕈ ᛫࠙ࠬ࠹ࠠࡑࡉ᛫ߩ⊒ഀวߪ㧘ᧄߩᛩਈࠍฃߌ㧘߆ߟ᛫࠙ࠬ࠹ࠠࡑࡉ᛫ᬌ↪ߩ ㆡಾߥⴊᷡᬌ߇ᓧࠄࠇߚߔߴߡߩⵍ㛎⠪ࠍኻ⽎ߦ㓸⸘ߒߚޕ
ోᕈ ⥃ᐥᬌᩏ୯㧘ࡃࠗ࠲࡞ࠨࠗࡦ㧘߮ᔃ㔚࿑ߦߟߡߪ㧘ᴦ㛎⮎ᛩਈ೨ߦቢੌߒߚ⋥ㄭߩ⹏ଔࠍ ࡌࠬࠗࡦ୯ߣቯ⟵ߒߚޕߔߴߡߩኂ⽎ߪ㧘ߘࠇߙࠇߩᛩਈ⟲ߏߣߦ㧘ICH ࿖㓙ක⮎↪⺆ 㓸㧔MedDRA㧕ߩེቭᄢಽ㘃߮ၮᧄ⺆ߦ㓸⸘ߒߚޕోᕈߩ࠺࠲ߪ⸥ㅀ⛔⸘㊂ࠍ↪ ߡⷐ⚂ߒߚޕ
(17) ⚿ᨐ ᴦ㛎ኻ⽎㓸࿅ ᧄ⹜㛎ߢߪஜᐽⵍ㛎⠪ 140 㧔↵ᕈ 61 㧘ᅚᕈ 79 㧕ࠍࡦ࠳ࡓൻߒ 70 ߇ 90 mg/mL LIV㧘 70 ߇ 5 mg/mL LIV ߩᛩਈࠍฃߌߚޕࡦ࠳ࡓൻߐࠇߚ 140 ߩ߁ߜ 137 ߇⹜㛎ࠍቢੌߒ㧘 90 mg/mL LIV ⟲ߩ 3 ߇ᧄ⹜㛎ࠍਛᱛߒߚ㧔ㅊ〔ਇ⢻߇ 2 㧘หᗧ᠗࿁߇ 1 㧕ޕᐕ㦂ߩᐔဋ୯ 㨇ᮡḰᏅ㧔SD㧕㨉ߪ 35.1㧔10.07㧕ᱦ㧘BMI ߩᐔဋ୯㧔SD㧕ߪ 25.3㧔2.34㧕kg/m2 ߢߞߚޕⵍ 㛎⠪ߩᄢᄙᢙߪ⊕ੱߢߞߚ㨇104 㧔74.3%㧕㨉ޕੱญ⛔⸘ቇ⊛ࡄࡔ࠲ߪ㧘ߕࠇ߽ 2 ⟲ 㑆ߢห᭽ߢߞߚޕᴦ㛎⮎ߩᛩਈߦ㑐ㅪߒߚ㊀ᄢߥᴦ㛎ታᣉ⸘↹ᦠ߆ࠄߩㅺ⣕߇ 2 㧔90 mg/mL LIV ⟲߮ 5 mg/mL LIV ⟲ߢฦ 1 㧕ߦႎ๔ߐࠇ㧘ߎࠇࠄߩⵍ㛎⠪ߢߪⷙቯᧂḩߩ↪㊂ߢᛩਈߐ ࠇߚޕ
9 㧔4㧕 ࠙ࠬ࠹ࠠࡑࡉ 2.7.6 ޘߩ⹜㛎ߩ߹ߣ NAP1002 ⹜㛎
⮎‛േᘒ߮∉ේᕈ ᧄ 6 mg/kg ࠍ 1 ᤨ㑆߆ߌߡන࿁㕒⣂ౝᛩਈߒߚᓟ㧘ᛩਈ⚳ੌ 30 ಽᓟߦᦨ㜞ⴊᷡਛ࠙ࠬ࠹ࠠ ࡑࡉỚᐲࠍ␜ߒ㧘ߘߩᐔဋ୯ߪ㧘90 mg/mL LIV ⟲ߢ 199.1 ȝg/mL ߮ 5 mg/mL LIV ⟲ߢ
193.2 ȝg/mL ߢߞߚޕCmax ߮ AUC ߩᐞᐔဋ୯ߩᲧߪ⚂ 1㧔Cmax ߢߪ 0.967㧘AUCinf ߮
AUClast ߢߪߣ߽ߦ 0.971㧕ߢࠅ㧘ߎࠇࠄߩᲧߩ 90%CI ߪ㧘↢‛ቇ⊛ห╬ᕈߩᮡḰ⊛ߥ▸࿐ߢ ࠆ 0.80㨪1.25 ౝߢߞߚޕ න࿁㕒⣂ౝᛩਈᓟ㧘139 ਛ 2 㧔1.4%㧘90 mg/mL LIV ⟲߮ 5 mg/mL LIV ⟲ߢฦ 1 㧕ߢ᛫ ࠙ࠬ࠹ࠠࡑࡉ᛫㓁ᕈߣߥߞߚ߇㧘᛫ଔߪૐ߆ߞߚ㧔1㧦50㧕ޕ
ోᕈ 140 ߩⵍ㛎⠪ߩ߁ߜ 80 㧔57.1%㧕ߦ 1 ઙએߩኂ⽎߇ႎ๔ߐࠇߚޕኂ⽎ࠍ 1 ઙએ ⊒ߒߚⵍ㛎⠪ߩഀวߪ㧘2 ⟲㑆ߢห⒟ᐲߢߞߚޕᦨ߽ᄙߊࠄࠇߚኂ⽎ߪ㧘㗡∩ 㨇18 㧔12.9%㧕㨉㧘ᖡᔃ㨇11 㧔7.9%㧕㨉㧘⢛ㇱ∩㨇8 㧔5.7%㧕㨉㧘᳇ᗵᨴ߮ⴊ▤⓫ ೝㇱⴊ㨇ฦ 7 㧔5.0%㧕㨉ߢߞߚޕ90 mg/mL LIV ⟲߮ 5 mg/mL LIV ⟲㑆ߢኂ⽎ߩ ⊒⁁ᴫߦᗧߩࠆᏅߪࠄࠇߥ߆ߞߚޕኂ⽎ߩ㊀∝ᐲߪᄢㇱಽ߇シᐲߢࠅ㧘ߕࠇ ߩᛩਈ⟲ߢ߽㜞ᐲߩኂ⽎ߪႎ๔ߐࠇߥ߆ߞߚޕᴦ㛎ᦼ㑆ਛߦ㧘ᱫ߿ኂ⽎ߦࠃࠆਛᱛ ߪࠄࠇߥ߆ߞߚ߇㧘SAE ߇ 1 ઙႎ๔ߐࠇߚޕᴦ㛎ᦼ㑆ਛߦ 90 mg/mL LIV ⟲ߩⵍ㛎⠪ߢ⊒ ߒߚ SAE ߪᵹ↥ߢࠅ㧘ᴦ㛎ᜂᒰකᏧߪᴦ㛎⮎ߣวℂ⊛ߦ㑐ㅪᕈ߇ࠆኂ⽎ߣ್ᢿߒߚޕ ᧄ⹜㛎ߢߪ㧘140 ਛ 7 㧔5.0%㧕ߦᵈㇱᔕߩኂ⽎߇ࠄࠇߚޕᦨ߽ᄙߊࠄ ࠇߚ㧔ోⵍ㛎⠪ߢߩ⊒ഀว߇ 1%㧕ᵈㇱᔕߪ㧘ᵈㇱⴊ㨇90 mg/mL LIV ⟲ 1 㧔1.4%㧕㧘5 mg/mL LIV ⟲ 2 㧔2.9%㧕㨉߮ᵈㇱ⚃㨇90 mg/mL LIV ⟲߮ 5 mg/mL LIV ⟲ߢฦ 1 㧔1.4%㧕㨉ߢߞߚޕ 㕒⣂ౝᛩਈቢੌᓟ 1 ᤨ㑆߹ߢߦ㧘140 ਛ 4 㧔2.9%㧕ߢ 1 ઙએߩኂ⽎߇ႎ๔ߐࠇ㧘ᦨ ߽ᄙߊࠄࠇߚኂ⽎ߪ㧘90 mg/mL LIV ⟲ߩⴊ▤⓫ೝㇱⴊ㨇2 㧔2.9%㧕㨉ߢߞߚޕ ోりᕈߩㆊᢅ∝ᔕߪࠄࠇߥ߆ߞߚޕ ⴊᶧቇ⊛ᬌᩏ߮ⴊᷡ↢ൻቇᬌᩏߦ㑐ㅪߒߚኂ⽎߇ߘࠇߙࠇ 2 ઙ߮ 3 ઙࠄࠇߚ߇㧘 ౣᬌᩏߢߪ߅߅ߨᱜᏱ୯ࠍ␜ߒߚޕᴦ㛎ᦼ㑆ࠍㅢߓ㧘ዩᬌᩏߦ㑐ㅪߒߚኂ⽎ߪࠄࠇߥ ߆ߞߚޕᴦ㛎⮎ߩᛩਈߦࠃࠅ㧘ࡃࠗ࠲࡞ࠨࠗࡦ߿ᔃ㔚࿑ࡄࡔ࠲ߦ⥃ᐥ⊛ߦᗧߩࠆᄌൻߪ ߺࠄࠇߥ߆ߞߚޕో⊛ߥోᕈᚲߪ 90 mg/mL LIV ߮ 5 mg/mL LIV ߩਔߢห᭽ߢࠅ㧘 ߕࠇ߽ᔋኈᕈߪ⦟ᅢߢߞߚޕ
⚿⺰ · ᧄ 6 mg/kg ࠍ 1 ᤨ㑆߆ߌߡන࿁㕒⣂ౝᛩਈߒߚᓟߩᦨ㜞ⴊᷡਛ࠙ࠬ࠹ࠠࡑࡉỚᐲߩᐔ ဋ୯ߪ㧘90 mg/mL LIV ⟲ߢ 199.1 ȝg/mL ߮ 5 mg/mL LIV ⟲ߢ 193.2 ȝg/mL ߣਔߢห᭽
ߢߞߚޕAUCinf ߩᐔဋ୯ߪ㧘90 mg/mL LIV ⟲ߢ 3218.3 ȝg day/mL ߮ 5 mg/mL LIV ⟲ߢ 3132.4 ȝg day/mL ߢߞߚޕ
· ࠙ࠬ࠹ࠠࡑࡉߩోりᦑ㔺㊂ߪ 5 mg/mL LIV ⟲ߣ 90 mg/mL LIV ⟲ߢห᭽ߢࠅ㧘Cmax ߮ AUC ߩᐞᐔဋ୯ߩᲧߩ 90%CI ߪ㧘↢‛ቇ⊛ห╬ᕈߩᮡḰ⊛ߥ▸࿐ߢࠆ 0.80㨪1.25 ౝߢ ߞߚޕ
10 㧔5㧕 ࠙ࠬ࠹ࠠࡑࡉ 2.7.6 ޘߩ⹜㛎ߩ߹ߣ NAP1002 ⹜㛎
· ᧄߩ 2 㑆ߦ߅ߡ㧘∉ේᕈߦᏅߪࠄࠇߥ߆ߞߚޕ∉ේᕈߩ⹏ଔ߇น⢻ߢ ߞߚ 139 ߩ߁ߜ㧘2 㧔1.4%㧘90 mg/mL LIV ⟲߮ 5 mg/mL LIV ⟲ߢฦ 1 㧕ߢᴦ㛎ᦼ 㑆ਛߦ᛫࠙ࠬ࠹ࠠࡑࡉ᛫߇㓁ᕈߣߥߞߚޕ
· ஜᐽⵍ㛎⠪ߦ߅ߌࠆᧄߩ LIV 2 㧔90 mg/mL LIV ߮ 5 mg/mL LIV㧕ࠍ↪ߚ 6 mg/kg ߩන࿁㕒⣂ౝᛩਈߩᔋኈᕈߪ⦟ᅢߢࠅ㧘㊀ⷐߥ㧘ߪᣂߚߥోᕈᚲߪࠄࠇߥ߆ ߞߚޕోᕈᚲߪ 90 mg/mL LIV ߣ 5 mg/mL LIV ߩਔߢห᭽ߢߞߚޕ
· ᧄ⹜㛎ߩ⚿ᨐ߆ࠄ㧘ᧄߩ LIV 2 ߩ㘃ૃᕈ߇␜ߐࠇߚޕ
11 㧔6㧕 ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
2.7.6.2 ➨ III ┦ᅜ㝿ඹྠヨ㦂㸸ᐶゎᑟධヨ㦂㸦CNTO1275CRD3001 ヨ㦂㸪ホ౯㈨ ᩱ㸸5.3.5.1.1㸧
2.7.6.2.1 ᴫせ
(1) 㦂ᐇィ⏬᭩␒ྕ CNTO1275CRD3001
(2) 㦂ࡢᶆ㢟 ᢠ TNF ⸆⒪࡛ຠᯝ༑ศཪࡣᚸᐜᛶࡢ࡞࠸୰➼ࡽ㔜ࡢάືᮇࢡ࣮ࣟࣥᝈ⪅ࢆᑐ㇟ ࡍࡿ㸪࢘ࢫࢸ࢟ࢾ࣐ࣈ㸦௨ୗ㸪ᮏ㸧ࡢᐶゎᑟධ⒪ἲ࠾ࡅࡿᏳᛶཬࡧ᭷ຠᛶࡢホ౯ࢆ┠ⓗ ࡋࡓ➨ III ┦㸪ࣛࣥࢲ࣒㸪㔜┣᳨㸪ࣉࣛࢭ࣎ᑐ↷㸪୪⾜⩌㛫㸪ከタඹྠヨ㦂
(3) 㦂㈐௵་ᖌ
(4) 㦂ᐇ་⒪ᶵ㛵 ᆅᇦ 6ᆅᇦ ࢪ㸪࣮ࣚࣟࢵࣃ㸪⡿㸪༡⡿㸪ࣇࣜ࢝㸪࢜ࢭࢽ ཧຍᅜ 23 ࣧᅜ ᪥ᮏ㸪㡑ᅜ㸪ࢳ࢙ࢥඹᅜ㸪ࣁ࣮ࣥ࢞ࣜ㸪࣏࣮ࣛࣥࢻ㸪ࢭࣝࣅ㸪 ࣮࢜ࢫࢺࣛࣜ㸪࣮࢜ࢫࢺࣜ㸪࣋ࣝࢠ࣮㸪ࣈࣛࢪࣝ㸪࢝ࢼࢲ㸪ࢹࣥ ࣐࣮ࢡ㸪ࣇࣛࣥࢫ㸪ࢻࢶ㸪ࣝࣛࣥࢻ㸪ࢫ࢚ࣛࣝ㸪ࢱࣜ㸪 ࢜ࣛࣥࢲ㸪ࢽ࣮ࣗࢪ࣮ࣛࣥࢻ㸪༡ࣇࣜ࢝㸪ࢫ࣌ࣥ㸪ⱥᅜ㸪⡿ᅜ ᐇタ 178 タ㸦᪥ᮏ 13 タ㸧
(5) බ⾲ᩥ⊩㸦ᘬ⏝ᩥ⊩㸧 ࡞ࡋ
(6) 㦂ᐇᮇ㛫 2011 ᖺ 6 ᭶᪥㹼2013 ᖺ 7 ᭶᪥
(7) 㛤Ⓨࡢ┦ ➨ III ┦
(8) ┠ⓗ ┠ⓗ 1. 1 ௨ୖࡢᢠ TNF㸦⭘⒆ቯṚᅉᏊ㸧⸆⒪࡛ຠᯝ༑ศཪࡣᚸᐜᛶࡢ࡞࠸୰➼ࡽ㔜 ࡢάືᮇࢡ࣮ࣟࣥᝈ⪅࠾࠸࡚㸪ᮏࡢ㟼⬦ෆᢞࡼࡿᐶゎᑟධ⒪ἲࡢ clinical response ࡛ࡢ᭷ຠᛶࢆホ౯ࡍࡿࠋ
12 (1) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
2. 1 ௨ୖࡢᢠ TNF ⸆⒪࡛ຠᯝ༑ศཪࡣᚸᐜᛶࡢ࡞࠸୰➼ࡽ㔜ࡢάືᮇࢡ࣮ࣟࣥ ᝈ⪅࠾࠸࡚㸪ᮏࡢ㟼⬦ෆᢞࡼࡿᐶゎᑟධ⒪ἲࡢᏳᛶࢆホ౯ࡍࡿࠋ
ḟ┠ⓗ 1. ᮏࡢ㟼⬦ෆᢞࡼࡿᐶゎᑟධ⒪ἲࡢ clinical remission ࡛ࡢ᭷ຠᛶࢆホ౯ࡍࡿࠋ
2. ᮏࡢ㟼⬦ෆᢞࡼࡿᐶゎᑟධ⒪ἲࡢᝈ≉␗ⓗᗣ㛵㐃⏕άࡢ㉁㸦QOL㸧ᨵၿ࡛ࡢ᭷ ຠᛶࢆホ౯ࡍࡿࠋ
3. ⾑Ύ C ᛂᛶࡓࢇⓑ㸦CRP㸧㸪౽୰࢝ࣝࣉࣟࢸࢡࢳࣥ㸪౽୰ࣛࢡࢺࣇ࢙ࣜࣥཬࡧࡑࡢࡢ ⸆ຊᏛⓗࣂ࣐࣮࣮࢜࢝ࡢኚືࢆྵࡵࡓᮏᢞࡢ⸆≀ືែཬࡧ⸆ຊᏛࢆホ౯ࡍࡿࠋ
4. ᐶゎᑟධヨ㦂 CNTO1275CRD3002 ేࡏ࡚㸪ᐶゎ⥔ᣢヨ㦂 CNTO1275CRD3003 ࡛ホ౯ࡍࡿ ᑐ㇟㞟ᅋࢆᥦ౪ࡍࡿࠋ
(9) 㦂᪉ἲ ᮏヨ㦂ࡣ㸪ࣛࣥࢲ࣒㸪㔜┣᳨㸪ࣉࣛࢭ࣎ᑐ↷㸪୪⾜⩌㛫㸪ከタඹྠヨ㦂࡛࠶ࡾ㸪⿕㦂⪅ ࡣ 0 㐌┠௨ୗࡢ࠸ࡎࢀࡢ༢ᅇ㟼⬦ෆᢞ⩌ 1㸸1㸸1 ࡢẚ࡛ࣛࣥࢲ࣒ࡾࡅࡽࢀࡓࠋ · ࣉࣛࢭ࣎⩌
· ᮏ 130 mg ⩌
· ᮏࡢయ㔜ู⏝㔞㸦㹼6 mg/kg㸧⩌㸦௨ୗ㸪ᮏ㹼6 mg/kg ⩌㸧
· ᮏ 260 mg㸦య㔜 55 kg㸧
· ᮏ 390 mg㸦య㔜 >55 kg㹼85 kg㸧
· ᮏ 520 mg㸦య㔜 >85 kg㸧
6 㐌┠㸪⿕㦂⪅ࢆᑐ㇟ࡋ࡚㸪せホ౯㡯┠࡛࠶ࡿ clinical response ࢆホ౯ࡋࡓࠋ0 㐌┠ ᮏ⩌ࡾࡅࡽࢀ㸪ࡘ 8 㐌┠ clinical response ࡀᚓࡽࢀࡓ⿕㦂⪅ࢆ㸪8 㐌┠㸪ᐶゎ⥔ᣢ ヨ㦂 CNTO1275CRD3003 ࡢせ࡞ᑐ㇟㞟ᅋࡋ࡚⛣⾜ྍ⬟ࡋࡓࠋᮏࡼࡿᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀ࡞ࡗࡓ⿕㦂⪅ཬࡧ 0 㐌┠ࣉࣛࢭ࣎⩌ࡾࡅࡽࢀࡓ⿕㦂⪅ 㸦clinical response ࡢ᭷↓ࡣၥࢃ࡞࠸㸧ࡣ㸪8 㐌┠ᐶゎ⥔ᣢヨ㦂 CNTO1275CRD3003 ࡢ⛣⾜㐺 ᱁ࡋࡓࡀ㸪せ࡞ᑐ㇟㞟ᅋࡣྵࡵ࡞࠸ࡇࡋࡓࠋᐶゎ⥔ᣢヨ㦂 CNTO1275CRD3003 ⛣⾜ࡋ࡞ࡗࡓ⿕㦂⪅ࡘ࠸࡚ࡣ㸪0 㐌┠ࡢ㦂⸆ᢞࡽ⣙ 20 㐌㛫ᚋᏳᛶ㏣㊧ㄪᰝࢆᐇ ࡋࡓࠋ ᮏヨ㦂ࢆ㏻ࡌ࡚㸪⊂❧ࢹ࣮ࢱࣔࢽࢱࣜࣥࢢጤဨࡀ㸪⿕㦂⪅ࡢᏳᛶࢹ࣮ࢱࢆࣔࢽࢱࣜࣥࢢࡋ ࡓࠋ ᮏヨ㦂࡛ࡣ㸪୰㛫ゎᯒࡣᐇࡋ࡞ࡗࡓࠋ
13 (2) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
(10) ⿕㦂⪅ᩘ㸦ィ⏬ཬࡧゎᯒ㸧 ィ⏬ ┠ᶆᩘࡣ 675 ࡋ㸪ྛᢞ⩌ 225 ࡎࡘࣛࣥࢲ࣒ࡍࡿࡇࡋࡓࠋᮏヨ㦂࡛⏝ࡍ ࡿ㟼⬦ෆᢞ〇㹙࢘ࢫࢸ࢟ࢾ࣐ࣈ 130 mg㸸ᐜ㔞 26 mL㸦5 mg/mL㸧㹛ࡢࣂࢵࢳᏳᐃᛶୖࡢၥ 㢟ࡀ☜ㄆࡉࢀࡓࡓࡵ㸪㦂౫㢗⪅ࡣ 20 ᖺ᭶ヨ㦂ࢆ୍୰᩿ࡋࡓࡀ㸪ࡑࢀ௨๓ྜィ 28 ࡀࣛࣥࢲ࣒ࡉࢀ࡚࠸ࡓࠋࡇࢀࡽࡢ⿕㦂⪅ࡢࢹ࣮ࢱࡣ㸪ࡇࡢၥ㢟ࢆㄆ▱ࡋࡓࡇࡼࡾ㸪ホ౯ ࣂࢫࢆ⏕ࡌࡿྍ⬟ᛶࡀ࠶ࡿࡇࡽ㸪ィ⏬ࡋࡓゎᯒࡣ⏝࠸࡞࠸ࡇࡋࡓࠋࡲࡓ㸪ᙜึ ィ⏬ࡋࡓ㸪せホ౯㡯┠ࡢゎᯒࡢ᳨ฟຊࢆᚓࡿࡓࡵᚲせ࡞ࢧࣥࣉࣝࢧࢬࡢ 675 ࢆ⥔ᣢࡍࡿ ࡓࡵ㸪⤫ィゎᯒィ⏬᭩グ㍕ࡋࡓ┠ᶆᩘࢆ 703 㸦675 㸩28 㸧ኚ᭦ࡍࡿࡇࡋࡓࠋ
᪥ᮏே⿕㦂⪅ᩘࡢタᐃ᰿ᣐ ᮏヨ㦂యࡢ┠ᶆᩘࡣ㸪➨ 2 ┦ヨ㦂㸦C0743T26 ヨ㦂㸧ࡢ⤖ᯝᇶ࡙ࡁ㸪6 㐌ࡢ clinical responder ࡢྜࢆࣉࣛࢭ࣎⩌ 25%㸪6 mg/kg ⩌ 40%ぢ✚ࡶࡾ㸪ࡲࡓ 8 㐌ࡢ clinical remission ࠾ࡅࡿ᳨ฟຊࡶ⪃៖ࡋ㸪1 ⩌ 225 㸦ྜィ 675 㸧タᐃࡋࡓࠋ᪥ᮏࡀᙜヱᅜ㝿ඹྠヨ㦂ཧ ຍࡋࡓሙྜ㸪᪥ᮏே㞟ᅋ㞟ᅋ࠾ࡅࡿ⤖ᯝࡢ୍㈏ᛶࡘ࠸࡚㸪ࠕᅜ㝿ඹྠ㦂㛵ࡍࡿᇶ ᮏⓗ⪃࠼᪉ࡘ࠸࡚ࠖ♧ࡉࢀࡿ᪉ἲ 1࠙D (Japan)㸭D (all) >0.5ࠚཬࡧ᪉ἲ 2࠙D (Japan) >0 ࡘ D (all )>0ࠚࢆ⏝࠸᳨࡚ウࡋࡓࠋ 㞟ᅋ࠾ࡅࡿ 6 mg/kg ⩌ࡢࣉࣛࢭ࣎⩌ᑐࡍࡿ clinical responder ࡢྜࡢᕪࢆ D (all)㸪᪥ᮏ ே㞟ᅋ࠾ࡅࡿ 6 mg/kg ⩌ࡢࣉࣛࢭ࣎⩌ᑐࡍࡿྜࡢᕪࢆ D (Japan)ࡋࡓࡁ㸪᪉ἲ 1 ࡛ࡣ㸪 6 mg/kg ⩌࠾࠸࡚ࣉࣛࢭ࣎⩌ᑐࡍࡿඃ㉺ᛶࡀ♧ࡉࢀࡘ D (Japan)㸭D (all)>0.5 ࢆ‶ࡓࡍ☜⋡ ࢆ⟬ฟࡋ㸪᪉ἲ 2 ࡛ࡣ 6 mg/kg ⩌࠾࠸࡚ࣉࣛࢭ࣎⩌ᑐࡍࡿඃ㉺ᛶࡀ♧ࡉࢀࡘ D (Japan)>0 ࢆ ‶ࡓࡍ☜⋡ࢆ⟬ฟࡋ᳨ウࡋࡓࠋࡑࡢ⤖ᯝ㸪ྛ᪉ἲ࠾࠸࡚᮲௳ࢆ‶ࡓࡍ☜⋡ࢆ 80㸣௨ୖࡍࡿ ࡓࡵࡣ㸪᪉ἲ 1 ࡛ 1 ⩌⣙ 50 㸦ྜィ 150 㸧㸪᪉ἲ 2 ࡛ 1 ⩌⣙ 20 㸦ྜィ 60 㸧ࡀᚲせ࡛ ࠶ࡗࡓࠋ ୍᪉㸪᪥ᮏ࠾ࡅࡿ㞟✚ྍ⬟ᩘࡢ᳨ウ࠾࠸࡚㸪ࢡ࣮ࣟࣥࡢ≉ᐃᝈ་⒪ཷ⤥⪅ドࡣ㸪 2009 ᖺᗘ࡛ 30,891 ௳ࡉࢀ࡚࠾ࡾ㸪ᝈ⪅ᩘࡋ࡚ࡣ⣙ 3 ே᥎ィࡉࢀࡓࠋ2011 ᖺ 3 ᭶Ⅼ ࠾ࡅࡿㄪᰝࡢ⤖ᯝ㸪ࢡ࣮ࣟࣥᝈ⪅ࡢ࠺ࡕᢠ TNF ⸆ࢆ⏝ࡋࡓ⤒㦂ࡢ࠶ࡿࢡ࣮ࣟࣥᝈ⪅ࡣ㸪 ⣙ 5,000 ே㹼14,000 ே⛬ᗘᐃࡉࢀࡓࠋࡑࡢ࠺ࡕ㸪ᢠ TNF ⸆࡛ຠᯝ༑ศ࡞ᝈ⪅ཪࡣᚸᐜᛶࡢ ࡞࠸ᝈ⪅ࡣ⣙ 10%㹼40%⛬ᗘ㸪ᮏ ヨ㦂ࡢᑐ㇟࡞ࡿᝈ⪅ᩘࡣ㸪⣙ 500㹼5,600 ே⛬ᗘᐃࡉࢀ ࡓࠋ ᮏヨ㦂࠾ࡅࡿ⤌ධࢀᮇ㛫ࡀ⣙ 2 ᖺ࡛࠶ࡿࡇ㸪⏦ㄳ⪅ࡢ⅖ᛶ⭠ᝈ㡿ᇦ㸦₽⒆ᛶ⭠⅖㸧 ࡢ㦂⤒㦂➼ࡽ㸪᪥ᮏᅜෆ࡛㦂ᐇྍ⬟࡞タࡣ 20 タ⛬ᗘ࡛࠶ࡿࡇ㸪ᅜෆ㦂ᐇᶵ 㛵࠾࠸࡚ᖺ㛫 1㹼3 ⛬ᗘࡢ⤌ධࢀࡣྍ⬟࡛࠶ࡿࡇ࡞ࢆ㋃ࡲ࠼㸪ᅜෆ࡛ 60 ⛬ᗘࡲ࡛ࡢ᪥ ᮏேᝈ⪅ࡢ㞟✚ࡣྍ⬟࡛࠶ࡿ⪃࠼ࡓࠋ ࡋࡓࡀࡗ࡚㸪๓㏙ࡢ᪥ᮏே㞟ᅋ㞟ᅋࡢ⤖ᯝࡢ୍㈏ᛶࢆ♧ࡍࡓࡵࡢ᪉ἲ 2 ࢆ‶ࡓࡍ 60 ࡢ ᪥ᮏேᝈ⪅ࡢ☜ಖࡣྍ⬟⪃࠼ࡓࡀ㸪60 ࠸࠺ᩘࡣୖグࡢᮏヨ㦂ᅜෆᑐ㇟ᝈ⪅ᩘࡢ 1%ࢆ ㉸࠼ࡿᩘ࡛࠶ࡾ㸪ᅜෆᩘࡢほⅬࡽࡶ㞟✚ࡀᐜ࡛᫆ࡣ࡞࠸ᩘᐃࡉࢀࡓࠋ
14 (3) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
௨ୖࡼࡾ㸪ᮏヨ㦂ཧຍࡋ㸪ゎᯒᑐ㇟ࡋ࡚ホ౯࡛ࡁࡿᩘࡀ 1 ⩌ 20 㸦ྜィ 60 㸧ࡢሙྜ㸪 ᪉ἲ 1 ࡛ࡣ 80㸣ࢆ‶ࡓࡍࡇࡣ࡛ࡁ࡞࠸ࡶࡢࡢ㸪᪉ἲ 2 ࠾࠸࡚⣙ 80㸣࡞ࡿࡇࡽ㸪᪥ᮏ ே㞟ᅋ㞟ᅋࡢ⤖ᯝࡢ୍㈏ᛶࢆ᳨ウࡍࡿࡇࡣྍ⬟⪃࠼ࡓࠋ
ゎᯒ ྜィ 769 ࡀࣛࣥࢲ࣒ࡉࢀࡓࡀ㸪≉᩿ࡾࡢ࡞࠸㝈ࡾ㸪ィ⏬ࡋࡓࡍ࡚ࡢゎᯒࡣ㸪ヨ㦂㛤 ᚋࣛࣥࢲ࣒ࡉࢀࡓ 741 ࢆᑐ㇟ᐇࡋࡓ㸦ࣉࣛࢭ࣎⩌㸸247 㸪ᮏ 130 mg ⩌㸸245 㸪 ᮏ㹼6 mg/kg ⩌㸸249 㸧ࠋ Ᏻᛶࡢゎᯒࡣ㸪ࣛࣥࢲ࣒ࡉࢀ㸪0 㐌┠㦂⸆ࢆᢞࡉࢀࡓ 740 ࢆᑐ㇟ࡋࡓ㸦ࣉࣛࢭ ࣎⩌ࡢ 1 ࡣ㸪ࣛࣥࢲ࣒ࡉࢀࡓࡀ㦂⸆ࢆᢞࡉࢀ࡞ࡗࡓ㸧ࠋ
(11) デ᩿ཬࡧ࡞㑅ᢥᇶ‽ ᮏヨ㦂ࡢᑐ㇟ࡣ㸪Crohn’s Disease Activity Index㸦CDAI㸧ࢫࢥࡀ 220 ௨ୖ 450 ௨ୗᐃ⩏ࡉࢀ ࡿ୰➼ࡽ㔜ࡢάືᮇࢡ࣮ࣟࣥ 3 ࢝᭶㛫௨ୖ⨯ᝈࡋ࡚࠾ࡾ㸪ࢡ࣮ࣟࣥ⒪࡛ᢎㄆࡉࢀ ࡓ⏝㔞ࡢ REMICADE®㸦ࣥࣇࣜ࢟ࢩ࣐ࣈ㸧㸪HUMIRA®㸦ࢲ࣒࣐ࣜࣈ㸧ཪࡣ CIMZIA® 㸦certolizumab pegol㸧ࢆ㐣ཤᢞࡉࢀࡓࡀ㸪୍ḟ↓ຠ࡛࠶ࡗࡓ㸪ึᮇຠᯝࢆ♧ࡋࡓࡶࡢࡢ ࡑࡢᚋຠᯝࡀᾘኻࡋࡓᝈ⪅㸪ⱝࡋࡃࡣࡇࢀࡽࡢ⸆ᑐࡋ࡚ᚸᐜᛶࡀ࡞ࡗࡓ㸪18 ṓ௨ୖࡢᝈ⪅ ࢆᑐ㇟ࡋࡓࠋࡲࡓ㸪㐣ཤ X ⥺᳨ᰝ㸪⤌⧊Ꮫⓗ᳨ᰝཪࡣෆど㙾᳨ᰝ࡛⭠⅖㸪ᅇ⭠⅖ཪࡣᅇ⤖ ⭠⅖ࡀ☜ㄆࡉࢀ࡚࠾ࡾ㸪㐣ཤ⏝࠸ࡓᢠ TNF ⸆ᑐࡋ࡚ 8 㐌㛫௨ୖࡢఇ⸆ᮇ㛫ࡀタᐃྍ⬟࡛࠶ ࡿᝈ⪅ࢆᑐ㇟ࡋࡓࠋ
(12) ⿕㦂⸆㸪⏝㔞ཬࡧᢞ᪉ἲ㸪ࣟࢵࢺ␒ྕ ᮏ㹙࢘ࢫࢸ࢟ࢾ࣐ࣈ㸦㑇ఏᏊ⤌࠼㸧㹛ࡢ㟼⬦ෆᢞ⏝〇ࡋ࡚㸪2 ⏝㔞㹙90 mg㸦⾲♧ 㔞 1 mL㸧ཪࡣ 45 mg㸦⾲♧㔞 0.5 mL㸧㹛ࡢ࢞ࣛࢫࣂࣝሸࡉࢀࡓ༢ᅇᢞ⏝㸪↓⳦ᾮ ࡀ౪⤥ࡉࢀࡓ㸦ࣂࣝࢡࣟࢵࢺ␒ྕ㸸 㸪 㸧ࠋ ᮏ〇ࡣ㸪1 mL ࠶ࡓࡾ 90 mg ࡢ࢘ࢫࢸ࢟ࢾ࣐ࣈࢆྵ᭷ࡋࡓࠋ࢘ࢫࢸ࢟ࢾ࣐ࣈࡢ㸪ྛࣂ ࣝ୰ࡢ〇ࡣ L-ࣄࢫࢳࢪࣥ㸪L-ࣄࢫࢳࢪࣥሷ㓟ሷ୍Ỉ≀㸪ࢩࣙ⢾㸪࣏ࣜࢯ࣮ࣝ࣋ࢺ 80 ࢆྵ ᭷ࡋ㸪pH ࡣ 6.0 ࡛࠶ࡗࡓࠋಖᏑࡣྵ᭷ࡋ࡚࠸࡞ࡗࡓࠋ
(13) ᑐ↷⸆㸪⏝㔞ཬࡧᢞ᪉ἲ㸪ࣟࢵࢺ␒ྕ ࣉࣛࢭ࣎ࡢ㟼⬦ෆᢞ⏝〇ࡋ࡚㸪࢞ࣛࢫࣂࣝሸࡉࢀࡓ༢ᅇᢞ⏝㸪↓⳦ᾮࡀ౪ ⤥ࡉࢀࡓ㸦ࣂࣝࢡࣟࢵࢺ␒ྕ㸸 㸪 㸧ࠋྛࣂࣝ୰ࡢ〇ࡣ L-ࣄࢫࢳࢪࣥ㸪L- ࣄࢫࢳࢪࣥሷ㓟ሷ୍Ỉ≀㸪ࢩࣙ⢾㸪࣏ࣜࢯ࣮ࣝ࣋ࢺ 80 ࢆྵ᭷ࡋ㸪pH ࡣ 6.0 ࡛࠶ࡗࡓࠋಖᏑ ࡣྵ᭷ࡋ࡚࠸࡞ࡗࡓࠋ
(14) ᢞᮇ㛫 ࡍ࡚ࡢ⿕㦂⪅ࡣ㸪0 㐌┠㸪ࣉࣛࢭ࣎㸪ᮏࡢᅛᐃ⏝㔞㸦130 mg㸧ཪࡣయ㔜ู⏝㔞㸦㹼 6 mg/kg㸧ࡢ࠸ࡎࢀࣛࣥࢲ࣒ࡾࡅࡽࢀ㸪༢ᅇ㟼⬦ෆᢞࡉࢀࡓࠋ6 㐌┠せホ౯㡯┠
15 (4) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
࡛࠶ࡿ clinical response ࢆホ౯ࡋ㸪8 㐌┠㐺᱁ࢆᐶゎ⥔ᣢヨ㦂 CNTO1275CRD3003 ⛣⾜ྍ⬟ ࡋࡓࠋᐶゎ⥔ᣢヨ㦂 CNTO1275CRD3003 ⛣⾜ࡋ࡞ࡗࡓ⿕㦂⪅ࡘ࠸࡚ࡣ㸪0 㐌┠ࡢ㦂⸆ ᢞࡽ⣙ 20 㐌㛫ᚋᏳᛶ㏣㊧ㄪᰝࢆᐇࡋࡓࠋ
(15) ホ౯㡯┠
· ⸆≀ືែ㸸⾑Ύ୰࢘ࢫࢸ࢟ࢾ࣐ࣈ⃰ᗘ
· චཎᛶ㸸ᢠ࢘ࢫࢸ࢟ࢾ࣐ࣈᢠయ
· ⸆ຊᏛ㸭ࣂ࣐࣮࣮࢜࢝㸸⾑Ύࢆ⏝࠸ࡓࣂ࣐࣮࣮࢜࢝㸪ᮎᲈ⾑ࡢ࣓ࢵࢭࣥࢪ࣮ࣕࣜ࣎᰾ 㓟㸦RNA㸧Ⓨ⌧㸪⢓⭷⏕᳨࠾ࡅࡿ RNA Ⓨ⌧ཬࡧᝈ⒵ࡢ⤌⧊Ꮫⓗホ౯㸪⾑୰ DNA ࡢゎᯒ
· ᭷ຠᛶ㸸CDAI ࢫࢥ㸪CRP ⃰ᗘ㸪౽୰ࣛࢡࢺࣇ࢙ࣜࣥཬࡧ࢝ࣝࣉࣟࢸࢡࢳࣥ⃰ᗘ㸪⒦Ꮝ ࡢホ౯㸪ቯᛶ⮋⓶ࡢホ౯㸪⭠ෆど㙾᳨ᰝ㸦⢓⭷⒵㸧㸦ᣦᐃタ࡛ྠពࡀᚓࡽࢀࡓ ⿕㦂⪅ࡢࡳ㸧
· ᝈ⪅ሗ࿌࢘ࢺ࣒࢝㸸Inflammatory Bowel Disease Questionnaire㸦IBDQ㸧㸪36-item Short- form Health Survey㸦SF-36㸧
· ་⒪⤒῭㸸་⒪㈨※ࡢ⏝㸪Productivity Visual Analog Scale㸪Work Limitations Questionnaire
· Ᏻᛶ㸸᭷ᐖ㇟㸪㔜⠜࡞᭷ᐖ㇟㸦SAE㸧㸪ࣂࢱࣝࢧࣥ㸪㦂⸆ࡢ㟼⬦ෆᢞ୰ཪ ࡣᢞᚋ 1 㛫௨ෆⓎ⌧ࡋࡓ᭷ᐖ㇟㸦௨ୗ㸪ࣥࣇ࣮ࣗࢪࣙࣥࣜࢡࢩࣙࣥ㸧㸪⮫ᗋ ᳨ᰝ㸦⾑ᾮᏛⓗ᳨ᰝཬࡧ⾑ᾮ⏕Ꮫ᳨ᰝ㸧㸪⌮Ꮫⓗᡤぢ㸪12 ㄏᑟᚰ㟁ᅗ
(16) ⤫ィᡭἲ せホ౯㡯┠ࡣ 6 㐌┠ࡢ clinical response ࡛࠶ࡾ㸪CDAI ࢫࢥ࠾ࡅࡿ࣮࣋ࢫࣛࣥࡽࡢ 100 ࣏ࣥࢺ௨ୖࡢῶᑡᐃ⩏ࡋࡓࠋ࣮࣋ࢫࣛࣥࡢ CDAI ࢫࢥࡀ 220 ௨ୖ 248 ௨ୗࡢ⿕㦂⪅ ࡘ࠸࡚ࡣ㸪CDAI ࢫࢥࡀ 150 ࣏ࣥࢺᮍ‶ࢆ㐩ᡂࡋ࡚࠸ࡓሙྜ㸪clinical response ࡀᚓࡽࢀࡓ ࡳ࡞ࡋࡓࠋ せ࡞ḟホ౯㡯┠ࡢ⤫ィᏛⓗ᳨ᐃࢆ⾜࠺㡰ࢆ௨ୗ♧ࡋࡓࠋ · 8 㐌┠ࡢ clinical remission㸦CDAI ࢫࢥ 150 ࣏ࣥࢺᮍ‶㸧
· 8 㐌┠ࡢ clinical response㸦CDAI ࢫࢥࡢ࣮࣋ࢫࣛࣥࡽࡢ 100 ࣏ࣥࢺ௨ୖࡢῶᑡ㸧 ࣮࣋ࢫࣛࣥࡢ CDAI ࢫࢥࡀ 220 ௨ୖ 248 ௨ୗࡢ⿕㦂⪅ࡘ࠸࡚ࡣ㸪CDAI ࢫࢥࡀ 150 ࣏ࣥࢺᮍ‶ࢆ㐩ᡂࡋ࡚࠸ࡓሙྜ㸪clinical response ࡀᚓࡽࢀࡓࡳ࡞ࡋࡓࠋ
· 6 㐌┠ࡢ 70-point response㸦CDAI ࢫࢥࡢ࣮࣋ࢫࣛࣥࡽࡢ 70 ࣏ࣥࢺ௨ୖࡢῶᑡ㸧
· 3 㐌┠ࡢ 70-point response㸦CDAI ࢫࢥࡢ࣮࣋ࢫࣛࣥࡽࡢ 70 ࣏ࣥࢺ௨ୖࡢῶᑡ㸧
ேཱྀ⤫ィᏛⓗ≉ᛶཬࡧ࣮࣋ࢫࣛࣥࡢᝈ≉ᛶࡢせ⣙㸪୪ࡧ᭷ຠᛶࡢゎᯒࡣ㸪ヨ㦂㛤ᚋ ࣛࣥࢲ࣒ࡉࢀࡓ 741 ࢆᑐ㇟ᐇࡋࡓࠋせホ౯㡯┠ཬࡧせ࡞ḟホ౯㡯┠ࡣ㸪୧ഃ᭷ ពỈ‽ 0.05 ࡢࡶ㸪Cochran-Mantel-Haenszel ࡢ᳨࢝ᐃࢆ⏝࠸㸪ヨ㦂ᆅᇦ㸦ࢪ㸪ᮾ࣮ࣚ
16 (5) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
ࣟࢵࣃ㸪ࡑࡢ㸧㸪CDAI ࢫࢥ㸦300 ௨ୗཪࡣ 300 ㉸㸧ཬࡧᢠ TNF ⸆⒪ᑐࡍࡿ initial response ࡢ᭷↓ࡼࡾᒙูࡋ㸪ᮏࡢྛᢞ⩌ࣉࣛࢭ࣎⩌ࢆẚ㍑ࡋࡓࠋయࡢ➨ I ✀ࡢ㐣ㄗ ࡢỈ‽ࢆ 0.05 ࢥࣥࢺ࣮ࣟࣝࡍࡿࡓࡵ㸪ヨ㦂యࡢᅛᐃ㡰ᗎἲࢆ᥇⏝ࡋ㸪せホ౯㡯┠㸪せ࡞ ḟホ౯㡯┠ࡢ㡰࡛㝵ᒙⓗ᳨ᐃࡋࡓࠋᮏヨ㦂࡛ࡣ㸪せホ౯㡯┠ࡘ࠸࡚ࣉࣛࢭ࣎⩌ẚ㍑ࡋ ࡚ᮏ㧗⏝㔞⩌᭷ពᕪࡀㄆࡵࡽࢀࡓሙྜ㸪ヨ㦂┠ⓗࡀ㐩ࡏࡽࢀࡓࡳ࡞ࡋࡓࠋ Ᏻᛶࡢゎᯒࡣ㸪ヨ㦂㛤ᚋࣛࣥࢲ࣒ࡉࢀ㸪0 㐌┠㦂⸆ࢆᢞࡉࢀࡓ 740 ࢆᑐ㇟ ࡋࡓ㸦ࣉࣛࢭ࣎⩌ࡢ 1 ࡣ㸪ࣛࣥࢲ࣒ࡉࢀࡓࡀ㸪㦂⸆ࢆᢞࡉࢀ࡞ࡗࡓ㸧ࠋࡲࡓ㸪ᮏࡢ Ᏻᛶࡣ㸪᭷ᐖ㇟ࡢ✀㢮ཬࡧⓎ⌧ྜ㸪⮫ᗋ᳨ᰝ್㸦⾑ᾮᏛⓗ᳨ᰝཬࡧ⾑ᾮ⏕Ꮫ᳨ᰝ㸧ࡢ࣋ ࣮ࢫࣛࣥࡽࡢኚ㔞ࢆせ⣙ࡍࡿࡇ࡛ホ౯ࡋࡓࠋ
(17) ⤖ᯝ 㦂ᑐ㇟㞟ᅋ ヨ㦂㛤ᚋྜィ 741 ࡀࣛࣥࢲ࣒ࡉࢀࡓ㸦ࣉࣛࢭ࣎⩌㸸247 㸪ᮏ 130 mg ⩌㸸245 㸪 ᮏ㹼6 mg/kg ⩌㸸249 㸧ࠋࡇࢀࡽࡢ⿕㦂⪅ࡢ࠺ࡕ㸪ዪᛶࡣ 424 㸦57.2%㸧㸪ⓑேࡣ 623 㸦84.1%㸧࡛࠶ࡾ㸪ᖺ㱋ࡢ୰ኸ್ࡣ 36.0 ṓ㸪య㔜ࡢ୰ኸ್ࡣ 67.0 kg ࡛࠶ࡗࡓࠋ࣮࣋ࢫࣛࣥ ࡢேཱྀ⤫ィᏛⓗ≉ᛶࡣ㸪3 ࡘࡢᢞ⩌࡛ྠᵝ࡛࠶ࡗࡓ㸦⾲ 2.7.6.2-1㸧ࠋ
17 (6) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
⾲ 2.7.6.2-1 CRD3001 ヨ㦂ࡢ࣮࣋ࢫࣛࣥࡢேཱྀ⤫ィᏛⓗ≉ᛶ 㸦ヨ㦂୰᩿๓⤌ࡳධࢀࡽࢀࡓ⿕᳨⪅ࢆ㝖ࡃ㸪 ࣛࣥࢲ࣒ࡉࢀࡓ⿕㦂⪅㸧 Ustekinumab Placebo 130 mg 6 mg/kga Combined Total Analysis set: Randomized subjects excluding those enrolled prior to study re-start 247 245 249 494 741 Age (years) N 247 245 249 494 741 Mean (SD) 37.3 (11.83) 37.4 (11.77) 37.3 (12.54) 37.4 (12.15) 37.3 (12.04) Median 36.0 37.0 36.0 36.0 36.0 IQ range (27.0; 46.0) (27.0; 45.0) (26.0; 45.0) (27.0; 45.0) (27.0; 45.0) Range (18; 71) (18; 70) (18; 71) (18; 71) (18; 71) Sex N 247 245 249 494 741 Male 118 (47.8%) 98 (40.0%) 101 (40.6%) 199 (40.3%) 317 (42.8%) Female 129 (52.2%) 147 (60.0%) 148 (59.4%) 295 (59.7%) 424 (57.2%) Race N 247 245 249 494 741 White 210 (85.0%) 202 (82.4%) 211 (84.7%) 413 (83.6%) 623 (84.1%) Black or African American 8 (3.2%) 7 (2.9%) 8 (3.2%) 15 (3.0%) 23 (3.1%) Asian 20 (8.1%) 20 (8.2%) 23 (9.2%) 43 (8.7%) 63 (8.5%) American Indian or Alaska Native 0 0 0 0 0 Native Hawaiian or other Pacific Islander 0 0 0 0 0 Other 5 (2.0%) 6 (2.4%) 3 (1.2%) 9 (1.8%) 14 (1.9%) Not Reported 4 (1.6%) 8 (3.3%) 4 (1.6%) 12 (2.4%) 16 (2.2%) Unknown 0 2 (0.8%) 0 2 (0.4%) 2 (0.3%) Weight (kg) N 247 245 249 494 741 Mean (SD) 71.51 (17.738) 68.44 (17.401) 69.46 (19.463) 68.95 (18.458) 69.80 (18.249) Median 69.10 65.90 66.00 66.00 67.00 IQ range (57.50; 82.60) (55.80; 77.50) (56.00; 79.30) (55.90; 78.00) (56.70; 80.00) Range (35.0; 141.8) (35.3; 124.0) (35.0; 172.8) (35.0; 172.8) (35.0; 172.8) Height (cm) N 247 245 249 494 741 Mean (SD) 170.65 (9.539) 168.70 (9.425) 169.66 (9.375) 169.18 (9.403) 169.67 (9.468) Median 170.00 168.00 169.30 168.90 169.00 IQ range (163.00; 176.50) (162.00; 175.00) (163.00; 175.50) (162.60; 175.30) (162.60; 175.50) Range (149.3; 197.0) (147.3; 196.0) (142.4; 196.0) (142.4; 196.0) (142.4; 197.0) a Weight-range based ustekinumab doses approximating 6 mg/kg: 260 mg (weight 55kg), 390 mg (weight > 55 kg and 85 kg), 520 mg (weight > 85 kg). [TSIDEM02.rtf] [CNTO1275\CRD3001\DBR_W8_W20\RE_W8_W20\tsidem02.sas] 16AUG2013, 15:55
ᮏヨ㦂ࢆ୰Ṇࡋࡓ 33 㸦4.5%㸧ࡢ࠺ࡕ㸪㒊ศ㸦3.1%㸪23 㸧ࡣ 8 㐌┠ࡼࡾ๓ࡢ୰Ṇ࡛࠶ࡗ ࡓ㹙ࣉࣛࢭ࣎⩌㸸2.8%㸦7 㸧㸪ᮏ 130 mg ⩌㸸2.9%㸦7 㸧㸪ᮏ㹼6 mg/kg ⩌㸸3.6%㸦9 㸧㹛ࠋ᭱ࡶከࡃሗ࿌ࡉࢀࡓ 8 㐌┠ࡼࡾ๓ࡢ୰Ṇ⌮⏤ࡣ㸪ྠព᧔ᅇ࡛࠶ࡗࡓࠋ ࣮࣋ࢫࣛࣥࡢᝈ≉ᛶࡣ㸪⌧ᅾ⏝ྍ⬟࡞⒪ἲ㸦≉ᢠ TNF ⸆㸧ࡀ᭷ຠ࡛ࡣ࡞࠸㸪㞴 ᛶࡢ୰➼ࡽ㔜ࡢࢡ࣮ࣟࣥࡢᝈ⪅㞟ᅋࢆ௦⾲ࡍࡿࡶࡢ࡛࠶ࡗࡓࠋࡲࡓ㸪࣮࣋ࢫࣛࣥ ࡢᝈ≉ᛶࡣ 3 ࡘࡢᢞ⩌࡛ྠᵝ࡛࠶ࡾ㸪࣮࣋ࢫࣛࣥࡢ⨯ᝈᮇ㛫ࡢ୰ኸ್ࡣ 10.14 ᖺ㸪CDAI ࢫࢥࡢ୰ኸ್ࡣ 317.0㸪⾑Ύ୰ CRP ⃰ᗘࡢ୰ኸ್ࡣ 9.88 mg/L ࡛࠶ࡗࡓࠋ⿕㦂⪅ࡢ 99.2% 㸦735/741 㸧ࡣ㸪㐣ཤ 1 ௨ୖࡢᢠ TNF ⸆⒪࡛ຠᯝ༑ศཪࡣᚸᐜᛶࡀ࡞࠸ࡇࡉࢀࡓࠋ ࡑࡢෆヂࡣ㸪ࣥࣇࣜ࢟ࢩ࣐ࣈࡀ 78.8%㸦584/741 㸧㸪ࢲ࣒࣐ࣜࣈࡀ 59.8%㸦443/741 㸧㸪 certolizumab pegol ࡀ 22.1%㸦164/741 㸧࡛࠶ࡗࡓࠋࡲࡓ㸪537/741 㸦72.5%㸧ࡢ⿕㦂⪅ࡀ࣮࣋
18 (7) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
ࢫࣛࣥ 1 ௨ୖࡢࢡ࣮ࣟࣥࡢ⒪ᑐࡍࡿే⏝⸆ࢆᢞࡉࢀ࡚࠾ࡾ㸪࣮࣋ࢫࣛࣥࡢ ࢡ࣮ࣟࣥ⒪⸆ࡢ⸆ศ㢮ࡈࡢే⏝⋡ࡣ㸪3 ࡘࡢᢞ⩌࡛ྠ⛬ᗘ࡛࠶ࡗࡓࠋྜィ 340/741 㸦45.9%㸧ࡀࢥࣝࢳࢥࢫࢸࣟࢻ㸦ࣈࢹࢯࢽࢻ➼㸧㸪233/741 㸦31.4%㸧ࡀචㄪ⠇⸆㸦ࢨࢳ ࢜ࣉࣜࣥ㸪6-࣓ࣝ࢝ࣉࢺࣉࣜࣥཪࡣ࣓ࢺࢺࣞ࢟ࢧ࣮ࢺ㸧ࢆᢞࡉࢀ࡚࠸ࡓࠋ
ᮏヨ㦂ࡘ࠸࡚㸪ヨ㦂㛤ᚋࡢࣉࣛࢭ࣎⩌ 130 mg ⩌ࡢ᭷ຠᛶゎᯒᑐ㇟㞟ᅋᏳᛶゎᯒᑐ ㇟㞟ᅋࡢᩘࡀ␗࡞ࡿ⌮⏤ࢆ㸪௨ୗㄝ᫂ࡍࡿࠋ ᮏヨ㦂࠾࠸࡚㸪ࡍ࡚ࡢ⿕㦂⪅ࡣ㸪Week 0 㸪ࣉࣛࢭ࣎⩌ཪࡣᐶゎᑟධ⒪ἲࡢ 2 ࡘࡢᮏ ⩌ࡢ࠸ࡎࢀࡾࡅࡽࢀࡓࠋࣉࣛࢭ࣎⩌㸦247 㸧㸪ᮏ 130 mg ⩌㸦245 㸧㸪ᮏ 6 mg/kg ⩌㸦249 㸧࡛࠶ࡗࡓ㸦࠙5.3.5.1.1ࠚCRD3001/CSR/Sec4.1.1㸧ࠋ᭷ຠᛶࡢゎᯒࡣ ITT 㸦intent-to-treat㸧ࡢཎ๎ᇶ࡙ࡁ㸪Ᏻᛶࡢゎᯒࡣᐇ㝿ࡢᢞ⩌ᇶ࡙ࡁィ⏬ࡉࢀࡓࡓࡵ㸪ࡾ ࡅࡽࢀࡓ࠾ࡾ㦂⸆ࡢᢞࢆཷࡅ࡞ࡗࡓୗグ 4 ࡼࡾ㸪ゎᯒᑐ㇟㞟ᅋࡢᩘࡀ␗࡞ࡿ 㸦࠙5.3.5.1.1ࠚCRD3001/SAP㸧ࠋ · ࣉࣛࢭ࣎⩌ࡾࡅࡽࢀࡓࡀ㦂⸆ࡢᢞࢆཷࡅ࡞ࡗࡓ 1 ࠋ
· ࣉࣛࢭ࣎⩌ࡾࡅࡽࢀࡓࡀ㸪ᐇ㝿ࡣᮏ㸦39.6 mg㸧ࢆᢞࡉࢀ㸪130 mg ⩌ࡋ࡚㸪 ⸆≀ືែཬࡧᏳᛶࡢゎᯒࡀ⾜ࢃࢀࡓ 1 ࠋ
· ᮏ 130 mg ⩌ࡾࡅࡽࢀࡓࡀ㸪ᐇ㝿ࡣ㸪㧗⏝㔞⩌㏆࠸ᢞࢆཷࡅࡓࡓࡵ㸪ᮏ 6 mg/kg ⩌ࡋ࡚㸪⸆≀ືែཬࡧᏳᛶࡢゎᯒࡀ⾜ࢃࢀࡓ 1 ࠋ࡞࠾㸪ᙜヱ⿕㦂⪅ࡢయ㔜 63.5 kg ᑐࡋᢞ㔞 219.6 mg ࡛࠶ࡗࡓࡓࡵ㸪య㔜⟬ࡢᢞ㔞ࡣ 3.5 mg/kg ࡛࠶ࡗࡓࠋ
· ᮏ 6 mg/kg ࡾࡅࡽࢀࡓࡀ㸪ᐇ㝿ࡢᢞ㔞ࡣ 3.1 mg ࡛㸪ᮏ 130 mg ⩌ࡋ࡚㸪⸆≀ ືែཬࡧᏳᛶࡢゎᯒࡀ⾜ࢃࢀࡓ 1 ࠋ࡞࠾㸪ᙜヱ⿕㦂⪅ࡣ㸪ᢞ୰᭷ᐖ㇟ࡀⓎ⌧ࡋ ࡓࡓࡵᢞࢆ୰᩿ࡋࡓࠋ
ゎᯒᑐ㇟㞟ᅋࡢෆヂ㸪୰Ṇཬࡧゎᯒᑐ㇟㞟ᅋࡽ㝖እࡉࢀࡓࢆ㸪⾲ 2.7.6.2-2 ཬࡧ⾲ 2.7.6.2-3 ♧ࡍࠋ
19 (8) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
⾲ 2.7.6.2-2 CRD3001 ヨ㦂ࡢゎᯒᑐ㇟㞟ᅋ㸦ヨ㦂య㸭᪥ᮏே㸧 Entire population Japanese population (1159 subjects) (83 subjects) Placebo 130 mg 6 mg/kg Total Placebo 130 mg 6 mg/kg Total Up to restart(82 subjects) IC - - - 82 - - - - Randomized 9 9 10 28 - - - - Treateda 9 9 10 28 - - - - Discontinuedb 2 2 0 4 - - - -
After restart IC - - - 1077 - - - 83 Randomized 247 245 249 741 18 19 19 56 Treateda 246 245 249 740 18 19 19 56 Discontinuedb 10 9 14 33 0 0 0 0 Efficacy analysis set 247 245 249 741 18 19 19 56 Safety analysis setc 245 246 249 740 18 19 19 56
All Safety analysis setc 245 246 249 740 18 19 19 56
a By planned/randomized treatment group. b Discontinued from study participation prior to Week 20(i.e. did not enter the maintenance study and did not complete Week 20 safety follow-up visit). c By actual treatment group. [TPMDASI01.rtf] [CNTO1275\CRD3003\DBR_CSR\RE_PMDA\tpmdasi01.sas] 19JUL2016, 21:14
20 (9) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
⾲ 2.7.6.2-3 CRD3001 ヨ㦂ࡢ୰Ṇཬࡧゎᯒᑐ㇟㞟ᅋࡽ㝖እࡉࢀࡓ Number Reasons (number of cases) of cases Subjects who terminated study participation before Week 20 (i.e. did not enter the maintenance study and did not complete Week 20 safety follow-up visit); Randomized Subjects Excluding Those Enrolled Prior to Study Re-start Entire Placebo 10 Withdrawal of consent (6), Lost to follow-up (2), Other (2) population 130 mg 9 Withdrawal of consent (5), Lost to follow-up (1), Other (3)
6 mg/kg 14 Withdrawal of consent (10), Lost to follow-up (2), Other (2)
Cases excluded from Efficacy analysis set; Randomized Subjects Entire Placebo 9 Enrolled Prior to Study Re-start (9) population 130 mg 9 Enrolled Prior to Study Re-start (9)
6 mg/kg 10 Enrolled Prior to Study Re-start (10)
Japanese Placebo 0 population 130 mg 0
6 mg/kg 0
Cases excluded form Safety analysis set; Treated Subjects Entire Placebo 9 Enrolled Prior to Study Re-start (9) population 130 mg 9 Enrolled Prior to Study Re-start (9)
6 mg/kg 10 Enrolled Prior to Study Re-start (10)
Japanese Placebo 0 population 130 mg 0
6 mg/kg 0
Source: 3001 CSR tables: TSIDS01; Tables for answering PMDA questions: TPMDASI01.
᭷ຠᛶ ᮏࡢᢞࡼࡾ clinical response ཬࡧ clinical remission ࡢᐶゎᑟධࡀ㐩ᡂࡉࢀࡓࠋヨ㦂యࡢ ᅛᐃ㡰ᗎἲᇶ࡙ࡁ㸪ᮏࡢ୧ᢞ⩌㸦㹼6 mg/kg ⩌ཬࡧ 130 mg ⩌㸧ࡘ࠸࡚㸪せホ౯㡯┠ཬ ࡧ 4 ࡘࡢせ࡞ḟホ౯㡯┠ࡍ࡚࡛⤫ィᏛⓗ࡞᭷ពᕪࡀ♧ࡉࢀࡓࠋ · 6 㐌┠ clinical response ࡀᚓࡽࢀࡓ⿕㦂⪅ࡢྜ㸦せホ౯㡯┠㸧ࡣ㸪ࣉࣛࢭ࣎⩌㸦21.5%㸪 53/247 㸧ẚ㍑ࡋ࡚㸪ᮏ㹼6 mg/kg ⩌㸦33.7%㸪84/249 㸧ཬࡧᮏ 130 mg ⩌㸦34.3%㸪 84/245 㸧࡛᭷ព㧗ࡗࡓ㸦ࡑࢀࡒࢀ p=0.003 ཬࡧ p=0.002㸧ࠋ
· Clinical response ࠾ࡅࡿᮏࡢຠᯝࡣ㸪㒊ศ㞟ᅋ࠾ࡅࡿゎᯒ࡛ࡶ࠾࠾ࡴࡡ୍㈏ࡋ࡚࠸ ࡓࠋ
· Clinical response ࠾ࡅࡿᮏࡢຠᯝࡣ㸪ࢹ࣮ࢱྲྀᢅ࠸つ๎ࡢ๓つᐃࡉࢀࡓኚ᭦ᑐ ࡋ࡚ࡶ㡹ᛶࢆ♧ࡋࡓࠋ
21 (10) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
· 8 㐌┠ clinical remission ࡀᚓࡽࢀࡓ⿕㦂⪅ࡢྜࡣ㸪ࣉࣛࢭ࣎⩌㸦7.3%㸪18/247 㸧 ẚ㍑ࡋ࡚ᮏ㹼6 mg/kg ⩌㸦20.9%㸪52/249 㸧ཬࡧᮏ 130 mg ⩌㸦15.9%㸪39/245 㸧࡛᭷ព㧗ࡃ㸦ࡑࢀࡒࢀ p<0.001 ཬࡧ p=0.003㸧㸪ᮏ⩌࡛ࡣ 130 mg ⩌ẚ㍑ࡋ࡚ 㹼6 mg/kg ⩌࡛㧗ࡗࡓࠋ
· Clinical remission ࠾ࡅࡿᮏࡢຠᯝࡣ㸪㒊ศ㞟ᅋ࠾ࡅࡿゎᯒ࡛ࡶ࠾࠾ࡴࡡ୍㈏ࡋ࡚ ࠸ࡓࠋ
· 8 㐌┠ clinical response ࡀᚓࡽࢀࡓ⿕㦂⪅ࡢྜࡣ㸪ࣉࣛࢭ࣎⩌㸦20.2%㸪50/247 㸧ẚ ㍑ࡋ࡚ᮏ㹼6 mg/kg ⩌㸦37.8%㸪94/249 㸧ཬࡧᮏ 130 mg ⩌㸦33.5%㸪82/245 㸧࡛᭷ ព㧗ࡗࡓ㸦ࡑࢀࡒࢀ p<0.001 ཬࡧ p=0.001㸧ࠋ
· 6 㐌┠ 70-point response ࡀᚓࡽࢀࡓ⿕㦂⪅ࡢྜࡣ㸪ࣉࣛࢭ࣎⩌㸦30.4%㸪75/247 㸧 ẚ㍑ࡋ࡚ᮏ㹼6 mg/kg ⩌㸦43.8%㸪109/249 㸧ཬࡧᮏ 130 mg ⩌㸦46.1%㸪113/245 㸧 ࡛᭷ព㧗ࡗࡓ㸦ࡑࢀࡒࢀ p=0.002 ཬࡧ p<0.001㸧ࠋ
· 3 㐌┠ 70-point response ࡀᚓࡽࢀࡓ⿕㦂⪅ࡢྜࡣ㸪ࣉࣛࢭ࣎⩌㸦27.1%㸪67/247 㸧 ẚ㍑ࡋ࡚ᮏ㹼6 mg/kg ⩌㸦40.6%㸪101/249 㸧ཬࡧᮏ 130 mg ⩌㸦38.4%㸪94/245 㸧࡛ ᭷ព㧗ࡗࡓ㸦ࡑࢀࡒࢀ p=0.001 ཬࡧ p=0.009㸧
· 3㸪6 ཬࡧ 8 㐌┠࠾ࡅࡿ CDAI ࢫࢥࡢ࣮࣋ࢫࣛࣥࡽࡢῶᑡ㔞ࡢ୰ኸ್ࡣ㸪ࣉࣛࢭ࣎ ⩌ẚ㍑ࡋ࡚ᮏ㹼6 mg/kg ⩌ཬࡧᮏ 130 mg ⩌࡛᭷ពࡁࡗࡓ㸦࠸ࡎࢀࡶ p<0.001㸧ࠋ
· 3 㐌┠࠾ࡅࡿ CDAI ࢫࢥࡢῶᑡ㔞ࡢ୰ኸ್ࡣ㸪ࣉࣛࢭ࣎⩌࡛ࡣ 22.0 ࡛࠶ࡿࡢᑐࡋ㸪 ᮏ㹼6 mg/kg ⩌࡛ 53.0 ཬࡧᮏ 130 mg ⩌࡛ 50.0 ࡛࠶ࡗࡓࠋ
· 6 㐌┠࡛ࡣ㸪ࡍ࡚ࡢᢞ⩌࠾࠸࡚ CDAI ࢫࢥࡢ୰ኸ್᭦࡞ࡿῶᑡࡀㄆࡵࡽࢀ㸪 ࡑࡢῶᑡ㔞ࡢ୰ኸ್ࡣ㸪ᮏ㹼6 mg/kg ⩌࡛ 59.0㸪ᮏ 130 mg ⩌࡛ 63.0㸪ࣉࣛࢭ࣎⩌࡛ 32.0 ࡛࠶ࡗࡓࠋ
· 8 㐌┠࡛ࡣ㸪CDAI ࢫࢥࡢ࣮࣋ࢫࣛࣥࡽࡢኚ㔞࡛♧ࡉࢀࡿ⒪ຠᯝࡣ㸪ࣉࣛࢭ ࣎⩌ẚ㍑ࡋ࡚ᮏࡢ୧ᢞ⩌࡛ࡁࡗࡓࠋCDAI ࢫࢥࡢῶᑡ㔞ࡢ୰ኸ್ࡣ㸪ᮏ ⩌࡛ࡣ 130 mg ⩌㸦55.0㸧ẚ㍑ࡋ࡚㹼6 mg/kg ⩌㸦69.0㸧࡛ࡁࡃ㸪ࣉࣛࢭ࣎⩌࡛ࡣ 17.0 ࡛࠶ࡗࡓࠋ
· 3㸪6 ཬࡧ 8 㐌┠࡛ࡣ㸪CRP ⃰ᗘࡢ࣮࣋ࢫࣛࣥࡽࡢῶᑡ㔞ࡢᖹᆒ್ࡣ㸪ࣉࣛࢭ࣎⩌ẚ ㍑ࡋ࡚ᮏࡢ୧ᢞ⩌࡛᭷ពࡁࡃ㸪ࡲࡓ CRP ⃰ᗘࡀṇᖖࡋࡓ⿕㦂⪅ࡢྜࡀ᭷ព 㧗ࡗࡓࠋ
· 6 㐌┠࡛ࡣ㸪౽୰ࣛࢡࢺࣇ࢙ࣜࣥཬࡧ࢝ࣝࣉࣟࢸࢡࢳࣥ⃰ᗘࡢ࣮࣋ࢫࣛࣥࡽࡢῶᑡ㔞 ࡢ୰ኸ್ࡣ㸪ࣉࣛࢭ࣎⩌ẚ㍑ࡋ࡚ᮏࡢ୧ᢞ⩌࡛᭷ពࡁࡃ㸪ࡲࡓ౽୰ࣛࢡࢺࣇ࢙ ࣜࣥཬࡧ࢝ࣝࣉࣟࢸࢡࢳࣥ⃰ᗘࡀṇᖖࡋࡓ⿕㦂⪅ࡢྜࡀ᭷ព㧗ࡗࡓࠋ
· ⾑Ύ୰࢘ࢫࢸ࢟ࢾ࣐ࣈ⃰ᗘࡢᅄศᩘ࡛༊ศࡋ࡚ホ౯ࡋࡓ⤖ᯝ㸪⾑Ύ୰࢘ࢫࢸ࢟ࢾ࣐ࣈ⃰ ᗘࡀ୰ኸ್ࢆ㉸࠼ࡿ⿕㦂⪅㞟ᅋ࡛㸪8 㐌┠ࡢ clinical remission ࡀᚓࡽࢀࡓ⿕㦂⪅ࡢྜࡀ㧗 ࡗࡓࠋࡋࡋ㸪ࡇࡢഴྥࡣ 6 㐌┠ཬࡧ 8 㐌┠ࡢ clinical response㸪ཪࡣ 6 㐌┠ࡢ CDAI ࢫࢥ
22 (11) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
ࡢኚ㔞࡛ࡣ᫂☜࡛ࡣ࡞ࡗࡓࠋCRP ⃰ᗘࡣ㸪⾑Ύ୰࢘ࢫࢸ࢟ࢾ࣐ࣈ⃰ᗘࡀ㧗࠸ప ୗࡍࡿഴྥࡀㄆࡵࡽࢀࡓࠋ
ᝈ⪅ሗ࿌࢘ࢺ࣒࢝ཬࡧ་⒪⤒῭ · 8 㐌┠࠾ࡅࡿ IBDQ ࢫࢥࡢ࣮࣋ࢫࣛࣥࡽࡢኚ㔞㸦ᖹᆒ್±SD㸧ࡣ㸪ࣉࣛࢭ࣎⩌ 㸦11.9±26.51㸧ẚ㍑ࡋ࡚ᮏ㹼6 mg/kg ⩌㸦22.1±28.59㸧ཬࡧᮏ 130 mg ⩌㸦18.1±28.02㸧 ࡛᭷ពࡁࡗࡓ㸦ࡑࢀࡒࢀ p<0.001 ཬࡧ p=0.013㸧ࠋ᭦㸪8 㐌┠ࡢ IBDQ ࢫࢥ࠾ ࠸࡚㸪࣮࣋ࢫࣛࣥࡽ 16 ࣏ࣥࢺ௨ୖࡢᨵၿࡀᚓࡽࢀࡓ⿕㦂⪅ࡢྜࡣ㸪ࣉࣛࢭ࣎⩌ 㸦36.5%㸪89/244 㸧ẚ㍑ࡋ࡚ᮏ㹼6 mg/kg ⩌㸦54.8%㸪136/248 㸧ཬࡧᮏ 130 mg ⩌ 㸦46.9%㸪114/243 㸧࡛᭷ព㧗ࡃ㸪ᗣ㛵㐃 QOL ࡢᨵၿࡀ♧ࡉࢀࡓࠋࡲࡓ㸪16 ࣏ࣥ ࢺ௨ୖࡢᨵၿࡀᚓࡽࢀࡓ⿕㦂⪅ࡢྜࡣ㸪ᮏ⩌࡛ࡣ 130 mg ⩌ẚ㍑ࡋ࡚㹼6 mg/kg ⩌࡛ 㧗ࡗࡓࠋ
· 8 㐌┠࡛ࡣ㸪ࣉࣛࢭ࣎⩌ẚ㍑ࡋ࡚ᮏ⩌࡛ SF-36 ࡢ㌟యⓗഃ㠃ࡢ QOL ࢧ࣐࣮ࣜ㸦PCS㸧 ཬࡧ⢭⚄ⓗഃ㠃ࡢ QOL ࢧ࣐࣮ࣜ㸦MCS㸧ࡢᩘ್ࡢᨵၿࡀㄆࡵࡽࢀ㸪≉ᮏ㹼6 mg/kg ⩌ ࡢ MCS ࠾࠸࡚㸪࣮࣋ࢫࣛࣥࡽࡢኚ㔞㸦p=0.006㸧ཬࡧ 5 ࣏ࣥࢺ௨ୖࡢᨵၿࢆ㐩 ᡂࡋࡓ⿕㦂⪅ࡢྜ㸦p=0.007㸧࡛㢧ⴭ࡛࠶ࡗࡓࠋ
· 8 㐌┠ࡲ࡛ࢡ࣮ࣟࣥ㛵㐃ࡢධ㝔ཬࡧᡭ⾡ࢆཷࡅࡓ⿕㦂⪅ࡣࡍ࡚ࡢᢞ⩌࡛ᑡ࡞ࡃ㸪8 㐌┠ࡲ࡛ࢡ࣮ࣟࣥ㛵㐃ࡢᡭ⾡ࢆཷࡅࡓ⿕㦂⪅ᩘࡣࣉࣛࢭ࣎⩌ẚ㍑ࡋ࡚ᮏ⩌࡛ᑡ࡞ ࡗࡓࠋ
⸆≀ືែཬࡧචཎᛶ · ᮏࡢᅛᐃ⏝㔞㸦130 mg㸧ཪࡣయ㔜ู⏝㔞㸦㹼6 mg/kg㸧ࡢ༢ᅇ㟼⬦ෆᢞᚋ㸪⾑Ύ୰࢘ࢫ ࢸ࢟ࢾ࣐ࣈ⃰ᗘࡢ୰ኸ್ࡣࡰ⏝㔞ẚᛶࢆ♧ࡋ㸪8 㐌┠ࡲ࡛ࡢࡍ࡚ࡢ᳨య᥇ྲྀᮇ࡛ ᳨ฟྍ⬟࡛࠶ࡗࡓࠋ0 㐌┠ࡢᢞ 1 㛫ᚋ࠾ࡅࡿ᭱㧗⾑Ύ୰࢘ࢫࢸ࢟ࢾ࣐ࣈ⃰ᗘࡢ୰ኸ್ ࡣ㸪ᮏ 130 mg ⩌࡛ 43.6 ȝg/mL㸪ᮏ㹼6 mg/kg ⩌࡛ 129.1 ȝg/mL ࡛࠶ࡗࡓࠋࡲࡓ㸪8 㐌┠ ࡢᐶゎᑟධ⤊ࡢ⾑Ύ୰࢘ࢫࢸ࢟ࢾ࣐ࣈ⃰ᗘࡢ୰ኸ್ࡣ㸪ᮏ 130 mg ⩌࡛ 2.1 ȝg/mL㸪 ᮏ㹼6 mg/kg ⩌࡛ 6.4 ȝg/mL ࡛࠶ࡗࡓࠋ
· ᮏࡢయ㔜ู⏝㔞㸦㹼6 mg/kg㸧ࡀᢞࡉࢀࡓ⿕㦂⪅࡛ࡣ㸪࢘ࢫࢸ࢟ࢾ࣐ࣈࡢᢞ㔞㸦⤯ᑐ 㔞㸧ࡢቑຍࡋࡓࡀࡗ࡚㸪⾑Ύ୰࢘ࢫࢸ࢟ࢾ࣐ࣈ⃰ᗘࡢ୰ኸ್ࡀ㧗ࡃ࡞ࡿഴྥࡀㄆࡵࡽࢀ ࡓࠋᐶゎᑟධ⒪ἲࡋ࡚ᮏࡢᅛᐃ⏝㔞㸦130 mg㸧ࡀ㟼⬦ෆᢞࡉࢀࡓ⿕㦂⪅࡛ࡣ㸪⾑Ύ ୰࢘ࢫࢸ࢟ࢾ࣐ࣈ⃰ᗘࡣయ㔜ࢃࡽࡎྠ⛬ᗘ࡛࠶ࡗࡓࠋࡇࡢ 8 㐌㛫ࡢヨ㦂⤌ࡳධࢀ ࡽࢀࡓ⿕㦂⪅ࡢయ㔜ࡢ⠊ᅖ࡛ࡣ㸪⾑Ύ୰࢘ࢫࢸ࢟ࢾ࣐ࣈ⃰ᗘయ㔜┤⥺ⓗ࡞㛵ಀࡣㄆࡵ ࡽࢀ࡞ࡗࡓࠋ
· ᮏࡀᢞࡉࢀ㸪ᢠ࢘ࢫࢸ࢟ࢾ࣐ࣈᢠయホ౯ࡢࡓࡵࡢ᳨యࡀ㐺ษ᥇ྲྀࡉࢀࡓ 484 ࡢ࠺ ࡕ㸪20 㐌┠ࡢᏳᛶࡢ᭱⤊ホ౯ࡲ࡛ᢠ࢘ࢫࢸ࢟ࢾ࣐ࣈᢠయࡀ㝧ᛶ࡛࠶ࡗࡓ⿕㦂⪅ࡣ 1 㸦0.2%㸧ࡢࡳ࡛࠶ࡗࡓࠋ
23 (12) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
Ᏻᛶ ᭷ᐖ㇟ࡢࢹ࣮ࢱࢆ 2.7.6.2.2 㸪㔜⠜࡞᭷ᐖ㇟ࡢヲ⣽ࢆ 2.7.6.2.3 ♧ࡍࠋ
· ᮏࡢᅛᐃ⏝㔞㸦130 mg㸧ཪࡣయ㔜ู⏝㔞㸦㹼6 mg/kg㸧ࡢ㟼⬦ෆᢞࡢᚸᐜᛶࡣⰋዲ࡛࠶ ࡾ㸪8 㐌┠ࡲ࡛ࡢᏳᛶࣉࣟࣇࣝࡣ⯡ⓗࣉࣛࢭ࣎⩌ྠᵝ࡛࠶ࡗࡓࠋ
· ᭷ᐖ㇟ࡼࡾ୰Ṇࡋࡓ⿕㦂⪅ࡣ㸪ࣉࣛࢭ࣎⩌࡛ࡣ 14/245 㸦5.7%㸧࡛࠶ࡾ㸪ᮏ 130 mg ⩌࡛ࡣ 3/246 㸦1.2%㸧㸪ᮏ㹼6 mg/kg ⩌࡛ࡣ 7/249 㸦2.8%㸧࡛࠶ࡗࡓࠋ᭱ࡶከࡃㄆࡵ ࡽࢀࡓ୰Ṇ⮳ࡗࡓ᭷ᐖ㇟ࡣ࠸ࡎࢀࡢᢞ⩌࡛ࡶࢡ࣮࡛ࣟࣥ࠶ࡾ㸪ࡑࡢⓎ⌧ᩘࡣࣉ ࣛࢭ࣎⩌࡛ 11 㸪ᮏ 130 mg ⩌࡛ 2 㸪ᮏ㹼6 mg/kg ⩌࡛ 1 ࡛࠶ࡗࡓࠋ
· ࢡ࣮ࣟࣥࢆ㝖ࡁ㸪࠸ࡎࢀࡢᢞ⩌࡛ࡶ 8 㐌┠ࡲ࡛ࡢ SAE ࡢⓎ⌧ࡣࡲࢀ࡛࠶ࡗࡓࠋ࠸ࡎࢀ ࡢᮏ⩌࡛ࡶ 2 ௨ୖⓎ⌧ࡋࡓ SAE ࡣ࡞ࡗࡓࠋ
· Ṛஸཬࡧ㦂ᢸᙜ་ᖌࡼࡾሗ࿌ࡉࢀࡓせᚰ⾑⟶࣋ࣥࢺࡣ࡞ࡗࡓࠋ20 㐌┠ࡢᏳᛶ ㏣㊧ㄪᰝᚋ㸪ᮏ㹼6 mg/kg ⩌ࡢ⿕㦂⪅ 1 ࠾࠸࡚㸪1 ௳ࡢᝏᛶ⭘⒆㸦ከⓎᛶ㦵㧊⭘㸧ࡀ ሗ࿌ࡉࢀࡓࠋ
· 8 㐌┠ࡲ࡛ឤᰁࢆⓎ⌧ࡋࡓ⿕㦂⪅ࡢྜࡣࡍ࡚ࡢᢞ⩌࡛ྠ⛬ᗘ࡛࠶ࡗࡓࡀ㸪㔜⠜ ࡞ឤᰁࡣᮏ 130 mg ⩌ཬࡧࣉࣛࢭ࣎⩌ẚ㍑ࡋ࡚ᮏ㹼6 mg/kg ⩌࡛ከࡃሗ࿌ࡉࢀࡓࠋ
· ᮏヨ㦂୰άືᛶ⤖᰾ࢆⓎ⌧ࡋࡓ⿕㦂⪅ࡣሗ࿌ࡉࢀ࡞ࡗࡓࠋᮏ㹼6 mg/kg ⩌࡛᪥ぢឤ ᰁ㸦ࣜࢫࢸࣜ⳦ᛶ㧊⭷⅖㸧ࡀ 1 ࠾࠸࡚ 1 ௳ሗ࿌ࡉࢀࡓࠋ
· ࢼࣇࣛ࢟ࢩ࣮ཪࡣ⾑Ύᵝᛂࡣሗ࿌ࡉࢀ࡞ࡗࡓࠋࣥࣇ࣮ࣗࢪࣙࣥࣜࢡࢩࣙࣥ ࡢⓎ⌧ྜࡣ㸪ࣉࣛࢭ࣎⩌ẚ㍑ࡋ࡚ᮏ⩌࡛ࢃࡎ㧗ࡗࡓࠋࡋࡋ㸪Ⓨ⌧ࡣࡲࢀ࡛ ᮏేྜ⩌࡛Ⓨ⌧ྜࡀ 1%㉸ࡢࣥࣇ࣮ࣗࢪࣙࣥࣜࢡࢩࣙࣥࡣ࡞ࡃ㸪࠸ࡎࢀࡶ㠀㔜⠜࡛ ࠶ࡗࡓࠋ
· ⾑ᾮᏛⓗ᳨ᰝ࠾࠸࡚㢧ⴭ࡞␗ᖖኚືࡀᩘࡢ⿕㦂⪅࡛ㄆࡵࡽࢀ㸪᭱ࡶከࡃㄆࡵࡽࢀࡓ㢧 ⴭ࡞␗ᖖኚື㸦2 ௨ୖࡢ⿕㦂⪅ 2 ᅇ௨ୖⓎ⌧㸧ࡣࣜࣥࣃ⌫⤯ᑐᩘῶᑡ࡛࠶ࡗࡓ㹙ࣉࣛࢭ ࣎⩌㸸 5.3%㸦13/243 㸧㸪ᮏ 130 mg ⩌㸸2.9%㸦7/243 㸧㸪ᮏ㹼6 mg/kg ⩌㸸4.0% 㸦10/248 㸧㹛ࠋ⾑ᾮ⏕Ꮫ᳨ᰝ࠾࠸࡚᭱ࡶከࡃㄆࡵࡽࢀࡓ㢧ⴭ࡞␗ᖖኚື㸦࠸ࡎࢀ ࡢᢞ⩌࡛ 2 ௨ୖࡢ⿕㦂⪅ 2 ᅇ௨ୖⓎ⌧㸧ࡣࣝࣈ࣑ࣥῶᑡࡢࡳ࡛࠶ࡗࡓ㹙ࣉࣛࢭ࣎ ⩌࡛ 2/243 㸦0.8%㸧ࡢࡳ㸪ᮏ⩌࡛ࡢヱᙜ࡞ࡋ㹛ࠋ
⤖ㄽ · ᮏヨ㦂㸦CNTO1275CRD3001 ヨ㦂㸧ࡢ⤖ᯝࡼࡾ㸪ᢠ TNF ⸆⒪࡛ຠᯝ༑ศཪࡣᚸᐜᛶࡢ ࡞࠸୰➼ࡽ㔜ࡢᡂேࢡ࣮ࣟࣥᝈ⪅࠾࠸࡚㸪᳨ウࡋࡓᮏ 2 ⏝㔞ࡼࡿᐶゎᑟධ ࡢ clinical response ཬࡧ clinical remission ࡛ࡢ᭷ຠᛶࡀ୍㈏ࡋ࡚᫂☜♧ࡉࢀࡓࠋ
· ୰➼ࡽ㔜ࡢᡂேࢡ࣮ࣟࣥᝈ⪅㞟ᅋ࠾࠸࡚㸪ᮏࡢ᭱ 6 mg/kg ࡲ࡛ࡢ༢ᅇ㟼⬦ ෆᢞࡼࡿᐶゎᑟධ⒪ἲࡢᚸᐜᛶࡣ㸪8 㐌㛫ࢃࡓࡾ⯡ⓗⰋዲ࡛࠶ࡗࡓࠋ
24 (13) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
· ᮏヨ㦂ࡢᏳᛶཬࡧ᭷ຠᛶࢹ࣮ࢱࡣ㸪୰➼ࡽ㔜ࡢᡂேࢡ࣮ࣟࣥᝈ⪅㞟ᅋ࠾࠸࡚ ᳨ウࡋࡓᮏ 2 ⏝㔞ࡢ㟼⬦ෆᢞࡼࡿᐶゎᑟධ⒪ἲᑐࡋ㸪࣋ࢿࣇࢵࢺࡀࣜࢫࢡࢆୖ ᅇࡿࡇࢆ♧ࡍࡶࡢ࡛࠶ࡗࡓࠋ
25 (14) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
2.7.6.2.2 ᭷ᐖ㇟ࡢࢹ࣮ࢱ
(1) ᭷ᐖ㇟ࡢⓎ⌧ྜ㸦ヨ㦂୰᩿๓⤌ࡳධࢀࡽࢀࡓ⿕㦂⪅ࢆ㝖ࡃ㸧㸦8 㐌┠ࡲ࡛㸧
⾲ 2.7.6.2-4 ᭷ᐖ㇟ࡢⓎ⌧ྜ㸦ᅉᯝ㛵ಀࢆၥࢃ࡞࠸ࡍ࡚ࡢ᭷ᐖ㇟㸭 㦂⸆ྜ⌮ⓗ㛵㐃ᛶࡀ࠶ࡿ᭷ᐖ㇟㸧㸦㦂⸆ࢆᢞࡉࢀࡓ⿕㦂⪅㸧 All TEAEs Reasonably related TEAEs Placebo Ustekinumab a Placebo Ustekinumab a Analysis Set: Treated Subjects Excluding Those Enrolled Prior to Study Re-start 245 495 245 495
Total number of subjects with TEAEs 159 (64.9%) 323 (65.3%) 67 (27.3%) 134 (27.1%)
System-organ class/preferred term ⫶⭠㞀ᐖ 79 (32.2%) 123 (24.8%) 22 (9.0%) 26 (5.3%) ᝏᚰ 18 (7.3%) 33 (6.7%) 9 (3.7%) 7 (1.4%) ⭡③ 13 (5.3%) 22 (4.4%) 6 (2.4%) 3 (0.6%) ྤ 9 (3.7%) 20 (4.0%) 2 (0.8%) 8 (1.6%) ࢡ࣮ࣟࣥ 24 (9.8%) 19 (3.8%) 4 (1.6%) 0 ౽⛎ 2 (0.8%) 9 (1.8%) 0 3 (0.6%) ୖ⭡㒊③ 1 (0.4%) 7 (1.4%) 0 2 (0.4%) ⫠ 0 5 (1.0%) 0 0 ୗ⑩ 9 (3.7%) 5 (1.0%) 2 (0.8%) 0 ⭡㒊⭾‶ 2 (0.8%) 4 (0.8%) 1 (0.4%) 0 ᾘⰋ 3 (1.2%) 4 (0.8%) 1 (0.4%) 0 ṑ③ 0 4 (0.8%) 0 0 ୗ⭡㒊③ 0 3 (0.6%) 0 0 ࣇࢱᛶཱྀෆ⅖ 2 (0.8%) 3 (0.6%) 0 2 (0.4%) 㰘⭠ 1 (0.4%) 3 (0.6%) 0 1 (0.2%) ཱྀࡢ㘒ឤぬ 0 3 (0.6%) 0 2 (0.4%) ⒦ 4 (1.6%) 2 (0.4%) 0 0 ⭠⟶⓶⒦ 0 2 (0.4%) 0 1 (0.2%) ⯉③ 0 2 (0.4%) 0 1 (0.2%) ᰾ 2 (0.8%) 2 (0.4%) 0 0 ⫠㛛࿘ᅖ③ 2 (0.8%) 2 (0.4%) 0 0 ┤⭠ 1 (0.4%) 2 (0.4%) 0 0 ┤⭠ฟ⾑ 3 (1.2%) 2 (0.4%) 0 0 ⭡㒊ᅽ③ 1 (0.4%) 1 (0.2%) 0 0 ⫠㛛┤⭠ᛌឤ 1 (0.4%) 1 (0.2%) 0 0 ⫠㛛┤⭠㞀ᐖ 0 1 (0.2%) 0 0 ⫠㛛┤⭠⊃✽ 0 1 (0.2%) 0 0 ⤖⭠⒦ 0 1 (0.2%) 0 1 (0.2%) 㱘ṑ 0 1 (0.2%) 0 0 ཱྀෆ⇱ 2 (0.8%) 1 (0.2%) 1 (0.4%) 1 (0.2%) ༑ᣦ⭠⫶㏫ὶ 0 1 (0.2%) 0 0 ฟ⾑ᛶ⫶₽⒆ 0 1 (0.2%) 0 0 ⫶㣗㐨㏫ὶᛶᝈ 1 (0.4%) 1 (0.2%) 0 0 ⾑౽ἥ 1 (0.4%) 1 (0.2%) 0 0 㰢ᚄ࣊ࣝࢽ 0 1 (0.2%) 0 0 ⭠⟶⊃✽ 0 1 (0.2%) 0 0 ᑠ⭠㛢ሰ 0 1 (0.2%) 0 0 ⬡⫫౽ 0 1 (0.2%) 0 0 ⭡㒊ᛌឤ 2 (0.8%) 0 1 (0.4%) 0 ⭠⅖ 1 (0.4%) 0 0 0 ⾑ᛶୗ⑩ 1 (0.4%) 0 1 (0.4%) 0 ౽ᅇᩘቑຍ 1 (0.4%) 0 1 (0.4%) 0 ṑ⫗㏥⦰ 1 (0.4%) 0 0 0
26 (15) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
All TEAEs Reasonably related TEAEs Placebo Ustekinumab a Placebo Ustekinumab a ⭠✸Ꮝ 1 (0.4%) 0 0 0 ཱྀ⭍ෆ₽⒆ᙧᡂ 2 (0.8%) 0 1 (0.4%) 0 ཱྀ⭍㞀ᐖ 1 (0.4%) 0 1 (0.4%) 0 ཱྀ⅖ 1 (0.4%) 0 1 (0.4%) 0 ࣞࢵࢳࣥࢢ 1 (0.4%) 0 0 0 ཱྀෆ⅖ 1 (0.4%) 0 0 0 ឤᰁ࠾ࡼࡧᐤ⏕ 55 (22.4%) 120 (24.2%) 17 (6.9%) 45 (9.1%) 㰯ဗ㢌⅖ 13 (5.3%) 23 (4.6%) 4 (1.6%) 7 (1.4%) ୖẼ㐨ឤᰁ 9 (3.7%) 22 (4.4%) 4 (1.6%) 7 (1.4%) ⫶⭠⅖ 4 (1.6%) 7 (1.4%) 1 (0.4%) 0 ࢘ࣝࢫᛶ⫶⭠⅖ 0 5 (1.0%) 0 1 (0.2%) ࣥࣇ࢚ࣝࣥࢨ 0 5 (1.0%) 0 2 (0.4%) ཱྀ⭍࣊ࣝ࣌ࢫ 1 (0.4%) 5 (1.0%) 0 3 (0.6%) ⫠㛛⮋⒆ 5 (2.0%) 4 (0.8%) 1 (0.4%) 1 (0.2%) እ㝜⭐┿⳦ឤᰁ 2 (0.8%) 4 (0.8%) 1 (0.4%) 3 (0.6%) Ẽ⟶ᨭ⅖ 4 (1.6%) 3 (0.6%) 1 (0.4%) 1 (0.2%) ⻏ᕢ⅖ 0 3 (0.6%) 0 0 ࢡࣟࢫࢺࣜࢪ࣒࢘ឤᰁ 0 3 (0.6%) 0 0 ୗẼ㐨ឤᰁ 2 (0.8%) 3 (0.6%) 0 2 (0.4%) 㰯⭍⅖ 6 (2.4%) 3 (0.6%) 1 (0.4%) 0 ᒀ㊰ឤᰁ 2 (0.8%) 3 (0.6%) 0 1 (0.2%) ẟໟ⅖ 0 2 (0.4%) 0 0 㰢ᚄ㒊⮋⒆ 0 2 (0.4%) 0 1 (0.2%) ဗ㢌⅖ 0 2 (0.4%) 0 1 (0.2%) ⮋⑁ᛶ⓶⑈ 0 2 (0.4%) 0 1 (0.2%) እ㝜㒊⭐࢝ࣥࢪࢲ 0 2 (0.4%) 0 2 (0.4%) ⭠⟶⮋⒆ 0 1 (0.2%) 0 1 (0.2%) ⮋⑁ᛶࡊ⒔ 0 1 (0.2%) 0 0 ᛴᛶᡥ᱈⅖ 0 1 (0.2%) 0 0 ⒦ឤᰁ 0 1 (0.2%) 0 0 ࢘ࣝࢫᛶ⤖⭷⅖ 0 1 (0.2%) 0 1 (0.2%) ⭤⬔⅖ 0 1 (0.2%) 0 1 (0.2%) ឤᰁᛶ⓶⅖ 0 1 (0.2%) 0 0 ⪥ឤᰁ 1 (0.4%) 1 (0.2%) 0 1 (0.2%) ẘ 0 1 (0.2%) 0 0 ⭠⳦ᛶᩋ⾑ 0 1 (0.2%) 0 0 ⓶┿⳦ឤᰁ 2 (0.8%) 1 (0.2%) 0 1 (0.2%) ᾘ⟶ឤᰁ 0 1 (0.2%) 0 0 ṑ⫗⅖ 0 1 (0.2%) 0 0 ༢⣧࣊ࣝ࣌ࢫ 1 (0.4%) 1 (0.2%) 0 1 (0.2%) ᖏ≧⑁⑈ 0 1 (0.2%) 0 1 (0.2%) ᳝㛫ᯈ⅖ 0 1 (0.2%) 0 0 ࣜࢫࢸࣜ⳦ᛶ㧊⭷⅖ 0 1 (0.2%) 0 1 (0.2%) ∎┿⳦ 0 1 (0.2%) 0 0 ཱྀ⭍࢝ࣥࢪࢲ 0 1 (0.2%) 0 1 (0.2%) እ⪥⅖ 1 (0.4%) 1 (0.2%) 0 0 ∎ᅖ⅖ 0 1 (0.2%) 0 0 㦵┙⮋⒆ 0 1 (0.2%) 0 0 ⫢࿘ᅖ⮋⒆ 0 1 (0.2%) 0 0 㝜⮋⒆ 0 1 (0.2%) 0 0 ⭡⭷⅖ 0 1 (0.2%) 0 0 ẟᕢᄞ⬊ 0 1 (0.2%) 0 0 ⭜➽⮋⒆ 0 1 (0.2%) 0 0 ṑ㧊⅖ 0 1 (0.2%) 0 0 Ẽ㐨ឤᰁ 0 1 (0.2%) 0 0 ⓶ୗ⤌⧊⮋⒆ 0 1 (0.2%) 0 1 (0.2%) ᡥ᱈⅖ 0 1 (0.2%) 0 0 ṑ⮋⒆ 1 (0.4%) 1 (0.2%) 0 0 ⭠⌫⳦ᛶᒀ㊰ឤᰁ 0 1 (0.2%) 0 1 (0.2%)
27 (16) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
All TEAEs Reasonably related TEAEs Placebo Ustekinumab a Placebo Ustekinumab a ࢘ࣝࢫឤᰁ 1 (0.4%) 1 (0.2%) 0 0 ࢘ࣝࢫᛶဗ㢌⅖ 0 1 (0.2%) 0 0 ࢘ࣝࢫᛶୖẼ㐨ឤᰁ 0 1 (0.2%) 0 0 እ㝜㒊⮋⒆ 0 1 (0.2%) 0 0 እ㝜㒊⅖ 0 1 (0.2%) 0 1 (0.2%) ཱྀ⭍⮋⒆ 2 (0.8%) 0 1 (0.4%) 0 ⮋⑈ 1 (0.4%) 0 0 0 ឤᰁᛶ⒦Ꮝ 2 (0.8%) 0 1 (0.4%) 0 㝈ᒁᛶឤᰁ 1 (0.4%) 0 0 0 ⢭ᕢ⅖ 1 (0.4%) 0 0 0 ࢘ࣝࢫᛶ⫵⅖ 1 (0.4%) 0 1 (0.4%) 0 㰯⅖ 1 (0.4%) 0 0 0 ṑឤᰁ 1 (0.4%) 0 1 (0.4%) 0 ➽㦵᱁⣔࠾ࡼࡧ⤖ྜ⤌⧊㞀ᐖ 39 (15.9%) 83 (16.8%) 6 (2.4%) 20 (4.0%) 㛵⠇③ 18 (7.3%) 41 (8.3%) 3 (1.2%) 6 (1.2%) ⫼㒊③ 6 (2.4%) 10 (2.0%) 0 1 (0.2%) ➽⫗③ 1 (0.4%) 8 (1.6%) 0 5 (1.0%) ᅄ⫥③ 1 (0.4%) 6 (1.2%) 0 3 (0.6%) 㛵⠇⅖ 3 (1.2%) 5 (1.0%) 0 1 (0.2%) ➽②⦰ 2 (0.8%) 5 (1.0%) 0 1 (0.2%) ➽㦵᱁③ 0 3 (0.6%) 0 1 (0.2%) ഃ⭡㒊③ 1 (0.4%) 2 (0.4%) 0 0 ➽㦵᱁⣔⬚③ 1 (0.4%) 2 (0.4%) 0 1 (0.2%) 㢡③ 0 2 (0.4%) 0 0 ⭠⅖ᛶ㛵⠇⅖ 1 (0.4%) 1 (0.2%) 0 0 ⒦Ꮝ 0 1 (0.2%) 0 1 (0.2%) ᳝㛫ᯈ✺ฟ 1 (0.4%) 1 (0.2%) 0 0 㛵⠇⭘⬽ 0 1 (0.2%) 0 1 (0.2%) ➽ຊపୗ 1 (0.4%) 1 (0.2%) 1 (0.4%) 1 (0.2%) ኚᙧᛶ㛵⠇ 0 1 (0.2%) 0 0 ⫪ᅇ᪕➽⭝ᯈೃ⩌ 0 1 (0.2%) 0 0 ഃᙃ 0 1 (0.2%) 0 0 ኚᙧᛶ⬨᳝ 0 1 (0.2%) 0 0 ㌟ᛶ࢚ࣜࢸ࣐ࢺ࣮ࢹࢫ 0 1 (0.2%) 0 0 㢡㛵⠇ೃ⩌ 0 1 (0.2%) 0 0 ⭝⅖ 1 (0.4%) 1 (0.2%) 1 (0.4%) 0 ⒦ᏍศἪ≀ 1 (0.4%) 0 0 0 㛵⠇◳┤ 1 (0.4%) 0 1 (0.4%) 0 ୰㊊㦵③ 1 (0.4%) 0 0 0 㢁㒊③ 2 (0.8%) 0 0 0 ୍⯡࣭㌟㞀ᐖ࠾ࡼࡧᢞ㒊ࡢ ≧ែ 33 (13.5%) 70 (14.1%) 10 (4.1%) 23 (4.6%) Ⓨ⇕ 15 (6.1%) 29 (5.9%) 3 (1.2%) 4 (0.8%) ⑂ປ 13 (5.3%) 15 (3.0%) 7 (2.9%) 5 (1.0%) ↓ຊ 1 (0.4%) 6 (1.2%) 0 4 (0.8%) ᮎᲈᛶᾋ⭘ 0 5 (1.0%) 0 2 (0.4%) ࣥࣇ࢚ࣝࣥࢨᵝᝈ 0 4 (0.8%) 0 0 ᛰឤ 0 2 (0.4%) 0 2 (0.4%) ⭆❐③ 0 1 (0.2%) 0 0 ࢝ࢸ࣮ࢸࣝ␃⨨㒊⑊③ 0 1 (0.2%) 0 0 ␗ᖖឤ 1 (0.4%) 1 (0.2%) 0 1 (0.2%) ⇕ឤ 1 (0.4%) 1 (0.2%) 1 (0.4%) 1 (0.2%) ㌟ᗣ≧ែపୗ 0 1 (0.2%) 0 0 ⅖ 0 1 (0.2%) 0 0 ὀධ㒊⾑⭘ 0 1 (0.2%) 0 1 (0.2%) ὀධ㒊⑊③ 0 1 (0.2%) 0 0 ὀධ㒊⭘⬽ 0 1 (0.2%) 0 0 ὀᑕ㒊⣚ᩬ 0 1 (0.2%) 0 1 (0.2%) ὀᑕ㒊⑊③ 0 1 (0.2%) 0 1 (0.2%)
28 (17) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
All TEAEs Reasonably related TEAEs Placebo Ustekinumab a Placebo Ustekinumab a ᑠ⤖⠇ 0 1 (0.2%) 0 0 㠀ᚰ⮚ᛶ⬚③ 2 (0.8%) 1 (0.2%) 0 1 (0.2%) ⇱ 0 1 (0.2%) 0 0 ⬚③ 1 (0.4%) 0 0 0 ᝏᐮ 2 (0.8%) 0 0 0 ᪩ᮇ‶⭡ 1 (0.4%) 0 0 0 ᒁᡤ⭘⬽ 1 (0.4%) 0 0 0 ᾋ⭘ 1 (0.4%) 0 0 0 ⑊③ 1 (0.4%) 0 0 0 ⬨᳝③ 1 (0.4%) 0 0 0 ⚄⤒⣔㞀ᐖ 32 (13.1%) 60 (12.1%) 10 (4.1%) 29 (5.9%) 㢌③ 22 (9.0%) 40 (8.1%) 6 (2.4%) 16 (3.2%) యᛶࡵࡲ࠸ 2 (0.8%) 5 (1.0%) 2 (0.8%) 3 (0.6%) Ⴔ╀ 0 4 (0.8%) 0 3 (0.6%) ∦㢌③ 2 (0.8%) 4 (0.8%) 0 3 (0.6%) 㘒ឤぬ 1 (0.4%) 3 (0.6%) 0 0 ᾋືᛶࡵࡲ࠸ 0 2 (0.4%) 0 2 (0.4%) ぬ␗ᖖ 0 2 (0.4%) 0 2 (0.4%) ឤぬ㕌㯞 1 (0.4%) 2 (0.4%) 1 (0.4%) 1 (0.2%) ᆘ㦵⚄⤒③ 0 2 (0.4%) 0 1 (0.2%) ⬻⾑⭘ 0 1 (0.2%) 0 0 ປసᛶࡵࡲ࠸ 0 1 (0.2%) 0 1 (0.2%) ኻ⚄ᑍ๓ࡢ≧ែ 0 1 (0.2%) 0 1 (0.2%) 㰯⭍⅖క࠺㢌③ 0 1 (0.2%) 0 0 ᡓ 0 1 (0.2%) 0 0 ⅎ⇕ឤ 1 (0.4%) 0 1 (0.4%) 0 㢁⭎ೃ⩌ 1 (0.4%) 0 0 0 ␗ᖖឤぬ 1 (0.4%) 0 0 0 ୗ⫥㟼Ṇ⬟ೃ⩌ 1 (0.4%) 0 0 0 ኻ⚄ 1 (0.4%) 0 0 0 ⓶࠾ࡼࡧ⓶ୗ⤌⧊㞀ᐖ 30 (12.2%) 60 (12.1%) 19 (7.8%) 34 (6.9%) Ⓨ⑈ 7 (2.9%) 11 (2.2%) 4 (1.6%) 7 (1.4%) ࡑ࠺ 1 (0.4%) 8 (1.6%) 1 (0.4%) 5 (1.0%) ࡊ⒔ 2 (0.8%) 4 (0.8%) 0 0 ⬺ẟ 2 (0.8%) 4 (0.8%) 1 (0.4%) 2 (0.4%) ⓶⅖ 1 (0.4%) 4 (0.8%) 1 (0.4%) 2 (0.4%) ‵⑈ 1 (0.4%) 4 (0.8%) 1 (0.4%) 2 (0.4%) ⣚ᩬ 3 (1.2%) 4 (0.8%) 2 (0.8%) 4 (0.8%) ᐷờ 4 (1.6%) 3 (0.6%) 2 (0.8%) 0 ⓶ኚ 1 (0.4%) 3 (0.6%) 0 2 (0.4%) ⤖⠇ᛶ⣚ᩬ 0 2 (0.4%) 0 0 ከờ 1 (0.4%) 2 (0.4%) 1 (0.4%) 1 (0.2%) ⓶㞀ᐖ 0 2 (0.4%) 0 1 (0.2%) ⶼ㯞⑈ 0 2 (0.4%) 0 2 (0.4%) ᄞ⬊ᛶࡊ⒔ 0 1 (0.2%) 0 1 (0.2%) ⓶ᄞ⭘ 0 1 (0.2%) 0 0 ᥋ゐᛶ⓶⅖ 0 1 (0.2%) 0 0 Ⓨờ㞀ᐖ 0 1 (0.2%) 0 1 (0.2%) 㐣ゅ 0 1 (0.2%) 0 0 ⓑ⾑⌫◚○ᛶ⾑⟶⅖ 0 1 (0.2%) 0 1 (0.2%) ◳ᛶⱏⓄ 0 1 (0.2%) 0 0 Ⅼ≧ฟ⾑ 0 1 (0.2%) 0 0 ㌟ᛶࡑ࠺ 0 1 (0.2%) 0 1 (0.2%) Ⓞ 1 (0.4%) 1 (0.2%) 1 (0.4%) 1 (0.2%) ⣸ᩬ 0 1 (0.2%) 0 1 (0.2%) ᩬ≧ୣ⑈≧⓶⑈ 0 1 (0.2%) 0 1 (0.2%) ⓶◳⤖ 1 (0.4%) 1 (0.2%) 1 (0.4%) 0 ⓶⭘⒗ 1 (0.4%) 1 (0.2%) 0 0 㢦㠃⭘⬽ 0 1 (0.2%) 0 1 (0.2%)
29 (18) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
All TEAEs Reasonably related TEAEs Placebo Ustekinumab a Placebo Ustekinumab a ෭ờ 2 (0.8%) 0 2 (0.8%) 0 ⢾ᒀᛶ㊊ኚ 1 (0.4%) 0 1 (0.4%) 0 ⣚Ⰽờ⑈ 1 (0.4%) 0 0 0 ෆฟ⾑Ⓨ⏕ࡢቑຍഴྥ 1 (0.4%) 0 0 0 ⚄⤒⓶⅖ 1 (0.4%) 0 1 (0.4%) 0 ∎◚ᦆ 1 (0.4%) 0 1 (0.4%) 0 ⓶⑊③ 1 (0.4%) 0 1 (0.4%) 0 ࡑ࠺ᛶ⓶⑈ 1 (0.4%) 0 1 (0.4%) 0 ྾ჾࠊ⬚㒌࠾ࡼࡧ⦪㝸㞀ᐖ 21 (8.6%) 31 (6.3%) 4 (1.6%) 8 (1.6%) ཱྀ⭍ဗ㢌③ 7 (2.9%) 10 (2.0%) 2 (0.8%) 4 (0.8%) တႿ 7 (2.9%) 8 (1.6%) 0 4 (0.8%) 㰯㛢 1 (0.4%) 3 (0.6%) 0 0 ྾ᅔ㞴 0 2 (0.4%) 0 0 㰯ฟ⾑ 1 (0.4%) 2 (0.4%) 0 1 (0.2%) ↓Ẽ⫵ 1 (0.4%) 1 (0.2%) 1 (0.4%) 0 㰯₽⒆ 0 1 (0.2%) 0 0 Ẽ㐨࠺ࡗ⾑ 0 1 (0.2%) 0 0 ࣞࣝࢠ࣮ᛶ㰯⅖ 0 1 (0.2%) 0 0 㰯₃ 2 (0.8%) 1 (0.2%) 0 0 㰯⭍࠺ࡗ⾑ 0 1 (0.2%) 0 0 ୖẼ㐨တೃ⩌ 0 1 (0.2%) 0 0 ⫵⮚⅖ 1 (0.4%) 0 0 0 ဗႃ⤠ᢋឤ 1 (0.4%) 0 1 (0.4%) 0 ୖẼ㐨࠺ࡗ⾑ 1 (0.4%) 0 0 0 ║㞀ᐖ 6 (2.4%) 19 (3.8%) 2 (0.8%) 8 (1.6%) ║⇱ 2 (0.8%) 3 (0.6%) 0 2 (0.4%) ᙬ⅖ 0 2 (0.4%) 0 1 (0.2%) ║⾑ 0 2 (0.4%) 0 0 ࣈࢻ࢘⭷⅖ 0 2 (0.4%) 0 1 (0.2%) どຊ㞀ᐖ 0 2 (0.4%) 0 2 (0.4%) ║▛②ᨥ 0 1 (0.2%) 0 0 」ど 0 1 (0.2%) 0 0 ║▛⣚ᩬ 0 1 (0.2%) 0 1 (0.2%) ║③ 1 (0.4%) 1 (0.2%) 1 (0.4%) 0 ゅ⭷⅖ 0 1 (0.2%) 0 0 ⩈᫂ 0 1 (0.2%) 0 1 (0.2%) ₽⒆ᛶゅ⭷⅖ 0 1 (0.2%) 0 0 㟝ど 1 (0.4%) 1 (0.2%) 0 0 ║ࡢ⅖ 2 (0.8%) 0 1 (0.4%) 0 ⮫ᗋ᳨ᰝ 8 (3.3%) 16 (3.2%) 0 2 (0.4%) ⾑୰ࣈࢻ࢘⢾ቑຍ 0 4 (0.8%) 0 0 ⾑୰ࣝࣈ࣑ࣥῶᑡ 0 2 (0.4%) 0 0 ࣊ࣔࢢࣟࣅࣥῶᑡ 0 2 (0.4%) 0 1 (0.2%) ⾑୰㟁ゎ㉁␗ᖖ 0 1 (0.2%) 0 0 ⾑୰චࢢࣟࣈࣜࣥ㹃ቑຍ 0 1 (0.2%) 0 0 ⾑୰ࣜࣥῶᑡ 0 1 (0.2%) 0 0 ⾑ᅽ␗ᖖ 0 1 (0.2%) 0 0 య ୖ᪼ 0 1 (0.2%) 0 1 (0.2%) ࣊ࣔࢢࣟࣅࣥ␗ᖖ 0 1 (0.2%) 0 0 ࣜࣥࣃ⌫ᩘῶᑡ 0 1 (0.2%) 0 0 ࣜࣥࣃ⌫ᩘቑຍ 0 1 (0.2%) 0 0 ዲ୰⌫ᩘቑຍ 0 1 (0.2%) 0 0 ㉥⾑⌫ᩘῶᑡ 0 1 (0.2%) 0 0 ࣅࢱ࣑ࣥ㹀㸯㸰ῶᑡ 0 1 (0.2%) 0 0 ⓑ⾑⌫ᩘῶᑡ 0 1 (0.2%) 0 0 ⓑ⾑⌫ᩘቑຍ 1 (0.4%) 1 (0.2%) 0 0 ⾑୰㕲ῶᑡ 1 (0.4%) 0 0 0 ⾑୰࣐ࢢࢿࢩ࣒࢘ῶᑡ 1 (0.4%) 0 0 0 ⾑୰࣒࢝ࣜ࢘ቑຍ 1 (0.4%) 0 0 0
30 (19) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
All TEAEs Reasonably related TEAEs Placebo Ustekinumab a Placebo Ustekinumab a ⾑ᅽୖ᪼ 1 (0.4%) 0 0 0 ࢡࣟࢫࢺࣜࢪ᳨࣒࢘ᰝ㝧ᛶ 1 (0.4%) 0 0 0 ⫢ᶵ⬟᳨ᰝ␗ᖖ 1 (0.4%) 0 0 0 ⾑ᑠᯈᩘቑຍ 1 (0.4%) 0 0 0 య㔜ῶᑡ 1 (0.4%) 0 0 0 യᐖࠊ୰ẘ࠾ࡼࡧฎ⨨ྜే 8 (3.3%) 15 (3.0%) 2 (0.8%) 0 ⠇㊊ື≀ညയ 0 2 (0.4%) 0 0 ࣞࣝࢠ࣮ᛶ㍺⾑ᛂ 0 1 (0.2%) 0 0 ື≀ညയ 0 1 (0.2%) 0 0 ⠇㊊ື≀่യ 0 1 (0.2%) 0 0 ⫼㒊ᦆയ 0 1 (0.2%) 0 0 ᧿㐣യ 0 1 (0.2%) 0 0 യ 1 (0.4%) 1 (0.2%) 0 0 㠎ᖏ 0 1 (0.2%) 0 0 ➽᩿ 0 1 (0.2%) 0 0 ⫗㞳ࢀ 0 1 (0.2%) 0 0 ∎ᦆയ 0 1 (0.2%) 0 0 ⾡ᚋ࣊ࣝࢽ 0 1 (0.2%) 0 0 ฎ⨨ࡼࡿᝏᚰ 0 1 (0.2%) 0 0 ฎ⨨ࡼࡿྤ 0 1 (0.2%) 0 0 ㏻ᨾ 0 1 (0.2%) 0 0 㦵᱁ᦆയ 1 (0.4%) 1 (0.2%) 0 0 ṑ∳◚ᢡ 2 (0.8%) 1 (0.2%) 1 (0.4%) 0 㐀ᙳᛂ 1 (0.4%) 0 0 0 ⎔ቃ᭚㟢 1 (0.4%) 0 0 0 ฎ⨨ࡼࡿࡵࡲ࠸ 1 (0.4%) 0 1 (0.4%) 0 ฎ⨨ࡼࡿ⑊③ 1 (0.4%) 0 0 0 ௦ㅰ࠾ࡼࡧᰤ㣴㞀ᐖ 9 (3.7%) 15 (3.0%) 1 (0.4%) 1 (0.2%) 㣗ḧῶ㏥ 3 (1.2%) 5 (1.0%) 1 (0.4%) 1 (0.2%) ప࣒࢝ࣜ࢘⾑ 3 (1.2%) 3 (0.6%) 0 0 ⬺Ỉ 1 (0.4%) 2 (0.4%) 0 0 యᾮ㈓␃ 0 1 (0.2%) 0 0 ③㢼 0 1 (0.2%) 0 0 㧗⾑⢾ 0 1 (0.2%) 0 0 ప࢝ࣝࢩ࣒࢘⾑ 0 1 (0.2%) 0 0 ప࣐ࢢࢿࢩ࣒࢘⾑ 0 1 (0.2%) 0 0 ⬡⫫ᛶᾋ⭘ 0 1 (0.2%) 0 0 ᰤ㣴㞀ᐖ 1 (0.4%) 1 (0.2%) 0 0 ప⾑⢾ 1 (0.4%) 0 0 0 ࣅࢱ࣑ࣥ㹀㸯㸰Ḟஈ 1 (0.4%) 0 0 0 ⾑⟶㞀ᐖ 1 (0.4%) 15 (3.0%) 1 (0.4%) 7 (1.4%) ₻⣚ 1 (0.4%) 5 (1.0%) 1 (0.4%) 4 (0.8%) ⾑ᰦᛶ㟼⬦⅖ 0 2 (0.4%) 0 1 (0.2%) ⾑⭘ 0 1 (0.2%) 0 1 (0.2%) ࡚ࡾ 0 1 (0.2%) 0 0 㧗⾑ᅽ 0 1 (0.2%) 0 0 ప⾑ᅽ 0 1 (0.2%) 0 1 (0.2%) ࣜࣥࣃᄞ⭘ 0 1 (0.2%) 0 0 ⓑ 0 1 (0.2%) 0 0 ⾲ᅾᛶ㟼⬦⅖ 0 1 (0.2%) 0 0 ⾲ᅾᛶ⾑ᰦᛶ㟼⬦⅖ 0 1 (0.2%) 0 0 ⾑ᾮ࠾ࡼࡧࣜࣥࣃ⣔㞀ᐖ 3 (1.2%) 13 (2.6%) 1 (0.4%) 5 (1.0%) ㈋⾑ 3 (1.2%) 5 (1.0%) 1 (0.4%) 2 (0.4%) ⓑ⾑⌫ῶᑡ 0 3 (0.6%) 0 1 (0.2%) ࣜࣥࣃ⠇ 0 3 (0.6%) 0 1 (0.2%) 㕲Ḟஈᛶ㈋⾑ 0 2 (0.4%) 0 0 ࣜࣥࣃ⌫ῶᑡ 0 1 (0.2%) 0 1 (0.2%) ≉Ⓨᛶ⾑⭘ 0 1 (0.2%) 0 0 ⾑ᑠᯈቑຍ 1 (0.4%) 0 0 0
31 (20) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
All TEAEs Reasonably related TEAEs Placebo Ustekinumab a Placebo Ustekinumab a ⏕Ṫ⣔࠾ࡼࡧஙᡣ㞀ᐖ 5 (2.0%) 8 (1.6%) 1 (0.4%) 2 (0.4%) ᭶⤒ᅔ㞴 1 (0.4%) 2 (0.4%) 0 1 (0.2%) ዪᛶ⏕Ṫჾ⒦ 0 2 (0.4%) 0 0 ࣂࣝࢺࣜࣥᄞ⭘ 0 1 (0.2%) 0 0 Ⰻᛶ๓❧⭢⫧ 0 1 (0.2%) 0 0 ஙᡣ③ 0 1 (0.2%) 0 0 Ꮚᐑ㢁㒊ୖ⓶␗ᙧᡂ 0 1 (0.2%) 0 0 ᭶⤒㐣ከ 0 1 (0.2%) 0 1 (0.2%) ᭶⤒㐜ᘏ 0 1 (0.2%) 0 1 (0.2%) つ๎᭶⤒ 1 (0.4%) 0 1 (0.4%) 0 ༸ᕢᄞ⬊ 1 (0.4%) 0 0 0 㝜③ 1 (0.4%) 0 0 0 ⭐ฟ⾑ 1 (0.4%) 0 0 0 ⭈࠾ࡼࡧᒀ㊰㞀ᐖ 3 (1.2%) 7 (1.4%) 0 1 (0.2%) ᒀᅔ㞴 0 3 (0.6%) 0 0 ⭈⤖▼ 1 (0.4%) 3 (0.6%) 0 0 㢖ᒀ 1 (0.4%) 1 (0.2%) 0 1 (0.2%) ᒀពษ㏕ 1 (0.4%) 0 0 0 ᚰ⮚㞀ᐖ 3 (1.2%) 5 (1.0%) 1 (0.4%) 2 (0.4%) ື 1 (0.4%) 2 (0.4%) 1 (0.4%) 0 ᚰᡣ⣽ື 0 1 (0.2%) 0 0 ᚰ 0 1 (0.2%) 0 0 ᚰ⭷⅖ 0 1 (0.2%) 0 1 (0.2%) 㢖⬦ 1 (0.4%) 1 (0.2%) 0 1 (0.2%) ᩚ⬦ 1 (0.4%) 0 0 0 ⪥࠾ࡼࡧ㏞㊰㞀ᐖ 2 (0.8%) 3 (0.6%) 0 1 (0.2%) ⪥③ 0 1 (0.2%) 0 0 ⪥ࡑ࠺ 0 1 (0.2%) 0 1 (0.2%) ⪥㬆 0 1 (0.2%) 0 0 ≀㓉࠸ 1 (0.4%) 0 0 0 ⪥₃ 1 (0.4%) 0 0 0 ⢭⚄㞀ᐖ 12 (4.9%) 3 (0.6%) 2 (0.8%) 0 ࠺ࡘ 4 (1.6%) 1 (0.2%) 0 0 ╀ 3 (1.2%) 1 (0.2%) 1 (0.4%) 0 ⮬ẅᛕ៖ 0 1 (0.2%) 0 0 Ᏻ 3 (1.2%) 0 0 0 Ẽศືᦂ 1 (0.4%) 0 0 0 ⴠࡕ╔ࡁࡢ࡞ࡉ 1 (0.4%) 0 1 (0.4%) 0 ╧╀㞀ᐖ 1 (0.4%) 0 0 0 ෆศἪ㞀ᐖ 0 2 (0.4%) 0 1 (0.2%) ࢡࢵࢩࣥࢢᵝ 0 2 (0.4%) 0 1 (0.2%) ච⣔㞀ᐖ 0 2 (0.4%) 0 0 㣗≀ࣞࣝࢠ࣮ 0 1 (0.2%) 0 0 㐣ᩄ 0 1 (0.2%) 0 0 ⫢⫹㐨⣔㞀ᐖ 0 1 (0.2%) 0 1 (0.2%) ⫹⟶⅖ 0 1 (0.2%) 0 1 (0.2%) Ⰻᛶࠊᝏᛶ࠾ࡼࡧヲ⣽᫂ࡢ᪂⏕ ≀㸦ᄞ⬊࠾ࡼࡧ࣏࣮ࣜࣉࢆྵࡴ㸧 2 (0.8%) 1 (0.2%) 0 0 ࢡࣟࢥࣝࢻࣥ 0 1 (0.2%) 0 0 ⫠㛛ᛶჾ㉕ 1 (0.4%) 0 0 0 ⬡⫫⭘ 1 (0.4%) 0 0 0 ♫⎔ቃ 1 (0.4%) 1 (0.2%) 0 0 ࣃ࣮ࢺࢼ࣮ࡢዷፎ 1 (0.4%) 1 (0.2%) 0 0 ዷፎࠊ⏘〟࠾ࡼࡧ࿘⏘ᮇࡢ≧ែ 1 (0.4%) 0 0 0 ዷፎ 1 (0.4%) 0 0 0
a Combining 130 mg group and 6 mg/kg group. TEAEs=Treatment Emergent Adverse Events [TJPCAE11A.RTF] [CNTO1275\Z_SCS\DBR_2015_07\RE_JPKK\PROD\TJPCAE11A.SAS] 28OCT2015, 23:46
32 (21) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
(2) ᭷ᐖ㇟ࡢⓎ⌧ྜ㸦ヨ㦂୰᩿๓⤌ࡳධࢀࡽࢀࡓ⿕㦂⪅ࢆྵࡴ㸧
1) 㞟ᅋ ⾲ 2.7.6.2-5 ᭷ᐖ㇟ࡢⓎ⌧ྜ㸦ᅉᯝ㛵ಀࢆၥࢃ࡞࠸ࡍ࡚ࡢ᭷ᐖ㇟㸭 㦂⸆ྜ⌮ⓗ㛵㐃ᛶࡀ࠶ࡿ᭷ᐖ㇟㸧㸦8 㐌┠ࡲ࡛㸧㸦㦂⸆ࢆᢞࡉࢀࡓ⿕㦂⪅㸧 All TEAEs Reasonably related TEAEs Placebo Ustekinumab a Placebo Ustekinumab a Analysis Set: Treated Subjects 254 514 254 514
Total number of subjects with TEAEs 166 (65.4%) 336 (65.4%) 67 (26.4%) 139 (27.0%)
System-organ class/preferred term ⫶⭠㞀ᐖ 85 (33.5%) 132 (25.7%) 22 (8.7%) 27 (5.3%) ᝏᚰ 18 (7.1%) 35 (6.8%) 9 (3.5%) 8 (1.6%) ⭡③ 14 (5.5%) 24 (4.7%) 6 (2.4%) 3 (0.6%) ࢡ࣮ࣟࣥ 29 (11.4%) 21 (4.1%) 4 (1.6%) 0 ྤ 9 (3.5%) 20 (3.9%) 2 (0.8%) 8 (1.6%) ౽⛎ 2 (0.8%) 9 (1.8%) 0 3 (0.6%) ୖ⭡㒊③ 1 (0.4%) 7 (1.4%) 0 2 (0.4%) ⫠ 1 (0.4%) 6 (1.2%) 0 0 ⭡㒊⭾‶ 2 (0.8%) 5 (1.0%) 1 (0.4%) 1 (0.2%) ୗ⑩ 9 (3.5%) 5 (1.0%) 2 (0.8%) 0 ᾘⰋ 3 (1.2%) 5 (1.0%) 1 (0.4%) 0 ࣇࢱᛶཱྀෆ⅖ 2 (0.8%) 4 (0.8%) 0 2 (0.4%) ṑ③ 0 4 (0.8%) 0 0 ୗ⭡㒊③ 0 3 (0.6%) 0 0 㰘⭠ 1 (0.4%) 3 (0.6%) 0 1 (0.2%) ཱྀࡢ㘒ឤぬ 0 3 (0.6%) 0 2 (0.4%) ⒦ 4 (1.6%) 2 (0.4%) 0 0 ⭠⟶⓶⒦ 0 2 (0.4%) 0 1 (0.2%) ⯉③ 0 2 (0.4%) 0 1 (0.2%) ᰾ 2 (0.8%) 2 (0.4%) 0 0 ⫠㛛࿘ᅖ③ 2 (0.8%) 2 (0.4%) 0 0 ┤⭠ 1 (0.4%) 2 (0.4%) 0 0 ┤⭠ฟ⾑ 4 (1.6%) 2 (0.4%) 0 0 ⭡㒊࣊ࣝࢽ 0 1 (0.2%) 0 0 ⭡㒊ᅽ③ 1 (0.4%) 1 (0.2%) 0 0 ⫠㛛┤⭠ᛌឤ 1 (0.4%) 1 (0.2%) 0 0 ⫠㛛┤⭠㞀ᐖ 0 1 (0.2%) 0 0 ⫠㛛┤⭠⊃✽ 0 1 (0.2%) 0 0 ⤖⭠⒦ 0 1 (0.2%) 0 1 (0.2%) 㱘ṑ 1 (0.4%) 1 (0.2%) 0 0 ཱྀෆ⇱ 2 (0.8%) 1 (0.2%) 1 (0.4%) 1 (0.2%) ༑ᣦ⭠⫶㏫ὶ 0 1 (0.2%) 0 0 ฟ⾑ᛶ⫶₽⒆ 0 1 (0.2%) 0 0 ⫶㣗㐨㏫ὶᛶᝈ 1 (0.4%) 1 (0.2%) 0 0 ⾑౽ἥ 1 (0.4%) 1 (0.2%) 0 0 㰢ᚄ࣊ࣝࢽ 0 1 (0.2%) 0 0 ⭠⟶⊃✽ 0 1 (0.2%) 0 0 ᑠ⭠㛢ሰ 1 (0.4%) 1 (0.2%) 0 0 ⬡⫫౽ 0 1 (0.2%) 0 0 ⭡㒊ᛌឤ 2 (0.8%) 0 1 (0.4%) 0 ⭠⅖ 1 (0.4%) 0 0 0 ⾑ᛶୗ⑩ 1 (0.4%) 0 1 (0.4%) 0 ౽ᅇᩘቑຍ 1 (0.4%) 0 1 (0.4%) 0 ṑ⫗㏥⦰ 1 (0.4%) 0 0 0 ⭠✸Ꮝ 1 (0.4%) 0 0 0 ཱྀ⭍ෆ₽⒆ᙧᡂ 2 (0.8%) 0 1 (0.4%) 0 ཱྀ⭍㞀ᐖ 1 (0.4%) 0 1 (0.4%) 0 ཱྀ⅖ 1 (0.4%) 0 1 (0.4%) 0
33 (22) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
All TEAEs Reasonably related TEAEs Placebo Ustekinumab a Placebo Ustekinumab a ࣞࢵࢳࣥࢢ 1 (0.4%) 0 0 0 ཱྀෆ⅖ 1 (0.4%) 0 0 0 ឤᰁ࠾ࡼࡧᐤ⏕ 58 (22.8%) 127 (24.7%) 17 (6.7%) 46 (8.9%) 㰯ဗ㢌⅖ 14 (5.5%) 24 (4.7%) 4 (1.6%) 7 (1.4%) ୖẼ㐨ឤᰁ 9 (3.5%) 22 (4.3%) 4 (1.6%) 7 (1.4%) ⫶⭠⅖ 4 (1.6%) 7 (1.4%) 1 (0.4%) 0 ࢘ࣝࢫᛶ⫶⭠⅖ 0 5 (1.0%) 0 1 (0.2%) ࣥࣇ࢚ࣝࣥࢨ 1 (0.4%) 5 (1.0%) 0 2 (0.4%) ཱྀ⭍࣊ࣝ࣌ࢫ 1 (0.4%) 5 (1.0%) 0 3 (0.6%) ⫠㛛⮋⒆ 5 (2.0%) 4 (0.8%) 1 (0.4%) 1 (0.2%) 㰯⭍⅖ 6 (2.4%) 4 (0.8%) 1 (0.4%) 0 ᒀ㊰ឤᰁ 3 (1.2%) 4 (0.8%) 0 1 (0.2%) እ㝜⭐┿⳦ឤᰁ 2 (0.8%) 4 (0.8%) 1 (0.4%) 3 (0.6%) Ẽ⟶ᨭ⅖ 5 (2.0%) 3 (0.6%) 1 (0.4%) 1 (0.2%) ⻏ᕢ⅖ 0 3 (0.6%) 0 0 ࢡࣟࢫࢺࣜࢪ࣒࢘ឤᰁ 0 3 (0.6%) 0 0 ẟໟ⅖ 0 3 (0.6%) 0 0 ୗẼ㐨ឤᰁ 2 (0.8%) 3 (0.6%) 0 2 (0.4%) ⭠⟶⮋⒆ 0 2 (0.4%) 0 2 (0.4%) 㰢ᚄ㒊⮋⒆ 0 2 (0.4%) 0 1 (0.2%) ဗ㢌⅖ 0 2 (0.4%) 0 1 (0.2%) ⮋⑁ᛶ⓶⑈ 0 2 (0.4%) 0 1 (0.2%) እ㝜㒊⭐࢝ࣥࢪࢲ 0 2 (0.4%) 0 2 (0.4%) ⮋⑁ᛶࡊ⒔ 0 1 (0.2%) 0 0 ᛴᛶᡥ᱈⅖ 0 1 (0.2%) 0 0 ⒦ឤᰁ 0 1 (0.2%) 0 0 ࢘ࣝࢫᛶ⤖⭷⅖ 0 1 (0.2%) 0 1 (0.2%) ⭤⬔⅖ 0 1 (0.2%) 0 1 (0.2%) ឤᰁᛶ⓶⅖ 0 1 (0.2%) 0 0 ⪥ឤᰁ 1 (0.4%) 1 (0.2%) 0 1 (0.2%) ẘ 0 1 (0.2%) 0 0 ⭠⳦ᛶᩋ⾑ 0 1 (0.2%) 0 0 ⓶┿⳦ឤᰁ 2 (0.8%) 1 (0.2%) 0 1 (0.2%) ᾘ⟶ឤᰁ 0 1 (0.2%) 0 0 ṑ⫗⅖ 0 1 (0.2%) 0 0 ༢⣧࣊ࣝ࣌ࢫ 1 (0.4%) 1 (0.2%) 0 1 (0.2%) ᖏ≧⑁⑈ 0 1 (0.2%) 0 1 (0.2%) ឤᰁᛶᄞ⭘ 0 1 (0.2%) 0 0 ᳝㛫ᯈ⅖ 0 1 (0.2%) 0 0 ࣜࢫࢸࣜ⳦ᛶ㧊⭷⅖ 0 1 (0.2%) 0 1 (0.2%) ∎┿⳦ 0 1 (0.2%) 0 0 ཱྀ⭍࢝ࣥࢪࢲ 0 1 (0.2%) 0 1 (0.2%) ୰ဗ㢌࢝ࣥࢪࢲ 0 1 (0.2%) 0 0 እ⪥⅖ 1 (0.4%) 1 (0.2%) 0 0 ∎ᅖ⅖ 0 1 (0.2%) 0 0 㦵┙⮋⒆ 0 1 (0.2%) 0 0 ⫢࿘ᅖ⮋⒆ 0 1 (0.2%) 0 0 㝜⮋⒆ 0 1 (0.2%) 0 0 ⭡⭷⅖ 0 1 (0.2%) 0 0 ẟᕢᄞ⬊ 0 1 (0.2%) 0 0 ⭜➽⮋⒆ 0 1 (0.2%) 0 0 ṑ㧊⅖ 0 1 (0.2%) 0 0 ⭈│⭈⅖ 1 (0.4%) 1 (0.2%) 0 0 Ẽ㐨ឤᰁ 0 1 (0.2%) 0 0 ⓶ୗ⤌⧊⮋⒆ 0 1 (0.2%) 0 1 (0.2%) ᡥ᱈⅖ 0 1 (0.2%) 0 0 ṑ⮋⒆ 1 (0.4%) 1 (0.2%) 0 0 ⭠⌫⳦ᛶᒀ㊰ឤᰁ 0 1 (0.2%) 0 1 (0.2%) ࢘ࣝࢫឤᰁ 1 (0.4%) 1 (0.2%) 0 0
34 (23) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
All TEAEs Reasonably related TEAEs Placebo Ustekinumab a Placebo Ustekinumab a ࢘ࣝࢫᛶဗ㢌⅖ 0 1 (0.2%) 0 0 ࢘ࣝࢫᛶୖẼ㐨ឤᰁ 0 1 (0.2%) 0 0 እ㝜㒊⮋⒆ 0 1 (0.2%) 0 0 እ㝜㒊⅖ 0 1 (0.2%) 0 1 (0.2%) ཱྀ⭍⮋⒆ 2 (0.8%) 0 1 (0.4%) 0 ་⒪ᶵჾ㛵㐃ឤᰁ 1 (0.4%) 0 0 0 ⮋⑈ 1 (0.4%) 0 0 0 ឤᰁᛶ⒦Ꮝ 2 (0.8%) 0 1 (0.4%) 0 㝈ᒁᛶឤᰁ 1 (0.4%) 0 0 0 ⢭ᕢ⅖ 1 (0.4%) 0 0 0 ࢘ࣝࢫᛶ⫵⅖ 1 (0.4%) 0 1 (0.4%) 0 ⾡ᚋ⮋⒆ 1 (0.4%) 0 1 (0.4%) 0 㰯⅖ 1 (0.4%) 0 0 0 ṑឤᰁ 1 (0.4%) 0 1 (0.4%) 0 ➽㦵᱁⣔࠾ࡼࡧ⤖ྜ⤌⧊㞀ᐖ 43 (16.9%) 85 (16.5%) 6 (2.4%) 20 (3.9%) 㛵⠇③ 19 (7.5%) 43 (8.4%) 3 (1.2%) 6 (1.2%) ⫼㒊③ 6 (2.4%) 10 (1.9%) 0 1 (0.2%) ➽⫗③ 1 (0.4%) 8 (1.6%) 0 5 (1.0%) ᅄ⫥③ 1 (0.4%) 6 (1.2%) 0 3 (0.6%) 㛵⠇⅖ 3 (1.2%) 5 (1.0%) 0 1 (0.2%) ➽②⦰ 2 (0.8%) 5 (1.0%) 0 1 (0.2%) ➽㦵᱁③ 0 3 (0.6%) 0 1 (0.2%) ഃ⭡㒊③ 1 (0.4%) 2 (0.4%) 0 0 ➽㦵᱁⣔⬚③ 1 (0.4%) 2 (0.4%) 0 1 (0.2%) 㢡③ 0 2 (0.4%) 0 0 ⭠⅖ᛶ㛵⠇⅖ 1 (0.4%) 1 (0.2%) 0 0 ⒦Ꮝ 1 (0.4%) 1 (0.2%) 0 1 (0.2%) ᳝㛫ᯈ✺ฟ 1 (0.4%) 1 (0.2%) 0 0 㛵⠇⭘⬽ 1 (0.4%) 1 (0.2%) 0 1 (0.2%) ➽ຊపୗ 1 (0.4%) 1 (0.2%) 1 (0.4%) 1 (0.2%) ኚᙧᛶ㛵⠇ 0 1 (0.2%) 0 0 ⫪ᅇ᪕➽⭝ᯈೃ⩌ 0 1 (0.2%) 0 0 ഃᙃ 0 1 (0.2%) 0 0 ኚᙧᛶ⬨᳝ 0 1 (0.2%) 0 0 ㌟ᛶ࢚ࣜࢸ࣐ࢺ࣮ࢹࢫ 0 1 (0.2%) 0 0 㢡㛵⠇ೃ⩌ 0 1 (0.2%) 0 0 ⭝⅖ 1 (0.4%) 1 (0.2%) 1 (0.4%) 0 ⒦ᏍศἪ≀ 2 (0.8%) 0 0 0 㛵⠇◳┤ 1 (0.4%) 0 1 (0.4%) 0 ୰㊊㦵③ 1 (0.4%) 0 0 0 㢁㒊③ 2 (0.8%) 0 0 0 ୍⯡࣭㌟㞀ᐖ࠾ࡼࡧᢞ㒊ࡢ ≧ែ 34 (13.4%) 72 (14.0%) 10 (3.9%) 24 (4.7%) Ⓨ⇕ 15 (5.9%) 30 (5.8%) 3 (1.2%) 4 (0.8%) ⑂ປ 13 (5.1%) 16 (3.1%) 7 (2.8%) 6 (1.2%) ↓ຊ 1 (0.4%) 6 (1.2%) 0 4 (0.8%) ᮎᲈᛶᾋ⭘ 1 (0.4%) 5 (1.0%) 0 2 (0.4%) ࣥࣇ࢚ࣝࣥࢨᵝᝈ 0 4 (0.8%) 0 0 ᛰឤ 0 2 (0.4%) 0 2 (0.4%) ⭆❐③ 0 1 (0.2%) 0 0 ࢝ࢸ࣮ࢸࣝ␃⨨㒊⑊③ 0 1 (0.2%) 0 0 ␗ᖖឤ 1 (0.4%) 1 (0.2%) 0 1 (0.2%) ⇕ឤ 1 (0.4%) 1 (0.2%) 1 (0.4%) 1 (0.2%) ㌟ᗣ≧ែపୗ 0 1 (0.2%) 0 0 ⅖ 0 1 (0.2%) 0 0 ὀධ㒊⾑⭘ 0 1 (0.2%) 0 1 (0.2%) ὀධ㒊⑊③ 0 1 (0.2%) 0 0 ὀධ㒊⭘⬽ 0 1 (0.2%) 0 0 ὀᑕ㒊⣚ᩬ 0 1 (0.2%) 0 1 (0.2%)
35 (24) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
All TEAEs Reasonably related TEAEs Placebo Ustekinumab a Placebo Ustekinumab a ὀᑕ㒊⑊③ 0 1 (0.2%) 0 1 (0.2%) ᑠ⤖⠇ 0 1 (0.2%) 0 0 㠀ᚰ⮚ᛶ⬚③ 2 (0.8%) 1 (0.2%) 0 1 (0.2%) ⇱ 0 1 (0.2%) 0 0 ⬚③ 1 (0.4%) 0 0 0 ᝏᐮ 2 (0.8%) 0 0 0 ᪩ᮇ‶⭡ 1 (0.4%) 0 0 0 ᒁᡤ⭘⬽ 1 (0.4%) 0 0 0 ᾋ⭘ 1 (0.4%) 0 0 0 ⑊③ 1 (0.4%) 0 0 0 ⬨᳝③ 1 (0.4%) 0 0 0 ⓶࠾ࡼࡧ⓶ୗ⤌⧊㞀ᐖ 30 (11.8%) 62 (12.1%) 19 (7.5%) 36 (7.0%) Ⓨ⑈ 7 (2.8%) 12 (2.3%) 4 (1.6%) 7 (1.4%) ࡑ࠺ 1 (0.4%) 9 (1.8%) 1 (0.4%) 6 (1.2%) ࡊ⒔ 2 (0.8%) 4 (0.8%) 0 0 ⬺ẟ 2 (0.8%) 4 (0.8%) 1 (0.4%) 2 (0.4%) ⓶⅖ 1 (0.4%) 4 (0.8%) 1 (0.4%) 2 (0.4%) ‵⑈ 1 (0.4%) 4 (0.8%) 1 (0.4%) 2 (0.4%) ⣚ᩬ 3 (1.2%) 4 (0.8%) 2 (0.8%) 4 (0.8%) ⶼ㯞⑈ 0 4 (0.8%) 0 4 (0.8%) ᐷờ 4 (1.6%) 3 (0.6%) 2 (0.8%) 0 ⓶ኚ 1 (0.4%) 3 (0.6%) 0 2 (0.4%) ⤖⠇ᛶ⣚ᩬ 0 2 (0.4%) 0 0 ከờ 1 (0.4%) 2 (0.4%) 1 (0.4%) 1 (0.2%) ⓶㞀ᐖ 0 2 (0.4%) 0 1 (0.2%) ᄞ⬊ᛶࡊ⒔ 0 1 (0.2%) 0 1 (0.2%) ⓶ᄞ⭘ 0 1 (0.2%) 0 0 ᥋ゐᛶ⓶⅖ 0 1 (0.2%) 0 0 Ⓨờ㞀ᐖ 0 1 (0.2%) 0 1 (0.2%) 㐣ゅ 0 1 (0.2%) 0 0 ⓑ⾑⌫◚○ᛶ⾑⟶⅖ 0 1 (0.2%) 0 1 (0.2%) ◳ᛶⱏⓄ 0 1 (0.2%) 0 0 Ⅼ≧ฟ⾑ 0 1 (0.2%) 0 0 ㌟ᛶࡑ࠺ 0 1 (0.2%) 0 1 (0.2%) Ⓞ 1 (0.4%) 1 (0.2%) 1 (0.4%) 1 (0.2%) ⣸ᩬ 0 1 (0.2%) 0 1 (0.2%) ᩬ≧ୣ⑈≧⓶⑈ 0 1 (0.2%) 0 1 (0.2%) ⓶◳⤖ 1 (0.4%) 1 (0.2%) 1 (0.4%) 0 ⓶⭘⒗ 1 (0.4%) 1 (0.2%) 0 0 㢦㠃⭘⬽ 0 1 (0.2%) 0 1 (0.2%) ෭ờ 2 (0.8%) 0 2 (0.8%) 0 ⢾ᒀᛶ㊊ኚ 1 (0.4%) 0 1 (0.4%) 0 ⣚Ⰽờ⑈ 1 (0.4%) 0 0 0 ෆฟ⾑Ⓨ⏕ࡢቑຍഴྥ 1 (0.4%) 0 0 0 ⚄⤒⓶⅖ 1 (0.4%) 0 1 (0.4%) 0 ∎◚ᦆ 1 (0.4%) 0 1 (0.4%) 0 ⓶⑊③ 1 (0.4%) 0 1 (0.4%) 0 ࡑ࠺ᛶ⓶⑈ 1 (0.4%) 0 1 (0.4%) 0 ⚄⤒⣔㞀ᐖ 32 (12.6%) 61 (11.9%) 10 (3.9%) 29 (5.6%) 㢌③ 22 (8.7%) 40 (7.8%) 6 (2.4%) 16 (3.1%) యᛶࡵࡲ࠸ 2 (0.8%) 5 (1.0%) 2 (0.8%) 3 (0.6%) Ⴔ╀ 0 4 (0.8%) 0 3 (0.6%) ∦㢌③ 2 (0.8%) 4 (0.8%) 0 3 (0.6%) 㘒ឤぬ 1 (0.4%) 3 (0.6%) 0 0 ᾋືᛶࡵࡲ࠸ 0 2 (0.4%) 0 2 (0.4%) ぬ␗ᖖ 0 2 (0.4%) 0 2 (0.4%) ឤぬ㕌㯞 1 (0.4%) 2 (0.4%) 1 (0.4%) 1 (0.2%) ᆘ㦵⚄⤒③ 0 2 (0.4%) 0 1 (0.2%) ⬻⾑⭘ 0 1 (0.2%) 0 0
36 (25) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
All TEAEs Reasonably related TEAEs Placebo Ustekinumab a Placebo Ustekinumab a ປసᛶࡵࡲ࠸ 0 1 (0.2%) 0 1 (0.2%) ㉳❧ᡓ 0 1 (0.2%) 0 0 ኻ⚄ᑍ๓ࡢ≧ែ 0 1 (0.2%) 0 1 (0.2%) 㰯⭍⅖క࠺㢌③ 0 1 (0.2%) 0 0 ᡓ 0 1 (0.2%) 0 0 ⅎ⇕ឤ 1 (0.4%) 0 1 (0.4%) 0 㢁⭎ೃ⩌ 1 (0.4%) 0 0 0 ␗ᖖឤぬ 1 (0.4%) 0 0 0 ୗ⫥㟼Ṇ⬟ೃ⩌ 1 (0.4%) 0 0 0 ኻ⚄ 1 (0.4%) 0 0 0 ྾ჾࠊ⬚㒌࠾ࡼࡧ⦪㝸㞀ᐖ 23 (9.1%) 35 (6.8%) 4 (1.6%) 9 (1.8%) ཱྀ⭍ဗ㢌③ 7 (2.8%) 11 (2.1%) 2 (0.8%) 4 (0.8%) တႿ 7 (2.8%) 9 (1.8%) 0 5 (1.0%) 㰯㛢 1 (0.4%) 3 (0.6%) 0 0 ྾ᅔ㞴 0 2 (0.4%) 0 0 㰯ฟ⾑ 1 (0.4%) 2 (0.4%) 0 1 (0.2%) ႍᜥ 0 1 (0.2%) 0 0 ↓Ẽ⫵ 1 (0.4%) 1 (0.2%) 1 (0.4%) 0 㰯₽⒆ 0 1 (0.2%) 0 0 ⫵ሰᰦ 1 (0.4%) 1 (0.2%) 0 0 Ẽ㐨࠺ࡗ⾑ 0 1 (0.2%) 0 0 ࣞࣝࢠ࣮ᛶ㰯⅖ 0 1 (0.2%) 0 0 㰯₃ 2 (0.8%) 1 (0.2%) 0 0 㰯⭍࠺ࡗ⾑ 1 (0.4%) 1 (0.2%) 0 0 ୖẼ㐨ࡢ⅖ 0 1 (0.2%) 0 0 ୖẼ㐨တೃ⩌ 0 1 (0.2%) 0 0 ⫵⮚⅖ 1 (0.4%) 0 0 0 ဗႃ⤠ᢋឤ 1 (0.4%) 0 1 (0.4%) 0 ୖẼ㐨࠺ࡗ⾑ 1 (0.4%) 0 0 0 ║㞀ᐖ 6 (2.4%) 20 (3.9%) 2 (0.8%) 8 (1.6%) ║⇱ 2 (0.8%) 3 (0.6%) 0 2 (0.4%) ᙬ⅖ 0 2 (0.4%) 0 1 (0.2%) ║⾑ 0 2 (0.4%) 0 0 ࣈࢻ࢘⭷⅖ 0 2 (0.4%) 0 1 (0.2%) どຊ㞀ᐖ 0 2 (0.4%) 0 2 (0.4%) ║▛②ᨥ 0 1 (0.2%) 0 0 ⤖⭷⅖ 0 1 (0.2%) 0 0 」ど 0 1 (0.2%) 0 0 ║▛⣚ᩬ 0 1 (0.2%) 0 1 (0.2%) ║③ 1 (0.4%) 1 (0.2%) 1 (0.4%) 0 ゅ⭷⅖ 0 1 (0.2%) 0 0 ⩈᫂ 0 1 (0.2%) 0 1 (0.2%) ₽⒆ᛶゅ⭷⅖ 0 1 (0.2%) 0 0 㟝ど 1 (0.4%) 1 (0.2%) 0 0 ║ࡢ⅖ 2 (0.8%) 0 1 (0.4%) 0 ⮫ᗋ᳨ᰝ 10 (3.9%) 18 (3.5%) 0 2 (0.4%) ⾑୰ࣈࢻ࢘⢾ቑຍ 0 4 (0.8%) 0 0 ⾑୰ࣝࣈ࣑ࣥῶᑡ 0 2 (0.4%) 0 0 ࣊ࣔࢢࣟࣅࣥῶᑡ 0 2 (0.4%) 0 1 (0.2%) ࣛࢽ࣑ࣥࣀࢺࣛࣥࢫࣇ࢙ࣛ ࣮ࢮቑຍ 0 1 (0.2%) 0 0 ⾑୰㟁ゎ㉁␗ᖖ 0 1 (0.2%) 0 0 ⾑୰චࢢࣟࣈࣜࣥ㹃ቑຍ 0 1 (0.2%) 0 0 ⾑୰ࣜࣥῶᑡ 0 1 (0.2%) 0 0 ⾑ᅽ␗ᖖ 0 1 (0.2%) 0 0 య ୖ᪼ 0 1 (0.2%) 0 1 (0.2%) ࣊ࣔࢢࣟࣅࣥ␗ᖖ 0 1 (0.2%) 0 0 ࣜࣥࣃ⌫ᩘῶᑡ 0 1 (0.2%) 0 0 ࣜࣥࣃ⌫ᩘቑຍ 0 1 (0.2%) 0 0
37 (26) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
All TEAEs Reasonably related TEAEs Placebo Ustekinumab a Placebo Ustekinumab a ዲ୰⌫ᩘቑຍ 0 1 (0.2%) 0 0 ㉥⾑⌫ᩘῶᑡ 0 1 (0.2%) 0 0 ࣅࢱ࣑ࣥ㹀㸯㸰ῶᑡ 0 1 (0.2%) 0 0 య㔜ῶᑡ 1 (0.4%) 1 (0.2%) 0 0 ⓑ⾑⌫ᩘῶᑡ 0 1 (0.2%) 0 0 ⓑ⾑⌫ᩘቑຍ 1 (0.4%) 1 (0.2%) 0 0 ⾑୰ࢡࣞࢳࢽࣥቑຍ 1 (0.4%) 0 0 0 ⾑୰㕲ῶᑡ 1 (0.4%) 0 0 0 ⾑୰࣐ࢢࢿࢩ࣒࢘ῶᑡ 1 (0.4%) 0 0 0 ⾑୰࣒࢝ࣜ࢘ቑຍ 1 (0.4%) 0 0 0 ⾑ᅽୖ᪼ 1 (0.4%) 0 0 0 ࢡࣟࢫࢺࣜࢪ᳨࣒࢘ᰝ㝧ᛶ 1 (0.4%) 0 0 0 ⫢ᶵ⬟᳨ᰝ␗ᖖ 1 (0.4%) 0 0 0 ࣜࣥࣃ⌫ᙧែ␗ᖖ 1 (0.4%) 0 0 0 ⾑ᑠᯈᩘቑຍ 1 (0.4%) 0 0 0 ௦ㅰ࠾ࡼࡧᰤ㣴㞀ᐖ 10 (3.9%) 17 (3.3%) 1 (0.4%) 2 (0.4%) 㣗ḧῶ㏥ 3 (1.2%) 5 (1.0%) 1 (0.4%) 1 (0.2%) ప࣒࢝ࣜ࢘⾑ 3 (1.2%) 3 (0.6%) 0 0 ⬺Ỉ 2 (0.8%) 2 (0.4%) 0 0 యᾮ㈓␃ 0 2 (0.4%) 0 1 (0.2%) ప࢝ࣝࢩ࣒࢘⾑ 0 2 (0.4%) 0 0 ③㢼 0 1 (0.2%) 0 0 㧗⾑⢾ 0 1 (0.2%) 0 0 ప࣐ࢢࢿࢩ࣒࢘⾑ 0 1 (0.2%) 0 0 ⬡⫫ᛶᾋ⭘ 0 1 (0.2%) 0 0 ᰤ㣴㞀ᐖ 1 (0.4%) 1 (0.2%) 0 0 ప⾑⢾ 1 (0.4%) 0 0 0 ࣅࢱ࣑ࣥ㹀㸯㸰Ḟஈ 1 (0.4%) 0 0 0 യᐖࠊ୰ẘ࠾ࡼࡧฎ⨨ྜే 8 (3.1%) 15 (2.9%) 2 (0.8%) 0 ⠇㊊ື≀ညയ 0 2 (0.4%) 0 0 ࣞࣝࢠ࣮ᛶ㍺⾑ᛂ 0 1 (0.2%) 0 0 ື≀ညയ 0 1 (0.2%) 0 0 ⠇㊊ື≀่യ 0 1 (0.2%) 0 0 ⫼㒊ᦆയ 0 1 (0.2%) 0 0 ᧿㐣യ 0 1 (0.2%) 0 0 യ 1 (0.4%) 1 (0.2%) 0 0 㠎ᖏ 0 1 (0.2%) 0 0 ➽᩿ 0 1 (0.2%) 0 0 ⫗㞳ࢀ 0 1 (0.2%) 0 0 ∎ᦆയ 0 1 (0.2%) 0 0 ⾡ᚋ࣊ࣝࢽ 0 1 (0.2%) 0 0 ฎ⨨ࡼࡿᝏᚰ 0 1 (0.2%) 0 0 ฎ⨨ࡼࡿྤ 0 1 (0.2%) 0 0 ㏻ᨾ 0 1 (0.2%) 0 0 㦵᱁ᦆയ 1 (0.4%) 1 (0.2%) 0 0 ṑ∳◚ᢡ 2 (0.8%) 1 (0.2%) 1 (0.4%) 0 㐀ᙳᛂ 1 (0.4%) 0 0 0 ⎔ቃ᭚㟢 1 (0.4%) 0 0 0 ฎ⨨ࡼࡿࡵࡲ࠸ 1 (0.4%) 0 1 (0.4%) 0 ฎ⨨ࡼࡿ⑊③ 1 (0.4%) 0 0 0 ⾑⟶㞀ᐖ 1 (0.4%) 15 (2.9%) 1 (0.4%) 7 (1.4%) ₻⣚ 1 (0.4%) 5 (1.0%) 1 (0.4%) 4 (0.8%) ⾑ᰦᛶ㟼⬦⅖ 0 2 (0.4%) 0 1 (0.2%) ⾑⭘ 0 1 (0.2%) 0 1 (0.2%) ࡚ࡾ 0 1 (0.2%) 0 0 㧗⾑ᅽ 0 1 (0.2%) 0 0 ప⾑ᅽ 0 1 (0.2%) 0 1 (0.2%) ࣜࣥࣃᄞ⭘ 0 1 (0.2%) 0 0 ⓑ 0 1 (0.2%) 0 0
38 (27) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
All TEAEs Reasonably related TEAEs Placebo Ustekinumab a Placebo Ustekinumab a ⾲ᅾᛶ㟼⬦⅖ 0 1 (0.2%) 0 0 ⾲ᅾᛶ⾑ᰦᛶ㟼⬦⅖ 0 1 (0.2%) 0 0 ⾑ᾮ࠾ࡼࡧࣜࣥࣃ⣔㞀ᐖ 4 (1.6%) 14 (2.7%) 1 (0.4%) 5 (1.0%) ㈋⾑ 4 (1.6%) 6 (1.2%) 1 (0.4%) 2 (0.4%) ⓑ⾑⌫ῶᑡ 0 3 (0.6%) 0 1 (0.2%) ࣜࣥࣃ⠇ 0 3 (0.6%) 0 1 (0.2%) 㕲Ḟஈᛶ㈋⾑ 0 2 (0.4%) 0 0 ࣜࣥࣃ⌫ῶᑡ 0 1 (0.2%) 0 1 (0.2%) ≉Ⓨᛶ⾑⭘ 0 1 (0.2%) 0 0 ⭠㛫⭷ࣜࣥࣃ⠇⭘⬽ 1 (0.4%) 0 0 0 ⾑ᑠᯈቑຍ 1 (0.4%) 0 0 0 ⏕Ṫ⣔࠾ࡼࡧஙᡣ㞀ᐖ 5 (2.0%) 8 (1.6%) 1 (0.4%) 2 (0.4%) ᭶⤒ᅔ㞴 1 (0.4%) 2 (0.4%) 0 1 (0.2%) ዪᛶ⏕Ṫჾ⒦ 0 2 (0.4%) 0 0 ࣂࣝࢺࣜࣥᄞ⭘ 0 1 (0.2%) 0 0 Ⰻᛶ๓❧⭢⫧ 0 1 (0.2%) 0 0 ஙᡣ③ 0 1 (0.2%) 0 0 Ꮚᐑ㢁㒊ୖ⓶␗ᙧᡂ 0 1 (0.2%) 0 0 ᭶⤒㐣ከ 0 1 (0.2%) 0 1 (0.2%) ᭶⤒㐜ᘏ 0 1 (0.2%) 0 1 (0.2%) つ๎᭶⤒ 1 (0.4%) 0 1 (0.4%) 0 ༸ᕢᄞ⬊ 1 (0.4%) 0 0 0 㝜③ 1 (0.4%) 0 0 0 ⭐ฟ⾑ 1 (0.4%) 0 0 0 ⭈࠾ࡼࡧᒀ㊰㞀ᐖ 4 (1.6%) 7 (1.4%) 0 1 (0.2%) ᒀᅔ㞴 1 (0.4%) 3 (0.6%) 0 0 ⭈⤖▼ 1 (0.4%) 3 (0.6%) 0 0 㢖ᒀ 1 (0.4%) 1 (0.2%) 0 1 (0.2%) ᒀពษ㏕ 1 (0.4%) 0 0 0 ᚰ⮚㞀ᐖ 4 (1.6%) 5 (1.0%) 1 (0.4%) 2 (0.4%) ື 1 (0.4%) 2 (0.4%) 1 (0.4%) 0 ᚰᡣ⣽ື 0 1 (0.2%) 0 0 ᚰ 0 1 (0.2%) 0 0 ᚰ⭷⅖ 0 1 (0.2%) 0 1 (0.2%) 㢖⬦ 1 (0.4%) 1 (0.2%) 0 1 (0.2%) ᩚ⬦ 1 (0.4%) 0 0 0 ᚰ⮚ෆ⾑ᰦ 1 (0.4%) 0 0 0 ⪥࠾ࡼࡧ㏞㊰㞀ᐖ 2 (0.8%) 3 (0.6%) 0 1 (0.2%) ⪥③ 0 1 (0.2%) 0 0 ⪥ࡑ࠺ 0 1 (0.2%) 0 1 (0.2%) ⪥㬆 0 1 (0.2%) 0 0 ≀㓉࠸ 1 (0.4%) 0 0 0 ⪥₃ 1 (0.4%) 0 0 0 ⢭⚄㞀ᐖ 12 (4.7%) 3 (0.6%) 2 (0.8%) 0 ࠺ࡘ 4 (1.6%) 1 (0.2%) 0 0 ╀ 3 (1.2%) 1 (0.2%) 1 (0.4%) 0 ⮬ẅᛕ៖ 0 1 (0.2%) 0 0 Ᏻ 3 (1.2%) 0 0 0 Ẽศືᦂ 1 (0.4%) 0 0 0 ⴠࡕ╔ࡁࡢ࡞ࡉ 1 (0.4%) 0 1 (0.4%) 0 ╧╀㞀ᐖ 1 (0.4%) 0 0 0 ෆศἪ㞀ᐖ 0 2 (0.4%) 0 1 (0.2%) ࢡࢵࢩࣥࢢᵝ 0 2 (0.4%) 0 1 (0.2%) ච⣔㞀ᐖ 0 2 (0.4%) 0 0 㣗≀ࣞࣝࢠ࣮ 0 1 (0.2%) 0 0 㐣ᩄ 0 1 (0.2%) 0 0 Ⰻᛶࠊᝏᛶ࠾ࡼࡧヲ⣽᫂ࡢ᪂⏕ ≀㸦ᄞ⬊࠾ࡼࡧ࣏࣮ࣜࣉࢆྵࡴ㸧 2 (0.8%) 2 (0.4%) 0 1 (0.2%) ࢡࣟࢥࣝࢻࣥ 0 1 (0.2%) 0 0
39 (28) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
All TEAEs Reasonably related TEAEs Placebo Ustekinumab a Placebo Ustekinumab a ከⓎᛶ㦵㧊⭘ 0 1 (0.2%) 0 1 (0.2%) ⫠㛛ᛶჾ㉕ 1 (0.4%) 0 0 0 ⬡⫫⭘ 1 (0.4%) 0 0 0 ⫢⫹㐨⣔㞀ᐖ 0 1 (0.2%) 0 1 (0.2%) ⫹⟶⅖ 0 1 (0.2%) 0 1 (0.2%) ዷፎࠊ⏘〟࠾ࡼࡧ࿘⏘ᮇࡢ≧ែ 1 (0.4%) 1 (0.2%) 0 0 ዷፎ 1 (0.4%) 1 (0.2%) 0 0 ♫⎔ቃ 1 (0.4%) 1 (0.2%) 0 0 ࣃ࣮ࢺࢼ࣮ࡢዷፎ 1 (0.4%) 1 (0.2%) 0 0
a Combining 130 mg group and 6 mg/kg group. TEAEs=Treatment Emergent Adverse Events Include all the AEs through Week 8 and the AEs after Week 8 occurred in the subjects who did not enter maintenance study. Adverse events are coded using MedDRA 15.0. [TPMDASF09A.rtf] [CNTO1275\CRD3003\DBR_CSR\RE_PMDA\tpmdasf09a.sas] 20SEP2016, 21:45
2) ᪥ᮏே㞟ᅋ ⾲ 2.7.6.2-6 ᭷ᐖ㇟ࡢⓎ⌧ྜ㸦ᅉᯝ㛵ಀࢆၥࢃ࡞࠸ࡍ࡚ࡢ᭷ᐖ㇟㸭 㦂⸆ྜ⌮ⓗ㛵㐃ᛶࡀ࠶ࡿ᭷ᐖ㇟㸧㸦8 㐌┠ࡲ࡛㸧㸦㦂⸆ࢆᢞࡉࢀࡓ⿕㦂⪅㸧 All TEAEs Reasonably related TEAEs Placebo Ustekinumab a Placebo Ustekinumab a Analysis Set: Treated Subjects (Japanese subjects only) 18 38 18 38
Total number of subjects with TEAEs 11 (61.1%) 19 (50.0%) 3 (16.7%) 4 (10.5%)
System-organ class/preferred term ⫶⭠㞀ᐖ 3 (16.7%) 6 (15.8%) 1 (5.6%) 0 ୖ⭡㒊③ 0 2 (5.3%) 0 0 ᝏᚰ 1 (5.6%) 2 (5.3%) 1 (5.6%) 0 ⭡㒊⭾‶ 0 1 (2.6%) 0 0 ࣇࢱᛶཱྀෆ⅖ 0 1 (2.6%) 0 0 㱘ṑ 0 1 (2.6%) 0 0 ᰾ 0 1 (2.6%) 0 0 ṑ③ 0 1 (2.6%) 0 0 ࢡ࣮ࣟࣥ 2 (11.1%) 0 0 0 ឤᰁ࠾ࡼࡧᐤ⏕ 3 (16.7%) 6 (15.8%) 0 1 (2.6%) 㰯ဗ㢌⅖ 0 4 (10.5%) 0 0 ဗ㢌⅖ 0 1 (2.6%) 0 0 ୖẼ㐨ឤᰁ 0 1 (2.6%) 0 0 እ㝜㒊⅖ 0 1 (2.6%) 0 1 (2.6%) ⫠㛛⮋⒆ 1 (5.6%) 0 0 0 ་⒪ᶵჾ㛵㐃ឤᰁ 1 (5.6%) 0 0 0 ឤᰁᛶ⒦Ꮝ 1 (5.6%) 0 0 0 ࣥࣇ࢚ࣝࣥࢨ 1 (5.6%) 0 0 0 ⓶࠾ࡼࡧ⓶ୗ⤌⧊㞀ᐖ 4 (22.2%) 3 (7.9%) 2 (11.1%) 2 (5.3%) ࡊ⒔ 1 (5.6%) 1 (2.6%) 0 0 Ⓨờ㞀ᐖ 0 1 (2.6%) 0 1 (2.6%) Ⓨ⑈ 0 1 (2.6%) 0 1 (2.6%) ⓶⅖ 1 (5.6%) 0 1 (5.6%) 0 ⣚ᩬ 1 (5.6%) 0 0 0 ⣚Ⰽờ⑈ 1 (5.6%) 0 0 0 ከờ 1 (5.6%) 0 1 (5.6%) 0 ୍⯡࣭㌟㞀ᐖ࠾ࡼࡧᢞ㒊ࡢ ≧ែ 3 (16.7%) 2 (5.3%) 1 (5.6%) 0 Ⓨ⇕ 1 (5.6%) 2 (5.3%) 0 0 ⇕ឤ 1 (5.6%) 0 1 (5.6%) 0
40 (29) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
All TEAEs Reasonably related TEAEs Placebo Ustekinumab a Placebo Ustekinumab a ᮎᲈᛶᾋ⭘ 1 (5.6%) 0 0 0 ⾑ᾮ࠾ࡼࡧࣜࣥࣃ⣔㞀ᐖ 0 1 (2.6%) 0 1 (2.6%) ㈋⾑ 0 1 (2.6%) 0 1 (2.6%) യᐖࠊ୰ẘ࠾ࡼࡧฎ⨨ྜే 0 1 (2.6%) 0 0 ⠇㊊ື≀่യ 0 1 (2.6%) 0 0 ➽㦵᱁⣔࠾ࡼࡧ⤖ྜ⤌⧊㞀ᐖ 1 (5.6%) 1 (2.6%) 0 0 㛵⠇⅖ 0 1 (2.6%) 0 0 ᳝㛫ᯈ✺ฟ 1 (5.6%) 0 0 0 ⚄⤒⣔㞀ᐖ 0 1 (2.6%) 0 0 㢌③ 0 1 (2.6%) 0 0 ྾ჾࠊ⬚㒌࠾ࡼࡧ⦪㝸㞀ᐖ 0 1 (2.6%) 0 0 ୖẼ㐨ࡢ⅖ 0 1 (2.6%) 0 0 ⮫ᗋ᳨ᰝ 1 (5.6%) 0 0 0 ⓑ⾑⌫ᩘቑຍ 1 (5.6%) 0 0 0 ⏕Ṫ⣔࠾ࡼࡧஙᡣ㞀ᐖ 1 (5.6%) 0 0 0 ᭶⤒ᅔ㞴 1 (5.6%) 0 0 0
a Combining 130 mg group and 6 mg/kg group. TEAEs=Treatment Emergent Adverse Events Include all the AEs through Week 8 and the AEs after Week 8 occurred in the subjects who did not enter maintenance study. Adverse events are coded using MedDRA 15.0. [TPMDASF09B.rtf] [CNTO1275\CRD3003\DBR_CSR\RE_PMDA\tpmdasf09b.sas] 20SEP2016, 21:45
41 (30)
(31) ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3001
(3) ୰Ṇ⮳ࡗࡓ᭷ᐖ㇟ࡢヲ⣽㸦ヨ㦂୰᩿๓⤌ࡳධࢀࡽࢀࡓ⿕㦂⪅ࢆྵࡴ㸧
1) 㞟ᅋ ⾲ 2.7.6.2 -7 ୰Ṇ⮳ࡗࡓ᭷ᐖ㇟ཬࡧ㦂⸆ྜ⌮ⓗ㛵㐃ᛶࡀ࠶ࡿ୰Ṇ⮳ࡗࡓ᭷ᐖ㇟㸦8 㐌┠ࡲ࡛㸧 2.7.6 㸦㦂⸆ࢆᢞࡉࢀࡓ⿕㦂⪅㸧 Study Agent Start Day Age Dose of AE / MedDRA Treatment Subject (yrs)/ Prior Duration Preferred Infusion Relation to Group ID Sex to AE (days) Term Verbatim Term Infectiona Reaction Serious Severity Study Agent Action Taken Outcome Placebo IV 1004-10013 4/F 0 mg 28/4 ࢡ࣮ࣟࣥ WORSENING OF No No Yes SEVERE NOT DRUG RECOVERED/RESOLVED CROHN'S DISEASE RELATED WITHDRAWN 1008-10707 4/F 0 mg 18/74 ࢡ࣮ࣟࣥ WORSENING OF No No No MODERATE DOUBTFUL DRUG RECOVERED/RESOLVED CROHN'S WITHDRAWN 1018-10722 4/F 0 mg 70/7 ࢡ࣮ࣟࣥ ACUTE FLARE OF No No Yes SEVERE NOT DRUG RECOVERED/RESOLVED CROHNS DISEASE RELATED WITHDRAWN 1036-10369 5/F 0 mg 22/56 ࢡ࣮ࣟࣥ FLARE OF CROHN'S No No No MODERATE POSSIBLE DRUG RECOVERED/RESOLVED WITHDRAWN WITH SEQUELAE 1043-10927 2/F 0 mg 57/6 ࢡ࣮ࣟࣥ WORSENING OF No No Yes SEVERE NOT DRUG RECOVERED/RESOLVED CROHN'S DISEASE RELATED WITHDRAWN 1043-11057 3/F 0 mg 27/Ongoing ዷፎ INTRAUTERINE No No No MILD NOT DRUG NOT RECOVERED/NOT GESTATION RELATED WITHDRAWN RESOLVED 1102-10181 7/M 0 mg 56/257 ⢾ᒀᛶ㊊ LEFT DIABETIC FOOT Yes No No MODERATE POSSIBLE DRUG RECOVERED/RESOLVED ኚ ULCER WITHDRAWN 2703-10887 2/F 0 mg 22/Ongoing ࢡ࣮ࣟࣥ WORSENING OF No No No MODERATE DOUBTFUL DRUG NOT RECOVERED/NOT CROHN'S DISEASE WITHDRAWN RESOLVED 3301-10739 3/F 0 mg 28/113 ࢡ࣮ࣟࣥ WORSENING No No No MODERATE DOUBTFUL DRUG RECOVERED/RESOLVED CROHN'S DISEASE WITHDRAWN 3314-10475 1/M 0 mg 47/38 ឤᰁᛶ⒦Ꮝ COLONIC FISTULA Yes No Yes SEVERE POSSIBLE DRUG RECOVERED/RESOLVED WITH ABCESS WITHDRAWN 3406-10747 3/F 0 mg 25/22 ࢡ࣮ࣟࣥ WORSENING OF No No Yes MODERATE NOT DRUG RECOVERED/RESOLVED MORBUS CROHN RELATED WITHDRAWN DISEASE 3407-10748 3/F 0 mg 43/3 ࢡ࣮ࣟࣥ WORSENING OF No No No MODERATE DOUBTFUL DRUG RECOVERED/RESOLVED CROHN'S DISESE WITHDRAWN ಶ 3409-10481 4/F 0 mg 20/24 ࢡ࣮ࣟࣥ WORSENING OF No No No MODERATE NOT DRUG RECOVERED/RESOLVED ࠎ CROHNS DISEASE RELATED WITHDRAWN ࡢヨ 3415-10286 2/F 0 mg ࢡ࣮ࣟࣥ WORSENING OF No No No SEVERE NOT DRUG NOT RECOVERED/NOT CROHN'S DESEASE RELATED WITHDRAWN RESOLVED 3419-10912 2/F 0 mg 7/31 ࢡ࣮ࣟࣥ WORSENING OF No No No SEVERE POSSIBLE DRUG RECOVERED/RESOLVED 㦂 CROHNS DISEASE WITHDRAWN ࡢࡲ 4216-11134 2/F 0 mg 53/87 ࢡ࣮ࣟࣥ DETERIORATION OF No No Yes MODERATE NOT DRUG RECOVERED/RESOLVED CROHN'S DISEASE RELATED WITHDRAWN ヨ 㦂 ࡵ
42
(32) ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3001 Study Agent Start Day Age Dose of AE / MedDRA Treatment Subject (yrs)/ Prior Duration Preferred Infusion Relation to Group ID Sex to AE (days) Term Verbatim Term Infectiona Reaction Serious Severity Study Agent Action Taken Outcome Ustekinumab 1008-10793 4/F 129.6 22/4 ࢡ࣮ࣟࣥ CROHN'S FLARE No No Yes MODERATE NOT DRUG RECOVERED/RESOLVED 130 mg IV mg RELATED WITHDRAWN 1072-10025 4/F 130.0 43/13 ⭠⟶⮋⒆ ABSCESS IN RIGHT Yes No Yes SEVERE POSSIBLE DRUG RECOVERED/RESOLVED 2.7.6 mg COLON WITHDRAWN 1073-10160 4/M 3.1 mg 1/9 Ⓨ⇕ WORSENING FEVER Yes Yes No MODERATE NOT DRUG RECOVERED/RESOLVED (103.7 F) RELATED WITHDRAWN 4112-10745 5/F 129.6 33/10 ࢡ࣮ࣟࣥ CROHN'S DISEASE No No Yes SEVERE NOT DRUG RECOVERED/RESOLVED mg RELAPSE RELATED WITHDRAWN Ustekinumab 1005-10200 5/M 389.7 2/Ongoing 㰢ᚄ࣊ࣝࢽ INDIRECT INGUINAL No No No SEVERE NOT DRUG NOT RECOVERED/NOT Approximating mg HERNIA RELATED WITHDRAWN RESOLVED 6 mg/kg IV 1025-11096 4/F 389.7 2/73 ࢡ࣮ࣟࣥ CROHN'S FLARE No No Yes SEVERE DOUBTFUL DRUG RECOVERED/RESOLVED mg WITHDRAWN 3302-10290 3/M 389.7 21/22 ࣜࢫࢸࣜ⳦ LISTERIA Yes No Yes SEVERE VERY DRUG RECOVERED/RESOLVED mg ᛶ㧊⭷⅖ MENINGITIS LIKELY WITHDRAWN 3314-10335 3/F 389.7 36/48 ⤖⭠⒦ INTERNAL COLONIC No No Yes SEVERE POSSIBLE DRUG RECOVERED/RESOLVED mg FISTULA WITHDRAWN 3423-10972 2/M 389.7 56/Ongoing ⾑୰චࢢࣟ HIGH TOTAL IGE No No No MODERATE NOT DRUG NOT RECOVERED/NOT mg ࣈࣜࣥ㹃ቑຍ RELATED WITHDRAWN RESOLVED 4111-10672 3/F 259.2 49/28 㝜⮋⒆ ANOVULVAR Yes No Yes SEVERE DOUBTFUL DRUG RECOVERED/RESOLVED mg ABSCESS WITHDRAWN 5607-10923 2/F 283.4 16/Ongoing ⓑ⾑⌫◚○ᛶ LEUCOCYTOCLASTIC No No No SEVERE VERY DRUG NOT RECOVERED/NOT mg ⾑⟶⅖ VASCULITIS LIKELY WITHDRAWN RESOLVED
a Infection as assessed by the investigator. Include all the AEs through Week 8 and the AEs after Week 8 occurred in the subjects who did not enter maintenance study. Adverse events are coded using MedDRA 15.0. [LPMDASF11A.rtf] [CNTO1275\CRD3003\DBR_CSR\RE_PMDA\lpmdasf11a.sas] 20SEP2016, 21:43
ಶ ࠎ ࡢヨ 㦂 ࡢࡲ ヨ 㦂 ࡵ
43
(33) ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3001
2) ᪥ᮏே㞟ᅋ ⾲ 2.7.6.2-8 ୰Ṇ⮳ࡗࡓ᭷ᐖ㇟ཬࡧ㦂⸆ྜ⌮ⓗ㛵㐃ᛶࡀ࠶ࡿ୰Ṇ⮳ࡗࡓ᭷ᐖ㇟㸦8 㐌┠ࡲ࡛㸧 㸦㦂⸆ࢆᢞࡉࢀࡓ⿕㦂⪅㸧 Study 2.7.6 Agent Start Day Age Dose of AE / Treatment Subject (yrs)/ Prior to Duration MedDRA Infusion Relation to Group ID Sex AE (days) Preferred Term Verbatim Term Infectiona Reaction Serious Severity Study Agent Action Taken Outcome Placebo IV 4216-11134 2/F 0 mg 53/87 ࢡ࣮ࣟࣥ DETERIORATION No No Yes MODERATE NOT DRUG RECOVERED/RESOLVED OF CROHN'S RELATED WITHDRAWN DISEASE
a Infection as assessed by the investigator. Include all the AEs through Week 8 and the AEs after Week 8 occurred in the subjects who did not enter maintenance study. Adverse events are coded using MedDRA 15.0. [LPMDASF11B.rtf] [CNTO1275\CRD3003\DBR_CSR\RE_PMDA\lpmdasf11b.sas] 20SEP2016, 21:43
ಶ ࠎ ࡢヨ 㦂 ࡢࡲ ヨ 㦂 ࡵ
44
(34) ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3001
2.7.6.2.3 㔜⠜࡞᭷ᐖ㇟ࡢࢹ࣮ࢱ
(1) 㔜⠜࡞᭷ᐖ㇟ࡢヲ⣽㸦ヨ㦂୰᩿๓⤌ࡳධࢀࡽࢀࡓ⿕㦂⪅ࢆྵࡴ㸧
1) 㞟ᅋ 2.7.6 ⾲ 2.7.6.2 -9 㔜⠜࡞᭷ᐖ㇟ཬࡧ㦂⸆ྜ⌮ⓗ㛵㐃ᛶࡀ࠶ࡿ㔜⠜࡞᭷ᐖ㇟㸦8 㐌┠ࡲ࡛㸧㸦㦂⸆ࢆᢞࡉࢀࡓ⿕㦂⪅㸧 Study Agent Start Day Age Dose of AE / Treatment Subject (yrs)/ Prior to Duration MedDRA Infusion Relation to Group ID Sex AE (days) Preferred Term Verbatim Term Infectiona Reaction Serious Severity Study Agent Action Taken Outcome Placebo IV 1004-10013 4/F 0 mg 28/4 ࢡ࣮ࣟࣥ WORSENING OF No No Yes SEVERE NOT DRUG RECOVERED/RESOLVED CROHN'S DISEASE RELATED WITHDRAWN 1018-10722 4/F 0 mg 70/7 ࢡ࣮ࣟࣥ ACUTE FLARE OF No No Yes SEVERE NOT DRUG RECOVERED/RESOLVED CROHNS DISEASE RELATED WITHDRAWN 154/45 ࢡ࣮ࣟࣥ EXACERBATION OF No No Yes SEVERE NOT NOT RECOVERED/RESOLVED CROHNS RELATED APPLICABLE 1036-10147 3/F 0 mg 1/4 ⭠✸Ꮝ COLON No No Yes MODERATE NOT DOSE NOT RECOVERED/RESOLVED PERFORATION RELATED CHANGED 1043-10927 2/F 0 mg 57/6 ࢡ࣮ࣟࣥ WORSENING OF No No Yes SEVERE NOT DRUG RECOVERED/RESOLVED CROHN'S DISEASE RELATED WITHDRAWN 1045-10670 4/F 0 mg 37/3 ୗ⑩ INCREASED No No Yes MODERATE NOT DOSE NOT RECOVERED/RESOLVED DIARRHEA RELATED CHANGED Ⓨ⇕ FEVER 102 F No No Yes MODERATE NOT DOSE NOT RECOVERED/RESOLVED RELATED CHANGED 1045-10911 3/M 0 mg 43/5 ప࣒࢝ࣜ࢘⾑ WORSENED No No Yes MODERATE NOT DOSE NOT RECOVERED/RESOLVED HYPOKALEMIA RELATED CHANGED 1045-11106 3/M 0 mg 48/5 ⫠㛛⮋⒆ PERIANAL ABSCESS Yes No Yes MODERATE NOT DOSE NOT RECOVERED/RESOLVED RELATED CHANGED 1065-10601 2/M 0 mg 32/7 ࢡ࣮ࣟࣥ EXACERBATION OF No No Yes MODERATE DOUBTFUL DOSE NOT RECOVERED/RESOLVED CROHN'S CHANGED SYMPTOMS 1069-10679 4/F 0 mg 15/10 ࢘ࣝࢫᛶ⫵⅖ VIRAL PNEUMONIA Yes No Yes SEVERE POSSIBLE DOSE NOT RECOVERED/RESOLVED CHANGED 2406-11079 3/F 0 mg 17/ ࢡ࣮ࣟࣥ FLARE CROHN'S No No Yes MODERATE DOUBTFUL DOSE NOT NOT RECOVERED/NOT Ongoing DISEASE CHANGED RESOLVED ಶ 3314-10475 1/M 0 mg 47/38 ឤᰁᛶ⒦Ꮝ COLONIC FISTULA Yes No Yes SEVERE POSSIBLE DRUG RECOVERED/RESOLVED ࠎ WITH ABCESS WITHDRAWN ࡢヨ 90/19 ⾡ᚋ⮋⒆ POST OPERATIVE Yes No Yes SEVERE POSSIBLE NOT RECOVERED/RESOLVED ABCESS APPLICABLE 㦂
100/22 ᚰ⮚ෆ⾑ᰦ INTRACARDIAC No No Yes SEVERE NOT NOT RECOVERED/RESOLVED ࡢࡲ THROMBUS RELATED APPLICABLE 142/1 㱘ṑ TOOTH CARIES Yes No Yes MILD NOT NOT RECOVERED/RESOLVED ヨ 㦂 RELATED APPLICABLE ࡵ
45
(35) ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3001 Study Agent Start Day Age Dose of AE / Treatment Subject (yrs)/ Prior to Duration MedDRA Infusion Relation to Group ID Sex AE (days) Preferred Term Verbatim Term Infectiona Reaction Serious Severity Study Agent Action Taken Outcome 3406-10747 3/F 0 mg 25/22 ࢡ࣮ࣟࣥ WORSENING OF No No Yes MODERATE NOT DRUG RECOVERED/RESOLVED MORBUS CROHN RELATED WITHDRAWN DISEASE 2.7.6 3419-10912 2/F 0 mg 40/108 ୗ⑩ PERSISTENT No No Yes SEVERE NOT DOSE NOT RECOVERED/RESOLVED DIARRHEA RELATED CHANGED 4107-10316 2/M 0 mg 11/9 ᰤ㣴㞀ᐖ MALNUTRITION No No Yes SEVERE NOT DOSE NOT RECOVERED/RESOLVED RELATED CHANGED 4107-10610 2/M 0 mg 143/27 ࢡ࣮ࣟࣥ ILEO COLONIC No No Yes SEVERE NOT DOSE NOT RECOVERED/RESOLVED CROHN'S DISEASE RELATED CHANGED WITH PERIANAL FISTULA, ANAL STENOSIS, MALNUTRITION, ANEMIA 4211-10853 4/M 0 mg 15/75 ࢡ࣮ࣟࣥ WORSENING OF THE No No Yes SEVERE NOT DOSE NOT RECOVERED/RESOLVED CROHN'S DISEASE RELATED CHANGED 4216-11134 2/F 0 mg 53/87 ࢡ࣮ࣟࣥ DETERIORATION OF No No Yes MODERATE NOT DRUG RECOVERED/RESOLVED CROHN'S DISEASE RELATED WITHDRAWN 4803-10691 3/F 0 mg 44/7 ࢡ࣮ࣟࣥ CROHN DISEASE No No Yes MODERATE NOT DOSE NOT RECOVERED/RESOLVED WORSENING RELATED CHANGED Ustekinumab 1007-10102 3/F 129.6 mg 28/4 ࢡ࣮ࣟࣥ CROHN'S DISEASE No No Yes SEVERE DOUBTFUL DOSE NOT RECOVERED/RESOLVED 130 mg IV FLARE CHANGED 1008-10793 4/F 129.6 mg 10/8 ⬺Ỉ DEHYDRATION No No Yes MODERATE DOUBTFUL DOSE NOT RECOVERED/RESOLVED CHANGED 22/4 ࢡ࣮ࣟࣥ CROHN'S FLARE No No Yes MODERATE NOT DRUG RECOVERED/RESOLVED RELATED WITHDRAWN 70/16 ႍᜥ ASTHMA No No Yes MODERATE DOUBTFUL DOSE NOT RECOVERED/RESOLVED EXACERBATION CHANGED 91/30 ⫵ሰᰦ PULMONARY No No Yes MODERATE DOUBTFUL DOSE NOT RECOVERED/RESOLVED EMBOLISM CHANGED 1046-10180 3/F 129.6 mg 53/7 㦵┙⮋⒆ RIGHT LOWER Yes No Yes SEVERE DOUBTFUL DOSE NOT RECOVERED/RESOLVED QUANDRANT CHANGED PELVIC ABSCESS 1060-10769 2/F 129.6 mg 5/3 ࢡ࣮ࣟࣥ SEVERE CROHN'S No No Yes SEVERE NOT DOSE NOT RECOVERED/RESOLVED DISEASE RELATED CHANGED ಶ 45/4 ప࢝ࣝࢩ࣒࢘⾑ HYPOCALCEMIA No No Yes SEVERE NOT DOSE NOT RECOVERED/RESOLVED ࠎ RELATED CHANGED ࡢヨ 46/50 ప࣒࢝ࣜ࢘⾑ HYPOKALEMIA No No Yes SEVERE NOT DOSE NOT RECOVERED/RESOLVED RELATED CHANGED 㦂
ప࣐ࢢࢿࢩ࣒࢘ HYPOMAGNESEMIA No No Yes SEVERE NOT DOSE NOT RECOVERED/RESOLVED ࡢࡲ ⾑ RELATED CHANGED 60/5 ⾑୰㟁ゎ㉁␗ᖖ ELECTROLYTES No No Yes MODERATE NOT DOSE NOT RECOVERED/RESOLVED ヨ 㦂 ABNORMALITIES RELATED CHANGED ࡵ
46
(36) ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3001 Study Agent Start Day Age Dose of AE / Treatment Subject (yrs)/ Prior to Duration MedDRA Infusion Relation to Group ID Sex AE (days) Preferred Term Verbatim Term Infectiona Reaction Serious Severity Study Agent Action Taken Outcome 1066-10169 2/F 129.6 mg 21/12 ࢡ࣮ࣟࣥ FLARE OF CROHN'S No No Yes MODERATE NOT DOSE NOT RECOVERED/RESOLVED DISEASE RELATED CHANGED 1072-10025 4/F 130.0 mg 43/13 ⭠⟶⮋⒆ ABSCESS IN RIGHT Yes No Yes SEVERE POSSIBLE DRUG RECOVERED/RESOLVED 2.7.6 COLON WITHDRAWN 1089-10884 5/F 129.6 mg 30/22 ⭈⤖▼ NEPHROLITHASIS No No Yes SEVERE NOT DOSE NOT RECOVERED/RESOLVED RELATED CHANGED 1091-10037 2/F 130.0 mg 305/19 ⭈│⭈⅖ PYELONEPHRITIS Yes No Yes SEVERE DOUBTFUL NOT RECOVERED/RESOLVED ANTEPARTUM APPLICABLE 1113-10243 2/F 129.6 mg 5/5 ࢡ࣮ࣟࣥ EXACERBATION OF No No Yes MODERATE NOT DOSE NOT RECOVERED/RESOLVED CROHNS DISEASE RELATED CHANGED 18/13 ࢡ࣮ࣟࣥ CROHN'S DISEASE No No Yes MODERATE NOT DOSE NOT RECOVERED/RESOLVED EXACERBATION RELATED CHANGED 2714-10916 4/F 129.6 mg 60/28 ⾲ᅾᛶ㟼⬦⅖ SUPERFICIAL RIGHT No No Yes MODERATE DOUBTFUL DOSE NOT RECOVERED/RESOLVED ARM BASILIC CHANGED PHLEBITIS 3306-10824 2/F 129.6 mg 62/10 ࢘ࣝࢫᛶ⫶⭠ VIRAL Yes No Yes MODERATE NOT DOSE NOT RECOVERED/RESOLVED ⅖ GASTROENTERITIS RELATED CHANGED 4112-10745 5/F 129.6 mg 33/10 ࢡ࣮ࣟࣥ CROHN'S DISEASE No No Yes SEVERE NOT DRUG RECOVERED/RESOLVED RELAPSE RELATED WITHDRAWN 4605-10842 2/M 129.6 mg 14/45 ࢡ࣮ࣟࣥ WORSENING No No Yes SEVERE NOT DOSE NOT RECOVERED/RESOLVED CROHN'S DISEASE RELATED CHANGED WITH SEQUELAE 5610-10835 4/F 129.6 mg 18/20 እ㝜㒊⮋⒆ VULVAL ABSCESSES Yes No Yes MODERATE DOUBTFUL DOSE NOT RECOVERED/RESOLVED (2CM), DUE TO CHANGED UNDERLYING PERIANAL FISTULA Ustekinumab 1007-10235 3/M 389.7 mg 49/2 ࢡ࣮ࣟࣥ CROHN'S DISEASE No No Yes MODERATE DOUBTFUL DOSE NOT RECOVERED/RESOLVED Approximatin CHANGED g 6 mg/kg IV 1007-10262 1/F 260.1 mg 5/2 ࢡ࣮ࣟࣥ CROHN'S FLARE/ No No Yes MODERATE DOUBTFUL DOSE NOT RECOVERED/RESOLVED EXACERBATION CHANGED 52/6 ⭡③ WORSENING No No Yes MODERATE DOUBTFUL DOSE NOT RECOVERED/RESOLVED ABDOMINAL PAIN CHANGED 1015-10185 3/F 520.2 mg 22/11 ᑠ⭠㛢ሰ HIGH GRADE No No Yes SEVERE NOT DOSE NOT RECOVERED/RESOLVED OBSTRUCTION IN RELATED CHANGED THE SMALL BOWEL ಶ 1025-11096 4/F 389.7 mg 2/73 ࢡ࣮ࣟࣥ CROHN'S FLARE No No Yes SEVERE DOUBTFUL DRUG RECOVERED/RESOLVED ࠎ WITHDRAWN ࡢヨ 1039-10385 5/M 520.2 mg 28/5 ㏻ᨾ ALOCHOL RELATED No No Yes MILD NOT DOSE NOT RECOVERED/RESOLVED MOTOR VEHICLE RELATED CHANGED 㦂
ACCIDENT ࡢࡲ 1057-10264 4/F 389.7 mg 14/21 ⭠⟶⮋⒆ SIGMOID ABSCESS Yes No Yes SEVERE POSSIBLE DOSE NOT RECOVERED/RESOLVED CHANGED ヨ 㦂 ࡵ
47
(37) ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3001 Study Agent Start Day Age Dose of AE / Treatment Subject (yrs)/ Prior to Duration MedDRA Infusion Relation to Group ID Sex AE (days) Preferred Term Verbatim Term Infectiona Reaction Serious Severity Study Agent Action Taken Outcome 1107-10978 2/F 259.2 mg 46/20 ࢡ࣮ࣟࣥ EXACERBATION OF No No Yes SEVERE NOT DOSE NOT RECOVERED/RESOLVED CROHN'S DISEASE RELATED CHANGED WITH SEQUELAE 56/10 ⭡⭷⅖ PERITONITIS Yes No Yes MODERATE NOT DOSE NOT RECOVERED/RESOLVED 2.7.6 RELATED CHANGED 2203-11058 4/M 520.2 mg 41/3 㐣ᩄ ALLERGIC No No Yes MODERATE NOT DOSE NOT RECOVERED/RESOLVED REACTION OF RELATED CHANGED UNKNOWN CAUSE 2716-10897 3/F 259.2 mg 8/8 ࢡ࣮ࣟࣥ CROHN'S DISEASE No No Yes MODERATE NOT DOSE NOT RECOVERED/RESOLVED EXACERBATION RELATED CHANGED 3302-10290 3/M 389.7 mg 21/22 ࣜࢫࢸࣜ⳦ᛶ LISTERIA Yes No Yes SEVERE VERY DRUG RECOVERED/RESOLVED 㧊⭷⅖ MENINGITIS LIKELY WITHDRAWN 3306-10548 6/M 389.7 mg 4/9 ᚰᡣ⣽ື AURICULLAR No No Yes SEVERE NOT DOSE NOT RECOVERED/RESOLVED FIBRILLATION RELATED CHANGED 43/8 ᚰ HEART FAILURE No No Yes SEVERE NOT DOSE NOT RECOVERED/RESOLVED WITH AURICULAR RELATED CHANGED FIBRILLATION 3309-10526 4/F 389.7 mg 40/5 ࣜࣥࣃᄞ⭘ PELVIC LYMPHOCEL No No Yes MODERATE NOT DOSE NOT RECOVERED/RESOLVED RELATED CHANGED 3314-10335 3/F 389.7 mg 36/48 ⤖⭠⒦ INTERNAL COLONIC No No Yes SEVERE POSSIBLE DRUG RECOVERED/RESOLVED FISTULA WITHDRAWN 3421-10675 5/M 389.7 mg 22/16 ⭠⳦ᛶᩋ⾑ SEPSIS WITH E.COLI Yes No Yes SEVERE NOT DOSE NOT RECOVERED/RESOLVED BACTEREMIA RELATED CHANGED 44/31 ᳝㛫ᯈ⅖ SPONDYLODISCITIS Yes No Yes MODERATE NOT DOSE NOT RECOVERED/RESOLVED RELATED CHANGED 199/Ongo ከⓎᛶ㦵㧊⭘ MULTIPLE No No Yes MODERATE POSSIBLE DOSE NOT NOT RECOVERED/NOT ing MYELOMA CHANGED RESOLVED 4111-10672 3/F 259.2 mg 49/28 ዪᛶ⏕Ṫჾ⒦ RECTOVAGINAL No No Yes SEVERE DOUBTFUL DOSE NOT RECOVERED/RESOLVED FISTULA CHANGED 㝜⮋⒆ ANOVULVAR Yes No Yes SEVERE DOUBTFUL DRUG RECOVERED/RESOLVED ABSCESS WITHDRAWN 4305-10959 5/F 259.2 mg 53/8 ฟ⾑ᛶ⫶₽⒆ GASTRIC ULCER No No Yes SEVERE NOT DOSE NOT RECOVERED/RESOLVED BLEEDING RELATED CHANGED 4602-10902 6/M 389.7 mg 33/40 ⫹⟶⅖ CHOLANGITIS Yes No Yes MODERATE POSSIBLE DOSE NOT RECOVERED/RESOLVED CHANGED ಶ 4603-10982 2/F 389.7 mg 34/14 ࢡࣟࢫࢺࣜࢪ࢘ CLOSTRIDIUM Yes No Yes SEVERE DOUBTFUL DOSE NOT RECOVERED/RESOLVED ࠎ ࣒ឤᰁ DIFFICULE CHANGED SUPERINFECTION ࡢヨ
a Infection as assessed by the investigator. 㦂 Include all the AEs through Week 8 and the AEs after Week 8 occurred in the subjects who did not enter maintenance study. ࡢࡲ Adverse events are coded using MedDRA 15.0. ヨ [LPMDASF10A.rtf] [CNTO1275\CRD3003\DBR_CSR\RE_PMDA\lpmdasf10a.sas] 20SEP2016, 21:43 㦂 ࡵ
48
(38) ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3001
2) ᪥ᮏே㞟ᅋ ⾲ 2.7.6.2 -10 㔜⠜࡞᭷ᐖ㇟ཬࡧ㦂⸆ྜ⌮ⓗ㛵㐃ᛶࡀ࠶ࡿ㔜⠜࡞᭷ᐖ㇟㸦8 㐌┠ࡲ࡛㸧㸦㦂⸆ࢆᢞࡉࢀࡓ⿕㦂⪅㸧 Study Agent Start Day Age Dose of AE / 2.7.6 Treatment Subject (yrs)/ Prior to Duration MedDRA Infusion Relation to Group ID Sex AE (days) Preferred Term Verbatim Term Infectiona Reaction Serious Severity Study Agent Action Taken Outcome Placebo IV 4211-10853 4/M 0 mg 15/75 ࢡ࣮ࣟࣥ WORSENING OF No No Yes SEVERE NOT DOSE NOT RECOVERED/RESOLVED THE CROHN'S RELATED CHANGED DISEASE 4216-11134 2/F 0 mg 53/87 ࢡ࣮ࣟࣥ DETERIORATION No No Yes MODERATE NOT DRUG RECOVERED/RESOLVED OF CROHN'S RELATED WITHDRAWN DISEASE
a Infection as assessed by the investigator. Include all the AEs through Week 8 and the AEs after Week 8 occurred in the subjects who did not enter maintenance study. Adverse events are coded using MedDRA 15.0. [LPMDASF10B.rtf] [CNTO1275\CRD3003\DBR_CSR\RE_PMDA\lpmdasf10b.sas] 20SEP2016, 21:43
ಶ ࠎ ࡢヨ 㦂 ࡢࡲ ヨ 㦂 ࡵ
49 ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
2.7.6.2.3.1 Narratives 㦂⸆ྜ⌮ⓗ㛵㐃ᛶࡀ࠶ࡿ SAE ཬࡧ㔜⠜࡞ឤᰁࢆⓎ⌧ࡋࡓ⿕㦂⪅ࡢヲ⣽ࢆ௨ୗ♧ࡍࠋ
Table of Narratives Subject Death Japanese Related SAE Serious Number infection 1057-10264 X X 1072-10025 X X 3302-10290 X X 3314-10335 X 3421-10675 X X 4602-10902 X X 1046-10180 X 1091-10037 X 1107-10978 X 3306-10824 X 4111-10672 X 4603-10982 X 5610-10835 X
(1) Subject CNTO1275CRD3001-1057-10264
1) Reason for narrative selection SAE Event of interest: Serious infection
2) Adverse Events Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day) (Verbatim Term) SAE Relatedness Trt? Outcome (Study day) 2012-06-19 Ⴔ╀ N MILD/ N/ DOSE NOT CHANGED/ Ongoing (8) (INCREASED LETHARGY) POSSIBLE NA NOT RECOVERED/NOT RESOLVED - 2012-06-25 ⭠⟶⮋⒆ Y SEVERE/ Y/ DOSE NOT CHANGED/ 2012-07-15 (14) (SIGMOID ABSCESS) POSSIBLE Y RECOVERED/RESOLVED (34)
3) Baseline Demographic Information Age (years): 4 Sex: Female Weight (kg): 71.2 Race: White Date of birth: Height (cm): 170.2
4) Induction Treatment Group Randomized Treatment Group: Ustekinumab Approximating 6 mg/kg IV Actual Treatment Group: Ustekinumab Approximating 6 mg/kg IV
5) Induction Treatment Received Visit Start Date Study Day Dose Number Actual Treatment Dose WEEK 0 2012-06-12 1 1 Ustekinumab Approximating 6 mg/kg IV 389.7 mg
6) Induction Disposition Did subject complete the induction study?: Y Did subject enter maintainance study?: Y
50 (39) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
7) Baseline Crohn's Disease History Date of diagnosis: 31DEC1995 Disease duration: 16.45 years Involved areas: ⤖⭠ࡢࡳ
8) Crohn's Disease Complications Before Baseline Intra-abdominal abscess: Never Sinus tracts/perforation: Never Fistula: Never Stricture complications of (CD): Never
9) Concomitant Crohn's Disease-Related Surgeries None reported
10) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 0 PREDNISONE 10 mg 10
11) Concomitant Medications Preferred Term Start Date End Date Reason Route ETHINYL ESTRADIOL - - OTHER (BIRTH CONTROL) ORAL W/NORGESTREL IRON 2012 2012 OTHER (IRON DEFICIENCY) INTRAVENOUS PREDNISONE 2012-01 2012-08- CROHN'S DISEASE ORAL 27 DIPHENHYDRAMINE 2012-06- 2012-06- OTHER (INFUSION INTRAVENOUS HYDROCHLORIDE 12 12 PREMEDICATION) PARACETAMOL 2012-06- 2012-06- OTHER (INFUSION PRE ORAL 12 12 MEDICATION) METRONIDAZOLE 2012-06- 2012-06- ADVERSE EVENT INTRAVENOUS 25 27 CIPROFLOXACIN 2012-06- 2012-06- ADVERSE EVENT INTRAVENOUS 26 27 CIPROFLOXACIN 2012-06- 2012-07- ADVERSE EVENT ORAL 27 15 METRONIDAZOLE 2012-06- 2012-07- ADVERSE EVENT ORAL 27 15
12) Narrative Text ⿕㦂⪅ࡣ 4 ṓࡢⓑேዪᛶ࡛㸪2012 ᖺ 6 ᭶ 12 ᪥ᐶゎᑟධ⒪ἲࡋ࡚ᮏ㸦㹼6 mg/kg ⩌㸧ࢆ 㟼⬦ෆᢞࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪ᶵ㣧㓇㸪S ≧ ⤖⭠⮋⒆ࡼࡿ⫼㒊③㸪⭠ෆど㙾᳨ᰝᐇࡳࡽࢀࡓ S ≧⤖⭠ࡢ㧗ᗘࡢ⅖ཬࡧᕥྑ⤖⭠᭤ ࡢ῝࠸₽⒆㸦2011 ᖺ 12 ᭶ 9 ᪥㸧୪ࡧ⸆ㄏⓎᛶ࣮ࣝࣉࢫ㸦㑇ఏᏊ⤌࠼⸆ࡢࣥࣇࣜ࢟ࢩ࣐ ࣈ㸪ࢲ࣒࣐ࣜࣈཬࡧ certolizumab pegol ࡼࡿ㸧࡛࠶ࡗࡓࠋᐙ᪘Ṕࡣ㸪ෙື⬦ᛶᚰᝈཬࡧ⤖⭠ ⒴㸦♽∗㸧࡛࠶ࡗࡓࠋ SAE/Serious infection㸸⭠⟶⮋⒆㸦Day 14㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2012 ᖺ 6 ᭶ 25 ᪥ୗ⫼㒊③㸦2 ࣧ᭶๓Ⓨ⌧ࡋ㸪2 ᪥๓ᝏ㸧 ࡀࡳࡽࢀࡓࡓࡵ㸪ධ㝔ࡋࡓࠋ⿕㦂⪅ࡣ③ࡳࢆᩘ್࡛⾲ࡍ⑊③ࢫࢣ࣮࡛ࣝ 10/10 ホ౯ࡋ㸪௮⮩ ࡞ࡿᝏࡍࡿッ࠼ࡓࠋ⌮Ꮫⓗ᳨ᰝ࡛ࡣ㸪㦵୧ഃཬࡪ⫼㒊య࡛ᅽ③ࡀࡳࡽࢀࡓࠋ2012
51 (40) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
ᖺ 6 ᭶ 25 ᪥ᐇࡋࡓ⭡㒊ཬࡧ㦵┙㒊ࡢࢥࣥࣆ࣮ࣗࢱ᩿ᒙᙳ㸦CT㸧ࢫ࡛࢟ࣕࣥࡣ㸪S ≧⤖⭠ ㏆ࣇࣞࢢ࣮ࣔࢿᵝኚࡀࡳࡽࢀ㸪S ≧⤖⭠ࡢୖ㒊 2.8×2.0 cm ࡢ༙ᅛయࡢ㈓␃≀ࡀࡳࡽࢀࡓࠋ ᾘჾᏛࡢᑓ㛛ᐙࡣ㸪S ≧⤖⭠ࣇࣞࢢ࣮ࣔࢿࢆక࠺⅖ࡀࡳࡽࢀࡿࡀ㸪⮋ྍ⬟࡞⮋⒆ࡣ࡞ ࠸デ᩿ࡋࡓࠋ⿕㦂⪅ࡣᢠ⏕≀㉁ࢆ 2 ᪥㛫㟼⬦ෆᢞࡉࢀࡓᚋ㸪ࢩࣉࣟࣇࣟ࢟ࢧࢩࣥཬࡧ࣓ࢺࣟ ࢽࢲࢰ࣮ࣝࡢ⤒ཱྀᢞ⛣⾜ࡋ㸪2012 ᖺ 6 ᭶ 27 ᪥㏥㝔ࡋࡓࠋ㏥㝔㸪⿕㦂⪅ࡣ⤒ཱྀᦤྲྀྍ⬟ ࡛࠶ࡾ㸪⭡㒊ࡣᰂࡽࡃ㸪⭡⭷≧ཬࡧᅽ③ࡣࡳࡽࢀ࡞ࡗࡓࠋ㏥㝔㸪⤒ཱྀࡢࢩࣉࣟࣇࣟ ࢟ࢧࢩࣥ㸪࣓ࢺࣟࢽࢲࢰ࣮ࣝ㸪prednisone ཬࡧࣃࣛࢭࢱ࣮ࣔࣝ㸭࢜࢟ࢩࢥࢻࣥࡀฎ᪉ࡉࢀࡓࠋ 2012 ᖺ 7 ᭶ 2 ᪥ࡢ㏣㊧ㄪᰝᐇࡉࢀࡓ CT ⭠㐠ືグ㘓ἲ࡛ࡣ㸪S ≧⤖⭠ 2 cm ࡢ⮋⒆ࢆక࠺ ࣇࣞࢢ࣮ࣔࢿࡀࡳࡽࢀࡓࠋ⮋⒆ࡣࢃࡎ࡞ᾮయࡀྵࡲࢀ㸪⮋⒆࿘㎶ཬࡧᑠ⭠ࡢ▷࠸༊ᇦཬࡪ ⅖ᛂࡀࡳࡽࢀࡓࠋᑠ⭠ࡣ⒦Ꮝࡣࡳࡽࢀ࡞ࡗࡓࠋ⭠ࡢࡑࡢࡢ㒊ศ␗ᖖࡣ࡞ࡃ㸪ࢡ࣮ࣟ ࣥࡢᡤぢࡣࡳࡽࢀ࡞ࡗࡓࠋ౽ᛶ≧ࡣ㸪Ỉᵝ౽ࡽ⢓ᾮࡢ╔ࡋࡓࡸࢃࡽ࠸౽࡛㸪౽ᅇᩘ ࡀከࡗࡓ㸦1 ᪥ 6 ᅇ㸧ࡀ㸪2012 ᖺ 7 ᭶ 3 ᪥㸪ࡁ࡞ᨵၿࡀࡳࡽࢀࡓࠋࡲࡓ㸪⿕㦂⪅ࡣ㛫Ḟⓗ ࡞ᐷờࢆッ࠼ࡓࠋ2012 ᖺ 7 ᭶ 15 ᪥ᢠ⏕≀㉁ᢞࢆ⤊ࡋ㸪ྠ᪥ S ≧⤖⭠⮋⒆ࡣᾘᩓࡋࡓ ሗ࿌ࡉࢀࡓࠋ
(2) Subject CNTO1275CRD3001-1072-10025
1) Reason for narrative selection SAE Discontinuation of study agent due to AE Event of interest: Serious infection
2) Adverse Events Start date End date (Study Preferred Term Intensity/ Inf/ Action Taken/ (Study day) (Verbatim Term) SAE Relatedness Trt? Outcome day) 2011-09- ື N MILD/ N/ NOT APPLICABLE/ 2011-09- 06 (HEART PALPITATIONS) NOT NA RECOVERED/RESOLVED 28 (-13) RELATED (10) 2011-09- ㈋⾑ N MODERATE/ N/ NOT APPLICABLE/ 2011-09- 06 (WORSENING ANEMIA) NOT NA RECOVERED/RESOLVED 14 (-13) RELATED (-5) 2011-09- ⭡③ N MILD/ N/ NOT APPLICABLE/ Ongoing 16 (ABDOMINAL PAIN) NOT NA NOT RECOVERED/NOT - (-3) RELATED RESOLVED 2011-09- ࣞࣝࢠ࣮ᛶ㍺⾑ᛂ Y MODERATE/ N/ NOT APPLICABLE/ 2011-09- 16 (ALLERGIC REACTION TO BLOOD NOT NA RECOVERED/RESOLVED 18 (-3) TRANSFUSION) RELATED (-1) 2011-09- ⶼ㯞⑈ N MODERATE/ N/ NOT APPLICABLE/ 2011-09- 16 (HIVES) NOT NA RECOVERED/RESOLVED 18 (-3) RELATED (-1) 2011-09- ࡑ࠺ N MODERATE/ N/ NOT APPLICABLE/ 2011-09- 16 (ITCHING) NOT NA RECOVERED/RESOLVED 18 (-3) RELATED (-1) 2011-09- ᝏᚰ N MILD/ N/ NOT APPLICABLE/ 2011-09- 16 (NAUSEA) NOT NA RECOVERED/RESOLVED 18 (-3) RELATED (-1) 2011-09- ⶼ㯞⑈ N MILD/ N/ DRUG INTERRUPTED/ 2011-09- 19 (HIVES) PROBABLE NA RECOVERED/RESOLVED 19 (1) (1) 2011-09- ࡑ࠺ N MILD/ N/ DRUG INTERRUPTED/ 2011-09- 19 (ITCHING) PROBABLE NA RECOVERED/RESOLVED 19 (1) (1)
52 (41) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
Start date End date (Study Preferred Term Intensity/ Inf/ Action Taken/ (Study day) (Verbatim Term) SAE Relatedness Trt? Outcome day) 2011-10- 㛵⠇③ N MILD/ N/ DOSE NOT CHANGED/ Ongoing 15 (ARTHRALGIAS) NOT NA NOT RECOVERED/NOT - (27) RELATED RESOLVED 2011-10- ⭠⟶⮋⒆ Y SEVERE/ Y/ DRUG WITHDRAWN/ 2011-11- 31 (ABSCESS IN RIGHT COLON) POSSIBLE Y RECOVERED/RESOLVED 12 (43) (55)
3) Baseline Demographic Information Age (years): 4 Sex: Female Weight (kg): 65.9 Race: White Date of birth: Height (cm): 160.0
4) Induction Treatment Group Randomized Treatment Group: Ustekinumab 130 mg IV Actual Treatment Group: Ustekinumab 130 mg IV
5) Induction Treatment Received Visit Start Date Study Day Dose Number Actual Treatment Dose WEEK 0 2011-09-19 1 1 Ustekinumab 130 mg IV 130 mg
6) Induction Disposition Did subject complete the induction study?: Y Did subject enter maintainance study?: N
7) Baseline Crohn's Disease History Date of diagnosis: 31DEC1995 Disease duration: 15.72 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪⭠⟶እ≧㸦㛵⠇⅖㸭㛵⠇③㸪ཎⓎᛶ◳ᛶ⫹⟶⅖㸧
8) Crohn's Disease Complications Before Baseline Intra-abdominal abscess: Never Sinus tracts/perforation: Never Fistula: Never Stricture complications of (CD): Never
9) Concomitant Crohn's Disease-Related Surgeries Surgery Date Result of lack of efficacy? ษ㝖㸫ᅇ⭠ 2011-11-02 Y
10) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 0 PREDNISONE 30 mg 30
11) Concomitant Medications Start End Preferred Term Date Date Reason Route URSODEOXYCHOLIC ACID 2010-11 - OTHER (SCHLEROSING ORAL CHOLANGITIS) CHLORDIAZEPOXIDE 2011- - OTHER (ABDOMINAL CRAMPING) ORAL W/CLIDINIUM 01-21 COLESEVELAM HYDROCHLORIDE 2011- - CROHN'S DISEASE ORAL 04-25 LOMOTIL 2011- - OTHER (DIARRHEA) ORAL 06-03
53 (42) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
Start End Preferred Term Date Date Reason Route PREDNISONE 2011- - CROHN'S DISEASE ORAL 08-11 VICODIN 2011- - OTHER (ABDOMINAL PAIN) ORAL 09-16 PROMETHAZINE 2011- - OTHER (NAUSEA) ORAL 09-16 CETIRIZINE HYDROCHLORIDE 2011- - OTHER (HIVES AND ITCHING) ORAL 09-16 DIPHENHYDRAMINE 2011- 2012- OTHER (PREDMEDICATED BEFORE ORAL HYDROCHLORIDE 09-19 09-19 MEDICATION INFUSION) DIPHENHYDRAMINE 2011- 2011- OTHER (ITCHING/HIVES) INTRAVENOUS HYDROCHLORIDE 09-19 09-19 DIPHENHYDRAMINE 2011- 2011- ADVERSE EVENT INTRAVENOUS HYDROCHLORIDE 11-02 11-08 HYDROMORPHONE 2011- 2011- ADVERSE EVENT INTRAVENOUS HYDROCHLORIDE 11-02 11-11 SODIUM CHLORIDE 2011- 2011- ADVERSE EVENT INTRAVENOUS 11-02 11-08 METHYLPREDNISOLONE SODIUM 2011- 2011- ADVERSE EVENT INTRAVENOUS SUCCINATE 11-02 11-11 ONDANSETRON 2011- 2011- ADVERSE EVENT INTRAVENOUS 11-02 11-11 PIP/TAZO 2011- 2011- ADVERSE EVENT INTRAVENOUS 11-02 11-12 ENOXAPARIN SODIUM 2011- 2011- ADVERSE EVENT SUBCUTANEOUS 11-04 11-12 SALBUTAMOL 2011- 2011- ADVERSE EVENT RESPIRATORY 11-05 11-07 (INHALATION) ERYTHROMYCIN 2011- 2011- ADVERSE EVENT ORAL 11-07 11-07 NEOMYCIN 2011- 2011- ADVERSE EVENT ORAL 11-07 11-07 PROMETHAZINE 2011- 2011- ADVERSE EVENT INTRAVENOUS 11-07 11-12 DEXTROSE AND SODIUM 2011- 2011- ADVERSE EVENT INTRAVENOUS CHLORIDE INJECTION 11-08 11-12 LABETALOL 2011- 2011- ADVERSE EVENT INTRAVENOUS 11-08 11-08 RINGER-LACTATE 2011- 2011- ADVERSE EVENT INTRAVENOUS 11-08 11-08 FAMOTIDINE 2011- 2011- ADVERSE EVENT ORAL 11-08 11-12 HYOSCINE 2011- 2011- ADVERSE EVENT TRANSDERMAL 11-08 11-08 MIDAZOLAM HYDROCHLORIDE 2011- 2011- ADVERSE EVENT INTRAVENOUS 11-08 11-08 VICODIN 2011- - ADVERSE EVENT ORAL 11-11 AZATHIOPRINE 2011- - CROHN'S DISEASE ORAL 11-12 ADALIMUMAB 2011- - CROHN'S DISEASE SUBCUTANEOUS 12-13
12) Narrative Text ⿕㦂⪅ࡣ 4 ṓࡢⓑேዪᛶ࡛㸪2011 ᖺ 9 ᭶ 19 ᪥ᐶゎᑟධ⒪ἲࡋ࡚ᮏ㸦130 mg ⩌㸧ࢆ㟼 ⬦ෆᢞࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪㈋⾑㸪㍍ᗘࡢ ୖẼ㐨ឤᰁ㸪⭡㒊②ᨥ㸪៏ᛶ⭡③㸪ୗ⑩㸪ᝏᚰ㸪ࣔࣝࣄࢿࣞࣝࢠ࣮㸪⫹ᄞษ㝖㸪ᖇ⋤ษ㛤㸪༸ ⟶⤖⣻㸪⫢⏕᳨ࡢࡓࡵࡢෆど㙾ⓗ㏫⾜ᛶ⫹㐨⮅⟶ᙳ㸦ERCP㸧ཬࡧ⊃✽ᑐࡍࡿࢫࢸࣥࢺ␃⨨
54 (43) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
࡛࠶ࡗࡓࠋ⤌ධࢀ๓ࡢ 2011 ᖺ 3 ᭶ 11 ᪥ࡽ 2011 ᖺ 6 ᭶ 11 ᪥ࡲ࡛㸪ࣥࣇࣜ࢟ࢩ࣐ࣈࢆ 4 ᅇᢞ ࡉࢀ࡚࠸ࡓࡇࡀሗ࿌ࡉࢀࡓࠋ2011 ᖺ 9 ᭶ 6 ᪥ࡢ⭠ෆど㙾᳨ᰝ࡛ࡣ㸪ᅇ⭠ࡣṇᖖぢ࠼ࡓࡀ㸪 እ⛉ⓗ࿀ྜ㒊ࡢ≧₽⒆㸪┤⭠㒊࡛ࡢṇᖖ⤌⧊ࡢ᫂ࡽ࡞㑄⛣ࢆక࠺ S ≧⤖⭠࡛ࡢᣢ⥆ⓗ⅖ࢆక ࠺άືᮇࡢ⤖⭠ᝈࡀࡳࡽࢀࡓࠋ SAE㸸ࣞࣝࢠ࣮ᛶ㍺⾑ᛂ㸦Day -3㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ㸪㦂⸆ࡼࡿᐶゎᑟධ⒪ἲ๓ࡢ 2011 ᖺ 9 ᭶ 14 ᪥㸪㈋⾑ᑐ ࡋ࡚ 12 㛫ࡅ࡚ 3 ༢ࡢ㉥⾑⌫㍺⾑ࢆཷࡅࡓ㹙2011 ᖺ 9 ᭶㸦᪥᫂㸧ࡢ࣊ࣔࢢࣟࣅ್ࣥ㸸 7 g/dL㸦ṇᖖ⠊ᅖ 12-16 g/dL㸧㹛ࠋ㍺⾑୰✺↛㸪ࡑ࠺㸪Ⓨ⑈㸪୪ࡧᾋືᛶࡵࡲ࠸ࢆక࠺๓ 㢌㒊ཬࡧᚋ㢌㒊ࡢ㢌③ࢆⓎ⌧ࡋ㸪ࢪࣇ࢙ࣥࣄࢻ࣑ࣛࣥࡀᢞࡉࢀࡓࠋࡉࡽࡑࡢᚋᩘ᪥㛫㸪⫼ 㒊③㸪▷ᮇ㛫ࡢ྾ᅔ㞴ࢆక࠺㛫Ḵⓗ࡞ື㸦⬚③ࡣ࡞ࡋ㸧㸪ᾋືᛶࡵࡲ࠸ឤ㸪ཬࡧ₻⣚ࢆⓎ⌧ ࡋࡓࠋࡇࢀࡽ㇟ࡢⓎ⌧⥆࠸࡚ኻ⚄ࡀࡳࡽࢀࡓࠋ2011 ᖺ 9 ᭶ 16 ᪥㸪㍺⾑ᑐࡍࡿࣞࣝࢠ ࣮ᛂデ᩿ࡉࢀ㸪ධ㝔ࡋࡓࠋࣂࢱࣝࢧࣥࡣ㸪య ࡣ 97.7°F㸪ᚰᢿᩘࡣ 62 ᢿ㸭ศ㸪྾ᩘ ࡣ 18 ᅇ㸭ศ㸪⾑ᅽࡣ 138/80 mmHg㸪ᐊෆ✵Ẽ྾ࡢ㓟⣲㣬ᗘࡣ 98%࡛࠶ࡗࡓࠋ⿕㦂⪅ࡣぬ 㓰ࡋ࡚࠾ࡾ㸪ぢᙜ㆑ࡀಖࡓࢀ㸪ᛴ㏕≧ࡢ࡞࠸㍍ᗘࡢᏳࡀࡳࡽࢀࡓࠋⓎ⑈ࡣሗ࿌ࡉࢀ࡞ࡗࡓࠋ ࢸ࣓ࣞࢺ࣮࡛ࣜࡣ㸪ᚰᐊᛶᮇእ⦰ཬࡧṇᖖ࡞Ὕㄪᚊࡀࡳࡽࢀࡓࠋධ㝔࣊ࣔࢢࣟࣅ್ࣥࡣ 11.6 g/dL㸪ⓑ⾑⌫ᩘ㸦WBC㸧ࡣ 15.5×103/mm3㹙ṇᖖ⠊ᅖ㸦NR㸧3.8-10.6×103/mm3㸧㹛࡛࠶ࡗࡓࠋ ྠ᪥ᐇࡋࡓᚰ㟁ᅗ㸪⬚㒊 X ⥺᳨ᰝ㸪㢌㒊ࢥࣥࣆ࣮ࣗࢱ᩿ᒙᙳ㸦CT㸧㸪⫢ᶵ⬟᳨ᰝཬࡧᒀ ୰⸆≀ࢫࢡ࣮ࣜࢽࣥࢢ࡛ࡣ㸪␗ᖖࡣ࡞ࡗࡓࠋ⁐⾑ࡶࡳࡽࢀ࡞ࡗࡓࠋ2011 ᖺ 9 ᭶ 17 ᪥ࡢ C ᛂᛶࡓࢇⓑ⃰ᗘࡣṇᖖ⠊ᅖෆ࡛࠶ࡾ㸪┤᥋ࢡ࣮࣒ࢫヨ㦂ࡣ㝜ᛶ࡛࠶ࡗࡓࠋ2011 ᖺ 9 ᭶ 18 ᪥࣊ ࣔࢢࣟࣅ್ࣥࡣ 10 g/dL ῶᑡࡋࡓࠋࢪࣇ࢙ࣥࣄࢻ࣑ࣛࣥࡼࡿᑐ⒪ἲࢆ⾜࠸㸪ࣂࢱࣝࢧ ࣥཬࡧ࣊ࣔࢢࣟࣅ್ࣥࡣᨵၿࡋ㸪Ᏻᐃࡋࡓ≧ែ࡞ࡗࡓࠋ2011 ᖺ 9 ᭶ 18 ᪥㸪ᮏ㇟ࡣᾘᩓࡋ ࡓุ᩿ࡉࢀ㸪⿕㦂⪅ࡣ㏥㝔ࡋࡓࠋ SAE㸸⭠⟶⮋⒆㸦Day 43㸧 CIOMS ࡼࡿ㸪2011 ᖺ 10 ᭶ 31 ᪥ࡢ 6 㐌┠ࡢ᮶㝔⾑౽࡛ࡣ࡞࠸ࡀ㢖ᅇࡢኪ㛫㌾౽ཬࡧ ྑഃ⭡㒊③ࢆッ࠼ࡓࡓࡵ㸪᳨ᰝࢆ⾜ࡗࡓࠋྠ᪥ࡢ⮫ᗋ᳨ᰝࡢ⤖ᯝ࡛ࡣ㸪ࢫࣃࣛࢠࣥ㓟࣑ࣀ ࢺࣛࣥࢫࣇ࢙࣮ࣛࢮ㸦AST㸧್ࡢ㍍ᗘቑຍࡀࡳࡽࢀ㸪࣊ࣔࢢࣟࣅ್ࣥࡣ 10.6㸦༢ཬࡧ NR ࡢグ ㍕࡞ࡋ㸧࡛࠶ࡾ㸪ⓑ⾑⌫ᩘཬࡧ⾑ᑠᯈᩘࡣṇᖖ⠊ᅖෆ࡛࠶ࡗࡓࠋ2011 ᖺ 11 ᭶ 1 ᪥⭡③ࡣᝏ ࡋࡓࠋ⩣᪥ࡢ⭡㒊ཬࡧ㦵┙㒊ࡢ CT ࢫ࡛࢟ࣕࣥࡣ㸪⅖ᛶ⭠ᝈ୍⮴ࡍࡿྑഃ⤖⭠ཬࡧᶓ⾜⤖ ⭠ࡢ⅖ᛶኚࡀࡳࡽࢀࡓࠋྑഃࡢ⤖⭠࿀ྜࡢ⦭ྜ⥺ࡑࡗ࡚㸪᪩ᮇࡢ⮋⒆⪃࠼ࡽࢀࡿᑡ㔞ࡢ ᾮయཬࡧ✵Ẽࡢ㈓␃ࡀࡳࡽࢀࡓࠋ2011 ᖺ 11 ᭶ 2 ᪥ྑഃ⤖⭠ࡢ⮋⒆デ᩿ࡉࢀ㸪ධ㝔ࡋࡓࠋධ 㝔ࡢ⌮Ꮫⓗᡤぢ࡛ࡣ㸪⭡㒊య㍍ᗘࡢᅽ③ཬࡧྑ୰⭡㒊㢧ⴭ࡞ᅽ③ࡀࡳࡽࢀࡓࠋᴟᗘࡢ⑊ ③ࡀࡳࡽࢀࡓࡢࡣࡼࡾࢃࡎୖ㒊ࡢྑഃ⣙ 2 ࣥࢳࡢ⟠ᡤ࡛࠶ࡗࡓࠋᢠ⏕≀㉁ཬࡧࢥࣝࢳࢥࢫ ࢸࣟࢻࡢὀᑕ⸆㸪㟼⬦ෆ⿵ᾮཬࡧ㙠③⸆ࡢᢞࢆ㛤ጞࡋࡓࠋ2011 ᖺ 11 ᭶ 8 ᪥㸪ᅇ⭠⤖⭠࿀ ྜ㒊㛵㐃ࡍࡿ㒊ࡢ⮋⒆ࢆ㝖ཤࡋ㸪㞄᥋ࡍࡿ⭠༊ᇦࢆ୍ḟ࿀ྜࡋࡓࠋ㝖ཤ⤌⧊ࡢ⌮Ꮫⓗ᳨ ᰝࡢ⤖ᯝ࡛ࡣ㸪ᅛ᭷➽ᒙᒁᡤⓗᏑᅾࡍࡿᑠ⮋⒆㸪㢧ⴭ࡞⅖ࢆ㉳ࡇࡋ࡚࠸ࡿࡀ㒊ศࡣṇᖖ ࡞ᑠ⭠㸪ཬࡧ⢓⭷ࡀ₽⒆ࡋࡓ⤖⭠㒊ࡀࡳࡽࢀࡓࠋ᫂☜࡞⫗ⱆ⭘ࡣ᳨ฟࡉࢀ࡞ࡗࡓࡀ㸪 ࢡ୍࣮ࣟࣥ⮴ࡍࡿ⤌⧊Ꮫⓗኚࡀࡳࡽࢀࡓࠋ⿕㦂⪅ࡢ⾡ᚋ⤒㐣ࡣⰋዲ࡛࠶ࡾ㸪⾡ᚋ 3 ᪥࡛㣗 ࡀྍ⬟࡛࠶ࡗࡓࠋᢠ⏕≀㉁ࡢᢞࢆ୰Ṇࡋࡓࡀ㸪Ⓨ⇕ࡣⓎࡋ࡞ࡗࡓࠋ
55 (44) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
2011 ᖺ 11 ᭶ 12 ᪥㸪⿕㦂⪅ࡣྑഃ⭠⟶⮋⒆ࡽᅇࡋ㸪ྠ᪥㸪Ᏻᐃࡋࡓ≧ែ࡛㏥㝔ࡋࡓࠋ㏥ 㝔๓ࡢ⮫ᗋ᳨ᰝࡢ⤖ᯝ࡛ࡣ㸪࣊ࣔࢢࣟࣅࣥ 8.8㸪WBC 13,000㸪⾑ᑠᯈᩘ 348,000㸦༢ཬࡧ NR ࡢ ࠸ࡎࢀࡶグ㍕࡞ࡋ㸧࡛࠶ࡗࡓࠋ㏥㝔㸪prednisone㸪⿕㦂⪅ࡢ࣓ࣥࢸࢼࣥࢫ⏝⸆࡛࠶ࡿ ursodiol ཬࡧ㕲Ḟஈᛶ㈋⾑ࡢࡓࡵࡢ㕲⿵⸆ࢆฎ᪉ࡉࢀࡓࠋࢨࢳ࢜ࣉࣜࣥᢞࡶ㛤ጞࡋࡓࠋ
(3) Subject CNTO1275CRD3001-3302-10290
1) Reason for narrative selection SAE Discontinuation of study agent due to AE Event of interest: Opportunistic infection Event of interest: Serious infection 2) Adverse Events Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day) (Verbatim Term) SAE Relatedness Trt? Outcome (Study day) 2012-07-18 ࣜࢫࢸࣜ⳦ᛶ㧊⭷⅖ Y SEVERE/ Y/ DRUG WITHDRAWN/ 2012-08-08 (21) (LISTERIA MENINGITIS) VERY LIKELY Y RECOVERED/RESOLVED (42)
3) Baseline Demographic Information ȋȌǣ ͵͵ ǣ ȋȌǣ ͷǤͲ ǣ ǣ ͳͻͺǦͳͲǦʹͻ ȋ Ȍǣ ͳͺͳǤͲ
4) Induction Treatment Group Randomized Treatment Group: Ustekinumab Approximating 6 mg/kg IV Actual Treatment Group: Ustekinumab Approximating 6 mg/kg IV 5) Induction Treatment Received Visit Start Date Study Day Dose Number Actual Treatment Dose WEEK 0 2012-06-28 1 1 Ustekinumab Approximating 6 mg/kg IV 389.7 mg
6) Induction Disposition Did subject complete the induction study?: N Reason for induction early termination: WITHDRAWAL OF CONSENT Date of early termination: 2012-07-30 Did subject enter maintainance study?: N 7) Baseline Crohn's Disease History Date of diagnosis: 09OCT2000 Disease duration: 11.72 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪⫠㛛࿘ᅖ
8) Crohn's Disease Complications Before Baseline Intra-abdominal abscess: Never Sinus tracts/perforation: Never Fistula: Never Stricture complications of (CD): Currently present
56 (45) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
9) Concomitant Crohn's Disease-Related Surgeries None reported 10) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 0 PREDNISONE 30 mg 30 EARLY TERMINATION PREDNISOLONE 20 mg 20 EARLY TERMINATION PREDNISOLONE 30 mg 30
11) Concomitant Medications Preferred Term Start Date End Date Reason Route PREDNISOLONE SODIUM SULFOBENZOATE 2012-05-18 2012-07-18 CROHN'S DISEASE ORAL ACICLOVIR 2012-07-18 2012-07-22 ADVERSE EVENT INTRAVENOUS AMOXICILLIN 2012-07-18 2012-08-08 ADVERSE EVENT INTRAVENOUS GENTAMICIN 2012-07-18 2012-07-23 ADVERSE EVENT INTRAVENOUS CEFTRIAXONE SODIUM 2012-07-18 2012-07-22 ADVERSE EVENT INTRAVENOUS PREDNISOLONE 2012-07-19 2012-07-21 ADVERSE EVENT ORAL PREDNISOLONE 2012-07-22 - ADVERSE EVENT ORAL
12) Narrative Text ⿕㦂⪅ࡣ 3 ṓࡢⓑே⏨ᛶ࡛㸪2012 ᖺ 6 ᭶ 28 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏ㸦㹼6 mg/kg ⩌㸧 ࢆ㟼⬦ෆᢞࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪ࢥࣝࢳࢥࢫࢸ ࣟࢻ౫Ꮡ㸪࣓ࢺࢺࣞ࢟ࢧ࣮ࢺཬࡧࢨࢳ࢜ࣉࣜࣥ᭹⏝ࡢ⒪ᢠᛶ࡛࠶ࡗࡓࠋ⿕㦂⪅ࡣ㠀ႚ ↮⪅࡛࠶ࡗࡓࠋ SAE/Serious infection/Opportunistic infection/Discontinuation of study agent due to AE㸸ࣜࢫࢸࣜ ⳦ᛶ㧊⭷⅖㸦Day 21㸧 ⿕㦂⪅ࡣ 2012 ᖺ 7 ᭶ 14 ᪥ࡼࡾⓎ⇕㸪2012 ᖺ 7 ᭶ 17 ᪥ࡼࡾྤ㸪㢌③ཬࡧ⩈᫂ࢆッ࠼࡚࠸ࡓࠋ 2012 ᖺ 7 ᭶ 18 ᪥ࡢᩆᛴእ᮶ཷデᐇࡉࢀࡓ⭜᳝✸่ࡢ⤖ᯝ㸪ࣜࣥࣃ⌫ 60%ཬࡧዲ୰⌫ 40% ࡛࠶ࡾ㸪㧊⭷⅖デ᩿ࡉࢀࡓࠋ㧊ᾮᇵ㣴᳨ᰝࡢ⤖ᯝࡣ㸪ࣜࢫࢸ࣭ࣜࣔࣀࢧࢺࢤࢿࢫ㝧ᛶ࡛࠶ ࡗࡓࠋ⿕㦂⪅ࡢᒃఫ༊ᇦ࡛ࣜࢫࢸࣜ⳦ࡼࡿ㞟ᅋឤᰁࡣ࡞ࡗࡓࡀ㸪⿕㦂⪅ࡣᒇእసᴗࢆࡋࡓ ࡢࡇ࡛࠶ࡗࡓࠋ ⿕㦂⪅ࡣྠ᪥ධ㝔ࡋ㸪ᙜึࢤࣥࢱ࣐ࢩࣥ㸪ࢭࣇࢺࣜ࢟ࢯࣥ㸦ࣟࢭࣇࣥ㸧㸪ࢩࢡࣟࣅࣝ ཬࡧࣔ࢟ࢩࢩࣜࣥࢆ㟼⬦ෆᢞࡉࢀࡓࡀ㸪ࣜࢫࢸࣜ⳦ᛶ㧊⭷⅖ࡢデ᩿ᚋࡣ㸪ࢤࣥࢱ࣐ࢩࣥ 400 mg ࡢ 5 ᪥㛫㟼⬦ෆᢞཬࡧࣔ࢟ࢩࢩࣜࣥ 1 ᪥ 12 g ࡢ 3 㐌㛫㟼⬦ෆᢞኚ᭦ࡉࢀࡓࠋ ⿕㦂⪅ࡣ⒪ࡀዌຠࡋࡓሗ࿌ࡉࢀࡓࠋ2012 ᖺ 7 ᭶ 19 ᪥Ⓨ⇕ཬࡧ㧊⭷่⃭≧ࡣᾘᩓࡋ㸪C ᛂᛶࡓࢇⓑ⃰ᗘࡶ 200 mg/L ࡽ 90 mg/L పୗࡋࡓࠋࢡ࣮ࣟࣥࡢ≧ࡣᏳᐃࡋࡓሗ࿌ࡉ ࢀࡓࠋ ⿕㦂⪅ࡣ 2012 ᖺ 7 ᭶ 30 ᪥㏥㝔ࡋ㸪2012 ᖺ 8 ᭶ 8 ᪥ᅇࡋࡓሗ࿌ࡉࢀࡓࠋᮏ㇟ ᑐࡍࡿ⒪㸦ࣔ࢟ࢩࢩࣜࣥࢆྵࡴ㸧ࡶࡲࡓ 2012 ᖺ 8 ᭶ 8 ᪥୰Ṇࡉࢀࡓࠋ
57 (46) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
(4) Subject CNTO1275CRD3001-3314-10335
1) Reason for narrative selection SAE Discontinuation of study agent due to AE
2) Adverse Events Start date End date (Study Preferred Term Intensity/ Inf/ Action Taken/ (Study day) (Verbatim Term) SAE Relatedness Trt? Outcome day) 2012-11 㰯⭍⅖ N MILD/ Y/ NOT APPLICABLE/ Ongoing - (SINUSITIS) NOT Y NOT RECOVERED/NOT - RELATED RESOLVED 2012-07- Ⓞ N MILD/ N/ DOSE NOT CHANGED/ 2012-09 07 (WORSENING OF PSORIASIS) POSSIBLE NA RECOVERED/RESOLVED - (10) 2012-08- Ⓨ⇕ N MILD/ N/ DOSE NOT CHANGED/ 2012-08- 02 (FEVER) NOT NA RECOVERED/RESOLVED 03 (36) RELATED (37) 2012-08- 㢌③ N MILD/ N/ DOSE NOT CHANGED/ 2012-08- 02 (HEADACHE) NOT NA RECOVERED/RESOLVED 03 (36) RELATED (37) 2012-08- ⤖⭠⒦ Y SEVERE/ N/ DRUG WITHDRAWN/ 2012-09- 02 (INTERNAL COLONIC POSSIBLE NA RECOVERED/RESOLVED 18 (36) FISTULA) (83)
3) Baseline Demographic Information Age (years): 3 Sex: Female Weight (kg): 66.5 Race: White Date of birth: Height (cm): 171.0
4) Induction Treatment Group Randomized Treatment Group: Ustekinumab Approximating 6 mg/kg IV Actual Treatment Group: Ustekinumab Approximating 6 mg/kg IV
5) Induction Treatment Received Visit Start Date Study Day Dose Number Actual Treatment Dose WEEK 0 2012-06-28 1 1 Ustekinumab Approximating 6 mg/kg IV 389.7 mg
6) Induction Disposition Did subject complete the induction study?: Y Did subject enter maintainance study?: N
7) Baseline Crohn's Disease History Date of diagnosis: 31DEC1999 Disease duration: 12.50 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪⫠㛛࿘ᅖ㸪⭠⟶እ≧㸦㛵⠇⅖㸭㛵⠇③㸧
8) Crohn's Disease Complications Before Baseline Intra-abdominal abscess: Never Sinus tracts/perforation: Never Fistula: Never Stricture complications of (CD): Never
58 (47) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
9) Concomitant Crohn's Disease-Related Surgeries Surgery Date Result of lack of efficacy? ษ㝖-ᅇ┣㒊 2012-09-18 N
10) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 0 BUDESONIDE 9 mg - WEEK 6 PREDNISOLONE 30 mg 30 WEEK 6 BUDESONIDE 0 mg - WEEK 8 PREDNISOLONE 0 mg 0 SAFETY FOLLOW-UP BETAMETHASONE 4 mg 26.68
11) Concomitant Medications Start Preferred Term Date End Date Reason Route EUGYNON /00022701/ 1995 - OTHER (CONTRACEPTION) ORAL ACEBUTOLOL HYDROCHLORIDE 2005 - OTHER (TACHYCARDIA (MEDICAL ORAL HISTORY)) PARACETAMOL 2012-01 2012-08 CROHN'S DISEASE ORAL TRAMADOL HYDROCHLORIDE 2012-01 2012-07 CROHN'S DISEASE ORAL BUDESONIDE 2012-05 2012-07- CROHN'S DISEASE ORAL 15 PREDNISOLONE SODIUM 2012-07- 2012-08- CROHN'S DISEASE ORAL SULFOBENZOATE 15 10 TRAMADOL HYDROCHLORIDE 2012-08 2012-09 ADVERSE EVENT INTRAVENOUS METRONIDAZOLE 2012-08- 2012-08- ADVERSE EVENT INTRAVENOUS 11 17 CEFTRIAXONE SODIUM 2012-08- 2012-08- ADVERSE EVENT INTRAVENOUS 11 17 SPASFON /00765801/ 2012-08- 2012-08 ADVERSE EVENT INTRAVENOUS 13 TRIMEBUTINE MALEATE 2012-08- 2012-09- CROHN'S DISEASE ORAL 17 17 AMOXI-CLAVULANICO 2012-08- 2012-09- ADVERSE EVENT ORAL 18 23 PARACETAMOL 2012-08- 2012-11 CROHN'S DISEASE ORAL 18 ESOMEPRAZOLE MAGNESIUM 2012-09 2012-10 CROHN'S DISEASE ORAL ENOXAPARIN SODIUM 2012-09 2012-10 ADVERSE EVENT SUBCUTANEOUS ADALIMUMAB 2012-10- 2012-10- CROHN'S DISEASE SUBCUTANEOUS 26 26 PARACETAMOL 2012-11 - ADVERSE EVENT ORAL ADALIMUMAB 2012-11- 2012-11- CROHN'S DISEASE SUBCUTANEOUS 09 09 ADALIMUMAB 2012-11- 2012-12- CROHN'S DISEASE SUBCUTANEOUS 23 06 AMOXI-CLAVULANICO 2012-12- - ADVERSE EVENT ORAL 03 BETAMETHASONE 2012-12- 2012-12- ADVERSE EVENT ORAL 04 05
12) Narrative Text ⿕㦂⪅ࡣ 3 ṓࡢⓑேዪᛶ࡛㸪2012 ᖺ 6 ᭶ 28 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏ㸦㹼6 mg/kg ⩌㸧 ࢆ㟼⬦ෆᢞࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪ᖇ⋤ษ㛤㸦2 ᅇ㸧㸪ᅇ┣㒊ษ㝖㸪Ⓞཬࡧ㢖⬦࡛࠶ࡗࡓࠋ
59 (48) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
SAE/Discontinuation of study agent due to an AE㸸⤖⭠⒦㸦Day 36㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2012 ᖺ 8 ᭶ 10 ᪥Ⓨ⇕㸪㢌③㸪ᝏᐮཬࡧྑ⭠㦵❐ࡢ③ࡳࡢ ࡓࡵධ㝔ࡋࡓࠋ⭡㒊ࡽ㦵┙㒊ࡢࢫ࡛࢟ࣕࣥ㸪⭡⭷ᚋ㠃᥋ゐࡋ㞃ࢀࡓ⨨࠶ࡿ⤖⭠⒦ࢆక࠺ ᶓ⾜⤖⭠⅖ࡀㄆࡵࡽࢀࡓࠋ≉ᐃࡢ㈓␃≀ࡣࡳࡽࢀ࡞ࡗࡓࠋࢥࣥࣆ࣮ࣗࢱ᩿ᒙᙳࢫ࢟ࣕࣥࡼ ࡾデ᩿ࡀ☜ᐃࡋࡓࠋྠ᪥ᐇࡉࢀࡓ⮫ᗋ᳨ᰝࡢ⤖ᯝ࡛ࡣ C ᛂᛶࡓࢇⓑ⃰ᗘࡣ 25 mg/L㸦ṇᖖ⠊ ᅖ <6 mg/L㸧࡛࠶ࡗࡓࠋ⬻ࢫ࡛࢟ࣕࣥࡣ␗ᖖࢆㄆࡵࡎ㸪⬨᳝✸่ࡢ⤖ᯝࡶ㧊⭷⅖ࢆ♧၀ࡍࡿࡶࡢ ࡛ࡣ࡞ࡗࡓࠋ ධ㝔୰㸪ࢥࣝࢳࢥࢫࢸࣟࢻ⸆ࡢᢞࡣ୰Ṇࡉࢀ㸪ࢭࣇࢺࣜ࢟ࢯࣥཬࡧ࣓ࢺࣟࢽࢲࢰ࣮ࣝࡢ ᢞࡀ⾜ࢃࢀࡓࠋ2012 ᖺ 8 ᭶ 17 ᪥㸪ᡭ⾡ィ⏬ࢆ❧࡚࡚⿕㦂⪅ࡣ㏥㝔ࡋࡓࠋ㏥㝔Ⓨ⇕ࡣ࡞ ࡃ㸪⭡③ࡣ㍍ῶࡋ࡚࠸ࡓࠋ2012 ᖺ 9 ᭶ 18 ᪥㸪ṇ୰㛤⭡⾡ࢆᐇࡋ㸪ᑠ⭠ࢆ⣙ 10 cm ཬࡧ⤖⭠ ࢆ⣙ 20 cm ษ㝖ࡋ࡚㸪ᅇ⭠ᶓ⾜⤖⭠ᕥഃࡢ➃ࠎ࿀ྜࢆ⾜ࡗࡓࠋᮏ㇟ࡣᾘᩓࡋࡓሗ࿌ࡉࢀࡓࠋ ⏕᳨ࡢ⤖ᯝ㸪⤖⭠ษ᩿⦕ࡲ࡛㐩ࡍࡿᛴᛶࡢ⭡⭷ᛂࢆక࠺άືᮇࡢ⫗ⱆ⭘ᛶ⅖ࡀࡳࡽࢀࡿࢡࣟ ࣮࡛ࣥ࠶ࡿࡇࡀุ᫂ࡋࡓࠋ⾡ᚋࡢ⤒㐣ࡣ㡰ㄪ࡛㸪⾡ᚋ 4 ᪥┠ࡲ࡛ṇᖖᶵ⬟ᡠࡾ㸪⭡㒊ࡶ ⒵ࡋࡘࡘ࠶ࡗࡓࠋ⾡ᚋ 5 ᪥┠ࡲ࡛ࣔ࢟ࢩࢩࣜࣥ㸭ࢡࣛࣈࣛࣥ㓟ࡀᢞࡉࢀ㸪㏥㝔ࡣ paracetamol㸪࢚ࢯ࣓ࣉࣛࢰ࣮ࣝཬࡧ࢚ࣀ࢟ࢧࣃࣜࣥࢆฎ᪉ࡉࢀࡓࠋ
(5) Subject CNTO1275CRD3001-3421-10675
1) Reason for narrative selection SAE Event of interest: Malignancy Event of interest: Serious infection 2) Adverse Events Start date End date (Study Preferred Term Intensity/ Inf/ Action Taken/ (Study day) (Verbatim Term) SAE Relatedness Trt? Outcome day) 2012-10- ⭠⳦ᛶᩋ⾑ Y SEVERE/ Y/ DOSE NOT CHANGED/ 2012-11- 23 (SEPSIS WITH E.COLI NOT Y RECOVERED/RESOLVED 07 (22) BACTEREMIA) RELATED (37) 2012-11- Ⓨ⑈ N MILD/ N/ DOSE NOT CHANGED/ 2012-11- 13 (EXANTHEMA AT THE BACK) NOT NA RECOVERED/RESOLVED 27 (43) RELATED (57) 2012-11- ᳝㛫ᯈ⅖ Y MODERATE/ Y/ DOSE NOT CHANGED/ 2012-12- 14 (SPONDYLODISCITIS) NOT Y RECOVERED/RESOLVED 14 (44) RELATED (74) 2012-12- ప࢝ࣝࢩ࣒࢘⾑ N MODERATE/ N/ DOSE NOT CHANGED/ 2012-12- 06 (HYPOCALCAEMIA) NOT NA RECOVERED/RESOLVED 12 (66) RELATED (72) 2012-12- ᝏᚰ N MODERATE/ N/ DOSE NOT CHANGED/ 2012-12- 07 (NAUSEA) NOT NA RECOVERED/RESOLVED 07 (67) RELATED (67) 2013-04- ከⓎᛶ㦵㧊⭘ Y MODERATE/ N/ DOSE NOT CHANGED/ Ongoing 18 (MULTIPLE MYELOMA) POSSIBLE NA NOT RECOVERED/NOT - (199) RESOLVED
3) Baseline Demographic Information ȋȌǣ ͷ ǣ ȋȌǣ ʹǤͳ ǣ ǣ ͳͻͷͷǦͲͳǦͲͳ ȋ Ȍǣ ͳǤͲ
60 (49) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
4) Induction Treatment Group Randomized Treatment Group: Ustekinumab Approximating 6 mg/kg IV Actual Treatment Group: Ustekinumab Approximating 6 mg/kg IV 5) Induction Treatment Received Visit Start Date Study Day Dose Number Actual Treatment Dose WEEK 0 2012-10-02 1 1 Ustekinumab Approximating 6 mg/kg IV 389.7 mg
6) Induction Disposition Did subject complete the induction study?: Y Did subject enter maintainance study?: N 7) Baseline Crohn's Disease History Date of diagnosis: 31MAR1979 Disease duration: 33.51 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪⫠㛛࿘ᅖ㸪⭠⟶እ≧㸦㛵⠇⅖㸭㛵⠇③㸧
8) Crohn's Disease Complications Before Baseline Intra-abdominal abscess: Previous history Sinus tracts/perforation: Never Fistula: Previous history Stricture complications of (CD): Previous history 9) Concomitant Crohn's Disease-Related Surgeries Surgery Date Result of lack of efficacy? ⤖⭠⊃✽㒊ᣑᙇ⾡ 2012-11-02 N
10) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 6 PREDNISOLONE 60 mg - WEEK 6 PREDNISOLONE 50 mg - WEEK 6 PREDNISOLONE 40 mg - WEEK 8 PREDNISOLONE 30 mg 30 WEEK 8 PREDNISOLONE 25 mg 25 SAFETY FOLLOW-UP PREDNISOLONE 20 mg 20
11) Concomitant Medications Start Preferred Term Date End Date Reason Route METAMIZOLE SODIUM 2012-10- 2012-10- OTHER (BACK PAIN) ORAL 22 23 CIPROFLOXACIN 2012-10- 2012-10- ADVERSE EVENT ORAL 23 24 PANTOPRAZOLE SODIUM 2012-10- - OTHER (GASTRIC ULCER ORAL SESQUIHYDRATE 23 PROPHYLAXIS) PIPERACILLIN W/TAZOBACTAM 2012-10- 2012-11- ADVERSE EVENT INTRAVENOUS /01606301/ 23 07 COLECALCIFEROL 2012-10- - OTHER (OSTEOPOROSIS ORAL 23 PROPHYLAXIS) PREDNISOLONE 2012-10- 2012-11- ADVERSE EVENT INTRAVENOUS 24 01 PREDNISOLONE 2012-11- 2012-11- ADVERSE EVENT INTRAVENOUS 02 09
61 (50) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
Start Preferred Term Date End Date Reason Route MESALAZINE 2012-11- - CROHN'S DISEASE ORAL 07 MESALAZINE 2012-11- - ADVERSE EVENT RECTAL 07 PREDNISOLONE 2012-11- 2012-11- ADVERSE EVENT INTRAVENOUS 10 16 VALORON N /00628301/ 2012-11- 2012-11- ADVERSE EVENT ORAL 12 13 POLYETHYL. GLYC. W/POTAS. 2012-11- 2012-11- OTHER (PREPATRATION FOR ORAL CHLOR./SOD. BICARB. 14 15 COLONOSCOPY) RIFAMYCIN 2012-11- 2012-12- ADVERSE EVENT INTRAVENOUS 14 05 FLUCLOXACILLIN SODIUM 2012-11- 2012-12 ADVERSE EVENT INTRAVENOUS 14 TARGIN 2012-11- 2013-01- OTHER (BACK PAIN) ORAL 14 24 LEVOFLOXACIN 2012-11- 2012-12 ADVERSE EVENT INTRAVENOUS 14 PREDNISOLONE 2012-11- 2012-11- ADVERSE EVENT ORAL 17 19 VITAMIN B12 NOS 2012-11- 2012-11- OTHER (VITAMIN B 12 INTRAVENOUS 17 17 DEFICIENCY) PREDNISOLONE 2012-11- 2012-11- ADVERSE EVENT ORAL 20 26 PREDNISOLONE 2012-11- - ADVERSE EVENT ORAL 27 FLUCLOXACILLIN SODIUM 2012-12 - ADVERSE EVENT ORAL LEVOFLOXACIN 2012-12 - ADVERSE EVENT ORAL CERTOPARIN SODIUM 2012-12- 2012-12- OTHER (PROPHYLAXIS AGAINST SUBCUTANEOUS 01 11 THROMBOSIS) RIFINAH 2012-12- 2012-12- ADVERSE EVENT INTRAVENOUS 06 10 POTASSIUM CHLORIDE 2012-12- 2012-12- ADVERSE EVENT ORAL 06 12 METAMIZOLE SODIUM 2012-12- 2013-01- ADVERSE EVENT ORAL 06 24 ONDANSETRON 2012-12- 2012-12- ADVERSE EVENT ORAL 07 07
12) Narrative Text ⿕㦂⪅ࡣ 5 ṓࡢⓑே⏨ᛶ࡛㸪2012 ᖺ 10 ᭶ 2 ᪥ᐶゎᑟධ⒪ἲࡋ࡚ᮏ㸦㹼6 mg/kg ⩌㸧ࢆ 㟼⬦ෆᢞࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪ᅇ┣㒊ษ㝖㸪S ≧⤖⭠㒊ศษ㝖㸦1989 ᖺ㸧㸪ᅇ⭠ᶓ⾜࿀ྜࢆక࠺ᅇ⭠⤖⭠࿀ྜ㒊ࡢษ㝖㸪ᅇ⭠ษ㝖ཬࡧ⊃✽ᙧᡂ ⾡㸦2000 ᖺ㸧㸪ᅇ⭠⤖⭠࿀ྜ㒊ษ㝖㸪ᅇ⭠ᶓ⾜࿀ྜ⾡ཬࡧ⊃✽ᙧᡂ⾡㸦2003 ᖺ㸧㸪ᑠ⭠ษ㝖 㸦20 cm㸧ཬࡧ⒵╔㞳⾡㸦2004 ᖺ㸧㸪୪ࡧᅇ⭠⤖⭠࿀ྜ㒊ษ㝖㸪ᅇ⭠ᶓ⾜࿀ྜ⾡㸪⒦Ꮝษ㝖 ཬࡧ⒵╔㞳⾡㸦2011 ᖺ㸧࡛࠶ࡗࡓࠋࡑࡢ㸪ព⩏᫂ࡢ༢ࢡ࣮ࣟࣥᛶ࣐࢞ࣥࢢࣟࣈࣜࣥ⾑ 㸦MGUS㸧㸦2006 ᖺ㸧㸪⮅⮚⬡⫫⭘ཬࡧ⫠㛛࿘ᅖ⮋⒆㸦1995 ᖺ㸧㸪እയᛶ⭁⮚◚㸦1991 ᖺ㸧୪ࡧࣅࢱ࣑ࣥ B12 Ḟஈࡀ࠶ࡗࡓࠋ ⿕㦂⪅ࡣ㸪ࣜࣥࣃቑṪᛶᝈ࡛࠶ࡿ MGUS ࡢࡓࡵ㝖እᇶ‽ 19 ゐࡋ࡚࠾ࡾ㸪㐳ཬⓗᮏヨ 㦂ࡢཧຍ⪅ࡋ࡚㐺᱁࡛࠶ࡿࡳ࡞ࡉࢀࡓࠋ SAE/Serious infection㸸⭠⳦ᛶᩋ⾑㸦Day 22㸧 CIOMS ࡼࡿ㸪2012 ᖺ 10 ᭶ 23 ᪥㸪⿕㦂⪅ࡣ᭱㧗࡛ 40°C ࡢⓎ⇕ཬࡧ⫼㒊③㸦⭜㒊㸧ࡢࡓ ࡵධ㝔ࡋࡓࡀ㸪ᙜึࡣࢡ࣮ࣟࣥࡢ⇞⪃࠼ࡽࢀ࡚࠸ࡓࠋ⮫ᗋ᳨ᰝ࡛ C ᛂᛶࡓࢇⓑ㸦CRP㸧
62 (51) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
ቑຍ㸦ṇ☜࡞್ࡣሗ࿌࡞ࡋ㸧ࡀㄆࡵࡽࢀ㸪⾑ᾮᇵ㣴᳨ᰝ࡛ࡣ⭠⳦ࡀ㝧ᛶ࡛࠶ࡗࡓࡓࡵ㸪⭠⳦ ࡼࡿᩋ⾑デ᩿ࡉࢀࡓࠋ⒪࡛ࡣ㸪ࢩࣉࣟࣇࣟ࢟ࢧࢩࣥࡢ⤒ཱྀᢞᚋ㸪⾑ᾮᇵ㣴ཬࡧឤཷᛶ ヨ㦂ᇶ࡙ࡁࣆ࣌ࣛࢩࣥ㸭ࢱࢰࣂࢡࢱ࣒ࡀ㟼⬦ෆᢞࡉࢀࡓࠋឤᰁᕢࡣ≉ᐃࡉࢀ࡞ࡗࡓࠋࡑ ࡢࡢ⒪࡛ࡣ㸪prednisone ཬࡧ࣓ࢱ࣑ࢰ࣮ࣝࡀᢞࡉࢀࡓࠋ2012 ᖺ 11 ᭶ 7 ᪥ᮏ㇟ࡣᾘᩓࡋ ࡓሗ࿌ࡉࢀ㸪ྠ᪥⿕㦂⪅ࡣ㏥㝔ࡋࡓࠋ SAE/Serious infection㸸᳝㛫ᯈ⅖㸦Day 44㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2012 ᖺ 11 ᭶ 14 ᪥ࡢ㏣㊧ㄪᰝࡢ᮶㝔㸪⃭ࡋ࠸⫼㒊③ࢆッ࠼ධ 㝔ࡋࡓࠋ2012 ᖺ 11 ᭶ 15 ᪥ࡢ CRP ⃰ᗘࡣ 46.2 mg/L㸦ṇᖖ⠊ᅖ <5.0 mg/L㸧࡛࠶ࡗࡓࠋ2012 ᖺ 11 ᭶ 13 ᪥ᐇࡋࡓ᰾☢Ẽඹ㬆⏬ീἲ㸦MRI㸧࡛௨ୗࡀㄆࡵࡽࢀࡓ㸸⬚᳝ୗ㒊ཬࡧ⬚⭜᳝⛣⾜㒊 ࡢ᳝㛫ᯈ⭍Ỉศῶᑡࢆక࠺⬨᳝㏥⾜ኚᛶ㸪⭜᳝᳝య㸦L1㸧ୖ⤊ᯈࡢࢩ࣮ࣗࣔࣝ⤖⠇㸪᳝య㧗ࡀ᫂ ࡽῶᑡࡋࡓ᳝㛫ᯈ㝽㸦T8/T9㸧㸪᳝యෆỈศ㈓␃㸪ୗ⤊ᯈཬࡧୖ⤊ᯈࡢᩚཬࡧྑഃ࿘㎶㡿 ᇦࡢ≉␗ᛂࠋឤᰁᛶ⬨᳝᳝㛫ᯈ⅖㸦T8/T9㸧デ᩿ࡉࢀ㸪ୖ㏙ࡢ⭠⳦ࡼࡿᩋ⾑ࡀཎᅉ࡛ ࠶ࡿྍ⬟ᛶࡀ᭱ࡶ㧗ࡗࡓࠋ⿕㦂⪅ࡣࣜࣇࣥࣆࢩࣥ㸪flucloxacillin㸦Staphylex㸧ཬࡧࣞ࣎ࣇ ࣟ࢟ࢧࢩࣥ㸦Tavanic㸧ࡀᢞࡉࢀࡓࠋ⫼㒊③ࡣ࢜࢟ࢩࢥࢻࣥཬࡧࢼࣟ࢟ࢯࣥࡀᢞࡉࢀࡓࠋ 2012 ᖺ 11 ᭶ 26 ᪥㏣㊧ㄪᰝࡢࡓࡵᐇࡉࢀࡓ MRI ࡛ࡣ㸪ᕢ࿘ᅖ⅖ᛂࡀ࠶ࡾ㸪⬨᳝ ᳝㛫ᯈ⅖ࡢᝏࡀࡳࡽࢀࡓࠋྠ᪥ࡢ CRP ⃰ᗘࡣ 4.8 mg/L ࡲ࡛ῶᑡࡋ࡚࠸ࡓࠋᗘᐇࡋࡓ⾑ᾮ ᇵ㣴᳨ᰝࡢ⤖ᯝࡣ㝜ᛶ࡛࠶ࡗࡓࠋ ⿕㦂⪅ࡢ⫼㒊③ࡣ㸪ᙜึࡣ㍍ῶࡋ࡚࠸ࡓࡶࡢࡢ㸪ᢠ⏕≀㉁ཬࡧ㙠③ࡢᢞࡶ㛵ࢃࡽࡎⓎ ࡋࡓࠋ2012 ᖺ 12 ᭶ 6 ᪥㸪T6/T7 ࡽ T10/T11 ᳝యࡢ⬨᳝ᅛᐃ⾡ࢆᐇࡋࡓࠋ2012 ᖺ 12 ᭶ 7 ᪥ ᐇࡋࡓ⾡ᚋࡢ⬨᳝ CT ࢫ࢟ࣕࣥࡣ㸪⬨᳝ᅛᐃ⾡ࡢ⾡ᚋᡤぢ࡛࠶ࡾ㸪ᕥഃࡢ⬨᳝ⱼࡡࡌࡽ⬨ ᰕ⟶ಶูᅽຊࡀࡾ㸪⦆ࡳࡣ࡞ࡃ㸪㦵ᢡࡶࡳࡽࢀ࡞ࡗࡓࠋ᳝య㸪᳝ᘪ᰿ཬࡧᲲ✺㉳ࡢ࠸ ࡃࡘ࡛ព⩏᫂ࡢከⓎᛶᩬ≧ኚࡀࡳࡽࢀࡓࠋ 2012 ᖺ 12 ᭶ 14 ᪥⬨᳝᳝㛫ᯈ⅖ࡣᅇ㸭ᾘᩓࡋࡓሗ࿌ࡉࢀ㸪ྠ᪥⿕㦂⪅ࡣ㏥㝔ࡋࡓࠋ SAE/Malignancy㸸ከⓎᛶ㦵㧊⭘㸦Day 199㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣᏳᛶࡢࡓࡵࡢ㏣㊧ㄪᰝᮇ㛫୰ከⓎᛶ㦵㧊⭘デ᩿ࡉࢀࡓࠋ 2012 ᖺ 12 ᭶ᐇࡉࢀࡓ㝧㟁Ꮚᨺฟ᩿ᒙᙳ㸦PET㸧㸭CT ᳨ᰝ࡛ࡣ㸪᳝㦵㸪ྑ⭠㦵⛸୪ࡧྑ ୖ⭎㦵ཬࡧ㦵ᖿ➃ከⓎᛶ㦵⁐ゎࡀㄆࡵࡽࢀࡓࠋࡲࡓ㸪㛗ᮇ㛫ࢃࡓࡿ៏ᛶ⅖ᛂక࠺ᑐ⛠ ⓗࡘᆒ㉁࡞㧗ᗘࡢ㦵㧊άᛶࡶࡳࡽࢀࡓࠋ2013 ᖺ 2 ᭶ 18 ᪥⾑Ύ༢ࢡ࣮ࣟࣥᛶචࢢࣟࣈࣜ ࣥ⾑ࡀࡳࡽࢀ㸪⥲ Ȗ ࢢࣟࣈࣜࣥࡢ 47%ࡀචࢢࣟࣈࣜࣥ G㸦IgG㸧Nᆺ࡛ᵓᡂࡉࢀ࡚࠸ࡓࠋ IgG N್ࡣ 152 mg/L㸦ṇᖖ⠊ᅖ 3.3-19.4 mg/L㸧࡛࠶ࡗࡓࠋ2013 ᖺ 3 ᭶ 6 ᪥ࡢ㦵㧊⣽⬊デ࡛ࡣ㸪 90%ࢆᙧ㉁⣽⬊ࡀ༨ࡵ㸪⤌⧊Ꮫᡤぢ࡛ࡣᙧ㉁⣽⬊ࡀ⏘⏕ࡍࡿN㍍㙐ࡢቑṪࡀࡳࡽࢀࡓࠋศᏊ⣽⬊ 㑇ఏᏛⓗᡤぢ࡛ࡣ IGH-CCNDI ࡢᵓᡂࡀࡳࡽࢀࡓࠋ ೃᛶከⓎᛶ㦵㧊⭘ࡢᑟධ⒪ἲࡣ㸪BCD ⒪ἲ㸦࣎ࣝࢸࢰ࣑ࣈ㸪ࢩࢡࣟ࣍ࢫࣇ࣑ࢻ㸪ࢹ࢟ࢧ ࣓ࢱࢰࣥ㸧ࡢᡭ㡰ᚑࡗ࡚ᐇࡉࢀ㸪㧗⏝㔞Ꮫ⒪ἲཬࡧ⮬ᐙᖿ⣽⬊⛣᳜ࡀィ⏬ࡉࢀࡓࠋ⿕㦂⪅ ࡣከⓎᛶ㦵㧊⭘ࡢࡓࡵ㸪2013 ᖺ 4 ᭶ 6 ᪥ࡽ 2013 ᖺ 4 ᭶ 18 ᪥ࡲ࡛ධ㝔ࡋࡓࠋ ࣮࣋ࢫࣛࣥࡢಖᏑ⾑Ύ᳨య㸦㦂⸆ᢞ๓㸧ࢆ㐳ཬⓗ⾑Ύࡓࢇⓑ㟁ẼὋື㸦SPEP㸧࡛ ᳨ᰝࡋࡓ⤖ᯝ㸪⃰ᗘ 32 g/L ࡢ Ȗ-M ࡓࢇⓑࡢࢫࣃࢡࡀ᳨ฟࡉࢀࡓࠋ
63 (52) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
(6) Subject CNTO1275CRD3001-4602-10902
1) Reason for narrative selection SAE Event of interest: Serious infection
2) Adverse Events Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day) (Verbatim Term) SAE Relatedness Trt? Outcome (Study day) 2012-12-06 ⇕ឤ N MILD/ N/ DOSE NOT CHANGED/ Ongoing (1) (WARM FEET) PROBABLE NA NOT RECOVERED/NOT RESOLVED - 2013-01-07 ⫹⟶⅖ Y MODERATE/ Y/ DOSE NOT CHANGED/ 2013-02-15 (33) (CHOLANGITIS) POSSIBLE Y RECOVERED/RESOLVED (72) 2013-01-11 ⬡⫫౽ N MILD/ N/ DOSE NOT CHANGED/ 2013-02-11 (37) (STEATORHOE) DOUBTFUL NA RECOVERED/RESOLVED (68)
3) Baseline Demographic Information Age (years): 6 Sex: Male Weight (kg): 75.8 Race: White Date of birth: - Height (cm): 174.0
4) Induction Treatment Group Randomized Treatment Group: Ustekinumab Approximating 6 mg/kg IV Actual Treatment Group: Ustekinumab Approximating 6 mg/kg IV
5) Induction Treatment Received Visit Start Date Study Day Dose Number Actual Treatment Dose WEEK 0 2012-12-06 1 1 Ustekinumab Approximating 6 mg/kg IV 389.7 mg
6) Induction Disposition Did subject complete the induction study?: Y Did subject enter maintainance study?: Y
7) Baseline Crohn's Disease History Date of diagnosis: 31DEC1960 Disease duration: 51.93 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪⫠㛛࿘ᅖ
8) Crohn's Disease Complications Before Baseline Intra-abdominal abscess: Never Sinus tracts/perforation: Never Fistula: Previous history Stricture complications of (CD): Previous history
9) Concomitant Crohn's Disease-Related Surgeries None reported
10) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 0 BUDESONIDE 9 mg - WEEK 0 FLUTICASON 27.5 -
64 (53) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
11) Concomitant Medications Preferred Term Start Date End Date Reason Route FOLINIC ACID - - OTHER (PREVENTION) ORAL ASCORBIC ACID - - OTHER (DIET SUPPLEMENT) ORAL VITAMIN B12 NOS 2004-08 - OTHER (PREVENTION) INTRAMUSCULAR BUDESONIDE 2008-12 - CROHN'S DISEASE ORAL TRAMADOL 2009-02 2012-12-13 CROHN'S DISEASE ORAL LEKOVIT CA 2009-04 - OTHER (PREVENTION OSTEOPOROSIS) ORAL OMEPRAZOLE 2009-04 - OTHER (PREVENTION PYROSIS) ORAL METOPROLOL 2011-12 - OTHER (HYPERTENSION) ORAL FLUTICASONE PROPIONATE 2012-10 - OTHER (COMMON COLD) NASAL DIAZEPAM 2012-11-01 - OTHER (RELAXATION) ORAL PARACETAMOL 2012-11-11 - OTHER (ABDOMINAL PAIN) ORAL AUGMENTIN /00756801/ 2013-01-08 2013-01-09 ADVERSE EVENT INTRAVENOUS
12) Narrative Text ⿕㦂⪅ࡣ 6 ṓࡢⓑே⏨ᛶ࡛㸪2012 ᖺ 12 ᭶ 6 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏ㸦㹼6 mg/kg ⩌㸧 ࢆ㟼⬦ෆᢞࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪⭡③㸪⭡ቨ࣊ ࣝࢽ㸪㐣ᩄ㸦ໟᖏ㸧㸪㧗⾑ᅽ㸪⭠ษ㝖ཬࡧ」ᩘᅇࡢᡭ⾡㸦ࢡ࣮ࣟࣥ㛵㐃㸪⮋⒆ཬࡧ⒦Ꮝ㸧 ࡛࠶ࡗࡓࠋ SAE/Serious infection㸸⫹⟶⅖㸦Day 33㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ๓᪥ࡽ⥆ࡃⓎ⇕ࡢࡓࡵ 2013 ᖺ 1 ᭶ 8 ᪥ධ㝔ࡋࡓࠋ⭡㒊㉸㡢Ἴ ᳨ᰝ࡛ࡣ㸪⤖▼ཬࡧ⫹Ἶࢆక࠺⫹ᄞᣑᙇ୪ࡧ⫹⟶୰ኸࡢᣑᙇࡀࡳࡽࢀࡓࠋෆど㙾ⓗ㏫⾜ᛶ⫹㐨 ⮅⟶ᙳ࡛ࡣ㸪⥲⫹⟶ᣑᙇཬࡧ⫹▼ࡀࡳࡽࢀࡓࠋᣓ⣙➽ษ㛤ཬࡧࣂ࣮ࣝࣥࡼࡿ⫹Ἶ㝖ཤࢆ㸪 ྜేࢆⓎࡍࡿࡇ࡞ࡃᐇࡋࡓࠋࣔ࢟ࢩࢩࣜࣥ㸭ࢡࣛࣈࣛࣥ㓟ࢆᢞࡉࢀࡓࠋ⿕㦂⪅ࡣ 2013 ᖺ 1 ᭶ 11 ᪥㏥㝔ࡋࡓࡀ㸪2013 ᖺ 2 ᭶ 11 ᪥ධ㝔ࡋ㸪2013 ᖺ 2 ᭶ 12 ᪥㛤⭡⫹ᄞฟ ⾡ࢆཷࡅࡓࠋ⫹ᄞࡢ⌮Ꮫⓗᡤぢ࡛ࡣ㸪⫹▼ཬࡧ៏ᛶ⫹ᄞ⅖ࡀㄆࡵࡽࢀ㸪άືᮇࡢ⅖ཬࡧ␗ ᙧᡂࡣ࡞ࡗࡓࠋචࢢࣟࣈࣜࣥ G4 ࡣ㝜ᛶ࡛࠶ࡾ㸪⮬ᕫචᛶࡢ⫹ᄞ⅖ࡣ♧၀ࡉࢀ࡞ࡗࡓࠋ 2013 ᖺ 2 ᭶ 15 ᪥⫹⟶⅖ࡣᾘᩓࡋࡓሗ࿌ࡉࢀ㸪ྠ᪥⿕㦂⪅ࡣ㏥㝔ࡋࡓࠋ
(7) Subject CNTO1275CRD3001-1046-10180
1) Reason for narrative selection SAE Event of interest: Serious infection
2) Adverse Events Start date End date (Study Preferred Term Intensity/ Inf/ Action Taken/ (Study day) (Verbatim Term) SAE Relatedness Trt? Outcome day) 2012-05- ࣜࣥࣃ⌫ῶᑡ N MILD/ N/ DOSE NOT CHANGED/ 2012-06- 23 (LYMPHOCYTOPENIA) POSSIBLE NA RECOVERED/RESOLVED 13 (22) (43) 2012-05- ⭠⟶⓶⒦ N MODERATE/ N/ DOSE NOT CHANGED/ 2012-06- 23 (PERI-UMBILICAL FISTULA) NOT NA RECOVERED/RESOLVED 13 (22) RELATED (43) 2012-06- 㦵┙⮋⒆ Y SEVERE/ Y/ DOSE NOT CHANGED/ 2012-06- 23 (RIGHT LOWER QUANDRANT DOUBTFUL Y RECOVERED/RESOLVED 29 (53) PELVIC ABSCESS) (59)
65 (54) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
Start date End date (Study Preferred Term Intensity/ Inf/ Action Taken/ (Study day) (Verbatim Term) SAE Relatedness Trt? Outcome day) 2012-06- 㕲Ḟஈᛶ㈋⾑ N MODERATE/ N/ DOSE NOT CHANGED/ Ongoing 27 (IRON DEFICIENCY ANEMIA) NOT NA NOT RECOVERED/NOT - (57) RELATED RESOLVED
3) Baseline Demographic Information Age (years): 3 Sex: Female Weight (kg): 43.8 Race: White Date of birth: Height (cm): 154.9
4) Induction Treatment Group Randomized Treatment Group: Ustekinumab 130 mg IV Actual Treatment Group: Ustekinumab 130 mg IV
5) Induction Treatment Received Visit Start Date Study Day Dose Number Actual Treatment Dose WEEK 0 2012-05-02 1 1 Ustekinumab 130 mg IV 129.6 mg
6) Induction Disposition Did subject complete the induction study?: Y Did subject enter maintainance study?: N
7) Baseline Crohn's Disease History Date of diagnosis: 31DEC1987 Disease duration: 24.34 years Involved areas: ⤖⭠ࡢࡳ㸪⫠㛛࿘ᅖ㸪⭠⟶እ≧㸦㛵⠇⅖㸭㛵⠇③㸧
8) Crohn's Disease Complications Before Baseline Intra-abdominal abscess: Previous history Sinus tracts/perforation: Currently present Fistula: Currently present Stricture complications of (CD): Previous history
9) Concomitant Crohn's Disease-Related Surgeries None reported
10) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 0 MOMETASONE 0.05 mg - WEEK 8 METHYLPREDNISOLONE 20 mg - WEEK 8 METHYLPREDNISOLONE 0 mg - WEEK 8 PREDNISONE 40 mg 40 WEEK 8 PREDNISONE 20 mg 20 SAFETY FOLLOW-UP PREDNISONE 10 mg 10 SAFETY FOLLOW-UP PREDNISONE 5 mg 5 SAFETY FOLLOW-UP PREDNISONE 0 mg 0
11) Concomitant Medications Start End Preferred Term Date Date Reason Route PARACETAMOL - - OTHER (FIBROMYALGIAS) ORAL
66 (55) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
Start End Preferred Term Date Date Reason Route SALBUTAMOL - - OTHER (ASTHMA) RESPIRATORY (INHALATION) MULTIVITAMINS - - OTHER (PREVENTATIVE CARE) ORAL MOMETASONE FUROATE - 2012- OTHER (ENVIROMENTAL ALLERGIES) NASAL 07-09 OMEPRAZOLE - - OTHER (GASTROESOPHAGEAL REFLUX ORAL DISEASE) PREDNISONE - 2012- CROHN'S DISEASE ORAL 04-11 PROBIOTICS - - CROHN'S DISEASE ORAL MONTELUKAST SODIUM - - OTHER (ASTHMA) ORAL CETIRIZINE HYDROCHLORIDE - - OTHER (ASTHMA) ORAL MOXIFLOXACIN 2011- 2012- CROHN'S DISEASE ORAL 06-28 06-23 FENTANYL 2012- 2012- OTHER (PRE-MEDICATION FOR INTRAVENOUS 04-16 04-16 PROCEDURE) MIDAZOLAM 2012- 2012- OTHER (PRE-MEDICATION FOR INTRAVENOUS 04-16 04-16 PROCEDURE) SODIUM CHLORIDE 2012- 2012- ADVERSE EVENT INTRAVENOUS 06-23 06-25 PARACETAMOL 2012- - ADVERSE EVENT ORAL 06-23 GALENIC /GLUCOSE/SODIUM 2012- 2012- ADVERSE EVENT INTRAVENOUS CL/POTASSIUM CL/ 06-23 06-28 HYDROMORPHONE 2012- 2012- ADVERSE EVENT INTRAVENOUS HYDROCHLORIDE 06-23 06-25 FENTANYL 2012- 2012- OTHER (SEDATIVE FOR CT-GUIDED INTRAVENOUS 06-23 06-23 ASPIRATION) MIDAZOLAM 2012- 2012- OTHER (SEDATION FOR CT-GUIDED INTRAVENOUS 06-23 06-23 ASPIRATION) PANTOPRAZOLE 2012- 2012- OTHER (GASTROESOPHAGEAL REFLUX ORAL 06-23 06-29 DISEASE) PIP/TAZO 2012- 2012- ADVERSE EVENT INTRAVENOUS 06-23 06-28 DIPHENHYDRAMINE 2012- 2012- OTHER (PREVENTATIVE TREATMENT INTRAVENOUS 06-25 06-25 PRIOR TO RECEIVING TRANSFUSION) FERROUS SULFATE 2012- - ADVERSE EVENT ORAL 06-27 AMOXI-CLAVULANICO 2012- 2012- ADVERSE EVENT ORAL 06-28 07-18 METHYLPREDNISOLONE 2012- 2012- CROHN'S DISEASE INTRAVENOUS 06-28 06-28 PREDNISONE 2012- 2012- CROHN'S DISEASE ORAL 06-28 08-01
12) Narrative Text ⿕㦂⪅ࡣ 3 ṓࡢⓑேዪᛶ࡛㸪2012 ᖺ 5 ᭶ 2 ᪥ᐶゎᑟධ⒪ἲࡋ࡚ᮏ㸦130 mg ⩌㸧ࢆ㟼⬦ ෆᢞࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪㈋⾑㸪⭈⤖▼㸪 ⥺⥔➽③㸪㦵┙⮋⒆㸪⒦Ꮝ㸦⓶㸪⫠㛛࿘ᅖ㸪⭼㸧㸪࢝ࣝࢩ࣒࢘ప್㸪ᇙఅᬛṑᢤṑ㸪⫶㣗㐨㏫ ὶ㸪S ≧⤖⭠ᣑ⬽㸪⤖⭠ษ㝖㸦⤖⭠ษ㝖ࡢ✸Ꮝࡢࡓࡵ㸧㸪ᅇ⭠⒦㐀タ㸪✵⭠⒦㐀タ㸪ႍᜥ㸪 ࣞࣝࢠ࣮ᛶ㰯⅖㸪௨ୗࡢ⸆ᑐࡍࡿ⸆≀ࣞࣝࢠ࣮ཪࡣ⪏ᛶ㸸ࢫࣆࣜࣥ㸦ⶼ㯞⑈㸧㸪 ࣥࣇࣜ࢟ࢩ࣐ࣈ㸦ᜥษࢀ㸧㸪࣓ࢺࢺࣞ࢟ࢧ࣮ࢺ㸦⑊③㸪ឤᰁཬࡧയ㸧㸪ࣔࣝࣄࢿ㸦ᝏᚰཬࡧ ྤ㸧㸪hydromorphone㸦ࡑ࠺㸧㸪ࣈࣉࣟࣇ࢙ࣥ㸦ⶼ㯞⑈㸧ཬࡧࢧࣝࣇ࡛࠶ࡗࡓࠋᐙ᪘ Ṕࡣ㸪ႍᜥ㸪ࣞࣝࢠ࣮ᛶ㰯⅖ཬࡧෙື⬦ᝈ࡛࠶ࡗࡓࠋ
67 (56) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
SAE/Serious infection㸸㦵┙⮋⒆㸦Day 53㸧 CIOMS ࡼࡿ㸪2012 ᖺ 6 ᭶ 23 ᪥㸪⿕㦂⪅ࡣⓎ⇕㸪ᝏᐮ㸪⭡③ቑᙉ㸦㛫Ḟᛶ࡛㗦ࡃ㸪ᙉᗘ 9/10 ࡢ③ࡳ㸧㸪⭡㒊⭾‶ឤཬࡧࡑࡢᚋୗ⑩࡞ࡗࡓ⭠⟶㐠ືࡢῶᑡ㸦࢞ࢫཬࡧ౽ࡢ㏻㐣㞀ᐖ㸧ࢆ ッ࠼㸪ᩆᛴእ᮶ࢆཷデࡋࡓࠋ⌮Ꮫⓗᡤぢ࡛ࡣ㸪⭠㞧㡢ῶᑡ㸪㦵ୖ㒊ཬࡧྑୗ⭡㒊୰➼ᗘࡢ⭡ 㒊ᅽ③ࡀࡳࡽࢀࡓࠋࢥࣥࣆ࣮ࣗࢱ᩿ᒙᙳ㸦CT㸧ࢫ࡛࢟ࣕࣥࡣ㸪ྑୗ⭡㒊ࣇࣞࢢ࣮ࣔࢿ㸭⮋ ⒆㸦┤ᚄ 4×4×7 cm㸧ཬࡧᑠ⭠㛢ሰࡀࡳࡽࢀࡓࠋྠ᪥እ⛉ฎ⨨ཬࡧᾘ⟶㸦GI㸧᳨ᰝࡢࡓࡵ㸪 ධ㝔ࡋࡓࠋ౽ࢢࣖࢵࢡヨ㦂ࡣ㝜ᛶ࡛࠶ࡾ㸪ᒀᇵ㣴᳨ᰝ࡛ࡣࢥࣥࢱ࣑ࢿ࣮ࢩࣙࣥ⪃࠼ࡽࢀࡿΰ ྜ⣽⳦ྀࡢࢥࣟࢽ࣮㸦25,000 colonies/mL㸧ࡀሗ࿌ࡉࢀࡓࠋCT ࢞ࢻୗ⤒⓶㔪ࡼࡿ྾ᘬࡼࡾ㸪 ࢃࡎ⾑ᾮࡢΰධࡋࡓᾮయ 1 mL ࡀ྾ᘬࡉࢀࡓࠋ㦵┙ࡽࡢ྾ᘬ≀ࡢࢢ࣒ࣛᰁⰍࡢ⤖ᯝ㸪ከᙧ ᰾㸦PMN㸧ⓑ⾑⌫ࡣࢇࡳࡽࢀࡎ㸪⣽⳦ᇵ㣴᳨ᰝࡣ㝜ᛶ࡛࠶ࡗࡓࠋධ㝔ᮇ㛫୰ࡢࡑࡢࡢ ⒪ࡋ࡚㸪⤯㣗୪ࡧࣆ࣌ࣛࢩࣜࣥ㸭ࢱࢰࣂࢡࢱ࣒㸪ࣔ࢟ࢩࢩࣜࣥ㸭ࢡࣛࣈࣛࣥ㓟㸪㟼⬦ෆ⿵ ᾮ㸦ሷࢼࢺ࣒ࣜ࢘㸧㸪◲㓟㕲㸪㉥⾑⌫ 1 ༢㸦៏ᛶ㈋⾑ᑐฎ㸧㸪ࣃࣛࢭࢱ࣮ࣔࣝ㸪ࣇ࢙ࣥࢱ ࢽࣝ㸪࣑ࢲࢰ࣒ࣛ㸪pantoprazole㸪ࢪࣇ࢙ࣥࣄࢻ࣑ࣛࣥ㸪prednisone ཬࡧ࣓ࢳࣝࣉࣞࢻࢽࢰࣟࣥࡢ ᢞࡀ⾜ࢃࢀࡓࠋ㏥㝔ࡣ㸪⭠⟶㐠ືࡣᅇࡋ㸪⭡㒊ࡢ≧ែࡣⰋዲࡔࡗࡓࠋ2012 ᖺ 6 ᭶ 29 ᪥ 㸪⿕㦂⪅ࡣྑୗ 4 ศࡢ 1 ࡢ㒊ศࡢ㦵┙⮋⒆ࡽᅇࡋ㸪㏥㝔ࡋࡓࠋ⤖⭠ษ㝖ࢆ┦ㄯࡍࡿࡓࡵ㸪 4 㐌㛫ᚋ㏣㊧ㄪᰝ᮶㝔ࡍࡿࡇࡋࡓࠋ
᳨ᰝ㡯┠ ṇᖖ⠊ᅖ㸭ᇶ‽⠊ᅖ 2012 ᖺ 6 ᭶ 23 ᪥ ࣝࣈ࣑ࣥ 3.4-5.0 g/dL 2.7 ࣊ࣔࢢࣟࣅࣥ 11.8-15.8 g/dL 9.3 ⓑ⾑⌫ᩘ 4.6-10.5 k/ȝL 11.3 ࣜࣥࣃ⌫ 18%-47% 6 ᖹᆒ㉥⾑⌫ᐜ✚ 81-97 L 69 ዲ୰⌫ 40%-75% 82 ⾑ᑠᯈᩘ 140-420 k/ȝL 548
(8) Subject CNTO1275CRD3001-1091-10037
1) Reason for narrative selection SAE Event of interest: Serious infection
2) Adverse Events Start date End date (Study Preferred Term Intensity/ Inf/ Action Taken/ (Study day) (Verbatim Term) SAE Relatedness Trt? Outcome day) 2011-10- ᒀ㊰ឤᰁ N MILD/ Y/ NOT APPLICABLE/ 2011-10- 10 (URINARY TRACT INFECTION) NOT Y RECOVERED/RESOLVED 19 (-9) RELATED (1) 2011-11- ㉳❧ᡓ N MILD/ N/ DOSE NOT CHANGED/ 2012-01- 03 (INTERMITTENT MILD POSTURAL DOUBTFUL NA RECOVERED/RESOLVED 27 (16) TREMORS) (101) 2012-01- ዷፎ N MILD/ N/ DOSE NOT CHANGED/ 2012-09- 13 (PREGNANCY) NOT NA RECOVERED/RESOLVED 05 (87) RELATED (323) 2012-08- ⭈│⭈⅖ Y SEVERE/ Y/ NOT APPLICABLE/ 2012-09- 18 (PYELONEPHRITIS ANTEPARTUM) DOUBTFUL Y RECOVERED/RESOLVED 05 (305) (323)
68 (57) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
3) Baseline Demographic Information Age (years): 2 Sex: Female Weight (kg): 63.6 Race: White Date of birth: Height (cm): 168.0
4) Induction Treatment Group Randomized Treatment Group: Ustekinumab 130 mg IV Actual Treatment Group: Ustekinumab 130 mg IV
5) Induction Treatment Received Visit Start Date Study Day Dose Number Actual Treatment Dose WEEK 0 2011-10-19 1 1 Ustekinumab 130 mg IV 130 mg
6) Induction Disposition Did subject complete the induction study?: Y Did subject enter maintainance study?: N
7) Baseline Crohn's Disease History Date of diagnosis: 31JAN2004 Disease duration: 7.72 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪⭠⟶እ≧㸦㛵⠇⅖㸭㛵⠇③㸧
8) Crohn's Disease Complications Before Baseline Intra-abdominal abscess: Never Sinus tracts/perforation: Never Fistula: Currently present Stricture complications of (CD): Previous history
9) Concomitant Crohn's Disease-Related Surgeries None reported
10) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 0 PREDNISONE 20 mg 20 SAFETY FOLLOW-UP PREDNISONE 10 mg 10 SAFETY FOLLOW-UP PREDNISOLONE 20 mg 20
11) Concomitant Medications Preferred Term Start Date End Date Reason Route EUGYNON /00022701/ 2011-04 2011-11- OTHER (BIRTH PROPHYLAXIS) ORAL 05 PREDNISONE 2011-06- - CROHN'S DISEASE ORAL 23 PARACETAMOL 2011-06- - OTHER (PAIN) ORAL 23 LIBRAX /00033301/ 2011-07- 2012-01- OTHER (ANXIETY) ORAL 18 13 OMEPRAZOLE 2011-07- 2011-12- OTHER (GASTROESOPHAGEAL ORAL 18 22 REFLUX) ONDANSETRON 2011-07- - OTHER (ANTI NAUSEA) ORAL 18 ATROPA BELLADONNA EXTRACT 2011-09- 2012-01- CROHN'S DISEASE ORAL 01 13 TRAMADOL 2011-09- - OTHER (PAIN) ORAL 01
69 (58) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
Preferred Term Start Date End Date Reason Route CIPROFLOXACIN 2011-10- 2011-10- ADVERSE EVENT ORAL 11 18 LOPERAMIDE 2011-11- 2011-11- OTHER (DIARRHEA) ORAL 13 13 DIPHENHYDRAMINE 2011-11- 2012-01- OTHER (INSOMNIA) ORAL HYDROCHLORIDE 14 13 HYOSCYAMINE 2011-11- 2012-01- OTHER (ABDOMINAL CRAMPING) ORAL 20 13 HYDROCODONE 2011-12- 2011-12- OTHER (PAIN CONTROL) ORAL 10 17 FOLIC ACID 2012-01- - OTHER (NUTRITIONAL SUPPLEMENT) ORAL 14 PRENATAL VITAMINS /01549301/ 2012-01- - OTHER (NUTRITIONAL SUPPLEMENT) ORAL 14 CEFAZOLIN SODIUM 2012-08- 2012-08- ADVERSE EVENT INTRAVENOUS 18 21 GENTAMICIN 2012-08- 2012-08- ADVERSE EVENT INTRAVENOUS 18 21 RINGER-LACTATE 2012-08- 2012-08- ADVERSE EVENT INTRAVENOUS 18 21 CEFALEXIN 2012-08- 2012-09- ADVERSE EVENT ORAL 21 05
12) Narrative Text ⿕㦂⪅ࡣ 2 ṓࡢⓑேዪᛶ࡛㸪2011 ᖺ 10 ᭶ 19 ᪥ᐶゎᑟධ⒪ἲࡋ࡚ᮏ㸦130 mg ⩌㸧ࢆ㟼 ⬦ෆᢞࡉࢀࡓࠋᮏ⿕㦂⪅ࡣ㸪ヨ㦂ࡀ㛤ࡉࢀࡿ๓ࣛࣥࢲ࣒ࡉࢀ࡚࠸ࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪⫹ᄞษ㝖㸪ᒀ ㊰ឤᰁ㸪⭠ษ㝖㸦2005 ᖺࡢ⒦Ꮝಟࢆྵࡴ㸧㸪⊃✽ᙧᡂཬࡧ⒦Ꮝಟ㸦3 ᅇ㸧㸪㣧㓇㸦㐌 1㹼2 ᅇ㸧㸪ႚ↮㸦1 ᪥ 1 ⟽㸧୪ࡧࢲ࣒࣐ࣜࣈ㸪ࢨࢳ࢜ࣉࣜࣥ㸪࢚ࢫࢩࢱࣟࣉ࣒ࣛ㸪ࢭࣇࢡࣟ ࣝཬࡧࣈࢹࢯࢽࢻᑐࡍࡿ⸆≀ࣞࣝࢠ࣮࡛࠶ࡗࡓࠋ SAE/Serious infection㸸⭈│⭈⅖㸦Day 305㸧 㦂⸆ࡀධᡭ࡛ࡁ࡞࠸ࡓࡵ㸪2011 ᖺ 12 ᭶ 15 ᪥⿕㦂⪅ࡣᐶゎ⥔ᣢヨ㦂ࡽ㝖እࡉࢀࡓࠋ CIOMS ࡼࡿ㸪2012 ᖺ 1 ᭶ 13 ᪥㸦Day 87㸧ࡢ⾑୰ࣄࢺ⤧ẟᛶࢦࢼࢻࢺࣟࣆࣥ ȕ ศ⏬᳨ᰝࡢ⤖ ᯝࡣ㝧ᛶ࡛࠶ࡾ㸪2012 ᖺ 2 ᭶ 1 ᪥ࡢࢻࢵࣉ࣮ࣛ㉸㡢Ἴࢫ࢟ࣕࣥࡣṇᖖ࡛࠶ࡗࡓࠋዷፎ୰㸪⿕㦂⪅ ࡣᝏᚰ㸪⭡③㸪⫼㒊③ཬࡧᝏᐮࢆッ࠼ 2012 ᖺ 8 ᭶ 18 ᪥ධ㝔ࡋࡓࠋධ㝔㸪⇕ࡣ࡞ࡃࣂࢱࣝ ࢧࣥࡣṇᖖ࡛࠶ࡗࡓࠋ⌮Ꮫⓗᡤぢ࡛ࡣ㸪⫘㦵⬨ᰕゅᅽ③㸦ྑഃ㸧ཬࡧ୧ୗ⫥ᾋ⭘㸦㊧㸧ࡀࡳ ࡽࢀࡓࠋᒀ᳨ᰝࡣⓑ⾑⌫㝧ᛶ㸦20-50㸧࡛㸪ᒀᇵ㣴᳨ᰝࡣࢢ࣒ࣛ㝜ᛶᱰ⳦㝧ᛶ㸦>100,000㸧࡛࠶ࡗ ࡓࠋ⭈ࢻࢵࣉ࣮ࣛ㉸㡢Ἴ᳨ᰝࡼࡾ୧ഃỈ⭈㸦ዷፎ⥆Ⓨ㸧ࡀุ᫂ࡋࡓࠋ2012 ᖺ 8 ᭶ 20 ᪥ࡢ ᒀᇵ㣴᳨ᰝࡢ⤖ᯝࡣ㸪⭠⳦>100,000 cfu/mL ࡛࠶ࡗࡓࡀ㸪2012 ᖺ 8 ᭶ 31 ᪥ࡢᒀᇵ㣴᳨ᰝ࡛ࡣ 㝜ᛶ࡛࠶ࡗࡓࠋ⒪ࡣࢭࣇࢰࣜࣥ㸪ࢤࣥࢱ࣐ࢩࣥ㸪㟼⬦ෆ⿵ᾮ㸦ங㓟ࣜࣥࢤࣝᾮ㸧ཬࡧᑐ ⒪ἲࡀ⏝࠸ࡽࢀࡓࠋ⿕㦂⪅ࡣ 2012 ᖺ 8 ᭶ 21 ᪥㏥㝔ࡋ㸪ࢭࣇࣞ࢟ࢩࣥࡢᢞࢆ㛤ጞࡋࡓࠋ 2012 ᖺ 9 ᭶ 5 ᪥㸪⿕㦂⪅ࡣዷፎ 37.6 㐌࡛ணᐃࡉࢀ࡚࠸ࡓ㏻ᖖࡢᖇ⋤ษ㛤ࢆཷࡅ࡚ᗣ࡞ዪඣ 㸦య㔜 5 ࣏ࣥࢻ 4 ࢜ࣥࢫ㸧ࢆฟ⏘ࡋ㸪ྠ᪥㸪⭈│⭈⅖ࡣᾘᩓࡋࡓሗ࿌ࡉࢀࡓࠋ
70 (59) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
(9) Subject CNTO1275CRD3001-1107-10978
1) Reason for narrative selection SAE Event of interest: Serious infection
2) Adverse Events Start date End date (Study Preferred Term Intensity/ Inf/ Action Taken/ (Study day) (Verbatim Term) SAE Relatedness Trt? Outcome day) 2012-11- ⭡③ N SEVERE/ N/ NOT APPLICABLE/ 2012-11- 29 (ABDOMINAL PAIN) NOT NA RECOVERED/RESOLVED 29 (-19) RELATED (-19) 2013-01- Ⓨ⇕ N MODERATE/ N/ DOSE NOT CHANGED/ 2013-01- 01 (FEVER) NOT NA RECOVERED/RESOLVED 18 (15) RELATED (32) 2013-01- 㛵⠇③ N MILD/ N/ DOSE NOT CHANGED/ 2013-01- 08 (ARTHRALGIA) NOT NA RECOVERED/RESOLVED 30 (22) RELATED (44) 2013-02- ࢡ࣮ࣟࣥ Y SEVERE/ N/ DOSE NOT CHANGED/ 2013-02- 01 (EXACERBATION OF CROHN'S NOT NA RECOVERED/RESOLVED WITH 20 (46) DISEASE) RELATED SEQUELAE (65) 2013-02- ⫢࿘ᅖ⮋⒆ N MODERATE/ Y/ DOSE NOT CHANGED/ 2013-02- 01 (PERIHEPATIC ABSCESS) NOT Y RECOVERED/RESOLVED 26 (46) RELATED (71) 2013-02- ࡑ࠺ N MILD/ N/ DOSE NOT CHANGED/ 2013-02- 04 (ITCHINESS) NOT NA RECOVERED/RESOLVED 20 (49) RELATED (65) 2013-02- ཱྀ⭍ဗ㢌③ N MILD/ N/ UNKNOWN/ 2013-02- 07 (SORE THROAT) NOT NA RECOVERED/RESOLVED 20 (52) RELATED (65) 2013-02- ᝏᚰ N MILD/ N/ DOSE NOT CHANGED/ 2013-02- 10 (NAUSEA) NOT NA RECOVERED/RESOLVED 16 (55) RELATED (61) 2013-02- ྤ N MILD/ N/ DOSE NOT CHANGED/ 2013-02- 10 (VOMITTING) NOT NA RECOVERED/RESOLVED 16 (55) RELATED (61) 2013-02- ⭡⭷⅖ Y MODERATE/ Y/ DOSE NOT CHANGED/ 2013-02- 11 (PERITONITIS) NOT Y RECOVERED/RESOLVED 20 (56) RELATED (65) 2013-02- Ⓨ⑈ N MILD/ N/ UNKNOWN/ 2013-02- 15 (RASH LEFT LEG AND FLANK) NOT NA RECOVERED/RESOLVED 19 (60) RELATED (64)
3) Baseline Demographic Information Age (years): 2 Sex: Female Weight (kg): 42.6 Race: White Date of birth: Height (cm): 157.5
4) Induction Treatment Group Randomized Treatment Group: Ustekinumab Approximating 6 mg/kg IV Actual Treatment Group: Ustekinumab Approximating 6 mg/kg IV
5) Induction Treatment Received Visit Start Date Study Day Dose Number Actual Treatment Dose WEEK 0 2012-12-18 1 1 Ustekinumab Approximating 6 mg/kg IV 259.2 mg
71 (60) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
6) Induction Disposition Did subject complete the induction study?: N Reason for induction early termination: OTHER Date of early termination: 2013-03-11 Did subject enter maintainance study?: N
7) Baseline Crohn's Disease History Date of diagnosis: 31DEC2004 Disease duration: 7.97 years Involved areas: ⤖⭠ࡢࡳ㸪⫠㛛࿘ᅖ
8) Crohn's Disease Complications Before Baseline Intra-abdominal abscess: Never Sinus tracts/perforation: Never Fistula: Currently present Stricture complications of (CD): Never
9) Concomitant Crohn's Disease-Related Surgeries Surgery Date Result of lack of efficacy? ⤖⭠ษ㝖-ཪࡣள 2013-02-06 Y
10) Concomitant Steroids None reported
11) Concomitant Medications Start Preferred Term Date End Date Reason Route ERYTHROMYCIN 2013-01- 2013-01- CROHN'S DISEASE ORAL 15 26 PARACETAMOL 2013-02- 2013-02- CROHN'S DISEASE ORAL 01 20 PARACETAMOL 2013-02- 2013-02- CROHN'S DISEASE RECTAL 01 01 AZTREONAM 2013-02- 2013-02- CROHN'S DISEASE INTRAVENOUS 01 17 CLINDAMYCIN 2013-02- 2013-02- CROHN'S DISEASE INTRAVENOUS 01 17 GASTROGRAFIN 2013-02- 2013-02- OTHER (PRE-MEDICATION FOR CT SCAN CHEST- ORAL 01 01 ABDOMEN-PELVIS) HEPARIN 2013-02- 2013-02- OTHER (PROPHYLACTIC) SUBCUTANEOUS 01 20 INFLUENZA VACCINE 2013-02- 2013-02- OTHER (PROPHYLAXIS- VACCINATION) INTRAMUSCULAR 01 01 LEVOFLOXACIN 2013-02- 2013-02- CROHN'S DISEASE INTRAVENOUS 01 01 METOCLOPRAMIDE 2013-02- 2013-02- CROHN'S DISEASE INTRAVENOUS 01 20 METRONIDAZOLE 2013-02- 2013-02- CROHN'S DISEASE INTRAVENOUS 01 01 MORPHINE SULFATE 2013-02- 2013-02- CROHN'S DISEASE INTRAVENOUS 01 06 MAGNESIUM SULFATE 2013-02- 2013-02- CROHN'S DISEASE INTRAVENOUS 02 11 POTASSIUM CHLORIDE 2013-02- 2013-02- CROHN'S DISEASE ORAL 02 02
72 (61) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
Start Preferred Term Date End Date Reason Route HEPARIN 2013-02- 2013-02- OTHER (PICC LINE PROTOCOL) INTRAVENOUS 03 20 LIDOCAINE 2013-02- 2013-02- OTHER (PICC LINE PLACEMENT) OTHER 03 03 POTASSIUM CHLORIDE 2013-02- 2013-02- ADVERSE EVENT INTRAVENOUS 03 11 CAMPHOR W/MENTHOL 2013-02- 2013-02- ADVERSE EVENT TOPICAL 04 20 PARACETAMOL 2013-02- 2013-02- OTHER (PREMEDICATION PRIOR TO BLOOD ORAL 05 12 TRANSFUSIONS) DIPHENHYDRAMINE 2013-02- 2013-02- OTHER (PRE- MEDICATION - PRIOR TO BLOOD INTRAVENOUS 05 12 TRANSFUSION) PHYTOMENADIONE 2013-02- 2013-02- OTHER (SUPPLEMENT) INTRAVENOUS 05 05 PHYTOMENADIONE 2013-02- 2013-02- OTHER (SUPPLEMENT) ORAL 05 05 BUPIVACAINE 2013-02- 2013-02- OTHER (EPIDURAL- POST OPERATIVE) OTHER W/FENTANYL 06 08 BENZOCAINE-MENTHOL 2013-02- 2013-02- ADVERSE EVENT ORAL 07 20 DIPHENHYDRAMINE 2013-02- 2013-02- ADVERSE EVENT ORAL 10 20 HYDROMORPHONE 2013-02- 2013-02- OTHER (POST OP) INTRAVENOUS 10 10 ONDANSETRON 2013-02- 2013-02- ADVERSE EVENT INTRAVENOUS 10 16 VANCOMYCIN 2013-02- 2013-02- CROHN'S DISEASE INTRAVENOUS 11 20 FUROSEMIDE 2013-02- 2013-02- OTHER (PRIOR TO INFUSIONS) INTRAVENOUS 12 15 MAGNESIUM OXIDE 2013-02- 2013-02- OTHER (SUPPLEMENT) ORAL 12 12 ALBUMIN HUMAN 2013-02- 2013-02- OTHER (SUPPLEMENT) INTRAVENOUS 14 14 ZINC OXIDE 2013-02- 2013-02- ADVERSE EVENT TOPICAL 15 19 OXYCODONE 2013-02- 2013-02- OTHER (PAIN MANAGEMENT) ORAL 16 26 FENTANYL CITRATE 2013-02- 2013-02- OTHER (PRE- MED FOR PROCEDURE (ABCESS INTRAVENOUS 20 20 DRAINAGE)) MIDAZOLAM 2013-02- 2013-02- OTHER (PREMEDICATION FOR PROCEDURE INTRAVENOUS 20 20 ( ABCESS DRAINAGE))
12) Narrative Text ⿕㦂⪅ࡣ 2 ṓࡢⓑேዪᛶ࡛㸪2012 ᖺ 12 ᭶ 18 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏ㸦㹼6 mg/kg ⩌㸧 ࢆ㟼⬦ෆᢞࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪⮋⒆ࢻࣞࢼ࣮ ࢪ㸪⒦ಟ㸪㈋⾑㸪ᡥ᱈ฟ㸪୪ࡧࣔ࢟ࢩࢩࣜࣥ㸪࣌ࢽࢩࣜࣥ㸪ࢩࣉࣟࣇࣟ࢟ࢧࢩࣥ㸪࣓ ࢺࣟࢽࢲࢰ࣮ࣝ㸪࣓ࣝ࢝ࣉࢺࣉࣜࣥ㸪prednisone ཬࡧࢭࣇࢡࣟࣝᑐࡍࡿ⸆≀ࣞࣝࢠ࣮࡛࠶ ࡗࡓࠋ⿕㦂⪅ࡢࢡ࣮ࣟࣥࡣࣥࣇࣜ࢟ࢩ࣐ࣈ㸪࣓ࣝ࢝ࣉࢺࣉࣜࣥ㸪ࢲ࣒࣐ࣜࣈཬࡧ certolizumab pegol ࡣ↓ຠ࡛࠶ࡗࡓࠋ SAE㸸ࢡ࣮ࣟࣥ㸦Day 46㸧 SAE/Serious infection㸸⭡⭷⅖㸦Day 56㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2013 ᖺ 2 ᭶ 1 ᪥㸪ᕥୗ⭡㒊ࡢ⭡③㸪Ⓨ⇕㸪Ỉᛶୗ⑩㸪ྤཬࡧ ⬺ຊࢆッ࠼ධ㝔ࡋࡓࠋ㠀⤒ཱྀᰤ㣴ࢆཷࡅ㸪⤒⓶ⓗ୰ᚰ㟼⬦࢝ࢸ࣮ࢸࣝࡀᤄධࡉࢀࡓࠋ⭡㒊ཬ
73 (62) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
ࡧ㦵┙㒊ࡢࢥࣥࣆ࣮ࣗࢱ᩿ᒙᙳ㸦CT㸧ࢫ࡛࢟ࣕࣥࡣ㸪ᕥ⤖⭠᭤㏆ഐᑠ⮋⒆ࡀ」ᩘࡳࡽࢀ㸪 ᭱ࡢ⮋⒆ࡣ⅖ࡢ࠶ࡿ⤖⭠⭡ቨࡢ 2.2 cm ࡢ㛫㝽ࢆᇙࡵ࡚࠸ࡓࠋᕥ⤖⭠᭤ୖ㒊ࡢᑠ⮋⒆ࡢ㞟ྜ యࡢࡁࡉࡣ 1.7×1.1 cm ࡛࠶ࡗࡓࠋ๓ᅇ㸪2013 ᖺ 1 ᭶ 16 ᪥ࡢࢫ࢟ࣕࣥẚ㍑ࡋ࡚㸪ᅇ⭠ᮎ➃ཬ ࡧ┣⭠⅖ᛶኚࡢቑࡀࡳࡽࢀࡓࠋ⤖⭠࿘ᅖࡢࣇࣞࢢ࣮ࣔࢿཬࡧ⮋⒆ࡢᡤぢࢆక࠺㢧ⴭ࡞ỗ ⭠⅖ࢆ࿊ࡋ࡚࠸ࡓࠋ2013 ᖺ 2 ᭶ 6 ᪥㸪⿕㦂⪅ࡣᅇ⭠⒦㐀タ⾡ࢆక࠺⭡ᘧ⤖⭠⾡ࢆཷࡅࡓࠋ 2013 ᖺ 2 ᭶ 7 ᪥ࡢ⭡Ỉᇵ㣴᳨ᰝࡢ⤖ᯝࡣ㸪Enterococcus avium 㝧ᛶ࡛࠶ࡗࡓࠋ2013 ᖺ 2 ᭶ 9 ᪥ࡢ ⏬ീࢫ࡛࢟ࣕࣥࡣ㸪ᕥୗ⫵ⴥ⫵⅖୍⮴ࡍࡿᾐ₶ᙳࡀࡳࡽࢀࡓࠋ⾑ᾮᇵ㣴᳨ᰝࡢ⤖ᯝࡣ㝜ᛶ࡛ ࠶ࡗࡓࠋ 2013 ᖺ 2 ᭶ 11 ᪥㸪⬚㒊 X ⥺࡛ྑᶓ㝸⭷ୗࡢ㐟㞳࢞ࢫ㸪₯ᅾᛶ↓Ẽ⫵ཪࡣ⫵⅖㝶కࡋࡓᕥ ⬚Ỉཬࡧᑡ㔞ࡢྑ⬚Ỉࡀࡳࡽࢀࡓࠋ⭡㒊ཬࡧ㦵┙㒊ࡢ CT ࢫ࡛࢟ࣕࣥࡣ㸪⤖⭠ள⾡ࡢᚋ㑇㸪 ⭡⭷⅖ࢆ♧၀ࡍࡿᗈ⠊࡞⭡⭷⫧ཌ㸦peritoneal enhancement㸧ࢆక࠺⭡Ỉ㸪┤⭠᩿➃ቨࡢ⫧ཌ㸪୧ ഃᛶࡢ⬚Ỉ㸪ཬࡧ㌟ᾋ⭘ࡀࡳࡽࢀࡓࠋ⌮Ꮫⓗᡤぢࡋ࡚ࡣ㸪ゐデ࡛ࡣ⭡㒊㍍ᗘࡢ◳ࡉࡀࡳࡽ ࢀࡓࡀᅽ③ࡣ࡞ࡃ㸪ᡭ⾡㒊⻏ᕢ⅖ࡢ࠸ཬࡧ୧⬯ᾋ⭘㸦1+㸧ࡀࡳࡽࢀࡓࠋ2013 ᖺ 2 ᭶ 19 ᪥ࡢ⭡㒊ཬࡧ㦵┙㒊ࡢ CT ࢫ࡛࢟ࣕࣥࡣ㸪⫢⮚ୗ⦕⮋⒆ࡢ㞟ྜయ㸪ྠᵝ㦵┙㒊⮋⒆ࡢ ᑠࡉ࡞㞟ྜయࡀࡳࡽࢀ㸪┤⭠ቨࡢ⫧ཌ㸪S ≧⤖⭠ࡢ⅖ᛶኚཬࡧ⫢⭘ࡀࡳࡽࢀࡓࠋ 2013 ᖺ 2 ᭶ 20 ᪥㸪⏬ീ⒪ࡼࡿ⮋⒆ࢻࣞࢼ࣮ࢪࡀᐇࡉࢀࡓࠋ⸆≀⒪ࡣࣂࣥࢥ࣐ ࢩࣥ㸪ࢬࢺࣞ࢜ࢼ࣒㸪ࢡࣜࣥࢲ࣐ࢩࣥ㸪ࣇࣟࢭ࣑ࢻཬࡧࢪࣇ࢙ࣥࣄࢻ࣑ࣛࣥࡀ⏝࠸ࡽࢀࡓࠋ 2013 ᖺ 2 ᭶ 20 ᪥㸪ࢡ࣮ࣟࣥཬࡧ⭡⭷⅖ࡣᾘᩓࡋࡓሗ࿌ࡉࢀ㸪ྠ᪥㸪⿕㦂⪅ࡣ㏥㝔ࡋࡓࠋ
(10) Subject CNTO1275CRD3001-3306-10824
1) Reason for narrative selection SAE Event of interest: Serious infection 2) Adverse Events Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day) (Verbatim Term) SAE Relatedness Trt? Outcome (Study day) 2012-10-23 ་⒪ᶵჾ㛵㐃ឤᰁ Y MODERATE/ Y/ NOT APPLICABLE/ 2012-10-25 (-13) (INFECTION ON PICCLINE) NOT RELATED Y RECOVERED/RESOLVED (-11) 2012-11-26 ᝏᚰ N MILD/ N/ DOSE NOT CHANGED/ 2012-12-17 (22) (NAUSEA) NOT RELATED NA RECOVERED/RESOLVED (43) 2013-01-05 ࢘ࣝࢫᛶ⫶⭠⅖ Y MODERATE/ Y/ DOSE NOT CHANGED/ 2013-01-14 (62) (VIRAL GASTROENTERITIS) NOT RELATED Y RECOVERED/RESOLVED (71) 2013-01-18 ⭠⟶⊃✽ N SEVERE/ N/ DOSE NOT CHANGED/ 2013-01-21 (75) (INTRA INTESTINAL STENOSIS) NOT RELATED NA RECOVERED/RESOLVED (78)
3) Baseline Demographic Information ȋȌǣ ʹͶ ǣ ȋȌǣ ͶͳǤͲ ǣ ǣ ͳͻͺͺǦͲͶǦͳ ȋ Ȍǣ ͳͶǤͲ
4) Induction Treatment Group Randomized Treatment Group: Ustekinumab 130 mg IV Actual Treatment Group: Ustekinumab 130 mg IV
74 (63) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
5) Induction Treatment Received Visit Start Date Study Day Dose Number Actual Treatment Dose WEEK 0 2012-11-05 1 1 Ustekinumab 130 mg IV 129.6 mg
6) Induction Disposition Did subject complete the induction study?: Y Did subject enter maintainance study?: Y
7) Baseline Crohn's Disease History Date of diagnosis: 31DEC2002 Disease duration: 9.85 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪⭠⟶እ≧㸦㛵⠇⅖㸭㛵⠇③㸧
8) Crohn's Disease Complications Before Baseline Intra-abdominal abscess: Never Sinus tracts/perforation: Never Fistula: Previous history Stricture complications of (CD): Previous history
9) Concomitant Crohn's Disease-Related Surgeries None reported
10) Concomitant Steroids
None reported 11) Concomitant Medications Preferred Term Start Date End Date Reason Route AZATHIOPRINE - - CROHN'S DISEASE ORAL MESALAZINE - - CROHN'S DISEASE ORAL CIPROFLOXACIN HYDROCHLORIDE 2012-10- 2012-10- OTHER (PREVIOUS HISTORY) INTRAVENOUS 10 19 METRONIDAZOLE 2012-10- 2012-10- OTHER (PREVIOUS HISTORY) INTRAVENOUS 10 19 PARACETAMOL 2012-10- 2012-10- ADVERSE EVENT INTRAVENOUS 24 29 METOCLOPRAMIDE HYDROCHLORIDE 2012-10- 2012-10- ADVERSE EVENT INTRAVENOUS 24 27 PIP/TAZO 2012-10- 2012-10- ADVERSE EVENT INTRAVENOUS 24 29 VANCOMYCIN HYDROCHLORIDE 2012-10- 2012-10- ADVERSE EVENT INTRAVENOUS 25 29 ALPRAZOLAM 2012-10- 2012-10- OTHER (PREVENTION ORAL 29 29 ANXIETY) CIPROFLOXACIN HYDROCHLORIDE 2012-10- 2012-11- OTHER ORAL 29 04 CLOXACILLIN SODIUM 2012-10- 2012-11- ADVERSE EVENT ORAL 29 04 PARACETAMOL 2012-10- - CROHN'S DISEASE ORAL 29 ULTRACET 2013-01- 2013-01- CROHN'S DISEASE ORAL 05 06 METOCLOPRAMIDE HYDROCHLORIDE 2013-01- 2013-01- ADVERSE EVENT INTRAVENOUS 05 16 PHLOROGLUCINOL 2013-01- 2013-01- ADVERSE EVENT INTRAVENOUS 05 16
75 (64) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
Preferred Term Start Date End Date Reason Route ACETORPHAN 2013-01- 2013-01- CROHN'S DISEASE ORAL 05 06 CIPROFLOXACIN HYDROCHLORIDE 2013-01- 2013-01- ADVERSE EVENT INTRAVENOUS 07 16 METRONIDAZOLE 2013-01- 2013-01- ADVERSE EVENT INTRAVENOUS 07 16 PARACETAMOL 2013-01- 2013-01- ADVERSE EVENT INTRAVENOUS 08 10 SACCHARATED IRON OXIDE 2013-01- 2013-01- ADVERSE EVENT INTRAVENOUS 08 10 NEFOPAM HYDROCHLORIDE 2013-01- 2013-01- ADVERSE EVENT INTRAVENOUS 09 10 ONDANSETRON 2013-01- 2013-01- ADVERSE EVENT INTRAVENOUS 09 09 LOPERAMIDE HYDROCHLORIDE 2013-01- 2013-01- ADVERSE EVENT ORAL 10 16 PANADEINE CO 2013-01- - CROHN'S DISEASE ORAL 20 ALL OTHER NON-THERAPEUTIC 2013-01- 2013-01- CROHN'S DISEASE OTHER PRODUCTS 21 29
12) Narrative Text ⿕㦂⪅ࡣ 2 ṓࡢⓑேዪᛶ࡛㸪2012 ᖺ 11 ᭶ 5 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏ㸦130 mg ⩌㸧ࢆ 㟼⬦ෆᢞࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪ႚ↮㸪ࣞࣝ ࢠ࣮㸪࿀ྜ㒊⒦Ꮝ㸦ᅇ⭠⒦㐀タక࠺ಟṇ⾡ཬࡧษ㝖㸧㸪⭠ࡢಟ⾡ཬࡧ⤖⭠ள㸦ᅇ⭠ S ≧⤖⭠࿀ྜ⾡㸧࡛࠶ࡗࡓࠋ⿕㦂⪅ࡣࣥࣇࣜ࢟ࢩ࣐ࣈཬࡧࢲ࣒࣐ࣜࣈࡢᢞᚋ⸆≀㐣ᩄࡢ ᪤ ࡀ࠶ࡾ㸪ࢨࢳ࢜ࣉࣜࣥཬࡧ࣓ࢧࣛࢪࣥࡣຠᯝ༑ศ࡛࠶ࡗࡓࠋ SAE/Serious infection㸸࢘ࣝࢫᛶ⫶⭠⅖㸦Day 62㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2013 ᖺ 1 ᭶ 5 ᪥Ⓨ⌧ࡋࡓ࢘ࣝࢫᛶ⫶⭠⅖ࡢࡓࡵ㸪⢓ᾮࢆక࠺ 㠀ฟ⾑ᛶୗ⑩㸦1 ᪥ 30 ᅇࡢ౽㸧㸪ᝏᚰ㸪ྤࢆక࠺ᗈỗᛶࡢ⭡③ࢆッ࠼ 2013 ᖺ 1 ᭶ 7 ᪥ᩆ ᛴ㒊ධ㝔ࡋࡓࠋ≧ࡀᨵၿࡋ࡞ࡗࡓࡓࡵ㸪⫢⮚ᾘჾ⛉㌿⛉࡞ࡗࡓࠋ2013 ᖺ 1 ᭶ 7 ᪥ ᐇࡉࢀࡓ⭡㒊ཬࡧ㦵┙㒊ࡢ㉸㡢Ἴ᳨ᰝ࡛ࡣ␗ᖖࡣㄆࡵࡽࢀ࡞ࡗࡓࠋ౽ᇵ㣴᳨ᰝ࡛ࡣ Acinetobacter calcaoceticus 㝧ᛶ࡛࠶ࡾ㸪⤒㦂ⓗࢩࣉࣟࣇࣟ࢟ࢧࢩࣥࡀᢞࡉࢀࡓࡀ㸪㦂ᢸᙜ ་ᖌࡣ㸪ᅉࡣ࢘ࣝࢫࡢྍ⬟ᛶࡀ᭱ࡶ㧗࠸⪃࠼ࡓࠋ㏣ຍ⒪࡛ࡣ paracetamol㸪࣓ࢺࢡࣟࣉࣛ ࣑ࢻ㸪࣓ࢺࣟࢽࢲࢰ࣮ࣝ㸪acetorphan㸪ࢺ࣐ࣛࢻ࣮ࣝ㸪࣓ࢧࣛࢪࣥ㸪ࢨࢳ࢜ࣉࣜࣥཬࡧ phloroglucinol dehydrate ࡀᢞࡉࢀࡓࠋ ⿕㦂⪅ࡢୗ⑩ࡢ㢖ᗘࡣῶᑡࡋ㸦1 ᪥ 5㹼6 ᅇࡢ㠀⢓ᾮ౽㸧㸪⅖ᛂ᳨ᰝ࡛ࡶྠᵝᨵၿࡋࡓ 㹙C ᛂᛶࡓࢇⓑ⃰ᗘࡣ 350 mg/L ࡽ 68 mg/L ῶᑡ㸦ṇᖖ⠊ᅖ 0-10 mg/L㸧㹛ࠋ2013 ᖺ 1 ᭶ 14 ᪥࢘ࣝࢫᛶ⫶⭠⅖ࡣᾘᩓࡋࡓሗ࿌ࡉࢀ㸪ྠ᪥㸪⿕㦂⪅ࡣ㏥㝔ࡋࡓࠋ
(11) Subject CNTO1275CRD3001-4111-10672
1) Reason for narrative selection SAE Discontinuation of study agent due to AE Event of interest: Serious infection
76 (65) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
2) Adverse Events Start date End date (Study Preferred Term Intensity/ Inf/ Action Taken/ (Study day) (Verbatim Term) SAE Relatedness Trt? Outcome day) 2012-09- ࢡ࣮ࣟࣥ N MODERATE/ N/ NOT APPLICABLE/ 2013-04- 12 (ANAEMIA, DUE TO CROHN'S NOT NA RECOVERED/RESOLVED 04 (-13) DISEASE ACTIVITY) RELATED (192) 2012-09- 㣗ḧῶ㏥ N MILD/ N/ NOT APPLICABLE/ 2012-10- 12 (HYPOREXIA) NOT NA RECOVERED/RESOLVED 16 (-13) RELATED (22) 2012-09- ⅖࣐࣮࣮࢝ୖ᪼ N MODERATE/ N/ NOT APPLICABLE/ Ongoing 12 (INCREASE IN INFLAMMATORY NOT NA NOT RECOVERED/NOT - (-13) MARKERS) RELATED RESOLVED 2012-09- ᝏᚰ N MILD/ N/ NOT APPLICABLE/ 2012-10- 12 (NAUSEA) NOT NA RECOVERED/RESOLVED 16 (-13) RELATED (22) 2012-09- Ⓨ⇕ N MILD/ N/ NOT APPLICABLE/ 2012-09- 15 (FEVER) NOT NA RECOVERED/RESOLVED 16 (-10) RELATED (-9) 2012-09- Ⓨ⇕ N MILD/ N/ DOSE NOT CHANGED/ 2012-09- 26 (FEVER) DOUBTFUL NA RECOVERED/RESOLVED 26 (2) (2) 2012-11- ᭶⤒ᅔ㞴 N MILD/ N/ DOSE NOT CHANGED/ 2012-11- 03 (DYSMENORREA) NOT NA RECOVERED/RESOLVED 03 (40) RELATED (40) 2012-11- 㝜⮋⒆ Y SEVERE/ Y/ DRUG WITHDRAWN/ 2012-12- 12 (ANOVULVAR ABSCESS) DOUBTFUL Y RECOVERED/RESOLVED 09 (49) (76) 2012-11- ዪᛶ⏕Ṫჾ⒦ Y SEVERE/ N/ DOSE NOT CHANGED/ 2012-12- 12 (RECTOVAGINAL FISTULA) DOUBTFUL NA RECOVERED/RESOLVED 09 (49) (76) 2012-11- Ⓨ⇕ N MODERATE/ Y/ DOSE NOT CHANGED/ 2012-11- 20 (FEVER) DOUBTFUL Y RECOVERED/RESOLVED 22 (57) (59) 2013-04- ㈋⾑ N MILD/ N/ DOSE NOT CHANGED/ Ongoing 04 (ANAEMIA) NOT NA NOT RECOVERED/NOT - (192) RELATED RESOLVED 2013-04- ᾘⰋ N MILD/ N/ DOSE NOT CHANGED/ Ongoing 04 (EPIGASTRIC BURNING) NOT NA NOT RECOVERED/NOT - (192) RELATED RESOLVED
3) Baseline Demographic Information Age (years): 3 Sex: Female Weight (kg): 49.0 Race: Not reported Date of birth: Height (cm): 169.0
4) Induction Treatment Group Randomized Treatment Group: Ustekinumab Approximating 6 mg/kg IV Actual Treatment Group: Ustekinumab Approximating 6 mg/kg IV
5) Induction Treatment Received Visit Start Date Study Day Dose Number Actual Treatment Dose WEEK 0 2012-09-25 1 1 Ustekinumab Approximating 6 mg/kg IV 259.2 mg
6) Induction Disposition Did subject complete the induction study?: Y Did subject enter maintainance study?: N
77 (66) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
7) Baseline Crohn's Disease History Date of diagnosis: 31OCT2004 Disease duration: 7.90 years Involved areas: ⤖⭠㸪⫠㛛࿘ᅖ㸪⭠⟶እ≧㸦㛵⠇⅖㸭㛵⠇③㸧
8) Crohn's Disease Complications Before Baseline Intra-abdominal abscess: Never Sinus tracts/perforation: Never Fistula: Previous history Stricture complications of (CD): Never
9) Concomitant Crohn's Disease-Related Surgeries Surgery Date Result of lack of efficacy? ࢻࣞࢼ࣮ࢪ-⤒⓶ษ㛤ཬࡧࢻࣞࢼ࣮ࢪ 2012-11-21 Y ࢻࣞࢼ࣮ࢪ-⤒⓶ษ㛤ཬࡧࢻࣞࢼ࣮ࢪ 2012-12-04 Y ࢻࣞࢼ࣮ࢪ-ࢩ࣮ࢺࣥ␃⨨ 2012-12-04 Y ࡑࡢ⫠㛛࿘ᅖ⒦ᡭ⾡㸦⒦Ꮝษ㛤㸪⒦Ꮝษ㝖࡞㸧 2012-12-04 Y ᅇ⭠⒦㐀タ 2012-12-04 Y
10) Concomitant Steroids None reported
11) Concomitant Medications Start End Preferred Term Date Date Reason Route FENTANYL CITRATE 2012- 2012- OTHER (CONSCIOUS SEDATION FOR INTRAVENOUS 09-12 09-12 ENDOSCOPY) PROPOFOL 2012- 2012- OTHER (CONSCIOUS SEDATION FOR INTRAVENOUS 09-12 09-12 COLONOSCOPY) PARACETAMOL 2012- 2012- ADVERSE EVENT ORAL 09-15 09-16 PARACETAMOL 2012- 2012- ADVERSE EVENT ORAL 09-26 09-26 PARACETAMOL 2012- 2012- ADVERSE EVENT ORAL 11-03 11-03 CIPROFLOXACIN 2012- 2012- ADVERSE EVENT ORAL 11-12 11-21 AMOXI-CLAVULANICO 2012- 2012- ADVERSE EVENT ORAL 11-21 12-16 DEXTROSE AND SODIUM 2012- 2012- ADVERSE EVENT INTRAVENOUS CHLORIDE INJECTION 11-26 12-07 PRIMAXIN 2012- 2012- ADVERSE EVENT INTRAVENOUS 11-26 12-04 HEPARIN SODIUM 2012- 2012- OTHER (POST-SURGICAL PROPHYLAXIS) SUBCUTANEOUS 12-09 12-19 CIPROFLOXACIN 2013- 2013- OTHER (CONCOMITANT TREATMENT WITH ORAL 03-26 03-30 ADALIMUMAB IN FISTULATING DISEASE) ADALIMUMAB 2013- - CROHN'S DISEASE SUBCUTANEOUS 03-28 ESOMEPRAZOLE MAGNESIUM 2013- - OTHER (EPIGASTRIC BURN) ORAL 04-04
12) Narrative Text ⿕㦂⪅ࡣ 3 ṓዪᛶ㸦ே✀ᮍሗ࿌㸧࡛㸪2012 ᖺ 9 ᭶ 25 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏ 㸦㹼6 mg/kg ⩌㸧ࢆ㟼⬦ෆᢞࡉࢀࡓࠋ
78 (67) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪ႚ↮㸪⤖⠇ᛶ ⣚ᩬ㸪ࢫࢸࣟࢻ౫Ꮡ㸪᭶⤒ᅔ㞴㸪ࢲ࣒࣐ࣜࣈཬࡧࣥࣇࣜ࢟ࢩ࣐ࣈ࡛ࡣຠᯝ༑ศ㸪ࢨ ࢳ࢜ࣉ࡛ࣜࣥࡣ⫶⭠⪏ᛶ࡛࠶ࡗࡓࠋᐙ᪘Ṕࡣ⤖⭠┤⭠⒴㸦ུẕ㸧࡛࠶ࡗࡓࠋ SAEs㸸㝜⮋⒆㸪ዪᛶ⏕Ṫჾ⒦㸦Day 49㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2012 ᖺ 11 ᭶ 12 ᪥Ⓨ⇕㸪⭐⮋⒆㸪ᣢ⥆ⓗ࡞⮋ฟཬࡧᒁᡤ③ࡀ ࠶ࡾ㸪┤⭠⭐⒦ཬࡧ⫠㛛࿘ᅖ⮋⒆デ᩿ࡉࢀࡓࠋ㦂⸆ࡣ㸪ຠᯝ༑ศࡢࡓࡵᢞࢆ୰Ṇࡋࡓࠋ 2012 ᖺ 11 ᭶ 21 ᪥⮋⒆ࡢእ⛉ⓗࢻࣞࢼ࣮ࢪࢆཷࡅࡓࠋࢩࣉࣟࣇࣟ࢟ࢧࢩࣥཬࡧࣔ࢟ࢩࢩࣜࣥ 㸭ࢡࣛࣈࣛࣥ㓟ࡶᢞࡉࢀࡓࠋࢻࣞࢼ࣮ࢪᚋࡶ⮋⒆ࡀᣢ⥆ࡋ㸪⫠㛛࿘ᅖ⮋⒆ཬࡧ㝜၁ࡽࡢ⮋ ฟࡀࡳࡽࢀࡓࡓࡵ㸪⿕㦂⪅ࡣ 2012 ᖺ 11 ᭶ 26 ᪥ධ㝔ࡋࡓࠋయ ࡣ 37.5°C ࡛࠶ࡗࡓࠋ 2012 ᖺ 11 ᭶㸦᪥᫂㸧ࡢ⮫ᗋ᳨ᰝ࡛ࡣ㸪࣐࣊ࢺࢡࣜࢵࢺ 27.9㸪࣊ࣔࢢࣟࣅࣥ 8.6㸪ⓑ⾑⌫ᩘ 10.44 ࡛࠶ࡗࡓ㸦༢ཬࡧṇᖖ⠊ᅖࡣグ㍕࡞ࡋ㸧ࠋ㦵┙㒊ࡢ᰾☢Ẽඹ㬆⏬ീἲ࡛ࡣ㸪ᕥࣂࣝࢺࣜ ࣥ⭢⮌ᚋ᪉ࡢ⫠㛛࿘ᅖࢆࡘ࡞ࡄ」㞧࡞⒦⟶ࡀࡳࡽࢀ㸪┤⭠⫠㛛ኚࢆ᭷ࡍࡿࢡ࣮ࣟࣥデ ᩿ࡉࢀࡓࠋ2012 ᖺ 12 ᭶ 4 ᪥㸪⮋⒆ࢻࣞࢼ࣮ࢪ୪ࡧᅇ⭠⒦㐀タ⾡ཬࡧࢩ࣮ࢺࣥ␃⨨⾡ࢆᐇ ࡋࡓࠋᡭ⾡ᚋ㸪ᡭ⾡ྜేࡣࡳࡽࢀ࡞ࡗࡓࠋ 2012 ᖺ 12 ᭶ 9 ᪥┤⭠⭐⒦ཬࡧ⫠㛛࿘ᅖ⮋⒆ࡣᅇࡋ㸪ྠ᪥㸪⿕㦂⪅ࡣ㏥㝔ࡋࡓࠋ
(12) Subject CNTO1275CRD3001-4603-10982
1) Reason for narrative selection SAE Event of interest: Serious infection
2) Adverse Events Start date End date (Study Preferred Term Intensity/ Inf/ Action Taken/ (Study day) (Verbatim Term) SAE Relatedness Trt? Outcome day) 2012-12- ࣥࣇ࢚ࣝࣥࢨ N MILD/ Y/ DOSE NOT CHANGED/ 2013-01- 26 (INFLUENZA) POSSIBLE N RECOVERED/RESOLVED 06 (8) (19) 2013-01- ࢡࣟࢫࢺࣜࢪ࣒࢘ឤᰁ Y SEVERE/ Y/ DOSE NOT CHANGED/ 2013-02- 21 (CLOSTRIDIUM DIFFICULE DOUBTFUL Y RECOVERED/RESOLVED 03 (34) SUPERINFECTION) (47)
3) Baseline Demographic Information Age (years): 2 Sex: Female Weight (kg): 62.6 Race: White Date of birth: - Height (cm): 162.0
4) Induction Treatment Group Randomized Treatment Group: Ustekinumab Approximating 6 mg/kg IV Actual Treatment Group: Ustekinumab Approximating 6 mg/kg IV
5) Induction Treatment Received Visit Start Date Study Day Dose Number Actual Treatment Dose WEEK 0 2012-12-19 1 1 Ustekinumab Approximating 6 mg/kg IV 389.7 mg
6) Induction Disposition Did subject complete the induction study?: Y Did subject enter maintainance study?: Y
79 (68) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
7) Baseline Crohn's Disease History Date of diagnosis: 24JAN2012 Disease duration: 0.91 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪⭠⟶እ≧㸦㛵⠇⅖㸭㛵⠇③㸧
8) Crohn's Disease Complications Before Baseline Intra-abdominal abscess: Never Sinus tracts/perforation: Never Fistula: Never Stricture complications of (CD): Never
9) Concomitant Crohn's Disease-Related Surgeries None reported
10) Concomitant Steroids None reported
11) Concomitant Medications Preferred Term Start Date End Date Reason Route COLESTYRAMINE - - CROHN'S DISEASE ORAL FOLIC ACID 2012-02- - CROHN'S DISEASE ORAL 16 METHOTREXATE 2012-02- 2013-05- CROHN'S DISEASE SUBCUTANEOUS 16 08 METRONIDAZOLE 2012-12- 2012-12- OTHER (CLOSTRIDIUM DIFFICILE ORAL 03 10 TREATMENT) MOVPREP 2012-12- 2012-12- OTHER (BOWEL PREPARATION) ORAL 09 09 FENTANYL 2012-12- 2012-12- OTHER (COLONOSCOPY SEDATION) INTRAVENOUS 10 10 MIDAZOLAM MALEATE 2012-12- 2012-12- OTHER (COLONOSCOPY SEDATION) INTRAVENOUS 10 10 HYOSCINE 2013-01- 2013-01- ADVERSE EVENT INTRAVENOUS BUTYLBROMIDE 23 25 MORPHINE 2013-01- 2013-01- ADVERSE EVENT SUBCUTANEOUS 23 24 METRONIDAZOLE 2013-01- 2013-02- ADVERSE EVENT ORAL 25 03 MOVPREP 2013-02- 2013-02- OTHER (BOWEL PREPARATION) ORAL 03 03 FENTANYL 2013-02- 2013-02- OTHER (COLONSOCOPY SEDATION) INTRAVENOUS 04 04 MIDAZOLAM MALEATE 2013-02- 2013-02- OTHER (COLONOSCOPY SEDATION) INTRAVENOUS 04 04
12) Narrative Text ⿕㦂⪅ࡣ 2 ṓࡢⓑேዪᛶ࡛㸪2012 ᖺ 12 ᭶ 19 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏ㸦㹼6 mg/kg ⩌㸧 ࢆ㟼⬦ෆᢞࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪ࢡࣟࢫࢺࣜࢪ ࣒࣭࢘ࢹࣇࢩࣞឤᰁཬࡧෙື⬦ᛶᚰᝈࡢᐙ᪘ᛶ༴㝤ᅉᏊ࡛࠶ࡗࡓࠋ
80 (69) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
SAE/Serious infection㸸ࢡࣟࢫࢺࣜࢪ࣒࢘ឤᰁ㸦Day 34㸧 CIOMS ࡼࡿ㸪2013 ᖺ 1 ᭶ 21 ᪥⿕㦂⪅ࡣ➽②ᨥ㸪⭡㒊ࡢ่③㸪⭡㒊⭾‶ឤཬࡧ⢓ᾮ⾑ ᾮࡀΰࡊࡗࡓỈᵝ౽ࡢ㢖ᗘቑຍ㸦1 ᪥ 10㹼20 ᅇ㸧ࢆッ࠼ࡓࠋኻ⚄ࡀⓎ⌧ࡋ㸪2013 ᖺ 1 ᭶ 22 ᪥ ධ㝔ࡋࡓࠋࣂࢱࣝࢧࣥࡣṇᖖ࡛࠶ࡾ㸪άⓎ࡞⭠㡢ཬࡧ₍↛ࡋࡓ⭡㒊ᅽ③ࡀࡳࡽࢀࡓࠋ 2013 ᖺ 1 ᭶ 23 ᪥ࡢ⮫ᗋ᳨ᰝ࡛ࡣ㸪ⓑ⾑⌫ᩘ 13.1 giga/L㸦ṇᖖ⠊ᅖ 4-10 giga/L㸧㸪C ᛂᛶࡓࢇ ⓑ⃰ᗘ 6 mg/L㸦ṇᖖ⠊ᅖ <6 mg/L㸧࡛࠶ࡗࡓࠋ2013 ᖺ 1 ᭶ 24 ᪥ࡢࢡࣟࢫࢺࣜࢪ࣒࣭࢘ࢹࣇ ࢩࣞẘ⣲᳨ᰝ࡛ࡣ㸪➇ྜ࣏࣓࣮ࣜࣛࢮ㐃㙐ᛂࡀ㝧ᛶ࡛࠶ࡗࡓࡀ㸪☜ㄆ᳨ᰝ࡛ࡣ㝜ᛶ࡛࠶ࡗࡓࠋ 㦂ᢸᙜ་ᖌࡣࢡࣟࢫࢺࣜࢪ࣒࣭࢘ࢹࣇࢩࣞ⭠⅖デ᩿ࡋࡓࠋ࣓ࢺࣟࢽࢲࢰ࣮ࣝ㸪 hyoscine butylbromide ཬࡧࣔࣝࣄࢿࡢᢞࢆཷࡅࡓࠋ2013 ᖺ 2 ᭶ 3 ᪥ᮏ㇟ࡣᾘᩓࡋࡓሗ࿌ ࡉࢀ㸪ྠ᪥⿕㦂⪅ࡣ㏥㝔ࡋࡓࠋ
(13) Subject CNTO1275CRD3001-5610-10835
1) Reason for narrative selection SAE Event of interest: Serious infection
2) Adverse Events Start date End date (Study Preferred Term Intensity/ Inf/ Action Taken/ (Study day) (Verbatim Term) SAE Relatedness Trt? Outcome day) 2012- እ㝜㒊⮋⒆ Y MODERATE/ Y/ DOSE NOT CHANGED/ 2012- 12-02 (VULVAL ABSCESSES (2CM), DUE TO DOUBTFUL Y RECOVERED/RESOLVED 12-21 (18) UNDERLYING PERIANAL FISTULA) (37) 2012- ࢝ࢸ࣮ࢸࣝ␃⨨㒊⑊③ N MILD/ N/ DOSE NOT CHANGED/ 2013- 12-14 (PAINFUL LEFT WRIST (PREVIOUS NOT NA RECOVERED/RESOLVED 01-15 (30) CANNULA SITE)) RELATED (62) 2012- ୖẼ㐨ឤᰁ N MILD/ Y/ DOSE NOT CHANGED/ 2012- 12-26 (UPPER RESPIRATORY TRACT INFECTION) NOT N RECOVERED/RESOLVED 12-26 (42) RELATED (42) 2013- ⮋⑁ᛶ⓶⑈ N MILD/ N/ DOSE NOT CHANGED/ 2013- 01-01 (PUSTULAR RASH (TO LEFT AND RIGHT NOT NA RECOVERED/RESOLVED 01-15 (48) HANDS, AND LEFT AND RIGHT FEET).) RELATED (62)
3) Baseline Demographic Information Age (years): 4 Sex: Female Weight (kg): 65.0 Race: White Date of birth: Height (cm): 154.9
4) Induction Treatment Group Randomized Treatment Group: Ustekinumab 130 mg IV Actual Treatment Group: Ustekinumab 130 mg IV
5) Induction Treatment Received Visit Start Date Study Day Dose Number Actual Treatment Dose WEEK 0 2012-11-15 1 1 Ustekinumab 130 mg IV 129.6 mg
6) Induction Disposition Did subject complete the induction study?: Y Did subject enter maintainance study?: Y
81 (70) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
7) Baseline Crohn's Disease History Date of diagnosis: 01DEC1999 Disease duration: 12.96 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪⫠㛛࿘ᅖ㸪⭠⟶እ≧㸦㛵⠇⅖㸭㛵⠇③㸧
8) Crohn's Disease Complications Before Baseline Intra-abdominal abscess: Previous history Sinus tracts/perforation: Never Fistula: Previous history Stricture complications of (CD): Previous history
9) Concomitant Crohn's Disease-Related Surgeries Surgery Date Result of lack of efficacy? ࢻࣞࢼ࣮ࢪ-ࢩ࣮ࢺࣥ␃⨨ 2012-12-13 N
10) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 0 PREDNISOLONE 10 mg 10
11) Concomitant Medications Start Preferred Term Date End Date Reason Route ALENDRONIC ACID - 2012-09- OTHER (OSTEOPOROSIS) ORAL 18 AMITRIPTYLINE - - OTHER (DEPRESSION AND ORAL ANALGESIA) LEKOVIT CA - - CROHN'S DISEASE ORAL CITALOPRAM - - OTHER (DEPRESSION) ORAL PANADEINE CO - - OTHER (ANALGESIA) ORAL DICLOFENAC - - OTHER (UNKNOWN) TOPICAL OMEPRAZOLE - - OTHER (GASTRO-OESOPHAGEAL ORAL REFLUX) PREDNISOLONE - - CROHN'S DISEASE ORAL PROPRANOLOL - - OTHER (PANIC ATTACKS) ORAL BUDESONIDE W/FORMOTEROL - - OTHER (ASTHMA) RESPIRATORY FUMARATE (INHALATION) SALBUTAMOL SULFATE - - OTHER (ASTHMA) RESPIRATORY (INHALATION) METRONIDAZOLE 2012-12- 2012-12- ADVERSE EVENT ORAL 04 28 PARACETAMOL 2012-12- 2012-12- ADVERSE EVENT ORAL 12 21 TRAMADOL 2012-12- 2012-12- ADVERSE EVENT ORAL 12 21 FENTANYL 2012-12- 2012-12- OTHER (ANAESTHETIC) INTRAVENOUS 13 13 RINGER-LACTATE 2012-12- 2012-12- OTHER (UNKNOWN) INTRAVENOUS 13 13 AMOXI-CLAVULANICO 2012-12- 2012-12- ADVERSE EVENT ORAL 14 21
12) Narrative Text ⿕㦂⪅ࡣ 4 ṓࡢⓑேዪᛶ࡛㸪2012 ᖺ 11 ᭶ 15 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏ㸦130 mg ⩌㸧ࢆ 㟼⬦ෆᢞࡉࢀࡓࠋ
82 (71) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3001 ヨ㦂
ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪⫠㛛࿘ᅖ⒦㸪 ⫠㛛࿘ᅖ⮋⒆㸪ႍᜥ㸪࠺ࡘ㸪⫶㣗㐨㏫ὶᛶᝈཬࡧࣃࢽࢵࢡⓎస࡛࠶ࡗࡓࠋ SAE/Serious infection㸸እ㝜㒊⮋⒆㸦Day 18㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2012 ᖺ 12 ᭶ 2 ᪥ࡽᣢ⥆ࡍࡿ㝜㒊ࡢ⑊③ཬࡧ⭘⬽ࡢᝏࢆッ ࠼ࡓࠋ2012 ᖺ 12 ᭶ 6 ᪥እ㝜㒊⮋⒆ࡀ⮬↛◚ࡋ㸪⑊③ࡀᝏࡋࡓࡓࡵ㸪2012 ᖺ 12 ᭶ 11 ᪥ ධ㝔ࡋࡓࠋ⮫ᗋ᳨ᰝ࡛ࡣ㸪C ᛂᛶࡓࢇⓑ⃰ᗘ 29 mg/dL㹙ṇᖖ⠊ᅖ㸦NR㸧<6 mg/dL㸧㸪ⓑ⾑⌫ ᩘ 12.6 giga/L㸦NR 4-11 giga/L㸧㸪ዲ୰⌫ᩘ 9.2 giga/L㸦NR 1.7-7.5 giga/L㸧࡛࠶ࡗࡓࠋ2012 ᖺ 12 ᭶ 13 ᪥㸪እ⛉ⓗࢻࣞࢼ࣮ࢪཬࡧࢩ࣮ࢺࣥ␃⨨ࢆཷࡅࡓࠋ㝜၁⮋⒆ᣔ࠸ᾮࡢᇵ㣴᳨ᰝࡢ⤖ᯝࡣ 㝜ᛶ࡛࠶ࡗࡓࠋࣔ࢟ࢩࢩࣜࣥ㸭ࢡࣛࣈࣛࣥ㓟㸪paracetamol㸪ࢺ࣐ࣛࢻ࣮ࣝཬࡧ࣓ࢺࣟࢽࢲࢰ࣮ ࣝࢆᢞࡉࢀࡓࠋᮏ㇟ࡣ 2012 ᖺ 12 ᭶ 21 ᪥ᾘᩓࡋࡓሗ࿌ࡉࢀ㸪⿕㦂⪅ࡣ 2012 ᖺ 12 ᭶ 14 ᪥㏥㝔ࡋࡓࠋ
83 (72) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
2.7.6.3 ➨ III ┦ᅜ㝿ඹྠヨ㦂㸸ᐶゎᑟධヨ㦂㸦CNTO1275CRD3002 ヨ㦂㸪ホ౯㈨ᩱ㸸 5.3.5.1.2㸧
2.7.6.3.1 ᴫせ
(1) 㦂ᐇィ⏬᭩␒ྕ CNTO1275CRD3002
(2) 㦂ࡢᶆ㢟 ୰➼ࡽ㔜ࡢάືᮇࢡ࣮ࣟࣥᝈ⪅ࢆᑐ㇟ࡍࡿ㸪࢘ࢫࢸ࢟ࢾ࣐ࣈ㸦௨ୗ㸪ᮏ㸧ࡢᐶゎ ᑟධ⒪ἲ࠾ࡅࡿᏳᛶཬࡧ᭷ຠᛶࡢホ౯ࢆ┠ⓗࡋࡓ➨ III ┦㸪ࣛࣥࢲ࣒㸪㔜┣᳨㸪ࣉࣛ ࢭ࣎ᑐ↷㸪୪⾜⩌㛫㸪ከタඹྠヨ㦂
(3) 㦂㈐௵་ᖌ
(4) 㦂ᐇ་⒪ᶵ㛵 ᆅᇦ 6ᆅᇦ ࢪ㸪࣮ࣚࣟࢵࣃ㸪⡿㸪༡⡿㸪ࣇࣜ࢝㸪࢜ࢭࢽ ཧຍᅜ 23 ࣧᅜ ᪥ᮏ㸪㡑ᅜ㸪ࣈࣝ࢞ࣜ㸪ࢡࣟࢳ㸪ࣁ࣮ࣥ࢞ࣜ㸪࣏࣮ࣛࣥࢻ㸪ࣟ ࢩ㸪ࢭࣝࣅ㸪࣮࢜ࢫࢺࣛࣜ㸪࣋ࣝࢠ࣮㸪ࣈࣛࢪࣝ㸪࢝ࢼࢲ㸪ࣇ ࣛࣥࢫ㸪ࢻࢶ㸪ࢫࣛࣥࢻ㸪ࢫ࢚ࣛࣝ㸪ࢱࣜ㸪࢜ࣛࣥࢲ㸪 ࢽ࣮ࣗࢪ࣮ࣛࣥࢻ㸪༡ࣇࣜ࢝㸪ࢫ࣌ࣥ㸪ⱥᅜ㸪⡿ᅜ ᐇタ 175 タ㸦᪥ᮏ 16 タ㸧
(5) බ⾲ᩥ⊩㸦ᘬ⏝ᩥ⊩㸧 ࡞ࡋ
(6) 㦂ᐇᮇ㛫 2011 ᖺ 6 ᭶᪥㹼2014 ᖺ 10 ᭶᪥
(7) 㛤Ⓨࡢ┦ ➨ III ┦
(8) ┠ⓗ ┠ⓗ 1. ୰➼ࡽ㔜ࡢάືᮇࢡ࣮ࣟࣥᝈ⪅࠾࠸࡚㸪ᮏࡢ㟼⬦ෆᢞࡼࡿᐶゎᑟධ⒪ἲ ࡢ clinical response ࡛ࡢ᭷ຠᛶࢆホ౯ࡍࡿࠋ
2. ୰➼ࡽ㔜ࡢάືᮇࢡ࣮ࣟࣥᝈ⪅࠾࠸࡚㸪ᮏࡢ㟼⬦ෆᢞࡼࡿᐶゎᑟධ⒪ἲ ࡢᏳᛶࢆホ౯ࡍࡿࠋ
84 (1) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
ḟ┠ⓗ 1. ᮏࡢ㟼⬦ෆᢞࡼࡿᐶゎᑟධ⒪ἲࡢ clinical remission ࡛ࡢ᭷ຠᛶࢆホ౯ࡍࡿࠋ
2. ᮏࡢ㟼⬦ෆᢞࡼࡿᐶゎᑟධ⒪ἲࡢᝈ≉␗ⓗᗣ㛵㐃⏕άࡢ㉁㸦QOL㸧ᨵၿ࡛ࡢ᭷ ຠᛶࢆホ౯ࡍࡿࠋ
3. ⾑Ύ C ᛂᛶࡓࢇⓑ㸦CRP㸧㸪౽୰࢝ࣝࣉࣟࢸࢡࢳࣥ㸪౽୰ࣛࢡࢺࣇ࢙ࣜࣥ㸪ཬࡧࡑࡢ ࡢ⸆ຊᏛⓗࣂ࣐࣮࣮࢜࢝ࡢኚືࢆྵࡵࡓᮏᢞࡢ⸆≀ືែཬࡧ⸆ຊᏛࢆホ౯ࡍࡿࠋ
4. ᐶゎᑟධヨ㦂 CNTO1275CRD3001 ేࡏ࡚㸪ᐶゎ⥔ᣢヨ㦂 CNTO1275CRD3003 ࡛ホ౯ࡍࡿ ᑐ㇟㞟ᅋࢆᥦ౪ࡍࡿࠋ
(9) 㦂᪉ἲ ᮏヨ㦂㸦ࣛࣥࢲ࣒㸪㔜┣᳨㸪ࣉࣛࢭ࣎ᑐ↷㸪୪⾜⩌㛫㸪ከタඹྠヨ㦂㸧࡛ࡣ㸪⿕㦂⪅ࡣ 0 㐌┠௨ୗࡢ࠸ࡎࢀࡢ༢ᅇ㟼⬦ෆᢞ⩌ 1㸸1㸸1 ࡢẚ࡛ࣛࣥࢲ࣒ࡾࡅࡽࢀࡓࠋ · ࣉࣛࢭ࣎⩌
· ᮏ 130 mg ⩌
· ᮏࡢయ㔜ู⏝㔞㸦㹼6 mg/kg㸧⩌㸦௨ୗ㸪ᮏ㹼6 mg/kg ⩌㸧
· ᮏ 260 mg㸦య㔜 55 kg㸧
· ᮏ 390 mg㸦య㔜 >55 kg㹼85 kg㸧
· ᮏ 520 mg㸦య㔜 >85 kg㸧
6 㐌┠㸪⿕㦂⪅ࢆᑐ㇟ࡋ࡚㸪せホ౯㡯┠࡛࠶ࡿ clinical response ࢆホ౯ࡋࡓࠋ0 㐌┠ ᮏ⩌ࡾࡅࡽࢀ㸪ࡘ 8 㐌┠ clinical response ࡀᚓࡽࢀࡓ⿕㦂⪅ࢆ㸪8 㐌┠㸪ᐶゎ⥔ᣢ ヨ㦂 CNTO1275CRD3003 ࡢせ࡞ᑐ㇟㞟ᅋࡋ࡚⛣⾜ྍ⬟ࡋࡓࠋᮏࡼࡿᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀ࡞ࡗࡓ⿕㦂⪅ཬࡧ 0 㐌┠ࣉࣛࢭ࣎⩌ࡾࡅࡽࢀࡓ⿕㦂⪅ 㸦clinical response ࡢ᭷↓ࡣၥࢃ࡞࠸㸧ࡣ㸪8 㐌┠ᐶゎ⥔ᣢヨ㦂 CNTO1275CRD3003 ࡢ⛣⾜㐺 ᱁ࡋࡓࡀ㸪せ࡞ᑐ㇟㞟ᅋࡣྵࡵ࡞࠸ࡇࡋࡓࠋᐶゎ⥔ᣢヨ㦂 CNTO1275CRD3003 ⛣⾜ࡋ࡞ࡗࡓ⿕㦂⪅ࡘ࠸࡚ࡣ㸪0 㐌┠ࡢ㦂⸆ᢞࡽ⣙ 20 㐌㛫ᚋᏳᛶ㏣㊧ㄪᰝࢆᐇ ࡋࡓࠋ ᮏヨ㦂ࢆ㏻ࡌ࡚㸪⊂❧ࢹ࣮ࢱࣔࢽࢱࣜࣥࢢጤဨࡀ㸪⿕㦂⪅ࡢᏳᛶࢹ࣮ࢱࢆࣔࢽࢱࣜࣥࢢࡋ ࡓࠋ ᮏヨ㦂࡛ࡣ㸪୰㛫ゎᯒࡣᐇࡋ࡞ࡗࡓࠋ
(10) ⿕㦂⪅ᩘ㸦ィ⏬ཬࡧゎᯒ㸧 ィ⏬ ┠ᶆᩘࡣ 600 ࡋ㸪ྛᢞ⩌ 200 ࡎࡘࣛࣥࢲ࣒ࡍࡿࡇࡋࡓࠋᮏヨ㦂࡛⏝ࡍ ࡿ㟼⬦ෆᢞ〇㹙࢘ࢫࢸ࢟ࢾ࣐ࣈ 130 mg㸸ᐜ㔞 26 mL㸦5 mg/mL㸧㹛ࡢࣂࢵࢳᏳᐃᛶୖࡢၥ 㢟ࡀ☜ㄆࡉࢀࡓࡓࡵ㸪㦂౫㢗⪅ࡣ 20 ᖺ᭶ヨ㦂ࢆ୍୰᩿ࡋࡓࡀ㸪ࡑࢀ௨๓ྜィ 12
85 (2) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
ࡀࣛࣥࢲ࣒ࡉࢀ࡚࠸ࡓࠋࡇࢀࡽࡢ⿕㦂⪅ࡢࢹ࣮ࢱࡣ㸪ࡇࡢၥ㢟ࢆㄆ▱ࡋࡓࡇࡼࡾホ౯ ࣂࢫࢆ⏕ࡌࡿྍ⬟ᛶࡀ࠶ࡿࡇࡽ㸪ィ⏬ࡋࡓゎᯒࡣ⏝࠸࡞࠸ࡇࡋࡓࠋࡲࡓ㸪ᙜึィ ⏬ࡋࡓ㸪せホ౯㡯┠ࡢゎᯒࡢ᳨ฟຊࢆᚓࡿࡓࡵᚲせ࡞ࢧࣥࣉࣝࢧࢬࡢ 600 ࢆ⥔ᣢࡍࡿࡓ ࡵ㸪⤫ィゎᯒィ⏬᭩グ㍕ࡋࡓ┠ᶆᩘࢆ 612 㸦600 㸩12 㸧ኚ᭦ࡍࡿࡇࡋࡓࠋ
᪥ᮏே⿕㦂⪅ᩘࡢタᐃ᰿ᣐ 3001 ヨ㦂ྠᵝ㸪᪥ᮏே㞟ᅋ㞟ᅋࡢ⤖ᯝࡢ୍㈏ᛶࢆ᳨ウࡍࡿࡓࡵᚲせ࡞ᩘࡣ㸪ࠕᅜ 㝿ඹྠ㦂㛵ࡍࡿᇶᮏⓗ⪃࠼᪉ࡘ࠸࡚ࠖ♧ࡉࢀࡿ᪉ἲ 2࠙D (Japan) >0 ࡘ D (all )>0ࠚ ࡼࡾ 1 ⩌⣙ 20 㸦ྜィ 60 㸧ぢ✚ࡶࡽࢀࡓࡀ㸪ᙜヱヨ㦂ࡢᑐ㇟⿕㦂⪅ᩘࡣᴟࡵ࡚ᑡ࡞࠸ࡇ ࡀணࡉࢀ㸪ࡉࡽࣉࣛࢭ࣎ᑐ↷ヨ㦂࡛࠶ࡿࡇࡶ⪃៖ࡍࡿ㸪㈐௵་ᖌೃ⿵ࡢணഛⓗ࡞ㄪᰝ ࡼࡾ 20 ⛬ᗘࡀ⌧ᐇⓗ㞟✚ྍ⬟࡞ᩘ⪃࠼ࡽࢀࡓࠋࡋࡓࡀࡗ࡚㸪㞟✚┠ᶆᩘࢆ 20 ࡋ㸪ྍ⬟࡞ሙྜࡣ㸪ࡼࡾከࡃࡢ᪥ᮏேᩘ☜ಖດࡵࡿࡇࡋࡓࠋ
ゎᯒ ྜィ 640 ࡀࣛࣥࢲ࣒ࡉࢀࡓࡀ㸪≉᩿ࡾࡢ࡞࠸㝈ࡾ㸪ィ⏬ࡋࡓࡍ࡚ࡢゎᯒࡣ㸪ヨ㦂㛤 ᚋࣛࣥࢲ࣒ࡉࢀࡓ 628 ࢆᑐ㇟ᐇࡋࡓ㹙ࣉࣛࢭ࣎⩌㸸210 㸪ᮏ 130 mg ⩌㸸209 㸪 ᮏ㹼6 mg/kg ⩌㸸209 㹛ࠋ ᭷ຠᛶࡢゎᯒᑐ㇟㞟ᅋࡣ㸪GCP ୖࡢᠱᛕࡽ㸪ࢹ࣮ࢱࡢṇ☜ᛶཬࡧጇᙜᛶࡀᢸಖ࡛ࡁ࡞࠸ࡍ ࡿ㦂౫㢗⪅ࡢุ᩿ࡼࡾ 1 ࡀ㝖እࡉࢀ㸪627 ࡛࠶ࡗࡓࠋࡋࡋ࡞ࡀࡽ㸪ᮏ⿕㦂⪅ࡀ㦂⸆ ࢆᢞࡉࢀࡓࡇࡣ☜ㄆࡉࢀࡓࡓࡵ㸪Ᏻᛶཬࡧ⸆≀ືែࡢゎᯒࡣᮏ⿕㦂⪅ࢆྵࡵࡿࡇࡋ ࡓࠋᏳᛶཬࡧ⸆≀ືែࡢゎᯒᑐ㇟㞟ᅋࡣ㸪ࣉࣛࢭ࣎⩌ࡾࡅࡽࢀࡓࡀ㦂⸆ࡣᢞࡉࢀ࡞ ࡗࡓ 1 ࢆ㝖࠸ࡓ㸪627 ࡛࠶ࡗࡓࠋ
(11) デ᩿ཬࡧ࡞㑅ᢥᇶ‽ ᮏヨ㦂ࡢᑐ㇟ࡣ㸪Crohn’s Disease Activity Index㸦CDAI㸧ࢫࢥࡀ 220 ௨ୖ 450 ௨ୗᐃ⩏ࡉࢀ ࡿ୰➼ࡽ㔜ࡢάືᮇࢡ࣮ࣟࣥ 3 ࢝᭶㛫௨ୖ⨯ᝈࡋ࡚࠾ࡾ㸪ຍ࠼࡚ 1㸧CRP ⃰ᗘࡀ 3.0 mg/L ㉸㸪2㸧ࢫࢡ࣮ࣜࢽࣥࢢࡢ౽୰࢝ࣝࣉࣟࢸࢡࢳࣥ⃰ᗘࡀ 250 mg/kg ㉸㸪3㸧࣮࣋ࢫࣛ ࣥ๓ 3 ࢝᭶௨ෆࡢෆど㙾᳨ᰝ࡛άືᛶࢡ࣮ࣟࣥࡢᚩೃࡢ࠸ࡎࢀࡀㄆࡵࡽࢀࡿ㸪18 ṓ௨ୖࡢᝈ ⪅ࡋࡓࠋࡲࡓ㸪㐣ཤ X ⥺᳨ᰝ㸪⤌⧊Ꮫⓗ᳨ᰝཪࡣෆど㙾᳨ᰝ࡛⭠⅖㸪ᅇ⭠⅖ཪࡣᅇ⤖⭠⅖ ࡀ☜ㄆࡉࢀ࡚࠸ࡿࡇ㸪㐣ཤ⏝࠸ࡓ᪤Ꮡ⒪ࡀຠᯝ༑ศ࡛࠶ࡾ㸪㐣ཤ 1 ✀㢮௨ୖࡢᢠ TNF ⸆⒪㸦ࣥࣇࣜ࢟ࢩ࣐ࣈ㸪ࢲ࣒࣐ࣜࣈ㸪certolizumab pegol㸧ᑐࡋ࡚ຠᯝ༑ศཪࡣᚸᐜᛶ ࡢ࡞࠸ࡇࡀ♧ࡉࢀ࡚࠸࡞࠸ࡇࡋࡓࠋ
(12) ⿕㦂⸆㸪⏝㔞ཬࡧᢞ᪉ἲ㸪ࣟࢵࢺ␒ྕ ᮏ㹙࢘ࢫࢸ࢟ࢾ࣐ࣈ㸦㑇ఏᏊ⤌࠼㸧㹛ࡢ㟼⬦ෆᢞ⏝〇ࡋ࡚㸪2 ⏝㔞㹙90 mg㸦⾲♧ 㔞 1 mL㸧ཪࡣ 45 mg㸦⾲♧㔞 0.5 mL㸧㹛ࡢ࢞ࣛࢫࣂࣝሸࡉࢀࡓ༢ᅇᢞ⏝㸪↓⳦ᾮ ࡀ౪⤥ࡉࢀࡓ㸦ࣂࣝࢡࣟࢵࢺ␒ྕ㸸 㸪 㸪 㸧ࠋ
86 (3) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
ᮏ〇ࡣ㸪1 mL ࠶ࡓࡾ 90 mg ࡢ࢘ࢫࢸ࢟ࢾ࣐ࣈࢆྵ᭷ࡋࡓࠋ࢘ࢫࢸ࢟ࢾ࣐ࣈࡢ㸪ྛࣂ ࣝ୰ࡢ〇ࡣ L-ࣄࢫࢳࢪࣥ㸪L-ࣄࢫࢳࢪࣥሷ㓟ሷ୍Ỉ≀㸪ࢩࣙ⢾㸪࣏ࣜࢯ࣮ࣝ࣋ࢺ 80 ࢆྵ ᭷ࡋ㸪pH ࡣ 6.0 ࡛࠶ࡗࡓࠋಖᏑࡣྵ᭷ࡋ࡚࠸࡞ࡗࡓࠋ
(13) ᑐ↷⸆㸪⏝㔞ཬࡧᢞ᪉ἲ㸪ࣟࢵࢺ␒ྕ ࣉࣛࢭ࣎ࡢ㟼⬦ෆᢞ⏝〇ࡋ࡚㸪࢞ࣛࢫࣂࣝሸࡉࢀࡓ༢ᅇᢞ⏝㸪↓⳦ᾮࡀ౪ ⤥ࡉࢀࡓ㸦ࣂࣝࢡࣟࢵࢺ␒ྕ㸸 㸪 㸪 㸪 㸧ࠋྛࣂࣝ୰ࡢ〇 ࡣ L-ࣄࢫࢳࢪࣥ㸪L-ࣄࢫࢳࢪࣥሷ㓟ሷ୍Ỉ≀㸪ࢩࣙ⢾㸪࣏ࣜࢯ࣮ࣝ࣋ࢺ 80 ࢆྵ᭷ࡋ㸪pH ࡣ 6.0 ࡛࠶ࡗࡓࠋಖᏑࡣྵ᭷ࡋ࡚࠸࡞ࡗࡓࠋ
(14) ᢞᮇ㛫 ࡍ࡚ࡢ⿕㦂⪅ࡣ㸪0 㐌┠㸪ࣉࣛࢭ࣎㸪ᮏࡢᅛᐃ⏝㔞㸦130 mg㸧ཪࡣయ㔜ู⏝㔞㸦㹼 6 mg/kg㸧ࡢ࠸ࡎࢀࣛࣥࢲ࣒ࡾࡅࡽࢀ㸪༢ᅇ㟼⬦ෆᢞࡉࢀࡓࠋ6 㐌┠せホ౯㡯┠ ࡛࠶ࡿ clinical response ࢆホ౯ࡋ㸪8 㐌┠㐺᱁ࢆᐶゎ⥔ᣢヨ㦂 CNTO1275CRD3003 ⛣⾜ྍ⬟ ࡋࡓࠋᐶゎ⥔ᣢヨ㦂 CNTO1275CRD3003 ⛣⾜ࡋ࡞ࡗࡓ⿕㦂⪅ࡘ࠸࡚ࡣ㸪0 㐌┠ࡢ㦂⸆ ᢞࡽ⣙ 20 㐌㛫ᚋᏳᛶ㏣㊧ㄪᰝࢆᐇࡋࡓࠋ
(15) ホ౯㡯┠
· ⸆≀ືែ㸸⾑Ύ୰࢘ࢫࢸ࢟ࢾ࣐ࣈ⃰ᗘ
· චཎᛶ㸸ᢠ࢘ࢫࢸ࢟ࢾ࣐ࣈᢠయ
· ⸆ຊᏛ㸭ࣂ࣐࣮࣮࢜࢝㸸⾑Ύࢆ⏝࠸ࡓࣂ࣐࣮࣮࢜࢝㸪ᮎᲈ⾑ࡢ࣓ࢵࢭࣥࢪ࣮ࣕࣜ࣎᰾ 㓟㸦RNA㸧Ⓨ⌧㸪⢓⭷⏕᳨࠾ࡅࡿ RNA Ⓨ⌧ཬࡧᝈ⒵ࡢ⤌⧊Ꮫⓗホ౯㸪⾑୰ DNA ࡢゎᯒ
· ᭷ຠᛶ㸸CDAI ࢫࢥ㸪CRP ⃰ᗘ㸪౽୰ࣛࢡࢺࣇ࢙ࣜࣥཬࡧ࢝ࣝࣉࣟࢸࢡࢳࣥ⃰ᗘ㸪⒦Ꮝ ࡢホ౯㸪ቯᛶ⮋⓶ࡢホ౯㸪⭠ෆど㙾᳨ᰝ㸦⢓⭷⒵㸧㸦ᣦᐃタ࡛ྠពࡀᚓࡽࢀࡓ ⿕㦂⪅ࡢࡳ㸧
· ᝈ⪅ሗ࿌࢘ࢺ࣒࢝㸸Inflammatory Bowel Disease Questionnaire㸦IBDQ㸧㸪36-item Short- form Health Survey㸦SF-36㸧
· ་⒪⤒῭㸸་⒪㈨※ࡢ⏝㸪Productivity Visual Analog Scale㸦VAS㸧㸪Work Limitations Questionnaire㸦WLQ㸧
· Ᏻᛶ㸸᭷ᐖ㇟㸪㔜⠜࡞᭷ᐖ㇟㸦SAE㸧㸪ࣂࢱࣝࢧࣥ㸪㦂⸆ࡢ㟼⬦ෆᢞ୰ཪ ࡣᢞᚋ 1 㛫௨ෆⓎ⌧ࡋࡓ᭷ᐖ㇟㸦௨ୗ㸪ࣥࣇ࣮ࣗࢪࣙࣥࣜࢡࢩࣙࣥ㸧㸪⮫ᗋ ᳨ᰝ㸦⾑ᾮᏛⓗ᳨ᰝཬࡧ⾑ᾮ⏕Ꮫ᳨ᰝ㸧㸪⌮Ꮫⓗᡤぢ㸪12 ㄏᑟᚰ㟁ᅗ
87 (4) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
(16) ⤫ィᡭἲ せホ౯㡯┠ࡣ 6 㐌┠ࡢ clinical response ࡛࠶ࡾ㸪CDAI ࢫࢥ࠾ࡅࡿ࣮࣋ࢫࣛࣥࡽࡢ 100 ࣏ࣥࢺ௨ୖࡢῶᑡᐃ⩏ࡋࡓࠋ࣮࣋ࢫࣛࣥࡢ CDAI ࢫࢥࡀ 220 ௨ୖ 248 ௨ୗࡢ⿕㦂⪅ ࡘ࠸࡚ࡣ㸪CDAI ࢫࢥࡀ 150 ࣏ࣥࢺᮍ‶ࢆ㐩ᡂࡋ࡚࠸ࡓሙྜ㸪clinical response ࡀᚓࡽࢀࡓ ࡳ࡞ࡋࡓࠋ せ࡞ḟホ౯㡯┠ࡢ⤫ィᏛⓗ᳨ᐃࢆ⾜࠺㡰ࢆ௨ୗ♧ࡋࡓࠋ · 8 㐌┠ࡢ clinical remission㸦CDAI ࢫࢥ 150 ࣏ࣥࢺᮍ‶㸧
· 8 㐌┠ࡢ clinical response㸦CDAI ࢫࢥࡢ࣮࣋ࢫࣛࣥࡽࡢ 100 ࣏ࣥࢺ௨ୖࡢῶᑡ㸧 ࣮࣋ࢫࣛࣥࡢ CDAI ࢫࢥࡀ 220 ௨ୖ 248 ௨ୗࡢ⿕㦂⪅ࡘ࠸࡚ࡣ㸪CDAI ࢫࢥࡀ 150 ࣏ࣥࢺᮍ‶ࢆ㐩ᡂࡋ࡚࠸ࡓሙྜ㸪clinical response ࡀᚓࡽࢀࡓࡳ࡞ࡋࡓࠋ
· 6 㐌┠ࡢ 70-point response㸦CDAI ࢫࢥࡢ࣮࣋ࢫࣛࣥࡽࡢ 70 ࣏ࣥࢺ௨ୖࡢῶᑡ㸧
· 3 㐌┠ࡢ 70-point response㸦CDAI ࢫࢥࡢ࣮࣋ࢫࣛࣥࡽࡢ 70 ࣏ࣥࢺ௨ୖࡢῶᑡ㸧
ேཱྀ⤫ィᏛⓗ≉ᛶཬࡧ࣮࣋ࢫࣛࣥࡢᝈ≉ᛶࡢせ⣙ࡣ㸪ヨ㦂㛤ᚋࣛࣥࢲ࣒ࡉࢀࡓ 628 ࢆᑐ㇟ᐇࡋࡓࠋ᭷ຠᛶࡢゎᯒࡣ㸪ヨ㦂㛤ᚋࣛࣥࢲ࣒ࡉࢀࡓ 1 ࡢ⿕㦂⪅ࡢࢹ࣮ ࢱࡀ㸪ࡑࡢṇ☜ᛶཬࡧጇᙜᛶࡀᢸಖ࡛ࡁ࡞࠸ࡍࡿ㦂౫㢗⪅ࡢุ᩿ࡼࡾ㝖እࡉࢀࡓࡇࡽ㸪 627 ࢆᑐ㇟ᐇࡋࡓࠋせホ౯㡯┠ཬࡧせ࡞ḟホ౯㡯┠ࡣ㸪୧ഃ᭷ពỈ‽ 0.05 ࡢࡶ㸪 Cochran-Mantel-Haenszel ࡢ᳨࢝ᐃࢆ⏝࠸㸪ヨ㦂ᆅᇦ㸦ࢪ㸪ᮾ࣮ࣚࣟࢵࣃ㸪ࡑࡢ㸧ཬ ࡧ CDAI ࢫࢥ㸦300 ௨ୗཪࡣ 300 ㉸㸧ࡼࡾᒙูࡋ㸪ᮏࡢྛᢞ⩌ࣉࣛࢭ࣎⩌ࢆẚ㍑ࡋ ࡓࠋయࡢ➨ I ✀ࡢ㐣ㄗࡢỈ‽ࢆ 0.05 ࢥࣥࢺ࣮ࣟࣝࡍࡿࡓࡵ㸪ヨ㦂యࡢᅛᐃ㡰ᗎἲࢆ᥇⏝ࡋ㸪 せホ౯㡯┠㸪せ࡞ḟホ౯㡯┠ࡢ㡰࡛㝵ᒙⓗ᳨ᐃࡋࡓࠋᮏヨ㦂࡛ࡣ㸪せホ౯㡯┠ࡘ࠸ ࡚ࣉࣛࢭ࣎⩌ẚ㍑ࡋ࡚ᮏ㧗⏝㔞⩌᭷ពᕪࡀㄆࡵࡽࢀࡓሙྜ㸪ヨ㦂┠ⓗࡀ㐩ࡏࡽࢀࡓࡳ ࡞ࡋࡓࠋ Ᏻᛶࡢゎᯒࡣ㸪ヨ㦂㛤ᚋࣛࣥࢲ࣒ࡉࢀ㸪0 㐌┠㦂⸆ࢆᢞࡉࢀࡓ 627 ࢆᑐ㇟ ࡋࡓ㸦ࣉࣛࢭ࣎⩌ࡢ 1 ࡣ㸪ࣛࣥࢲ࣒ࡉࢀࡓࡀ㸪㦂⸆ࢆᢞࡉࢀ࡞ࡗࡓ㸧ࠋࡲࡓ㸪ᮏࡢ Ᏻᛶࡣ㸪᭷ᐖ㇟ࡢ✀㢮ཬࡧⓎ⌧ྜ㸪⮫ᗋ᳨ᰝ್㸦⾑ᾮᏛⓗ᳨ᰝཬࡧ⾑ᾮ⏕Ꮫ᳨ᰝ㸧ࡢ࣋ ࣮ࢫࣛࣥࡽࡢኚ㔞ࢆせ⣙ࡍࡿࡇ࡛ホ౯ࡋࡓࠋ
(17) ⤖ᯝ 㦂ᑐ㇟㞟ᅋ ヨ㦂㛤ᚋྜィ 628 ࡀࣛࣥࢲ࣒ࡉࢀࡓ㸦ࣉࣛࢭ࣎⩌㸸210 㸪ᮏ 130 mg ⩌㸸209 㸪 ᮏ㹼6 mg/kg ⩌㸸209 㸧ࠋࡇࢀࡽࡢ⿕㦂⪅ࡢ࠺ࡕ㸪ዪᛶࡣ 335 㸦53.3%㸧㸪ⓑேࡣ 526 㸦83.8%㸧࡛࠶ࡾ㸪ᖺ㱋ࡢ୰ኸ್ࡣ 37.0 ṓ㸪య㔜ࡢ୰ኸ್ࡣ 70.8 kg ࡛࠶ࡗࡓࠋ࣮࣋ࢫࣛࣥ ࡢேཱྀ⤫ィᏛⓗ≉ᛶࡣ㸪3 ࡘࡢᢞ⩌࡛࠾࠾ࡴࡡྠᵝ࡛࠶ࡗࡓ㸦⾲ 2.7.6.3-1㸧ࠋ
88 (5) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
⾲ 2.7.6.3-1 ࣮࣋ࢫࣛࣥࡢேཱྀ⤫ィᏛⓗ≉ᛶ 㸦CRD3002 ヨ㦂㸸ヨ㦂୰᩿๓⤌ࡳධࢀࡽࢀࡓ⿕㦂⪅ࢆ㝖ࡃ㸪 ࣛࣥࢲ࣒ࡉࢀࡓ⿕㦂⪅㸧 Ustekinumab Placebo 130 mg 6 mg/kga Combined Total Analysis set: Randomized subjects excluding those enrolled prior to study re-start 210 209 209 418 628 Age (years) N 210 209 209 418 628 Mean (SD) 40.2 (13.10) 39.1 (13.78) 38.4 (13.12) 38.7 (13.45) 39.2 (13.34) Median 39.0 37.0 36.0 36.0 37.0 IQ range (30.0; 50.0) (28.0; 49.0) (27.0; 49.0) (28.0; 49.0) (29.0; 49.0) Range (18; 77) (18; 75) (18; 74) (18; 75) (18; 77) Sex N 210 209 209 418 628 Male 99 (47.1%) 104 (49.8%) 90 (43.1%) 194 (46.4%) 293 (46.7%) Female 111 (52.9%) 105 (50.2%) 119 (56.9%) 224 (53.6%) 335 (53.3%) Race N 210 209 209 418 628 White 177 (84.3%) 175 (83.7%) 174 (83.3%) 349 (83.5%) 526 (83.8%) Black or African American 7 (3.3%) 6 (2.9%) 7 (3.3%) 13 (3.1%) 20 (3.2%) Asian 17 (8.1%) 17 (8.1%) 16 (7.7%) 33 (7.9%) 50 (8.0%) American Indian or Alaska Native 0 0 1 (0.5%) 1 (0.2%) 1 (0.2%) Native Hawaiian or other Pacific Islander 0 0 2 (1.0%) 2 (0.5%) 2 (0.3%) Other 7 (3.3%) 10 (4.8%) 6 (2.9%) 16 (3.8%) 23 (3.7%) Not Reported 0 1 (0.5%) 3 (1.4%) 4 (1.0%) 4 (0.6%) Unknown 2 (1.0%) 0 0 0 2 (0.3%) Weight (kg) N 210 209 209 418 628 Mean (SD) 74.02 (19.919) 74.36 (21.329) 71.87 (18.825) 73.11 (20.130) 73.41 (20.049) Median 70.00 70.50 71.70 70.90 70.80 IQ range (60.20; 85.40) (59.00; 85.00) (58.00; 82.30) (58.00; 84.00) (58.70; 84.10) Range (40.0; 155.6) (37.0; 184.0) (35.0; 154.0) (35.0; 184.0) (35.0; 184.0) Height (cm) N 210 209 209 418 628 Mean (SD) 169.68 (9.700) 170.93 (9.939) 168.73 (9.923) 169.83 (9.980) 169.78 (9.880) Median 169.55 172.00 168.20 170.00 170.00 IQ range (161.50; 177.00) (164.00; 177.00) (161.50; 175.30) (162.60; 177.00) (162.60; 177.00) Range (139.7; 195.0) (144.0; 198.1) (147.0; 195.6) (144.0; 198.1) (139.7; 198.1)
a Weight-range based ustekinumab doses approximating 6 mg/kg: 260 mg (weight 55 kg), 390 mg (weight > 55 kg and 85 kg), 520 mg (weight > 85 kg). [TSIDEM02.rtf] [CNTO1275\CRD3002\DBR_W20\RE_W20\tsidem02.sas] 26NOV2014, 16:52
ᮏヨ㦂ࢆ୰Ṇࡋࡓ 23 㸦3.7%㸧ࡢ࠺ࡕ㸪㒊ศ㸦2.2%㸪14 㸧ࡣ 8 㐌┠ࡼࡾ๓ࡢ୰Ṇ࡛࠶ࡗ ࡓ㹙ࣉࣛࢭ࣎⩌㸸4.3%㸦9 㸧㸪ᮏ 130 mg ⩌㸸1.4%㸦3 㸧㸪ᮏ㹼6 mg/kg ⩌㸸1.0%㸦2 㸧㹛ࠋ᭱ࡶከࡃሗ࿌ࡉࢀࡓ 8 㐌┠ࡼࡾ๓ࡢ୰Ṇ⌮⏤ࡣ㸪ྠព᧔ᅇ࡛࠶ࡗࡓࠋ ࣮࣋ࢫࣛࣥࡢᝈ≉ᛶࡣ㸪㌟ᛶࡢ᪤Ꮡ⒪ຠᯝ༑ศཪࡣᚸᐜᛶࡢ࡞࠸㸪୰➼ࡽ 㔜ࡢࢡ࣮ࣟࣥࡢᝈ⪅㞟ᅋࢆ௦⾲ࡍࡿࡶࡢ࡛࠶ࡗࡓࠋࡲࡓ㸪࣮࣋ࢫࣛࣥࡢᝈ≉ᛶࡣ 3 ࡘ ࡢᢞ⩌࡛࠾࠾ࡴࡡྠᵝ࡛࠶ࡾ㸪CDAI ࢫࢥࡢ୰ኸ್ࡣ 292.5㸪CRP ⃰ᗘࡢ୰ኸ್ࡣ 8.05 mg/L ࡛࠶ࡗࡓࠋࣛࣥࢲ࣒ࡉࢀࡓ 628 ࡢ࠺ࡕ㸪㒊ศ㹙ࣉࣛࢭ࣎⩌㸸91.0%㸦191 㸧㸪ᮏ 130 mg ⩌㸸92.3%㸦193 㸧㸪ᮏ㹼6 mg/kg ⩌㸸92.8%㸦194 㸧㹛ࡢ⿕㦂⪅࡛ࡣ㸪࣮࣋ࢫࣛ ࣥ CRP ⃰ᗘࡢ␗ᖖ㸦3.0 mg/L ㉸㸧㸪౽୰࢝ࣝࣉࣟࢸࢡࢳࣥ⃰ᗘࡢୖ᪼㸦250 mg/kg ㉸㸧ཪࡣ
89 (6) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
౽୰ࣛࢡࢺࣇ࢙ࣜࣥ⃰ᗘࡢ␗ᖖ㸦7.24 ȝg/g ㉸㸧ࡀㄆࡵࡽࢀࡓࠋ࣮࣋ࢫࣛࣥࡢࢡ࣮ࣟࣥࡢ⨯ ᮇ㛫ࡢ୰ኸ್ࡣ㸪ࣉࣛࢭ࣎⩌㸦8.28 ᖺ㸧ࡀᮏࡢ୧ᢞ⩌㹙130 mg ⩌㸸5.61 ᖺ㸪㹼6 mg/kg ⩌㸸6.21 ᖺ㹛ࡼࡾࢃࡎ㛗ࡗࡓࡀ㸪ࡢேཱྀ⤫ィᏛⓗ≉ᛶࡸ⮫ᗋᣦᶆࡢࣂࣛࣥࢫࡀྲྀࢀ࡚࠸ ࡿࡇࡽ㸪ࡇࡢᕪࡣヨ㦂⤖ᯝᙳ㡪ࢆ࠼ࡿྍ⬟ᛶࡣᑡ࡞࠸ࡶࡢ⪃࠼ࡽࢀࡓࠋ ᮏヨ㦂ࡢ㑅ᢥᇶ‽ᚑ࠸㸪⿕㦂⪅ࡢ 99.4%ࡣࢥࣝࢳࢥࢫࢸࣟࢻཪࡣචㄪ⠇⸆࡛ࡢ๓⒪ࡀ ຠᯝ༑ศ࡛࠶ࡗࡓࠋᢠ TNF ⸆⒪Ṕࢆ᭷ࡍࡿࡇࡶྍࡋࡓࡀ㸪ຠᯝ༑ศཪࡣᚸᐜᛶࡢ࡞ ࠸ࡇࡀ♧ࡉࢀ࡚࠸࡞࠸ࡇࡋࡓࠋྜィ࡛ 31.4%㸦197/628 㸧ࡢ⿕㦂⪅ࡀᢠ TNF ⸆⒪Ṕࢆ ᭷ࡋ࡚࠾ࡾ㸪ࡑࢀࡽࡢ⿕㦂⪅ࡢ࠺ࡕ 98.5%㸦194/197 㸧ࡀ㸪㑅ᢥᇶ‽ᚑ࠸ᢠ TNF ⸆ࡀຠᯝ ༑ศཪࡣᚸᐜᛶࡢ࡞࠸ࡇࡀ♧ࡉࢀ࡚࠸࡞ࡗࡓࠋ୍᪉㸪68.6%㸦431/628 㸧ࡢ⿕㦂⪅ࡣ㸪ᢠ TNF ⸆ᮍ⒪࡛࠶ࡗࡓࠋࡲࡓ㸪77.9%㸦489/628 㸧ࡢ⿕㦂⪅ࡀ࣮࣋ࢫࣛࣥ 1 ௨ୖࡢࢡࣟ ࣮ࣥే⏝⸆ࢆᢞࡉࢀ࡚࠾ࡾ㸪⸆ศ㢮ࡈࡢే⏝ྜࡣ 3 ࡘࡢᢞ⩌࡛ྠ⛬ᗘ࡛࠶ࡗࡓࠋ࣋ ࣮ࢫࣛࣥ࠾࠸࡚㸪⣙ 39.3%㸦247/628 㸧ࡢ⿕㦂⪅ࡀࢥࣝࢳࢥࢫࢸࣟࢻ㸦ࣈࢹࢯࢽࢻ➼㸧㸪 ⣙ 3534.9%㸦219/628 㸧ࡢ⿕㦂⪅ࡀචㄪ⠇⸆㸦6-࣓ࣝ࢝ࣉࢺࣉࣜࣥ㸪ࢨࢳ࢜ࣉࣜࣥཪࡣ࣓ࢺ ࢺࣞ࢟ࢧ࣮ࢺ㸧ࢆᢞࡉࢀ࡚࠸ࡓࠋ
ᮏヨ㦂ࡘ࠸࡚㸪GCP ୖࡢᠱᛕࢃࡿලయⓗ࡞ෆᐜ㸪᭷ຠᛶゎᯒᑐ㇟ࡽ㝖እࡋ⸆≀ື ែཬࡧᏳᛶࡢゎᯒᑐ㇟ྵࡵࡓ⌮⏤ࢆ㸪௨ୗㄝ᫂ࡍࡿࠋ ᮏヨ㦂࠾࠸࡚㸪⏦ㄳ⪅ࡣ㸪ヨ㦂୰ 1 ࡘࡢ㦂ᐇ་⒪ᶵ㛵㸦タ␒ྕ 1127㸧࡛⏕ࡌࡓ㔜 ࡞ GCP 㐓⬺ࡢሗ࿌ࢆཷࡅ㸪┘ᰝࢆᐇࡋࡓࠋࡑࡢ⤖ᯝ㸪ᙜヱタ࡛⤌ࡳධࢀࡽࢀࡓ⿕㦂⪅ 2 ࡢ࠺ࡕ 1 ࡀ㸪ഇ㐀ࡉࢀ࡚࠸ࡿྍ⬟ᛶࡀ࠶ࡿࡇࡀศࡾ㸪ヱᙜࡍࡿ⿕㦂⪅ࡢࡍ࡚ࡢࢹ࣮ࢱࢆ ࢹ࣮ࢱ࣮࣋ࢫࡽ๐㝖ࡋࡓࠋᚑࡗ࡚㸪ࡍ࡚ࡢゎᯒᑐ㇟㞟ᅋࡢ⿕㦂⪅ᩘࡣ㸪ࡇࡢ⿕㦂⪅ 1 ࡀ㝖 ࢀ࡚࠸ࡿࠋᙜヱタ࡛⤌ࡳධࢀࡽࢀࡓ⿕㦂⪅ 2 ࡢ࠺ࡕࡢ 1 㸦⿕㦂⪅ 20961㸧ࡣ㸪㦂ཧ ຍࡢྠព㸪㦂⸆ᢞ㸪ヨ㦂ཧຍࢆ☜ㄆ࡛ࡁࡓࡀ㸪⏦ㄳ⪅ࡣ㸪ࡑࡢ⿕㦂⪅ࡢࢹ࣮ࢱࡢṇ☜ᛶཬ ࡧጇᙜᛶࢆᢸಖ࡛ࡁ࡞ࡗࡓࡓࡵ㸪᭷ຠᛶࡢゎᯒࡽࡑࡢ⿕㦂⪅ࡢࢹ࣮ࢱࢆ㝖࠸ࡓࠋࡋࡋ࡞ࡀ ࡽ㸪ࡑࡢ⿕㦂⪅ࡣ㦂⸆ࡀᢞࡉࢀ࡚࠸ࡓࡓࡵ㸪⸆≀ືែཬࡧᏳᛶࡢゎᯒᑐ㇟㞟ᅋࡣྵࡵࡿ ࡇࡋࡓ࠙5.3.5.1.2ࠚCRD3002/CSR/Sec4.4.4㸧ࠋ ゎᯒᑐ㇟㞟ᅋࡢෆヂ㸪୰Ṇཬࡧゎᯒᑐ㇟㞟ᅋࡽ㝖እࡉࢀࡓࢆ㸪⾲ 2.7.6.3-2 ཬࡧ⾲ 2.7.6.3-3 ♧ࡍࠋ
90 (7) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
⾲ 2.7.6.3-2 CRD3002 ヨ㦂ࡢゎᯒᑐ㇟㞟ᅋ㸦ヨ㦂య㸭᪥ᮏே㸧 Entire population Japanese population (1030 subjects) (33 subjects) Placebo 130 mg 6 mg/kg Total Placebo 130 mg 6 mg/kg Total Up to restart(34 subjects) IC - - - 34 - - - - Randomized 4 4 4 12 - - - - Treateda 4 4 4 12 - - - - Discontinuedb 1 0 1 2 - - - -
After restart IC - - - 996 - - - 33 Randomized 210 209 209 628 9 8 9 26 Treateda 209 209 209 627 9 8 9 26 Discontinuedb 12 9 2 23 2 1 0 3 Efficacy analysis set 209 209 209 627 9 8 9 26 Safety analysis setc 208 212 207 627 9 8 9 26
All Safety analysis setc 208 212 207 627 9 8 9 26
a By planned/randomized treatment group. b Discontinued from study participation prior to Week 20(i.e. did not enter the maintenance study and did not complete Week 20 safety follow-up visit). c By actual treatment group. [TPMDASI02.rtf] [CNTO1275\CRD3003\DBR_CSR\RE_PMDA\tpmdasi02.sas] 19JUL2016, 21:14
91 (8) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
⾲ 2.7.6.3-3 CRD3002 ヨ㦂ࡢ୰Ṇཬࡧゎᯒᑐ㇟㞟ᅋࡽ㝖እࡉࢀࡓ Number Reasons (number of cases) of cases Subjects who terminated study participation before Week 20 (i.e. did not enter the maintenance study and did not complete Week 20 safety follow-up visit); Randomized Subjects Excluding Those Enrolled Prior to Study Re-start Entire Placebo 12 Withdrawal of consent (7), Lost to follow-up (4), Other (1) population 130 mg 9 Withdrawal of consent (7), Lost to follow-up (2)
6 mg/kg 2 Withdrawal of consent (1), Lost to follow-up (1)
Cases excluded from Efficacy analysis set; Randomized Subjects Entire Placebo 5 Enrolled Prior to Study Re-start (4); Site 1127 (1) population 130 mg 4 Enrolled Prior to Study Re-start (4)
6 mg/kg 4 Enrolled Prior to Study Re-start (4)
Japanese Placebo 0 population 130 mg 0
6 mg/kg 0
Cases excluded form Safety analysis set; Treated Subjects Entire Placebo 4 Enrolled Prior to Study Re-start (4) population 130 mg 4 Enrolled Prior to Study Re-start (4)
6 mg/kg 4 Enrolled Prior to Study Re-start (4)
Japanese Placebo 0 population 130 mg 0
6 mg/kg 0
Source: 3002 CSR tables: TSIDS01; TSIDEM01; Tables for answering PMDA questions: TPMDASI02
᭷ຠᛶ ᮏᢞࡼࡾ㸪㌟ᛶࡢ᪤Ꮡ⒪ຠᯝ༑ศཪࡣᚸᐜᛶࡢ࡞࠸୰➼ࡽ㔜ࡢάືᮇࢡ ࣮ࣟࣥᝈ⪅࠾࠸࡚㸪clinical response ཬࡧ clinical remission ࡀᚓࡽࢀࡓࠋ · ヨ㦂యࡢᅛᐃ㡰ᗎἲᇶ࡙ࡁ㸪ᮏࡢ୧ᢞ⩌㹙130 mg ⩌ཬࡧ㹼6 mg/kg ⩌㹛ࡘ࠸࡚㸪 せホ౯㡯┠ཬࡧ 4 ࡘࡢせ࡞ḟホ౯㡯┠ࡍ࡚࡛⤫ィᏛⓗ࡞᭷ពᕪࡀ♧ࡉࢀࡓࠋ
· 6 㐌┠ clinical response ࡀᚓࡽࢀࡓ⿕㦂⪅ࡢྜ㸦せホ౯㡯┠㸧ࡣ㸪ࣉࣛࢭ࣎⩌ 㸦28.7%㸪60/209 㸧ẚ㍑ࡋ࡚ᮏ㹼6 mg/kg ⩌㸦55.5%㸪116/209 㸧ཬࡧᮏ 130 mg ⩌㸦51.7%㸪108/209 㸧࡛᭷ព㧗ࡗࡓ㸦ࡶ p<0.001㸧ࠋ
· Clinical response ࠾ࡅࡿᮏࡢຠᯝࡣ㸪㒊ศ㞟ᅋ㸦ᢠ TNF ⸆ᮍ⒪ࡢ⿕㦂⪅ࡶྵࡵ㸧 ࠾ࡅࡿゎᯒ࡛ࡶ࠾࠾ࡴࡡ୍㈏ࡋ࡚࠾ࡾ㸪ࢹ࣮ࢱྲྀᢅ࠸つ๎ࡢ๓つᐃࡉࢀࡓኚ ᭦ᑐࡋ࡚ࡶ㡹ᛶࢆ♧ࡋࡓࠋ
92 (9) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
· 8 㐌┠ clinical remission ࡀᚓࡽࢀࡓ⿕㦂⪅ࡢྜࡣ㸪ࣉࣛࢭ࣎⩌㸦19.6%㸪41/209 㸧 ẚ㍑ࡋ࡚ᮏ㹼6 mg/kg ⩌㸦40.2%㸪84/209 㸧ཬࡧᮏ 130 mg ⩌㸦30.6%㸪64/209 㸧 ࡛᭷ព㧗ࡗࡓ㸦ࡑࢀࡒࢀ p<0.001 ཬࡧ p=0.009㸧ࠋ
· Clinical remission ࠾ࡅࡿᮏࡢຠᯝࡣ㸪㒊ศ㞟ᅋ㸦ᢠ TNF ⸆ᮍ⒪ࡢ⿕㦂⪅ࡶྵ ࡵ㸧࠾ࡅࡿゎᯒ࡛ࡶ࠾࠾ࡴࡡ୍㈏ࡋ࡚࠸ࡓࠋ
· 8 㐌┠ clinical response ࡀᚓࡽࢀࡓ⿕㦂⪅ࡢྜࡣ㸪ࣉࣛࢭ࣎⩌㸦32.1%㸪67/209 㸧 ẚ㍑ࡋ࡚ᮏ㹼6 mg/kg ⩌㸦57.9%㸪121/209 㸧ཬࡧᮏ 130 mg ⩌㸦47.4%㸪99/209 㸧 ࡛᭷ព㧗ࡗࡓ㸦ࡶ p<0.001㸧ࠋ
· 6 㐌┠ 70-point response ࡀᚓࡽࢀࡓ⿕㦂⪅ࡢྜࡣ㸪ࣉࣛࢭ࣎⩌㸦38.8%㸪81/209 㸧 ẚ㍑ࡋ࡚ᮏ㹼6 mg/kg ⩌㸦64.6%㸪135/209 㸧ཬࡧᮏ 130 mg ⩌㸦58.9%㸪123/209 㸧࡛᭷ព㧗ࡗࡓ㸦ࡶ p<0.001㸧ࠋ
· 3 㐌┠ 70-point response ࡀᚓࡽࢀࡓ⿕㦂⪅ࡢྜࡣ㸪ࣉࣛࢭ࣎⩌㸦31.6%㸪66/209 㸧 ẚ㍑ࡋ࡚ᮏ㹼6 mg/kg ⩌㸦50.7%㸪106/209 㸧ཬࡧᮏ 130 mg ⩌㸦49.3%㸪103/209 㸧࡛᭷ព㧗ࡗࡓ㸦ࡶ p<0.001㸧ࠋ
· ከࡃࡢ⮫ᗋホ౯㡯┠࠾࠸࡚ᮏࡼࡿ᪩ᮇࡢ response ࡀㄆࡵࡽࢀ㸪ࡑࡢຠᯝࡣ࣮࣋ࢫࣛ ࣥᚋࡢ᭱ึࡢእ᮶ゼၥ᪥㸦3 㐌┠㸧ㄆࡵࡽࢀࡓࠋせ࡞ḟホ౯㡯┠࡛࠶ࡿ 3 㐌┠ࡢ 70-point response ຍ࠼㸪3 㐌┠ clinical response ࡀᚓࡽࢀࡓ⿕㦂⪅ࡢྜࡶࣉࣛࢭ࣎⩌ ẚ㍑ࡋ࡚ᮏ⩌࡛᭷ព㧗ࡗࡓࠋ3 㐌┠ clinical remission ࡀᚓࡽࢀࡓ⿕㦂⪅ࡢྜࡣࣉ ࣛࢭ࣎⩌ẚ㍑ࡋ࡚ᮏ⩌ࡀ㧗ࡗࡓࡶࡢࡢ㸪ᮏ㹼6 mg/kg ⩌࡛ࡢࡳ᭷ព㧗ࡗࡓࠋ
· CDAI ࢫࢥࡢ࣮࣋ࢫࣛࣥࡽࡢῶᑡ㔞ࡢ୰ኸ್ࡣ㸪ࡍ࡚ࡢホ౯ᮇ࡛㸪ࣉࣛࢭ࣎⩌ ẚ㍑ࡋ࡚ᮏ⩌࡛᭷ពࡁࡗࡓࠋ
· CRP ⃰ᗘࡢ࣮࣋ࢫࣛࣥࡽࡢῶᑡ㔞ࡢᖹᆒ್ཬࡧ CRP ⃰ᗘࡀṇᖖࡋࡓ⿕㦂⪅ࡢྜࡣ㸪 ࡍ࡚ࡢホ౯ᮇ࡛㸪ࣉࣛࢭ࣎⩌ẚ㍑ࡋ࡚ᮏ⩌࡛᭷ព㧗ࡗࡓࠋ
· 6 㐌┠ࡢ౽୰ࣛࢡࢺࣇ࢙ࣜࣥཬࡧ౽୰࢝ࣝࣉࣟࢸࢡࢳࣥ⃰ᗘࡢ࣮࣋ࢫࣛࣥࡽࡢῶᑡ㔞 ࡢ୰ኸ್㸪ཬࡧ౽୰ࣛࢡࢺࣇ࢙ࣜࣥཬࡧ౽୰࢝ࣝࣉࣟࢸࢡࢳࣥ⃰ᗘࡀṇᖖࡋࡓ⿕㦂⪅ࡢ ྜࡣࣉࣛࢭ࣎⩌ẚ㍑ࡋ࡚ᮏ⩌࡛᭷ព㧗ࡗࡓࠋ
· ௨ୗࡢ⮫ᗋホ౯㡯┠ࡢゎᯒ࡛ࡣ㸪ᮏ 130 mg ⩌ẚ㍑ࡋ࡚ᮏ㹼6 mg/kg ⩌࡛㧗࠸᭷ຠᛶ ࡀㄆࡵࡽࢀࡓࠋ
· 8 㐌┠ࡢ clinical remission㸸ᮏ㹼6 mg/kg ⩌ࡢ⒪ຠᯝ㸦20.6%㸧ࡣ㸪ᮏ 130 mg ⩌ 㸦11.0%㸧ࡢࡰ 2 ಸ࡛࠶ࡗࡓࠋ
· 8 㐌┠ࡢ clinical response㸸ᮏ㹼6 mg/kg ⩌ࡢ⒪ຠᯝ㸦25.8%㸧ࡣ㸪ᮏ 130 mg ⩌ 㸦15.3%㸧ࡼࡾࡁࡗࡓࠋ
· 8 㐌┠ࡢ 70-point response㸸ᮏ㹼6 mg/kg ⩌ࡢ⒪ຠᯝ㸦22.5%㸧ࡣ㸪ᮏ 130 mg ⩌ 㸦13.9%㸧ࡼࡾࡁࡗࡓࠋ
93 (10) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
· 8 㐌┠ࡢ CDAI ࢫࢥࡢ࣮࣋ࢫࣛࣥࡽࡢኚ㔞㸸ᮏ㹼6 mg/kg ⩌ࡢ⒪ຠᯝ㸦-65.0㸧 ࡣ㸪ᮏ 130 mg ⩌㸦-41.0㸧ࡼࡾࡁࡗࡓࠋ
· ௨ୗࡢ⅖࣐࣮࣮࡛࢝ࡣ㸪ᮏ 130 mg ⩌ẚ㍑ࡋ࡚㸪ᮏ㹼6 mg/kg ⩌࡛㧗࠸᭷ຠᛶࡀㄆ ࡵࡽࢀࡓࠋ
· CRP ⃰ᗘࡢ࣮࣋ࢫࣛࣥࡽࡢኚ㔞ࡢᖹᆒ್㸸8 㐌┠ࡢᮏ㹼6 mg/kg ⩌ࡢ⒪ຠᯝ 㸦-8.42 mg/L㸧ࡣ㸪ᮏ 130 mg ⩌㸦-3.83 mg/L㸧ẚ㍑ࡋ࡚ࡁࡗࡓࠋ
· 6 㐌┠ࡢ౽୰ࣛࢡࢺࣇ࢙ࣜࣥ⃰ᗘࡢ࣮࣋ࢫࣛࣥࡽࡢኚ㔞ࡢ୰ኸ್㸸ᮏ㹼6 mg/kg ⩌ࡢ⒪ຠᯝ㸦-25.93 ȝg/g㸧ࡣ㸪ᮏ 130 mg ⩌㸦-10.35 ȝg/g㸧ẚ㍑ࡋ࡚ࡁࡗࡓࠋ
· 6 㐌┠ࡢ౽୰࢝ࣝࣉࣟࢸࢡࢳࣥ⃰ᗘࡢ࣮࣋ࢫࣛࣥࡽࡢኚ㔞ࡢ୰ኸ್㸸ᮏ 㹼6 mg/kg ⩌ࡢ⒪ຠᯝ㸦-106.32 mg/kg㸧ࡣ㸪ᮏ 130 mg ⩌㸦-55.03 mg/kg㸧ẚ㍑ࡋ࡚ ࡁࡗࡓࠋ
· ⾑Ύ୰࢘ࢫࢸ࢟ࢾ࣐ࣈ⃰ᗘࡢᅄศᩘ࡛༊ศࡋ࡚ホ౯ࡋࡓ⤖ᯝ㸪⾑Ύ୰࢘ࢫࢸ࢟ࢾ࣐ࣈ⃰ ᗘࡀ㧗࠸ 8 㐌┠ࡢ clinical remission ࡀᚓࡽࢀࡓ⿕㦂⪅ࡢྜࡀ㧗ࡗࡓࠋࡋࡋ㸪ࡇࡢ ഴྥࡣ 6 㐌┠ཬࡧ 8 㐌┠ࡢ clinical response㸪ཪࡣ 6 㐌┠ࡢ CDAI ࢫࢥࡢኚ㔞࡛ࡣ᫂☜࡛ ࡣ࡞ࡗࡓࠋ6 㐌┠ࡢ CRP ⃰ᗘࡣ㸪ᮏ 130 mg ⩌࡛ࡣ⾑Ύ୰࢘ࢫࢸ࢟ࢾ࣐ࣈ⃰ᗘࡀ㧗࠸ పୗࡍࡿഴྥࡀㄆࡵࡽࢀࡓࠋᮏ㹼6 mg/kg ⩌࡛ࡣࡑࡢᵝ࡞ഴྥࡣㄆࡵࡽࢀ࡞ࡗࡓࡀ㸪 6 㐌┠ࡢ CRP ⃰ᗘࡣ⾑Ύ୰࢘ࢫࢸ࢟ࢾ࣐ࣈ⃰ᗘࡀ➨ 1 ᅄศᩘ௨ୗࡢ⿕㦂⪅㞟ᅋ࡛᭱ࡶ㧗 ್࡛࠶ࡗࡓࠋ
⸆≀ືែཬࡧචཎᛶ · ᮏࡢᅛᐃ⏝㔞㸦130 mg㸧ཪࡣయ㔜ู⏝㔞㸦㹼6 mg/kg㸧ࡢ༢ᅇ㟼⬦ෆᢞᚋ㸪⾑Ύ୰࢘ࢫ ࢸ࢟ࢾ࣐ࣈ⃰ᗘࡢ୰ኸ್ࡣࡰ⏝㔞ẚᛶࢆ♧ࡋ㸪8 㐌┠ࡲ࡛ࡢࡍ࡚ࡢ᳨య᥇ྲྀᮇ࡛ ᳨ฟྍ⬟࡛࠶ࡗࡓࠋ0 㐌┠ࡢᢞ 1 㛫ᚋ࠾ࡅࡿ᭱㧗⾑Ύ୰࢘ࢫࢸ࢟ࢾ࣐ࣈ⃰ᗘࡢ୰ኸ್ ࡣ㸪ᮏ 130 mg ⩌࡛ 39.81 ȝg/mL㸪ᮏ㹼6 mg/kg ⩌࡛ 124.37 ȝg/mL ࡛࠶ࡗࡓࠋࡲࡓ㸪8 㐌 ┠ࡢᐶゎᑟධ⒪ἲ⤊ࡢ⾑Ύ୰࢘ࢫࢸ࢟ࢾ࣐ࣈ⃰ᗘࡢ୰ኸ್ࡣ㸪ᮏ 130 mg ⩌࡛ 2.02 ȝg/mL㸪ᮏ㹼6 mg/kg ⩌࡛ 6.31 ȝg/mL ࡛࠶ࡗࡓࠋ
· ᮏࡢయ㔜ู⏝㔞㸦㹼6 mg/kg㸧ࡀᢞࡉࢀࡓ⿕㦂⪅࡛ࡣ㸪࢘ࢫࢸ࢟ࢾ࣐ࣈࡢᢞ㔞㸦⤯ᑐ 㔞㸧ࡢቑຍࡋࡓࡀࡗ࡚㸪⾑Ύ୰࢘ࢫࢸ࢟ࢾ࣐ࣈ⃰ᗘࡢ୰ኸ್ࡀ㧗ࡃ࡞ࡿഴྥࡀㄆࡵࡽࢀ ࡓࠋᮏࡢᅛᐃ⏝㔞㸦130 mg㸧ࡀ㟼⬦ෆᢞࡉࢀࡓ⿕㦂⪅࡛ࡣ㸪⾑Ύ୰࢘ࢫࢸ࢟ࢾ࣐ࣈ⃰ ᗘࡣయ㔜ࢃࡽࡎྠ⛬ᗘ࡛࠶ࡗࡓࠋࡇࡢ 8 㐌㛫ࡢヨ㦂⤌ࡳධࢀࡽࢀࡓ⿕㦂⪅ࡢయ㔜 ࡢ⠊ᅖ࡛ࡣ㸪⾑Ύ୰࢘ࢫࢸ࢟ࢾ࣐ࣈ⃰ᗘయ㔜┤⥺ⓗ࡞㛵ಀࡣㄆࡵࡽࢀ࡞ࡗࡓࠋ
· ᮏࡀᢞࡉࢀ㸪ᢠ࢘ࢫࢸ࢟ࢾ࣐ࣈᢠయホ౯ࡢࡓࡵࡢ᳨యࡀ㐺ษ᥇ྲྀࡉࢀࡓ 411 ࡢ࠺ ࡕ㸪20 㐌┠ࡢᏳᛶࡢ᭱⤊ホ౯ࡲ࡛ᢠ࢘ࢫࢸ࢟ࢾ࣐ࣈᢠయࡀ㝧ᛶ࡛࠶ࡗࡓ⿕㦂⪅ࡣ 1 㸦0.2%㸧ࡢࡳ࡛࠶ࡗࡓࠋ
94 (11) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
ᝈ⪅ሗ࿌࢘ࢺ࣒࢝ཬࡧ་⒪⤒῭ · 8 㐌┠࠾ࡅࡿ IBDQ ࢫࢥࡢ࣮࣋ࢫࣛࣥࡽࡢኚ㔞ࡢᖹᆒ್ࡣ㸪ࣉࣛࢭ࣎⩌ẚ㍑ࡋ ࡚ᮏ⩌࡛᭷ពࡁࡗࡓࠋ᭦㸪8 㐌┠ࡢ IBDQ ࢫࢥ࠾࠸࡚⮫ᗋⓗពࡢ࠶ࡿᨵ ၿ㸦࣮࣋ࢫࣛࣥࡽ 16 ࣏ࣥࢺ௨ୖࡢቑຍ㸧ࡀᚓࡽࢀࡓ⿕㦂⪅ࡢྜࡣ㸪ࣉࣛࢭ࣎⩌ ẚ㍑ࡋ࡚ᮏ⩌࡛᭷ព㧗ࡃ㸪ᝈ≉␗ⓗ࡞ᗣ㛵㐃 QOL ࡢᨵၿࡀ♧ࡉࢀࡓࠋࡑࡢ⒪ຠ ᯝࡣ㸪ᮏ 130 mg ⩌㸦17.6%㸧ẚ㍑ࡋ࡚ᮏ㹼6 mg/kg ⩌㸦27.0%㸧࡛ࡁࡗࡓࠋ
· 8 㐌┠࡛ࡣ㸪ࣉࣛࢭ࣎⩌ẚ㍑ࡋ࡚ᮏ⩌࡛ SF-36 ࡢ㌟యⓗഃ㠃ࡢ QOL ࢧ࣐࣮ࣜ㸦PCS㸧㸪 ⢭⚄ⓗഃ㠃ࡢ QOL ࢧ࣐࣮ࣜ㸦MCS㸧ཬࡧ 8 ศ㔝ࡍ࡚ࡢᩘ್ࡢᨵၿࡀㄆࡵࡽࢀࡓࠋ᭦㸪 PCS ཬࡧ MCS ࢫࢥ࠾࠸࡚⮫ᗋⓗពࡢ࠶ࡿᨵၿ㸦࣮࣋ࢫࣛࣥࡽ 5 ࣏ࣥࢺ௨ୖ ࡢቑຍ㸧ࢆ㐩ᡂࡋࡓ⿕㦂⪅ࡢྜࡶ㸪ࣉࣛࢭ࣎⩌ẚ㍑ࡋ࡚ᮏ⩌࡛᭷ព㧗ࡃ㸪⯡ⓗ ࡞ᗣ㛵㐃 QOL ࡢᨵၿࡀ♧ࡉࢀࡓࠋPCS ࠾ࡅࡿ⒪ຠᯝࡣ㸪ᮏ 130 mg ⩌㸦12.8%㸧 ẚ㍑ࡋ࡚ᮏ㹼6 mg/kg ⩌㸦18.0%㸧࡛ࡁࡗࡓࠋ
· ་⒪⤒῭ࡢゎᯒ㸦ࢡ࣮ࣟࣥ㛵㐃ࡢධ㝔ཬࡧᡭ⾡㸪ᦆኻປാ㛫㸪ᑵປไ㝈㸧࡛ࡣ㸪ᮏ ⩌ࣉࣛࢭ࣎⩌ࡢ㛫᭷ព࡞ᕪࡣㄆࡵࡽࢀ࡞ࡗࡓࠋࡋࡋ㸪 8 㐌┠ࡢ Productivity VAS ࡢ ࣮࣋ࢫࣛࣥࡽࡢኚ㔞ࡢ୰ኸ್ࡣ㸪ࣉࣛࢭ࣎⩌ẚ㍑ࡋ࡚ᮏ⩌࡛᭷ពࡁࡗࡓࠋ
Ᏻᛶ ᭷ᐖ㇟ࡢࢹ࣮ࢱࢆ 2.7.6.3.2㸪㔜⠜࡞᭷ᐖ㇟ࡢヲ⣽ࢆ 2.7.6.3.3 ♧ࡍࠋ
· ᮏࡢᅛᐃ⏝㔞㸦130 mg㸧ཪࡣయ㔜ู⏝㔞㸦㹼6 mg/kg㸧ࡢ㟼⬦ෆᢞࡢᚸᐜᛶࡣⰋዲ࡛࠶ ࡾ㸪8 㐌┠ࡲ࡛ࡢᏳᛶࣉࣟࣇࣝࡣ⯡ⓗࣉࣛࢭ࣎ྠᵝ࡛࠶ࡗࡓࠋ
· 8 㐌┠ࡲ࡛᭷ᐖ㇟ࢆ 1 ௳௨ୖⓎ⌧ࡋࡓ⿕㦂⪅ࡢྜࡣ࠸ࡎࢀࡢᢞ⩌࡛ࡶྠ⛬ᗘ࡛࠶ࡾ㸪 ჾᐁูศ㢮࡛ࡣࠕ⫶⭠㞀ᐖࠖཬࡧࠕឤᰁ࠾ࡼࡧᐤ⏕ࠖࡀ᭱ࡶከࡗࡓࠋ
· ୰Ṇ⮳ࡗࡓ᭷ᐖ㇟ࡢⓎ⌧ྜࡣపࡃ㸪ࣉࣛࢭ࣎⩌ᮏేྜ⩌࡛ྠ⛬ᗘ࡛࠶ࡗࡓࠋᮏ 130 mg ⩌࡛ࡣ㸪ᮏ㹼6 mg/kg ⩌ࡼࡾ᭷ᐖ㇟ࡼࡿ୰Ṇࡀከࡗࡓࠋ᭱ࡶከࡃࡳࡽ ࢀࡓ୰Ṇ⮳ࡗࡓ᭷ᐖ㇟ࡣࢡ࣮࡛ࣟࣥ࠶ࡗࡓࠋ
· 8 㐌┠ࡲ࡛ࡢ SAE ࡢⓎ⌧ྜࡣపࡃ㸪࠸ࡎࢀࡢᢞ⩌࡛ࡶྠ⛬ᗘ࡛࠶ࡗࡓࠋ⫠㛛⮋⒆㸪⭠ 㛢ሰཬࡧࢡ࣮ࣟࣥࢆ㝖ࡁ㸪࠸ࡎࢀࡢᢞ⩌࡛ࡶ 2 ௨ୖⓎ⌧ࡋࡓ SAE ࡣ࡞ࡗࡓࠋ
· 8 㐌┠ࡲ࡛ឤᰁཬࡧ㔜⠜࡞ឤᰁࢆⓎ⌧ࡋࡓ⿕㦂⪅ࡢྜࡣ㸪ࡍ࡚ࡢᢞ⩌࡛ྠ⛬ ᗘ࡛࠶ࡗࡓࠋᮏࡢ୧ᢞ⩌࠾࠸࡚㸪᪥ぢឤᰁࡢⓎ⌧ࡣ࡞ࡃ㸪⤖᰾ࡢሗ࿌ࡶ࡞ ࡗࡓࠋ
· Ṛஸཬࡧせᚰ⾑⟶࣋ࣥࢺࡣ࠸ࡎࢀࡢᢞ⩌࠾࠸࡚ࡶ࡞ࡗࡓࠋࣉࣛࢭ࣎⩌ࡢ⿕㦂⪅ 1 ࡛ 1 ௳ࡢ㠀㔜⠜࡞ᇶᗏ⣽⬊⒴ࡀሗ࿌ࡉࢀࡓࠋ
· Ⓨ⌧ࡋࡓࣥࣇ࣮ࣗࢪࣙࣥࣜࢡࢩࣙࣥࡣ㠀㔜⠜࡛㸪Ⓨ⌧ྜࡣࡍ࡚ࡢᢞ⩌࡛ྠ⛬ᗘ ࡛࠶ࡗࡓࠋࡍ࡚ࡢᢞ⩌࡛Ⓨ⌧ྜࡀ 1%㉸࡛࠶ࡗࡓࣥࣇ࣮ࣗࢪࣙࣥࣜࢡࢩࣙࣥࡣ࡞ ࡃ㸪ࢼࣇࣛ࢟ࢩุ࣮᩿ࡉࢀࡓ㇟ࡶ࡞ࡗࡓࠋ
95 (12) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
· ⾑ᾮᏛⓗ᳨ᰝ࠾࠸࡚㸪8 㐌┠ࡲ࡛࠸ࡎࢀࡢᢞ⩌࠾࠸࡚ㄆࡵࡽࢀࡓ㢧ⴭ࡞␗ᖖኚ ື㸦2 ௨ୖࡢ⿕㦂⪅ 2 ᅇ௨ୖⓎ⌧㸧ࡣࣜࣥࣃ⌫ῶᑡ࡛࠶ࡗࡓࡀ㸪࠸ࡎࢀࡢᢞ⩌࠾࠸ ࡚ࡶࣜࣥࣃ⌫ῶᑡࡢⓎ⌧ྜࡣ 6%ᮍ‶࡛࠶ࡗࡓࠋ
· ⾑ᾮ⏕Ꮫ᳨ᰝ࠾࠸࡚㸪8 㐌┠ࡲ࡛࠸ࡎࢀࡢᢞ⩌࠾࠸࡚ࡶ㢧ⴭ࡞␗ᖖኚື㸦2 ௨ ୖࡢ⿕㦂⪅ 2 ᅇ௨ୖⓎ⌧㸧ࡣ࡞ࡗࡓࠋ
⤖ㄽ · ᮏヨ㦂㸦CNTO1275CRD3002 ヨ㦂㸧ࡢ⤖ᯝࡼࡾ㸪᪤Ꮡ⒪࡛ຠᯝ༑ศ࡛࠶ࡗࡓ୰➼ ࡽ㔜ࡢᡂேࢡ࣮ࣟࣥᝈ⪅࠾࠸࡚㸪᳨ウࡋࡓᮏࡢ 2 ⏝㔞ࡼࡿᐶゎᑟධࡢ clinical response ཬࡧ clinical remission ࡛ࡢ᭷ຠᛶࡀ୍㈏ࡋ࡚᫂☜♧ࡉࢀࡓࠋ
· ୰➼ࡽ㔜ࡢᡂேࢡ࣮ࣟࣥᝈ⪅㞟ᅋ࠾࠸࡚㸪ᮏࡢ᭱ 6 mg/kg ࡲ࡛ࡢ༢ᅇ㟼⬦ ෆᢞࡼࡿᐶゎᑟධ⒪ἲࡢᚸᐜᛶࡣ㸪8 㐌㛫ࢃࡓࡾ⯡ⓗⰋዲ࡛࠶ࡗࡓࠋ
· ᮏヨ㦂ࡢᏳᛶཬࡧ᭷ຠᛶࢹ࣮ࢱࡣ㸪ᮏࡢ㟼⬦ෆᢞࡼࡿᐶゎᑟධ⒪ἲᑐࡋ㸪࣋ࢿ ࣇࢵࢺࡀࣜࢫࢡࢆୖᅇࡿࡇࢆ♧ࡍࡶࡢ࡛࠶ࡗࡓࠋࡲࡓ㸪ࡇࡢ୰➼ࡽ㔜ࡢᡂேࢡ ࣮ࣟࣥᝈ⪅㞟ᅋ࡛ࡣ㸪㹼6 mg/kg ࡢᢞ㔞࠾࠸࡚㸪Ᏻᛶࡢࣜࢫࢡࡀ㧗ࡲࡿࡇࡶ࡞ࡃ㸪 ࡼࡾ㧗࠸࣋ࢿࣇࢵࢺࡀᚓࡽࢀࡓࠋ
96 (13) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
2.7.6.3.2 ᭷ᐖ㇟ࡢࢹ࣮ࢱ
(1) ᭷ᐖ㇟ࡢⓎ⌧ྜ㸦ヨ㦂୰᩿๓⤌ࡳධࢀࡽࢀࡓ⿕㦂⪅ࢆ㝖ࡃ㸧
⾲ 2.7.6.3-4 ᭷ᐖ㇟ࡢⓎ⌧ྜ 㸦ᅉᯝ㛵ಀࢆၥࢃ࡞࠸ࡍ࡚ࡢ᭷ᐖ㇟㸭㦂⸆ྜ⌮ⓗ㛵㐃ᛶࡀ࠶ࡿ᭷ᐖ㇟㸧 㸦8 㐌┠ࡲ࡛㸧㸦㦂⸆ࢆᢞࡉࢀࡓ⿕㦂⪅㸧 All TEAEs Reasonably related TEAEs Placebo Ustekinumab a Placebo Ustekinumab a Analysis Set: Treated Subjects Excluding Those Enrolled Prior to Study Re- start 208 419 208 419
Total number of subjects with TEAEs 113 (54.3%) 221 (52.7%) 37 (17.8%) 53 (12.6%)
System-organ class/preferred term ⫶⭠㞀ᐖ 42 (20.2%) 84 (20.0%) 4 (1.9%) 15 (3.6%) ᝏᚰ 5 (2.4%) 18 (4.3%) 1 (0.5%) 6 (1.4%) ⭡③ 7 (3.4%) 15 (3.6%) 2 (1.0%) 3 (0.7%) ࢡ࣮ࣟࣥ 10 (4.8%) 15 (3.6%) 0 2 (0.5%) ྤ 3 (1.4%) 14 (3.3%) 1 (0.5%) 3 (0.7%) ᾘⰋ 5 (2.4%) 5 (1.2%) 1 (0.5%) 2 (0.5%) ཱྀ⭍ෆ₽⒆ᙧᡂ 3 (1.4%) 4 (1.0%) 0 0 ᑠ⭠㛢ሰ 2 (1.0%) 4 (1.0%) 0 0 ᰾ 0 3 (0.7%) 0 0 ┤⭠ฟ⾑ 1 (0.5%) 3 (0.7%) 0 1 (0.2%) ṑ③ 0 3 (0.7%) 0 0 ⭡㒊⭾‶ 2 (1.0%) 2 (0.5%) 0 0 ୗ⭡㒊③ 1 (0.5%) 2 (0.5%) 0 0 ୖ⭡㒊③ 2 (1.0%) 2 (0.5%) 0 0 ࣇࢱᛶཱྀෆ⅖ 3 (1.4%) 2 (0.5%) 0 0 ౽⛎ 0 2 (0.5%) 0 0 㱘ṑ 0 2 (0.5%) 0 0 ୗ⑩ 2 (1.0%) 2 (0.5%) 0 1 (0.2%) ⫶㣗㐨㏫ὶᛶᝈ 1 (0.5%) 2 (0.5%) 0 1 (0.2%) 㐣ᩄᛶ⭠ೃ⩌ 0 2 (0.5%) 0 0 ⫠㛛࿘ᅖ③ 0 2 (0.5%) 0 0 ⫠ 0 1 (0.2%) 0 0 ⒦ 0 1 (0.2%) 0 0 ⫠㛛࣏࣮ࣜࣉ 0 1 (0.2%) 0 0 ⫠㛛┤⭠ᛌឤ 1 (0.5%) 1 (0.2%) 0 0 ⭠⅖ 0 1 (0.2%) 0 0 ཱྀෆ⇱ 0 1 (0.2%) 0 1 (0.2%) ᚰ❐㒊ᛌឤ 0 1 (0.2%) 0 0 ኚⰍ౽ 0 1 (0.2%) 0 0 ᨺᒂ 1 (0.5%) 1 (0.2%) 0 0 ⫶⅖ 2 (1.0%) 1 (0.2%) 0 0 ⾑౽ἥ 2 (1.0%) 1 (0.2%) 0 0 㰢ᚄ࣊ࣝࢽ 0 1 (0.2%) 0 0 ᇙఅṑ 0 1 (0.2%) 0 0 ⭡㒊⭘⒗ 1 (0.5%) 0 0 0 ⫠㛛ฟ⾑ 1 (0.5%) 0 0 0 㣗୰ẘ 1 (0.5%) 0 0 0 ౽ᅇᩘቑຍ 1 (0.5%) 0 1 (0.5%) 0 ྤ⾑ 1 (0.5%) 0 0 0 ฟ⾑ 1 (0.5%) 0 0 0 ཱྀࡢឤぬ㕌㯞 1 (0.5%) 0 0 0 ⭠㛢ሰ 1 (0.5%) 0 0 0
97 (14) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
All TEAEs Reasonably related TEAEs Placebo Ustekinumab a Placebo Ustekinumab a ┤⭠ 1 (0.5%) 0 0 0 ᑠ⭠✸Ꮝ 1 (0.5%) 0 0 0 ឤᰁ࠾ࡼࡧᐤ⏕ 46 (22.1%) 83 (19.8%) 9 (4.3%) 17 (4.1%) 㰯ဗ㢌⅖ 10 (4.8%) 24 (5.7%) 1 (0.5%) 3 (0.7%) ୖẼ㐨ឤᰁ 10 (4.8%) 11 (2.6%) 3 (1.4%) 5 (1.2%) 㰯⭍⅖ 4 (1.9%) 8 (1.9%) 1 (0.5%) 1 (0.2%) Ẽ⟶ᨭ⅖ 6 (2.9%) 6 (1.4%) 0 1 (0.2%) ⫶⭠⅖ 0 4 (1.0%) 0 0 ࣥࣇ࢚ࣝࣥࢨ 2 (1.0%) 4 (1.0%) 0 0 ⻏ᕢ⅖ 1 (0.5%) 3 (0.7%) 1 (0.5%) 1 (0.2%) ᒀ㊰ឤᰁ 2 (1.0%) 3 (0.7%) 0 1 (0.2%) ⫠㛛⮋⒆ 2 (1.0%) 2 (0.5%) 0 1 (0.2%) ୰⪥⅖ 0 2 (0.5%) 0 0 ဗ㢌⅖ 0 2 (0.5%) 0 0 㰯⅖ 0 2 (0.5%) 0 0 ⭐ឤᰁ 0 2 (0.5%) 0 1 (0.2%) እ㝜㒊⭐࢝ࣥࢪࢲ 0 2 (0.5%) 0 1 (0.2%) ᛴᛶ㰯⭍⅖ 1 (0.5%) 1 (0.2%) 1 (0.5%) 1 (0.2%) ┿⳦ᛶ⫠㛛ឤᰁ 0 1 (0.2%) 0 0 ⣽⳦ᛶ⭐ 0 1 (0.2%) 0 0 ࢝ࢸ࣮ࢸࣝ␃⨨㒊ឤᰁ 0 1 (0.2%) 0 0 ⭤⬔⅖ 0 1 (0.2%) 0 1 (0.2%) ་⒪ᶵჾ㛵㐃ឤᰁ 0 1 (0.2%) 0 0 ⪥ឤᰁ 0 1 (0.2%) 0 0 ẟໟ⅖ 0 1 (0.2%) 0 0 㰢ᚄ㒊⮋⒆ 0 1 (0.2%) 0 0 ᖏ≧⑁⑈ 1 (0.5%) 1 (0.2%) 1 (0.5%) 1 (0.2%) ឤᰁᛶ⓶₽⒆ 0 1 (0.2%) 0 0 ㏞㊰⅖ 0 1 (0.2%) 0 0 㝈ᒁᛶឤᰁ 0 1 (0.2%) 0 0 ཱྀ⭍࢝ࣥࢪࢲ 0 1 (0.2%) 0 0 ཱྀ⭍࣊ࣝ࣌ࢫ 2 (1.0%) 1 (0.2%) 1 (0.5%) 1 (0.2%) Ẽ㐨ឤᰁ 0 1 (0.2%) 0 0 ⣽⳦ᛶẼ㐨ឤᰁ 0 1 (0.2%) 0 0 ࢘ࣝࢫᛶẼ㐨ឤᰁ 1 (0.5%) 1 (0.2%) 0 0 ṑ⮋⒆ 0 1 (0.2%) 0 0 ࢘ࣝࢫឤᰁ 0 1 (0.2%) 0 0 ࢘ࣝࢫᛶဗ㢌⅖ 0 1 (0.2%) 0 0 ࢡࣟࢫࢺࣜࢪ࣒࣭࢘ࢹࣇࢩࣞឤᰁ 1 (0.5%) 0 0 0 ⓶┿⳦ឤᰁ 1 (0.5%) 0 0 0 ࢘ࣝࢫᛶ⫶⭠⅖ 1 (0.5%) 0 0 0 ᛶჾ⮋⒆ 1 (0.5%) 0 0 0 ṑ⫗⅖ 2 (1.0%) 0 0 0 㹁ᆺ⫢⅖ 1 (0.5%) 0 0 0 ༢⣧࣊ࣝ࣌ࢫ 1 (0.5%) 0 0 0 㣗㐨࢝ࣥࢪࢲ 1 (0.5%) 0 0 0 ⫵⅖ 1 (0.5%) 0 0 0 ṑ㧊⅖ 1 (0.5%) 0 0 0 ṑឤᰁ 1 (0.5%) 0 1 (0.5%) 0 ➽㦵᱁⣔࠾ࡼࡧ⤖ྜ⤌⧊㞀ᐖ 18 (8.7%) 47 (11.2%) 4 (1.9%) 2 (0.5%) 㛵⠇③ 4 (1.9%) 17 (4.1%) 1 (0.5%) 1 (0.2%) ⫼㒊③ 3 (1.4%) 9 (2.1%) 0 0 ➽⫗③ 4 (1.9%) 6 (1.4%) 2 (1.0%) 1 (0.2%) 㢁㒊③ 1 (0.5%) 3 (0.7%) 0 0 㛵⠇⅖ 4 (1.9%) 2 (0.5%) 1 (0.5%) 0 㛵⠇⭘⬽ 1 (0.5%) 2 (0.5%) 0 0 ➽②⦰ 1 (0.5%) 2 (0.5%) 0 0 ᅄ⫥③ 1 (0.5%) 2 (0.5%) 0 0 㦵ᢡ③ 0 1 (0.2%) 0 0
98 (15) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
All TEAEs Reasonably related TEAEs Placebo Ustekinumab a Placebo Ustekinumab a ᳝㛫ᯈ㞀ᐖ 0 1 (0.2%) 0 0 ➽⥭ᙇ 0 1 (0.2%) 0 0 ➽㦵᱁③ 2 (1.0%) 1 (0.2%) 1 (0.5%) 0 ⭠㦵⅖ 0 1 (0.2%) 0 0 ⒦ᏍศἪ≀ 1 (0.5%) 0 0 0 ഃ⭡㒊③ 1 (0.5%) 0 0 0 㢡③ 1 (0.5%) 0 0 0 ୍⯡࣭㌟㞀ᐖ࠾ࡼࡧᢞ㒊ࡢ≧ែ 21 (10.1%) 44 (10.5%) 7 (3.4%) 13 (3.1%) Ⓨ⇕ 10 (4.8%) 17 (4.1%) 2 (1.0%) 3 (0.7%) ⑂ປ 4 (1.9%) 7 (1.7%) 2 (1.0%) 3 (0.7%) ↓ຊ 0 5 (1.2%) 0 3 (0.7%) 㠀ᚰ⮚ᛶ⬚③ 1 (0.5%) 5 (1.2%) 0 0 ᮎᲈᛶᾋ⭘ 3 (1.4%) 3 (0.7%) 1 (0.5%) 1 (0.2%) ⬚㒊ᛌឤ 0 1 (0.2%) 0 1 (0.2%) 㢦㠃③ 0 1 (0.2%) 0 1 (0.2%) ⒵Ⰻ 0 1 (0.2%) 0 0 ࣥࣇ࢚ࣝࣥࢨᵝᝈ 1 (0.5%) 1 (0.2%) 1 (0.5%) 1 (0.2%) ὀධ㒊⾑⟶እ₃ฟ 0 1 (0.2%) 0 0 ᒁᡤ⭘⬽ 0 1 (0.2%) 0 0 ᛰឤ 0 1 (0.2%) 0 0 ᑠ⤖⠇ 0 1 (0.2%) 0 0 ⑊③ 0 1 (0.2%) 0 1 (0.2%) άື≧ែపୗ 1 (0.5%) 0 1 (0.5%) 0 ཱྀῬ 1 (0.5%) 0 0 0 ⚄⤒⣔㞀ᐖ 23 (11.1%) 38 (9.1%) 10 (4.8%) 16 (3.8%) 㢌③ 14 (6.7%) 30 (7.2%) 6 (2.9%) 13 (3.1%) ∦㢌③ 3 (1.4%) 4 (1.0%) 2 (1.0%) 1 (0.2%) 㰯⭍⅖క࠺㢌③ 0 2 (0.5%) 0 0 ኻ⚄ 0 2 (0.5%) 0 0 ⅎ⇕ឤ 0 1 (0.2%) 0 0 ὀពຊ㞀ᐖ 0 1 (0.2%) 0 0 ᾋືᛶࡵࡲ࠸ 1 (0.5%) 1 (0.2%) 1 (0.5%) 1 (0.2%) యᛶࡵࡲ࠸ 2 (1.0%) 1 (0.2%) 0 1 (0.2%) Ⴔ╀ 0 1 (0.2%) 0 0 㘒ឤぬ 2 (1.0%) 1 (0.2%) 1 (0.5%) 1 (0.2%) ഴ╀ 0 1 (0.2%) 0 1 (0.2%) ኻㄒ 1 (0.5%) 0 0 0 ᡭ᰿⟶ೃ⩌ 1 (0.5%) 0 0 0 ከⓎᛶ◳ 1 (0.5%) 0 0 0 ኻ⚄ᑍ๓ࡢ≧ែ 1 (0.5%) 0 0 0 ⓶࠾ࡼࡧ⓶ୗ⤌⧊㞀ᐖ 10 (4.8%) 20 (4.8%) 4 (1.9%) 5 (1.2%) Ⓨ⑈ 2 (1.0%) 4 (1.0%) 1 (0.5%) 1 (0.2%) ࡑ࠺ 1 (0.5%) 3 (0.7%) 0 1 (0.2%) ࡊ⒔ 0 2 (0.5%) 0 1 (0.2%) ࡑ࠺ᛶ⓶⑈ 0 2 (0.5%) 0 1 (0.2%) ⬺ẟ 2 (1.0%) 1 (0.2%) 2 (1.0%) 0 ࡊ⒔ᵝ⓶⅖ 0 1 (0.2%) 0 1 (0.2%) Ⓞᵝ⓶⅖ 0 1 (0.2%) 0 1 (0.2%) ⓶⇱ 0 1 (0.2%) 0 0 ‵⑈ 1 (0.5%) 1 (0.2%) 0 0 ᔐධ∎ 0 1 (0.2%) 0 0 ᐷờ 0 1 (0.2%) 0 0 ග⥺㐣ᩄᛶᛂ 0 1 (0.2%) 0 0 ⣚ᩬᛶ⓶⑈ 0 1 (0.2%) 0 0 ᩬ≧ୣ⑈≧⓶⑈ 0 1 (0.2%) 0 0 ୣ⑈ᛶ⓶⑈ 0 1 (0.2%) 0 0 ⓶⥺᮲ 0 1 (0.2%) 0 0 ⶼ㯞⑈ 0 1 (0.2%) 0 1 (0.2%) ⓶⅖ 1 (0.5%) 0 0 0
99 (16) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
All TEAEs Reasonably related TEAEs Placebo Ustekinumab a Placebo Ustekinumab a ከờ 1 (0.5%) 0 1 (0.5%) 0 ⓶⬺ 1 (0.5%) 0 1 (0.5%) 0 ⓶ኚ 2 (1.0%) 0 0 0 ྾ჾࠊ⬚㒌࠾ࡼࡧ⦪㝸㞀ᐖ 9 (4.3%) 18 (4.3%) 2 (1.0%) 5 (1.2%) တႿ 4 (1.9%) 9 (2.1%) 1 (0.5%) 1 (0.2%) ཱྀ⭍ဗ㢌③ 1 (0.5%) 3 (0.7%) 0 1 (0.2%) 㰯㛢 2 (1.0%) 2 (0.5%) 1 (0.5%) 1 (0.2%) 㰯⇱ 0 2 (0.5%) 0 0 㰯ฟ⾑ 2 (1.0%) 1 (0.2%) 0 1 (0.2%) ဗ㢌ࡢ⅖ 0 1 (0.2%) 0 0 ⮬↛Ẽ⬚ 0 1 (0.2%) 0 0 ୖẼ㐨တೃ⩌ 0 1 (0.2%) 0 1 (0.2%) ႍᜥ 1 (0.5%) 0 0 0 㰯₃ 1 (0.5%) 0 0 0 㰯⭍࠺ࡗ⾑ 1 (0.5%) 0 1 (0.5%) 0 ⮫ᗋ᳨ᰝ 2 (1.0%) 13 (3.1%) 1 (0.5%) 5 (1.2%) ⾑ᅽୖ᪼ 1 (0.5%) 3 (0.7%) 0 0 ⫢ᶵ⬟᳨ᰝ␗ᖖ 0 3 (0.7%) 0 2 (0.5%) ⾑ᑠᯈᩘቑຍ 0 2 (0.5%) 0 0 ࣛࢽ࣑ࣥࣀࢺࣛࣥࢫࣇ࢙࣮ࣛࢮ ቑຍ 1 (0.5%) 1 (0.2%) 1 (0.5%) 1 (0.2%) ⾑୰ࣝࣈ࣑ࣥῶᑡ 0 1 (0.2%) 0 0 ⾑୰ࢡࣞࢳࣥቑຍ 0 1 (0.2%) 0 1 (0.2%) య ୖ᪼ 0 1 (0.2%) 0 1 (0.2%) ࣊ࣔࢢࣟࣅࣥῶᑡ 0 1 (0.2%) 0 0 ዲ୰⌫ᩘቑຍ 0 1 (0.2%) 0 0 య㔜ቑຍ 0 1 (0.2%) 0 0 ⢭⚄㞀ᐖ 5 (2.4%) 13 (3.1%) 0 3 (0.7%) ╀ 3 (1.4%) 5 (1.2%) 0 2 (0.5%) Ᏻ 0 4 (1.0%) 0 0 ࠺ࡘ 1 (0.5%) 2 (0.5%) 0 0 ᨷᧁᛶ 0 1 (0.2%) 0 1 (0.2%) ╧╀㞀ᐖ 0 1 (0.2%) 0 0 Ᏻ㞀ᐖ 1 (0.5%) 0 0 0 ⾑ᾮ࠾ࡼࡧࣜࣥࣃ⣔㞀ᐖ 5 (2.4%) 12 (2.9%) 1 (0.5%) 1 (0.2%) ㈋⾑ 3 (1.4%) 6 (1.4%) 0 0 ⓑ⾑⌫ῶᑡ 0 3 (0.7%) 0 0 㕲Ḟஈᛶ㈋⾑ 0 1 (0.2%) 0 0 ࣜࣥࣃ⠇③ 0 1 (0.2%) 0 1 (0.2%) ࣜࣥࣃ⌫ῶᑡ 0 1 (0.2%) 0 0 ⾑ᑠᯈῶᑡ 0 1 (0.2%) 0 0 ዲ୰⌫ῶᑡ 1 (0.5%) 0 0 0 ỗ⾑⌫ῶᑡ 1 (0.5%) 0 1 (0.5%) 0 ║㞀ᐖ 5 (2.4%) 12 (2.9%) 4 (1.9%) 1 (0.2%) ║⇱ 0 2 (0.5%) 0 0 ⓑෆ㞀 0 1 (0.2%) 0 0 ୖᙉ⭷⅖ 0 1 (0.2%) 0 0 ║ࡢࣞࣝࢠ࣮ 0 1 (0.2%) 0 0 ║่⃭ 0 1 (0.2%) 0 0 ║⌫ᾋ⭘ 0 1 (0.2%) 0 0 ║③ 1 (0.5%) 1 (0.2%) 0 0 ᙬ⅖ 0 1 (0.2%) 0 0 ࣈࢻ࢘⭷⅖ 0 1 (0.2%) 0 0 㟝ど 0 1 (0.2%) 0 1 (0.2%) どຊపୗ 0 1 (0.2%) 0 0 どຊ㞀ᐖ 2 (1.0%) 1 (0.2%) 2 (1.0%) 0 ║▛ᾋ⭘ 1 (0.5%) 0 1 (0.5%) 0 ▛ᩬ 1 (0.5%) 0 1 (0.5%) 0 ◪Ꮚయᾋ㐟≀ 1 (0.5%) 0 1 (0.5%) 0
10 0 (17) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
All TEAEs Reasonably related TEAEs Placebo Ustekinumab a Placebo Ustekinumab a യᐖࠊ୰ẘ࠾ࡼࡧฎ⨨ྜే 6 (2.9%) 10 (2.4%) 2 (1.0%) 0 ⠇㊊ື≀ညയ 0 1 (0.2%) 0 0 ⬻┞ 0 1 (0.2%) 0 0 യ 2 (1.0%) 1 (0.2%) 1 (0.5%) 0 㢌㒊ᦆയ 0 1 (0.2%) 0 0 ⒕࣊ࣝࢽ 0 1 (0.2%) 0 0 㛵⠇ᦆയ 0 1 (0.2%) 0 0 㠎ᖏ 1 (0.5%) 1 (0.2%) 0 0 ᅄ⫥ᦆയ 1 (0.5%) 1 (0.2%) 0 0 ➽ᦆയ 0 1 (0.2%) 0 0 ⫗㞳ࢀ 0 1 (0.2%) 0 0 ⫘㦵㦵ᢡ 0 1 (0.2%) 0 0 ⫼㒊ᦆയ 1 (0.5%) 0 0 0 ║ࡢ⇕യ 1 (0.5%) 0 1 (0.5%) 0 ௦ㅰ࠾ࡼࡧᰤ㣴㞀ᐖ 3 (1.4%) 10 (2.4%) 1 (0.5%) 1 (0.2%) ⢾ᒀ 0 3 (0.7%) 0 0 ప࣒࢝ࣜ࢘⾑ 0 3 (0.7%) 0 0 㣗ḧῶ㏥ 0 2 (0.5%) 0 1 (0.2%) ⬺Ỉ 1 (0.5%) 1 (0.2%) 0 0 పࣝࣈ࣑ࣥ⾑ 0 1 (0.2%) 0 0 యᾮ㈓␃ 1 (0.5%) 0 1 (0.5%) 0 ࣅࢱ࣑ࣥ㹂Ḟஈ 1 (0.5%) 0 0 0 ⏕Ṫ⣔࠾ࡼࡧஙᡣ㞀ᐖ 2 (1.0%) 6 (1.4%) 0 0 ஙᡣ③ 0 2 (0.5%) 0 0 ஙᡣᄞ⬊ 0 1 (0.2%) 0 0 ᭶⤒ᅔ㞴 1 (0.5%) 1 (0.2%) 0 0 ዪᛶ⏕Ṫჾ⒦ 0 1 (0.2%) 0 0 ᭶⤒㐣ከ 0 1 (0.2%) 0 0 ᛶᅔ㞴 1 (0.5%) 0 0 0 ⾑⟶㞀ᐖ 3 (1.4%) 5 (1.2%) 3 (1.4%) 2 (0.5%) 㧗⾑ᅽ 1 (0.5%) 2 (0.5%) 1 (0.5%) 0 ₻⣚ 2 (1.0%) 1 (0.2%) 2 (1.0%) 1 (0.2%) ࡚ࡾ 0 1 (0.2%) 0 1 (0.2%) 㟼⬦⅖ 0 1 (0.2%) 0 0 ⪥࠾ࡼࡧ㏞㊰㞀ᐖ 0 4 (1.0%) 0 2 (0.5%) ᅇ㌿ᛶࡵࡲ࠸ 0 2 (0.5%) 0 1 (0.2%) ⪥ࡑ࠺ 0 1 (0.2%) 0 0 ⪥㬆 0 1 (0.2%) 0 1 (0.2%) ᚰ⮚㞀ᐖ 1 (0.5%) 3 (0.7%) 0 1 (0.2%) ື 0 1 (0.2%) 0 0 Ὕᛶ㢖⬦ 0 1 (0.2%) 0 0 㢖⬦ 0 1 (0.2%) 0 1 (0.2%) ᚰᡣ⣽ື 1 (0.5%) 0 0 0 ච⣔㞀ᐖ 1 (0.5%) 3 (0.7%) 0 0 Ꮨ⠇ᛶࣞࣝࢠ࣮ 1 (0.5%) 3 (0.7%) 0 0 ⭈࠾ࡼࡧᒀ㊰㞀ᐖ 0 3 (0.7%) 0 0 ኻ⚗ 0 1 (0.2%) 0 0 ⭈⤖▼ 0 1 (0.2%) 0 0 ᒀ㛢 0 1 (0.2%) 0 0 Ⰻᛶࠊᝏᛶ࠾ࡼࡧヲ⣽᫂ࡢ᪂⏕≀ 㸦ᄞ⬊࠾ࡼࡧ࣏࣮ࣜࣉࢆྵࡴ㸧 1 (0.5%) 1 (0.2%) 1 (0.5%) 0 ⚄⤒⭘ 0 1 (0.2%) 0 0 ࢡࣟࢥࣝࢻࣥ 1 (0.5%) 0 1 (0.5%) 0 ⫢⫹㐨⣔㞀ᐖ 2 (1.0%) 0 1 (0.5%) 0 ⫹⟶⤖▼ 1 (0.5%) 0 0 0 㧗ࣅࣜࣝࣅࣥ⾑ 1 (0.5%) 0 1 (0.5%) 0
a Combining 130 mg group and 6 mg/kg group. TEAEs=Treatment Emergent Adverse Events [TJPCAE11B.RTF] [CNTO1275\Z_SCS\DBR_2015_07\RE_JPKK\PROD\TJPCAE11B.SAS] 28OCT2015, 23:46
10 1 (18) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
(2) ᭷ᐖ㇟ࡢⓎ⌧ྜ㸦ヨ㦂୰᩿๓⤌ࡳධࢀࡽࢀࡓ⿕㦂⪅ࢆྵࡴ㸧
1) 㞟ᅋ ⾲ 2.7.6.3-5 ᭷ᐖ㇟ࡢⓎ⌧ྜ㸦ᅉᯝ㛵ಀࢆၥࢃ࡞࠸ࡍ࡚ࡢ᭷ᐖ㇟㸭 㦂⸆ྜ⌮ⓗ㛵㐃ᛶࡀ࠶ࡿ᭷ᐖ㇟㸧㸦8 㐌┠ࡲ࡛㸧㸦㦂⸆ࢆᢞࡉࢀࡓ⿕㦂⪅㸧 All TEAEs Reasonably related TEAEs Placebo Ustekinumab a Placebo Ustekinumab a Analysis Set: Treated Subjects 212 427 212 427
Total number of subjects with TEAEs 117 (55.2%) 224 (52.5%) 37 (17.5%) 54 (12.6%)
System-organ class/preferred term ⫶⭠㞀ᐖ 43 (20.3%) 85 (19.9%) 4 (1.9%) 15 (3.5%) ᝏᚰ 5 (2.4%) 18 (4.2%) 1 (0.5%) 6 (1.4%) ࢡ࣮ࣟࣥ 10 (4.7%) 16 (3.7%) 0 2 (0.5%) ⭡③ 7 (3.3%) 15 (3.5%) 2 (0.9%) 3 (0.7%) ྤ 3 (1.4%) 14 (3.3%) 1 (0.5%) 3 (0.7%) ᾘⰋ 5 (2.4%) 5 (1.2%) 1 (0.5%) 2 (0.5%) ཱྀ⭍ෆ₽⒆ᙧᡂ 3 (1.4%) 4 (0.9%) 0 0 ᑠ⭠㛢ሰ 2 (0.9%) 4 (0.9%) 0 0 ᰾ 0 3 (0.7%) 0 0 ┤⭠ฟ⾑ 1 (0.5%) 3 (0.7%) 0 1 (0.2%) ṑ③ 0 3 (0.7%) 0 0 ⭡㒊⭾‶ 2 (0.9%) 2 (0.5%) 0 0 ୗ⭡㒊③ 1 (0.5%) 2 (0.5%) 0 0 ୖ⭡㒊③ 2 (0.9%) 2 (0.5%) 0 0 ࣇࢱᛶཱྀෆ⅖ 3 (1.4%) 2 (0.5%) 0 0 ౽⛎ 0 2 (0.5%) 0 0 㱘ṑ 0 2 (0.5%) 0 0 ୗ⑩ 2 (0.9%) 2 (0.5%) 0 1 (0.2%) ⫶㣗㐨㏫ὶᛶᝈ 1 (0.5%) 2 (0.5%) 0 1 (0.2%) 㐣ᩄᛶ⭠ೃ⩌ 0 2 (0.5%) 0 0 ⫠㛛࿘ᅖ③ 0 2 (0.5%) 0 0 ⫠ 0 1 (0.2%) 0 0 ⒦ 1 (0.5%) 1 (0.2%) 0 0 ⫠㛛࣏࣮ࣜࣉ 0 1 (0.2%) 0 0 ⫠㛛┤⭠ᛌឤ 1 (0.5%) 1 (0.2%) 0 0 ⭠⅖ 0 1 (0.2%) 0 0 ཱྀෆ⇱ 0 1 (0.2%) 0 1 (0.2%) ᚰ❐㒊ᛌឤ 0 1 (0.2%) 0 0 ኚⰍ౽ 0 1 (0.2%) 0 0 ᨺᒂ 1 (0.5%) 1 (0.2%) 0 0 ⫶⅖ 2 (0.9%) 1 (0.2%) 0 0 ⾑౽ἥ 2 (0.9%) 1 (0.2%) 0 0 㰢ᚄ࣊ࣝࢽ 0 1 (0.2%) 0 0 㝈ᒁᛶ⭡⭍ෆᾮ㈓␃ 0 1 (0.2%) 0 0 ᇙఅṑ 0 1 (0.2%) 0 0 ⭡㒊⭘⒗ 1 (0.5%) 0 0 0 ⫠㛛ฟ⾑ 1 (0.5%) 0 0 0 㣗୰ẘ 1 (0.5%) 0 0 0 ౽ᅇᩘቑຍ 1 (0.5%) 0 1 (0.5%) 0 ྤ⾑ 1 (0.5%) 0 0 0 ฟ⾑ 1 (0.5%) 0 0 0 ཱྀࡢឤぬ㕌㯞 1 (0.5%) 0 0 0 ⭠㛢ሰ 1 (0.5%) 0 0 0 ┤⭠ 1 (0.5%) 0 0 0 ᑠ⭠✸Ꮝ 1 (0.5%) 0 0 0 ឤᰁ࠾ࡼࡧᐤ⏕ 50 (23.6%) 84 (19.7%) 9 (4.2%) 18 (4.2%) 㰯ဗ㢌⅖ 10 (4.7%) 24 (5.6%) 1 (0.5%) 3 (0.7%) ୖẼ㐨ឤᰁ 11 (5.2%) 11 (2.6%) 3 (1.4%) 5 (1.2%)
10 2 (19) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
All TEAEs Reasonably related TEAEs Placebo Ustekinumab a Placebo Ustekinumab a 㰯⭍⅖ 4 (1.9%) 8 (1.9%) 1 (0.5%) 1 (0.2%) Ẽ⟶ᨭ⅖ 6 (2.8%) 7 (1.6%) 0 2 (0.5%) ⫶⭠⅖ 0 4 (0.9%) 0 0 ࣥࣇ࢚ࣝࣥࢨ 2 (0.9%) 4 (0.9%) 0 0 ⻏ᕢ⅖ 1 (0.5%) 3 (0.7%) 1 (0.5%) 1 (0.2%) ᒀ㊰ឤᰁ 2 (0.9%) 3 (0.7%) 0 1 (0.2%) ⫠㛛⮋⒆ 4 (1.9%) 2 (0.5%) 0 1 (0.2%) ୰⪥⅖ 0 2 (0.5%) 0 0 ဗ㢌⅖ 0 2 (0.5%) 0 0 㰯⅖ 0 2 (0.5%) 0 0 ⭐ឤᰁ 0 2 (0.5%) 0 1 (0.2%) እ㝜㒊⭐࢝ࣥࢪࢲ 0 2 (0.5%) 0 1 (0.2%) ᛴᛶ㰯⭍⅖ 1 (0.5%) 1 (0.2%) 1 (0.5%) 1 (0.2%) ┿⳦ᛶ⫠㛛ឤᰁ 0 1 (0.2%) 0 0 ⣽⳦ᛶ⭐ 0 1 (0.2%) 0 0 ࢝ࢸ࣮ࢸࣝ␃⨨㒊ឤᰁ 0 1 (0.2%) 0 0 ⭤⬔⅖ 0 1 (0.2%) 0 1 (0.2%) ་⒪ᶵჾ㛵㐃ឤᰁ 0 1 (0.2%) 0 0 ⪥ឤᰁ 0 1 (0.2%) 0 0 ẟໟ⅖ 0 1 (0.2%) 0 0 㰢ᚄ㒊⮋⒆ 0 1 (0.2%) 0 0 ᖏ≧⑁⑈ 1 (0.5%) 1 (0.2%) 1 (0.5%) 1 (0.2%) ឤᰁᛶ⓶₽⒆ 0 1 (0.2%) 0 0 ㏞㊰⅖ 0 1 (0.2%) 0 0 㝈ᒁᛶឤᰁ 0 1 (0.2%) 0 0 ཱྀ⭍࢝ࣥࢪࢲ 0 1 (0.2%) 0 0 ཱྀ⭍࣊ࣝ࣌ࢫ 2 (0.9%) 1 (0.2%) 1 (0.5%) 1 (0.2%) Ẽ㐨ឤᰁ 0 1 (0.2%) 0 0 ⣽⳦ᛶẼ㐨ឤᰁ 0 1 (0.2%) 0 0 ࢘ࣝࢫᛶẼ㐨ឤᰁ 1 (0.5%) 1 (0.2%) 0 0 ṑ⮋⒆ 0 1 (0.2%) 0 0 ࢘ࣝࢫឤᰁ 0 1 (0.2%) 0 0 ࢘ࣝࢫᛶဗ㢌⅖ 0 1 (0.2%) 0 0 ࢡࣟࢫࢺࣜࢪ࣒࣭࢘ࢹࣇࢩࣞឤᰁ 1 (0.5%) 0 0 0 ⓶┿⳦ឤᰁ 2 (0.9%) 0 0 0 ࢘ࣝࢫᛶ⫶⭠⅖ 1 (0.5%) 0 0 0 ᛶჾ⮋⒆ 1 (0.5%) 0 0 0 㝜㒊࣊ࣝ࣌ࢫ 1 (0.5%) 0 0 0 ṑ⫗⅖ 2 (0.9%) 0 0 0 㹁ᆺ⫢⅖ 1 (0.5%) 0 0 0 ༢⣧࣊ࣝ࣌ࢫ 1 (0.5%) 0 0 0 㣗㐨࢝ࣥࢪࢲ 1 (0.5%) 0 0 0 ⫵⅖ 1 (0.5%) 0 0 0 ṑ㧊⅖ 1 (0.5%) 0 0 0 ṑឤᰁ 1 (0.5%) 0 1 (0.5%) 0 ➽㦵᱁⣔࠾ࡼࡧ⤖ྜ⤌⧊㞀ᐖ 18 (8.5%) 48 (11.2%) 4 (1.9%) 2 (0.5%) 㛵⠇③ 4 (1.9%) 18 (4.2%) 1 (0.5%) 1 (0.2%) ⫼㒊③ 3 (1.4%) 9 (2.1%) 0 0 ➽⫗③ 4 (1.9%) 6 (1.4%) 2 (0.9%) 1 (0.2%) 㢁㒊③ 1 (0.5%) 3 (0.7%) 0 0 㛵⠇⅖ 4 (1.9%) 2 (0.5%) 1 (0.5%) 0 㛵⠇⭘⬽ 1 (0.5%) 2 (0.5%) 0 0 ➽②⦰ 1 (0.5%) 2 (0.5%) 0 0 ᅄ⫥③ 1 (0.5%) 2 (0.5%) 0 0 㦵ᢡ③ 0 1 (0.2%) 0 0 ᳝㛫ᯈ㞀ᐖ 0 1 (0.2%) 0 0 ➽⥭ᙇ 0 1 (0.2%) 0 0 ➽㦵᱁③ 2 (0.9%) 1 (0.2%) 1 (0.5%) 0 ⭠㦵⅖ 0 1 (0.2%) 0 0
10 3 (20) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
All TEAEs Reasonably related TEAEs Placebo Ustekinumab a Placebo Ustekinumab a ⒦ᏍศἪ≀ 1 (0.5%) 0 0 0 ഃ⭡㒊③ 1 (0.5%) 0 0 0 㢡③ 1 (0.5%) 0 0 0 ୍⯡࣭㌟㞀ᐖ࠾ࡼࡧᢞ㒊ࡢ≧ែ 21 (9.9%) 46 (10.8%) 7 (3.3%) 13 (3.0%) Ⓨ⇕ 10 (4.7%) 17 (4.0%) 2 (0.9%) 3 (0.7%) ⑂ປ 4 (1.9%) 7 (1.6%) 2 (0.9%) 3 (0.7%) ↓ຊ 0 5 (1.2%) 0 3 (0.7%) 㠀ᚰ⮚ᛶ⬚③ 1 (0.5%) 5 (1.2%) 0 0 ᮎᲈᛶᾋ⭘ 3 (1.4%) 3 (0.7%) 1 (0.5%) 1 (0.2%) ࣥࣇ࢚ࣝࣥࢨᵝᝈ 1 (0.5%) 2 (0.5%) 1 (0.5%) 1 (0.2%) ⬚㒊ᛌឤ 0 1 (0.2%) 0 1 (0.2%) ⬚③ 0 1 (0.2%) 0 0 㢦㠃③ 0 1 (0.2%) 0 1 (0.2%) ⒵Ⰻ 0 1 (0.2%) 0 0 ὀධ㒊⾑⟶እ₃ฟ 0 1 (0.2%) 0 0 ᒁᡤ⭘⬽ 0 1 (0.2%) 0 0 ᛰឤ 0 1 (0.2%) 0 0 ᑠ⤖⠇ 0 1 (0.2%) 0 0 ⑊③ 0 1 (0.2%) 0 1 (0.2%) άື≧ែపୗ 1 (0.5%) 0 1 (0.5%) 0 ཱྀῬ 1 (0.5%) 0 0 0 ⚄⤒⣔㞀ᐖ 23 (10.8%) 39 (9.1%) 10 (4.7%) 16 (3.7%) 㢌③ 14 (6.6%) 30 (7.0%) 6 (2.8%) 13 (3.0%) ∦㢌③ 3 (1.4%) 4 (0.9%) 2 (0.9%) 1 (0.2%) 㰯⭍⅖క࠺㢌③ 0 2 (0.5%) 0 0 ኻ⚄ 0 2 (0.5%) 0 0 ⅎ⇕ឤ 0 1 (0.2%) 0 0 ᡭ᰿⟶ೃ⩌ 1 (0.5%) 1 (0.2%) 0 0 ὀពຊ㞀ᐖ 0 1 (0.2%) 0 0 ᾋືᛶࡵࡲ࠸ 1 (0.5%) 1 (0.2%) 1 (0.5%) 1 (0.2%) యᛶࡵࡲ࠸ 2 (0.9%) 1 (0.2%) 0 1 (0.2%) Ⴔ╀ 0 1 (0.2%) 0 0 㘒ឤぬ 2 (0.9%) 1 (0.2%) 1 (0.5%) 1 (0.2%) ഴ╀ 0 1 (0.2%) 0 1 (0.2%) ኻㄒ 1 (0.5%) 0 0 0 ከⓎᛶ◳ 1 (0.5%) 0 0 0 ኻ⚄ᑍ๓ࡢ≧ែ 1 (0.5%) 0 0 0 ྾ჾࠊ⬚㒌࠾ࡼࡧ⦪㝸㞀ᐖ 9 (4.2%) 20 (4.7%) 2 (0.9%) 5 (1.2%) တႿ 4 (1.9%) 9 (2.1%) 1 (0.5%) 1 (0.2%) ཱྀ⭍ဗ㢌③ 1 (0.5%) 3 (0.7%) 0 1 (0.2%) 㰯㛢 2 (0.9%) 2 (0.5%) 1 (0.5%) 1 (0.2%) 㰯⇱ 0 2 (0.5%) 0 0 ⮬↛Ẽ⬚ 0 2 (0.5%) 0 0 㰯ฟ⾑ 2 (0.9%) 1 (0.2%) 0 1 (0.2%) ဗ㢌ࡢ⅖ 0 1 (0.2%) 0 0 ⫵⫗ⱆ⭘ 0 1 (0.2%) 0 0 ୖẼ㐨တೃ⩌ 0 1 (0.2%) 0 1 (0.2%) ႍᜥ 1 (0.5%) 0 0 0 㰯₃ 1 (0.5%) 0 0 0 㰯⭍࠺ࡗ⾑ 1 (0.5%) 0 1 (0.5%) 0 ⓶࠾ࡼࡧ⓶ୗ⤌⧊㞀ᐖ 12 (5.7%) 20 (4.7%) 4 (1.9%) 5 (1.2%) Ⓨ⑈ 3 (1.4%) 4 (0.9%) 1 (0.5%) 1 (0.2%) ࡑ࠺ 1 (0.5%) 3 (0.7%) 0 1 (0.2%) ࡊ⒔ 0 2 (0.5%) 0 1 (0.2%) ⬺ẟ 2 (0.9%) 2 (0.5%) 2 (0.9%) 0 ࡑ࠺ᛶ⓶⑈ 0 2 (0.5%) 0 1 (0.2%) ࡊ⒔ᵝ⓶⅖ 0 1 (0.2%) 0 1 (0.2%) Ⓞᵝ⓶⅖ 0 1 (0.2%) 0 1 (0.2%) ⓶⇱ 0 1 (0.2%) 0 0
10 4 (21) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
All TEAEs Reasonably related TEAEs Placebo Ustekinumab a Placebo Ustekinumab a ‵⑈ 2 (0.9%) 1 (0.2%) 0 0 ᔐධ∎ 0 1 (0.2%) 0 0 ᐷờ 0 1 (0.2%) 0 0 ග⥺㐣ᩄᛶᛂ 0 1 (0.2%) 0 0 ⣚ᩬᛶ⓶⑈ 0 1 (0.2%) 0 0 ᩬ≧ୣ⑈≧⓶⑈ 0 1 (0.2%) 0 0 ୣ⑈ᛶ⓶⑈ 0 1 (0.2%) 0 0 ⓶⥺᮲ 0 1 (0.2%) 0 0 ⶼ㯞⑈ 0 1 (0.2%) 0 1 (0.2%) ⓶⅖ 1 (0.5%) 0 0 0 ከờ 1 (0.5%) 0 1 (0.5%) 0 ⓶⬺ 1 (0.5%) 0 1 (0.5%) 0 ⓶ኚ 2 (0.9%) 0 0 0 ⮫ᗋ᳨ᰝ 2 (0.9%) 13 (3.0%) 1 (0.5%) 5 (1.2%) ⾑ᅽୖ᪼ 1 (0.5%) 3 (0.7%) 0 0 ⫢ᶵ⬟᳨ᰝ␗ᖖ 0 3 (0.7%) 0 2 (0.5%) ⾑ᑠᯈᩘቑຍ 0 2 (0.5%) 0 0 ࣛࢽ࣑ࣥࣀࢺࣛࣥࢫࣇ࢙࣮ࣛࢮ ቑຍ 1 (0.5%) 1 (0.2%) 1 (0.5%) 1 (0.2%) ⾑୰ࣝࣈ࣑ࣥῶᑡ 0 1 (0.2%) 0 0 ⾑୰ࢡࣞࢳࣥቑຍ 0 1 (0.2%) 0 1 (0.2%) య ୖ᪼ 0 1 (0.2%) 0 1 (0.2%) ࣊ࣔࢢࣟࣅࣥῶᑡ 0 1 (0.2%) 0 0 ዲ୰⌫ᩘቑຍ 0 1 (0.2%) 0 0 య㔜ቑຍ 0 1 (0.2%) 0 0 ⢭⚄㞀ᐖ 5 (2.4%) 13 (3.0%) 0 3 (0.7%) ╀ 3 (1.4%) 5 (1.2%) 0 2 (0.5%) Ᏻ 0 4 (0.9%) 0 0 ࠺ࡘ 1 (0.5%) 2 (0.5%) 0 0 ᨷᧁᛶ 0 1 (0.2%) 0 1 (0.2%) ╧╀㞀ᐖ 0 1 (0.2%) 0 0 Ᏻ㞀ᐖ 1 (0.5%) 0 0 0 ⾑ᾮ࠾ࡼࡧࣜࣥࣃ⣔㞀ᐖ 5 (2.4%) 12 (2.8%) 1 (0.5%) 1 (0.2%) ㈋⾑ 3 (1.4%) 6 (1.4%) 0 0 ⓑ⾑⌫ῶᑡ 0 3 (0.7%) 0 0 㕲Ḟஈᛶ㈋⾑ 0 1 (0.2%) 0 0 ࣜࣥࣃ⠇③ 0 1 (0.2%) 0 1 (0.2%) ࣜࣥࣃ⌫ῶᑡ 0 1 (0.2%) 0 0 ⾑ᑠᯈῶᑡ 0 1 (0.2%) 0 0 ዲ୰⌫ῶᑡ 1 (0.5%) 0 0 0 ỗ⾑⌫ῶᑡ 1 (0.5%) 0 1 (0.5%) 0 ║㞀ᐖ 5 (2.4%) 12 (2.8%) 4 (1.9%) 1 (0.2%) ║⇱ 0 2 (0.5%) 0 0 ⓑෆ㞀 0 1 (0.2%) 0 0 ୖᙉ⭷⅖ 0 1 (0.2%) 0 0 ║ࡢࣞࣝࢠ࣮ 0 1 (0.2%) 0 0 ║่⃭ 0 1 (0.2%) 0 0 ║⌫ᾋ⭘ 0 1 (0.2%) 0 0 ║③ 1 (0.5%) 1 (0.2%) 0 0 ᙬ⅖ 0 1 (0.2%) 0 0 ࣈࢻ࢘⭷⅖ 0 1 (0.2%) 0 0 㟝ど 0 1 (0.2%) 0 1 (0.2%) どຊపୗ 0 1 (0.2%) 0 0 どຊ㞀ᐖ 2 (0.9%) 1 (0.2%) 2 (0.9%) 0 ║▛ᾋ⭘ 1 (0.5%) 0 1 (0.5%) 0 ▛ᩬ 1 (0.5%) 0 1 (0.5%) 0 ◪Ꮚయᾋ㐟≀ 1 (0.5%) 0 1 (0.5%) 0 യᐖࠊ୰ẘ࠾ࡼࡧฎ⨨ྜే 6 (2.8%) 10 (2.3%) 2 (0.9%) 0 ⠇㊊ື≀ညയ 0 1 (0.2%) 0 0
10 5 (22) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
All TEAEs Reasonably related TEAEs Placebo Ustekinumab a Placebo Ustekinumab a ⬻┞ 0 1 (0.2%) 0 0 യ 2 (0.9%) 1 (0.2%) 1 (0.5%) 0 㢌㒊ᦆയ 0 1 (0.2%) 0 0 ⒕࣊ࣝࢽ 0 1 (0.2%) 0 0 㛵⠇ᦆയ 0 1 (0.2%) 0 0 㠎ᖏ 1 (0.5%) 1 (0.2%) 0 0 ᅄ⫥ᦆയ 1 (0.5%) 1 (0.2%) 0 0 ➽ᦆയ 0 1 (0.2%) 0 0 ⫗㞳ࢀ 0 1 (0.2%) 0 0 ⫘㦵㦵ᢡ 0 1 (0.2%) 0 0 ⫼㒊ᦆയ 1 (0.5%) 0 0 0 ║ࡢ⇕യ 1 (0.5%) 0 1 (0.5%) 0 ௦ㅰ࠾ࡼࡧᰤ㣴㞀ᐖ 3 (1.4%) 10 (2.3%) 1 (0.5%) 1 (0.2%) ⢾ᒀ 0 3 (0.7%) 0 0 ప࣒࢝ࣜ࢘⾑ 0 3 (0.7%) 0 0 㣗ḧῶ㏥ 0 2 (0.5%) 0 1 (0.2%) ⬺Ỉ 1 (0.5%) 1 (0.2%) 0 0 పࣝࣈ࣑ࣥ⾑ 0 1 (0.2%) 0 0 యᾮ㈓␃ 1 (0.5%) 0 1 (0.5%) 0 ࣅࢱ࣑ࣥ㹂Ḟஈ 1 (0.5%) 0 0 0 ⏕Ṫ⣔࠾ࡼࡧஙᡣ㞀ᐖ 2 (0.9%) 6 (1.4%) 0 0 ஙᡣ③ 0 2 (0.5%) 0 0 ஙᡣᄞ⬊ 0 1 (0.2%) 0 0 ᭶⤒ᅔ㞴 1 (0.5%) 1 (0.2%) 0 0 ዪᛶ⏕Ṫჾ⒦ 0 1 (0.2%) 0 0 ᭶⤒㐣ከ 0 1 (0.2%) 0 0 ᛶᅔ㞴 1 (0.5%) 0 0 0 ⾑⟶㞀ᐖ 3 (1.4%) 5 (1.2%) 3 (1.4%) 2 (0.5%) 㧗⾑ᅽ 1 (0.5%) 2 (0.5%) 1 (0.5%) 0 ₻⣚ 2 (0.9%) 1 (0.2%) 2 (0.9%) 1 (0.2%) ࡚ࡾ 0 1 (0.2%) 0 1 (0.2%) 㟼⬦⅖ 0 1 (0.2%) 0 0 ⪥࠾ࡼࡧ㏞㊰㞀ᐖ 0 4 (0.9%) 0 2 (0.5%) ᅇ㌿ᛶࡵࡲ࠸ 0 2 (0.5%) 0 1 (0.2%) ⪥ࡑ࠺ 0 1 (0.2%) 0 0 ⪥㬆 0 1 (0.2%) 0 1 (0.2%) ⭈࠾ࡼࡧᒀ㊰㞀ᐖ 0 4 (0.9%) 0 0 Ỉ⭈ 0 1 (0.2%) 0 0 Ỉᒀ⟶ 0 1 (0.2%) 0 0 ኻ⚗ 0 1 (0.2%) 0 0 ⭈⤖▼ 0 1 (0.2%) 0 0 ᒀ㛢 0 1 (0.2%) 0 0 ᚰ⮚㞀ᐖ 1 (0.5%) 3 (0.7%) 0 1 (0.2%) ື 0 1 (0.2%) 0 0 Ὕᛶ㢖⬦ 0 1 (0.2%) 0 0 㢖⬦ 0 1 (0.2%) 0 1 (0.2%) ᚰᡣ⣽ື 1 (0.5%) 0 0 0 ච⣔㞀ᐖ 1 (0.5%) 3 (0.7%) 0 0 Ꮨ⠇ᛶࣞࣝࢠ࣮ 1 (0.5%) 3 (0.7%) 0 0 Ⰻᛶࠊᝏᛶ࠾ࡼࡧヲ⣽᫂ࡢ᪂⏕≀ 㸦ᄞ⬊࠾ࡼࡧ࣏࣮ࣜࣉࢆྵࡴ㸧 1 (0.5%) 1 (0.2%) 1 (0.5%) 0 ⚄⤒⭘ 0 1 (0.2%) 0 0 ࢡࣟࢥࣝࢻࣥ 1 (0.5%) 0 1 (0.5%) 0 ⫢⫹㐨⣔㞀ᐖ 2 (0.9%) 0 1 (0.5%) 0 ⫹⟶⤖▼ 1 (0.5%) 0 0 0 㧗ࣅࣜࣝࣅࣥ⾑ 1 (0.5%) 0 1 (0.5%) 0
10 6 (23) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
All TEAEs Reasonably related TEAEs Placebo Ustekinumab a Placebo Ustekinumab a
a Combining 130 mg group and 6 mg/kg group. TEAEs=Treatment Emergent Adverse Events Include all the AEs through Week 8 and the AEs after Week 8 occurred in the subjects who did not enter maintenance study. Adverse events are coded using MedDRA 17.0. [TPMDASF10A.rtf] [CNTO1275\CRD3003\DBR_CSR\RE_PMDA\tpmdasf10a.sas] 20SEP2016, 21:45
2) ᪥ᮏே㞟ᅋ ⾲ 2.7.6.3-6 ᭷ᐖ㇟ࡢⓎ⌧ྜ㸦ᅉᯝ㛵ಀࢆၥࢃ࡞࠸ࡍ࡚ࡢ᭷ᐖ㇟㸭 㦂⸆ྜ⌮ⓗ㛵㐃ᛶࡀ࠶ࡿ᭷ᐖ㇟㸧㸦8 㐌┠ࡲ࡛㸧㸦㦂⸆ࢆᢞࡉࢀࡓ⿕㦂⪅㸧 All TEAEs Reasonably related TEAEs Placebo Ustekinumab a Placebo Ustekinumab a Analysis Set: Treated Subjects (Japanese subjects only) 9 17 9 17
Total number of subjects with TEAEs 4 (44.4%) 8 (47.1%) 2 (22.2%) 1 (5.9%)
System-organ class/preferred term ⫶⭠㞀ᐖ 0 4 (23.5%) 0 0 ୗ⭡㒊③ 0 1 (5.9%) 0 0 ࢡ࣮ࣟࣥ 0 1 (5.9%) 0 0 㱘ṑ 0 1 (5.9%) 0 0 ᑠ⭠㛢ሰ 0 1 (5.9%) 0 0 ឤᰁ࠾ࡼࡧᐤ⏕ 2 (22.2%) 4 (23.5%) 0 0 㰯ဗ㢌⅖ 2 (22.2%) 2 (11.8%) 0 0 ་⒪ᶵჾ㛵㐃ឤᰁ 0 1 (5.9%) 0 0 ࣥࣇ࢚ࣝࣥࢨ 0 1 (5.9%) 0 0 ୍⯡࣭㌟㞀ᐖ࠾ࡼࡧᢞ㒊ࡢ ≧ែ 2 (22.2%) 1 (5.9%) 2 (22.2%) 0 Ⓨ⇕ 2 (22.2%) 1 (5.9%) 2 (22.2%) 0 ⚄⤒⣔㞀ᐖ 1 (11.1%) 1 (5.9%) 1 (11.1%) 1 (5.9%) 㢌③ 1 (11.1%) 1 (5.9%) 1 (11.1%) 1 (5.9%)
a Combining 130 mg group and 6 mg/kg group. TEAEs=Treatment Emergent Adverse Events Include all the AEs through Week 8 and the AEs after Week 8 occurred in the subjects who did not enter maintenance study. Adverse events are coded using MedDRA 17.0. [TPMDASF10B.rtf] [CNTO1275\CRD3003\DBR_CSR\RE_PMDA\tpmdasf10b.sas] 20SEP2016, 21:45
10 7 (24)
࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3002 (3) ୰Ṇ⮳ࡗࡓ᭷ᐖ㇟ࡢヲ⣽㸦ヨ㦂୰᩿๓⤌ࡳධࢀࡽࢀࡓ⿕㦂⪅ࢆྵࡴ㸧
1) 㞟ᅋ ⾲ 2.7.6.3-7 ୰Ṇ⮳ࡗࡓ᭷ᐖ㇟㸦8 㐌┠ࡲ࡛㸧㸦㦂⸆ࢆᢞࡉࢀࡓ⿕㦂⪅㸧
Study 2.7.6 Agent Study Day Age Dose of AE/ MedDRA Relation to Treatment Subject (yrs)/ Prior to Duration Preferred Infusion Study Group ID Sex AE (days) Term Verbatim Term Infectiona Reaction Serious Severity Drug Action Taken Outcome Placebo IV 1049-20829 3/F 0 mg 47/Ongoing 㹁ᆺ⫢⅖ HEPATITIS C Yes No No MODERATE NOT DRUG NOT RECOVERED/NOT RELATED WITHDRAWN RESOLVED 1119-20897 2/F 0 mg 9/4 ࢡ࣮ࣟࣥ WORSENING No No Yes MODERATE NOT DRUG RECOVERED/RESOLVED CROHN'S RELATED WITHDRAWN WITH SEQUELAE DISEASE 4705-20606 2/F 0 mg 14/6 ࢡ࣮ࣟࣥ CROHN'S FLARE No No Yes SEVERE NOT DRUG RECOVERED/RESOLVED RELATED WITHDRAWN 5302-20695 4/F 0 mg 15/10 ᑠ⭠㛢ሰ SMALL BOWEL No No Yes SEVERE NOT DRUG RECOVERED/RESOLVED OBSTRUCTION RELATED WITHDRAWN 5615-20084 4/M 0 mg 57/271 ⫠㛛⮋⒆ PERI-ANAL Yes No Yes MODERATE NOT DRUG RECOVERED/RESOLVED ABSCESSES RELATED WITHDRAWN WITH SEQUELAE Ustekinumab 1029-20618 6/F 194.9 1/1 ⬚㒊ᛌឤ TIGHTNESS IN No Yes No MODERATE POSSIBLE DRUG RECOVERED/RESOLVED 130 mg IV mg CHEST WITHDRAWN 2212-20633 4/F 129.6 3/15 ࢡ࣮ࣟࣥ EXACERBATION No No Yes MODERATE NOT DRUG RECOVERED/RESOLVED mg OF CROHN'S RELATED WITHDRAWN DISEASE 2213-20598 6/M 129.6 21/Ongoing ࢡ࣮ࣟࣥ CROHN'S FLARE No No No MODERATE NOT DRUG NOT RECOVERED/NOT mg RELATED WITHDRAWN RESOLVED 3604-20820 3/M 129.6 58/36 ⫠㛛⮋⒆ PERIANAL Yes No Yes SEVERE NOT DRUG RECOVERED/RESOLVED mg ABSCESS RELATED WITHDRAWN WITH SEQUELAE Ustekinumab 1117-20973 5/F 520.2 6/Ongoing Ⓨ⑈ SKIN RASH No No No MILD POSSIBLE DRUG NOT RECOVERED/NOT Approximating mg WITHDRAWN RESOLVED 6 mg/kg IV
a Infection as assessed by the investigator. Include all the AEs through Week 8 and the AEs after Week 8 occurred in the subjects who did not enter maintenance study.
Adverse events are coded using MedDRA 17.0. ಶ
[LPMDASF15A.rtf] [CNTO1275\CRD3003\DBR_CSR\RE_PMDA\lpmdasf15a.sas] 20SEP2016, 21:43 ࠎ ࡢヨ
㦂
ࡢࡲ 㸦 25 ヨ 㸧 ࡵ 㦂
108
࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3002 ⾲ 2.7.6.3-8 㦂⸆ྜ⌮ⓗ㛵㐃ᛶࡀ࠶ࡿ୰Ṇ⮳ࡗࡓ᭷ᐖ㇟㸦8 㐌┠ࡲ࡛㸧㸦㦂⸆ࢆᢞࡉࢀࡓ⿕㦂⪅㸧 Study Agent Study Day Age Dose of AE/ MedDRA Treatment Subject (yrs)/ Prior to Duration Preferred Infusion Relation to Group ID Sex AE (days) Term Verbatim Term Infectiona Reaction Serious Severity Study Drug Action Taken Outcome
Ustekinumab 1029-20618 6/F 194.9 1/1 ⬚㒊ᛌឤ TIGHTNESS IN No Yes No MODERATE POSSIBLE DRUG RECOVERED/RESOLVED 2.7.6 130 mg IV mg CHEST WITHDRAWN Ustekinumab 1117-20973 5/F 520.2 6/Ongoing Ⓨ⑈ SKIN RASH No No No MILD POSSIBLE DRUG NOT RECOVERED/NOT Approximating mg WITHDRAWN RESOLVED 6 mg/kg IV
a Infection as assessed by the investigator. Include all the AEs through Week 8 and the AEs after Week 8 occurred in the subjects who did not enter maintenance study. Adverse events are coded using MedDRA 17.0. [LPMDASF14A.rtf] [CNTO1275\CRD3003\DBR_CSR\RE_PMDA\lpmdasf14a.sas] 20SEP2016, 21:43
ಶ ࠎ ࡢヨ 㦂 ࡢࡲ 㸦 26 ヨ 㸧 ࡵ 㦂
109
࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3002 2) ᪥ᮏே㞟ᅋ ⾲ 2.7.6.3-9 ୰Ṇ⮳ࡗࡓ᭷ᐖ㇟㸦8 㐌┠ࡲ࡛㸧㸦㦂⸆ࢆᢞࡉࢀࡓ⿕㦂⪅㸧 Study Agent Study Day of Subject Age (yrs)/ Dose AE/ MedDRA Infusion Relation to Treatment Group ID Sex Prior to AE Duration (days) Preferred Term Verbatim Term Infectiona Reaction Serious Severity Study Drug Action Taken Outcome 2.7.6
No Data to Report
a Infection as assessed by the investigator. Include all the AEs through Week 8 and the AEs after Week 8 occurred in the subjects who did not enter maintenance study. Adverse events are coded using MedDRA 17.0. [LPMDASF15B.rtf] [CNTO1275\CRD3003\DBR_CSR\RE_PMDA\lpmdasf15b.sas] 20SEP2016, 21:43
⾲ 2.7.6.3-10 㦂⸆ྜ⌮ⓗ㛵㐃ᛶࡀ࠶ࡿ୰Ṇ⮳ࡗࡓ᭷ᐖ㇟㸦8 㐌┠ࡲ࡛㸧㸦㦂⸆ࢆᢞࡉࢀࡓ⿕㦂⪅㸧 Study Agent Study Day of Subject Age (yrs)/ Dose AE/ MedDRA Infusion Relation to Treatment Group ID Sex Prior to AE Duration (days) Preferred Term Verbatim Term Infectiona Reaction Serious Severity Study Drug Action Taken Outcome
No Data to Report
a Infection as assessed by the investigator. Include all the AEs through Week 8 and the AEs after Week 8 occurred in the subjects who did not enter maintenance study. Adverse events are coded using MedDRA 17.0. [LPMDASF14B.rtf] [CNTO1275\CRD3003\DBR_CSR\RE_PMDA\lpmdasf14b.sas] 20SEP2016, 21:43
ಶ ࠎ ࡢヨ 㦂 ࡢࡲ 㸦 27 ヨ 㸧 ࡵ 㦂
110
࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3002
2.7.6.3.3 㔜⠜࡞᭷ᐖ㇟ࡢࢹ࣮ࢱ
(1) 㔜⠜࡞᭷ᐖ㇟ࡢヲ⣽㸦ヨ㦂୰᩿๓⤌ࡳධࢀࡽࢀࡓ⿕㦂⪅ࢆྵࡴ㸧
1) 㞟ᅋ 2.7.6 ⾲ 2.7.6.3-11 㔜⠜࡞᭷ᐖ㇟ཬࡧ㦂⸆ྜ⌮ⓗ㛵㐃ᛶࡀ࠶ࡿ㔜⠜࡞᭷ᐖ㇟㸦8 㐌┠ࡲ࡛㸧㸦㦂⸆ࢆᢞࡉࢀࡓ⿕㦂⪅㸧 Study Agent Study Day Age Dose of AE/ Treatment Subject (yrs)/ Prior to Duration MedDRA Infusion Relation to Group ID Sex AE (days) Preferred Term Verbatim Term Infectiona Reaction Serious Severity Study Drug Action Taken Outcome Placebo IV 1004-20631 3/M 0 mg 88/2 㢌③ HEADACHE No No Yes SEVERE NOT DOSE NOT RECOVERED/ RELATED CHANGED RESOLVED 1006-20484 2/M 0 mg 55/2 ࢡ࣮ࣟࣥ CROHN'S No No Yes MODERATE NOT DOSE NOT RECOVERED/ EXACERBATION RELATED CHANGED RESOLVED 1007-20647 3/F 0 mg 10/5 ࢡ࣮ࣟࣥ CROHN'S FLARE No No Yes SEVERE DOUBTFUL DOSE NOT RECOVERED/ CHANGED RESOLVED 1119-20897 2/F 0 mg 9/4 ࢡ࣮ࣟࣥ WORSENING No No Yes MODERATE NOT DRUG RECOVERED/ CROHN'S DISEASE RELATED WITHDRAWN RESOLVED WITH SEQUELAE 1134-20970 3/F 0 mg 49/14 ⫹⟶⤖▼ GALLSTONES WITH No No Yes MODERATE NOT DOSE NOT RECOVERED/ DILATED COMMON RELATED CHANGED RESOLVED BILE DUCT 2212-20054 5/M 0 mg 5/1 ⭠㛢ሰ BOWEL No No Yes MODERATE NOT DOSE NOT RECOVERED/ OBSTRUCTION RELATED CHANGED RESOLVED WITH SEQUELAE 2711-20704 2/F 0 mg 14/5 ᭶⤒ᅔ㞴 DYSMENORRHEA No No Yes SEVERE DOUBTFUL DOSE NOT RECOVERED/ CHANGED RESOLVED 3417-20795 4/M 0 mg 57/5 ⫠㛛⮋⒆ ABSCESS PERIANAL Yes No Yes MODERATE NOT DOSE NOT RECOVERED/ RELATED CHANGED RESOLVED 3610-20397 4/F 0 mg 21/6 ⫠㛛⮋⒆ PERIANAL ABSCESS Yes No Yes MODERATE NOT DOSE NOT RECOVERED/ RELATED CHANGED RESOLVED 4705-20606 2/F 0 mg 14/6 ࢡ࣮ࣟࣥ CROHN'S FLARE No No Yes SEVERE NOT DRUG RECOVERED/ RELATED WITHDRAWN RESOLVED ಶ 2/F 109/9 㝜㒊࣊ࣝ࣌ࢫ GENITAL HERPES Yes No Yes MILD NOT NOT RECOVERED/ ࠎ RELATED APPLICABLE RESOLVED ࡢヨ 5302-20695 4/F 0 mg 15/10 ᑠ⭠㛢ሰ SMALL BOWEL No No Yes SEVERE NOT DRUG RECOVERED/ OBSTRUCTION RELATED WITHDRAWN RESOLVED 㦂
4/F 16/9 ᑠ⭠✸Ꮝ PERITONITIS AFTER Yes No Yes SEVERE NOT NOT RECOVERED/ ࡢࡲ
㸦 SMALL BOWEL RELATED APPLICABLE RESOLVED 28 PERFORATION ヨ 㸧 ࡵ 㦂
111
࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3002 Study Agent Study Day Age Dose of AE/ Treatment Subject (yrs)/ Prior to Duration MedDRA Infusion Relation to Group ID Sex AE (days) Preferred Term Verbatim Term Infectiona Reaction Serious Severity Study Drug Action Taken Outcome 5309-20149 4/M 0 mg 29/62 ỗ⾑⌫ῶᑡ PANCYTOPENIA ON No No Yes SEVERE POSSIBLE DOSE NOT RECOVERED/ FBC CHANGED RESOLVED
WITH 2.7.6 SEQUELAE 5309-20244 3/M 0 mg 49/2 ㈋⾑ ANAEMIA No No Yes SEVERE NOT DOSE NOT RECOVERED/ RELATED CHANGED RESOLVED 5607-20288 6/F 0 mg 15/24 ࢡ࣮ࣟࣥ WORSENING OF No No Yes MODERATE DOUBTFUL DOSE NOT RECOVERED/ CROHNS DISEASE CHANGED RESOLVED WITH SEQUELAE 6/F 29/1 ᚰᡣ⣽ື FAST ATRIAL No No Yes SEVERE NOT NOT RECOVERED/ FIBRILLATION RELATED APPLICABLE RESOLVED 6/F ⫵⅖ HOSPITAL Yes No Yes SEVERE NOT DOSE NOT RECOVERED/ ACQUIRED RELATED CHANGED RESOLVED PNEUMONIA 5615-20084 4/M 0 mg 57/271 ⫠㛛⮋⒆ PERI-ANAL Yes No Yes MODERATE NOT DRUG RECOVERED/ ABSCESSES RELATED WITHDRAWN RESOLVED WITH SEQUELAE Ustekinumab 1005-20229 2/F 129.6 20/3 ࢡ࣮ࣟࣥ CROHN'S No No Yes MODERATE DOUBTFUL DOSE NOT RECOVERED/ 130 mg IV mg EXACERBATION CHANGED RESOLVED 1032-20466 3/F 129.6 45/3 ࢡ࣮ࣟࣥ CROHN'S DISEASE No No Yes SEVERE NOT DOSE NOT RECOVERED/ mg EXACERBATION RELATED CHANGED RESOLVED 1048-20746 2/M 129.6 4/5 ⮬↛Ẽ⬚ SPONTANEOUS No No Yes SEVERE DOUBTFUL DOSE NOT RECOVERED/ mg PNEUMOTHORAX CHANGED RESOLVED 1114-20051 5/F 129.6 35/1 㠀ᚰ⮚ᛶ⬚③ NON-CARDIAC No No Yes MODERATE NOT DOSE NOT RECOVERED/ mg CHEST PAIN RELATED CHANGED RESOLVED 2212-20633 4/F 129.6 3/15 ࢡ࣮ࣟࣥ EXACERBATION OF No No Yes MODERATE NOT DRUG RECOVERED/ mg CROHN'S DISEASE RELATED WITHDRAWN RESOLVED 4/F 45/46 ࢡ࣮ࣟࣥ CROHN'S ILEITIS No No Yes MODERATE NOT NOT RECOVERED/ (COMPLICATED) RELATED APPLICABLE RESOLVED 4/F 104/8 㝈ᒁᛶ⭡⭍ෆ INTRA-ABDOMINAL Yes No Yes SEVERE DOUBTFUL NOT RECOVERED/ ᾮ㈓␃ FLUID COLLECTION APPLICABLE RESOLVED 3314-20944 3/F 129.6 22/11 ୗ⑩ DIARRHEA Yes No Yes MODERATE POSSIBLE DOSE NOT RECOVERED/ mg CHANGED RESOLVED ಶ 3/F 46/2 ᑠ⭠㛢ሰ SMALL BOWEL No No Yes MODERATE NOT DOSE NOT RECOVERED/ ࠎ OBSTRUCTION RELATED CHANGED RESOLVED ࡢヨ 3/F 47/2 ㈋⾑ WORSENING OF No No Yes MODERATE NOT DOSE NOT RECOVERED/ ANEMIA RELATED CHANGED RESOLVED 㦂
3/F 54/8 ࢡ࣮ࣟࣥ WORSENING OF No No Yes SEVERE NOT DOSE NOT RECOVERED/ ࡢࡲ
㸦 CROHN'S DISEASE RELATED CHANGED RESOLVED 29 3404-20986 2/M 129.6 8/10 ⒕࣊ࣝࢽ INCISIONAL HERNIA No No Yes MODERATE DOUBTFUL DOSE NOT RECOVERED/ ヨ 㸧 ࡵ mg CHANGED RESOLVED 㦂
112
࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3002 Study Agent Study Day Age Dose of AE/ Treatment Subject (yrs)/ Prior to Duration MedDRA Infusion Relation to Group ID Sex AE (days) Preferred Term Verbatim Term Infectiona Reaction Serious Severity Study Drug Action Taken Outcome 2/M 35/Ongoing ⒵Ⰻ DISORDER OF POST- No No Yes MILD DOUBTFUL DOSE NOT UNKNOWN OPERATIVE WOUND CHANGED
HEALING 2.7.6 3604-20820 3/M 129.6 58/36 ⫠㛛⮋⒆ PERIANAL ABSCESS Yes No Yes SEVERE NOT DRUG RECOVERED/ mg RELATED WITHDRAWN RESOLVED WITH SEQUELAE 4002-20328 4/M 129.6 28/3 ⫠㛛⮋⒆ PERI-ANAL ABSCESS Yes No Yes MODERATE POSSIBLE DOSE NOT RECOVERED/ mg CHANGED RESOLVED 5606-20407 7/F 129.6 17/19 ࢡ࣮ࣟࣥ FLARE IN CROHN'S No No Yes SEVERE NOT DOSE NOT RECOVERED/ mg DISEASE RELATED CHANGED RESOLVED Ustekinumab 1013-20022 7/F 390.0 146/3 ⬚③ ATYPICAL CHEST No No Yes SEVERE NOT DOSE NOT RECOVERED/ Approximating mg PAIN RELATED CHANGED RESOLVED 6 mg/kg IV 1015-20011 2/M 390.0 54/15 ⮬↛Ẽ⬚ SPONTANEOUS LEFT No No Yes SEVERE NOT DOSE NOT RECOVERED/ mg SIDED RELATED CHANGED RESOLVED PNEUMOTHORAX 1022-20641 3/F 259.2 6/3 ᑠ⭠㛢ሰ POSSIBLE SMALL No No Yes MODERATE NOT DOSE NOT RECOVERED/ mg BOWEL RELATED CHANGED RESOLVED OBSTRUCTION 1025-20928 2/F 389.7 44/3 ⭠⅖ COLITIS, DUE TO No No Yes SEVERE NOT DOSE NOT RECOVERED/ mg CHEMICAL RELATED CHANGED RESOLVED IRRITATION FOLLOWING COLONOSCOPY 3415-20142 5/M 389.7 92/Ongoing ⫵⫗ⱆ⭘ LUNG OPACITIES No No Yes MILD NOT DOSE NOT UNKNOWN mg RIGHT UPPER LUNG RELATED CHANGED LOBE 3606-20372 4/F 259.2 54/12 ⫶⭠⅖ INFECTIOUS Yes No Yes MILD DOUBTFUL DOSE NOT RECOVERED/ mg GASTROENTERITIS CHANGED RESOLVED 4202-20293 3/M 389.7 21/14 ᑠ⭠㛢ሰ TEMPORAL No No Yes MODERATE NOT DOSE NOT RECOVERED/ mg OBSTRUCTION OF RELATED CHANGED RESOLVED SMALL BOWEL 4212-20536 4/M 259.2 3/70 ࢡ࣮ࣟࣥ WORSENING OF No No Yes MODERATE NOT DOSE NOT RECOVERED/ mg CROHN'S DISEASE RELATED CHANGED RESOLVED ಶ 5302-20747 2/M 389.7 5/7 ࢡ࣮ࣟࣥ CROHN'S No No Yes SEVERE NOT DOSE NOT RECOVERED/ ࠎ
mg EXACERBATION RELATED CHANGED RESOLVED ࡢヨ
a Infection as assessed by the investigator. 㦂
Include all the AEs through Week 8 and the AEs after Week 8 occurred in the subjects who did not enter maintenance study. ࡢࡲ
㸦 Adverse events are coded using MedDRA 17.0. 30 [LPMDASF22A.rtf] [CNTO1275\CRD3003\DBR_CSR\RE_PMDA\lpmdasf22a.sas] 20SEP2016, 21:43 ヨ 㸧 ࡵ 㦂
113
࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3002 2) ᪥ᮏே㞟ᅋ ⾲ 2.7.6.3-12 㔜⠜࡞᭷ᐖ㇟ཬࡧ㦂⸆ྜ⌮ⓗ㛵㐃ᛶࡀ࠶ࡿ㔜⠜࡞᭷ᐖ㇟ 㸦8 㐌┠ࡲ࡛㸧㸦㦂⸆ࢆᢞࡉࢀࡓ⿕㦂⪅㸧 Study
Agent Study Day 2.7.6 Age Dose of AE/ Subject (yrs)/ Prior to Duration MedDRA Infusion Relation to Treatment Group ID Sex AE (days) Preferred Term Verbatim Term Infectiona Reaction Serious Severity Study Drug Action Taken Outcome Ustekinumab 4202-20293 3/M 389.7 21/14 ᑠ⭠㛢ሰ TEMPORAL No No Yes MODERATE NOT DOSE NOT RECOVERED/ Approximating 6 mg OBSTRUCTION OF RELATED CHANGED RESOLVED mg/kg IV SMALL BOWEL 4212-20536 4/M 259.2 3/70 ࢡ࣮ࣟࣥ WORSENING OF No No Yes MODERATE NOT DOSE NOT RECOVERED/ mg CROHN'S DISEASE RELATED CHANGED RESOLVED
a Infection as assessed by the investigator. Include all the AEs through Week 8 and the AEs after Week 8 occurred in the subjects who did not enter maintenance study. Adverse events are coded using MedDRA 17.0. [LPMDASF22B.rtf] [CNTO1275\CRD3003\DBR_CSR\RE_PMDA\lpmdasf22b.sas] 20SEP2016, 21:43
ಶ ࠎ ࡢヨ 㦂 ࡢࡲ 㸦 31 ヨ 㸧 ࡵ 㦂
114 ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
2.7.6.3.3.1 Narratives SAE㸦᪥ᮏேⓎ⌧ࡋࡓ㇟ࡢࡳ㸧㸪㦂⸆ྜ⌮ⓗ㛵㐃ᛶࡀ࠶ࡿ SAE ཬࡧ㔜⠜࡞ឤᰁ ࡢヲ⣽ࢆ⿕㦂⪅ࡈ௨ୗ♧ࡍࠋ
Table of Narratives Subject Death Japanese Related SAE Serious Number infection 4202-20293 X 4212-20536 X 3314-20944 X X 4002-20328 X X 2212-20633 X 2401-20315 X 3604-20820 X 3606-20372 X
(1) CNTO1275CRD3002-4202-20293
1) Reason for narrative selection SAE
2) Adverse Events Start date End date (Study Preferred Term Intensity/ Inf/ Action Taken/ (Study day) (Verbatim Term) SAE Relatedness Trt? Outcome day) 2013-02- ᑠ⭠㛢ሰ Y MODERATE/ N/ DOSE NOT CHANGED/ 2013-02- 01 (TEMPORAL OBSTRUCTION OF SMALL NOT NA RECOVERED/RESOLVED 14 (21) BOWEL) RELATED (34)
3) Baseline Demographic Information Age (years): 3 Sex: Male Weight (kg): 57.9 Race: Asian Date of birth: Height (cm): 170.5
4) Induction Treatment Group Randomized Treatment Group: Ustekinumab Approximating 6 mg/kg IV Actual Treatment Group: Ustekinumab Approximating 6 mg/kg IV
5) Induction Treatment Received Visit Start Date Study Day Dose Number Actual Treatment Dose WEEK 0 2013-01-12 1 1 Ustekinumab Approximating 6 mg/kg IV 389.7 mg
6) Induction Disposition Did subject complete the induction study?: Y Did subject enter maintenance study?: Y
7) Baseline Crohn's Disease History Date of diagnosis: 31DEC2001 Disease duration: 11.04 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪⫠㛛࿘ᅖ
11 5 㸦32㸧 ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
8) Crohn's Disease Complications Before Baseline Intra-abdominal abscess: Never Sinus tracts/perforation: Never Fistula: Currently present Stricture complications of (CD): Currently present
9) Concomitant Crohn's Disease-Related Surgeries None reported
10) Concomitant Steroids None reported
11) Concomitant Medications Preferred Term Start Date End Date Reason Route METRONIDAZOLE 2012-09-21 2013-08-16 CROHN'S DISEASE ORAL AZATHIOPRINE 2012-10-15 - CROHN'S DISEASE ORAL OTHER NUTRIENTS 2013-02-04 2014-03-26 CROHN'S DISEASE ORAL
12) Narrative Text ⿕㦂⪅ࡣ 3 ṓࡢ᪥ᮏே⏨ᛶ࡛㸪2013 ᖺ 1 ᭶ 12 ᪥ᐶゎᑟධ⒪ἲࡋ࡚ᮏ㸦㹼6 mg/kg ⩌㸧 ࢆ㟼⬦ෆᢞࡉࢀࡓࠋ SAE㸸ᑠ⭠㛢ሰ㸦Day 21㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ᮶㝔ணᐃ᪥ࡢ 2013 ᖺ 2 ᭶ 1 ᪥㸪7㹼8 ᪥๓ࡼࡾᣢ⥆ࡍࡿ⭡㒊⭾‶ ⭡③ࢆッ࠼ࡓࠋྠ᪥㸪⿕㦂⪅ࡣධ㝔ࡋࡓࠋ⌮Ꮫⓗᡤぢ࡛ࡣ⭡㒊ࡣᰂ㌾࡛࠶ࡗࡓࡀ㸪⭾‶ࡋ࡚࠾ ࡾ㸪㊴③ࡣ࡞ࡗࡓࠋ⭡㒊ࢥࣥࣆ࣮ࣗࢱ᩿ᒙᙳ㸦CT㸧ࢫ࡛࢟ࣕࣥࡣ㸪ᅇ⭠⊃✽༊ᇦ㏆ࡢ ᑠ⭠ᾮయ㈓␃ཬࡧᣑᙇࡀㄆࡵࡽࢀࡓࠋ㐟㞳࢞ࢫ㸪⭡Ỉཬࡧ⭡⭍ෆ⮋⒆ࡣ࡞ࡗࡓࠋࡇࢀࡽࡢᡤ ぢࡼࡾ㸪ࢡ࣮ࣟࣥࡼࡿ⭠ኚࡢᝏ㉳ᅉࡋࡓᅇ⭠㛢ሰࡀᙉࡃ♧၀ࡉࢀࡓࠋ⿕㦂⪅ࣞ࢘ ࢫ⟶ࢆᤄධࡋ㸪⭠ࡢῶᅽࢆ⾜ࡗࡓࠋ2013 ᖺ 2 ᭶ 2 ᪥ࡣ⿕㦂⪅ࡢ≧ࡣᨵၿࡋ㸪ྠ᪥ࡢ⭡㒊 X ⥺᳨ᰝ࡛ࡣ㸪⭠ෆ࢞ࢫཬࡧ⭠ෆᾮࡢῶᑡࡀㄆࡵࡽࢀࡓࠋࣞ࢘ࢫ⟶ࡽࡢᾮࡣ࡞ࡗࡓࠋ2013 ᖺ 2 ᭶ 3 ᪥ࡢ࣮ࣚࢻ㐀ᙳ㸦࢞ࢫࢺࣟࢢࣛࣇࣥ㸧ࢆ⏝࠸ࡓᅇ⭠㐀ᙳ࡛ࡣ㸪ከᩘࡢ⊃✽ཬࡧ⊃✽ ๓㸦 㸧ᣑᙇࡀ☜ㄆࡉࢀࡓࡀ㸪㐀ᙳࡣ⊃✽㒊ࢆ㏻㐣ࡋࡓࠋᮏ㇟ࡣࢡ࣮ࣟࣥࡼࡿ ⭠ኚࡢᝏ㉳ᅉࡍࡿࡶࡢ࡛ࡣ࡞ࡃ㸪ヨ㦂ཧຍ๓ࡽᏑᅾࡋࡓ⭠⊃✽㒊㣗≀ṧ´ࡀࡋ ࡓࡇ࡛Ⓨ⌧ࡋࡓุ᩿ࡉࢀࡓࠋࡇࡢⅬ࡛ࣞ࢘ࢫ⟶ࢆᢤ⟶ࡋ㸪ࢡ࣮ࣟࣥᑐࡋ㸪ᰤ㣴 㸦ࣛࢥ࣮ࣝ NF㸧ࡼࡿ⒪ࢆ⾜ࡗࡓࠋ⿕㦂⪅ࡣ 2013 ᖺ 2 ᭶ 5 ᪥ὶື㣗ࢆ⤒ཱྀᦤྲྀࡋ㸪ࡑࡢᚋ ࡣᅛᙧ㣗ษࡾ᭰࠼ࡓࠋ2013 ᖺ 2 ᭶ 13 ᪥ࡢ CT ࢫ࡛࢟ࣕࣥࡣ㸪౫↛ࡋ࡚ᅇ⭠ࡢ⊃✽ࡀㄆࡵࡽ ࢀࡓࡀ㸪ᅇ⭠༊ᇦࡢ⊃✽๓ࡣ࡞ࡗࡓࠋ⿕㦂⪅ࡣ 2013 ᖺ 2 ᭶ 14 ᪥ᑠ⭠㛢ሰࡽᅇࡋ㸪ྠ᪥ ㏥㝔ࡋࡓࠋ
(2) CNTO1275CRD3002-4212-20536
1) Reason for narrative selection SAE
11 6 㸦33㸧 ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
2) Adverse Events Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day) (Verbatim Term) SAE Relatedness Trt? Outcome (Study day) 2013-08-09 ࢡ࣮ࣟࣥ Y MODERATE/ N/ DOSE NOT CHANGED/ 2013-10-17 (3) (WORSENING OF CROHN'S DISEASE) NOT RELATED NA RECOVERED/RESOLVED (72) 2013-08-29 ་⒪ᶵჾ㛵㐃ឤᰁ N MILD/ Y/ DOSE NOT CHANGED/ 2013-09-07 (23) (CENTRAL LINE INFECTION) NOT RELATED Y RECOVERED/RESOLVED (32)
3) Baseline Demographic Information Age (years): 4 Sex: Male Weight (kg): 49.8 Race: Asian Date of birth: Height (cm): 169.3
4) Induction Treatment Group Randomized Treatment Group: Ustekinumab Approximating 6 mg/kg IV Actual Treatment Group: Ustekinumab Approximating 6 mg/kg IV
5) Induction Treatment Received Visit Start Date Study Day Dose Number Actual Treatment Dose WEEK 0 2013-08-07 1 1 Ustekinumab Approximating 6 mg/kg IV 259.2 mg
6) Induction Disposition Did subject complete the induction study?: Y Did subject enter maintenance study?: Y
7) Baseline Crohn's Disease History Date of diagnosis: 01SEP1996 Disease duration: 16.93 years Involved areas: ᅇ⭠ࡢࡳ㸪⫠㛛࿘ᅖ
8) Crohn's Disease Complications Before Baseline Intra-abdominal abscess: Never Sinus tracts/perforation: Previous history Fistula: Currently present Stricture complications of (CD): Currently present
9) Concomitant Crohn's Disease-Related Surgeries None reported
10) Concomitant Steroids None reported
11) Concomitant Medications Preferred Term Start Date End Date Reason Route RABBIT VACCINIA EXTRACT - - CROHN'S ORAL DISEASE TROPHICARD - - CROHN'S ORAL DISEASE BIFIDOBACTERIUM NOS - - CROHN'S ORAL DISEASE DULOXETINE HYDROCHLORIDE - - CROHN'S ORAL DISEASE
11 7 㸦34㸧 ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
Preferred Term Start Date End Date Reason Route EPERISONE HYDROCHLORIDE - - CROHN'S ORAL DISEASE FERROUS SODIUM CITRATE - - CROHN'S ORAL DISEASE FLUNITRAZEPAM - - CROHN'S ORAL DISEASE GABAPENTIN - - CROHN'S ORAL DISEASE LIMAPROST ALFADEX - - CROHN'S ORAL DISEASE LOXOPROFEN SODIUM - 2014-01- CROHN'S ORAL 27 DISEASE MECOBALAMIN - - CROHN'S ORAL DISEASE MESALAZINE - - CROHN'S ORAL DISEASE KETOPROFEN - - CROHN'S TRANSDERMAL DISEASE REBAMIPIDE - 2014-01- CROHN'S ORAL 27 DISEASE TOCOPHEROL - - CROHN'S ORAL DISEASE ZOLPIDEM TARTRATE - - CROHN'S ORAL DISEASE FAMOTIDINE 2013-06- 2014-01- CROHN'S ORAL 25 20 DISEASE HEPARIN SODIUM 2013-08- 2013-08- ADVERSE EVENT INTRAVENOUS 09 09 PETHIDINE HYDROCHLORIDE 2013-08- 2013-08- ADVERSE EVENT INTRAVENOUS 09 09 POVIDONE-IODINE 2013-08- 2013-08- ADVERSE EVENT TOPICAL 09 09 DEXTROSE AND SODIUM CHLORIDE INJECTION 2013-08- 2013-08- ADVERSE EVENT INTRAVENOUS 09 11 BLOOD SUBSTITUTES AND PERFUSION SOLUTIONS 2013-08- 2013-08- ADVERSE EVENT INTRAVENOUS 09 09 LIDOCAINE HYDROCHLORIDE 2013-08- 2013-08- ADVERSE EVENT INTRAVENOUS 09 09 NEOLAMIN 3B /00520001/ 2013-08- 2013-08- ADVERSE EVENT INTRAVENOUS 10 11 ALBUMIN HUMAN 2013-08- 2013-08- ADVERSE EVENT INTRAVENOUS 10 11 OSMOSAL /00501801/ 2013-08- 2013-08- ADVERSE EVENT INTRAVENOUS 10 11 GLYCINE MAX SEED OIL 2013-08- 2013-08- ADVERSE EVENT INTRAVENOUS 11 16 SOLUTIONS FOR PARENTERAL NUTRITION 2013-08- 2013-08- ADVERSE EVENT INTRAVENOUS 12 15 HYDROXYZINE EMBONATE 2013-08- 2013-08- ADVERSE EVENT INTRAMUSCULAR 13 14 AMINO ACIDS NOS W/COPPER/ELECTROLYTES 2013-08- 2013-08- ADVERSE EVENT INTRAVENOUS NOS/GLU 14 14 AMINO ACIDS NOS W/COPPER/ELECTROLYTES 2013-08- 2013-09- ADVERSE EVENT INTRAVENOUS NOS/GLU 16 05 POVIDONE-IODINE 2013-08- 2013-08- ADVERSE EVENT INTRAVENOUS 16 16 HYOSCINE BUTYLBROMIDE 2013-08- 2013-08- ADVERSE EVENT INTRAMUSCULAR 20 20 DIMETICONE 2013-08- 2013-08- ADVERSE EVENT ORAL 20 20 MIDAZOLAM 2013-08- 2013-08- ADVERSE EVENT INTRAVENOUS 20 20 COLYTE /00751601/ 2013-08- 2013-08- ADVERSE EVENT ORAL 20 20
11 8 㸦35㸧 ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
Preferred Term Start Date End Date Reason Route PETHIDINE HYDROCHLORIDE 2013-08- 2013-08- ADVERSE EVENT INTRAVENOUS 20 20 LIDOCAINE HYDROCHLORIDE 2013-08- 2013-08- ADVERSE EVENT TOPICAL 20 20 HYDROXYZINE EMBONATE 2013-08- 2013-08- ADVERSE EVENT INTRAMUSCULAR 22 22 POVIDONE-IODINE 2013-08- 2013-08- ADVERSE EVENT INTRAVENOUS 23 23 INTRALIPID /00272201/ 2013-08- 2013-08- ADVERSE EVENT INTRAVENOUS 27 29 CEFEPIME HYDROCHLORIDE 2013-08- 2013-09- ADVERSE EVENT INTRAVENOUS 29 02 FLURBIPROFEN AXETIL 2013-08- 2013-08- ADVERSE EVENT INTRAVENOUS 29 29 HYDROXYZINE EMBONATE 2013-08- 2013-08- ADVERSE EVENT INTRAMUSCULAR 29 30 SODIUM CHLORIDE 2013-08- 2013-09- ADVERSE EVENT INTRAVENOUS 29 07 SODIUM CHLORIDE 2013-08- 2013-09- ADVERSE EVENT INTRAVENOUS 29 02 DEXTROSE AND SODIUM CHLORIDE INJECTION 2013-08- 2013-08- ADVERSE EVENT INTRAVENOUS 29 30 METAMIZOLE SODIUM 2013-08- 2013-08- ADVERSE EVENT INTRAVENOUS 29 29 VANCOMYCIN HYDROCHLORIDE 2013-08- 2013-09- ADVERSE EVENT INTRAVENOUS 29 02 CEFAZOLIN SODIUM 2013-09- 2013-09- ADVERSE EVENT INTRAVENOUS 03 07 HYDROXYZINE EMBONATE 2013-09- 2013-09- ADVERSE EVENT INTRAMUSCULAR 04 04 AMINO ACIDS NOS W/ELECTROLYTES 2013-09- 2013-09- ADVERSE EVENT INTRAVENOUS NOS/GLUCOSE/TH 06 11 NUTRIENTS NOS 2013-09- 2013-09- ADVERSE EVENT ORAL 07 08 NUTRIENTS NOS 2013-09- 2013-09- ADVERSE EVENT ORAL 09 12 OSMOSAL /00501801/ 2013-09- 2013-09- ADVERSE EVENT INTRAVENOUS 12 12 ASCORBIC ACID W/BIOTIN/CALCIUM CARB/07421001/ 2013-09- 2013-09- ADVERSE EVENT ORAL 13 14 NUTRIENTS NOS 2013-09- 2013-09- ADVERSE EVENT ORAL 15 30 DIMETICONE 2013-09- 2013-09- ADVERSE EVENT ORAL 27 27 MIDAZOLAM 2013-09- 2013-09- ADVERSE EVENT INTRAVENOUS 27 27 COLYTE /00751601/ 2013-09- 2013-09- ADVERSE EVENT ORAL 27 27 PETHIDINE HYDROCHLORIDE 2013-09- 2013-09- ADVERSE EVENT INTRAVENOUS 27 27 PRONASE 2013-09- 2013-09- ADVERSE EVENT INTRAVENOUS 27 27 DEXTROSE AND SODIUM CHLORIDE INJECTION 2013-09- 2013-09- ADVERSE EVENT INTRAVENOUS 27 27 LIDOCAINE HYDROCHLORIDE 2013-09- 2013-09- ADVERSE EVENT TOPICAL 27 27 LIDOCAINE HYDROCHLORIDE 2013-09- 2013-09- ADVERSE EVENT TOPICAL 27 27 HYDROXYZINE EMBONATE 2013-09- 2013-09- ADVERSE EVENT INTRAMUSCULAR 28 30 NEOLAMIN 3B /00520001/ 2013-09- 2013-10- ADVERSE EVENT INTRAVENOUS 28 01 OSMOSAL /00501801/ 2013-09- 2013-10- ADVERSE EVENT INTRAVENOUS 28 01
11 9 㸦36㸧 ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
Preferred Term Start Date End Date Reason Route NUTRIENTS NOS 2013-10- 2013-10- ADVERSE EVENT ORAL 01 01 NUTRIENTS NOS 2013-10- 2013-10- ADVERSE EVENT ORAL 02 02 NUTRIENTS NOS 2013-10- 2013-10- ADVERSE EVENT ORAL 03 06 SODIUM CHLORIDE 2013-10- 2013-10- ADVERSE EVENT INTRAVENOUS 03 04
12) Narrative Text ⿕㦂⪅ࡣ 4 ṓࡢ᪥ᮏே⏨ᛶ࡛㸪2013 ᖺ 8 ᭶ 7 ᪥ᐶゎᑟධ⒪ἲࡋ࡚ᮏ㸦㹼6 mg/kg ⩌㸧ࢆ 㟼⬦ෆᢞࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪✸Ꮝᛶ⭡⭷⅖㸪 ᅇ⭠✸Ꮝ㸪ᅇ┣㒊ษ㝖㸦2003 ᖺ㸧㸪ᅇ⭠⭤⬔⒦ࡼࡿᅇ⭠ษ㝖ཬࡧ⒦㛢㙐㸦2000 ᖺ㸧㸪᰾ᡭ ⾡㸦2003 ᖺ㸧࡛࠶ࡗࡓࠋ⿕㦂⪅ࡣႚ↮⪅࡛࠶ࡗࡓࠋ SAE㸸ࢡ࣮ࣟࣥ㸦Day 3㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2013 ᖺ 8 ᭶ 9 ᪥⾑౽ࡢࡓࡵ㸪ᩆᛴᦙ㏦ࡉࢀ㸪ࢡ࣮ࣟࣥᝏࡢ ࡓࡵ㸪ධ㝔ࡋࡓࠋྠ᪥ࡑࡢᚋ㸪⿕㦂⪅ࡣ㢌③㸪ᾋືᛶࡵࡲ࠸ཬࡧᝏᚰࢆッ࠼ࡓࠋ⌮Ꮫⓗ᳨ᰝ࡛ࡣ㸪 ⭠㞧㡢ࡢቑຍ௨እ㸪᫂ࡽ࡞ᡤぢࡣ࡞ࡗࡓࠋྠ᪥ࡢୗ㒊ᾘჾෆど㙾᳨ᰝ࡛ࡣ㸪ᑠࡉ࠸⎔≧ࡢ ₽⒆ཬࡧ⫠㛛₽⒆ࡢ㐍ᒎࡀㄆࡵࡽࢀࡓࠋ㢌㒊ཬࡧ⬚㒊ࢥࣥࣆ࣮ࣗࢱ᩿ᒙᙳ㸦CT㸧ࢫ࢟ࣕࣥ ࡛ࡣ㸪⬻ࡢᒁᡤኚཬࡧ᪂つࡢ⫵ኚࡣ࡞ࡗࡓࠋ⭡㒊 CT ࢫ࡛࢟ࣕࣥࡣ㍍ᗘࡢᑠ⭠ቨ⫧ཌ㸪୪ ࡧ࿀ྜ㒊➃ࡢᑠ⭠㸪ୖ⾜⤖⭠ཬࡧ S ≧⤖⭠㍍ᗘࡢ⫧ཌཬࡧᣑᙇࡀㄆࡵࡽࢀࡓࠋ 2013 ᖺ 8 ᭶ 10 ᪥ᗘᐇࡋࡓ⭡㒊 CT ᳨ᰝ࡛ࡣ㸪ᅇ┣ษ㝖㒊࿘㎶ࡢ⭠⟶ᾋ⭘ᛶࡢ⫧ཌ ࡀㄆࡵࡽࢀ㸪ࡇࢀࡣࢡ࣮ࣟࣥࡼࡿάືᮇࡢ⅖㉳ᅉࡍࡿ⪃࠼ࡽࢀࡓࠋୖ⾜⤖⭠ࡢᣑᙇࡣ㸪 ๓ᅇࡢ CT ࢫ࢟ࣕࣥ⤖ᯝẚ㍑ࡋ࡚ᨵၿࡋ࡚࠸ࡓࠋ2013 ᖺ 8 ᭶ 20 ᪥ࡢୗ㒊ᾘჾෆど㙾᳨ᰝ ࡛ࡣ㸪ᑠ⭠ഃࡢ࿀ྜ㒊➃ཬࡧ S ≧⤖⭠ࡽ┤⭠㸦⫠㛛⦕ࡽ 15 cm㸧ࡲ࡛ࡢ㒊㸪ࡧࡽࢇ㸪ὸ ࠸₽⒆ཬࡧ⮋ᛶศἪ≀ࡀᩓᅾᛶㄆࡵࡽࢀࡓࠋ2013 ᖺ 9 ᭶ 27 ᪥ࡢᾘჾෆど㙾᳨ᰝ࡛ࡣ㸪ୖ 㒊ᾘ⟶␗ᖖᡤぢࡣ࡞ࡗࡓࡀ㸪ୗ㒊ᾘჾෆど㙾᳨ᰝ࡛ࡣ㸪⭠࿀ྜ㒊ὸ࠸₽⒆ཬࡧ⮋ ᛶศἪ≀ࡀㄆࡵࡽࢀࡓࠋ≧ែࡣࡸࡸᨵၿࡋࡓࡀ㸪S ≧⤖⭠ࡢࡧࡽࢇཬࡧὸ࠸₽⒆ࡣᣢ⥆ࡋࡓࠋ 2013 ᖺ 9 ᭶ 28 ᪥ࡢ⭡㒊 CT ࢫ࡛࢟ࣕࣥࡣ㸪ᅇ┣ษ㝖㒊࿘㎶ࡢ⭠⟶ᾋ⭘ᛶࡢ⫧ཌࡀࡳࡽࢀ㸪 ࢡ࣮ࣟࣥࡢᝏ㸪㦵┙ෆࡢᑠ⭠ᣑᙇࡢ㍍ᗘᝏཬࡧ⭡Ỉ㔞ࡢቑຍ㉳ᅉࡍࡿ⪃࠼ࡽࢀࡓࠋ 2013 ᖺ 8 ᭶ 9 ᪥ࡽ 2013 ᖺ 10 ᭶ 30 ᪥ࡲ࡛ࡢ⮫ᗋ᳨ᰝ್ࡣ௨ୗࡢኚືࡀㄆࡵࡽࢀࡓ㸸ࣛ ࢽ࣑ࣥࣀࢺࣛࣥࢫࣇ࢙࣮ࣛࢮ 49-76 IU/L㹙ṇᖖ⠊ᅖ㸦NR㸧4-44 IU/L㹛㸪Ȗ-ࢢࣝࢱ࣑ࣝࢺࣛࣥࢫ ࣇ࢙࣮ࣛࢮ 115-475 IU/L㸦NR 16-73 IU/L㸧㸪࣐࣊ࢺࢡࣜࢵࢺ 29.8%-37%㸦NR 40%-55%㸧㸪࣊ࣔ ࢢࣟࣅࣥ 8.4-11.3 g/dL㸦NR 14-18 g/dL㸧㸪㉥⾑⌫ᩘ 270-391×104/mcL㸦NR 400-570×104/mcL㸧㸪 ⥲ࡓࢇⓑ 3.6-5.8 g/dL㸦NR 6-8 g/dL㸧㸪ⓑ⾑⌫ᩘ 27-80×102/mcL㸦NR 40-90×102/mcL㸧ࠋ ⿕㦂⪅ࡣ㸪2013 ᖺ 10 ᭶ 17 ᪥ࢡ࣮ࣟࣥࡢᝏࡽᅇࡋ㸪ྠ᪥㏥㝔ࡋࡓࠋ
(3) CNTO1275CRD3002-3314-20944
1) Reason for narrative selection SAE Event of interest: Serious infection
12 0 㸦37㸧 ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
2) Adverse Events Start date End date (Study Preferred Term Intensity/ Inf/ Action Taken/ (Study day) (Verbatim Term) SAE Relatedness Trt? Outcome day) 2014-05- ㈋⾑ N MODERATE/ N/ DOSE NOT CHANGED/ 2014-07- 22 (ANEMIA) NOT NA RECOVERED/RESOLVED 04 (18) RELATED (61) 2014-05- ୗ⑩ Y MODERATE/ Y/ DOSE NOT CHANGED/ 2014-06- 26 (DIARRHEA) POSSIBLE Y RECOVERED/RESOLVED 05 (22) (32) 2014-06- ᑠ⭠㛢ሰ Y MODERATE/ N/ DOSE NOT CHANGED/ 2014-06- 19 (SMALL BOWEL NOT NA RECOVERED/RESOLVED 20 (46) OBSTRUCTION) RELATED (47) 2014-06- ㈋⾑ Y MODERATE/ N/ DOSE NOT CHANGED/ 2014-06- 20 (WORSENING OF ANEMIA) NOT NA RECOVERED/RESOLVED 21 (47) RELATED (48) 2014-06- ࢡ࣮ࣟࣥ Y SEVERE/ N/ DOSE NOT CHANGED/ 2014-07- 27 (WORSENING OF CROHN'S NOT NA RECOVERED/RESOLVED 04 (54) DISEASE) RELATED (61) 2014-07- 㟼⬦⅖ N MILD/ N/ DOSE NOT CHANGED/ Ongoing 01 (CHEMICALLY-INDUCED NOT NA NOT RECOVERED/NOT - (58) PHLEBITIS) RELATED RESOLVED
3) Baseline Demographic Information Age (years): 3 Sex: Female Weight (kg): 78.0 Race: Not reported Date of birth: Height (cm): 171.0
4) Induction Treatment Group Randomized Treatment Group: Ustekinumab 130 mg IV Actual Treatment Group: Ustekinumab 130 mg IV
5) Induction Treatment Received Visit Start Date Study Day Dose Number Actual Treatment Dose WEEK 0 2014-05-05 1 1 Ustekinumab 130 mg IV 129.6 mg
6) Induction Disposition Did subject complete the induction study?: Y Did subject enter maintenance study?: Y
7) Baseline Crohn's Disease History Date of diagnosis: 31JAN2001 Disease duration: 13.26 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪⫠㛛࿘ᅖ㸪⭠⟶እ≧㸦㛵⠇⅖㸭㛵⠇③㸧
8) Crohn's Disease Complications Before Baseline Intra-abdominal abscess: Never Sinus tracts/perforation: Never Fistula: Currently present Stricture complications of (CD): Currently present
9) Concomitant Crohn's Disease-Related Surgeries None reported
10) Concomitant Steroids None reported
12 1 㸦38㸧 ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
11) Concomitant Medications Start Preferred Term Date End Date Reason Route NORMENSAL 2012-07 - OTHER (ORAL CONTRACEPTIVE) ORAL SOLUTIONS FOR PARENTERAL 2014-03 2014-04- CROHN'S DISEASE NASOGASTRIC NUTRITION 18 ULTRACET 2014-03 2014-05- CROHN'S DISEASE ORAL 30 ENOXAPARIN SODIUM 2014-03 2014-04- OTHER (PROPHYLAXY) SUBCUTANEOUS 21 DESLORATADINE 2014-04- 2014-04- OTHER (PREVENTION BEFORE MRI ORAL 15 17 EXAM) HYDROXYZINE 2014-04- 2014-04- OTHER (PREVENTION BEFORE MRI ORAL 16 17 EXAM) LOPERAMIDE HYDROCHLORIDE 2014-04- 2014-04- CROHN'S DISEASE ORAL 17 22 LOPERAMIDE HYDROCHLORIDE 2014-04- 2014-04- CROHN'S DISEASE ORAL 24 28 LOPERAMIDE HYDROCHLORIDE 2014-05- 2014-05- CROHN'S DISEASE ORAL 08 08 ALPRAZOLAM 2014-05- 2014-05- OTHER (ANXIETY (MEDICAL ORAL 13 31 HISTORY)) PAROXETINE HYDROCHLORIDE 2014-05- 2014-05- OTHER (ANXIETY (MEDICAL ORAL 27 31 HISTORY)) CEFTRIAXONE 2014-05- 2014-06- ADVERSE EVENT INTRAVENOUS 31 04 ORNIDAZOLE 2014-05- 2014-06- ADVERSE EVENT INTRAVENOUS 31 04 PARACETAMOL 2014-05- 2014-06- ADVERSE EVENT INTRAVENOUS 31 03 SPASFON /00765801/ 2014-05- 2014-06- ADVERSE EVENT ORAL 31 03 TRAMADOL HYDROCHLORIDE 2014-05- 2014-06- ADVERSE EVENT INTRAVENOUS 31 03 METRONIDAZOLE 2014-06- 2014-06- ADVERSE EVENT INTRAVENOUS 04 05 ENOXAPARIN SODIUM 2014-06- 2014-06- OTHER (VEINOUS THROMBOLIS SUBCUTANEOUS 04 04 PROPHYLAXY) CIPROFLOXACIN 2014-06- 2014-06- ADVERSE EVENT ORAL 05 08 METRONIDAZOLE 2014-06- 2014-06- ADVERSE EVENT ORAL 05 08 PARACETAMOL 2014-06- 2014-06- CROHN'S DISEASE ORAL 12 12 ULTRACET 2014-06- 2014-06- CROHN'S DISEASE ORAL 13 18 PARACETAMOL 2014-06- 2014-06- CROHN'S DISEASE ORAL 15 18 ENOXAPARIN SODIUM 2014-06- 2014-06- OTHER (VEINOUS THROMBOSIS SUBCUTANEOUS 19 23 PROPHYLAXY) PARACETAMOL 2014-06- 2014-06- ADVERSE EVENT ORAL 19 20 TRAMADOL HYDROCHLORIDE 2014-06- 2014-06- ADVERSE EVENT ORAL 19 19 RED BLOOD CELLS 2014-06- 2014-06- ADVERSE EVENT INTRAVENOUS 20 20 PARACETAMOL 2014-06- 2014-06- ADVERSE EVENT ORAL 21 22 HYDROXYZINE 2014-06- 2014-06- OTHER (MADICAL HISTORY ORAL 23 23 (ANXIETY)) ULTRACET 2014-06- 2014-06- CROHN'S DISEASE ORAL 26 26 NEFOPAM HYDROCHLORIDE 2014-06- 2014-07- ADVERSE EVENT ORAL 27 02
12 2 㸦39㸧 ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
Start Preferred Term Date End Date Reason Route PARACETAMOL 2014-06- 2014-06- ADVERSE EVENT ORAL 27 27 PANTOPRAZOLE SODIUM 2014-06- 2014-07- ADVERSE EVENT ORAL SESQUIHYDRATE 27 03 ENOXAPARIN SODIUM 2014-06- 2014-07- OTHER (VEINOUS THROMBOSIS SUBCUTANEOUS 27 03 PROPHYLAXY) PARACETAMOL 2014-06- 2014-07- ADVERSE EVENT ORAL 27 01 CEFTRIAXONE SODIUM 2014-06- 2014-07- ADVERSE EVENT INTRAVENOUS 27 01 SPASFON /00765801/ 2014-06- 2014-06- ADVERSE EVENT ORAL 27 28 ORNIDAZOLE 2014-06- 2014-07- ADVERSE EVENT INTRAVENOUS 27 01 PERIKABIVEN 2014-06- 2014-06- ADVERSE EVENT INTRAVENOUS 28 30 PARACETAMOL 2014-07- 2014-07- ADVERSE EVENT ORAL 03 03
12) Narrative Text ⿕㦂⪅ࡣ 3 ṓዪᛶ㸦ே✀᫂㸧࡛㸪2014 ᖺ 5 ᭶ 5 ᪥ᐶゎᑟධ⒪ἲࡋ࡚ᮏ㸦130 mg ⩌㸧 ࢆ㟼⬦ෆᢞࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪ᆶษ㝖 㸦2000 ᖺ㸧㸪⮋⒆ࢻࣞࢼ࣮ࢪ㸦2008 ᖺ㸧㸪ᕥ⤖⭠㒊ศษ㝖⾡㸦2008 ᖺ㸧㸪୍ⓗྑ⤖⭠⒦㐀タ ⾡㸦2009 ᖺ㸧㸪୪ࡧ」ᩘᅇࡢ⭠ෆど㙾ཬࡧෆど㙾᳨ᰝ࡛࠶ࡗࡓࠋࡲࡓ㸪⫠㛛࿘ᅖ⮋⒆ཬࡧ ⒦ࡢ」ᩘᅇࡢⓎ୪ࡧ⤖⭠⊃✽㸪᭦㸪ከⓎᛶ㛵⠇③㸪ᕥ⭸③ᾐ₶㸦gonalgia infiltration㸧㸪 Ⓞ㸪⤖⠇ᛶ⣚ᩬཬࡧᏳࡢ᪤ ࡶ࠶ࡗࡓࠋ௨ୗࡢ⸆ᑐࡍࡿ㐣ᩄཪࡣࣞࣝࢠ࣮ࡀ࠶ࡗࡓ㸸 㔜ࢡ࣒ࣟ㓟࣒࢝ࣜ࢘㸪ሷࢥࣂࣝࢺ㸪◲㓟ࢽࢵࢣࣝ㸪ࢭࢫ࢟ࢸࣝ࣌ࣥ ࣛࢡࢺࣥ㸪ࣥࣇࣜ࢟ࢩ ࣐ࣈ㸪ࢲ࣒࣐ࣜࣈ㸪certolizumab pegolࠋࢡ࣮ࣟࣥࡢᐙ᪘Ṕ㸦࠸ࡇཬࡧུẕ㸧ཬࡧႚ↮Ṕࡀ ࠶ࡗࡓ㸦1 ᖺ௨ୖ๓⚗↮㸧ࠋ SAE/Serious infection㸸ୗ⑩㸦Day 22㸧 CIOMS ࡼࡿ㸪2014 ᖺ 5 ᭶ 23 ᪥ᬑẁࡣ␗࡞ࡿ㣗㸦ࢣࣂࣈ㸧ࢆࡋࡓᚋ㸪୰➼ᗘࡽ 㧗ᗘࡢ⭡③ࢆక࠺ 1 ᪥ 14㹼16 ᅇࡢୗ⑩ࢆⓎ⌧ࡋࡓࠋ2014 ᖺ 5 ᭶ 26 ᪥ࡣୗ⑩㸪ྤཬࡧ⾑౽ࡀ Ⓨ⌧ࡋࡓࠋ⿕㦂⪅ࡣ 2014 ᖺ 5 ᭶ 31 ᪥ධ㝔ࡋࡓࡀ㸪Ⓨ⇕ࡣ࡞ࡃ㸪⾑ᅽࡶᏳᐃࡋ࡚࠸ࡓࠋ2014 ᖺ 5 ᭶ 31 ᪥ࡢࢡࣟࢫࢺࣜࢪ࣒࣭࢘ࢹࣇࢩࣞẘ⣲᳨ᰝ࡛ࡣ㸪⿕㦂⪅ࡣࢡࣟࢫࢺࣜࢪ࣒࣭࢘ࢹࣇ ࢩࣞࡢ㠀ẘ⣲ཎᛶᰴࡢಖ⳦⪅࡛࠶ࡗࡓࡀ㸪ࢡࣟࢫࢺࣜࢪ࣒࣭࢘ࢹࣇࢩࣞឤᰁࡣ࡞ࡗࡓࠋ ྠ᪥㸦2014 ᖺ 5 ᭶ 31 ᪥㸧ࡢ⮫ᗋ᳨ᰝ࡛ࡣ㸪௨ୗࡢ㡯┠␗ᖖ್ࡀㄆࡵࡽࢀ㸪ࡇࢀࡽࡢ⤖ᯝࡼ ࡾ㸪⅖ᛶೃ⩌ࡀ♧၀ࡉࢀࡓ㸸C ᛂᛶࡓࢇⓑ㸦CRP㸧⃰ᗘ 89.9 mg/L㹙ṇᖖ⠊ᅖ㸦NR㸧 <1.0㹛㸪࣊ࣔࢢࣟࣅࣥ 9.5 g/dL㸦NR 12-15.4 g/dL㸧㸪⾑ᑠᯈᩘ 479×109/L㸦NR 150-400×109/L㸧ࠋ 2014 ᖺ 6 ᭶ 4 ᪥ࡢ౽᳨ᰝ࡛ࡣ㸪ẘ⣲ཎᛶࢡࣟࢫࢺࣜࢪ࣒࣭࢘ࢹࣇࢩࣞࡣ᳨ฟࡉࢀࡎ㸪ࢧࣝࣔ ࢿࣛ㸪㉥⑩⳦㸪࢝ࣥࣆࣟࣂࢡࢱ࣮ཬࡧ Yersinia enterocolitica ࡢ࠸ࡎࢀࡶ㝜ᛶ࡛࠶ࡗࡓࠋࢭࣇࢺࣜ ࢟ࢯࣥ㸪ornidazole㸪࣓ࢺࣟࢽࢲࢰ࣮ࣝ㸪ࢩࣉࣟࣇࣟ࢟ࢧࢩࣥཬࡧ phloroglucinol ࡼࡿ⒪ࢆ ⾜ࡗࡓࠋ⿕㦂⪅ࡣᢠ⏕≀㉁ࡢᢞࡢࡳ࡛ᨵၿࡋࡓࡓࡵ㸪ࢡ࣮ࣟࣥࡢⓎస㉳ᅉࡍࡿࡢ࡛ࡣ࡞ࡃ㸪 㣗୰ẘࡀࢃࢀࡓࠋ⿕㦂⪅ࡣ 2014 ᖺ 6 ᭶ 5 ᪥ୗ⑩ࡽᅇࡋ㸪ྠ᪥㏥㝔ࡋࡓࠋ
12 3 㸦40㸧 ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
SAE㸸ᑠ⭠㛢ሰ㸦Day 46㸧㸪㈋⾑㸦Day 47㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2014 ᖺ 6 ᭶ 19 ᪥㸪ྤཬࡧ⭡③ࡢࡓࡵධ㝔ࡋࡓࠋ⏬ീ᳨ᰝ࡛ ࡣ㸪ᅇ⭠ᣑᙇࢆక࠺ᑠ⭠㛢ሰࡀㄆࡵࡽࢀࡓࠋྠ᪥ࡢ⮫ᗋ᳨ᰝ್ࡣ㸪CRP 69.5 mg/L㸦NR<1.0㸧ཬ ࡧ࣊ࣔࢢࣟࣅࣥ 8.7 g/dL㸦NR 12-15.4 g/dL㸧࡛࠶ࡗࡓࠋ⿕㦂⪅ࡣ 2014 ᖺ 6 ᭶ 20 ᪥ᑠ⭠㛢ሰ ࡽᅇࡋࡓࡀ㸪㈋⾑ࡣᝏࡋ㸪ධ㝔ᮇ㛫ࡀᘏ㛗ࡉࢀࡓࠋྠ᪥ࡢ⮫ᗋ᳨ᰝ್ࡣῶᑡࡋࡓ㸸࣊ࣔࢢࣟ ࣅࣥ 7.3 g/dL㸦NR 12-15.4 g/dL㸧㸪࣐࣊ࢺࢡࣜࢵࢺ 24.8%㸦NR 37%-46%㸧㸪ᖹᆒ㉥⾑⌫࣊ࣔࢢࣟ ࣅࣥ㸦MCH㸧24.9 pg㸦NR 28-33 pg㸧㸪ᖹᆒ㉥⾑⌫࣊ࣔࢢࣟࣅࣥ⃰ᗘ㸦MCHC㸧29.4 g/dL㸦NR 32-36 g/dL㸧㸪⾑Ύ㕲 14 μg/100 mL㸦NR 60-180 μg/100 mL㸧㸪ࢺࣛࣥࢫࣇ࢙ࣜࣥ 1.74 g/L㸦NR 2.00-3.60 g/L㸧㸪CRP 50.8 mg/L㸦NR<1.0㸧㸪⥲㕲⤖ྜ⬟ 243 μg/100 mL㸦NR 279-502 μg/100 mL㸧㸪 ࢺࣛࣥࢫࣇ࢙ࣜࣥ㣬ᗘ 6%㸦NR 25%-35%㸧ཬࡧ㉥⾑⌫ᩘ 2.93×1012/L㸦NR 3.8-5.4×1012/L㸧ࠋ 㦂ᢸᙜ་ᖌࡣ㸪㈋⾑ࡢཎᅉࡋ࡚᪤Ꮡࡢࢡ࣮ࣟࣥࡀࢃࢀࡿุ᩿ࡋࡓࠋ⿕㦂⪅ࡣ㉥⾑⌫ 2 ༢ ࢆ㍺⾑ࡉࢀ㸪࣊ࣔࢢࣟࣅࣥࡣ 10.5 g/dL ᅇࡋ㸪Ᏻᐃࡋࡓࠋ㈋⾑ࡣ 2014 ᖺ 6 ᭶ 21 ᪥ᾘᩓࡋ ࡓࡀ㸪⿕㦂⪅ࡣᘬࡁ⥆ࡁ⤒㐣ほᐹࡀ⾜ࢃࢀࡓࠋ2014 ᖺ 6 ᭶ 23 ᪥ࡢࣇࣂ࣮ࢫࢥ࣮ࣉࢆ⏝࠸ࡓ ┤⭠ S ≧⤖⭠㙾᳨ᰝ㸦rectosigmoidoscopy㸧࡛ࡣ㸪⫠㛛⦕ࡢ 5 ࡢ᪉ྥ៏ᛶࡢ⫠ࡀ☜ㄆࡉࢀ㸪 ⒦Ꮝእཱྀ㒊㸦fistula orifice㸧ࡢ㛵㐃ࡀࢃࢀࡓࠋࡲࡓ㸪⫠㛛⟶⢓⭷ࡣⴭ᫂࡞⅖ࡀㄆࡵࡽࢀ㸪 ᫆ฟ⾑ᛶ࡛࠶ࡾ㸪⮬↛ฟ⾑ࢆకࡗࡓࠋṧ␃౽ࡣ⾑౽࡛ࡣ࡞ࡃ㸪⢓ᾮࡣṇᖖ࡛࠶ࡗࡓࠋ⿕㦂⪅ࡣ 2014 ᖺ 6 ᭶ 24 ᪥㏥㝔ࡋࡓࠋ SAE㸸ࢡ࣮ࣟࣥ㸦Day 54㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2014 ᖺ 6 ᭶ 27 ᪥㸪⭡③㸪ୗ⑩ཬࡧᚰ❐㒊③ࡀⓎ⌧ࡋ㸪ࢡ࣮ࣟ ࣥࡢᝏࡀࢃࢀࡓࡓࡵ㸪ྠ᪥ධ㝔ࡋࡓࠋ⿕㦂⪅ࡢ౽ᅇᩘࡣቑຍࡋ㸪1 ᪥ 5㹼10 ᅇ࡛࠶ࡗࡓࠋ ⮫ᗋ᳨ᰝ࡛㛢ሰࡣ㝖እࡉࢀࡓࠋ⮫ᗋ᳨ᰝ್ࡣ௨ୗࡢ࠾ࡾ࡛࠶ࡗࡓ㸸CRP 39 mg/L㸦NR <1.0㸧㸪 ࣊ࣔࢢࣟࣅࣥ 10.5 g/dL㸦NR 12-15.4 g/dL㸧ཬࡧⓑ⾑⌫ᩘ 3500/mm3㸦NR ᫂㸧ࠋධ㝔୰ࡢ⾑ᾮཬ ࡧᒀᇵ㣴㸪୪ࡧᒀ᳨ᰝࡢ⤖ᯝ␗ᖖࡣㄆࡵࡽࢀ࡞ࡗࡓࠋ⿕㦂⪅ࡣ㸪2014 ᖺ 7 ᭶ 4 ᪥ࢡ࣮ࣟ ࣥࡢᝏࡽᅇࡋ㸪㏻ᖖ㣗ᡠࡗࡓࠋྠ᪥㏥㝔ࡋࡓࠋ
(4) CNTO1275CRD3002-4002-20328
1) Reason for narrative selection SAE Event of interest: Serious infection
2) Adverse Events Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day) (Verbatim Term) SAE Relatedness Trt? Outcome (Study day) 2013-03-12 ⫠㛛⮋⒆ Y MODERATE/ Y/ DOSE NOT CHANGED/ 2013-03-14 (28) (PERI-ANAL ABSCESS) POSSIBLE N RECOVERED/RESOLVED (30)
3) Baseline Demographic Information Age (years): 4 Sex: Male Weight (kg): 75.0 Race: White Date of birth: Height (cm): 175.0
4) Induction Treatment Group Randomized Treatment Group: Ustekinumab 130 mg IV Actual Treatment Group: Ustekinumab 130 mg IV
12 4 㸦41㸧 ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
5) Induction Treatment Received Visit Start Date Study Day Dose Number Actual Treatment Dose WEEK 0 2013-02-13 1 1 Ustekinumab 130 mg IV 129.6 mg
6) Induction Disposition Did subject complete the induction study?: Y Did subject enter maintenance study?: Y
7) Baseline Crohn's Disease History Date of diagnosis: 31DEC1997 Disease duration: 15.12 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪⫠㛛࿘ᅖ
8) Crohn's Disease Complications Before Baseline Intra-abdominal abscess: Never Sinus tracts/perforation: Never Fistula: Currently present Stricture complications of (CD): Never
9) Concomitant Crohn's Disease-Related Surgeries Surgery Date Result of lack of efficacy? ࢻࣞࢼ࣮ࢪ-⤒⓶ษ㛤ཬࡧࢻࣞࢼ࣮ࢪ 2013-03-13 N
10) Concomitant Steroids None reported
11) Concomitant Medications Preferred Term Start Date End Date Reason Route MESALAZINE 2012-11 2013-08-19 CROHN'S DISEASE ORAL
12) Narrative Text ⿕㦂⪅ࡣ 4 ṓࡢⓑே⏨ᛶ࡛㸪2013 ᖺ 2 ᭶ 13 ᪥ᐶゎᑟධ⒪ἲࡋ࡚ᮏ㸦130 mg ⩌㸧ࢆ㟼 ⬦ෆᢞࡉࢀࡓࠋ CIOMS ࡼࡿ㸪⿕㦂⪅ࡣႚ↮⪅࡛࠶ࡗࡓࠋ SAE/Serious infection㸸⫠㛛⮋⒆㸦Day 28㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2013 ᖺ 3 ᭶ 12 ᪥⫠㛛ࡢ⑊③ཬࡧ⭘⬽㸪୪ࡧ⒦Ꮝ㛤ཱྀ㒊ࡽ ࡢศἪ≀ࢆッ࠼㸪ᩆᛴᦙ㏦ࡉࢀࡓࠋデᐹ࡛⫠㛛࿘ᅖ⮋⒆㸪㒊ศⓗࢻࣞࢼ࣮ࢪ㸪ᒁᡤ◳⤖㸪ᅽ③ཬ ࡧ⫠㛛ࡢ 2 ࡢ᪉ྥᾮฟࢆక࠺⒦Ꮝࡀ☜ㄆࡉࢀࡓࠋ⭡㒊ࡣᰂࡽࡃ㸪ᅽ③ࡣ࡞ࡗࡓࠋ⿕㦂 ⪅ࡣྠ᪥ධ㝔ࡋࡓࠋ⮫ᗋ᳨ᰝ್ࡣ㸪ⓑ⾑⌫ᩘ 14.4 k/μL㹙ṇᖖ⠊ᅖ㸦NR㸧4.50-11.00 k/μL㹛㸪ዲ୰ ⌫ 79.4%㸦NR 40.0%-74.0%㸧࡛࠶ࡗࡓࠋ ⿕㦂⪅ࡣ㸪2013 ᖺ 3 ᭶ 13 ᪥㌟㯞㓉ୗ࡛⮋⒆ࡢษ㛤ᡭ⾡ࢆཷࡅࡓࠋ⫠㛛࿘ᅖ⮋⒆ࡣ௨๓ ࡽ࠶ࡿ⒦Ꮝ㞄᥋ࡋ㸪1 ࡽ 2 ࡢ᪉ྥ⨨ࡋ࡚࠸ࡓࠋ⾡ᚋࡢᝈ⪅ࡢ≧ែࡣᏳᐃࡋ࡚࠾ࡾ㸪 Ⓨ⇕ཬࡧᡭ⾡ࡽࡢฟ⾑ࡶ࡞ࡗࡓࠋ2013 ᖺ 3 ᭶ 14 ᪥⫠㛛⮋⒆ࡣᾘᩓࡋࡓሗ࿌ࡉࢀ㸪ྠ ᪥⿕㦂⪅ࡣ㏥㝔ࡋࡓࠋ
12 5 㸦42㸧 ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
(5) CNTO1275CRD3002-2212-20633
1) Reason for narrative selection SAE Discontinuation of study agent due to AE Event of interest: Serious infection
2) Adverse Events Start date End date (Study Preferred Term Intensity/ Inf/ Action Taken/ (Study day) (Verbatim Term) SAE Relatedness Trt? Outcome day) 2013-12 እ㝜㒊⭐࢝ࣥࢪࢲ㻌 N MILD/ Y/ NOT APPLICABLE/ 2014-02- - (VAGINAL CANDIDIASIS) POSSIBLE N RECOVERED/RESOLVED 23 (90) 2013-11- ࢡ࣮ࣟࣥ㻌 Y MODERATE/ N/ DRUG WITHDRAWN/ 2013-12- 28 (EXACERBATION OF CROHN'S NOT NA RECOVERED/RESOLVED 12 (3) DISEASE) RELATED (17) 2014-01- ࢡ࣮ࣟࣥ㻌 Y MODERATE/ N/ NOT APPLICABLE/ 2014-02- 09 (CROHN'S ILEITIS (COMPLICATED)) NOT NA RECOVERED/RESOLVED 23 (45) RELATED (90) 2014-03- 㝈ᒁᛶ⭡⭍ෆᾮ㈓␃㻌 Y SEVERE/ Y/ NOT APPLICABLE/ 2014-03- 09 (INTRA-ABDOMINAL FLUID DOUBTFUL Y RECOVERED/RESOLVED 16 (104) COLLECTION) (111)
3) Baseline Demographic Information Age (years): 4 Sex: Female Weight (kg): 66.1 Race: White Date of birth: Height (cm): 160.5
4) Induction Treatment Group Randomized Treatment Group: Ustekinumab 130 mg IV Actual Treatment Group: Ustekinumab 130 mg IV
5) Induction Treatment Received Visit Start Date Study Day Dose Number Actual Treatment Dose WEEK 0 2013-11-26 1 1 Ustekinumab 130 mg IV 129.6 mg
6) Induction Disposition Did subject complete the induction study?: Y Did subject enter maintenance study?: N
7) Baseline Crohn's Disease History Date of diagnosis: 31DEC2000 Disease duration: 12.91 years Involved areas: ᅇ⭠ࡢࡳ㸪⫠㛛࿘ᅖ
8) Crohn's Disease Complications Before Baseline Intra-abdominal abscess: Never Sinus tracts/perforation: Never Fistula: Never Stricture complications of (CD): Previous history
9) Concomitant Crohn's Disease-Related Surgeries Surgery Date Result of lack of efficacy? ษ㝖-ᅇ┣㒊 2014-02-07 N
12 6 㸦43㸧 ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
10) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 0 PREDNISOLONE 20 mg 20 WEEK 3 METHYLPREDNISOLONE 40 mg - WEEK 3 PREDNISOLONE 40 mg 40 WEEK 3 METHYLPREDNISOLONE 0 mg - WEEK 3 PREDNISOLONE 0 mg 0 WEEK 6 PREDNISOLONE 30 mg 30 WEEK 8 PREDNISOLONE 25 mg 25 WEEK 8 METHYLPREDNISOLONE 40 mg - WEEK 8 METHYLPREDNISOLONE 30 mg - WEEK 8 PREDNISOLONE 0 mg 0 SAFETY FOLLOW-UP PREDNISOLONE 25 mg 25 SAFETY FOLLOW-UP PREDNISOLONE 0 mg 0 SAFETY FOLLOW-UP DEXAMETHASONE 0 mg - SAFETY FOLLOW-UP HYDROCORTISONE 0 mg - SAFETY FOLLOW-UP METHYLPREDNISOLONE 0 mg - SAFETY FOLLOW-UP PREDNISOLONE 0 mg 0 SAFETY FOLLOW-UP HYDROCORTISONE 100 mg - SAFETY FOLLOW-UP DEXAMETHASONE 4 mg - SAFETY FOLLOW-UP PREDNISOLONE 40 mg 40 SAFETY FOLLOW-UP PREDNISOLONE 30 mg 30 SAFETY FOLLOW-UP PREDNISOLONE 20 mg 20 SAFETY FOLLOW-UP PREDNISOLONE 15 mg 15 SAFETY FOLLOW-UP PREDNISOLONE 10 mg 10 SAFETY FOLLOW-UP PREDNISOLONE 5 mg 5
11) Concomitant Medications Preferred Term Start Date End Date Reason Route MESALAZINE 2000 2013-11-29 CROHN'S DISEASE ORAL ORAL CONTRACEPTIVE NOS 2003 - OTHER (CONTRACEPTION) ORAL CALCIUM 2013-09 - OTHER (CALCIUM REPLACEMENT) ORAL KENDURAL C 2013-09 2013-11-21 CROHN'S DISEASE ORAL JORIX 2013-09 - OTHER (TREATMENT OF JOINTS) ORAL PREDNISOLONE 2013-09 2013-10-22 CROHN'S DISEASE ORAL RABEPRAZOLE 2013-09 2014-02-06 OTHER (EPIGASTRIC BURNING) ORAL FISH OIL 2013-09 - OTHER (JOINT TREATMENT) ORAL VITAMIN D NOS 2013-09 - OTHER (LOW VITAMIN D PREVENTION) ORAL PREDNISOLONE 2013-10-23 2013-11-29 CROHN'S DISEASE ORAL PARACETAMOL 2013-11-21 - OTHER (ANALGESIA) ORAL MOVICOL /01749801/ 2013-11-23 2013-11-25 OTHER (EXACERBATION TO CD) ORAL OXYCODONE HYDROCHLORIDE 2013-11-28 2013-11-29 ADVERSE EVENT ORAL ONDANSETRON 2013-11-28 2013-11-29 ADVERSE EVENT SUBLINGUAL ENOXAPARIN SODIUM 2013-11-29 2013-12-12 ADVERSE EVENT SUBCUTANEOUS OXYCODONE HYDROCHLORIDE 2013-11-29 2013-12-07 ADVERSE EVENT ORAL METHYLPREDNISOLONE 2013-11-29 2013-12-03 ADVERSE EVENT INTRAVENOUS MORPHINE 2013-11-29 2013-11-29 ADVERSE EVENT INTRAVENOUS CIPROFLOXACIN 2013-11-30 2013-12-04 ADVERSE EVENT INTRAVENOUS MESALAZINE 2013-11-30 - CROHN'S DISEASE ORAL METRONIDAZOLE 2013-11-30 2013-12-04 ADVERSE EVENT INTRAVENOUS MORPHINE 2013-11-30 2013-12-04 ADVERSE EVENT SUBCUTANEOUS CLOTRIMAZOLE 2013-12 2014-01-19 OTHER (CANDIASIS) OTHER PHOSPHATE-SANDOZ 2013-12-02 2013-12-12 ADVERSE EVENT ORAL PREDNISOLONE 2013-12-03 2013-12-18 ADVERSE EVENT ORAL OXYCODONE 2013-12-04 2013-12-05 ADVERSE EVENT ORAL POTASSIUM CHLORIDE 2013-12-05 2013-12-12 ADVERSE EVENT ORAL CIPROFLOXACIN 2013-12-05 2013-12-23 ADVERSE EVENT ORAL
12 7 㸦44㸧 ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
Preferred Term Start Date End Date Reason Route METRONIDAZOLE 2013-12-05 2013-12-23 ADVERSE EVENT ORAL OXYCODONE 2013-12-05 2013-12-06 ADVERSE EVENT ORAL PREDNISOLONE 2013-12-19 2014-01-09 CROHN'S DISEASE ORAL PREDNISOLONE 2014-01-10 2014-01-15 CROHN'S DISEASE ORAL CIPROFLOXACIN 2014-01-16 2014-01-20 ADVERSE EVENT ORAL ENOXAPARIN SODIUM 2014-01-16 2014-03-11 ADVERSE EVENT SUBCUTANEOUS METHYLPREDNISOLONE 2014-01-16 2014-01-16 ADVERSE EVENT INTRAVENOUS METOCLOPRAMIDE 2014-01-16 2014-01-16 CROHN'S DISEASE ORAL METRONIDAZOLE 2014-01-16 2014-01-20 ADVERSE EVENT INTRAVENOUS MORPHINE 2014-01-16 2014-01-16 ADVERSE EVENT INTRAVENOUS ONDANSETRON 2014-01-16 2014-01-16 ADVERSE EVENT SUBLINGUAL OXYCODONE 2014-01-16 2014-02-17 ADVERSE EVENT ORAL METHYLPREDNISOLONE 2014-01-17 2014-01-21 ADVERSE EVENT INTRAVENOUS MOVICOL /01749801/ 2014-01-18 - CROHN'S DISEASE ORAL METRONIDAZOLE 2014-01-20 2014-02-07 ADVERSE EVENT ORAL MORPHINE 2014-01-21 2014-01-22 ADVERSE EVENT SUBCUTANEOUS PREDNISOLONE 2014-01-22 2014-02-07 CROHN'S DISEASE ORAL CIPROFLOXACIN 2014-01-25 2014-02-07 ADVERSE EVENT ORAL CEFAZOLIN SODIUM 2014-02-07 2014-02-07 ADVERSE EVENT INTRAVENOUS DEXAMETHASONE 2014-02-07 2014-02-07 ADVERSE EVENT INTRAVENOUS DROPERIDOL 2014-02-07 2014-02-07 ADVERSE EVENT INTRAVENOUS FENTANYL 2014-02-07 2014-02-07 ADVERSE EVENT INTRAVENOUS HYDROCORTISONE 2014-02-07 2014-02-12 ADVERSE EVENT INTRAVENOUS KETAMINE 2014-02-07 2014-02-07 ADVERSE EVENT INTRAVENOUS METARAMINOL 2014-02-07 2014-02-07 ADVERSE EVENT INTRAVENOUS METRONIDAZOLE 2014-02-07 2014-02-10 ADVERSE EVENT INTRAVENOUS MIDAZOLAM 2014-02-07 2014-02-07 ADVERSE EVENT INTRAVENOUS PARECOXIB 2014-02-07 2014-02-07 ADVERSE EVENT INTRAVENOUS PROPOFOL 2014-02-07 2014-02-07 ADVERSE EVENT INTRAVENOUS ROCURONIUM 2014-02-07 2014-02-07 ADVERSE EVENT INTRAVENOUS SUGAMMADEX 2014-02-07 2014-02-07 ADVERSE EVENT INTRAVENOUS CIPROFLOXACIN 2014-02-09 2014-02-12 ADVERSE EVENT ORAL PANTOPRAZOLE 2014-02-09 2014-02-21 ADVERSE EVENT ORAL METRONIDAZOLE 2014-02-10 2014-02-17 ADVERSE EVENT ORAL OXYCODONE HYDROCHLORIDE 2014-02-11 2014-02-17 ADVERSE EVENT ORAL PREDNISOLONE 2014-02-13 2014-02-19 CROHN'S DISEASE ORAL FOSFOSODA /01544501/ 2014-02-14 2014-02-17 ADVERSE EVENT RECTAL LACTULOSE 2014-02-15 2014-02-17 ADVERSE EVENT ORAL METOCLOPRAMIDE 2014-02-16 2014-02-20 ADVERSE EVENT ORAL METRONIDAZOLE 2014-02-17 2014-02-22 ADVERSE EVENT INTRAVENOUS ONDANSETRON 2014-02-17 2014-02-17 ADVERSE EVENT ORAL TRAMADOL 2014-02-17 2014-02-20 ADVERSE EVENT ORAL AMPICILLIN 2014-02-18 2014-02-21 ADVERSE EVENT INTRAVENOUS CEFTRIAXONE 2014-02-18 2014-02-20 ADVERSE EVENT INTRAVENOUS PREDNISOLONE 2014-02-20 2014-02-26 CROHN'S DISEASE ORAL SPEKTRAMOX 2014-02-21 2014-02-21 ADVERSE EVENT ORAL CIPROFLOXACIN 2014-02-23 2014-03-03 ADVERSE EVENT ORAL METRONIDAZOLE 2014-02-23 - ADVERSE EVENT ORAL RABEPRAZOLE 2014-02-23 - CROHN'S DISEASE ORAL PREDNISOLONE 2014-02-27 2014-03-05 CROHN'S DISEASE ORAL METHOTREXATE 2014-03-04 - CROHN'S DISEASE SUBCUTANEOUS FOLIC ACID 2014-03-05 - CROHN'S DISEASE ORAL PREDNISOLONE 2014-03-06 2014-03-13 CROHN'S DISEASE ORAL CIPROFLOXACIN 2014-03-12 2014-03-12 ADVERSE EVENT INTRAVENOUS ENOXAPARIN SODIUM 2014-03-12 2014-03-15 ADVERSE EVENT SUBCUTANEOUS METRONIDAZOLE 2014-03-12 2014-03-16 ADVERSE EVENT INTRAVENOUS
12 8 㸦45㸧 ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
Preferred Term Start Date End Date Reason Route TRAMADOL 2014-03-12 2014-03-12 ADVERSE EVENT ORAL CEFTRIAXONE 2014-03-13 2014-03-15 ADVERSE EVENT INTRAVENOUS PANTOPRAZOLE 2014-03-14 2014-03-19 ADVERSE EVENT ORAL PREDNISOLONE 2014-03-14 2014-03-21 CROHN'S DISEASE ORAL PREDNISOLONE 2014-03-22 2014-03-29 CROHN'S DISEASE ORAL
12) Narrative Text ⿕㦂⪅ࡣ 4 ṓࡢⓑேዪᛶ࡛㸪2013 ᖺ 11 ᭶ 26 ᪥ᐶゎᑟධ⒪ἲࡋ࡚ᮏ㸦130 mg ⩌㸧ࢆ㟼 ⬦ෆᢞࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪ᅇ┣ᘚ⊃✽㸪ᖇ ⋤ษ㛤㸦2 ᅇ㸧㸪ᅇ┣㒊⮋⒆ࡢྑ༙⤖⭠ษ㝖⾡୪ࡧࢨࢳ࢜ࣉࣜࣥཬࡧ 6-࣓ࣝ࢝ࣉࢺࣉࣜࣥ ᑐࡍࡿࣞࣝࢠ࣮ᛂ㸦➽ຊపୗཬࡧ㧗య 㸧࡛࠶ࡗࡓࠋ⿕㦂⪅ࡣඖႚ↮⪅࡛࠶ࡾ㸪ᐙ᪘Ṕࡣ᪩ ᮇෙື⬦ᝈ࡛࠶ࡗࡓࠋ SAE/Permanent discontinuation of study agent due to AE㸸ࢡ࣮ࣟࣥ㸦Day 3㸧 CIOMS ࡼࡿ㸪2013 ᖺ 11 ᭶ 28 ᪥㸦Day 3㸧㸪ᗈỗᛶ⭡③㸦ྑ⭠㦵❐ᙉ࠸③ࡳ㸧ཬࡧ㛫 Ḟᛶࡢᝏᚰࢆッ࠼㸪ᩆᛴᦙ㏦ࡉࢀࡓࠋྤཬࡧୗ⑩ࡣ࡞ࡗࡓࠋ⿕㦂⪅ࡣ㸪⃰ࡃ㯤ࡳࢆ࠾ࡧࡓ⭐ ศἪ≀ࡶッ࠼㸪ධ㝔ࡋࡓࠋ 2013 ᖺ 11 ᭶ 29 ᪥ࡢ⭡㒊 X ⥺᳨ᰝ࡛ࡣ㸪࢞ࢫࡢ␃ࡋࡓ⭠ಀ㋟ࡀࡳࡽࢀࡓࠋྠ᪥ࡢ⭡㒊㉸㡢 Ἴ᳨ᰝ࡛ࡣ㸪㈓␃≀ཬࡧ⮋⒆ࡣ࡞࠸ࡀ㸪ᑠ⭠άືᮇࡢ⅖ᛶኚࡀࡳࡽࢀࡓࠋ⭠ቨᾋ⭘ཬࡧᕥ ഃᗈࡀࡿቑ⏕ࡋࡓ⾑⟶ࢆక࠺ᑠ⭠ಀ㋟㸦5 cm ཬࡧ 10 cm㸧ࡢศ⠇ᆺ⫧ཌࡀࡳࡽࢀࡓࠋࡉࡽ㸪 ୗ⭡㒊ཬࡧ⫢ୗ㒊ᑡ㔞ࡢ㐟㞳ᾮయࡀࡳࡽࢀࡓࠋ2013 ᖺ 12 ᭶ 5 ᪥ࡢ MR ࢚ࣥࢸࣟࢢࣛࣇ࣮ 㸦magnetic resonance enterography㸧࡛ࡣ㸪⣙ 10 cm ཬࡪ↓ගἑ࡞⅖ᛶ⭘⒗ࢆక࠺ᅇ⭠ᮎ➃ࡢ ⅖ࡀࡳࡽࢀࡓࠋ 2013 ᖺ 12 ᭶ 11 ᪥ᐇࡉࢀࡓ⭼ᣔ࠸ᾮࡢἪᒀ⏕Ṫჾ⮫ᗋᚤ⏕≀᳨ᰝ࡛ࡣ㸪Trichomonas vaginalis ཬࡧ㓝ẕ⣽⬊ࡣ㝜ᛶ࡛࠶ࡾ㸪ከᙧཬࡧୖ⓶⣽⬊୪ࡧࢃࡎ࡞ࢢ࣒ࣛ㝧ᛶ⌫⳦ཬࡧᱰ⳦ ࡀㄆࡵࡽࢀࡓࠋ2013 ᖺ 12 ᭶ 11 ᪥ࡢᒀ୰ Chlamydia trachomatis ཬࡧ Neisseria gonorrhoeas ࡢࣜ ࣝࢱ࣒࣏࣓࣮ࣜࣛࢮ㐃㙐ᛂ᳨ᰝࡢ⤖ᯝࡣ㝜ᛶ࡛࠶ࡗࡓࠋ ⿕㦂⪅ࡣࢫࢸࣟࢻࢆ㟼⬦ෆᢞࡉࢀ㸪2013 ᖺ 12 ᭶ 12 ᪥ࢡ࣮ࣟࣥቑᝏࡽᅇࡋࡓࠋࣉ ࣞࢻࢽࢰࣟࣥࢆ 8 㐌ࡅ࡚ῶࡋ 20 mg ࡢ⥔ᣢᢞࡍࡿࡇࡋ࡚㸪ྠ᪥㏥㝔ࡋࡓࠋᮏ⿕㦂 ⪅ࡢ⒪ࢫࢸࣟࢻࢆ⏝ࡋࡓࡇࡼࡾ㸪⥔ᣢヨ㦂ࡢ⛣⾜ࡀ㐺᱁࡞ࡾ㸪ᮏ㇟ᑐࡍ ࡿฎ⨨ࡣࠕᢞ୰Ṇࠖグ㘓ࡉࢀࡓࠋ SAE㸸ࢡ࣮ࣟࣥ㸦Day 45㸧 CIOMS ࡼࡿ㸪㛫Ḟᛶࡢᝏᚰ㸪ྤཬࡧ⾑ᒀࢆక࠺ྑഃ⭡③ཬࡧྑ⭠㦵❐③ࡢᝏ㸦1 㐌㛫㸧 ࡢࡓࡵ㸪2014 ᖺ 1 ᭶ 16 ᪥ධ㝔ࡋࡓࠋ2014 ᖺ 1 ᭶ 16 ᪥ࡢ⭡㒊 X ⥺᳨ᰝ࡛ࡣ㸪㠀≉␗ⓗ࡞⭠ෆ ࢞ࢫࡀࡳࡽࢀ㸪⭠㛢ሰཪࡣ⭠ቨᾋ⭘ཬࡧ⭡⭍ෆ㐟㞳࢞ࢫࢆ♧ࡍ X ⥺᳨ᰝീࡣࡳࡽࢀ࡞ࡗࡓࠋྠ ᪥ࡢ⮫ᗋ᳨ᰝ್ࡣ㸪C ᛂᛶࡓࢇⓑ㸦CRP㸧⃰ᗘ 222.4 mg/L㹙ṇᖖ⠊ᅖ㸦NR㸧<5 mg/L㸧㹛㸪࣊ ࣔࢢࣟࣅࣥ 103 g/L㸦NR 115-160 g/L㸧㸪࣐࣊ࢺࢡࣜࢵࢺ 0.31㸦NR 0.32-0.47㸧㸪ⓑ⾑⌫ᩘ 29.0×109/L㸦NR 4-11×109/L㸧㸪⾑ᑠᯈᩘ 463×109/L㸦NR 150-400×109/L㸧㸪ዲ୰⌫ᩘ 26.39×109/L 㸦1.8-7.5×109/L㸧࡛࠶ࡗࡓࠋ2014 ᖺ 1 ᭶ 17 ᪥ࡢ౽㢧ᚤ㙾᳨ᰝ࡛ࡣⓑ⾑⌫ࡀ㝧ᛶ࡛࠶ࡾ㸪౽ࡣࢡ ࣟࢫࢺࣜࢪ࣒࣭࢘ࢹࣇࢩ࢚ࣞࣥࢸࣟࢺ࢟ࢩࣥ A ᆺཬࡧ㸭ཪࡣ B ᆺ୪ࡧࢡࣟࢫࢺࣜࢪ࢘
12 9 㸦46㸧 ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
࣒࣭ࢹࣇࢩࣞࢢࣝࢱ࣑ࣥ㓟ࢹࣄࢻࣟࢤࢼ࣮ࢮࡀ㝧ᛶ࡛࠶ࡗࡓࠋ2014 ᖺ 1 ᭶ 17 ᪥ࡢ⭡㒊㉸㡢 Ἴ᳨ᰝ࡛ࡣ㸪ᅇ⭠ᮎ➃ࡢ⅖ཬࡧ⅖ᛶ⭘⒗ࡀࡳࡽࢀࡓࠋ 2014 ᖺ 1 ᭶ 23 ᪥ᐇࡋࡓ⭡㒊ཬࡧ㦵┙㒊ࡢࢥࣥࣆ࣮ࣗࢱ᩿ᒙᙳ㸦CT㸧ࢫ࡛࢟ࣕࣥࡣ㸪⭠ ಀ㋟ᣑᙇࡣ࡞ࡃ㸪ᅇ⭠ᮎ➃ࡢ⊃✽ཬࡧྑᒓჾከᩘࡢ㝸ቨࡀᙧᡂࡉࢀࡓᄞ⬊ᛶࡢ⭘⒗ࡀࡳࡽ ࢀࡓࠋ2014 ᖺ 1 ᭶ 24 ᪥ࡢ㦵┙㒊ࡢ㉸㡢Ἴ᳨ᰝ࡛ࡣ㸪ྑᒓჾࡁ࡞ᄞ⬊ᛶࡢ⭘⒗ࡀࡳࡽࢀࡓࠋ 2014 ᖺ 1 ᭶ 25 ᪥ࡢ⭘⒆᳨࣐࣮࣮࢝ᰝࡣ㝜ᛶ࡛㸪ෆศἪ᳨ᰝࡢ⤖ᯝࡣ ȕ-HCG 㝜ᛶ࡛࠶ࡗࡓࠋ 2014 ᖺ 2 ᭶ 7 ᪥㸪┤どୗ࡛ࡢᅇ⭠⤖⭠ษ㝖㸦open ileocolic resection㸧㸪⒵╔㞳ཬࡧ㦵┙⮋ ⒆ࡢࢻࣞࢼ࣮ࢪࢆ⾜ࡗࡓࠋ⌮Ꮫⓗᡤぢ࡛ࡣ㸪⅖ᛶ⭘⒗ࢆక࠺ࢡ࣮ࣟࣥᛶࡢᅇ⭠ᮎ➃⅖ࡀࡳ ࡽࢀ㸪㐣ཤࡢ⭠✸ᏍࡢṧᏑᚩೃ㛵㐃ࡋࡓ༸⟶༸ᕢ⮋⒆ࡀࢃࢀࡓࠋᅇ⭠ษ㝖࿘㎶࡛ࡣ⅖ࡀࡳ ࡽࢀࡓࡀ㸪┣⭠ษ㝖࿘㎶␗ᖖࡣࡳࡽࢀ࡞ࡗࡓࠋ2014 ᖺ 2 ᭶ 7 ᪥ࡢ῝㒊⭡Ỉࡢᚤ⏕≀Ꮫⓗ᳨ᰝ ࡛ࡣ㸪ከᙧ⣽⬊ཬࡧࢢ࣒ࣛ㝧ᛶ⌫⳦ࡀࡳࡽࢀ㸪ᇵ㣴᳨ᰝ࡛ࡣ Streptococcus milleri ⩌ࡢ㧗ᗘࡢቑṪཬࡧ᎘Ẽᛶΰྜ⣽⳦ࡢ㍍ᗘࡢቑṪࡀࡳࡽࢀࡓࠋ 2014 ᖺ 2 ᭶ 17 ᪥ᗘᐇࡋࡓ⭡㒊 X ⥺᳨ᰝ࡛ࡣ㸪ᑠ⭠ཬࡧ⭠」ᩘࡢ㙾㠃ീࡀࡳࡽࢀࡓ ࡀ㸪␗ᖖ⭾⬽ࡣㄆࡵࡽࢀࡎ㸪⭠㛢ሰ࡛ࡣ࡞ࡃ㯞⑷ᛶࣞ࢘ࢫࡀࢃࢀࡓࠋ⩣᪥ࡢ⭡㒊ཬࡧ㦵┙㒊 ࡢ CT ࢫ࡛࢟ࣕࣥࡣ㸪⭠㏆ᾘኻ୰ࡳࡽࢀࡿ౽ሰᰦࡀㄆࡵࡽࢀ㸪ᮏ⟠ᡤࡽ㏆ࡢᑠ⭠ᣑ ᙇࡣ๓ᅇࡢ CT ࢫ࢟ࣕࣥࡽᝏࡋ࡚࠸ࡓࠋ㦵┙ෆ⊂❧ࡋࡓᾮయ㈓␃ཬࡧ enhancing rim ࡀࡳ ࡽࢀ㸪ඛࡳࡽࢀࡓ㍍ᗘࡢ୧ഃ⬚Ỉࡣࡳࡽࢀ࡞ࡗࡓࠋ2014 ᖺ 2 ᭶ 23 ᪥ࢡ࣮ࣟࣥᅇ⭠⅖ࡽ ᅇࡋ㸪ྠ᪥㏥㝔ࡋࡓࠋ SAE/Serious infection㸸㝈ᒁᛶ⭡⭍ෆᾮ㈓␃㸦Day 104㸧 CIOMS ࡼࡿ㸪2㹼3 ᪥㛫⥆࠸ࡓ⭡③ࡢࡓࡵ㸪2014 ᖺ 3 ᭶ 12 ᪥ධ㝔ࡋࡓࠋ2014 ᖺ 3 ᭶ 13 ᪥ᐇࡋࡓ㦵┙㒊ࡢ CT ࢫ࡛࢟ࣕࣥࡣ㸪࿀ྜ㒊ศୖ㒊⊂❧ࡋࡓ㈓␃≀㸦┤ᚄ 24 mm㸧ࡀࡳࡽ ࢀࡓࠋከᩘࡢᑠࡉ࡞ᑠ⬊ࢆక࠺ᗈ⠊ᅖཬࡪ fat stranding ཬࡧ㞄᥋ࡍࡿᅇ⭠ಀ㋟ࡢ⫧ཌࡀࡳࡽࢀ ࡓࠋSAE ࡛࠶ࡿ㝈ᒁᛶ⭡⭍ෆᾮ㈓␃ࡀሗ࿌ࡉࢀ㸪ᮏ㇟ࡣ eCRF ࡛㦂ᢸᙜ་ᖌࡼࡾឤᰁ ุ᩿ࡉࢀࡓࠋᐃᮇ⾑ᾮ᳨ᰝ࡛ࡣ⅖ᛶ࣐࣮࣮࢝ࡢቑຍࡀࡳࡽࢀ㸪2014 ᖺ 3 ᭶ 13 ᪥ࡽ 2014 ᖺ 3 ᭶ 16 ᪥ࡢ⮫ᗋ᳨ᰝ್ࡣ㸪CRP 40.9-98.7 mg/L㸦NR<5.0 mg/L㸧㸪ⓑ⾑⌫ᩘ 11.6-13.6 giga/L㸦NR 4- 11 giga/L㸧㸪ዲ୰⌫ᩘ 8.17-11.89 giga/L㸦NR 1.8-7.5 giga/L㸧࡛࠶ࡗࡓࠋ⿕㦂⪅ࡣࢩࣉࣟࣇࣟ࢟ࢧ ࢩࣥ㸪ࢭࣇࢺࣜ࢟ࢯࣥཬࡧ࣓ࢺࣟࢽࢲࢰ࣮ࣝࢆᢞࡉࢀ࡚㏥㝔ࡋ㸪2014 ᖺ 3 ᭶ 16 ᪥ᮏ㇟ ࡽᅇࡋࡓࠋ
(6) CNTO1275CRD3002-2401-20315
1) Reason for narrative selection SAE Event of interest: Serious infection
2) Adverse Events Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day) (Verbatim Term) SAE Relatedness Trt? Outcome (Study day) 2013-01-16 ⭈│⭈⅖ Y SEVERE/ Y/ NOT APPLICABLE/ 2013-02-04 (-19) (PYELONEPHRITIS) NOT RELATED Y RECOVERED/RESOLVED (1) 2013-02-12 ∦㢌③ N MILD/ N/ DOSE NOT CHANGED/ 2013-02-13 (9) (MIGRAINE) NOT RELATED NA RECOVERED/RESOLVED (10)
13 0 㸦47㸧 ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
3) Baseline Demographic Information Age (years): 2 Sex: Male Weight (kg): 104.8 Race: White Date of birth: Height (cm): 180.0
4) Induction Treatment Group Randomized Treatment Group: Ustekinumab Approximating 6 mg/kg IV Actual Treatment Group: Ustekinumab Approximating 6 mg/kg IV
5) Induction Treatment Received Visit Start Date Study Day Dose Number Actual Treatment Dose WEEK 0 2013-02-04 1 1 Ustekinumab Approximating 6 mg/kg IV 520.2 mg
6) Induction Disposition Did subject complete the induction study?: Y Did subject enter maintenance study?: Y
7) Baseline Crohn's Disease History Date of diagnosis: 18JAN2012 Disease duration: 1.05 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪⭠⟶እ≧㸦ࣇࢱᛶཱྀෆ⅖㸧㻌
8) Crohn's Disease Complications Before Baseline Intra-abdominal abscess: Never Sinus tracts/perforation: Never Fistula: Never Stricture complications of (CD): Never
9) Concomitant Crohn's Disease-Related Surgeries None reported
10) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 0 METHYLPREDNISOLONE 16 mg 20
11) Concomitant Medications Preferred Term Start Date End Date Reason Route AZATHIOPRINE 2012-09-21 2013-05-03 CROHN'S DISEASE ORAL METHYLPREDNISOLONE 2012-10-17 2013-05-03 CROHN'S DISEASE ORAL HYOSCINE BUTYLBROMIDE 2013-01-16 2013-01-20 ADVERSE EVENT ORAL LEVOFLOXACIN 2013-01-16 2013-01-20 ADVERSE EVENT ORAL DICLOFENAC 2013-01-16 2013-01-20 ADVERSE EVENT ORAL PARACETAMOL 2013-01-21 2013-02-04 ADVERSE EVENT ORAL POTASSIUM CHLORIDE 2013-01-21 2013-01-22 ADVERSE EVENT INTRAVENOUS SODIUM CHLORIDE 2013-01-21 2013-01-22 ADVERSE EVENT INTRAVENOUS TEMOCILLIN DISODIUM 2013-01-21 2013-01-22 ADVERSE EVENT INTRAVENOUS TAMSULOSIN HYDROCHLORIDE 2013-01-21 2013-02-04 ADVERSE EVENT ORAL PARACETAMOL 2013-01-21 2013-01-21 ADVERSE EVENT INTRAVENOUS TRAMADOL HYDROCHLORIDE 2013-01-21 2013-02-04 ADVERSE EVENT ORAL
13 1 㸦48㸧 ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
12) Narrative Text ⿕㦂⪅ࡣ 2 ṓࡢⓑே⏨ᛶ࡛㸪ࢫࢡ࣮ࣜࢽࣥࢢᮇⓎ⌧ࡋࡓୗグ㇟㸦⭈│⭈⅖㸧ࡢᅇᚋ㸪 2013 ᖺ 2 ᭶ 4 ᪥ᐶゎᑟධ⒪ἲࡋ࡚ᮏ㸦㹼6 mg/kg ⩌㸧ࢆ㟼⬦ෆᢞࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪ࡧࡽࢇᛶ㣗㐨 ⅖㸦ࣟࢧࣥࢮࣝࢫศ㢮 Grade B㸧㸪┿⳦ᛶ㣗㐨⅖ࡢ࠸㸪⫶㣗㐨ᣓ⣙➽ᶵ⬟㸪⭠㦵❐③ཬࡧ ᕥഃࡢ⅖ᛶೃ⩌࡛࠶ࡗࡓࠋ⿕㦂⪅ࡣႚ↮⪅࡛࠶ࡗࡓࠋ SAE/Serious infection㸸⭈│⭈⅖㸦Day-19㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2013 ᖺ 1 ᭶ 16 ᪥ᕥഃࡢ⭡③ཬࡧྤࢆッ࠼㸪ᩆᛴእ᮶㸦ER㸧 ࢆཷデࡋࡓࠋ⿕㦂⪅ࡣᩘ࢝᭶㛫㸪ୗ⑩ࢆⓎ⌧ࡋ࡚࠸ࡓ㸦1 ᪥ 2㹼3 ᅇ㸧ࠋ2013 ᖺ 1 ᭶ 16 ᪥ࡢ㐀ᙳ 㸦㟼⬦ෆᢞ㸧ࢆ⏝࠸ࡓ⭡㒊ࡢࢥࣥࣆ࣮ࣗࢱ᩿ᒙᙳ㸦CT㸧ࢫ࡛࢟ࣕࣥࡣ㸪㐲ᒀ⟶⤖▼ཬ ࡧᒀ⟶-Ỉ⭈㸦ᕥ⭈│య㍈᪉ྥ┤ᚄ 20 mm㸧ࡀࡳࡽࢀࡓࠋ⿕㦂⪅ࡣ⭈│⭈⅖デ᩿ࡉࢀࡓࠋ hyoscine butylbromide㸪ࢪࢡࣟࣇ࢙ࢼࢡཬࡧࣞ࣎ࣇࣟ࢟ࢧࢩࣥࡀᢞࡉࢀࡓࠋ 2013 ᖺ 1 ᭶ 21 ᪥⭡③ࡢᝏࡼࡾ ER ࢆࡧཷデࡋ㸪ྠ᪥ධ㝔ࡋࡓࠋྠ᪥ᐇࡋࡓ㐀 ᙳ࠶ࡾཪࡣ࡞ࡋࡢ⭈ CT ࢫ࡛࢟ࣕࣥࡣ㸪ᕥᒀ⟶㸦excretory tree㸧ࡢ୰➼ᗘᣑᙇࡢཎᅉ⪃࠼ࡽ ࢀࡿ㐲ᒀ⟶ෆࡢ⤖▼㸦2-3 mm㸧ཬࡧ୧ഃ⭈ᐇ㉁࠾ࡅࡿᆒ୍࡞ྲྀࡾ㎸ࡳ㸦ྑഃ࡛≉㢧ⴭ㸧 ࢆㄆࡵ㸪୧ഃᛶ⭈│⭈⅖ࡀࢃࢀࡓࠋ⭈ෆ⮋⒆ཪࡣᒀ⟶እࡢ␗ᖖࡣ᳨ฟ࡛ࡁ࡞ࡗࡓࠋ⮫ᗋ᳨ᰝ ್ࡣ㸪C ᛂᛶࡓࢇⓑ 18㸦ṇᖖ⠊ᅖ<12㸪༢ࡣᮍሗ࿌㸧㸪ⓑ⾑⌫ᩘ 16000㸦༢ཬࡧṇᖖ⠊ᅖ ࡢグ㍕࡞ࡋ㸧࡛࠶ࡾ㸪㢧ᚤ㙾ࡼࡿᒀ᳨ᰝࡣ㝜ᛶ࡛࠶ࡗࡓࠋࢡ࣮ࣟࣥᝏࡢྜే㉳ᅉࡋ࡚ ⭈│⭈⅖ࡀⓎ⌧ࡋࡓሗ࿌ࡉࢀࡓࠋ㟼⬦ෆ⿵ᾮ㸪ࣃࣛࢭࢱ࣮ࣔࣝ㸪temocillin disodium㸪ሷࢼࢺ ࣒ࣜ࢘㸪ሷ࣒࢝ࣜ࢘㸪ࢺ࣐ࣛࢻ࣮ࣝሷ㓟ሷ㸪ࢱ࣒ࢫࣟࢩࣥሷ㓟ሷࡀᢞࡉࢀࡓࠋ⿕㦂⪅ࡣ 2013 ᖺ 1 ᭶ 22 ᪥㏥㝔ࡋ㸪2013 ᖺ 2 ᭶ 4 ᪥⭈│⭈⅖ࡣᾘᩓࡋࡓሗ࿌ࡉࢀࡓࠋ
(7) CNTO1275CRD3002-3604-20820
1) Reason for narrative selection SAE Discontinuation of study agent due to AE Event of interest: Serious infection
2) Adverse Events Start date End date (Study Preferred Term Intensity/ Inf/ Action Taken/ (Study day) (Verbatim Term) SAE Relatedness Trt? Outcome day) 2014-05- ⫠㛛⮋⒆ Y SEVERE/ Y/ DRUG WITHDRAWN/ 2014-06- 16 (PERIANAL NOT N RECOVERED/RESOLVED WITH 20 (58) ABSCESS) RELATED SEQUELAE (93)
3) Baseline Demographic Information Age (years): 3 Sex: Male Weight (kg): 58.0 Race: White Date of birth: Height (cm): 176.0
4) Induction Treatment Group Randomized Treatment Group: Ustekinumab 130 mg IV Actual Treatment Group: Ustekinumab 130 mg IV
13 2 㸦49㸧 ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
5) Induction Treatment Received Visit Start Date Study Day Dose Number Actual Treatment Dose WEEK 0 2014-03-20 1 1 Ustekinumab 130 mg IV 129.6 mg
6) Induction Disposition Did subject complete the induction study?: N Reason for induction early termination: WITHDRAWAL OF CONSENT Date of early termination: 2014-09-12 Did subject enter maintenance study?: N
7) Baseline Crohn's Disease History Date of diagnosis: 30JUN2009 Disease duration: 4.72 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪⫠㛛࿘ᅖ
8) Crohn's Disease Complications Before Baseline Intra-abdominal abscess: Never Sinus tracts/perforation: Never Fistula: Currently present Stricture complications of (CD): Never
9) Concomitant Crohn's Disease-Related Surgeries Surgery Date Result of lack of efficacy? ࡑࡢ⫠㛛࿘ᅖ⒦ᡭ⾡㸦⒦Ꮝษ㛤㸪⒦Ꮝษ㝖࡞㸧 2014-05-16 N ேᕤ⫠㛛ࡢ㐀タ 2014-05-19 N
10) Concomitant Steroids None reported
11) Concomitant Medications Preferred Term Start Date End Date Reason Route MESALAZINE 2009-09-29 - CROHN'S DISEASE ORAL
12) Narrative Text ⿕㦂⪅ࡣ 3 ṓࡢⓑே⏨ᛶ࡛㸪2014 ᖺ 3 ᭶ 20 ᪥ᐶゎᑟධ⒪ἲࡋ࡚ᮏ㸦130 mg ⩌㸧ࢆ㟼 ⬦ෆᢞࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪⫠㛛ཬࡧ㝜ᄞ ࿘ᅖ⒦ᑐࡍࡿᡭ⾡㸦2010 ᖺ㸧࡛࠶ࡗࡓࠋ SAE/Serious infection/Permanent discontinuation of study agent due to AE㸸⫠㛛⮋⒆㸦Day 58㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2014 ᖺ 5 ᭶ 16 ᪥㸪ୗ⭡㒊③ཬࡧ⑊③ࢆక࠺⫠㛛࿘ᅖࡢྠᚰ ᛶࡢ⭘⬽ࡢࡓࡵධ㝔ࡋࡓࠋ⿕㦂⪅ࡣ 3 ᅇࡢ౽ࡀ࠶ࡗࡓࡀ㸪⾑౽ཪࡣ㯮Ⰽ౽࡛ࡣ࡞ࡗࡓࠋ⌮Ꮫ ⓗᡤぢ࡛ࡣ⭡㒊ࡣᰂ㌾࡛㸪ᅽ③ࢆㄆࡵࡓࡀ㸪➽ᛶ㜵ᚚࡣ࡞ࡗࡓࠋ┤⭠᳨ᰝ࡛ࡣ㢧ⴭ࡞⫠㛛⊃✽㸪 ⫠㛛࿘ᅖ㒊ࡢ⾑㸪ᅽ③ཬࡧ῝ࡉ 1.5 cm ࡢ⫠ࡀㄆࡵࡽࢀࡓࠋ2014 ᖺ 5 ᭶ 16 ᪥ࡢ⮫ᗋ᳨ᰝ್ࡣ㸪 C ᛂᛶࡓࢇⓑ⃰ᗘ 132.20 mg/L㹙ṇᖖ⠊ᅖ㸦NR㸧<5.2㹛㸪࣊ࣔࢢࣟࣅࣥ 120 g/L㸦NR 130- 165 g/L㸧㸪ⓑ⾑⌫ᩘ 18.49 giga/L㸪ዲ୰⌫ 83.6%ཬࡧ 15.46 giga/L ࡛࠶ࡗࡓࠋࢥࣥࣆ࣮ࣗࢱ᩿ᒙ ᙳࢫ࡛࢟ࣕࣥࡣ㸪⫠㛛࿘ᅖ⮋⒆ࡀㄆࡵࡽࢀࡓࠋ⿕㦂⪅ࡣ㸪2014 ᖺ 5 ᭶ 16 ᪥⫠㛛࿘ᅖ⒦ᡭ⾡
13 3 㸦50㸧 ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
㸦⭘⒆ษ㛤⾡㸧㸪5 ᭶ 18 ᪥㸪20 ᪥㸪21 ᪥ཬࡧ 22 ᪥ࢱ࣏ࣥࣥࡢ㸪5 ᭶ 19 ᪥⭡⭍㙾ୗ࡛ S ≧⤖⭠ேཱྀ⫠㛛ᙧᡂ⾡ࢆ⾜ࡗࡓࠋ⤌⧊Ꮫⓗ᳨ᰝ࡛ࡣ㸪┿⓶ᒙ⒕ࡋࡓ⭺ཎ⧄⥔ᇶ㉁㸪୪ࡧ ࡑࡢ࿘㎶㒊ᕧ⣽⬊ࢆక࠺୰➼ᗘࡢ៏ᛶ⅖ᛶᾐ₶ࡀㄆࡵࡽࢀࡓࡀ㸪ᝏᛶ⭘⒆ࢆ♧ࡍ⤌⧊ീࡣ ࡞ࡗࡓࠋ௨ୖࡢ⤌⧊Ꮫⓗᡤぢࡼࡾ㸪⫠㛛࿘ᅖࡢ⧄⥔ୖ⓶⭘ࡀ♧၀ࡉࢀࡓࠋ 2014 ᖺ 6 ᭶ 20 ᪥㸪ᚋ㑇ࡣ࠶ࡗࡓࡀ㸪㇟ࡣᾘᩓࡋࡓࠋྠ᪥㸪⿕㦂⪅ࡣ㏥㝔ࡋࡓࡀ㸪་ᖌࡼ ࡾ㐠ືࢆ᥍࠼㸪1 ᪥ 1 ᅇໟᖏࢆࡋ㸪እ⛉ࢆ㐌 2 ᅇ௨ୖཷデࡍࡿࡼ࠺່ࡵࡽࢀࡓࠋ ⿕㦂⪅ࡣ 2014 ᖺ 9 ᭶ 12 ᪥ྠពࢆ᧔ᅇࡋࡓࡓࡵ㸪ࡑࡢᚋࡢ⥔ᣢ⒪ἲヨ㦂㸦CRD3003 ヨ㦂㸧 ࡣཧຍࡋ࡞ࡗࡓࠋ
(8) CNTO1275CRD3002-3606-20372
1) Reason for narrative selection SAE Event of interest: Serious infection
2) Adverse Events Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day) (Verbatim Term) SAE Relatedness Trt? Outcome (Study day) 2013-06-02 ⫶⭠⅖ Y MILD/ Y/ DOSE NOT CHANGED/ 2013-06-13 (54) (INFECTIOUS GASTROENTERITIS) DOUBTFUL Y RECOVERED/RESOLVED (65)
3) Baseline Demographic Information Age (years): 4 Sex: Female Weight (kg): 44.1 Race: White Date of birth: Height (cm): 165.5
4) Induction Treatment Group Randomized Treatment Group: Ustekinumab Approximating 6 mg/kg IV Actual Treatment Group: Ustekinumab Approximating 6 mg/kg IV
5) Induction Treatment Received Visit Start Date Study Day Dose Number Actual Treatment Dose WEEK 0 2013-04-10 1 1 Ustekinumab Approximating 6 mg/kg IV 259.2 mg
6) Induction Disposition Did subject complete the induction study?: Y Did subject enter maintenance study?: Y
7) Baseline Crohn's Disease History Date of diagnosis: 13NOV2007 Disease duration: 5.41 years Involved areas: ⤖⭠ࡢࡳ㸪⭠⟶እ≧㸦㛵⠇⅖㸭㛵⠇③㸧
8) Crohn's Disease Complications Before Baseline Intra-abdominal abscess: Never Sinus tracts/perforation: Never Fistula: Never Stricture complications of (CD): Never
13 4 㸦51㸧 ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
9) Concomitant Crohn's Disease-Related Surgeries None reported
10) Concomitant Steroids None reported
11) Concomitant Medications Start Preferred Term Date End Date Reason Route MESALAZINE 2007-12- - CROHN'S DISEASE ORAL 04 AZATHIOPRINE 2011-12- 2012-10- CROHN'S DISEASE ORAL 15 19 DIHYDROXYALUMINUM SODIUM 2012-06- - OTHER (ULCER PREVENTION) ORAL CARBONATE 27 ACENOCOUMAROL 2012-11- - OTHER (PREVENTION OF DEEP VEIN ORAL 13 THROMBOSIS) METHYLPREDNISOLONE 2013-01- 2013-02- CROHN'S DISEASE ORAL 03 04 FERRANEM 2013-02- - OTHER (ANAEMIA) ORAL 22 PENTOXIFYLLINE 2013-02- 2013-04- CROHN'S DISEASE ORAL 22 07 METOCLOPRAMIDE HYDROCHLORIDE 2013-06- 2013-06- ADVERSE EVENT INTRAVENOUS 02 04 METRONIDAZOLE 2013-06- 2013-07- ADVERSE EVENT ORAL 02 02 LOPERAMIDE HYDROCHLORIDE 2013-06- 2013-07- ADVERSE EVENT ORAL 04 07 PANCREATIN 2013-06- 2013-06- ADVERSE EVENT ORAL 04 10
12) Narrative Text ⿕㦂⪅ࡣ 4 ṓࡢⓑேዪᛶ࡛㸪2013 ᖺ 4 ᭶ 10 ᪥ᐶゎᑟධ⒪ἲࡋ࡚ᮏ㸦㹼6 mg/kg ⩌㸧ࢆ 㟼⬦ෆᢞࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪㈋⾑㸦ࢡ࣮ࣟ ࣥࡀᝏࡋ㸪㉥⾑⌫㍺⾑ࢆᚲせࡋࡓ㸧㸪୧⭸ࡢᡭ⾡㸪⾑ᾮ〇㍺⾑㸦ᩋ⾑ཬࡧ⫵⅖ࡢࡓ ࡵ㸧㸪㱘ṑ㸪⫶⅖㸪Ꮝ࣊ࣝࢽ㸪ୗ⫥ᾋ⭘ࢆక࠺పࡓࢇⓑ⾑㸪ႃ㢌㞀ᐖ㸦Ẽ⟶ษ㛤ࡢࡓࡵ㸧㸪 ᕥୗ⫥ࡢ㟼⬦⾑ᰦ㸪྾㸦⫵⅖ཬࡧపࡓࢇⓑ⾑ࡼࡿ⫵Ỉ⭘ࡢࡓࡵ㸪ᶵᲔⓗẼཬࡧẼ ⟶ษ㛤ࢆ⾜ࡗࡓ㸧㸪ᩋ⾑㸪୪ࡧ⫹▼ཬࡧ⭈⤖▼ࡢ࠸࡛࠶ࡗࡓࠋ⿕㦂⪅ࡣ㠀ႚ↮⪅࡛࠶ ࡗࡓࠋ SAE/Serious infection㸸⫶⭠⅖㸦Day 54㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣྤ㸦1 ᅇ㸧㸪୪ࡧ㌾౽ཬࡧỈᵝᛶୗ⑩㸦1 ᪥ 8㹼10 ᅇ㸪ከ࠸ ࡁࡣ 10㹼15 ᅇ㸧ࢆッ࠼㸪2013 ᖺ 6 ᭶ 2 ᪥ධ㝔ࡋࡓࠋ⿕㦂⪅ࡣ㣗ḧࡀ࡞ࡃ㸪య㔜ࡀ 2㹼3 kg ῶ ᑡࡋࡓࠋⓎ⇕㸪⭡③㸪⬚③ཪࡣ྾ᅔ㞴ࡣ࡞ࡗࡓࠋ2013 ᖺ 6 ᭶ 2 ᪥ࡢ⮫ᗋ᳨ᰝ࡛ࡣ㸪ୗグࡢ㡯 ┠␗ᖖࡀㄆࡵࡽࢀࡓ㸸C ᛂᛶࡓࢇⓑ⃰ᗘ 68.2 mg/L㹙ṇᖖ⠊ᅖ㸦NR㸧0-5 mg/L㹛㸪ࣜࣥࣃ⌫ 6.4%㸦NR 25%-40%㸧㸪 ዲ୰⌫ 84.4%㸦NR 50%-70%㸧㸪⾑ᑠᯈᩘ 662 g/L㸦NR 150-450 g/L㸧ཬ ࡧⓑ⾑⌫ᩘ 26.6 g/L㸦NR 4.4-11.3 g/L㸧ࠋ2013 ᖺ 6 ᭶ 4 ᪥ࡢ౽⣽⳦᳨ᰝ࡛ࡣ㸪ࢡࣟࢫࢺࣜࢪ࢘ ࣒࣭ࢹࣇࢩࣞᢠཎཬࡧࢺ࢟ࢩࣥ A㸭B ࡣ㝜ᛶ࡛࠶ࡾ㸪ࢧࣝࣔࢿࣛ㸪㉥⑩⳦㸪⭠⳦ O124㸪 Yersinia enterocolitica ཪࡣ࢝ࣥࣆࣟࣂࢡࢱ࣮ࡢቑṪࡣ࡞ࡗࡓࠋሷ㓟࣓ࢺࢡࣟࣉ࣑ࣛࢻ㸪࣓ࢺࣟ ࢽࢲࢰ࣮ࣝ㸪ሷ㓟࣑ࣟ࣌ࣛࢻ㸪ࣃࣥࢡࣞࢳࣥ㸪࣓ࢧࣛࢪࣥ㸪pantoprazole㸪acenocoumarol ཬࡧ
13 5 㸦52㸧 ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3002 ヨ㦂
5%ࣈࢻ࢘⢾ᾮ࡛⒪ࢆ⾜ࡗࡓࠋ⒪ࡼࡾ⿕㦂⪅ࡢ≧ࡣᨵၿࡋ㸪౽ᅇᩘࡀῶࡾ㸪㣗ḧࡀቑ ຍࡋ㸪⅖ࣃ࣓࣮ࣛࢱࡶṇᖖ್࡞ࡗࡓ㸦ṇᖖ್ᮍධᡭ㸧ࠋ2013 ᖺ 6 ᭶ 13 ᪥ឤᰁᛶ⫶⭠⅖ࡣ ᾘᩓࡋ㸪ྠ᪥⿕㦂⪅ࡣ㏥㝔ࡋࡓࠋ
13 6 㸦53㸧 ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
2.7.6.4 ➨ III ┦ᅜ㝿ඹྠヨ㦂㸸ᐶゎ⥔ᣢヨ㦂㸦CNTO1275CRD3003 ヨ㦂㸪ホ౯㈨ᩱ㸸 5.3.5.1.3-1㸧
2.7.6.4.1 ᴫせ
(1) 㦂ᐇィ⏬᭩␒ྕ CNTO1275CRD3003
(2) 㦂ࡢᶆ㢟 ୰➼ࡽ㔜ࡢάືᮇࢡ࣮ࣟࣥᝈ⪅ࢆᑐ㇟ࡍࡿ࢘ࢫࢸ࢟ࢾ࣐ࣈ㸦௨ୗ㸪ᮏ㸧ࡢᐶゎ⥔ ᣢ⒪ἲࡢᏳᛶཬࡧ᭷ຠᛶࡢホ౯ࢆ┠ⓗࡋࡓ➨ III ┦㸪ࣛࣥࢲ࣒㸪㔜┣᳨㸪ࣉࣛࢭ࣎ᑐ↷㸪 ୪⾜⩌㛫㸪ከタඹྠヨ㦂
(3) 㦂㈐௵་ᖌ
(4) 㦂ᐇ་⒪ᶵ㛵 ᆅᇦ 6 ᆅᇦ ࢪ㸪࣮ࣚࣟࢵࣃ㸪⡿㸪༡⡿㸪ࣇࣜ࢝㸪࢜ࢭࢽ ཧຍᅜ 27 ࣧᅜ ᪥ᮏ㸪㡑ᅜ㸪ࣈࣝ࢞ࣜ㸪ࢡࣟࢳ㸪ࢳ࢙ࢥඹᅜ㸪ࣁ࣮ࣥ࢞ࣜ㸪 ࣏࣮ࣛࣥࢻ㸪ࣟࢩ㸪ࢭࣝࣅ㸪࣮࢜ࢫࢺࣛࣜ㸪࣮࢜ࢫࢺࣜ㸪࣋ ࣝࢠ࣮㸪ࣈࣛࢪࣝ㸪࢝ࢼࢲ㸪ࢹ࣐࣮ࣥࢡ㸪ࣇࣛࣥࢫ㸪ࢻࢶ㸪ࢫ ࣛࣥࢻ㸪ࣝࣛࣥࢻ㸪ࢫ࢚ࣛࣝ㸪ࢱࣜ㸪࢜ࣛࣥࢲ㸪ࢽ࣮ࣗࢪ ࣮ࣛࣥࢻ㸪༡ࣇࣜ࢝㸪ࢫ࣌ࣥ㸪ⱥᅜ㸪⡿ᅜ ᐇタ 260 タ㸦᪥ᮏ 20 タ㸧
(5) බ⾲ᩥ⊩㸦ᘬ⏝ᩥ⊩㸧 ࡞ࡋ
(6) 㦂ᐇᮇ㛫 2011 ᖺ 9 ᭶᪥㹼2015 ᖺ 6 ᭶᪥
(7) 㛤Ⓨࡢ┦ ➨ III ┦
(8) ┠ⓗ ┠ⓗ 1. ᐶゎᑟධヨ㦂 CNTO1275CRD3001 ཪࡣ CNTO1275CRD3002 ࡛㸪ᮏࡢ㟼⬦ෆᢞࡼࡾ clinical response ࡀᚓࡽࢀࡓ㸪୰➼ࡽ㔜ࡢάືᮇࢡ࣮ࣟࣥᝈ⪅ࢆᑐ㇟㸪ᮏࡢ⓶ ୗᢞࡼࡿ 2 ࡘࡢᐶゎ⥔ᣢ⒪ἲ࠾ࡅࡿ clinical remission ࢆホ౯ࡍࡿࠋ
13 7 (1) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
2. ୰➼ࡽ㔜ࡢάືᮇࢡ࣮ࣟࣥᝈ⪅ࢆᑐ㇟㸪ᮏࡢ⓶ୗᢞࡼࡿ 2 ࡘࡢᐶゎ⥔ᣢ ⒪ἲ࠾ࡅࡿᏳᛶࢆホ౯ࡍࡿࠋ
ḟ┠ⓗ 1. Clinical response ࡀᚓࡽࢀࡓ⿕㦂⪅࠾ࡅࡿᮏࡢ᭷ຠᛶࢆ㸪clinical response ࡢ⥔ᣢࡼࡾ ホ౯ࡍࡿࠋ
2. Clinical remission ࡀᚓࡽࢀࡓ⿕㦂⪅࠾ࡅࡿᮏࡢ᭷ຠᛶࢆ㸪clinical remission ࡢ⥔ᣢࡼ ࡾホ౯ࡍࡿࠋ
3. ᮏࡢ᭷ຠᛶࢆ㸪corticosteroid-free remission ࡼࡾホ౯ࡍࡿࠋ
4. C ᛂᛶࡓࢇⓑ㸦CRP㸧㸪౽୰࢝ࣝࣉࣟࢸࢡࢳࣥ㸪౽୰ࣛࢡࢺࣇ࢙ࣜࣥ㸪ཬࡧࡑࡢࡢ⸆ ຊᏛⓗࣂ࣐࣮࣮࢜࢝ࡢኚືࢆྵࡵ㸪ᮏᢞࡼࡿ⸆≀ືែ㸪චཎᛶ㸪ཬࡧ⸆ຊᏛࢆ ホ౯ࡍࡿࠋ
5. ᗣ㛵㐃⏕άࡢ㉁㸦QOL㸧ᑐࡍࡿᮏࡢຠᯝࢆホ౯ࡍࡿࠋ
(9) 㦂᪉ἲ ᮏヨ㦂ࡣ㸪ࣛࣥࢲ࣒㸪㔜┣᳨㸪ࣉࣛࢭ࣎ᑐ↷㸪୪⾜⩌㛫㸪ከタඹྠヨ㦂࡛࠶ࡾ㸪ᐶゎᑟ ධヨ㦂 CNTO1275CRD3001 ཪࡣ CNTO1275CRD3002 ࠾࠸࡚ᮏࡢ㟼⬦ෆᢞࡼࡾ clinical response ࡀᚓࡽࢀࡓ୰➼ࡽ㔜ࡢάືᮇࢡ࣮ࣟࣥᝈ⪅ࢆ㸪0 㐌┠௨ୗࡢ࠸ࡎࢀࡢ⓶ୗ ᢞ⩌ 1㸸1㸸1 ࡢẚ࡛ࣛࣥࢲ࣒ࡾࡅࡓࠋࡇࢀࡽࡢ⿕㦂⪅ࢆᮏヨ㦂ࡢせ࡞ᑐ㇟㞟ᅋࡋ㸪 44 㐌┠せホ౯㡯┠࡛࠶ࡿ clinical remission ࢆホ౯ࡋࡓࠋ · ࣉࣛࢭ࣎⩌
· ᮏ 90 mg 12 㐌㛫 1 ᅇ⓶ୗᢞ㸦SC q12w㸧㸦᭱⤊ᢞ㸸36 㐌┠㸧
· ᮏ 90 mg 8 㐌㛫 1 ᅇ⓶ୗᢞ㸦SC q8w㸧㸦᭱⤊ᢞ㸸40 㐌┠㸧
ୖグࡢࣛࣥࢲ࣒ࡉࢀࡓ⿕㦂⪅ࡀ 8 㐌┠ࡽ 32 㐌┠ࡢ᮶㝔᪥ࡲ࡛ response ࡢᾘኻ㸦LOR㸧 ᇶ‽ࢆ‶ࡓࡋࡓሙྜ㸪ᮏ 90 mg SC q8w ࡢ⏝㔞ㄪ⠇ࢆྍ⬟ࡋࡓ㸦⏝㔞ㄪ⠇ࡣྛ⿕㦂⪅࡛ 1 ᅇࡢࡳㄆࡵࡽࢀࡓ㸧ࠋ⏝㔞ㄪ⠇ࢆ⾜ࡗࡓ⿕㦂⪅ࡘ࠸࡚ࡣ㸪ࡑࡢຠᯝࢆ᳨ドࡍࡿࡓࡵ⏝㔞ㄪ⠇ࡢ 16 㐌㛫ᚋホ౯ࢆ⾜࠸㸪clinical response ࡀᚓࡽࢀ࡞ࡗࡓሙྜࡣ㦂⸆ᢞࢆ୰Ṇࡋࡓࠋ ࡲࡓ㸪ᐶゎᑟධヨ㦂ࡢ 8 㐌┠ᮏࡼࡿ clinical response ࡀᚓࡽࢀ࡞ࡗࡓ⿕㦂⪅㸪ཬࡧᐶゎ ᑟධヨ㦂࡛ࣉࣛࢭ࣎ࢆᢞࡉࢀࡓࡍ࡚ࡢ⿕㦂⪅㸦clinical response ࡢ᭷↓ࢆၥࢃ࡞࠸㸧ࡶᮏヨ㦂 ࡢ⤌ࡳධࢀᑐ㇟ࡋࡓࡀ㸪せ࡞ᑐ㇟㞟ᅋࡣྵࡵ࡞ࡗࡓࠋࡇࡢ࠺ࡕ㸪ࣉࣛࢭ࣎ࡢ㟼⬦ෆᢞ ࡼࡿᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡓ⿕㦂⪅ࡣ㸪ᮏᐶゎ⥔ᣢヨ㦂ࢆ㏻ࡌ࡚ࣉࣛࢭ࣎ ࢆ⓶ୗᢞࡋࡓࠋࣉࣛࢭ࣎ࡢ㟼⬦ෆᢞࡼࡿᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀ࡞ࡗࡓ ⿕㦂⪅ࡣ㸪ᮏヨ㦂ࡢ 0 㐌┠ᮏ 130 mg ࢆ㟼⬦ෆᢞࡋࡓࠋࡑࡢᚋ㸪8 㐌┠ clinical response ࡀᚓࡽࢀࡓ⿕㦂⪅ࡣᮏ 90 mg ࡢ⓶ୗᢞࢆ㛤ጞࡋ㸪32 㐌┠ࡲ࡛ q12w ࡼࡿ⓶ୗᢞࢆ⥅⥆ࡋ ࡓࠋ8 㐌┠ clinical response ࡀᚓࡽࢀ࡞ࡗࡓ⿕㦂⪅ࡣ㸪㦂⸆ࡢᢞࢆ୰Ṇࡋࡓࠋᮏࡢ㟼⬦ ෆᢞࡼࡿᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀ࡞ࡗࡓ⿕㦂⪅ࡣ㸪ᮏヨ㦂ࡢ 0 㐌┠ᮏ
13 8 (2) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
90 mg ࢆ⓶ୗᢞࡋࡓࠋࡑࡢᚋ㸪8 㐌┠ clinical response ࡀᚓࡽࢀࡓ⿕㦂⪅ࡣ㸪40 㐌┠ࡲ࡛ᮏ 90 mg q8w ࡼࡿ⓶ୗᢞࢆ⥅⥆ࡋࡓࠋ8 㐌┠ clinical response ࡀᚓࡽࢀ࡞ࡗࡓ⿕㦂⪅ࡣ㸪 㦂⸆ࡢᢞࢆ୰Ṇࡋࡓࠋ ᭦㸪44 㐌┠ࡢᏳᛶཬࡧ᭷ຠᛶホ౯⤊⥅⥆ᢞࡀ᭷┈࡛࠶ࡿ㦂ᢸᙜ་ᖌࡀุ᩿ࡋ ࡓ⿕㦂⪅ࡣ㸪㛗ᮇ⥅⥆ᢞᮇࡋ࡚᭱㛗 272 㐌┠ࡲ࡛ᮏヨ㦂ࢆ⥅⥆ࡋࡓࠋ ᮏヨ㦂ࡢ㔜┣᳨ᮇ㸦44 㐌┠ࡲ࡛㸧࡛ࡣ㸪⊂❧ࢹ࣮ࢱࣔࢽࢱࣜࣥࢢጤဨࡀ⿕㦂⪅ࡢᏳᛶࢹ ࣮ࢱࢆࣔࢽࢱࣜࣥࢢࡋࡓࠋ࡞࠾㸪ᮏヨ㦂࡛ࡣ㸪୰㛫ゎᯒࡣᐇࡋ࡞ࡗࡓࠋ
(10) ⿕㦂⪅ᩘ㸦ィ⏬ཬࡧゎᯒ㸧 ィ⏬ 㦂ᐇィ⏬᭩࡛ࡣ㸪1275 ࡢ⿕㦂⪅ࡀ 2 ࡘࡢᐶゎᑟධヨ㦂 CNTO1275CRD3001 ཪࡣ CNTO1275CRD3002 ⤌ࡳධࢀࡽࢀࡿᐃࡋࡓࠋࡇࢀࡽࡢᐶゎᑟධヨ㦂࡛⏝ࡍࡿ㟼⬦ෆᢞ 〇㹙࢘ࢫࢸ࢟ࢾ࣐ࣈ 130 mg㸸ᐜ㔞 26 mL㸦5 mg/mL㸧㹛ࡢࣂࢵࢳᏳᐃᛶୖࡢၥ㢟ࡀ☜ㄆࡉࢀ ࡓࡓࡵ㸪㦂౫㢗⪅ࡣ 20 ᖺ᭶ヨ㦂ࢆ୍୰᩿ࡋࡓࠋࡇࡢᏳᐃᛶୖࡢၥ㢟ࢆホ౯⪅ࡀㄆ▱ ࡋࡓࡇࡼࡾ㸪ホ౯ࣂࢫࡀ⏕ࡌࡿྍ⬟ᛶࡀ࠶ࡿࡇࡽ㸪ヨ㦂ࡢ୍୰᩿๓⤌ࡳධࢀ ࡽࢀࡓ⿕㦂⪅㸦ࣛࣥࢲ࣒ࡉࢀࡓ⿕㦂⪅㸸9 㸪ࣛࣥࢲ࣒ࡉࢀ࡞ࡗࡓ⿕㦂⪅㸸17 㸧ࡢࢹ࣮ ࢱࡣィ⏬ࡋࡓ᭷ຠᛶࡢゎᯒࡣ⏝࠸࡞࠸ࡇࡋࡓࠋࡋࡓࡀࡗ࡚㸪ࡇࢀࡽࡢྛヨ㦂࡛ᙜึணᐃࡉ ࢀࡓ⿕㦂⪅ᩘࢆ☜ಖࡍࡿࡓࡵ㸪40 ࡀᐶゎᑟධヨ㦂᪂ࡓ⤌ࡳධࢀࡽࢀࡓࠋ
᪥ᮏே⿕㦂⪅ᩘࡢタᐃ᰿ᣐ ᮏヨ㦂యࡢ┠ᶆᩘࡣ㸪44 㐌ࡢclinical remissionࡢྜࢆࣉࣛࢭ࣎⩌15%㸪8㐌㛫㝸⓶ୗᢞ ⩌ࡢྜࢆ35%ぢ✚ࡶࡾ㸪┠ᶆᩘࢆ1⩌100㸦ྜィ300㸧タᐃࡋࡓࠋࠕᅜ㝿ඹྠ 㦂㛵ࡍࡿᇶᮏⓗ⪃࠼᪉ࡘ࠸࡚ࠖ♧ࡉࢀࡓ᪉ἲࡼࡾ㸪᪥ᮏே㞟ᅋ㞟ᅋࡢ⤖ᯝࡢ୍㈏ᛶ ࢆ᳨ウࡍࡿࡓࡵᚲせ࡞ᩘࡣ㸪᪉ἲ1࠙D(Japan)㸭D(all)㸼0.5ࠚ࡛1⩌⣙25㸦ྜィ75 㸧㸪 ᪉ἲ2࠙D(Japan)㸼0 ࡘD(all)㸼0ࠚ࡛1⩌⣙10㸦ྜィ30㸧࡛࠶ࡗࡓࠋࡇࢀࡽࡢᩘࢆ☜ಖ ࡍࡿࡓࡵᚲせ࡞ᩘࡣ㸪3001 ヨ㦂ࡢࡳཧຍࡋࡓሙྜ㸪᪉ἲ1࡛1⩌⣙120㸦ྜィ360㸧㸪 ᪉ἲ2࡛1⩌⣙50㸦ྜィ150㸧ぢ✚ࡶࡽࢀ㸪๓㏙ࡢ⌮⏤ࡼࡾ㸪⌧ᐇⓗ࡛ࡣ࡞࠸⪃࠼ࡽࢀࡓࠋ ࡑࡢࡓࡵ㸪ඛࡶ㏙ࡓ࠾ࡾ㸪3002 ヨ㦂ࡶཧຍࡋ㸪20 ⛬ᗘࢆ┠ᶆྍ⬟࡞㝈ࡾከࡃࡢ ᪥ᮏேᩘ☜ಖດࡵࡿࡇࡋ㸪ࡲࡓ㸪3001 ヨ㦂࠾࠸࡚ࡶ㸪60 ⛬ᗘࢆ┠ᶆྍ⬟࡞㝈 ࡾከࡃࡢ᪥ᮏேᩘ☜ಖດࡵࡿࡇࡋࡓࠋ୧ヨ㦂ࡽᮏヨ㦂ࡢ⛣⾜⋡ࢆ 90㸣௬ᐃࡋ ࡓሙྜ㸪ᮏヨ㦂ཧຍࡍࡿ᪥ᮏேᩘࡣ 70 ௨ୖ㸪ࡑࡢ࠺ࡕせ᭷ຠᛶゎᯒᑐ㇟㞟ᅋࡋ ࡚ࡣ⣙ 20 ࡀぢ㎸ࡲࢀࡓࠋ 3001 ཬࡧ 3002 ࡢ୧ヨ㦂ཧຍࡋ㸪ྍ⬟࡞㝈ࡾከࡃࡢ᪥ᮏேᩘ☜ಖດࡵࡓࡋ࡚ࡶ㸪୧ ヨ㦂ࡽ⛣⾜ࡋࣛࣥࢲ࣒ࡉࢀࡿᩘࡣ㝈ࡽࢀࡿࡓࡵ㸪⤖ᯝࡢ୍㈏ᛶࢆ᳨ウࡍࡿࡇࡣ㞴ࡋ࠸ ⪃࠼ࡽࢀ㸪㞟✚ࡉࢀࡓಶูࢹ࣮ࢱࢆࡶ⪃ᐹࡍࡿࡇࡋࡓࠋ
ゎᯒ ᮏࡢᐶゎᑟධヨ㦂ࢆࡋࡓྜィ 1281 ࡢ⿕㦂⪅ࡀᮏヨ㦂⤌ࡳධࢀࡽࢀࡓࠋྛᑐ㇟㞟ᅋ ࠾ࡅࡿ⿕㦂⪅ᩘࡣ௨ୗࡢ࠾ࡾ࡛࠶ࡗࡓࠋ
13 9 (3) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
· ᮏヨ㦂ࡢせ࡞ᑐ㇟㞟ᅋ㸦ࣛࣥࢲ࣒ࡉࢀࡓ⿕㦂⪅㸸ᐶゎᑟධヨ㦂ࡢ 8 㐌┠ᮏࡢ㟼⬦ ෆᢞࡼࡿᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡓ⿕㦂⪅㸧ࡣ 397 㸦31.0%㸧࡛࠶ࡾ㸪 ௨ୗࡢᢞ⩌ࣛࣥࢲ࣒ࡾࡅࡽࢀࡓࠋ
· ࣉࣛࢭ࣎⩌㸸133
· ᮏ 90 mg SC q12w ⩌㸸132
· ᮏ 90 mg SC q8w ⩌㸸132
· 884 㸦69.0%㸧ࡣᮏヨ㦂⤌ࡳධࢀࡽࢀࡓࡀ㸪ࣛࣥࢲ࣒ࡉࢀ࡞ࡗࡓ㸦ࣛࣥࢲ࣒ࡉࢀ ࡞ࡗࡓ⿕㦂⪅㸧ࠋࡇࢀࡽࡢ⿕㦂⪅ࡢෆヂࡣ௨ୗࡢ࠾ࡾ࡛࠶ࡿࠋ
· ࣉࣛࢭ࣎ࡼࡿᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀ㸪ᮏヨ㦂࡛ࡶࣉࣛࢭ࣎ࢆ⥅⥆㸸 123
· ࣉࣛࢭ࣎ࡼࡿᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡎ㸪ᮏヨ㦂ࡢ 0 㐌┠ᮏ 130 mg ࢆ㟼⬦ෆᢞ㸸285 ࡞࠾㸪ࡇࢀࡽࡢ⿕㦂⪅࡛ 8 㐌┠ clinical response ࡀᚓࡽࢀࡓሙྜ㸪ᮏ 90 mg q12w ࡛ ᢞࢆ⥅⥆ࡋࡓࠋ
· ᮏࡼࡿᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡎ㸪ᮏヨ㦂ࡢ 0 㐌┠ᮏ 90 mg ࢆ ⓶ୗᢞ㸸476 ࡞࠾㸪ࡇࢀࡽࡢ⿕㦂⪅࡛ 8 㐌┠ clinical response ࡀᚓࡽࢀࡓሙྜ㸪ᮏ 90 mg q8w ࡛ᢞ ࢆ⥅⥆ࡋࡓࠋ
(11) デ᩿ཬࡧ࡞㑅ᢥᇶ‽ ᮏヨ㦂ࡢᑐ㇟ࡣ㸪ᐶゎᑟධヨ㦂 CNTO1275CRD3001 ཪࡣ CNTO1275CRD3002 ࡢ 0 㐌┠㦂 ⸆ࢆᢞࡉࢀ㸪8 㐌┠ Crohn’s Disease Activity Index㸦CDAI㸧ࢫࢥࡢホ౯ࢆࡋࡓ⿕㦂⪅ ࡋࡓࠋᐶゎᑟධヨ㦂 CNTO1275CRD3001 ࡛ࡣ㸪୰➼ࡽ㔜ࡢάືᮇࢡ࣮ࣟࣥ⨯ᝈࡋ࡚ ࠾ࡾ㸪㐣ཤ 1 ௨ୖࡢᢠ TNF㸦⭘⒆ቯṚᅉᏊ㸧⸆⒪ࢆཷࡅࡓࡀຠᯝ༑ศ࡛࠶ࡗࡓ㸪ࡇࢀ ࡽࡢ⸆ᑐࡋ࡚ᚸᐜᛶࡀ࡞ࡗࡓᝈ⪅ࢆᑐ㇟ࡋࡓࠋࡲࡓ㸪ᐶゎᑟධヨ㦂 CNTO1275CRD3002 ࡛ࡣ㸪୰➼ࡽ㔜ࡢάືᮇࢡ࣮ࣟࣥ⨯ᝈࡋ࡚࠾ࡾ㸪᪤Ꮡ⒪㸦ࢥࣝࢳࢥࢫࢸࣟࢻཬࡧ චㄪ⠇⸆㸧ࡀຠᯝ༑ศ࡛࠶ࡿ㸪άືᛶ⅖ࢆ᭷ࡍࡿ⿕㦂⪅ࢆᑐ㇟ࡋࡓࠋ
(12) ⿕㦂⸆㸪⏝㔞ཬࡧᢞ᪉ἲ㸪ࣟࢵࢺ␒ྕ ᮏ㹙࢘ࢫࢸ࢟ࢾ࣐ࣈ㸦㑇ఏᏊ⤌࠼㸧㹛ࡢ⓶ୗᢞ⏝〇ࡣ㸪ࣉࣞࣇࣝࢻࢩࣜࣥࢪ㹙Ỉ⁐ ᾮ୰㸦1 mL㸧ᮏ 90 mg ࢆྵ᭷㹛ධࢀࡽࢀࡓ༢ᅇᢞ⏝㸪↓⳦ᾮࡋ࡚౪⤥ࡉࢀࡓ㸦ࣂࣝ ࢡࣟࢵࢺ␒ྕ㸸 㸪 㸪 㸪㸪㸪 㸪 㸧ࠋ࢘ࢫࢸ࢟ࢾ ࣐ࣈࡢ㸪ྛࣉࣞࣇࣝࢻࢩࣜࣥࢪ୰ࡣ L-ࣄࢫࢳࢪࣥ㸪ࢩࣙ⢾㸪࣏ࣜࢯ࣮ࣝ࣋ࢺ 80 ࢆྵ᭷ ࡋ㸪pH ࡣ 6.0 ࡛࠶ࡗࡓࠋಖᏑࡣྵ᭷ࡋ࡚࠸࡞ࡗࡓࠋ ᮏ㹙࢘ࢫࢸ࢟ࢾ࣐ࣈ㸦㑇ఏᏊ⤌࠼㸧㹛ࡢ㟼⬦ෆᢞ⏝〇ࡣ㸪2 ⏝㔞ࡢ࢞ࣛࢫࣂࣝ 㹙90 mg㸦⾲♧㔞 1 mL㸧ཪࡣ 45 mg㸦⾲♧㔞 0.5 mL㸧ࢆྵ᭷㹛ධࢀࡽࢀࡓ༢ᅇᢞ⏝㸪↓⳦ᾮ
14 0 (4) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
ࡋ࡚౪⤥ࡉࢀࡓ㸦ࣂࣝࢡࣟࢵࢺ␒ྕ㸸 㸪 㸪 㸧ࠋᮏࡢᾮయ〇ࡣ㸪 1 mL ࠶ࡓࡾ 90 mg ࡢ࢘ࢫࢸ࢟ࢾ࣐ࣈࢆྵ᭷ࡋࡓࠋ࢘ࢫࢸ࢟ࢾ࣐ࣈࡢ㸪ྛࣂࣝ୰ࡣ L- ࣄࢫࢳࢪࣥ㸪L-ࣄࢫࢳࢪࣥሷ㓟ሷỈ≀㸪ࢩࣙ⢾㸪࣏ࣜࢯ࣮ࣝ࣋ࢺ 80 ࢆྵ᭷ࡋ㸪pH ࡣ 6.0 ࡛࠶ ࡗࡓࠋಖᏑࡣྵ᭷ࡋ࡚࠸࡞ࡗࡓࠋ
(13) ᑐ↷⸆㸪⏝㔞ཬࡧᢞ᪉ἲ㸪ࣟࢵࢺ␒ྕ ࣉࣛࢭ࣎ࡢ⓶ୗᢞ⏝〇ࡣ㸪1.0 mL ࡢࣉࣞࣇࣝࢻࢩࣜࣥࢪධࢀࡽࢀࡓ༢ᅇᢞ⏝㸪↓⳦ ᾮࡋ࡚౪⤥ࡉࢀࡓ㸦ࣂࣝࢡࣟࢵࢺ␒ྕ㸸 㸪 㸪 㸪 㸪 㸧ࠋྛ ࣉࣞࣇࣝࢻࢩࣜࣥࢪ୰ࡣ L-ࣄࢫࢳࢪࣥ㸪ࢩࣙ⢾㸪࣏ࣜࢯ࣮ࣝ࣋ࢺ 80 ࢆྵ᭷ࡋ㸪pH ࡣ 6.0 ࡛ ࠶ࡗࡓࠋ
(14) ᢞᮇ㛫 ᮏヨ㦂ࡢᐶゎ⥔ᣢᮇࡣ 44 㐌┠ࡲ࡛ࡋ㸪ࡑࡢᚋࡣ㛗ᮇ⥅⥆ᢞᮇࡋ࡚᭱㛗 272 㐌┠ࡲ࡛⥅ ⥆ࡋࡓࠋ
(15) ホ౯㡯┠
· ⸆≀ືែ㸸⾑Ύ୰࢘ࢫࢸ࢟ࢾ࣐ࣈ⃰ᗘ
· චཎᛶ㸸ᢠ࢘ࢫࢸ࢟ࢾ࣐ࣈᢠయ
· ⸆ຊᏛ㸭ࣂ࣐࣮࣮࢜࢝㸸⾑Ύࢆ⏝࠸ࡓࣂ࣐࣮࣮࢜࢝㸪ᮎᲈ⾑ࡢ࣓ࢵࢭࣥࢪ࣮ࣕࣜ࣎᰾ 㓟㸦RNA㸧Ⓨ⌧㸪⢓⭷⏕᳨࠾ࡅࡿ RNA Ⓨ⌧㸪୪ࡧᝈཬࡧ⒵ࡢ⤌⧊Ꮫⓗホ౯
· ᭷ຠᛶ㸸CDAI ࢫࢥ㸪CRP ⃰ᗘ㸪౽୰ࣛࢡࢺࣇ࢙ࣜࣥཬࡧ࢝ࣝࣉࣟࢸࢡࢳࣥ⃰ᗘ㸪⒦Ꮝ ࡢホ౯㸪ቯᛶ⮋⓶ࡢホ౯㸪⭠ෆど㙾᳨ᰝ㸦⢓⭷⒵㸧㸦ᣦᐃタ࡛ྠពࡀᚓࡽࢀࡓ ⿕㦂⪅ࡢࡳ㸧
· ᝈ⪅ሗ࿌࢘ࢺ࣒࢝㸸Inflammatory Bowel Disease Questionnaire㸦IBDQ㸧㸪36-item Short- form Health Survey㸦SF-36㸧
· Ᏻᛶ㸸᭷ᐖ㇟㸪㔜⠜࡞᭷ᐖ㇟㸦SAE㸧㸪⮫ᗋ᳨ᰝ㸪ࣂࢱࣝࢧࣥ㸪㦂⸆ࡢ㟼⬦ ෆᢞ୰ཪࡣᢞᚋ 1 㛫௨ෆⓎ⌧ࡋࡓ᭷ᐖ㇟㸦௨ୗ㸪ࣥࣇ࣮ࣗࢪࣙࣥࣜࢡࢩࣙ ࣥ㸧㸪ὀᑕ㒊ᛂ㸪⌮Ꮫⓗᡤぢ
· ་⒪⤒῭㸸་⒪㈨※ࡢ⏝㸪Productivity Visual Analog Scale㸦VAS㸧㸪Work Limitations Questionnaire
(16) ⤫ィᡭἲ ゎᯒᑐ㇟㞟ᅋ ᭷ຠᛶࡢゎᯒࡣ㸪ᐶゎᑟධヨ㦂 CNTO1275CRD3001 ཪࡣ CNTO1275CRD3002 ࡢ࠸ࡎࢀࡢヨ 㦂ࡢ 8 㐌┠ᮏࡢ㟼⬦ෆᢞࡼࡿᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡓ⿕㦂⪅㸦せ࡞
14 1 (5) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
ᑐ㇟㞟ᅋ㸧ࢆᑐ㇟ᐇࡋࡓࠋ࡞࠾㸪ࡇࡢせ࡞ᑐ㇟㞟ᅋࡣ㸪ヨ㦂ࡢ୰᩿๓⤌ࡳධࢀࡽࢀࡓ ⿕㦂⪅ࡣྵࡵ࡞ࡗࡓࠋᮏヨ㦂ཪࡣᐶゎᑟධヨ㦂ࡢ࠸ࡎࢀ࡛ᮏࢆ 1 ᅇ௨ୖᢞࡉࢀࡓࡍ࡚ ࡢ⿕㦂⪅ࢆ⸆≀ືែゎᯒᑐ㇟㞟ᅋࡋࡓࠋࡲࡓ㸪0 㐌┠㦂⸆ࢆᢞࡉࢀࡓࡍ࡚ࡢ⿕㦂⪅ࢆ Ᏻᛶゎᯒᑐ㇟㞟ᅋࡋࡓࠋ
せホ౯㡯┠ 44 㐌┠ࡢ clinical remission㸦CDAI ࢫࢥࡀ 150 ࣏ࣥࢺᮍ‶㸧
せ࡞ḟホ౯㡯┠ せ࡞ḟホ౯㡯┠ࡘ࠸࡚⤫ィᏛⓗ᳨ᐃࢆ⾜࠺㡰ࢆ௨ୗ♧ࡋࡓࠋ 1. 44 㐌┠ࡢ clinical response㸦CDAI ࢫࢥ࠾ࡅࡿᐶゎᑟධヨ㦂 CNTO1275CRD3001 ཪࡣ CNTO1275CRD3002 ࡢ 0 㐌┠ࡽ 100 ࣏ࣥࢺ௨ୖࡢῶᑡ㸧
2. 44 㐌┠ࡢ clinical remission㸦ᮏヨ㦂ࡢ 0 㐌┠ᮏࡼࡿ clinical remission ࡀᚓࡽࢀ࡚࠸ࡓ ⿕㦂⪅㸧
3. 44 㐌┠ࡢ corticosteroid-free remission
4. 44 㐌┠ࡢ clinical remission㹙ᢠ TNF ⸆ຠᯝ༑ศཪࡣᚸᐜᛶࡀ࡞ࡗࡓ⿕㦂⪅ࡢ㒊ศ㞟 ᅋ㸦ᐶゎᑟධヨ㦂 CNTO1275CRD3001 ࡽࡢ⛣⾜⿕㦂⪅㸧㹛
ேཱྀ⤫ィᏛⓗ≉ᛶཬࡧ࣮࣋ࢫࣛࣥࡢᝈ≉ᛶࢆせ⣙ࡋࡓࠋ 44 㐌┠ clinical remission ࡀᚓࡽࢀࡓ⿕㦂⪅ࡢྜ㸦せホ౯㡯┠㸧ࡣ㸪୧ഃ᭷ពỈ‽ 0.05 ࡢ ࡶ㸪Cochran Mantel Haenszel ࡢ᳨࢝ᐃࢆ⏝࠸㸪0 㐌┠ࡢ clinical remission ࡢ᭷↓㸪ᮏࡢ ᐶゎᑟධ⏝㔞㹙130 mg ཪࡣయ㔜ู⏝㔞㸦㹼6 mg/kg㸧㹛ཬࡧᐶゎᑟධヨ㦂㸦CNTO1275CRD3001 ཪࡣ CNTO1275CRD3002㸧ࡼࡾᒙูࡋ㸪ᮏࡢྛᢞ⩌ࣉࣛࢭ࣎⩌ࢆẚ㍑ࡋࡓࠋᮏヨ㦂࡛ ࡣ㸪ࣉࣛࢭ࣎⩌ẚ㍑ࡋ࡚ᮏ 90 mg SC q8w ⩌᭷ពᕪࡀㄆࡵࡽࢀࡓሙྜ㸪ヨ㦂┠ⓗࡀ㐩ࡏ ࡽࢀࡓࡳ࡞ࡋࡓࠋ ྠᵝ㸪せḟホ౯㡯┠ࡣ㸪୧ഃ᭷ពỈ‽ 0.05 ࡢࡶ㸪Cochran Mantel Haenszel ࡢ࢝ ᳨ᐃࢆ⏝࠸㸪0 㐌┠ࡢ clinical remission ࡢ᭷↓㸪ᮏࡢᐶゎᑟධ⏝㔞㹙130 mg ཪࡣయ㔜ู⏝㔞 㸦㹼6 mg/kg㸧㹛ཬࡧᐶゎᑟධヨ㦂㸦CNTO1275CRD3001 ཪࡣ CNTO1275CRD3002㸧ࡼࡾᒙู ࡋ㸪ᮏࡢྛᢞ⩌ࣉࣛࢭ࣎⩌ࢆẚ㍑ࡋࡓࠋ ᮏヨ㦂ࡢせホ౯㡯┠ཬࡧせḟホ౯㡯┠࠾ࡅࡿయࡢ➨୍✀ࡢ㐣ㄗࡢỈ‽ࢆ 0.05 ࢥࣥ ࢺ࣮ࣟࣝࡍࡿࡓࡵ㸪ヨ㦂యཬࡧ⡿ᅜᅛ᭷ࡢᅛᐃ㡰ᗎἲࢆ᥇⏝ࡋࡓࠋࡍ࡚ࡢ⤫ィᏛⓗ࡞᳨ᐃࡣ ୧ഃ᭷ពỈ‽ 0.05 ࡛ᐇࡋ㸪ྡ┠ୖࡢ p ್ࢆ⾲♧ࡋࡓࠋ Ᏻᛶࡢゎᯒࡣ㸪᭷ᐖ㇟ࡢⓎ⌧ྜཬࡧ✀㢮㸪⮫ᗋ᳨ᰝ್㸦⾑ᾮᏛⓗ᳨ᰝཬࡧ⾑ᾮ⏕Ꮫ᳨ ᰝ㸧ࡢ࣮࣋ࢫࣛࣥࡽࡢኚ㔞ࢆせ⣙ࡍࡿࡇ࡛ホ౯ࡋࡓࠋᏳᛶࡢせ⣙ࡣ㸪ᢞ⩌㛫ࡢ೫ࡾ ࡢ࡞࠸ẚ㍑ࢆ⾜࠺ࡓࡵࡢࣛࣥࢲ࣒ࡉࢀࡓ⿕㦂⪅㸦せ࡞ᑐ㇟㞟ᅋ㸧㸪ࣉࣛࢭ࣎ཬࡧᮏࡀᢞ ࡉࢀࡓ⿕㦂⪅࠾ࡅࡿ⯡ⓗ࡞Ᏻᛶࢆホ౯ࡍࡿࡓࡵࡢ㦂⸆ࡀᢞࡉࢀࡓࡍ࡚ࡢ⿕㦂⪅㸦ࣛ ࣥࢲ࣒ࡉࢀࡓ⿕㦂⪅ཬࡧࣛࣥࢲ࣒ࡉࢀ࡞ࡗࡓ⿕㦂⪅㸧ࢆᑐ㇟ᐇࡋࡓࠋ
14 2 (6) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
(17) ⤖ᯝ ᮏሗ࿌࡛ࡣ㸪ᮏᐶゎ⥔ᣢヨ㦂ࡢ 44 㐌┠ࡲ࡛ࡢ⤖ᯝࢆ♧ࡋࡓࠋ
㦂ᑐ㇟㞟ᅋ せ࡞ᑐ㇟㞟ᅋ㸦ࣛࣥࢲ࣒ࡉࢀࡓ⿕㦂⪅㸧㸸 ྜィ 397 ࡢ⿕㦂⪅ࡀᮏヨ㦂࡛ࣛࣥࢲ࣒ࡉࢀࡓ㸦ࣉࣛࢭ࣎⩌㸸133 㸪ᮏ 90 mg SC q12w ⩌㸸132 㸪ᮏ 90 mg SC q8w ⩌㸸132 㸧ࠋࡇࢀࡽࡢ⿕㦂⪅ࡢ࠺ࡕ㸪ዪᛶࡣ 224 㸦56.4%㸧㸪 ⓑேࡣ 337 㸦84.9%㸧࡛࠶ࡾ㸪ᖺ㱋ࡢ୰ኸ್ࡣ 36.0 ṓ㸪య㔜ࡢ୰ኸ್ࡣ 69.0 kg ࡛࠶ࡗࡓࠋ࣮࣋ ࢫࣛࣥࡢேཱྀ⤫ィᏛⓗ≉ᛶࡣ㸪ྛᢞ⩌࡛ྠᵝ࡛࠶ࡗࡓ㸦⾲ 2.7.6.4-1㸧ࠋ
14 3 (7)
(8 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 ⾲ 2.7.6.4-1 CRD3003 ヨ㦂ࡢ࣮࣋ࢫࣛࣥࡢேཱྀ⤫ィᏛⓗ≉ᛶ㸦ࣛࣥࢲ࣒ࡉࢀࡓ⿕㦂⪅㸧 ustekinumab placebo SCa 90 mg SC q12w 90 mg SC q8w Combined Total Analysis set: Randomized subjects 133 132 132 264 397
Age (years) 2.7.6 N 133 132 132 264 397 Mean (SD) 39.5 (12.69) 38.6 (13.65) 37.9 (13.20) 38.3 (13.40) 38.7 (13.17) Median 38.0 36.5 35.0 35.0 36.0 IQ range (29.0; 50.0) (27.0; 48.0) (27.0; 46.5) (27.0; 47.0) (28.0; 48.0) Range (18; 75) (18; 74) (18; 72) (18; 74) (18; 75)
Sex N 133 132 132 264 397 Male 59 (44.4%) 58 (43.9%) 56 (42.4%) 114 (43.2%) 173 (43.6%) Female 74 (55.6%) 74 (56.1%) 76 (57.6%) 150 (56.8%) 224 (56.4%)
Race N 133 132 132 264 397 White 115 (86.5%) 111 (84.1%) 111 (84.1%) 222 (84.1%) 337 (84.9%) Black or African American 5 (3.8%) 5 (3.8%) 3 (2.3%) 8 (3.0%) 13 (3.3%) Asian 7 (5.3%) 12 (9.1%) 13 (9.8%) 25 (9.5%) 32 (8.1%) American Indian or Alaska Native 0 0 0 0 0 Native Hawaiian or other Pacific Islander 0 0 0 0 0 Other 2 (1.5%) 2 (1.5%) 4 (3.0%) 6 (2.3%) 8 (2.0%) Not Reported 2 (1.5%) 2 (1.5%) 1 (0.8%) 3 (1.1%) 5 (1.3%) Unknown 2 (1.5%) 0 0 0 2 (0.5%)
Weight (kg)
N 129 130 130 260 389 ಶ
Mean (SD) 72.31 (17.265) 69.99 (19.606) 70.61 (16.885) 70.30 (18.264) 70.97 (17.941) ࠎ
Median 70.50 66.10 70.00 67.50 69.00 ࡢヨ IQ range (58.70; 81.90) (56.80; 81.00) (56.40; 80.30) (56.60; 80.60) (57.90; 81.10) Range (41.0; 131.0) (35.0; 172.8) (35.0; 127.8) (35.0; 172.8) (35.0; 172.8) 㦂 ࡢࡲ Height (cm) ヨ ࡵ N 129 130 130 260 389 㦂 )
144
(9 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 ustekinumab placebo SCa 90 mg SC q12w 90 mg SC q8w Combined Total Mean (SD) 170.80 (9.918) 169.40 (10.350) 169.12 (10.122) 169.26 (10.218) 169.77 (10.132) Median 170.20 169.00 168.95 169.00 170.00 IQ range (164.00; 177.00) (162.60; 176.00) (161.00; 175.30) (162.00; 175.75) (162.60; 176.50)
Range (149.4; 193.0) (142.4; 196.0) (147.3; 195.6) (142.4; 196.0) (142.4; 196.0) 2.7.6
a Subjects who were in clinical response to ustekinumab IV induction dosing and were randomized to placebo SC on entry into the maintenance study. [TSIDEM02A.rtf] [CNTO1275\CRD3003\DBR_CSR\RE_CSR\tsidem02a.sas] 07OCT2015, 18:14
ಶ ࠎ ࡢヨ 㦂 ࡢࡲ ヨ ࡵ 㦂 )
145 ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
㦂⸆ࡢᢞࢆ୰Ṇࡋࡓ⿕㦂⪅ࡢྜࡣ㸪ྛᢞ⩌࡛ྠ⛬ᗘ࡛࠶ࡗࡓ㹙ࣉࣛࢭ࣎⩌㸸23.3% 㸦31 㸧㸪ᮏ 90 mg SC q12w ⩌㸸22.0%㸦29 㸧㸪ᮏ 90 mg SC q8w ⩌㸸22.7%㸦30 㸧㹛 㸦⾲ 2.7.6.4-2㸧ࠋせ࡞ᑐ㇟㞟ᅋ࡛᭱ࡶከࡃሗ࿌ࡉࢀࡓ㦂⸆ࡢᢞ୰Ṇ⌮⏤ࡣ㸪ຠᯝ༑ศཪ ࡣ᭷ᐖ㇟࡛࠶ࡗࡓࠋ44 㐌┠ࡼࡾ๓ᮏヨ㦂ࢆ୰Ṇࡋࡓ⿕㦂⪅ࡢྜࡣ㸪ࣉࣛࢭ࣎⩌࡛ 9.8% 㸦13 㸧㸪ᮏ 90 mg SC q12w ⩌࡛ 6.8%㸦9 㸧㸪ᮏ 90 mg SC q8w ⩌࡛ 10.6%㸦14 㸧࡛࠶ ࡗࡓࠋ᭱ࡶከࡃሗ࿌ࡉࢀࡓ୰Ṇ⌮⏤ࡣ㸪ྠព᧔ᅇ࡛࠶ࡗࡓ㸦⾲ 2.7.6.4-3㸧ࠋ ࣮࣋ࢫࣛࣥࡢᝈ≉ᛶࡣ㸪᪤Ꮡࡢ⒪ἲࡀ᭷ຠ࡛ࡣ࡞࠸㸪㞴ᛶࡢ୰➼ࡽ㔜ࡢࢡࣟ ࣮ࣥࡢᝈ⪅㞟ᅋࢆ௦⾲ࡍࡿࡶࡢ࡛࠶ࡗࡓࠋࡲࡓ㸪࣮࣋ࢫࣛࣥࡢᝈ≉ᛶࡣ 3 ࡘࡢᢞ⩌࡛ ྠᵝ࡛࠶ࡾ㸪࣮࣋ࢫࣛࣥࡢ⨯ᝈᮇ㛫ࡢ୰ኸ್ࡣ 7.57 ᖺ㸪CDAI ࢫࢥࡢ୰ኸ್ࡣ 311.0㸪⾑ Ύ୰ CRP ⃰ᗘࡢ୰ኸ್ࡣ 9.27 mg/L ࡛࠶ࡗࡓࠋ ࣛࣥࢲ࣒ࡉࢀࡓ⿕㦂⪅㸦397 㸧ࡢ࠺ࡕ㸪ᢠ TNF ⸆ࡀຠᯝ༑ศ࡛࠶ࡗࡓ⿕㦂⪅ࡣ 44.8% 㸦178 㸧㸪ᢠ TNF ⸆ࡢᢞṔࡀ࠶ࡾ㸪ຠᯝ༑ศཪࡣᚸᐜᛶࡀ࡞࠸ࡇࡀ㐣ཤ♧ࡉࢀ࡚࠸࡞ ࠸⿕㦂⪅ࡣ 15.6%㸦62 㸧㸪ᮏヨ㦂ࡢ⤌ࡳධࢀ๓ᢠ TNF ⸆⒪ࡀ⾜ࢃࢀ࡞ࡗࡓ⿕㦂⪅ࡣ 39.5%㸦157 㸧࡛࠶ࡗࡓࠋࡲࡓ㸪79.3%㸦315 㸧ࡢ⿕㦂⪅ࡀ࣮࣋ࢫࣛࣥࢡ࣮ࣟࣥᑐ ࡍࡿే⏝⸆ࢆ 1 ௨ୖᢞࡉࢀ࡚࠾ࡾ㸪ྠⅬ࡛ࡢ⸆ศ㢮ࡈࡢే⏝⋡ࡣ㸪3 ࡘࡢᢞ⩌࡛ྠ ⛬ᗘ࡛࠶ࡗࡓࠋྜィ 181 㸦45.6%㸧ࡀࢥࣝࢳࢥࢫࢸࣟࢻ㸦ࣈࢹࢯࢽࢻ➼㸧㸪143 㸦36.0%㸧 ࡀචㄪ⠇⸆㸦ࢨࢳ࢜ࣉࣜࣥ㸪6-࣓ࣝ࢝ࣉࢺࣉࣜࣥཪࡣ࣓ࢺࢺࣞ࢟ࢧ࣮ࢺ㸧ࢆᢞࡉࢀ࡚࠸ࡓࠋ
⾲ 2.7.6.4-2 CRD3003 ヨ㦂ࡢゎᯒᑐ㇟㞟ᅋ㸦ࣛࣥࢲ࣒ࡉࢀࡓ⿕㦂⪅㸪ヨ㦂య/᪥ᮏே㸧 Entire population Japanese population (397 subjects) (21 subjects) 90 mg/ 90 mg/ 90 mg/ 90 mg/ Placebo q12w q8w Placebo q12w q8w Up to restart(9 subjects) Randomized 2 3 4 - - - Treateda 2 3 4 - - - Discontinuedb 1 0 1 - - -
After restart Randomized 131 129 128 4 8 9 Treateda 131 129 127 4 8 9 Discontinuedb 30 29 29 2 2 1 Efficacy analysis set 131 129 128 4 8 9 Safety analysis setc 131 129 127 4 8 9 90 mg SC q8W Dose- adjusted/Discontinued thereafter 51 29 28 1 1 2
All Treateda 133 132 131 4 8 9
a By planned/randomized treatment group. b Discontinued study agent prior to Week 44. c By actual treatment group. [TPMDASI03A.rtf] [CNTO1275\CRD3003\DBR_CSR\RE_PMDA\tpmdasi03a.sas] 19JUL2016, 21:40
14 6 (10) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
⾲ 2.7.6.4-3 CRD3003 ヨ㦂ࡢ୰Ṇཬࡧゎᯒᑐ㇟㞟ᅋࡽ㝖እࡉࢀࡓ 㸦ࣛࣥࢲ࣒ࡉࢀࡓ⿕㦂⪅㸧 Number Reasons (number of cases) of cases Subjects who discontinued study agent prior to Week 44; Randomized Subjects Entire Placebo 31 Adverse event (9), Lack of efficacy (15), Lost to follow-up - not due to population lack of efficacy or AE (1), Withdrawal of consent for administration of study agent - not due to lack of efficacy or AE (6)
90 mg/q12w 29 Adverse event (12), Lack of efficacy (14), Protocol violation (1), Withdrawal of consent for administration of study agent - not due to lack of efficacy or AE (2)
90 mg/q8w 30 Adverse event (6), Lack of efficacy (15), Protocol violation (1), Lost to follow-up - not due to lack of efficacy or AE (1), Withdrawal of consent for administration of study agent - not due to lack of efficacy or AE (7)
Cases excluded from Efficacy analysis set; Randomized Subjects Entire Placebo 2 Enrolled Prior to Study Re-start (2) population 90 mg/q12w 3 Enrolled Prior to Study Re-start (3)
90 mg/q8w 4 Enrolled Prior to Study Re-start (4)
Japanese Placebo 0 population 90 mg/q12w 0
90 mg/q8w 0
Cases excluded form Safety analysis set; treated subjects who were randomized Entire Placebo 0 population 90 mg/q12w 0
90 mg/q8w 0
Japanese Placebo 0 population 90 mg/q12w 0
90 mg/q8w 0
Source: 3003 CSR tables: TSIDS03A; Tables for answering PMDA questions: TPMDASI03A.
ࡑࡢࡢᑐ㇟㞟ᅋ㸦ࣛࣥࢲ࣒ࡉࢀ࡞ࡗࡓ⿕㦂⪅㸧㸸 ྜィ 884 ࡀᮏヨ㦂⤌ࡳධࢀࡽࢀࡓࡀ㸪ࣛࣥࢲ࣒ࡣࡉࢀ࡞ࡗࡓ㸦ࣉࣛࢭ࣎ࡼࡿᐶゎᑟ ධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡓ⿕㦂⪅㸸123 㸪ࣉࣛࢭ࣎ࡼࡿᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀ࡞ࡗࡓ⿕㦂⪅㸸285 㸪ᮏࡼࡿᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀ ࡞ࡗࡓ⿕㦂⪅㸸476 㸧ࠋ࣮࣋ࢫࣛࣥࡢேཱྀ⤫ィᏛⓗ≉ᛶࡣ㸪ࣛࣥࢲ࣒ࡉࢀࡓ⿕㦂⪅ ࣛࣥࢲ࣒ࡉࢀ࡞ࡗࡓ⿕㦂⪅࡛ྠᵝ࡛࠶ࡗࡓ㸦⾲ 2.7.6.4-4㸧ࠋ
14 7 (11)
(12 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 ⾲ 2.7.6.4-4 CRD3003 ヨ㦂ࡢ࣮࣋ࢫࣛࣥࡢேཱྀ⤫ィᏛⓗ≉ᛶ㸦ࣛࣥࢲ࣒ࡉࢀ࡞ࡗࡓ⿕㦂⪅㸧 Non-responders to IV Responders to placebo IV Non-responders to placebo IV induction dosing Non-responders to ustekinumab IV induction dosing ustekinumab ustekinumab
130 mg IV at 130 mg IV at ustekinumab 90 ustekinumab 90 2.7.6 W0 ĺ W0 ĺ 90 mg mg SC at W0 ĺ mg SC at W0 ĺ discontinuation SC q12w (from discontinuation 90 mg SC q8w placebo SCa at Week 8 Week 8) Combined at Week 8 (from Week 8) Combined Total Analysis set: Non- randomized subjects 123 121 164 285 221 255 476 884
Age (years) N 123 121 164 285 221 255 476 884 Mean (SD) 39.1 (12.46) 39.2 (12.17) 38.9 (12.48) 39.0 (12.33) 38.5 (13.01) 36.5 (11.99) 37.4 (12.50) 38.2 (12.45) Median 38.0 37.0 38.0 38.0 38.0 34.0 36.0 37.0 IQ range (30.0; 47.0) (30.0; 48.0) (27.0; 48.0) (29.0; 48.0) (26.0; 47.0) (26.0; 45.0) (26.0; 46.0) (28.0; 47.0) Range (18; 73) (18; 68) (19; 72) (18; 72) (18; 70) (18; 74) (18; 74) (18; 74)
Sex N 123 121 164 285 221 255 476 884 Male 59 (48.0%) 58 (47.9%) 78 (47.6%) 136 (47.7%) 96 (43.4%) 105 (41.2%) 201 (42.2%) 396 (44.8%) Female 64 (52.0%) 63 (52.1%) 86 (52.4%) 149 (52.3%) 125 (56.6%) 150 (58.8%) 275 (57.8%) 488 (55.2%)
Race N 123 121 164 285 221 255 476 884 White 104 (84.6%) 105 (86.8%) 141 (86.0%) 246 (86.3%) 190 (86.0%) 212 (83.1%) 402 (84.5%) 752 (85.1%) Black or African American 6 (4.9%) 4 (3.3%) 3 (1.8%) 7 (2.5%) 10 (4.5%) 6 (2.4%) 16 (3.4%) 29 (3.3%) Asian 6 (4.9%) 8 (6.6%) 16 (9.8%) 24 (8.4%) 11 (5.0%) 27 (10.6%) 38 (8.0%) 68 (7.7%) American Indian or Alaska Native 0 0 0 0 0 1 (0.4%) 1 (0.2%) 1 (0.1%) Native Hawaiian or other Pacific Islander 0 0 0 0 0 1 (0.4%) 1 (0.2%) 1 (0.1%) ಶ Other 5 (4.1%) 2 (1.7%) 3 (1.8%) 5 (1.8%) 6 (2.7%) 3 (1.2%) 9 (1.9%) 19 (2.1%) ࠎ ࡢヨ Not Reported 2 (1.6%) 0 1 (0.6%) 1 (0.4%) 4 (1.8%) 5 (2.0%) 9 (1.9%) 12 (1.4%) Unknown 0 2 (1.7%) 0 2 (0.7%) 0 0 0 2 (0.2%) 㦂
ࡢࡲ Weight (kg) N 120 120 161 281 221 251 472 873 ヨ ࡵ Mean (SD) 75.09 (18.545) 74.38 (20.545) 70.84 (17.900) 72.35 (19.120) 71.54 (20.282) 70.96 (21.248) 71.23 (20.781) 72.12 (19.981) 㦂 )
148
(13 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 Non-responders to IV Responders to placebo IV Non-responders to placebo IV induction dosing Non-responders to ustekinumab IV induction dosing ustekinumab ustekinumab 130 mg IV at 130 mg IV at ustekinumab 90 ustekinumab 90 W0 ĺ W0 ĺ 90 mg mg SC at W0 ĺ mg SC at W0 ĺ
discontinuation SC q12w (from discontinuation 90 mg SC q8w 2.7.6 placebo SCa at Week 8 Week 8) Combined at Week 8 (from Week 8) Combined Total Median 72.00 69.65 68.20 69.00 69.00 67.10 68.20 68.90 IQ range (61.35; 87.25) (58.20; 89.25) (57.40; 80.40) (57.60; 83.00) (57.10; 81.00) (55.50; 82.50) (56.05; 81.90) (57.40; 82.90) Range (44.1; 141.8) (44.3; 155.6) (35.0; 142.0) (35.0; 155.6) (35.0; 150.1) (39.8; 184.0) (35.0; 184.0) (35.0; 184.0)
Height (cm) N 120 120 161 281 221 251 472 873 Mean (SD) 170.34 (9.971) 170.42 (9.504) 170.65 (9.904) 170.55 (9.718) 169.78 (9.662) 168.37 (9.032) 169.03 (9.349) 169.70 (9.572) Median 169.30 170.00 170.20 170.20 169.30 168.00 168.55 169.30 IQ range (164.25; 177.65) (163.95; 176.75) (162.50; 177.00) (162.60; 177.00) (162.60; 178.00) (162.60; 175.00) (162.60; 175.30) (162.60; 176.40) Range (139.7; 192.5) (149.8; 197.0) (147.3; 195.6) (147.3; 197.0) (147.0; 198.1) (148.0; 195.0) (147.0; 198.1) (139.7; 198.1)
a Subjects who were in clinical response to placebo IV induction dosing and received placebo SC on entry into the maintenance study. [TSIDEM02B.rtf] [CNTO1275\CRD3003\DBR_CSR\RE_CSR\tsidem02b.sas] 07OCT2015, 18:14
ಶ ࠎ ࡢヨ 㦂 ࡢࡲ ヨ ࡵ 㦂 )
149 ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
㦂⸆ࡢᢞࢆ୰Ṇࡋࡓ⿕㦂⪅ࡣ 455 㸦51.5%㸧࡛࠶ࡾ㸪᭱ࡶከࡃሗ࿌ࡉࢀࡓ㦂⸆ࡢᢞ ୰Ṇ⌮⏤ࡣຠᯝ༑ศ࡛࠶ࡗࡓࠋ44 㐌ࡼࡾ๓ᮏヨ㦂ࢆ୰Ṇࡋࡓ⿕㦂⪅ࡢྜࡣ㸪ࣉࣛࢭ࣎ࡼ ࡿᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡓ⿕㦂⪅࡛ 14.6%㸦18/123 㸧㸪clinical response ࡀᚓ ࡽࢀ࡞ࡗࡓ⿕㦂⪅࡛ 15.8%㸦45/285 㸧࡛࠶ࡗࡓࠋ୍᪉㸪ᮏࡼࡾ clinical response ࡀᚓࡽࢀ ࡞ࡗࡓ⿕㦂⪅࡛ 20.6%㸦98/476 㸧࡛࠶ࡗࡓࠋ᭱ࡶከࡃሗ࿌ࡉࢀࡓ୰Ṇ⌮⏤ࡣ㸪ྠព᧔ᅇ࡛࠶ ࡗࡓࠋ ࣮࣋ࢫࣛࣥࡢᝈ≉ᛶࡣ㸪᪤Ꮡࡢ⒪ἲࡀ᭷ຠ࡛ࡣ࡞࠸㸪㞴ᛶࡢ୰➼ࡽ㔜ࡢࢡࣟ ࣮ࣥࡢᝈ⪅㞟ᅋࢆ௦⾲ࡍࡿࡶࡢ࡛࠶ࡗࡓࠋ࣮࣋ࢫࣛࣥࡢ⨯ᝈᮇ㛫ࡢ୰ኸ್ࡣ 9.19 ᖺ㸪 CDAI ࢫࢥࡢ୰ኸ್ࡣ 298.0㸪⾑Ύ୰ CRP ⃰ᗘࡢ୰ኸ್ࡣ 8.1 mg/L ࡛࠶ࡗࡓࠋ ࣛࣥࢲ࣒ࡉࢀ࡞ࡗࡓ⿕㦂⪅㸦884 㸧ࡢ࠺ࡕ㸪ᢠ TNF ⸆ࡀຠᯝ༑ศ࡛࠶ࡗࡓ⿕㦂⪅ࡣ 57.6%㸦509 㸧㸪ᢠ TNF ⸆ࡢᢞṔࡀ࠶ࡾ㸪ຠᯝ༑ศཪࡣᚸᐜᛶࡀ࡞࠸ࡇࡀ㐣ཤ♧ࡉࢀ ࡚࠸࡞࠸⿕㦂⪅ࡣ 14.3%㸦126 㸧㸪ᮏヨ㦂ࡢ⤌ࡳධࢀ๓ᢠ TNF ⸆⒪ࡀ⾜ࢃࢀ࡞ࡗࡓ⿕ 㦂⪅ࡣ 28.2%㸦249 㸧࡛࠶ࡗࡓࠋࢡ࣮ࣟࣥࡢ⒪ᑐࡍࡿే⏝⸆ࡢ⏝≧ἣࡣ㸪ࣛࣥࢲ࣒ ࡉࢀࡓ⿕㦂⪅ࣛࣥࢲ࣒ࡉࢀ࡞ࡗࡓ⿕㦂⪅࡛ྠᵝ࡛࠶ࡗࡓࠋࡲࡓ㸪㐣ཤࢥࣝࢳࢥࢫࢸࣟ ࢻཬࡧචㄪ⠇⸆ࢆ⏝ࡋࡓ⿕㦂⪅ࡢྜࡣ㸪ࣛࣥࢲ࣒ࡉࢀࡓ⿕㦂⪅ࣛࣥࢲ࣒ࡉࢀ࡞ࡗ ࡓ⿕㦂⪅࡛ྠ⛬ᗘ࡛࠶ࡗࡓࠋ
⾲ 2.7.6.4-5 CRD3003 ヨ㦂ࡢゎᯒᑐ㇟㞟ᅋ㸦ࣛࣥࢲ࣒ࡉࢀ࡞ࡗࡓ⿕㦂⪅㸪ヨ㦂య㸧 Entire population (884 subjects) 130mgIV 90mgSC 90 discontinue discontinue Placebo mg/q12w 90 mg/q8w d thereafter d thereafter Up to restart(17 subjects) Not randomized 3 4 4 1 5 Treateda 3 4 4 1 5 Discontinuedb 2 0 2 1 5
After restart Not randomized 120 160 251 120 216 Treateda 120 160 251 120 216 Discontinuedb 28 32 49 120 216 Efficacy analysis set 120 159 251 120 216 Safety analysis seta 120 160 251 120 216
All Safety analysis seta 120 160 251 120 216
a By actual treatment group. b Discontinued study agent prior to Week 44. [TPMDASI03B.rtf] [CNTO1275\CRD3003\DBR_CSR\RE_PMDA\tpmdasi03b.sas] 06JUL2016, 05:37
15 0 (14) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
⾲ 2.7.6.4-6 CRD3003 ヨ㦂ࡢゎᯒᑐ㇟㞟ᅋ㸦ࣛࣥࢲ࣒ࡉࢀ࡞ࡗࡓ⿕㦂⪅㸪᪥ᮏே㸧 Japanese population (53 subjects) 130mgIV 90mgSC 90 discontinue discontinue Placebo mg/q12w 90 mg/q8w d thereafter d thereafter After restart Not randomized 4 11 22 7 9 Treateda 4 11 22 7 9 Discontinuedb 2 3 6 7 9 Efficacy analysis set 4 11 22 7 9 Safety analysis seta 4 11 22 7 9
a By actual treatment group. b Discontinued study agent prior to Week 44. [TPMDASI03C.rtf] [CNTO1275\CRD3003\DBR_CSR\RE_PMDA\tpmdasi03c.sas] 06JUL2016, 22:46
15 1 (15) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
⾲ 2.7.6.4-7 CRD3003 ヨ㦂ࡢ୰Ṇཬࡧゎᯒᑐ㇟㞟ᅋࡽ㝖እࡉࢀࡓ 㸦ࣛࣥࢲ࣒ࡉࢀ࡞ࡗࡓ⿕㦂⪅㸧 Number Reasons (number of cases) of cases Subjects who discontinued study agent prior to Week 44; Non-Randomized Subjects Entire Placebo 30 Adverse event (7), Lack of efficacy (15), Lost to follow-up - not due to population lack of efficacy or AE (2), Withdrawal of consent for administration of study agent - not due to lack of efficacy or AE (6)
90 mg/q12w 32 Adverse event (9), Lack of efficacy (14), Lost to follow-up - not due to lack of efficacy or AE (3), Withdrawal of consent for administration of study agent - not due to lack of efficacy or AE (6)
90 mg/q8w 51 Adverse event (16), Lack of efficacy (25), Protocol violation (1), Lost to follow-up - not due to lack of efficacy or AE (1), Withdrawal of consent for administration of study agent - not due to lack of efficacy or AE (8)
130 mg IV 121 Adverse event (5), Lack of efficacy (112), Lost to follow-up - not due to discontinued lack of efficacy or AE (2), Withdrawal of consent for administration of thereafter study agent - not due to lack of efficacy or AE (2)
90 mg SC 221 Adverse event (9), Lack of efficacy (192), Protocol violation (1), Lost to discontinued follow-up - not due to lack of efficacy or AE (5), Withdrawal of consent thereafter for administration of study agent - not due to lack of efficacy or AE (14)
Japanese Placebo 2 Adverse event (1), Lack of efficacy (1) population 90 mg/q12w 3 Adverse event (2), Lack of efficacy (1) 90 mg/q8w 6 Adverse event (2), Lack of efficacy (1), Withdrawal of consent for administration of study agent - not due to lack of efficacy or AE (3)
130 mg IV 7 Lack of efficacy (6), Withdrawal of consent for administration of study discontinued agent - not due to lack of efficacy or AE (1) thereafter 90 mg SC 9 Lack of efficacy (6), Withdrawal of consent for administration of study discontinued agent - not due to lack of efficacy or AE (3) thereafter Cases excluded form Safety analysis set; Treated Subjects Entire Placebo 0 population 90 mg/q12w 0 90 mg/q8w 0 130 mg IV 0 discontinued thereafter 90 mg SC 0 discontinued thereafter Japanese Placebo 0 population 90 mg/q12w 0 90 mg/q8w 0 130 mg IV 0 discontinued thereafter 90 mg SC 0 discontinued thereafter Source: 3003 CSR tables: TSIDS03B, TJPDS03B; Tables for answering PMDA questions: TPMDASI03B.
15 2 (16) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
᭷ຠᛶ ᮏヨ㦂࡛ࡣ㸪ᮏ 90 mg SC q12w ⩌ཬࡧᮏ 90 mg SC q8w ⩌ࡶ㸪44 㐌┠࡛ࡢ clinical response ཬࡧ clinical remission ᇶ࡙ࡃᐶゎ⥔ᣢ⒪ἲࡢ᭷ຠᛶࡀ♧ࡉࢀࡓࠋࡲࡓ㸪せホ౯㡯┠ ࡢ㡹ᛶࢆྵࡴࢹ࣮ࢱయࡢ⤖ᯝࡼࡾ㸪せ࡞⏝ἲ࣭⏝㔞ࡋ࡚ᮏ 90 mg SC q8w ࡀᨭᣢࡉ ࢀࡓࠋࡇࡢ⏝ἲ࣭⏝㔞ࡣ㸪ᮏ 90 mg SC q12w ẚ㍑ࡋ࡚ከࡃࡢホ౯㡯┠࡛⒪ຠᯝࡀ㧗ࡗࡓࠋ
ᮏࡼࡿᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡓ⿕㦂⪅࡛ࡢ⮫ᗋຠᯝ せホ౯㡯┠ · 44 㐌┠ clinical remission ࡀᚓࡽࢀࡓ⿕㦂⪅ࡢྜࡣ㸪ࣉࣛࢭ࣎⩌㸦35.9%㸪47/131 㸧 ẚ㍑ࡋ࡚ᮏ 90 mg SC q12w ⩌㸦48.8%㸪63/129 㸧ཬࡧᮏ 90 mg SC q8w ⩌㸦53.1%㸪 68/128 㸧࡛᭷ព㧗ࡗࡓ㸦ࡑࢀࡒࢀ p=0.040 ཬࡧ p=0.005㸧ࠋ
· ឤᗘศᯒ࡛ࡣᮏ 90 mg SC q8w ࡢ⏝ἲ࣭⏝㔞ࡢ㡹ᛶࡀ♧ࡉࢀࡓ㸦᭱ࡶಖᏲⓗ࡞ゎ ᯒ᪉ἲࢆ㝖ࡃࡍ࡚ࡢゎᯒ࠾࠸࡚᭷ពᕪࡀㄆࡵࡽࢀࡓ㸧ࠋࡋࡋ㸪⒪ຠᯝࡢഴ ྥࡣゎᯒྠᵝ࡛࠶ࡾ㸪ࡑࡢ⛬ᗘࡶ⯡ⓗྠ⛬ᗘ࡛࠶ࡗࡓࡀ㸪ᮏ 90 mg SC q12w ࡢ⏝ἲ࣭⏝㔞࡛ࡢឤᗘศᯒ࡛ࡣ⯡ⓗ᭷ពᕪࡣㄆࡵࡽࢀ࡞ࡗࡓࠋ
· ᐶゎ⥔ᣢᮇࡢ clinical remission ࠾ࡅࡿᮏࡢ⒪ຠᯝࡣ㸪㒊ศ㞟ᅋ㛫࡛⯡ⓗྠ ⛬ᗘ࡛࠶ࡗࡓࠋࡋࡋ㸪ࡇࢀࡽࡢゎᯒ࡛ࡣయ㔜 CRP ⃰ᗘࡀ⏝㔞ᙳ㡪ࢆ࠼ࡿඹ ኚ㔞࡛࠶ࡿྍ⬟ᛶࡀ♧၀ࡉࢀࡓࠋ
せ࡞ḟホ౯㡯┠ · 44 㐌┠ clinical response ࡀᚓࡽࢀࡓ⿕㦂⪅ࡢྜࡣ㸪ࣉࣛࢭ࣎⩌㸦44.3%㸪58/131 㸧 ẚ㍑ࡋ࡚ᮏ 90 mg SC q12w ⩌㸦58.1%㸪75/129 㸧ཬࡧᮏ 90 mg SC q8w ⩌㸦59.4%㸪 76/128 㸧࡛᭷ព㧗ࡗࡓ㸦ࡑࢀࡒࢀ p=0.033 ཬࡧ p=0.018㸧ࠋ
· ࣮࣋ࢫࣛࣥ clinical remission ࡀᚓࡽࢀ࡚࠸ࡓ⿕㦂⪅ࡣせ࡞ᑐ㇟㞟ᅋࡢ⣙ 60%࡛࠶ࡗ ࡓࡀ㸪ࡇࡢ࠺ࡕ 44 㐌┠ clinical remission ࡀᚓࡽࢀࡓ⿕㦂⪅ࡢྜࡣ㸪ࣉࣛࢭ࣎⩌㸦45.6%㸪 36/79 㸧ẚ㍑ࡋ࡚ᮏ 90 mg SC q8w ⩌㸦66.7%㸪52/78 㸧࡛᭷ព㧗ࡗࡓ 㸦p=0.007㸧ࠋࡲࡓ㸪ᮏ 90 mg SC q12w ⩌ࡣ 56.4%㸦44/78 㸧࡛࠶ࡾ㸪ࣉࣛࢭ࣎⩌ࡢ 45.6%ẚ㍑ࡋ࡚㧗ࡗࡓࡀ㸪⤫ィᏛⓗ࡞᭷ពᕪࡣㄆࡵࡽࢀ࡞ࡗࡓ㸦p=0.189㸧ࠋ
· 44 㐌┠ corticosteroid-free remission ࡀᚓࡽࢀࡓ⿕㦂⪅ࡢྜࡣ㸪ࣉࣛࢭ࣎⩌㸦29.8%㸪 39/131 㸧ẚ㍑ࡋ࡚ᮏ 90 mg SC q12w ⩌㸦42.6%㸪55/129 㸧ཬࡧᮏ 90 mg SC q8w ⩌㸦46.9%㸪60/128 㸧࡛㧗ࡗࡓࠋᮏホ౯㡯┠࡛ࡢ୧ᮏ⩌ࣉࣛࢭ࣎⩌ࡢẚ㍑࠾ࡅ ࡿྡ┠ୖࡢ p ್ࡣ p<0.05 ࡛࠶ࡗࡓࡀ㸪ヨ㦂యࡢᅛᐃ㡰ᗎἲ࡛ࡣࣉࣛࢭ࣎⩌ࡢ᭷ពᕪࡀ ㄆࡵࡽࢀࡓࡢࡣᮏ 90 mg SC q8w ⩌ࡢࡳ࡛࠶ࡗࡓ⪃࠼ࡽࢀࡓ㸦p=0.004㸧ࠋ⡿ᅜᅛ᭷ࡢ ᳨ᐃ᪉ἲ࡛ࡣ㸪୧ᮏ⩌ࡶࣉࣛࢭ࣎⩌ࡢ⤫ィᏛⓗ࡞᭷ពᕪࡣㄆࡵࡽࢀ࡞ࡗࡓࠋ
· ᢠ TNF ⸆ຠᯝ༑ศ࡛࠶ࡗࡓ⿕㦂⪅ࡢ㒊ศ㞟ᅋ࡛ࡣ㸪44 㐌┠ clinical remission ࡀᚓࡽ ࢀࡓ⿕㦂⪅ࡢྜࡣ㸪ࣉࣛࢭ࣎⩌㸦26.2%㸪16/61 㸧ẚ㍑ࡋ࡚ᮏ 90 mg SC q12w ⩌ 㸦38.6%㸪22/57 㸧ཬࡧᮏ 90 mg SC q8w ⩌㸦41.1%㸪23/56 㸧࡛㧗ࡗࡓࠋࡇࢀࡽࡢ
15 3 (17) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
⒪ຠᯝࡣయ㞟ᅋྠ⛬ᗘ࡛࠶ࡗࡓࡀ㸪ࡇࡢ㒊ศ㞟ᅋྵࡲࢀࡓ⿕㦂⪅ࡣᮏヨ㦂ࡢせ࡞ ᑐ㇟㞟ᅋࡢ 44.8%࡛࠶ࡾ㸪ࣉࣛࢭ࣎⩌ࡢ᭷ពᕪࢆ♧ࡍࡓࡵࡢ༑ศ࡞᳨ฟຊࡣ࡞ࡗࡓࠋ
ࡑࡢࡢ⮫ᗋ㌿ᖐ ௨ୗࡢḟホ౯㡯┠ࡘ࠸࡚ࡣ㸪ከ㔜ᛶࡢㄪᩚࡣ⾜ࢃ࡞ࡗࡓࠋࡇࢀࡽࡢホ౯㡯┠࡛ࡣ㸪⤫ィ Ꮫⓗ࡞᭷ពᕪࡣྡ┠ୖࡢ p ್ᇶ࡙࠸࡚ᥦ♧ࡋࡓࠋ
Clinical remission ཬࡧ clinical response ࡢ⥔ᣢ · Clinical remission ࡀ⥔ᣢࡉࢀࡓ⿕㦂⪅ࡢྜࡣ㸪ࣉࣛࢭ࣎⩌㸦26.0%㸪34/131 㸧ẚ㍑ࡋ ࡚ᮏ 90 mg SC q12w ⩌㸦40.3%㸪52/129 㸧ཬࡧᮏ 90 mg SC q8w ⩌㸦46.1%㸪59/128 㸧 ࡛᭷ព㧗ࡗࡓ㸦ࡑࢀࡒࢀ p=0.023 ཬࡧ p<0.001㸧ࠋ
· Clinical response ࡀ⥔ᣢࡉࢀࡓ⿕㦂⪅ࡢྜࡣ㸪ࣉࣛࢭ࣎⩌㸦38.2%㸪50/131 㸧ẚ㍑ࡋ࡚ ᮏ 90 mg SC q12w ⩌㸦53.5%㸪69/129 㸧ཬࡧᮏ 90 mg SC q8w ⩌㸦53.1%㸪68/128 㸧 ࡛᭷ព㧗ࡗࡓ㸦࠸ࡎࢀࡶ p=0.019㸧ࠋ
⏝㔞ㄪ⠇ · LOR ᇶ‽ࢆ‶ࡓࡋࡓᮏ 90 mg SC q12w ⩌ࡢ⿕㦂⪅࡛ࡣ㸪ᮏ 90 mg SC q8w ࡢ⏝㔞ㄪ⠇ ࡼࡾ㸪⏝㔞ㄪ⠇ࢆ⾜ࢃ࡞ࡗࡓ⿕㦂⪅㸦q8wЍq8w㸧ࢆୖᅇࡿ᭦࡞ࡿ⮫ᗋຠᯝࡀᚓࡽࢀࡓࠋ
· LOR ᇶ‽ࢆ㐺⏝ࡋ࡞࠸ゎᯒ㸦ᙜึࡾࡅࡽࢀࡓᢞ⩌ࢆ⥔ᣢ㸧࡛ࡣ㸪ᮏ 90 mg SC q12w ࡛㛤ጞࡋ㸪LOR ᇶ‽ᛂࡌ࡚ q8w ㄪ⠇ࡋࡓ⿕㦂⪅㸪ᮏ 90 mg SC q8w ࡛⥅⥆ᢞ ࡉࢀࡓ⿕㦂⪅࡛㸪᭱⤊ⓗࡣ clinical response ཬࡧ clinical remission ࡀᚓࡽࢀࡓ⿕㦂⪅ࡢ ྜࡀྠ⛬ᗘ࡞ࡿࡇࡀ♧၀ࡉࢀࡓࠋ
ࢥࣝࢳࢥࢫࢸࣟࢻ㛵㐃ࡍࡿ᭷ຠᛶ · 44 㐌┠௨๓ࡢ 90 ᪥㛫௨ୖࢥࣝࢳࢥࢫࢸࣟࢻࢆే⏝ࡋ࡚࠸࡞࠸᮲௳ࢆ㏣ຍࡋࡓሙྜࡢ 44 㐌┠ࡢ clinical remission 㸪44 㐌┠௨๓ࡢ 30 ᪥㛫௨ୖࢥࣝࢳࢥࢫࢸࣟࢻࢆే⏝ࡋ࡚࠸࡞ ࠸᮲௳ࢆ㏣ຍࡋࡓሙྜࡢ 44 㐌┠ࡢ clinical remission ࢆࡑࢀࡒࢀゎᯒࡋࡓࠋࡑࢀࡽࡢ⿕㦂⪅ ࡢྜࡣ㸪ࣉࣛࢭ࣎⩌ẚ㍑ࡋ࡚ᮏ⩌࡛᭷ព㧗ࡗࡓࠋ
· 44 㐌┠ clinical response ࡀᚓࡽࢀ㸪ࡘ 44 㐌┠ࢥࣝࢳࢥࢫࢸࣟࢻࢆే⏝ࡋ࡚࠸࡞ ࡗࡓ⿕㦂⪅ࡢྜࡣ㸪ࣉࣛࢭ࣎⩌㸦36.6%㸪48/131 㸧ẚ㍑ࡋ࡚ᮏ 90 mg SC q12w ⩌ 㸦51.2%㸪66/129 㸧ཬࡧᮏ 90 mg SC q8w ⩌㸦50.8%㸪65/128 㸧࡛᭷ព㧗ࡗࡓࠋ
· ࣮࣋ࢫࣛࣥࢥࣝࢳࢥࢫࢸࣟࢻࢆే⏝ࡋ࡚࠾ࡾ㸪44 㐌┠ clinical remission ཪࡣ clinical response ࡀᚓࡽࢀ㸪ࡘ 44 㐌┠ࢥࣝࢳࢥࢫࢸࣟࢻࢆే⏝ࡋ࡚࠸࡞࠸⿕㦂⪅ࡢ ྜࡣ㸪ࣉࣛࢭ࣎⩌ẚ㍑ࡋ࡚ᮏేྜ⩌࡛᭷ព㧗ࡗࡓࠋࡲࡓ㸪44 㐌┠ࡲ࡛ࢥࣝࢳࢥ ࢫࢸࣟࢻࡢ⏝ࡀ୰Ṇྍ⬟࡞ࡗࡓ⿕㦂⪅ࡢྜࡣ㸪ࣉࣛࢭ࣎⩌ẚ㍑ࡋ࡚ᮏ 90 mg SC q12w ⩌ཬࡧᮏ 90 mg SC q8w ⩌࡛㧗ࡗࡓࠋ
15 4 (18) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
ࡑࡢࡢホ౯㡯┠ · ⮫ᗋⓗ᭷ຠᛶࡢ⤒ⓗ࡞ゎᯒ࡛ࡣ㸪ᮏ 90 mg SC q12w ⩌ᮏ 90 mg SC q8w ⩌࡛⯡ⓗ ྠ⛬ᗘ࡛࠶ࡾ㸪20 㐌┠ࡽࣉࣛࢭ࣎⩌ࡢ㞳ࡀㄆࡵࡽࢀࡓࠋ
· 44 㐌┠࡛ࡣ㸪ᐶゎᑟධᮇᚓࡽࢀࡓ CDAI ࢫࢥࡣ㸪ᮏ⩌࡛ࡣᨵၿࡀ⥔ᣢࡉࢀࡓࡀ㸪ࣉ ࣛࢭ࣎⩌࡛ࡣᝏࡀㄆࡵࡽࢀࡓࠋCDAI ࢫࢥࡢᐶゎ⥔ᣢヨ㦂ࡢ࣮࣋ࢫࣛࣥࡽࡢኚ 㔞ࡢ୰ኸ್ࡣ㸪ࣉࣛࢭ࣎⩌ 74.0 ᑐࡋ㸪ᮏ 90 mg SC q12w ⩌ཬࡧᮏ 90 mg SC q8w ⩌࡛ ࡣࡑࢀࡒࢀ-10.0 ཬࡧ-6.0 ࡛࠶ࡗࡓ㸦ࡑࢀࡒࢀ p=0.030 ཬࡧ p<0.001㸧ࠋ
· ᢠ TNF ⸆⒪Ṕࡢ࡞࠸⿕㦂⪅㸦ᐶゎᑟධヨ㦂 CNTO1275CRD3002 ࡽ⤌ࡳධࢀࡽࢀࡓ⿕㦂 ⪅㸧ࡣ㸪ᢠ TNF ⸆⒪ᑐࡋ࡚ຠᯝ༑ศ࡛࠶ࡗࡓ⿕㦂⪅ẚ㍑ࡋ࡚㸪clinical remission ࡀ ᚓࡽࢀࡓ⿕㦂⪅ࡢྜࡀ⯡ⓗ㧗ࡗࡓࠋᢠ TNF ⸆⒪Ṕࡢ࡞࠸⿕㦂⪅࠾࠸࡚㸪44 㐌 ┠ clinical remission ࡀᚓࡽࢀࡓ⿕㦂⪅ࡢྜࡣ㸪ࣉࣛࢭ࣎⩌㸦49.0%㸪25/51 㸧ẚ㍑ࡋ ࡚ᮏ 90 mg SC q12w ⩌㸦56.6%㸪30/53 㸧ཬࡧᮏ 90 mg SC q8w ⩌㸦65.4%㸪34/52 㸧 ࡛㧗ࡃ㸪ᮏ 90 mg SC q8w ⩌࡛ࡣ᭷ពᕪࡀㄆࡵࡽࢀࡓ㸦p=0.041㸧ࠋ
· 16 㐌┠௨㝆㸪ᐶゎᑟධᢞࡽࡢ࣮࣮࢟ࣕࣜ࢜ࣂ࣮ຠᯝࡣㄆࡵࡽࢀ࡞ࡗࡓࠋ
· 44 㐌┠⒦Ꮝ㛢㙐ຠᯝࡀㄆࡵࡽࢀࡓ⿕㦂⪅ࡢྜࡣ㸪ᮏేྜ⩌࡛ 80.0%㸦12/15 㸧㸪ࣉ ࣛࢭ࣎⩌࡛ 45.5%㸦5/11 㸧࡛࠶ࡗࡓࠋ
⅖࣐࣮࣮࢝ · ᐶゎᑟධヨ㦂ࡢ 0 㐌┠ࡽᮏヨ㦂ࡢ࣮࣋ࢫࣛࣥ㸦0 㐌┠㸧ࡲ࡛ࡢ CRP ⃰ᗘࡢῶᑡ㔞ࡢ ୰ኸ್ࡣ㸪ࣉࣛࢭ࣎⩌ẚ㍑ࡋ࡚୧ᮏ⩌࡛ 44 㐌┠ࡲ࡛᭷ព⥔ᣢࡉࢀࡓࠋ⤒ⓗ࡞᳨ウ ࡛ࡣ㸪ᮏ 90 mg SC q12w ⩌ẚ㍑ࡋ࡚㸪ᮏ 90 mg SC q8w ⩌࡛ࡼࡾ୍㈏ࡋ࡚⅖ࡀࢥࣥ ࢺ࣮ࣟࣝࡉࢀࡓࠋ
· ᮏヨ㦂ࡢ 0 㐌┠࠾ࡅࡿ౽୰ࣛࢡࢺࣇ࢙ࣜࣥཬࡧ࢝ࣝࣉࣟࢸࢡࢳࣥ⃰ᗘࡢపୗࡣ 20 㐌┠ ࣉࣛࢭ࣎⩌ẚ㍑ࡋ࡚୧ᮏ⩌࡛⥔ᣢࡉࢀ㸪ࡲࡓ 44 㐌┠࡛ࡣ᭷ពᕪࡀㄆࡵࡽࢀࡓࠋ
· ౽୰ࣛࢡࢺࣇ࢙ࣜࣥ⃰ᗘࡀṇᖖࡋࡓ⿕㦂⪅ࡢྜࡣ㸪୧ᮏ⩌࡛ࡣ୍ᐃ࡛࠶ࡗࡓ⤒ ⓗࢃࡎୖ᪼ࡋ㸪44 㐌┠࡛ࡣࣉࣛࢭ࣎⩌ẚ㍑ࡋ࡚୧ᮏ⩌࡛᭷ព㧗ࡗࡓࠋ ࣉࣛࢭ࣎⩌࡛ࡣ㸪౽୰ࣛࢡࢺࣇ࢙ࣜࣥ⃰ᗘࡀṇᖖࡋࡓ⿕㦂⪅ࡢྜࡣ⤒ⓗపୗࡋ ࡓࠋ
· 44 㐌┠౽୰࢝ࣝࣉࣟࢸࢡࢳࣥ⃰ᗘࡀ 250 ȝg/g ௨ୗཪࡣ 100 ȝg/g ௨ୗ࡛࠶ࡗࡓ⿕㦂⪅ ࡢྜࡣ㸪ࣉࣛࢭ࣎⩌ẚ㍑ࡋ࡚୧ᮏ⩌࡛᭷ព㧗ࡗࡓࠋ
15 5 (19) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
ᝈ⪅ሗ࿌࢘ࢺ࣒࢝ཬࡧ་⒪⤒῭ ᝈ⪅ሗ࿌࢘ࢺ࣒࢝ · 44 㐌┠ࡢ IBDQ ࢫࢥࡢᮏヨ㦂ࡢ࣮࣋ࢫࣛࣥ㸦0 㐌┠㸧ࡽࡢኚ㔞ࡢ୰ኸ್ࡣ㸪ࣉࣛ ࢭ࣎⩌㸦-14.5㸧ẚ㍑ࡋ࡚㸪ᮏ 90 mg SC q12w ⩌㸦-2.5㸧ཬࡧᮏ 90 mg SC q8w ⩌㸦-2.0㸧 ࡛᭷ពᑠࡉࡗࡓ㸦ࡑࢀࡒࢀ p<0.001 ཬࡧ p=0.003㸧ࠋ
· 44 㐌┠ࡢ IBDQ ࢫࢥ㸦4 ศ㔝ࡍ࡚ࡢࢫࢥ㸧࠾ࡅࡿኚ㔞ࡢ୰ኸ್ࡣ㸪ࣉࣛࢭ࣎⩌ ẚ㍑ࡋ࡚୧ᮏ⩌࡛᭷ពᑠࡉࡗࡓࠋ
· 44 㐌┠ IBDQ ࢫࢥ࡛ 16 ࣏ࣥࢺ௨ୖࡢᨵၿࡀᚓࡽࢀࡓ⿕㦂⪅ࡢྜࡣ㸪ࣉࣛࢭ࣎⩌࡛ ࡣ 50.4%㸦60/119 㸧㸪ᮏ 90 mg SC q12w ⩌ཬࡧᮏ 90 mg SC q8w ⩌࡛ࡣࡑࢀࡒࢀ 61.3%㸦73/119 㸧ཬࡧ 67.9%㸦76/112 㸧࡛࠶ࡗࡓ㸦ࡑࢀࡒࢀ p=0.140 ཬࡧ p=0.014㸧ࠋ
· 44 㐌┠ࡢ SF-36 ࡢ㌟యⓗഃ㠃ࡢ QOL ࢧ࣐࣮ࣜ㸦PCS㸧ࢫࢥ࠾ࡅࡿᮏヨ㦂ࡢ࣮࣋ࢫࣛ ࣥࡽࡢኚ㔞㸦ᖹᆒ್±SD㸧ࡣ㸪ࣉࣛࢭ࣎⩌ 㸦-3.56±9.326㸧ẚ㍑ࡋ࡚㸪ᮏ 90 mg SC q8w ⩌㸦-0.93±7.139㸧࡛᭷ពᑠࡉࡃ 㸦p=0.003㸧㸪ᮏ 90 mg SC q12w ⩌㸦-2.30±9.311㸧࡛ࡣᑠࡉࡗࡓࡶࡢࡢ᭷ពᕪࡣㄆࡵࡽ ࢀ࡞ࡗࡓࠋ44 㐌┠ࡢ SF-36 ࡢ⢭⚄ⓗഃ㠃ࡢ QOL ࢧ࣐࣮ࣜ㸦MCS㸧ࢫࢥ࠾ࡅࡿᮏヨ 㦂ࡢ࣮࣋ࢫࣛࣥࡽࡢኚ㔞㸦ᖹᆒ್±SD㸧ࡣ㸪ࣉࣛࢭ࣎⩌㸦-4.38±11.058㸧ẚ㍑ࡋ࡚㸪 ᮏ 90 mg SC q12w ⩌㸦-1.89±12.679㸧ཬࡧᮏ 90 mg SC q8w ⩌㸦-1.67±9.759㸧࡛᭷ពᑠ ࡉࡗࡓࠋ
· SF-36 PCS ࢫࢥ࠾࠸࡚ᐶゎᑟධヨ㦂ࡢ࣮࣋ࢫࣛࣥࡽࡢ⮫ᗋⓗពࡢ࠶ࡿᨵၿ㸦5 ࣏ࣥࢺ௨ୖࡢᨵၿ㸧ࡀㄆࡵࡽࢀࡓ⿕㦂⪅ࡢྜࡣ㸪ࣉࣛࢭ࣎⩌ẚ㍑ࡋ࡚ᮏ 90 mg SC q8w ⩌࡛᭷ព㧗ࡗࡓࠋࡲࡓ㸪SF-36 MCS ࢫࢥ࠾࠸࡚ 44 㐌┠⮫ᗋⓗពࡢ࠶ࡿ ᨵၿ㸦5 ࣏ࣥࢺ௨ୖࡢᨵၿ㸧ࡀㄆࡵࡽࢀࡓ⿕㦂⪅ࡢྜࡣ㸪ࣉࣛࢭ࣎⩌ẚ㍑ࡋ࡚ᮏ 90 mg SC q12w ⩌ཬࡧᮏ 90 mg SC q8w ⩌࡛᭷ព㧗ࡗࡓࠋ
· 44 㐌┠࠾ࡅࡿ SF-36 ࡢศ㔝ูࢫࢥࡢ 0 㐌┠ࡽࡢኚ㔞ࡢᖹᆒ್ࡣ㸪⯡ⓗࣉࣛࢭ ࣎⩌ẚ㍑ࡋ࡚ᮏ 90 mg SC q8w ⩌࡛పࡗࡓ㹙ࠕయⓗᗣឤࠖ㸦p=0.055㸧ཬࡧࠕ᪥ ᖖᙺᶵ⬟㸦⢭⚄㸧ࠖ㸦p=0.058㸧ࢆ㝖ࡁ㸪࠸ࡎࢀࡶ p<0.05㹛ࠋ
་⒪⤒῭ · 44 㐌┠ࡢ Productivity VAS ࡢ࣮࣋ࢫࣛࣥࡽࡢኚ㔞ࡢ୰ኸ್ࡣ㸪ࣉࣛࢭ࣎⩌㸦1.4㸧 ẚ㍑ࡋ࡚ᮏ 90 mg SC q12w ⩌㸦0.0㸧ཬࡧᮏ 90 mg SC q8w ⩌㸦0.1㸧࡛᭷ពᑠࡉࡗ ࡓ㸦ࡑࢀࡒࢀ p=0.006 ཬࡧ p=0.017㸧ࠋ
· ᮏヨ㦂ࡢ 44 㐌┠ࡲ࡛ࡢ་⒪㈨※㸦ධ㝔ཬࡧᡭ⾡㸧ࡢ⏝ࡣᑡ࡞ࡃ㸪ᢞ⩌㛫࡛ᕪࡣㄆࡵࡽ ࢀ࡞ࡗࡓࠋ
15 6 (20) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
ࣛࣥࢲ࣒ࡉࢀ࡞ࡗࡓ⿕㦂⪅ · ᮏࡢ㟼⬦ෆᢞࡼࡿᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀ࡞ࡗࡓ⿕㦂⪅࡛ࡣ㸪ᮏ 90 mg ࡢ㏣ຍࡢ⓶ୗᢞࡢ 8 㐌ᚋ㸪༙ᩘ௨ୖࡢ⿕㦂⪅࡛ clinical response ࡀᚓࡽࢀࡓࠋ ࡇࢀࡽࡢᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏ 90 mg SC q8w ࡢᢞࢆ⥅⥆ࡋࡓ⿕㦂⪅ࡢ࠺ࡕ㸪44 㐌┠ clinical response ࢆ⥔ᣢࡋࡓ⿕㦂⪅ࡢྜࡣ 68.1%㸦171/251 㸧㸪clinical remission ࢆ⥔ᣢࡋ ࡓ⿕㦂⪅ࡢྜࡣ 50.2%㸦126/251 㸧࡛࠶ࡗࡓࠋ
· ࣉࣛࢭ࣎ࡢ㟼⬦ෆᢞࡼࡿᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀ࡞ࡗࡓ⿕㦂⪅࡛ࡣ㸪 ᮏࡢ㟼⬦ෆᢞࡢ 8 㐌ᚋ㸪༙ᩘ௨ୖࡢ⿕㦂⪅࡛ clinical response ࡀᚓࡽࢀࡓࠋᐶゎ⥔ᣢ ⒪ἲࡋ࡚ᮏ 90 mg q12w ࡢᢞࢆ⥅⥆ࡋࡓࡇࢀࡽࡢ⿕㦂⪅ࡢ࠺ࡕ㸪44 㐌┠ clinical response ࢆ⥔ᣢࡋࡓ⿕㦂⪅ࡢྜࡣ 66.7%㸦106/159 㸧㸪clinical remission ࢆ⥔ᣢࡋࡓ⿕㦂 ⪅ࡢྜࡣ 49.7%㸦79/159 㸧࡛࠶ࡗࡓࠋ
᭷ຠᛶ⸆≀ືែ㸭චཎᛶ · ᐶゎ⥔ᣢᮇ࡛ࡣ⯡ⓗ㸪⾑Ύ୰࢘ࢫࢸ࢟ࢾ࣐ࣈ⃰ᗘ⮫ᗋⓗ᭷ຠᛶ㸦clinical response ཬ ࡧ clinical remission㸧ṇࡢ┦㛵ࡀㄆࡵࡽࢀࡓࠋࡲࡓ㸪⾑Ύ୰࢘ࢫࢸ࢟ࢾ࣐ࣈ⃰ᗘࡀ㧗ࡗ ࡓ⿕㦂⪅࠾࠸࡚㸪CRP ࡛ホ౯ࡉࢀࡓ⅖࣐࣮࣮࢝ࡢప್ࡀㄆࡵࡽࢀࡓࠋ
· 24 㐌┠ clinical remission ࡀᚓࡽࢀࡓ⿕㦂⪅ࡢྜࡣ㸪24 㐌┠ࡢ⾑Ύ୰࢘ࢫࢸ࢟ࢾ࣐ࣈ⃰ ᗘࡢࢺࣛࣇ್ࡀ㧗್࡛࠶ࡿ㧗ࡗࡓࠋClinical remission ࡀᚓࡽࢀࡓ⿕㦂⪅ࡢྜࡀ᭱ࡶ పࡗࡓ㸪⾑Ύ୰࢘ࢫࢸ࢟ࢾ࣐ࣈ⃰ᗘࡀ➨ 1 ᅄศᩘ௨ୗࡢ⿕㦂⪅㞟ᅋ࡛ࡣ㸪㒊ศࡢ⿕ 㦂⪅ࡀᮏ 90 mg SC q12w ࢆᢞࡉࢀ࡚࠸ࡓࠋ
· ᮏࡢᐶゎ⥔ᣢ⒪ἲࢆཷࡅ࡚࠸ࡓ⿕㦂⪅࡛ࡣ㸪ᢠ࢘ࢫࢸ࢟ࢾ࣐ࣈᢠయࡢⓎ⌧ᚋ㸪⮫ᗋⓗ ᭷ຠᛶᑐࡍࡿ᫂ࡽ࡞ᙳ㡪ࡣㄆࡵࡽࢀ࡞ࡗࡓࠋ࡞࠾㸪ᢠ࢘ࢫࢸ࢟ࢾ࣐ࣈᢠయࡢⓎ⌧ࡀ ࡳࡽࢀࡓ⿕㦂⪅ࡣ㝈ࡽࢀ࡚࠸ࡓࡓࡵ㸪ࡇࢀࡽࡢゎᯒ⤖ᯝࡢホ౯ࡣὀពࢆせࡍࡿࠋ
⸆≀ືែཬࡧචཎᛶ · ᮏ 90 mg q8w ཬࡧᮏ 90 mg q12w ࡢ⓶ୗᢞࡼࡿᐶゎ⥔ᣢ⒪ἲࡢᐇᚋ㸪ࡑࡢᢞ㛤 ጞࡽࡑࢀࡒࢀ⣙ 8 㐌ᚋཪࡣ⣙ 12 㐌ᚋᐃᖖ≧ែ㐩ࡋࡓࠋᐃᖖ≧ែࡢ⾑Ύ୰࢘ࢫࢸ࢟ࢾ ࣐ࣈ⃰ᗘࡢࢺࣛࣇ್ࡢ୰ኸ್ࡣ㸪ᮏ 90 mg SC q12w ⩌㸦0.61㹼0.76 ȝg/mL㸧ẚ㍑ࡋ࡚ᮏ 90 mg SC q8w ⩌㸦1.97㹼2.24 ȝg/mL㸧࡛⣙ 3 ಸ㧗ࡗࡓࠋ
· ᮏ 90 mg q8w ཬࡧᮏ 90 mg q12w ࡢ⓶ୗᢞࡼࡿᐶゎ⥔ᣢ⒪ἲࡢᐇᚋ㸪⾑Ύ୰࢘ࢫ ࢸ࢟ࢾ࣐ࣈ⃰ᗘࡣࡰࡍ࡚ࡢ⿕㦂⪅࡛ 44 㐌┠ࡲ࡛⥔ᣢࡉࢀ㸪ࢺࣛࣇ⃰ᗘࡀ᳨ฟ࡛ࡁ࡞ ࡗࡓ⿕㦂⪅ࡢྜࡣ㸪ᮏ 90 mg SC q12w ⩌㹙11.1%㸦9/81 㸧㹼19.1%㸦21/110 㸧㹛 ẚ㍑ࡋ࡚ᮏ 90 mg SCq8w ⩌㹙3.2%㸦4/124 㸧㹼4.9%㸦4/81 㸧㹛࡛పࡗࡓࠋ
· 㟼⬦ෆᢞࡼࡿᐶゎᑟධ⏝㔞ࡢᕪ␗ࡀᐶゎ⥔ᣢᮇ୰ࡢ⾑Ύ୰࢘ࢫࢸ࢟ࢾ࣐ࣈ⃰ᗘ࠼ ࡿᙳ㡪ࡣ㸪ᮏヨ㦂ࡢ 16 㐌┠ࡲ࡛ᾘኻࡋࡓࠋ
15 7 (21) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
· ᮏ 90 mg SC q12w ⩌࠾ࡅࡿ⾑Ύ୰࢘ࢫࢸ࢟ࢾ࣐ࣈ⃰ᗘࡢࢺࣛࣇ್ࡢ୰ኸ್ࡣ㸪య㔜ࡀ ᭱ࡶ㔜࠸ࢢ࣮ࣝࣉ࡛᭱ࡶపࡗࡓࠋ୍᪉㸪ᮏ 90 mg SC q8w ⩌࡛ࡣ⾑Ύ୰࢘ࢫࢸ࢟ࢾ࣐ࣈ ⃰ᗘయ㔜ࡢ㛵㐃୍㈏ࡋࡓഴྥࡣㄆࡵࡽࢀ࡞ࡗࡓࠋ
· LOR ࡢࡓࡵ⏝㔞ㄪ⠇ࡀᚲせ࡛࠶ࡗࡓ⿕㦂⪅࡛ࡣ㸪LOR ࡀㄆࡵࡽࢀ࡞ࡗࡓ⿕㦂⪅ẚ㍑ࡋ ࡚⾑Ύ୰࢘ࢫࢸ࢟ࢾ࣐ࣈ⃰ᗘࡀపࡗࡓࠋᮏ 90 mg SC q12w ࡽᮏ 90 mg SC q8w ࡢ ⏝㔞ㄪ⠇㸦ᢞ㢖ᗘࡢቑຍ㸧ᚋ㸪⾑Ύ୰࢘ࢫࢸ࢟ࢾ࣐ࣈ⃰ᗘࡢࢺࣛࣇ್ࡢᖹᆒ್ࡢୖ᪼ࡀ ㄆࡵࡽࢀࡓࠋ
· ᮏヨ㦂ࡢ 0 㐌┠ᮏ 90 mg ࢆ㏣ຍ⓶ୗᢞᚋ㸪ᮏヨ㦂ࡢ 8 㐌┠ clinical response ࡀᚓࡽ ࢀࡓ⿕㦂⪅ࡢ⾑Ύ୰࢘ࢫࢸ࢟ࢾ࣐ࣈ⃰ᗘࡣ㸪ᐶゎᑟධヨ㦂࡛ clinical response ࡀᚓࡽࢀࡓ⿕ 㦂⪅㸦ࣛࣥࢲ࣒ࡉࢀࡓ⿕㦂⪅㸧࡛ㄆࡵࡽࢀࡓ⃰ᗘྠ⛬ᗘ࡞ࡗࡓࠋ
· ᢠ࢘ࢫࢸ࢟ࢾ࣐ࣈᢠయホ౯ࡢࡓࡵࡢ᳨యࡀ㐺ษ᥇ྲྀࡉࢀࡓ 1,154 ࡢᮏᢞࡢ࠺ࡕ㸪 ⒪ 52 㐌┠ࡲ࡛ᢠ࢘ࢫࢸ࢟ࢾ࣐ࣈᢠయࡀ㝧ᛶ࡞ࡗࡓ⿕㦂⪅ࡣ 27 㸦2.3%㸧࡛࠶ࡾ㸪 ࡑࡢ㒊ศࡢᢠయ౯ࡣ 1㸸800 ௨ୗ࡛࠶ࡗࡓࠋᮏヨ㦂࡛ᢠ࢘ࢫࢸ࢟ࢾ࣐ࣈᢠయࡀ㝧ᛶ࡞ࡗ ࡓࡇࢀࡽࡢ 27 ࡢᮏᢞࡢ࠺ࡕ㸪17 㸦63.0%㸧࡛ࡣ୰ᢠయࡀ㝧ᛶ࡛࠶ࡗࡓࠋ
Ᏻᛶ ࣛࣥࢲ࣒ᚋ㦂⸆ࢆᢞࡉࢀࡓ⿕㦂⪅࠾ࡅࡿ 44 㐌┠ཪࡣ⏝㔞ㄪ⠇ࡢᐇⅬࡲ࡛Ⓨ ⌧ࡋࡓᅉᯝ㛵ಀࢆၥࢃ࡞࠸ࡍ࡚ࡢ᭷ᐖ㇟ཬࡧ㦂⸆ྜ⌮ⓗ㛵㐃ᛶࡀ࠶ࡿ᭷ᐖ㇟ࢆࡑࢀ ࡒࢀ⾲ 2.7.6.4-9 ཬࡧ⾲ 2.7.6.4-10 ♧ࡍࠋ࡞࠾㸪㦂⸆ࢆᢞࡉࢀࡓࡍ࡚ࡢ⿕㦂⪅࠾ࡅࡿ 44 㐌┠ࡲ࡛Ⓨ⌧ࡋࡓᅉᯝ㛵ಀࢆၥࢃ࡞࠸ࡍ࡚ࡢ᭷ᐖ㇟ཬࡧ㦂⸆ྜ⌮ⓗ㛵㐃ᛶࡀ࠶ࡿ᭷ ᐖ㇟ࢆ⾲ 2.7.6.4-11 ♧ࡍࠋࡲࡓ㸪SAE ࡢヲ⣽ࢆ 2.7.6.4.2(2)㡯♧ࡍࠋ
· ⯡ⓗ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ 44 㐌┠ࡲ࡛ᮏ 90 mg ࢆ q12w ཪࡣ q8w ࡛⓶ୗᢞࡍࡿ⏝ ἲ࣭⏝㔞ࡢᚸᐜᛶࡣⰋዲ࡛࠶ࡗࡓࠋ㦂⸆ࢆᢞࡉࢀࡓࡍ࡚ࡢ⿕㦂⪅࠾ࡅࡿయࡢᏳ ᛶࣉࣟࣇࣝࡣ㸪⯡ⓗせ࡞ᑐ㇟㞟ᅋ㸦ࣛࣥࢲ࣒ࡉࢀࡓ⿕㦂⪅㸧࡛ࡳࡽࢀࡓࣉ ࣟࣇ୍ࣝ㈏ࡍࡿࡶࡢ࡛࠶ࡗࡓࠋ
· せ࡞ᑐ㇟㞟ᅋ㸦ࣛࣥࢲ࣒ࡉࢀࡓ⿕㦂⪅㸧࡛ࡣ㸪44 㐌┠ཪࡣ⏝㔞ㄪ⠇ࡢᐇⅬࡲ࡛ ㄆࡵࡽࢀࡓ᭷ᐖ㇟㸪SAE ཬࡧឤᰁࡢⓎ⌧ྜࡣᢞ⩌㛫࡛ྠ⛬ᗘ࡛࠶ࡗࡓࠋࣉࣛࢭ࣎ ⩌㸪ᮏ 90 mg SC q12w ⩌ཬࡧᮏ 90 mg SC q8w ⩌࠾ࡅࡿ᭷ᐖ㇟㸪SAE ཬࡧឤᰁࡢ Ⓨ⌧ྜࢆ⾲ 2.7.6.4-8 ♧ࡍࠋ
⾲ 2.7.6.4-8 44 㐌┠ཪࡣ⏝㔞ㄪ⠇ࡢᐇⅬࡲ࡛Ⓨ⌧ࡋࡓ᭷ᐖ㇟ࡢᴫせ 㸦ࣛࣥࢲ࣒ᚋ㦂⸆ࢆᢞࡉࢀࡓ⿕㦂⪅㸧 ࣉࣛࢭ࣎⩌ ᮏ 90 mg SC q12w ⩌ ᮏ 90 mg SC q8w ⩌ N=133 N=132 N=131 ᭷ᐖ㇟ 111 (83.5%) 106 (80.3%) 107 (81.7%) SAE 20 (15.0%) 16 (12.1%) 13 (9.9%) ឤᰁ 66 (49.6%) 61 (46.2%) 63 (48.1%)
15 8 (22) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
· ⏝㔞ㄪ⠇ࡢᐇ௨㝆ࡢࢹ࣮ࢱࢆゎᯒྵࡵࡓሙྜ࡛ࡶ㸪ྛᢞ⩌࠾ࡅࡿ᭷ᐖ㇟ࡢⓎ ⌧ഴྥ᫂ࡽ࡞ᕪ␗ࡣㄆࡵࡽࢀ࡞ࡗࡓࠋ
· せ࡞ᑐ㇟㞟ᅋ㸦ࣛࣥࢲ࣒ࡉࢀࡓ⿕㦂⪅㸧ࡢྛᢞ⩌࡛᭱ࡶከࡃㄆࡵࡽࢀࡓ SAE ࡣࢡࣟ ࣮࡛ࣥ࠶ࡾ㸪ࡑࡢⓎ⌧ྜࡣ㸪ࣉࣛࢭ࣎⩌࡛ 5.3%㸦7/133 㸧㸪ᮏ 90 mg SC q12w ⩌ ࡛ 3.8%㸦5/132 㸧㸪ᮏ 90 mg SC q8w ⩌࡛ 3.1%㸦4/131 㸧࡛࠶ࡗࡓࠋ
· 44 㐌┠ࡲ࡛Ṛஸཬࡧせᚰ⾑⟶࣋ࣥࢺࡣㄆࡵࡽࢀ࡞ࡗࡓࠋ
· 44 㐌┠ࡲ࡛ࡢせ࡞ᑐ㇟㞟ᅋ㸦ࣛࣥࢲ࣒ࡉࢀࡓ⿕㦂⪅㸧࠾ࡅࡿ㔜⠜࡞ឤᰁࡢⓎ⌧ ྜࡣ㸪ࣉࣛࢭ࣎⩌࡛ 2.3%㸦3/133 㸧㸪ᮏ 90 mg SC q12w ⩌࡛ 5.3%㸦7/132 㸧㸪ᮏ 90 mg SC q8w ⩌࡛ 2.3%㸦3/131 㸧࡛࠶ࡾ㸪㦂⸆ࢆᢞࡉࢀࡓࡍ࡚ࡢ⿕㦂⪅࠾ࡅࡿ ྜྠ⛬ᗘ࡛࠶ࡗࡓࠋ
· ᮏヨ㦂࡛ࣉࣛࢭ࣎⩌㸦⓶ୗᢞ㸧ࡾࡅࡽࢀࡓ⿕㦂⪅࠾࠸࡚㸪44 㐌┠ࡲ࡛ཎⓎᛶ ࡢάືᛶ⫵⤖᰾㸦presumed primary active pulmonary TB㸧ࡀ 1 ሗ࿌ࡉࢀࡓࠋࡇࡢⓎ⌧ࡣ㸪 ᮏࡢ㟼⬦ෆᢞࡽ⣙ 10 ࢝᭶ᚋ࡛࠶ࡗࡓࠋ
· ᮏヨ㦂࡛ࡣ 1 ᪥ぢឤᰁࡀሗ࿌ࡉࢀࡓࠋᮏ㇟ࡣ㠀㔜⠜ࡢ᭷ᐖ㇟㸦㣗㐨࢝ࣥࢪࢲ㸧 ࡛࠶ࡾ㸪ᮏࡢ㟼⬦ෆᢞࡼࡿᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡎ㸪ᮏヨ㦂࡛ᮏ 90 mg SC q8w ࡢᢞࢆཷࡅ࡚࠸ࡓ⿕㦂⪅㸦ࣛࣥࢲ࣒ࡉࢀ࡞ࡗࡓ⿕㦂⪅㸧࡛ࡢⓎ⌧࡛ ࠶ࡗࡓࠋ࡞࠾㸪ᮏ⿕㦂⪅ࡣ㸪ᮏ㇟ࡢデ᩿ࣥࣇࣜ࢟ࢩ࣐ࣈࢆే⏝ࡋ࡚࠸ࡓࠋ
· せ࡞ᑐ㇟㞟ᅋ㸦ࣛࣥࢲ࣒ࡉࢀࡓ⿕㦂⪅㸧࠾࠸࡚㸪44 㐌┠ࡲ࡛ 2 㸦ࣉࣛࢭ࣎⩌ཬ ࡧᮏ 90 mg SC q8w ⩌࡛ྛ 1 㸧ᝏᛶ⭘⒆㸦ࡶᇶᗏ⣽⬊⒴㸧ࡀሗ࿌ࡉࢀࡓࠋࡲࡓ㸪 ࣛࣥࢲ࣒ࡉࢀ࡞ࡗࡓ⿕㦂⪅࡛ࡣ㸪8 ௳ᝏᛶ⭘⒆ࡀሗ࿌ࡉࢀࡓࠋࡇࡢෆヂࡣ㸪3 㸦ᮏ ࡀᢞࡉࢀࡓ⿕㦂⪅࡛ 2 㸪ࣉࣛࢭ࣎ࡀᢞࡉࢀࡓ⿕㦂⪅࡛ 1 㸧࡛ሗ࿌ࡉࢀࡓ 6 ௳ࡢ 㠀࣓ࣛࣀ࣮࣐ᛶ⓶⒴ཬࡧ 1 㸦ᮏ 90 mg SC q12w ࡀᢞࡉࢀࡓ⿕㦂⪅㸧࡛ሗ࿌ࡉࢀࡓ 2 ௳ࡢࡢᝏᛶ⭘⒆㹙㌿⛣ᛶࡢᑠ⭠⭢⒴㸦metastatic adenocarcinoma of the small bowel㸧ཬࡧഅ Ⓨⓗ࡞࢝ࣝࢳࣀࢻ⭘⒆㸦incidental carcinoid tumor㸧㹛࡛࠶ࡗࡓࠋ
· 㦂⸆ࡀᢞࡉࢀࡓࡍ࡚ࡢ⿕㦂⪅࡛ሗ࿌ࡉࢀࡓὀᑕ㒊ᛂࡢⓎ⌧ྜ㹙ࣉࣛࢭ࣎ࡼ ࡿⓎ⌧ྜ㸸1.7%㸦18/1032 㸧㸪ᮏࡼࡿⓎ⌧ྜ㸸3.0%㸦28/947 㸧㹛ࡣపࡃ㸪44 㐌┠ࡲ࡛㔜⠜࡞ὀᑕ㒊ᛂࡢⓎ⌧ࡣ࡞ࡗࡓࠋ
· ᮏヨ㦂࡛ࡣ㸪44 㐌┠ࡲ࡛㔜⠜࡞ࣥࣇ࣮ࣗࢪࣙࣥࣜࢡࢩࣙࣥ㸦ᮏᑐࡍࡿࢼࣇ ࣛ࢟ࢩ࣮ᛂཪࡣ㐜ᘏᆺ㐣ᩄᛂࡢྍ⬟ᛶ㸧ࡣሗ࿌ࡉࢀ࡞ࡗࡓࠋ
· ᮏヨ㦂࡛ࡣ㸪ᢠ࢘ࢫࢸ࢟ࢾ࣐ࣈᢠయࡢⓎ⌧ὀᑕ㒊ᛂࡢ㛵㐃ᛶࡣㄆࡵࡽࢀ࡞ࡗࡓࠋ
· ⾑ᾮᏛⓗ᳨ᰝཬࡧ⾑ᾮ⏕Ꮫ᳨ᰝ࠾ࡅࡿ࣮࣋ࢫࣛࣥᚋࡢ㢧ⴭ࡞␗ᖖኚືࡣࡲࢀ࡛࠶ࡾ㸪 ࡑࢀࡽࡢ␗ᖖኚືࡀㄆࡵࡽࢀࡓ⿕㦂⪅ࡢྜࡣᢞ⩌㛫࡛ࡰྠ⛬ᗘ࡛࠶ࡗࡓࠋ
· ᮏࡢᏳᛶࣉࣟࣇࣝࡣ㸪⿕㦂⪅ࡢయ㔜ࡢ୰ኸ್ࡼࡿ༊ศ࡛ࡰྠᵝ࡛࠶ࡗࡓࠋ
15 9 (23) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
⤖ㄽ · ᮏヨ㦂㸦CNTO1275CRD3003 ヨ㦂㸧ࡢ⤖ᯝࡼࡾ㸪୰➼ࡽ㔜ࡢᡂேࢡ࣮ࣟࣥᝈ⪅ ࠾࠸࡚㸪ᮏ 90 mg SC q12w ཬࡧᮏ 90 mg SC q8w ࡢ⏝ἲ࣭⏝㔞ࡀ clinical response ཬࡧ clinical remission ࡢ⥔ᣢ᭷ຠ࡛࠶ࡿࡇࡀ୍㈏ࡋ࡚᫂☜♧ࡉࢀࡓࠋ
· ᮏヨ㦂᳨࡛ウࡋࡓホ౯㡯┠㸦≉㸪ጇᙜ࡛ㄝᚓຊࡢ࠶ࡿ᭷ຠᛶホ౯㡯┠㸧ࡢ㒊ศ࠾࠸ ࡚㸪ᮏ 90 mg SC q12w ẚ㍑ࡋ࡚ᮏ 90 mg SC q8w ࡼࡿ⏝ἲ࣭⏝㔞ࡣ㸪ࡼࡾ㧗࠸᭷ຠ ᛶࢆ♧ࡋࡓࠋ
· ୰➼ࡽ㔜ࡢᡂேࢡ࣮ࣟࣥᝈ⪅㞟ᅋ࠾࠸࡚㸪ᮏ 90 mg q12w ཬࡧᮏ 90 mg q8w ࡢ⓶ୗᢞࡼࡿᐶゎ⥔ᣢ⒪ἲࡢᚸᐜᛶࡣ㸪44 㐌㛫ࢃࡓࡾ⯡ⓗⰋዲ࡛࠶ࡗࡓࠋ
· ᮏヨ㦂ࡢᏳᛶཬࡧ᭷ຠᛶࢹ࣮ࢱࡣ㸪ᮏࡢ⓶ୗᢞࡼࡿᐶゎ⥔ᣢ⒪ἲᑐࡋ㸪࣋ࢿࣇ ࢵࢺࡀࣜࢫࢡࢆୖᅇࡿࡇࢆ♧ࡍࡶࡢ࡛࠶ࡗࡓࠋ
16 0 (24) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
2.7.6.4.2 ᭷ᐖ㇟ࡢࢹ࣮ࢱ
(1) ᭷ᐖ㇟ࡢⓎ⌧ྜ
⾲ 2.7.6.4-9 44 㐌┠ཪࡣ⏝㔞ㄪ⠇ࡢᐇⅬࡲ࡛ࡢᅉᯝ㛵ಀࢆၥࢃ࡞࠸ࡍ࡚ࡢ᭷ᐖ㇟ ࡢⓎ⌧ྜ㸦ࣛࣥࢲ࣒ᚋ㦂⸆ࢆᢞࡉࢀࡓ⿕㦂⪅㸧 ustekinumabb placebo SCa,b 90 mg SC q12w 90 mg SC q8w Combined Analysis set: Treated subjects who were randomized 133 132 131 263
Average duration of follow-up (Weeks) 32.0 36.6 35.2 35.9
Total number of subjects with 1 or more treatment- emergent adverse events 111 (83.5%) 106 (80.3%) 107 (81.7%) 213 (81.0%)
System-organ class/preferred term ឤᰁ࠾ࡼࡧᐤ⏕ 65 (48.9%) 60 (45.5%) 63 (48.1%) 123 (46.8%) 㰯ဗ㢌⅖ 10 (7.5%) 17 (12.9%) 14 (10.7%) 31 (11.8%) ୖẼ㐨ឤᰁ 21 (15.8%) 9 (6.8%) 13 (9.9%) 22 (8.4%) ࣥࣇ࢚ࣝࣥࢨ 5 (3.8%) 8 (6.1%) 5 (3.8%) 13 (4.9%) ᒀ㊰ឤᰁ 3 (2.3%) 8 (6.1%) 4 (3.1%) 12 (4.6%) 㰯⭍⅖ 2 (1.5%) 6 (4.5%) 4 (3.1%) 10 (3.8%) ࢘ࣝࢫᛶ⫶⭠⅖ 1 (0.8%) 5 (3.8%) 4 (3.1%) 9 (3.4%) ⫶⭠⅖ 5 (3.8%) 4 (3.0%) 4 (3.1%) 8 (3.0%) Ẽ⟶ᨭ⅖ 4 (3.0%) 1 (0.8%) 6 (4.6%) 7 (2.7%) እ㝜⭐┿⳦ឤᰁ 1 (0.8%) 1 (0.8%) 4 (3.1%) 5 (1.9%) ဗ㢌⅖ 1 (0.8%) 2 (1.5%) 2 (1.5%) 4 (1.5%) ⤖⭷⅖ 0 3 (2.3%) 0 3 (1.1%) ⭤⬔⅖ 1 (0.8%) 1 (0.8%) 2 (1.5%) 3 (1.1%) ⪥ឤᰁ 0 2 (1.5%) 1 (0.8%) 3 (1.1%) ⓶┿⳦ឤᰁ 1 (0.8%) 2 (1.5%) 1 (0.8%) 3 (1.1%) 㰯⅖ 0 0 3 (2.3%) 3 (1.1%) ࢘ࣝࢫឤᰁ 1 (0.8%) 1 (0.8%) 2 (1.5%) 3 (1.1%) ⫠㛛⮋⒆ 3 (2.3%) 2 (1.5%) 0 2 (0.8%) ᆶ⅖ 0 2 (1.5%) 0 2 (0.8%) ⻏ᕢ⅖ 0 1 (0.8%) 1 (0.8%) 2 (0.8%) ៏ᛶ㰯⭍⅖ 0 2 (1.5%) 0 2 (0.8%) ࡏࡘ 1 (0.8%) 1 (0.8%) 1 (0.8%) 2 (0.8%) 㯏⢏⭘ 1 (0.8%) 1 (0.8%) 1 (0.8%) 2 (0.8%) ୗẼ㐨ឤᰁ 0 0 2 (1.5%) 2 (0.8%) ⫵⅖ 2 (1.5%) 0 2 (1.5%) 2 (0.8%) ⓑⓄឤᰁ 0 1 (0.8%) 1 (0.8%) 2 (0.8%) ᡥ᱈⅖ 0 1 (0.8%) 1 (0.8%) 2 (0.8%) እ㝜㒊⭐࢝ࣥࢪࢲ 0 0 2 (1.5%) 2 (0.8%) ⭡㒊ឤᰁ 0 1 (0.8%) 0 1 (0.4%) ⫠㛛࢝ࣥࢪࢲ 0 0 1 (0.8%) 1 (0.4%) ⳦⾑ 0 1 (0.8%) 0 1 (0.4%) ࢝ࣥࣆࣟࣂࢡࢱ࣮⫶⭠⅖ 0 1 (0.8%) 0 1 (0.4%) ࢡ࣑ࣛࢪឤᰁ 0 1 (0.8%) 0 1 (0.4%) ࢡࣟࢫࢺࣜࢪ࣒࣭࢘ࢹࣇࢩࣞ⭠⅖ 1 (0.8%) 0 1 (0.8%) 1 (0.4%) ࢡࣟࢫࢺࣜࢪ࣒࣭࢘ࢹࣇࢩࣞឤᰁ 1 (0.8%) 0 1 (0.8%) 1 (0.4%) ᠁ᐊ⅖ 0 1 (0.8%) 0 1 (0.4%) ⭠⳦ᛶᒀ㊰ឤᰁ 0 0 1 (0.8%) 1 (0.4%) ║ឤᰁ 0 1 (0.8%) 0 1 (0.4%) ࣀࣟ࢘ࣝࢫᛶ⫶⭠⅖ 0 1 (0.8%) 0 1 (0.4%) ⣽⳦ᛶᾘ⟶ឤᰁ 0 0 1 (0.8%) 1 (0.4%) ࢘ࣝࢫᛶᾘ⟶ឤᰁ 0 0 1 (0.8%) 1 (0.4%) 㝜㒊࣊ࣝ࣌ࢫ 1 (0.8%) 0 1 (0.8%) 1 (0.4%) ṑ⫗⅖ 0 0 1 (0.8%) 1 (0.4%) 㰢ᚄ㒊⮋⒆ 0 1 (0.8%) 0 1 (0.4%) ᖏ≧⑁⑈ 2 (1.5%) 0 1 (0.8%) 1 (0.4%) ษ㛤㒊ឤᰁ 0 0 1 (0.8%) 1 (0.4%) ႃ㢌⅖ 0 1 (0.8%) 0 1 (0.4%) ࣐ࢥࣉࣛࢬ࣐ឤᰁ 0 0 1 (0.8%) 1 (0.4%) 㰯๓ᗞ⅖ 0 0 1 (0.8%) 1 (0.4%)
16 1 (25) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
ustekinumabb placebo SCa,b 90 mg SC q12w 90 mg SC q8w Combined ║ᖏ≧⑁⑈ 0 0 1 (0.8%) 1 (0.4%) ཱྀ⭍࢝ࣥࢪࢲ 0 0 1 (0.8%) 1 (0.4%) ཱྀ⭍࣊ࣝ࣌ࢫ 3 (2.3%) 0 1 (0.8%) 1 (0.4%) ⪥ୗ⭢⅖ 0 0 1 (0.8%) 1 (0.4%) ⾡ᚋឤᰁ 0 1 (0.8%) 0 1 (0.4%) ṑ㧊⅖ 0 0 1 (0.8%) 1 (0.4%) Ẽ㐨ឤᰁ 0 1 (0.8%) 0 1 (0.4%) 㰯⭍Ẽ⟶ᨭ⅖ 0 1 (0.8%) 0 1 (0.4%) ⓶ឤᰁ 0 1 (0.8%) 0 1 (0.4%) ṑឤᰁ 1 (0.8%) 0 1 (0.8%) 1 (0.4%) Ẽ⟶Ẽ⟶ᨭ⅖ 1 (0.8%) 1 (0.8%) 0 1 (0.4%) ⣽⳦ᛶ⭐⅖ 0 0 1 (0.8%) 1 (0.4%) Ỉ① 0 0 1 (0.8%) 1 (0.4%) ⭡㒊⮋⒆ 1 (0.8%) 0 0 0 ⣽⳦ᛶ⤖⭷⅖ 1 (0.8%) 0 0 0 ឤᰁᛶୗ⑩ 1 (0.8%) 0 0 0 ༢⣧࣊ࣝ࣌ࢫ 2 (1.5%) 0 0 0 ឤᰁᛶᄞ⭘ 1 (0.8%) 0 0 0 ὀධ㒊⻏ᕢ⅖ 1 (0.8%) 0 0 0 ∎ᅖ⅖ 1 (0.8%) 0 0 0 ࣞࣥࢧ⌫⳦ᛶဗ㢌⅖ 2 (1.5%) 0 0 0 ⭈│⭈⅖ 1 (0.8%) 0 0 0 ࢘ࣝࢫᛶẼ㐨ឤᰁ 1 (0.8%) 0 0 0 ᑠ⭠ෆ⣽⳦㐣ቑṪ 1 (0.8%) 0 0 0 ⤖᰾ 1 (0.8%) 0 0 0 ⫶⭠㞀ᐖ 63 (47.4%) 56 (42.4%) 47 (35.9%) 103 (39.2%) ࢡ࣮ࣟࣥ 19 (14.3%) 16 (12.1%) 16 (12.2%) 32 (12.2%) ⭡③ 16 (12.0%) 13 (9.8%) 11 (8.4%) 24 (9.1%) ୗ⑩ 7 (5.3%) 11 (8.3%) 5 (3.8%) 16 (6.1%) ᝏᚰ 9 (6.8%) 10 (7.6%) 4 (3.1%) 14 (5.3%) ౽⛎ 4 (3.0%) 6 (4.5%) 3 (2.3%) 9 (3.4%) ྤ 9 (6.8%) 5 (3.8%) 4 (3.1%) 9 (3.4%) ୖ⭡㒊③ 3 (2.3%) 4 (3.0%) 2 (1.5%) 6 (2.3%) ⒦ 4 (3.0%) 3 (2.3%) 2 (1.5%) 5 (1.9%) ⭡㒊⭾‶ 3 (2.3%) 2 (1.5%) 1 (0.8%) 3 (1.1%) ࣇࢱᛶཱྀෆ⅖ 2 (1.5%) 3 (2.3%) 0 3 (1.1%) ᾘⰋ 1 (0.8%) 3 (2.3%) 0 3 (1.1%) ⭠⊃✽ 1 (0.8%) 1 (0.8%) 2 (1.5%) 3 (1.1%) ⫠㛛࿘ᅖ③ 1 (0.8%) 3 (2.3%) 0 3 (1.1%) ᑠ⭠㛢ሰ 0 1 (0.8%) 2 (1.5%) 3 (1.1%) ୗ⭡㒊③ 0 1 (0.8%) 1 (0.8%) 2 (0.8%) ⫠ 0 2 (1.5%) 0 2 (0.8%) 㱘ṑ 0 0 2 (1.5%) 2 (0.8%) ᨺᒂ 0 1 (0.8%) 1 (0.8%) 2 (0.8%) 㣗୰ẘ 0 2 (1.5%) 0 2 (0.8%) ⫶⅖ 1 (0.8%) 0 2 (1.5%) 2 (0.8%) ⫶㣗㐨㏫ὶᛶᝈ 2 (1.5%) 1 (0.8%) 1 (0.8%) 2 (0.8%) ྤ⾑ 0 0 2 (1.5%) 2 (0.8%) ᰾ 2 (1.5%) 1 (0.8%) 1 (0.8%) 2 (0.8%) ⫠㛛ࡑ࠺ 0 1 (0.8%) 0 1 (0.4%) ⫠㛛┤⭠ᛌឤ 0 0 1 (0.8%) 1 (0.4%) ཱྀ၁⅖ 0 0 1 (0.8%) 1 (0.4%) ౽ពษ㏕ 0 1 (0.8%) 0 1 (0.4%) ⾑ᛶୗ⑩ 0 1 (0.8%) 0 1 (0.4%) ༑ᣦ⭠₽⒆ 0 0 1 (0.8%) 1 (0.4%) ᄟୗ㞀ᐖ 1 (0.8%) 0 1 (0.8%) 1 (0.4%) ⭠⅖ 0 1 (0.8%) 0 1 (0.4%) ౽ኻ⚗ 0 1 (0.8%) 0 1 (0.4%) ኚⰍ౽ 0 1 (0.8%) 0 1 (0.4%) ⫶⭠⟶⒦ 0 1 (0.8%) 0 1 (0.4%) ⾑౽ἥ 0 1 (0.8%) 0 1 (0.4%) ᅇ⭠⒦ 0 1 (0.8%) 0 1 (0.4%) ᅇ⭠⊃✽ 1 (0.8%) 0 1 (0.8%) 1 (0.4%) ⭠⟶⒦ 0 1 (0.8%) 0 1 (0.4%) ⭠㛢ሰ 0 0 1 (0.8%) 1 (0.4%) ཱྀ⭍ෆ₽⒆ᙧᡂ 2 (1.5%) 1 (0.8%) 0 1 (0.4%)
16 2 (26) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
ustekinumabb placebo SCa,b 90 mg SC q12w 90 mg SC q8w Combined 㣗㐨⅖ 0 0 1 (0.8%) 1 (0.4%) ཱྀ⭍⢓⭷Ỉ⑁ᙧᡂ 0 1 (0.8%) 0 1 (0.4%) ཱྀࡢ㘒ឤぬ 0 0 1 (0.8%) 1 (0.4%) ṑ࿘ 1 (0.8%) 0 1 (0.8%) 1 (0.4%) ᄞ⅖ 0 0 1 (0.8%) 1 (0.4%) ┤⭠ฟ⾑ 1 (0.8%) 0 1 (0.8%) 1 (0.4%) ⫠㛛ࡢ⅖ 2 (1.5%) 0 0 0 ⫠㛛⓶ᆶ 1 (0.8%) 0 0 0 ṑᛌឤ 1 (0.8%) 0 0 0 ⭠⭤⬔⒦ 1 (0.8%) 0 0 0 ౽ᅇᩘቑຍ 1 (0.8%) 0 0 0 ฟ⾑ 1 (0.8%) 0 0 0 ⭠✸Ꮝ 1 (0.8%) 0 0 0 ┤⭠ࡋࡪࡾ 1 (0.8%) 0 0 0 ṑ③ 1 (0.8%) 0 0 0 ➽㦵᱁⣔࠾ࡼࡧ⤖ྜ⤌⧊㞀ᐖ 35 (26.3%) 35 (26.5%) 37 (28.2%) 72 (27.4%) 㛵⠇③ 19 (14.3%) 22 (16.7%) 18 (13.7%) 40 (15.2%) ⫼㒊③ 6 (4.5%) 5 (3.8%) 6 (4.6%) 11 (4.2%) ➽⫗③ 1 (0.8%) 5 (3.8%) 1 (0.8%) 6 (2.3%) ᅄ⫥③ 0 0 5 (3.8%) 5 (1.9%) 㛵⠇⅖ 3 (2.3%) 3 (2.3%) 1 (0.8%) 4 (1.5%) ➽ຊపୗ 0 1 (0.8%) 1 (0.8%) 2 (0.8%) 㦵⢒㧼 0 1 (0.8%) 1 (0.8%) 2 (0.8%) ᾮᄞ⭘ 0 0 2 (1.5%) 2 (0.8%) ᙎⓎᣦ 0 1 (0.8%) 1 (0.8%) 2 (0.8%) ᾮໟ⅖ 0 0 1 (0.8%) 1 (0.4%) 㛵⠇ⁱฟᾮ 0 0 1 (0.8%) 1 (0.4%) ➽②⦰ 0 1 (0.8%) 0 1 (0.4%) ➽⥭ᙇ 0 0 1 (0.8%) 1 (0.4%) ➽㦵᱁⣔⬚③ 1 (0.8%) 1 (0.8%) 0 1 (0.4%) ➽㦵᱁◳┤ 2 (1.5%) 1 (0.8%) 0 1 (0.4%) 㢁㒊③ 0 1 (0.8%) 0 1 (0.4%) ኚᙧᛶ㛵⠇ 0 1 (0.8%) 0 1 (0.4%) 㦵ῶᑡ 0 0 1 (0.8%) 1 (0.4%) 㢡③ 0 1 (0.8%) 0 1 (0.4%) ⭸⭣㛵⠇③ೃ⩌ 0 0 1 (0.8%) 1 (0.4%) ⫪ᅇ᪕➽⭝ᯈೃ⩌ 0 0 1 (0.8%) 1 (0.4%) ⭝㠧⅖ 0 0 1 (0.8%) 1 (0.4%) ᩳ㢁 0 0 1 (0.8%) 1 (0.4%) ⫘㌾㦵⅖ 1 (0.8%) 0 0 0 ⥺⥔➽③ 1 (0.8%) 0 0 0 ഃ⭡㒊③ 1 (0.8%) 0 0 0 㰢ᚄ㒊③ 1 (0.8%) 0 0 0 㛵⠇⭘⬽ 1 (0.8%) 0 0 0 ⭜㒊⬨ᰕ⟶⊃✽ 1 (0.8%) 0 0 0 㛵⠇࿘ᅖ⅖ 1 (0.8%) 0 0 0 ࣐ࣜ࢘ࢳᛶከⓎ➽③ 1 (0.8%) 0 0 0 㛵⠇࣐ࣜ࢘ࢳ 1 (0.8%) 0 0 0 㢡㛵⠇ೃ⩌ 1 (0.8%) 0 0 0 ⭝③ 1 (0.8%) 0 0 0 ୍⯡࣭㌟㞀ᐖ࠾ࡼࡧᢞ㒊ࡢ≧ែ 29 (21.8%) 27 (20.5%) 24 (18.3%) 51 (19.4%) Ⓨ⇕ 10 (7.5%) 11 (8.3%) 8 (6.1%) 19 (7.2%) ⑂ປ 6 (4.5%) 8 (6.1%) 6 (4.6%) 14 (5.3%) ὀᑕ㒊⣚ᩬ 0 1 (0.8%) 7 (5.3%) 8 (3.0%) ࣥࣇ࢚ࣝࣥࢨᵝᝈ 5 (3.8%) 2 (1.5%) 5 (3.8%) 7 (2.7%) ↓ຊ 1 (0.8%) 1 (0.8%) 1 (0.8%) 2 (0.8%) ὀᑕ㒊⑊③ 1 (0.8%) 2 (1.5%) 0 2 (0.8%) ᛰឤ 0 2 (1.5%) 0 2 (0.8%) ᮎᲈᛶᾋ⭘ 1 (0.8%) 0 2 (1.5%) 2 (0.8%) ⭆❐③ 0 0 1 (0.8%) 1 (0.4%) ᝏᐮ 1 (0.8%) 1 (0.8%) 0 1 (0.4%) ෭ឤ 0 0 1 (0.8%) 1 (0.4%) ὀᑕ㒊ෆฟ⾑ 0 0 1 (0.8%) 1 (0.4%) ὀᑕ㒊⚄⤒ᦆയ 0 0 1 (0.8%) 1 (0.4%) ὀᑕ㒊▱ぬ␗ᖖ 0 0 1 (0.8%) 1 (0.4%) ὀᑕ㒊Ⓨ⑈ 0 0 1 (0.8%) 1 (0.4%)
16 3 (27) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
ustekinumabb placebo SCa,b 90 mg SC q12w 90 mg SC q8w Combined ὀᑕ㒊⭘⬽ 0 0 1 (0.8%) 1 (0.4%) ὀᑕ㒊ⶼ㯞⑈ 0 1 (0.8%) 0 1 (0.4%) ὀᑕ㒊ᑠỈ⑁ 0 0 1 (0.8%) 1 (0.4%) ᒁᡤ⭘⬽ 0 0 1 (0.8%) 1 (0.4%) 㠀ᚰ⮚ᛶ⬚③ 2 (1.5%) 1 (0.8%) 0 1 (0.4%) ᮎᲈ⭘⬽ 0 0 1 (0.8%) 1 (0.4%) 㦵ୖ③ 0 1 (0.8%) 0 1 (0.4%) ⬚㒊ᛌឤ 2 (1.5%) 0 0 0 ᄞ⬊ 1 (0.8%) 0 0 0 㢦㠃ᾋ⭘ 1 (0.8%) 0 0 0 㝈ᒁᛶᾋ⭘ 1 (0.8%) 0 0 0 ⑊③ 1 (0.8%) 0 0 0 ཱྀῬ 1 (0.8%) 0 0 0 ࣡ࢡࢳࣥ᥋✀㒊⅖ 1 (0.8%) 0 0 0 ࣡ࢡࢳࣥ᥋✀㒊⭘⬽ 1 (0.8%) 0 0 0 ⓶࠾ࡼࡧ⓶ୗ⤌⧊㞀ᐖ 25 (18.8%) 19 (14.4%) 28 (21.4%) 47 (17.9%) Ⓨ⑈ 5 (3.8%) 4 (3.0%) 7 (5.3%) 11 (4.2%) ࡑ࠺ 3 (2.3%) 2 (1.5%) 5 (3.8%) 7 (2.7%) ࡊ⒔ 1 (0.8%) 1 (0.8%) 2 (1.5%) 3 (1.1%) ᥋ゐᛶ⓶⅖ 0 1 (0.8%) 2 (1.5%) 3 (1.1%) ‵⑈ 1 (0.8%) 2 (1.5%) 1 (0.8%) 3 (1.1%) ࡑ࠺ᛶ⓶⑈ 1 (0.8%) 1 (0.8%) 2 (1.5%) 3 (1.1%) Ỉ⑁ 0 1 (0.8%) 1 (0.8%) 2 (0.8%) ከờ 0 0 2 (1.5%) 2 (0.8%) ᡥᖹⱏⓄ 0 2 (1.5%) 0 2 (0.8%) ᐷờ 4 (3.0%) 2 (1.5%) 0 2 (0.8%) ⶼ㯞⑈ 1 (0.8%) 2 (1.5%) 0 2 (0.8%) ᪥ගゅ 0 0 1 (0.8%) 1 (0.4%) ⬺ẟ 4 (3.0%) 1 (0.8%) 0 1 (0.4%) ෭ờ 0 0 1 (0.8%) 1 (0.4%) 〟⒔ᛶ₽⒆ 0 1 (0.8%) 0 1 (0.4%) Ⓞᵝ⓶⅖ 0 0 1 (0.8%) 1 (0.4%) ⓶⬡Ḟஈᛶ‵⑈ 0 0 1 (0.8%) 1 (0.4%) ⣚ᩬ 0 0 1 (0.8%) 1 (0.4%) ⤖⠇ᛶ⣚ᩬ 0 1 (0.8%) 0 1 (0.4%) ờ⭢⅖ 0 0 1 (0.8%) 1 (0.4%) 㐣ゅ 0 1 (0.8%) 0 1 (0.4%) ờ⑈ 0 0 1 (0.8%) 1 (0.4%) Ⓞ 0 0 1 (0.8%) 1 (0.4%) ⬡₃ᛶ⓶⅖ 0 0 1 (0.8%) 1 (0.4%) ⓶㞀ᐖ 0 0 1 (0.8%) 1 (0.4%) ⓶ኚ 3 (2.3%) 0 1 (0.8%) 1 (0.4%) ⓶₽⒆ 1 (0.8%) 1 (0.8%) 0 1 (0.4%) ⥙≧⓶ᩬ 1 (0.8%) 0 0 0 ⣚ᩬᛶ⓶⑈ 1 (0.8%) 0 0 0 ⚄⤒⣔㞀ᐖ 24 (18.0%) 19 (14.4%) 24 (18.3%) 43 (16.3%) 㢌③ 15 (11.3%) 15 (11.4%) 16 (12.2%) 31 (11.8%) ∦㢌③ 3 (2.3%) 1 (0.8%) 5 (3.8%) 6 (2.3%) ᾋືᛶࡵࡲ࠸ 2 (1.5%) 2 (1.5%) 1 (0.8%) 3 (1.1%) యᛶࡵࡲ࠸ 1 (0.8%) 0 2 (1.5%) 2 (0.8%) Ⴔ╀ 0 1 (0.8%) 1 (0.8%) 2 (0.8%) 㘒ឤぬ 1 (0.8%) 0 2 (1.5%) 2 (0.8%) ኻ⚄ 2 (1.5%) 1 (0.8%) 1 (0.8%) 2 (0.8%) ᡭ᰿⟶ೃ⩌ 0 1 (0.8%) 0 1 (0.4%) ୗ⫥㟼Ṇ⬟ೃ⩌ 0 1 (0.8%) 0 1 (0.4%) 㰯⭍⅖క࠺㢌③ 0 0 1 (0.8%) 1 (0.4%) ᡓ 0 0 1 (0.8%) 1 (0.4%) ឤぬ㕌㯞 1 (0.8%) 0 0 0 グ᠈㞀ᐖ 1 (0.8%) 0 0 0 ๓ࢆక࠺∦㢌③ 1 (0.8%) 0 0 0 ᮎᲈᛶࢽ࣮ࣗࣟࣃࢳ࣮ 1 (0.8%) 0 0 0 ᯇᯝయᄞ⬊ 1 (0.8%) 0 0 0 ឤぬ㞀ᐖ 1 (0.8%) 0 0 0 ഴ╀ 1 (0.8%) 0 0 0 ୕ཫ⚄⤒③ 2 (1.5%) 0 0 0 ྾ჾࠊ⬚㒌࠾ࡼࡧ⦪㝸㞀ᐖ 15 (11.3%) 13 (9.8%) 15 (11.5%) 28 (10.6%)
16 4 (28) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
ustekinumabb placebo SCa,b 90 mg SC q12w 90 mg SC q8w Combined တႿ 3 (2.3%) 4 (3.0%) 7 (5.3%) 11 (4.2%) ཱྀ⭍ဗ㢌③ 4 (3.0%) 2 (1.5%) 3 (2.3%) 5 (1.9%) 㰯⭍࠺ࡗ⾑ 1 (0.8%) 1 (0.8%) 2 (1.5%) 3 (1.1%) 㰯㛢 6 (4.5%) 1 (0.8%) 1 (0.8%) 2 (0.8%) ୖẼ㐨တೃ⩌ 0 1 (0.8%) 1 (0.8%) 2 (0.8%) ႍᜥ 0 0 1 (0.8%) 1 (0.4%) ྾ᅔ㞴 0 1 (0.8%) 0 1 (0.4%) ປసᛶ྾ᅔ㞴 0 1 (0.8%) 0 1 (0.4%) ဗ㢌⣚ᩬ 0 1 (0.8%) 0 1 (0.4%) ‵ᛶတႿ 0 1 (0.8%) 0 1 (0.4%) 㰯₃ 2 (1.5%) 0 1 (0.8%) 1 (0.4%) 㰯ฟ⾑ 1 (0.8%) 0 0 0 㰯⭍ᛌឤ 1 (0.8%) 0 0 0 ⮫ᗋ᳨ᰝ 8 (6.0%) 12 (9.1%) 11 (8.4%) 23 (8.7%) ⫢ᶵ⬟᳨ᰝ␗ᖖ 2 (1.5%) 0 4 (3.1%) 4 (1.5%) ዲ୰⌫ᩘቑຍ 0 1 (0.8%) 2 (1.5%) 3 (1.1%) య㔜ῶᑡ 3 (2.3%) 3 (2.3%) 0 3 (1.1%) ᚰᢿᩘቑຍ 0 2 (1.5%) 0 2 (0.8%) ࣛࢽ࣑ࣥࣀࢺࣛࣥࢫࣇ࢙࣮ࣛࢮቑຍ 0 0 1 (0.8%) 1 (0.4%) ࢫࣃࣛࢠࣥ㓟࣑ࣀࢺࣛࣥࢫࣇ࢙࣮ࣛࢮቑຍ 0 0 1 (0.8%) 1 (0.4%) ⾑୰ࣝ࢝ࣜ࣍ࢫࣇࢱ࣮ࢮቑຍ 0 1 (0.8%) 0 1 (0.4%) ⾑୰ࣈࢻ࢘⢾ቑຍ 0 1 (0.8%) 0 1 (0.4%) ⾑୰࣒࢝ࣜ࢘ῶᑡ 0 0 1 (0.8%) 1 (0.4%) ᣑᙇᮇ⾑ᅽୖ᪼ 0 1 (0.8%) 0 1 (0.4%) య ୖ᪼ 0 0 1 (0.8%) 1 (0.4%) ࢡࣟࢫࢺࣜࢪ᳨࣒࢘ᰝ㝧ᛶ 0 1 (0.8%) 0 1 (0.4%) ⫢㓝⣲ୖ᪼ 0 1 (0.8%) 0 1 (0.4%) ࣄࢺங㢌⭘࢘ࣝࢫ᳨ᰝ㝧ᛶ 0 1 (0.8%) 0 1 (0.4%) ⾑ᑠᯈᩘቑຍ 0 0 1 (0.8%) 1 (0.4%) ⾑Ύࣇ࢙ࣜࢳࣥῶᑡ 0 1 (0.8%) 0 1 (0.4%) ࢺࣛࣥࢫ࣑ࢼ࣮ࢮୖ᪼ 0 1 (0.8%) 0 1 (0.4%) ࣅࢱ࣑ࣥ㹂ῶᑡ 0 0 1 (0.8%) 1 (0.4%) ⓑ⾑⌫ᩘቑຍ 0 0 1 (0.8%) 1 (0.4%) ⾑୰ࣝࣈ࣑ࣥῶᑡ 1 (0.8%) 0 0 0 ⾑୰ࢡࣞࢳࢽࣥቑຍ 1 (0.8%) 0 0 0 ዲ㓟⌫ᩘቑຍ 1 (0.8%) 0 0 0 ࣐࣊ࢺࢡࣜࢵࢺῶᑡ 1 (0.8%) 0 0 0 ⥲⺮ⓑῶᑡ 1 (0.8%) 0 0 0 യᐖࠊ୰ẘ࠾ࡼࡧฎ⨨ྜే 8 (6.0%) 9 (6.8%) 7 (5.3%) 16 (6.1%) യ 1 (0.8%) 1 (0.8%) 1 (0.8%) 2 (0.8%) ㊊㦵ᢡ 0 1 (0.8%) 1 (0.8%) 2 (0.8%) ⫗㞳ࢀ 0 1 (0.8%) 1 (0.8%) 2 (0.8%) ࣞࣝࢠ࣮ᛶ㍺⾑ᛂ 0 1 (0.8%) 0 1 (0.4%) ㊊㛵⠇㒊㦵ᢡ 0 0 1 (0.8%) 1 (0.4%) ⠇㊊ື≀ညയ 0 0 1 (0.8%) 1 (0.4%) ㌿ಽ 0 1 (0.8%) 0 1 (0.4%) യ 0 1 (0.8%) 0 1 (0.4%) 㠎ᖏ 2 (1.5%) 1 (0.8%) 0 1 (0.4%) ༙᭶ᯈᦆയ 0 1 (0.8%) 0 1 (0.4%) ฎ⨨ࡼࡿࡵࡲ࠸ 0 0 1 (0.8%) 1 (0.4%) ฎ⨨ࡼࡿ⑊③ 2 (1.5%) 0 1 (0.8%) 1 (0.4%) ⬨ᰕᦆയ 0 1 (0.8%) 0 1 (0.4%) ⭝᩿ 0 1 (0.8%) 0 1 (0.4%) യ 0 0 1 (0.8%) 1 (0.4%) 㢌㒊ᦆയ 1 (0.8%) 0 0 0 እയᚋ㢁㒊ೃ⩌ 1 (0.8%) 0 0 0 ⓶᧿㐣യ 1 (0.8%) 0 0 0 ⾑ᾮ࠾ࡼࡧࣜࣥࣃ⣔㞀ᐖ 3 (2.3%) 9 (6.8%) 5 (3.8%) 14 (5.3%) ㈋⾑ 0 5 (3.8%) 3 (2.3%) 8 (3.0%) ⓑ⾑⌫ቑຍ 0 2 (1.5%) 1 (0.8%) 3 (1.1%) ࣜࣥࣃ⌫ῶᑡ 0 1 (0.8%) 1 (0.8%) 2 (0.8%) 㕲Ḟஈᛶ㈋⾑ 2 (1.5%) 0 1 (0.8%) 1 (0.4%) ⓑ⾑⌫ῶᑡ 1 (0.8%) 1 (0.8%) 0 1 (0.4%) ⾑ᑠᯈቑຍ 0 1 (0.8%) 0 1 (0.4%) ௦ㅰ࠾ࡼࡧᰤ㣴㞀ᐖ 3 (2.3%) 7 (5.3%) 7 (5.3%) 14 (5.3%) ⬺Ỉ 0 1 (0.8%) 2 (1.5%) 3 (1.1%)
16 5 (29) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
ustekinumabb placebo SCa,b 90 mg SC q12w 90 mg SC q8w Combined 㣗ḧῶ㏥ 0 2 (1.5%) 0 2 (0.8%) ప࣒࢝ࣜ࢘⾑ 0 2 (1.5%) 0 2 (0.8%) ࣅࢱ࣑ࣥ㹀㸯㸰Ḟஈ 0 0 2 (1.5%) 2 (0.8%) ࣅࢱ࣑ࣥ㹂Ḟஈ 1 (0.8%) 1 (0.8%) 1 (0.8%) 2 (0.8%) ③㢼 1 (0.8%) 0 1 (0.8%) 1 (0.4%) 㧗ࢥࣞࢫࢸ࣮ࣟࣝ⾑ 0 0 1 (0.8%) 1 (0.4%) 㧗⾑⢾ 0 1 (0.8%) 0 1 (0.4%) 㕲Ḟஈ 0 1 (0.8%) 0 1 (0.4%) ࣅࢱ࣑ࣥ㹀㸴Ḟஈ 1 (0.8%) 0 0 0 ⢭⚄㞀ᐖ 4 (3.0%) 9 (6.8%) 5 (3.8%) 14 (5.3%) ࠺ࡘ 2 (1.5%) 3 (2.3%) 2 (1.5%) 5 (1.9%) Ᏻ 1 (0.8%) 2 (1.5%) 0 2 (0.8%) ╀ 1 (0.8%) 1 (0.8%) 1 (0.8%) 2 (0.8%) ࣃࢽࢵࢡⓎస 0 1 (0.8%) 1 (0.8%) 2 (0.8%) ␗ᖖ࡞ክ 0 1 (0.8%) 0 1 (0.4%) 㘒≧ែ 1 (0.8%) 0 1 (0.8%) 1 (0.4%) ᢚ࠺ࡘẼศ 0 1 (0.8%) 0 1 (0.4%) ╧╀㞀ᐖ 0 0 1 (0.8%) 1 (0.4%) ⮬ẅᛕ៖ 0 1 (0.8%) 0 1 (0.4%) ║㞀ᐖ 8 (6.0%) 8 (6.1%) 5 (3.8%) 13 (4.9%) ║⢭⑂ປ 0 0 1 (0.8%) 1 (0.4%) ║▛⅖ 0 1 (0.8%) 0 1 (0.4%) ⓑෆ㞀 1 (0.8%) 1 (0.8%) 0 1 (0.4%) 㟠⢏⭘ 0 0 1 (0.8%) 1 (0.4%) ⤖⭷ฟ⾑ 0 1 (0.8%) 0 1 (0.4%) ࣞࣝࢠ࣮ᛶ⤖⭷⅖ 0 0 1 (0.8%) 1 (0.4%) ║⇱ 0 0 1 (0.8%) 1 (0.4%) ║▛‵⑈ 0 0 1 (0.8%) 1 (0.4%) ║่⃭ 0 1 (0.8%) 0 1 (0.4%) ║㒊⭘⬽ 1 (0.8%) 1 (0.8%) 0 1 (0.4%) ᙬ⅖ 0 1 (0.8%) 0 1 (0.4%) ὶᾦቑຍ 0 1 (0.8%) 0 1 (0.4%) ࡪ࠺⭷⅖ 0 1 (0.8%) 0 1 (0.4%) 㟝ど 0 0 1 (0.8%) 1 (0.4%) ║ࡑ࠺ 1 (0.8%) 0 0 0 ᙬẟᵝయ⅖ 1 (0.8%) 0 0 0 ゅ⭷⅖ 1 (0.8%) 0 0 0 ║⾑ 2 (1.5%) 0 0 0 どຊపୗ 1 (0.8%) 0 0 0 どຊ㞀ᐖ 1 (0.8%) 0 0 0 ⭈࠾ࡼࡧᒀ㊰㞀ᐖ 4 (3.0%) 1 (0.8%) 8 (6.1%) 9 (3.4%) ᒀᅔ㞴 0 0 3 (2.3%) 3 (1.1%) ⭈⤖▼ 2 (1.5%) 1 (0.8%) 1 (0.8%) 2 (0.8%) ⭈③ 0 0 2 (1.5%) 2 (0.8%) ⭤⬔②⦰ 0 0 1 (0.8%) 1 (0.4%) ኻ⚗ 0 0 1 (0.8%) 1 (0.4%) ⺮ⓑᒀ 0 0 1 (0.8%) 1 (0.4%) ኪ㛫㢖ᒀ 1 (0.8%) 0 0 0 㢖ᒀ 1 (0.8%) 0 0 0 ⾑⟶㞀ᐖ 2 (1.5%) 3 (2.3%) 5 (3.8%) 8 (3.0%) 㧗⾑ᅽ 0 2 (1.5%) 2 (1.5%) 4 (1.5%) ࡚ࡾ 0 0 2 (1.5%) 2 (0.8%) ῝㒊㟼⬦⾑ᰦ 0 1 (0.8%) 0 1 (0.4%) ᮏែᛶ㧗⾑ᅽ 0 1 (0.8%) 0 1 (0.4%) ₻⣚ 2 (1.5%) 0 1 (0.8%) 1 (0.4%) Ⰻᛶࠊᝏᛶ࠾ࡼࡧヲ⣽᫂ࡢ᪂⏕≀㸦ᄞ⬊࠾ࡼࡧ ࣏࣮ࣜࣉࢆྵࡴ㸧 4 (3.0%) 2 (1.5%) 3 (2.3%) 5 (1.9%) ᇶᗏ⣽⬊⒴ 1 (0.8%) 0 1 (0.8%) 1 (0.4%) ༸ᕢⰋᛶ⭘⒆ 0 1 (0.8%) 0 1 (0.4%) ၚᾮ⭢ࡢⰋᛶ᪂⏕≀ 0 1 (0.8%) 0 1 (0.4%) ⭠⭢⭘ 0 0 1 (0.8%) 1 (0.4%) ࢣࣛࢺ࢝ࣥࢺ࣮࣐ 0 0 1 (0.8%) 1 (0.4%) ༸ᕢ⭢⭘ 0 0 1 (0.8%) 1 (0.4%) ࢡࣟࢥࣝࢻࣥ 1 (0.8%) 0 0 0 㧊⭷⭘ 1 (0.8%) 0 0 0 Ꮚᐑᖹ➽⭘ 1 (0.8%) 0 0 0
16 6 (30) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
ustekinumabb placebo SCa,b 90 mg SC q12w 90 mg SC q8w Combined ච⣔㞀ᐖ 2 (1.5%) 1 (0.8%) 3 (2.3%) 4 (1.5%) Ꮨ⠇ᛶࣞࣝࢠ࣮ 2 (1.5%) 0 2 (1.5%) 2 (0.8%) ⸆≀㐣ᩄ 0 0 1 (0.8%) 1 (0.4%) 㐣ᩄ 0 1 (0.8%) 0 1 (0.4%) ⫢⫹㐨⣔㞀ᐖ 0 0 3 (2.3%) 3 (1.1%) ⫹▼ 0 0 2 (1.5%) 2 (0.8%) ⫢ᶵ⬟␗ᖖ 0 0 1 (0.8%) 1 (0.4%) ዷፎࠊ⏘〟࠾ࡼࡧ࿘⏘ᮇࡢ≧ែ 1 (0.8%) 1 (0.8%) 2 (1.5%) 3 (1.1%) ዷፎ 1 (0.8%) 1 (0.8%) 2 (1.5%) 3 (1.1%) ⏕Ṫ⣔࠾ࡼࡧஙᡣ㞀ᐖ 6 (4.5%) 2 (1.5%) 1 (0.8%) 3 (1.1%) ஙᡣ③ 0 1 (0.8%) 0 1 (0.4%) Ꮚᐑ㢁㒊ୖ⓶␗ᙧᡂ 0 1 (0.8%) 0 1 (0.4%) ༸ᕢᄞ⬊ 0 0 1 (0.8%) 1 (0.4%) ஙᡣศἪ 1 (0.8%) 0 0 0 ஙᡣ⭘⒗ 1 (0.8%) 0 0 0 ᭶⤒ᅔ㞴 2 (1.5%) 0 0 0 ዪᛶ⏕Ṫჾ⒦ 1 (0.8%) 0 0 0 ᭶⤒㐣ከ 1 (0.8%) 0 0 0 ᭶⤒๓ೃ⩌ 1 (0.8%) 0 0 0 ᚰ⮚㞀ᐖ 1 (0.8%) 1 (0.8%) 1 (0.8%) 2 (0.8%) ᚰᡣ⣽ື 0 1 (0.8%) 0 1 (0.4%) ື 1 (0.8%) 0 1 (0.8%) 1 (0.4%) ⪥࠾ࡼࡧ㏞㊰㞀ᐖ 2 (1.5%) 1 (0.8%) 1 (0.8%) 2 (0.8%) ⪥㬆 0 0 1 (0.8%) 1 (0.4%) ᅇ㌿ᛶࡵࡲ࠸ 2 (1.5%) 1 (0.8%) 0 1 (0.4%) ෆศἪ㞀ᐖ 0 1 (0.8%) 1 (0.8%) 2 (0.8%) ⭈ᶵ⬟ 0 0 1 (0.8%) 1 (0.4%) ⏥≧⭢⅖ 0 1 (0.8%) 0 1 (0.4%) ♫⎔ቃ 1 (0.8%) 1 (0.8%) 1 (0.8%) 2 (0.8%) ࣃ࣮ࢺࢼ࣮ࡢዷፎ 0 1 (0.8%) 1 (0.8%) 2 (0.8%) ≀㉁⏝⪅ 1 (0.8%) 0 0 0
a Subjects who were in clinical response to ustekinumab IV induction dosing and were randomized to placebo SC on entry into this maintenance study. b Includes data up to the time of dose adjustment (i.e., time of meeting loss of response criteria). [TSFAE01A.rtf] [CNTO1275\CRD3003\DBR_CSR\RE_CSR\tsfae01a.sas] 07OCT2015, 17:58
16 7 (31) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
⾲ 2.7.6.4-10 44 㐌┠ཪࡣ⏝㔞ㄪ⠇ࡢᐇⅬࡲ࡛ࡢ㦂⸆ྜ⌮ⓗ㛵㐃ᛶࡀ࠶ࡿ ᭷ᐖ㇟ࡢⓎ⌧ྜ㸦ࣛࣥࢲ࣒ᚋ㦂⸆ࢆᢞࡉࢀࡓ⿕㦂⪅㸧 ustekinumabb placebo SCa,b 90 mg SC q12w 90 mg SC q8w Combined Analysis set: Treated subjects who were randomized 133 132 131 263
Avg duration of follow-up (weeks) 32.0 36.6 35.2 35.9
Total number of subjects with 1 or more reasonably related treatment-emergent adverse events 42 (31.6%) 34 (25.8%) 39 (29.8%) 73 (27.8%)
System-organ class/preferred term ឤᰁ࠾ࡼࡧᐤ⏕ 20 (15.0%) 15 (11.4%) 21 (16.0%) 36 (13.7%) ୖẼ㐨ឤᰁ 9 (6.8%) 2 (1.5%) 6 (4.6%) 8 (3.0%) 㰯ဗ㢌⅖ 3 (2.3%) 2 (1.5%) 4 (3.1%) 6 (2.3%) ⓶┿⳦ឤᰁ 0 2 (1.5%) 1 (0.8%) 3 (1.1%) ࣥࣇ࢚ࣝࣥࢨ 1 (0.8%) 2 (1.5%) 1 (0.8%) 3 (1.1%) 㰯⭍⅖ 1 (0.8%) 1 (0.8%) 2 (1.5%) 3 (1.1%) እ㝜⭐┿⳦ឤᰁ 0 0 3 (2.3%) 3 (1.1%) ⤖⭷⅖ 0 2 (1.5%) 0 2 (0.8%) ⪥ឤᰁ 0 2 (1.5%) 0 2 (0.8%) ⭡㒊ឤᰁ 0 1 (0.8%) 0 1 (0.4%) ⫠㛛࢝ࣥࢪࢲ 0 0 1 (0.8%) 1 (0.4%) Ẽ⟶ᨭ⅖ 0 0 1 (0.8%) 1 (0.4%) ⻏ᕢ⅖ 0 1 (0.8%) 0 1 (0.4%) ࢡࣟࢫࢺࣜࢪ࣒࣭࢘ࢹࣇࢩࣞឤᰁ 0 0 1 (0.8%) 1 (0.4%) ⭠⳦ᛶᒀ㊰ឤᰁ 0 0 1 (0.8%) 1 (0.4%) ࡏࡘ 0 1 (0.8%) 0 1 (0.4%) ⫶⭠⅖ 1 (0.8%) 1 (0.8%) 0 1 (0.4%) ࢘ࣝࢫᛶ⫶⭠⅖ 0 0 1 (0.8%) 1 (0.4%) ࢘ࣝࢫᛶᾘ⟶ឤᰁ 0 0 1 (0.8%) 1 (0.4%) 㰢ᚄ㒊⮋⒆ 0 1 (0.8%) 0 1 (0.4%) ษ㛤㒊ឤᰁ 0 0 1 (0.8%) 1 (0.4%) ୗẼ㐨ឤᰁ 0 0 1 (0.8%) 1 (0.4%) ║ᖏ≧⑁⑈ 0 0 1 (0.8%) 1 (0.4%) ဗ㢌⅖ 0 1 (0.8%) 0 1 (0.4%) ⫵⅖ 1 (0.8%) 0 1 (0.8%) 1 (0.4%) 㰯⅖ 0 0 1 (0.8%) 1 (0.4%) ⓶ឤᰁ 0 1 (0.8%) 0 1 (0.4%) ⓑⓄឤᰁ 0 0 1 (0.8%) 1 (0.4%) ᒀ㊰ឤᰁ 0 1 (0.8%) 0 1 (0.4%) Ỉ① 0 0 1 (0.8%) 1 (0.4%) ࢘ࣝࢫឤᰁ 0 0 1 (0.8%) 1 (0.4%) እ㝜㒊⭐࢝ࣥࢪࢲ 0 0 1 (0.8%) 1 (0.4%) ⫠㛛⮋⒆ 1 (0.8%) 0 0 0 ⭤⬔⅖ 1 (0.8%) 0 0 0 ༢⣧࣊ࣝ࣌ࢫ 2 (1.5%) 0 0 0 㯏⢏⭘ 1 (0.8%) 0 0 0 ཱྀ⭍࣊ࣝ࣌ࢫ 2 (1.5%) 0 0 0 ࣞࣥࢧ⌫⳦ᛶဗ㢌⅖ 1 (0.8%) 0 0 0 ṑឤᰁ 1 (0.8%) 0 0 0 ⤖᰾ 1 (0.8%) 0 0 0 ୍⯡࣭㌟㞀ᐖ࠾ࡼࡧᢞ㒊ࡢ≧ែ 9 (6.8%) 7 (5.3%) 13 (9.9%) 20 (7.6%) ὀᑕ㒊⣚ᩬ 0 1 (0.8%) 7 (5.3%) 8 (3.0%) ⑂ປ 2 (1.5%) 3 (2.3%) 2 (1.5%) 5 (1.9%) Ⓨ⇕ 3 (2.3%) 1 (0.8%) 3 (2.3%) 4 (1.5%) ᝏᐮ 1 (0.8%) 1 (0.8%) 0 1 (0.4%) ὀᑕ㒊⚄⤒ᦆയ 0 0 1 (0.8%) 1 (0.4%) ὀᑕ㒊⑊③ 1 (0.8%) 1 (0.8%) 0 1 (0.4%) ὀᑕ㒊▱ぬ␗ᖖ 0 0 1 (0.8%) 1 (0.4%) ὀᑕ㒊Ⓨ⑈ 0 0 1 (0.8%) 1 (0.4%) ὀᑕ㒊⭘⬽ 0 0 1 (0.8%) 1 (0.4%) ὀᑕ㒊ⶼ㯞⑈ 0 1 (0.8%) 0 1 (0.4%) ὀᑕ㒊ᑠỈ⑁ 0 0 1 (0.8%) 1 (0.4%) ⬚㒊ᛌឤ 1 (0.8%) 0 0 0 ࣥࣇ࢚ࣝࣥࢨᵝᝈ 1 (0.8%) 0 0 0 ⫶⭠㞀ᐖ 14 (10.5%) 9 (6.8%) 8 (6.1%) 17 (6.5%) ᝏᚰ 4 (3.0%) 3 (2.3%) 3 (2.3%) 6 (2.3%)
16 8 (32) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
ustekinumabb placebo SCa,b 90 mg SC q12w 90 mg SC q8w Combined ࢡ࣮ࣟࣥ 5 (3.8%) 3 (2.3%) 2 (1.5%) 5 (1.9%) ⭡③ 3 (2.3%) 0 1 (0.8%) 1 (0.4%) ୖ⭡㒊③ 1 (0.8%) 0 1 (0.8%) 1 (0.4%) ⒦ 0 1 (0.8%) 0 1 (0.4%) ࣇࢱᛶཱྀෆ⅖ 0 1 (0.8%) 0 1 (0.4%) ౽⛎ 1 (0.8%) 1 (0.8%) 0 1 (0.4%) ୗ⑩ 3 (2.3%) 0 1 (0.8%) 1 (0.4%) ⫶⭠⟶⒦ 0 1 (0.8%) 0 1 (0.4%) ⭠⊃✽ 0 1 (0.8%) 0 1 (0.4%) ཱྀ⭍ෆ₽⒆ᙧᡂ 1 (0.8%) 1 (0.8%) 0 1 (0.4%) ཱྀࡢ㘒ឤぬ 0 0 1 (0.8%) 1 (0.4%) ᑠ⭠㛢ሰ 0 1 (0.8%) 0 1 (0.4%) ྤ 2 (1.5%) 1 (0.8%) 0 1 (0.4%) ᄟୗ㞀ᐖ 1 (0.8%) 0 0 0 ⫶⅖ 1 (0.8%) 0 0 0 ⓶࠾ࡼࡧ⓶ୗ⤌⧊㞀ᐖ 8 (6.0%) 5 (3.8%) 8 (6.1%) 13 (4.9%) Ⓨ⑈ 4 (3.0%) 2 (1.5%) 2 (1.5%) 4 (1.5%) ‵⑈ 0 1 (0.8%) 1 (0.8%) 2 (0.8%) ࡑ࠺ 0 1 (0.8%) 1 (0.8%) 2 (0.8%) ⬺ẟ 2 (1.5%) 1 (0.8%) 0 1 (0.4%) Ỉ⑁ 0 0 1 (0.8%) 1 (0.4%) Ⓞᵝ⓶⅖ 0 0 1 (0.8%) 1 (0.4%) ⓶⬡Ḟஈᛶ‵⑈ 0 0 1 (0.8%) 1 (0.4%) ⬡₃ᛶ⓶⅖ 0 0 1 (0.8%) 1 (0.4%) ⓶ኚ 1 (0.8%) 0 1 (0.8%) 1 (0.4%) ᐷờ 1 (0.8%) 0 0 0 ⚄⤒⣔㞀ᐖ 7 (5.3%) 4 (3.0%) 8 (6.1%) 12 (4.6%) 㢌③ 3 (2.3%) 4 (3.0%) 5 (3.8%) 9 (3.4%) ᾋືᛶࡵࡲ࠸ 0 1 (0.8%) 1 (0.8%) 2 (0.8%) Ⴔ╀ 0 1 (0.8%) 0 1 (0.4%) ∦㢌③ 3 (2.3%) 0 1 (0.8%) 1 (0.4%) 㘒ឤぬ 0 0 1 (0.8%) 1 (0.4%) 㰯⭍⅖క࠺㢌③ 0 0 1 (0.8%) 1 (0.4%) ኻ⚄ 1 (0.8%) 0 0 0 ୕ཫ⚄⤒③ 1 (0.8%) 0 0 0 ⮫ᗋ᳨ᰝ 3 (2.3%) 6 (4.5%) 3 (2.3%) 9 (3.4%) ᚰᢿᩘቑຍ 0 2 (1.5%) 0 2 (0.8%) ⫢ᶵ⬟᳨ᰝ␗ᖖ 1 (0.8%) 0 2 (1.5%) 2 (0.8%) ᣑᙇᮇ⾑ᅽୖ᪼ 0 1 (0.8%) 0 1 (0.4%) య ୖ᪼ 0 0 1 (0.8%) 1 (0.4%) ࢡࣟࢫࢺࣜࢪ᳨࣒࢘ᰝ㝧ᛶ 0 1 (0.8%) 0 1 (0.4%) ⫢㓝⣲ୖ᪼ 0 1 (0.8%) 0 1 (0.4%) ࣄࢺங㢌⭘࢘ࣝࢫ᳨ᰝ㝧ᛶ 0 1 (0.8%) 0 1 (0.4%) ࢺࣛࣥࢫ࣑ࢼ࣮ࢮୖ᪼ 0 1 (0.8%) 0 1 (0.4%) ⾑୰ࣝࣈ࣑ࣥῶᑡ 1 (0.8%) 0 0 0 ዲ㓟⌫ᩘቑຍ 1 (0.8%) 0 0 0 ⥲⺮ⓑῶᑡ 1 (0.8%) 0 0 0 ➽㦵᱁⣔࠾ࡼࡧ⤖ྜ⤌⧊㞀ᐖ 10 (7.5%) 2 (1.5%) 3 (2.3%) 5 (1.9%) 㛵⠇③ 7 (5.3%) 1 (0.8%) 1 (0.8%) 2 (0.8%) ⫼㒊③ 2 (1.5%) 0 1 (0.8%) 1 (0.4%) ➽⫗③ 0 1 (0.8%) 0 1 (0.4%) ᅄ⫥③ 0 0 1 (0.8%) 1 (0.4%) 㛵⠇⭘⬽ 1 (0.8%) 0 0 0 ྾ჾࠊ⬚㒌࠾ࡼࡧ⦪㝸㞀ᐖ 4 (3.0%) 1 (0.8%) 2 (1.5%) 3 (1.1%) ྾ᅔ㞴 0 1 (0.8%) 0 1 (0.4%) 㰯⭍࠺ࡗ⾑ 0 0 1 (0.8%) 1 (0.4%) ୖẼ㐨တೃ⩌ 0 0 1 (0.8%) 1 (0.4%) 㰯㛢 2 (1.5%) 0 0 0 ཱྀ⭍ဗ㢌③ 1 (0.8%) 0 0 0 㰯⭍ᛌឤ 1 (0.8%) 0 0 0 㰯₃ 1 (0.8%) 0 0 0 ⪥࠾ࡼࡧ㏞㊰㞀ᐖ 0 1 (0.8%) 1 (0.8%) 2 (0.8%) ⪥㬆 0 0 1 (0.8%) 1 (0.4%) ᅇ㌿ᛶࡵࡲ࠸ 0 1 (0.8%) 0 1 (0.4%) ⫢⫹㐨⣔㞀ᐖ 0 0 2 (1.5%) 2 (0.8%) ⫹▼ 0 0 1 (0.8%) 1 (0.4%)
16 9 (33) ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
ustekinumabb placebo SCa,b 90 mg SC q12w 90 mg SC q8w Combined ⫢ᶵ⬟␗ᖖ 0 0 1 (0.8%) 1 (0.4%) ⏕Ṫ⣔࠾ࡼࡧஙᡣ㞀ᐖ 0 2 (1.5%) 0 2 (0.8%) ஙᡣ③ 0 1 (0.8%) 0 1 (0.4%) Ꮚᐑ㢁㒊ୖ⓶␗ᙧᡂ 0 1 (0.8%) 0 1 (0.4%) ෆศἪ㞀ᐖ 0 1 (0.8%) 0 1 (0.4%) ⏥≧⭢⅖ 0 1 (0.8%) 0 1 (0.4%) ║㞀ᐖ 0 0 1 (0.8%) 1 (0.4%) 㟝ど 0 0 1 (0.8%) 1 (0.4%) ⾑⟶㞀ᐖ 2 (1.5%) 0 1 (0.8%) 1 (0.4%) ࡚ࡾ 0 0 1 (0.8%) 1 (0.4%) ₻⣚ 2 (1.5%) 0 0 0 ⢭⚄㞀ᐖ 1 (0.8%) 0 0 0 ࠺ࡘ 1 (0.8%) 0 0 0
a Subjects who were in clinical response to ustekinumab IV induction dosing and were randomized to placebo SC on entry into this maintenance study. b Includes data up to the time of dose adjustment (i.e., time of meeting loss of response criteria). [TSFAE05A.rtf] [CNTO1275\CRD3003\DBR_CSR\RE_CSR\tsfae05a.sas] 07OCT2015, 17:59
17 0 (34)
(35 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 ⾲ 2.7.6.4-11 44 㐌┠ࡲ࡛ࡢ᭷ᐖ㇟ࡢⓎ⌧ྜ㸦ᅉᯝ㛵ಀࢆၥࢃ࡞࠸ࡍ࡚ࡢ᭷ᐖ㇟㸭㦂⸆ྜ⌮ⓗ㛵㐃ᛶࡀ࠶ࡿ᭷ᐖ㇟㸧 㸦㦂⸆ࢆᢞࡉࢀࡓࡍ࡚ࡢ⿕㦂⪅㸧 All TEAEs Reasonably related TEAEs Placebo a Ustekinumab Placebo a Ustekinumab Analysis Set: Treated subjects 242 1157 242 1157
2.7.6 Total number of subjects with TEAEs 198 (81.8%) 869 (75.1%) 67 (27.7%) 318 (27.5%)
System-organ class/preferred term ឤᰁ࠾ࡼࡧᐤ⏕ 117 (48.3%) 484 (41.8%) 33 (13.6%) 146 (12.6%) 㰯ဗ㢌⅖ 22 (9.1%) 124 (10.7%) 5 (2.1%) 22 (1.9%) ୖẼ㐨ឤᰁ 23 (9.5%) 89 (7.7%) 8 (3.3%) 33 (2.9%) 㰯⭍⅖ 7 (2.9%) 44 (3.8%) 2 (0.8%) 12 (1.0%) ⫶⭠⅖ 8 (3.3%) 37 (3.2%) 1 (0.4%) 2 (0.2%) ᒀ㊰ឤᰁ 9 (3.7%) 37 (3.2%) 1 (0.4%) 12 (1.0%) ࣥࣇ࢚ࣝࣥࢨ 7 (2.9%) 36 (3.1%) 1 (0.4%) 6 (0.5%) ࢘ࣝࢫᛶ⫶⭠⅖ 6 (2.5%) 26 (2.2%) 0 1 (0.1%) Ẽ⟶ᨭ⅖ 5 (2.1%) 25 (2.2%) 1 (0.4%) 5 (0.4%) ཱྀ⭍࣊ࣝ࣌ࢫ 4 (1.7%) 18 (1.6%) 2 (0.8%) 9 (0.8%) ࢘ࣝࢫឤᰁ 5 (2.1%) 15 (1.3%) 0 4 (0.3%) ⫠㛛⮋⒆ 8 (3.3%) 14 (1.2%) 2 (0.8%) 3 (0.3%) ⤖⭷⅖ 2 (0.8%) 13 (1.1%) 1 (0.4%) 3 (0.3%) ဗ㢌⅖ 2 (0.8%) 13 (1.1%) 1 (0.4%) 3 (0.3%) ⪥ឤᰁ 1 (0.4%) 12 (1.0%) 0 6 (0.5%) እ㝜⭐┿⳦ឤᰁ 3 (1.2%) 12 (1.0%) 0 4 (0.3%) ཱྀ⭍࢝ࣥࢪࢲ 1 (0.4%) 11 (1.0%) 1 (0.4%) 2 (0.2%) ṑ⮋⒆ 1 (0.4%) 10 (0.9%) 1 (0.4%) 3 (0.3%) ⭤⬔⅖ 0 9 (0.8%) 0 3 (0.3%) ⫵⅖ 2 (0.8%) 9 (0.8%) 1 (0.4%) 1 (0.1%) 㰯⅖ 1 (0.4%) 7 (0.6%) 1 (0.4%) 2 (0.2%) ⓶ୗ⤌⧊⮋⒆ 0 7 (0.6%) 0 3 (0.3%) እ㝜㒊⭐࢝ࣥࢪࢲ 0 7 (0.6%) 0 2 (0.2%) ⓶┿⳦ឤᰁ 0 6 (0.5%) 0 4 (0.3%) ୗẼ㐨ឤᰁ 2 (0.8%) 6 (0.5%) 0 2 (0.2%) ࣞࣥࢧ⌫⳦ᛶဗ㢌⅖ 4 (1.7%) 6 (0.5%) 2 (0.8%) 3 (0.3%) ಶ ࢡࣟࢫࢺࣜࢪ࣒࣭࢘ࢹࣇࢩࣞឤᰁ 2 (0.8%) 5 (0.4%) 0 1 (0.1%) ࠎ ࡢヨ ẟໟ⅖ 2 (0.8%) 5 (0.4%) 0 2 (0.2%) 㯏⢏⭘ 1 (0.4%) 5 (0.4%) 1 (0.4%) 2 (0.2%) 㦂 ᡥ᱈⅖ 0 5 (0.4%) 0 0 ࡢࡲ ࢘ࣝࢫᛶᾘ⟶ឤᰁ 0 4 (0.3%) 0 1 (0.1%) ᖏ≧⑁⑈ 3 (1.2%) 4 (0.3%) 1 (0.4%) 2 (0.2%) ヨ ┤⭠⮋⒆ ࡵ 2 (0.8%) 4 (0.3%) 0 0 㦂 )
171
(36 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 All TEAEs Reasonably related TEAEs Placebo a Ustekinumab Placebo a Ustekinumab ࣈࢻ࢘⌫⳦⓶ឤᰁ 0 4 (0.3%) 0 0 ⭡㒊⮋⒆ 1 (0.4%) 3 (0.3%) 0 1 (0.1%) ᛴᛶ㰯⭍⅖ 0 3 (0.3%) 0 1 (0.1%) ᛴᛶᡥ᱈⅖ 0 3 (0.3%) 0 2 (0.2%)
⻏ᕢ⅖ 1 (0.4%) 3 (0.3%) 0 1 (0.1%) 2.7.6 ៏ᛶ㰯⭍⅖ 0 3 (0.3%) 0 0 ࢡࣟࢫࢺࣜࢪ࣒࣭࢘ࢹࣇࢩࣞ⭠⅖ 2 (0.8%) 3 (0.3%) 1 (0.4%) 0 ⣽⳦ᛶ⤖⭷⅖ 2 (0.8%) 3 (0.3%) 0 1 (0.1%) ࡏࡘ 1 (0.4%) 3 (0.3%) 0 1 (0.1%) 㝜㒊࣊ࣝ࣌ࢫ 1 (0.4%) 3 (0.3%) 0 1 (0.1%) ⪥ୗ⭢⅖ 0 3 (0.3%) 0 1 (0.1%) Ẽ㐨ឤᰁ 2 (0.8%) 3 (0.3%) 0 0 ࢘ࣝࢫᛶẼ㐨ឤᰁ 2 (0.8%) 3 (0.3%) 0 1 (0.1%) ṑឤᰁ 4 (1.7%) 3 (0.3%) 3 (1.2%) 1 (0.1%) ⣽⳦ᛶ⭐⅖ 0 3 (0.3%) 0 0 ⒦ឤᰁ 0 2 (0.2%) 0 1 (0.1%) ᆶ⅖ 0 2 (0.2%) 0 0 ⳦⾑ 0 2 (0.2%) 0 1 (0.1%) ་⒪ᶵჾ㛵㐃ឤᰁ 0 2 (0.2%) 0 1 (0.1%) ᠁ᐊ⅖ 0 2 (0.2%) 0 0 ⭠⳦ᛶᒀ㊰ឤᰁ 0 2 (0.2%) 0 2 (0.2%) ║ឤᰁ 0 2 (0.2%) 0 0 ṑ⫗⅖ 0 2 (0.2%) 0 0 ࣊ࣜࢥࣂࢡࢱ࣮ឤᰁ 0 2 (0.2%) 0 0 ⮋⑈ 0 2 (0.2%) 0 1 (0.1%) ษ㛤㒊ឤᰁ 1 (0.4%) 2 (0.2%) 0 1 (0.1%) ㏞㊰⅖ 0 2 (0.2%) 0 1 (0.1%) ႃ㢌⅖ 1 (0.4%) 2 (0.2%) 0 0 㣗㐨࢝ࣥࢪࢲ 0 2 (0.2%) 0 1 (0.1%) እ⪥⅖ 0 2 (0.2%) 0 0 ┤⭠࿘ᅖ⮋⒆ 0 2 (0.2%) 0 0 ⭡⭷⅖ 0 2 (0.2%) 0 0 ⾡ᚋឤᰁ 0 2 (0.2%) 0 0 ಶ ⓶ឤᰁ 0 2 (0.2%) 0 1 (0.1%) ࠎ ⓑⓄឤᰁ 1 (0.4%) 2 (0.2%) 0 1 (0.1%) ࡢヨ ㊊㒊ⓑⓄ 0 2 (0.2%) 0 1 (0.1%) Ẽ⟶Ẽ⟶ᨭ⅖ 1 (0.4%) 2 (0.2%) 0 0 㦂 ⭐⮋⒆ 0 2 (0.2%) 0 0 ࡢࡲ ⭡㒊ឤᰁ 0 1 (0.1%) 0 1 (0.1%) ᅄ⫥⮋⒆ 0 1 (0.1%) 0 0 ヨ ࡵ ờ⭢⮋⒆ 0 1 (0.1%) 0 1 (0.1%) 㦂 )
172
(37 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 All TEAEs Reasonably related TEAEs Placebo a Ustekinumab Placebo a Ustekinumab ṑᵴ㦵⅖ 0 1 (0.1%) 0 0 ⫠㛛࢝ࣥࢪࢲ 0 1 (0.1%) 0 1 (0.1%) ┿⳦ᛶ⫠㛛ឤᰁ 0 1 (0.1%) 0 0 ࢝ࣥࣆࣟࣂࢡࢱ࣮⫶⭠⅖ 0 1 (0.1%) 0 0
ࢡ࣑ࣛࢪឤᰁ 0 1 (0.1%) 0 0 2.7.6 ࢘ࣝࢫᛶ⤖⭷⅖ 0 1 (0.1%) 0 0 ឤᰁᛶ‵⑈ 0 1 (0.1%) 0 0 ឤᰁᛶ⭠⅖ 0 1 (0.1%) 0 1 (0.1%) ⣽⳦ᛶ⭠⅖ 0 1 (0.1%) 0 0 ⣽⳦ᛶ⫶⭠⅖ 0 1 (0.1%) 0 0 ࣀࣟ࢘ࣝࢫᛶ⫶⭠⅖ 0 1 (0.1%) 0 0 ⣽⳦ᛶᾘ⟶ឤᰁ 0 1 (0.1%) 0 0 ┿⳦ᛶᛶჾឤᰁ 0 1 (0.1%) 0 1 (0.1%) 㰢ᚄ㒊⮋⒆ 0 1 (0.1%) 0 1 (0.1%) 㹁ᆺ⫢⅖ 0 1 (0.1%) 0 0 ఏᰁᛶ༢᰾⫢⅖ 0 1 (0.1%) 0 1 (0.1%) ༢⣧࣊ࣝ࣌ࢫ 2 (0.8%) 1 (0.1%) 2 (0.8%) 1 (0.1%) ឤᰁᛶ⒦Ꮝ 0 1 (0.1%) 0 0 ⴥᛶ⫵⅖ 0 1 (0.1%) 0 0 㝈ᒁᛶឤᰁ 0 1 (0.1%) 0 0 ⢓⭷ឤᰁ 0 1 (0.1%) 0 0 ࣐ࢥࣉࣛࢬ࣐ឤᰁ 0 1 (0.1%) 0 0 㰯๓ᗞ⅖ 0 1 (0.1%) 0 0 ║ᖏ≧⑁⑈ 0 1 (0.1%) 0 1 (0.1%) ୰⪥⅖ 0 1 (0.1%) 0 1 (0.1%) ∎ᅖ⅖ 1 (0.4%) 1 (0.1%) 0 1 (0.1%) ṑෙ࿘ᅖ⅖ 0 1 (0.1%) 0 0 ṑ࿘⅖ 2 (0.8%) 1 (0.1%) 0 0 ẟᕢᄞ⬊ 0 1 (0.1%) 0 0 ⫵⅖⌫⳦ᛶ⫵⅖ 0 1 (0.1%) 0 0 ࣈࢻ࢘⌫⳦ᛶ⫵⅖ 0 1 (0.1%) 0 1 (0.1%) ṑ㧊⅖ 0 1 (0.1%) 0 0 ⮋⑁ᛶ⓶⑈ 0 1 (0.1%) 0 0 ಶ ࣟࢱ࢘ࣝࢫឤᰁ 0 1 (0.1%) 0 0 ࠎ ᩋ⾑ 0 1 (0.1%) 0 1 (0.1%) ࡢヨ 㰯⭍Ẽ⟶ᨭ⅖ 0 1 (0.1%) 0 0 ᑠ⭠ෆ⣽⳦㐣ቑṪ 1 (0.4%) 1 (0.1%) 0 0 㦂 ㌾㒊⤌⧊ឤᰁ 0 1 (0.1%) 0 0 ࡢࡲ ࣈࢻ࢘⌫⳦ឤᰁ 1 (0.4%) 1 (0.1%) 0 0 ࢫࢺ࣮࣐㒊⮋⒆ 0 1 (0.1%) 0 0 ヨ ࡵ Ẽ⟶⅖ 0 1 (0.1%) 0 0 㦂 )
173
(38 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 All TEAEs Reasonably related TEAEs Placebo a Ustekinumab Placebo a Ustekinumab ⣽⳦ᛶᒀ㊰ឤᰁ 0 1 (0.1%) 0 1 (0.1%) ⭐ឤᰁ 0 1 (0.1%) 0 0 Ỉ① 0 1 (0.1%) 0 1 (0.1%) ๓ᗞ⚄⤒⅖ 0 1 (0.1%) 0 0
࢘ࣝࢫᛶⓎ⑈ 0 1 (0.1%) 0 0 2.7.6 ࢘ࣝࢫᛶୖẼ㐨ឤᰁ 3 (1.2%) 1 (0.1%) 1 (0.4%) 1 (0.1%) യឤᰁ 1 (0.4%) 1 (0.1%) 0 0 ⮋⒆ 1 (0.4%) 0 0 0 ឤᰁᛶୗ⑩ 2 (0.8%) 0 0 0 ࣊ࣔࣇࣝࢫឤᰁ 1 (0.4%) 0 0 0 ឤᰁᛶᄞ⭘ 1 (0.4%) 0 0 0 ὀධ㒊⻏ᕢ⅖ 1 (0.4%) 0 0 0 ๓❧⭢ឤᰁ 1 (0.4%) 0 0 0 ⭈│⭈⅖ 1 (0.4%) 0 0 0 ⤖᰾ 1 (0.4%) 0 1 (0.4%) 0 ࢺࣜࢥࣔࢼࢫᛶእ㝜㒊⭐⅖ 2 (0.8%) 0 0 0 ⫶⭠㞀ᐖ 116 (47.9%) 459 (39.7%) 23 (9.5%) 72 (6.2%) ࢡ࣮ࣟࣥ 34 (14.0%) 150 (13.0%) 6 (2.5%) 11 (1.0%) ⭡③ 26 (10.7%) 99 (8.6%) 3 (1.2%) 11 (1.0%) ᝏᚰ 19 (7.9%) 85 (7.3%) 8 (3.3%) 20 (1.7%) ྤ 13 (5.4%) 56 (4.8%) 2 (0.8%) 8 (0.7%) ୗ⑩ 16 (6.6%) 45 (3.9%) 2 (0.8%) 5 (0.4%) ୖ⭡㒊③ 8 (3.3%) 33 (2.9%) 2 (0.8%) 5 (0.4%) ౽⛎ 5 (2.1%) 28 (2.4%) 1 (0.4%) 4 (0.3%) ⒦ 6 (2.5%) 19 (1.6%) 0 2 (0.2%) ᑠ⭠㛢ሰ 1 (0.4%) 19 (1.6%) 0 1 (0.1%) ࣇࢱᛶཱྀෆ⅖ 5 (2.1%) 18 (1.6%) 0 3 (0.3%) ⭡㒊⭾‶ 5 (2.1%) 17 (1.5%) 1 (0.4%) 3 (0.3%) ⫶㣗㐨㏫ὶᛶᝈ 3 (1.2%) 16 (1.4%) 0 1 (0.1%) ᰾ 6 (2.5%) 14 (1.2%) 0 1 (0.1%) ୗ⭡㒊③ 2 (0.8%) 13 (1.1%) 0 2 (0.2%) ⫠ 3 (1.2%) 13 (1.1%) 0 0 ᾘⰋ 4 (1.7%) 13 (1.1%) 0 0 ಶ ⫠㛛࿘ᅖ③ 0 13 (1.1%) 0 0 ࠎ ┤⭠ฟ⾑ 2 (0.8%) 12 (1.0%) 0 0 ࡢヨ ⫶⅖ 1 (0.4%) 10 (0.9%) 1 (0.4%) 2 (0.2%) ⾑౽ἥ 1 (0.4%) 10 (0.9%) 1 (0.4%) 2 (0.2%) 㦂 ཱྀ⭍ෆ₽⒆ᙧᡂ 2 (0.8%) 10 (0.9%) 1 (0.4%) 2 (0.2%) ࡢࡲ 㱘ṑ 2 (0.8%) 8 (0.7%) 0 0 ⫠㛛┤⭠ᛌឤ 0 6 (0.5%) 0 0 ヨ ࡵ ᨺᒂ 1 (0.4%) 6 (0.5%) 1 (0.4%) 0 㦂 )
174
(39 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 All TEAEs Reasonably related TEAEs Placebo a Ustekinumab Placebo a Ustekinumab ᄟୗ㞀ᐖ 0 5 (0.4%) 0 1 (0.1%) ౽ᅇᩘቑຍ 3 (1.2%) 5 (0.4%) 0 1 (0.1%) ⭡㒊ᛌឤ 0 4 (0.3%) 0 0 㣗୰ẘ 1 (0.4%) 4 (0.3%) 0 0
⭠㛢ሰ 0 4 (0.3%) 0 0 2.7.6 ⭠⊃✽ 1 (0.4%) 4 (0.3%) 0 1 (0.1%) ⫠㛛⊃✽ 0 3 (0.3%) 0 0 ⾑ᛶୗ⑩ 1 (0.4%) 3 (0.3%) 0 1 (0.1%) ࡧࡽࢇᛶ㣗㐨⅖ 0 3 (0.3%) 0 0 ྤ⾑ 1 (0.4%) 3 (0.3%) 0 0 ཱྀࡢ㘒ឤぬ 0 3 (0.3%) 0 3 (0.3%) ṑ③ 5 (2.1%) 3 (0.3%) 0 0 ⫠㛛ࡢ⅖ 2 (0.8%) 2 (0.2%) 0 0 ⫠㛛ࡑ࠺ 0 2 (0.2%) 0 0 ౽ពษ㏕ 1 (0.4%) 2 (0.2%) 0 0 ᑠ⭠⅖ 0 2 (0.2%) 0 0 ⭠⟶⓶⒦ 0 2 (0.2%) 0 0 ౽ኻ⚗ 0 2 (0.2%) 0 0 ⣅ሢ 0 2 (0.2%) 0 0 ኚⰍ౽ 0 2 (0.2%) 0 0 ⫶⭠ฟ⾑ 0 2 (0.2%) 0 1 (0.1%) ⫶⭠㡢␗ᖖ 0 2 (0.2%) 0 0 ⭠⟶⒦ 0 2 (0.2%) 0 0 ⭠⟶⊃✽ 1 (0.4%) 2 (0.2%) 0 0 ⭠㛢ሰ 0 2 (0.2%) 0 0 ⢓ᾮ౽ 0 2 (0.2%) 0 0 ཱྀෆ⅖ 1 (0.4%) 2 (0.2%) 0 2 (0.2%) ᇙఅṑ 0 2 (0.2%) 0 0 ⭡㒊⒵╔ 0 1 (0.1%) 0 0 ⭡㒊࣊ࣝࢽ 0 1 (0.1%) 0 0 ⭡㒊◳┤ 0 1 (0.1%) 0 0 ⫠㛛ࡧࡽࢇ 0 1 (0.1%) 0 0 ⫠㛛⓶ᆶ 1 (0.4%) 1 (0.1%) 0 0 ಶ ⫠㛛┤⭠⊃✽ 0 1 (0.1%) 0 0 ࠎ ၚᾮḞஈ 0 1 (0.1%) 0 0 ࡢヨ ⫹Ồ㓟྾Ⰻ 0 1 (0.1%) 0 0 ౽㏻つ๎ 0 1 (0.1%) 0 0 㦂 Ẽ⮯ 0 1 (0.1%) 0 0 ࡢࡲ ཱྀ၁⅖ 0 1 (0.1%) 0 0 ⭠⅖ 0 1 (0.1%) 0 0 ヨ ࡵ ⤖⭠⒦ 0 1 (0.1%) 0 0 㦂 )
175
(40 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 All TEAEs Reasonably related TEAEs Placebo a Ustekinumab Placebo a Ustekinumab ࿘ᮇᛶྤೃ⩌ 0 1 (0.1%) 0 0 ṑᛌឤ 1 (0.4%) 1 (0.1%) 0 0 ཱྀෆ⇱ 0 1 (0.1%) 0 1 (0.1%) ༑ᣦ⭠₽⒆ 0 1 (0.1%) 0 0
༑ᣦ⭠⅖ 0 1 (0.1%) 0 0 2.7.6 ⣽⳦ྀ␗ᖖ 0 1 (0.1%) 0 0 ⭠⅖ 1 (0.4%) 1 (0.1%) 0 0 ࠾ࡃࡧ 0 1 (0.1%) 0 0 ౽㔞ቑຍ 0 1 (0.1%) 0 0 ࡧࡽࢇᛶ⫶⅖ 0 1 (0.1%) 0 0 ⫶༑ᣦ⭠⅖ 0 1 (0.1%) 0 0 ⫶⭠⟶⒦ 0 1 (0.1%) 0 1 (0.1%) ṑ⫗₽⒆ 0 1 (0.1%) 0 0 ⯉③ 0 1 (0.1%) 0 1 (0.1%) ฟ⾑ 1 (0.4%) 1 (0.1%) 0 0 Ꮝ࣊ࣝࢽ 0 1 (0.1%) 0 0 ཱྀࡢឤぬ㕌㯞 0 1 (0.1%) 0 1 (0.1%) ᅇ⭠⒦ 0 1 (0.1%) 0 0 ᅇ⭠⊃✽ 1 (0.4%) 1 (0.1%) 0 0 㯞⑷ᛶࣞ࢘ࢫ 0 1 (0.1%) 0 0 㐣ᩄᛶ⭠ೃ⩌ 1 (0.4%) 1 (0.1%) 0 0 ࣓ࣞࢼ 0 1 (0.1%) 0 0 㣗㐨ᛌឤ 0 1 (0.1%) 0 0 㣗㐨⊃✽ 0 1 (0.1%) 0 0 㣗㐨⅖ 0 1 (0.1%) 0 0 ཱྀ⭍ෆᛌឤ 0 1 (0.1%) 0 0 ཱྀ⭍⢓⭷Ỉ⑁ᙧᡂ 0 1 (0.1%) 0 0 ཱྀ⭍ෆ③ 1 (0.4%) 1 (0.1%) 0 1 (0.1%) ⮅⅖ 0 1 (0.1%) 0 0 ṑ࿘ 1 (0.4%) 1 (0.1%) 0 0 ᄞ⅖ 0 1 (0.1%) 0 0 ┤⭠ࡋࡪࡾ 1 (0.4%) 1 (0.1%) 0 0 ࣞࢵࢳࣥࢢ 0 1 (0.1%) 0 1 (0.1%) ಶ ᑠ⭠⊃✽ 0 1 (0.1%) 0 0 ࠎ ⯉₽⒆ 0 1 (0.1%) 0 0 ࡢヨ ⭠⭤⬔⒦ 1 (0.4%) 0 0 0 ṑ⫗ฟ⾑ 1 (0.4%) 0 0 0 㦂 ⭠✸Ꮝ 1 (0.4%) 0 0 0 ࡢࡲ ࣐࣮࣭ࣟࣜ࣡ࢫೃ⩌ 1 (0.4%) 0 0 0 ᄟୗ③ 1 (0.4%) 0 1 (0.4%) 0 ヨ ࡵ ➽㦵᱁⣔࠾ࡼࡧ⤖ྜ⤌⧊㞀ᐖ 64 (26.4%) 247 (21.3%) 14 (5.8%) 30 (2.6%) 㦂 )
176
(41 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 All TEAEs Reasonably related TEAEs Placebo a Ustekinumab Placebo a Ustekinumab 㛵⠇③ 39 (16.1%) 133 (11.5%) 11 (4.5%) 17 (1.5%) ⫼㒊③ 7 (2.9%) 44 (3.8%) 2 (0.8%) 2 (0.2%) ➽⫗③ 1 (0.4%) 19 (1.6%) 0 4 (0.3%) ᅄ⫥③ 0 19 (1.6%) 0 4 (0.3%)
㛵⠇⅖ 9 (3.7%) 15 (1.3%) 0 1 (0.1%) 2.7.6 ➽㦵᱁③ 2 (0.8%) 12 (1.0%) 0 1 (0.1%) 㢁㒊③ 3 (1.2%) 9 (0.8%) 1 (0.4%) 0 ➽ຊపୗ 0 5 (0.4%) 0 1 (0.1%) 㦵⢒㧼 0 5 (0.4%) 0 0 ⭝⅖ 1 (0.4%) 5 (0.4%) 0 0 ഃ⭡㒊③ 0 4 (0.3%) 0 0 㰢ᚄ㒊③ 0 4 (0.3%) 0 1 (0.1%) ⫪ᅇ᪕➽⭝ᯈೃ⩌ 1 (0.4%) 4 (0.3%) 0 0 㛵⠇⭘⬽ 2 (0.8%) 3 (0.3%) 1 (0.4%) 0 ➽②⦰ 1 (0.4%) 3 (0.3%) 0 0 ➽㦵᱁◳┤ 3 (1.2%) 3 (0.3%) 1 (0.4%) 1 (0.1%) ኚᙧᛶ㛵⠇ 0 3 (0.3%) 0 1 (0.1%) ᾮᄞ⭘ 0 3 (0.3%) 0 0 ᙎⓎᣦ 0 3 (0.3%) 0 0 ᳝㛫ᯈ✺ฟ 0 2 (0.2%) 0 0 ➽㦵᱁⣔⬚③ 2 (0.8%) 2 (0.2%) 0 0 㦵ῶᑡ 0 2 (0.2%) 0 0 㢡③ 0 2 (0.2%) 0 0 㛵⠇࿘ᅖ⅖ 1 (0.4%) 2 (0.2%) 0 0 ከⓎᛶ㛵⠇⅖ 0 2 (0.2%) 0 1 (0.1%) ⭝③ 0 2 (0.2%) 0 0 ⭝㠧⅖ 0 2 (0.2%) 0 0 ⭠⅖ᛶ㛵⠇⅖ 0 1 (0.1%) 0 0 㦵③ 0 1 (0.1%) 0 0 ᾮໟ⅖ 0 1 (0.1%) 0 0 ᑿ㦵③ 0 1 (0.1%) 0 0 ⫘㌾㦵⅖ 1 (0.4%) 1 (0.1%) 0 0 ᳝㛫㛵⠇ೃ⩌ 0 1 (0.1%) 0 0 ಶ ᣦኚᙧ 0 1 (0.1%) 0 0 ࠎ ⒦ᏍศἪ≀ 1 (0.4%) 1 (0.1%) 0 0 ࡢヨ ㊊ኚᙧ 0 1 (0.1%) 0 0 ᳝㛫ᯈኚᛶ 0 1 (0.1%) 0 0 㦂 㛵⠇ⁱฟᾮ 1 (0.4%) 1 (0.1%) 0 0 ࡢࡲ 㛵⠇◳┤ 0 1 (0.1%) 0 0 ➽⥭ᙇ 1 (0.4%) 1 (0.1%) 0 0 ヨ ࡵ ➽ᨥ⦰ 1 (0.4%) 1 (0.1%) 0 1 (0.1%) 㦂 )
177
(42 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 All TEAEs Reasonably related TEAEs Placebo a Ustekinumab Placebo a Ustekinumab 㦵ቯṚ 0 1 (0.1%) 0 0 ⭸⭣㛵⠇③ೃ⩌ 0 1 (0.1%) 0 0 ⬨ᰕ⟶⊃✽ 0 1 (0.1%) 0 0 ⬨ᰕኚᙧ 0 1 (0.1%) 0 0
ኚᙧᛶ⬨᳝ 0 1 (0.1%) 0 0 2.7.6 ⬨᳝③ 0 1 (0.1%) 0 0 ⭷⅖ 0 1 (0.1%) 0 0 㢡㛵⠇ೃ⩌ 0 1 (0.1%) 0 0 ᩳ㢁 0 1 (0.1%) 0 0 㦵႙ኻ 2 (0.8%) 0 1 (0.4%) 0 ⥺⥔➽③ 1 (0.4%) 0 0 0 ⭜㒊⬨ᰕ⟶⊃✽ 1 (0.4%) 0 0 0 ࣐ࣜ࢘ࢳᛶከⓎ➽③ 1 (0.4%) 0 0 0 㛵⠇࣐ࣜ࢘ࢳ 1 (0.4%) 0 0 0 ⓶࠾ࡼࡧ⓶ୗ⤌⧊㞀ᐖ 31 (12.8%) 213 (18.4%) 9 (3.7%) 75 (6.5%) Ⓨ⑈ 8 (3.3%) 45 (3.9%) 5 (2.1%) 18 (1.6%) ࡑ࠺ 2 (0.8%) 26 (2.2%) 0 7 (0.6%) ࡊ⒔ 1 (0.4%) 19 (1.6%) 0 7 (0.6%) ⬺ẟ 1 (0.4%) 16 (1.4%) 1 (0.4%) 8 (0.7%) ‵⑈ 2 (0.8%) 11 (1.0%) 0 3 (0.3%) ᐷờ 1 (0.4%) 11 (1.0%) 1 (0.4%) 3 (0.3%) ⶼ㯞⑈ 2 (0.8%) 9 (0.8%) 0 1 (0.1%) Ⓞ 0 8 (0.7%) 0 3 (0.3%) ከờ 0 7 (0.6%) 0 3 (0.3%) ⓶ኚ 2 (0.8%) 7 (0.6%) 0 2 (0.2%) ᥋ゐᛶ⓶⅖ 0 6 (0.5%) 0 0 ⓶⇱ 0 6 (0.5%) 0 2 (0.2%) ࡑ࠺ᛶ⓶⑈ 1 (0.4%) 6 (0.5%) 0 1 (0.1%) ⓶ᄞ⭘ 1 (0.4%) 5 (0.4%) 0 0 ⣚ᩬ 1 (0.4%) 5 (0.4%) 0 3 (0.3%) ⤖⠇ᛶ⣚ᩬ 0 5 (0.4%) 0 0 ᪥ගゅ 1 (0.4%) 4 (0.3%) 0 0 Ỉ⑁ 0 4 (0.3%) 0 2 (0.2%) ಶ ⓶⅖ 0 4 (0.3%) 0 2 (0.2%) ࠎ ᩬ≧ୣ⑈≧⓶⑈ 1 (0.4%) 3 (0.3%) 1 (0.4%) 2 (0.2%) ࡢヨ 㓇ࡉ 0 3 (0.3%) 0 0 ෭ờ 0 2 (0.2%) 0 0 㦂 㐣ゅ 0 2 (0.2%) 0 1 (0.1%) ࡢࡲ ᡥᖹⱏⓄ 1 (0.4%) 2 (0.2%) 0 0 ග⥺㐣ᩄᛶᛂ 0 2 (0.2%) 0 0 ヨ ࡵ ⣚ᩬᛶ⓶⑈ 1 (0.4%) 2 (0.2%) 0 1 (0.1%) 㦂 )
178
(43 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 All TEAEs Reasonably related TEAEs Placebo a Ustekinumab Placebo a Ustekinumab ㌟ᛶ⓶⑈ 0 2 (0.2%) 0 1 (0.1%) ୣ⑈ᛶ⓶⑈ 0 2 (0.2%) 0 1 (0.1%) ⓶ᒁ㠃 0 2 (0.2%) 0 1 (0.1%) ⓶₽⒆ 1 (0.4%) 2 (0.2%) 0 1 (0.1%)
〟⒔ᛶ₽⒆ 0 1 (0.1%) 0 0 2.7.6 ࣞࣝࢠ࣮ᛶ⓶⅖ 0 1 (0.1%) 0 1 (0.1%) Ⓞᵝ⓶⅖ 0 1 (0.1%) 0 1 (0.1%) ␗ờᛶ‵⑈ 0 1 (0.1%) 0 0 ᩬ≧ฟ⾑ 1 (0.4%) 1 (0.1%) 0 0 ⓶⬡Ḟஈᛶ‵⑈ 0 1 (0.1%) 0 1 (0.1%) ⇕ᛶ⣚ᩬ 0 1 (0.1%) 0 0 ờ⭢⅖ 1 (0.4%) 1 (0.1%) 0 0 ከẟ 0 1 (0.1%) 0 0 ᶵᲔᛶⶼ㯞⑈ 0 1 (0.1%) 0 1 (0.1%) ờ⑈ 0 1 (0.1%) 0 0 ∎ࡢ㞀ᐖ 0 1 (0.1%) 0 1 (0.1%) ቯᛶ⮋⓶ 0 1 (0.1%) 0 1 (0.1%) ᩬ≧⓶⑈ 0 1 (0.1%) 0 1 (0.1%) 㯞⑈ᵝⓎ⑈ 0 1 (0.1%) 0 0 ᑠỈ⑁ᛶ⓶⑈ 0 1 (0.1%) 0 0 ⬡₃ᛶ⓶⅖ 0 1 (0.1%) 0 1 (0.1%) ⓶㞀ᐖ 0 1 (0.1%) 0 0 ⓶⬺ 1 (0.4%) 1 (0.1%) 0 1 (0.1%) ⓶ட 0 1 (0.1%) 0 0 ⓶Ⰽ⣲㐣 0 1 (0.1%) 0 0 ⓶ᾋ⭘ 0 1 (0.1%) 0 1 (0.1%) 㢦㠃⭘⬽ 0 1 (0.1%) 0 0 ୰ẘᛶ⓶⑈ 0 1 (0.1%) 0 1 (0.1%) ࢺࣆ࣮ᛶ⓶⅖ 1 (0.4%) 0 0 0 ⸆⑈ 1 (0.4%) 0 0 0 ⥙≧⓶ᩬ 1 (0.4%) 0 0 0 ࣞࣝࢠ࣮ᛶࡑ࠺ 1 (0.4%) 0 0 0 ୍㐣ᛶᲲ⼥ゎᛶ⓶ 1 (0.4%) 0 1 (0.4%) 0 ಶ ୍⯡࣭㌟㞀ᐖ࠾ࡼࡧᢞ㒊ࡢ≧ែ 46 (19.0%) 195 (16.9%) 12 (5.0%) 74 (6.4%) ࠎ Ⓨ⇕ 20 (8.3%) 69 (6.0%) 3 (1.2%) 10 (0.9%) ࡢヨ ⑂ປ 11 (4.5%) 47 (4.1%) 2 (0.8%) 15 (1.3%) ὀᑕ㒊⣚ᩬ 2 (0.8%) 22 (1.9%) 2 (0.8%) 22 (1.9%) 㦂 ࣥࣇ࢚ࣝࣥࢨᵝᝈ 9 (3.7%) 14 (1.2%) 1 (0.4%) 1 (0.1%) ࡢࡲ ↓ຊ 2 (0.8%) 13 (1.1%) 0 5 (0.4%) ᮎᲈᛶᾋ⭘ 2 (0.8%) 11 (1.0%) 2 (0.8%) 2 (0.2%) ヨ ࡵ 㠀ᚰ⮚ᛶ⬚③ 1 (0.4%) 10 (0.9%) 0 0 㦂 )
179
(44 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 All TEAEs Reasonably related TEAEs Placebo a Ustekinumab Placebo a Ustekinumab ὀᑕ㒊⑊③ 0 7 (0.6%) 0 6 (0.5%) ⬚㒊ᛌឤ 2 (0.8%) 6 (0.5%) 1 (0.4%) 3 (0.3%) ὀᑕ㒊ࡑ࠺ឤ 0 6 (0.5%) 0 6 (0.5%) ᮎᲈ⭘⬽ 1 (0.4%) 6 (0.5%) 0 2 (0.2%)
ᛰឤ 0 5 (0.4%) 0 0 2.7.6 ᝏᐮ 1 (0.4%) 3 (0.3%) 1 (0.4%) 2 (0.2%) ὀᑕ㒊⭘⬽ 0 3 (0.3%) 0 3 (0.3%) ὀᑕ㒊ⶼ㯞⑈ 0 3 (0.3%) 0 3 (0.3%) ෭ឤ 0 2 (0.2%) 0 1 (0.1%) ὀᑕ㒊ෆฟ⾑ 0 2 (0.2%) 0 1 (0.1%) ὀᑕ㒊Ⓨ⑈ 0 2 (0.2%) 0 2 (0.2%) 㦵ୖ③ 0 2 (0.2%) 0 0 ⭆❐③ 0 1 (0.1%) 0 0 ⬚③ 0 1 (0.1%) 0 1 (0.1%) ␗ᙧᡂ 0 1 (0.1%) 0 0 㢦㠃ᾋ⭘ 0 1 (0.1%) 0 0 ␗ᖖឤ 0 1 (0.1%) 0 1 (0.1%) ⒵Ⰻ 0 1 (0.1%) 0 1 (0.1%) ὀධ㒊Ⓨ⑈ 0 1 (0.1%) 0 0 ὀᑕ㒊⅖ 0 1 (0.1%) 0 1 (0.1%) ὀᑕ㒊⚄⤒ᦆയ 0 1 (0.1%) 0 1 (0.1%) ὀᑕ㒊ᾋ⭘ 0 1 (0.1%) 0 0 ὀᑕ㒊▱ぬ␗ᖖ 0 1 (0.1%) 0 1 (0.1%) ὀᑕ㒊ᑠỈ⑁ 0 1 (0.1%) 0 1 (0.1%) ᒁᡤ⭘⬽ 0 1 (0.1%) 0 0 ⑊③ 1 (0.4%) 1 (0.1%) 0 1 (0.1%) ⬨᳝③ 0 1 (0.1%) 0 1 (0.1%) ᄞ⬊ 1 (0.4%) 0 0 0 㝈ᒁᛶᾋ⭘ 1 (0.4%) 0 0 0 ཱྀῬ 1 (0.4%) 0 0 0 ࣡ࢡࢳࣥ᥋✀㒊⅖ 1 (0.4%) 0 0 0 ࣡ࢡࢳࣥ᥋✀㒊⭘⬽ 1 (0.4%) 0 0 0 ⚄⤒⣔㞀ᐖ 39 (16.1%) 178 (15.4%) 11 (4.5%) 52 (4.5%) ಶ 㢌③ 23 (9.5%) 112 (9.7%) 6 (2.5%) 37 (3.2%) ࠎ ∦㢌③ 6 (2.5%) 22 (1.9%) 2 (0.8%) 2 (0.2%) ࡢヨ ᾋືᛶࡵࡲ࠸ 4 (1.7%) 10 (0.9%) 0 6 (0.5%) 㘒ឤぬ 3 (1.2%) 7 (0.6%) 2 (0.8%) 2 (0.2%) 㦂 యᛶࡵࡲ࠸ 1 (0.4%) 6 (0.5%) 0 4 (0.3%) ࡢࡲ ឤぬ㕌㯞 2 (0.8%) 6 (0.5%) 1 (0.4%) 2 (0.2%) ኻ⚄ 2 (0.8%) 6 (0.5%) 1 (0.4%) 1 (0.1%) ヨ ࡵ Ⴔ╀ 0 5 (0.4%) 0 2 (0.2%) 㦂 )
180
(45 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 All TEAEs Reasonably related TEAEs Placebo a Ustekinumab Placebo a Ustekinumab ᡓ 0 5 (0.4%) 0 1 (0.1%) ぬ␗ᖖ 0 4 (0.3%) 0 4 (0.3%) ᆘ㦵⚄⤒③ 0 4 (0.3%) 0 0 ᡭ᰿⟶ೃ⩌ 0 2 (0.2%) 0 0
㰯⭍⅖క࠺㢌③ 0 2 (0.2%) 0 1 (0.1%) 2.7.6 ⥭ᙇᛶ㢌③ 0 2 (0.2%) 0 0 ➽ⴎ⦰ᛶഃ⣴◳ 0 1 (0.1%) 0 0 ⮬ᚊ⚄⤒ࢽ࣮ࣗࣟࣃࢳ࣮ 0 1 (0.1%) 0 0 ᖹ⾮㞀ᐖ 0 1 (0.1%) 0 0 㢁㧊⚄⤒᰿㞀ᐖ 0 1 (0.1%) 0 0 ②ᨥ 0 1 (0.1%) 0 0 ⬺㧊 0 1 (0.1%) 0 1 (0.1%) ປసᛶࡵࡲ࠸ 0 1 (0.1%) 0 1 (0.1%) 㢌㒊ᛌឤ 0 1 (0.1%) 0 0 ▱ぬ㐣ᩄ 0 1 (0.1%) 0 0 ព㆑ᾘኻ 0 1 (0.1%) 0 0 ⭜㧊⚄⤒᰿㞀ᐖ 0 1 (0.1%) 0 0 グ᠈㞀ᐖ 0 1 (0.1%) 0 0 ᮎᲈᛶࢽ࣮ࣗࣟࣃࢳ࣮ 1 (0.4%) 1 (0.1%) 0 0 Ⴅぬ㘒ㄗ 0 1 (0.1%) 0 0 ࿘ᮇᛶᅄ⫥㐠ື㞀ᐖ 0 1 (0.1%) 0 0 ኻ⚄ᑍ๓ࡢ≧ែ 1 (0.4%) 1 (0.1%) 0 1 (0.1%) ⚄⤒᰿㞀ᐖ 0 1 (0.1%) 0 0 ୗ⫥㟼Ṇ⬟ೃ⩌ 0 1 (0.1%) 0 0 ឤぬ㞀ᐖ 0 1 (0.1%) 0 0 ࡃࡶ⭷ୗฟ⾑ 0 1 (0.1%) 0 0 ഃ㢌ⴥ࡚ࢇࢇ 0 1 (0.1%) 0 0 ୕ཫ⚄⤒③ 1 (0.4%) 1 (0.1%) 1 (0.4%) 0 ど㔝Ḟᦆ 0 1 (0.1%) 0 0 ๓ࢆక࠺∦㢌③ 1 (0.4%) 0 0 0 ᯇᯝయᄞ⬊ 1 (0.4%) 0 0 0 ഴ╀ 1 (0.4%) 0 0 0 ྾ჾࠊ⬚㒌࠾ࡼࡧ⦪㝸㞀ᐖ 27 (11.2%) 135 (11.7%) 2 (0.8%) 24 (2.1%) ಶ တႿ 9 (3.7%) 48 (4.1%) 0 5 (0.4%) ࠎ ཱྀ⭍ဗ㢌③ 5 (2.1%) 32 (2.8%) 1 (0.4%) 10 (0.9%) ࡢヨ 㰯㛢 9 (3.7%) 16 (1.4%) 1 (0.4%) 4 (0.3%) 㰯₃ 4 (1.7%) 12 (1.0%) 0 1 (0.1%) 㦂 㰯⭍࠺ࡗ⾑ 3 (1.2%) 10 (0.9%) 0 3 (0.3%) ࡢࡲ ྾ᅔ㞴 0 8 (0.7%) 0 2 (0.2%) ႍᜥ 0 7 (0.6%) 0 0 ヨ ࡵ 㰯ฟ⾑ 1 (0.4%) 4 (0.3%) 0 0 㦂 )
181
(46 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 All TEAEs Reasonably related TEAEs Placebo a Ustekinumab Placebo a Ustekinumab ‵ᛶတႿ 1 (0.4%) 3 (0.3%) 0 1 (0.1%) ࣞࣝࢠ࣮ᛶ㰯⅖ 0 3 (0.3%) 0 0 ୖẼ㐨တೃ⩌ 0 3 (0.3%) 0 1 (0.1%) ↓Ẽ⫵ 0 2 (0.2%) 0 0
ဗ㢌⣚ᩬ 0 2 (0.2%) 0 1 (0.1%) 2.7.6 ៏ᛶ㛢ሰᛶ⫵ᝈ 0 1 (0.1%) 0 0 ဗႃ⇱ 0 1 (0.1%) 0 0 ປసᛶ྾ᅔ㞴 0 1 (0.1%) 0 0 㰯⢓⭷㞀ᐖ 0 1 (0.1%) 0 1 (0.1%) 㰯Ⲗ 1 (0.4%) 1 (0.1%) 0 0 㰯୰㝸ᙃ᭤ 0 1 (0.1%) 0 0 㠀ឤᰁᛶẼ⟶ᨭ⅖ 0 1 (0.1%) 0 0 㰯⭍ᛌឤ 0 1 (0.1%) 0 1 (0.1%) ဗ㢌ᾋ⭘ 0 1 (0.1%) 0 1 (0.1%) ⬚Ỉ 0 1 (0.1%) 0 0 ဗႃ่⃭ឤ 0 1 (0.1%) 0 0 ဗႃ⤠ᢋឤ 0 1 (0.1%) 0 1 (0.1%) ⾑⟶㐠ືᛶ㰯⅖ 0 1 (0.1%) 0 1 (0.1%) 㰯㛢ሰ 1 (0.4%) 0 0 0 യᐖࠊ୰ẘ࠾ࡼࡧฎ⨨ྜే 20 (8.3%) 87 (7.5%) 1 (0.4%) 3 (0.3%) യ 3 (1.2%) 12 (1.0%) 0 0 യ 1 (0.4%) 7 (0.6%) 0 0 ⫗㞳ࢀ 0 7 (0.6%) 0 0 ฎ⨨ࡼࡿ⑊③ 3 (1.2%) 7 (0.6%) 0 0 ༙᭶ᯈᦆയ 0 4 (0.3%) 0 0 ⠇㊊ື≀ညയ 0 3 (0.3%) 0 0 ㌿ಽ 0 3 (0.3%) 0 0 ᡭ㦵ᢡ 0 3 (0.3%) 0 0 㠎ᖏ 4 (1.7%) 3 (0.3%) 0 0 യ 0 3 (0.3%) 0 0 ୖ㢛⅖ 0 2 (0.2%) 0 0 ㊊㦵ᢡ 1 (0.4%) 2 (0.2%) 0 0 ୖ⭎㦵㦵ᢡ 0 2 (0.2%) 0 0 ಶ ษ㛤㒊③ 0 2 (0.2%) 0 0 ࠎ ➽᩿ 0 2 (0.2%) 0 0 ࡢヨ ฎ⨨ࡼࡿࡵࡲ࠸ 0 2 (0.2%) 0 1 (0.1%) ⭡㒊ᦆയ 0 1 (0.1%) 0 0 㦂 ⭡㒊㞳㛤 0 1 (0.1%) 0 0 ࡢࡲ ࣝࢥ࣮ࣝ୰ẘ 0 1 (0.1%) 0 0 ࣞࣝࢠ࣮ᛶ㍺⾑ᛂ 0 1 (0.1%) 0 0 ヨ ࡵ ⾡ᚋ㈋⾑ 0 1 (0.1%) 0 0 㦂 )
182
(47 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 All TEAEs Reasonably related TEAEs Placebo a Ustekinumab Placebo a Ustekinumab ࿀ྜ㒊⊃✽ 1 (0.4%) 1 (0.1%) 0 0 ື≀ညയ 0 1 (0.1%) 0 0 ㊊㛵⠇㒊㦵ᢡ 0 1 (0.1%) 0 0 ⠇㊊ື≀่യ 0 1 (0.1%) 0 0
㦵യ 0 1 (0.1%) 0 0 2.7.6 ⬚㒊ᦆയ 0 1 (0.1%) 0 0 㙐㦵㦵ᢡ 0 1 (0.1%) 0 0 ⫶⭠࿀ྜ㒊₃ฟ 0 1 (0.1%) 0 0 㢌㒊ᦆയ 2 (0.8%) 1 (0.1%) 0 0 ⇕ᑕ 0 1 (0.1%) 0 0 ὀධక࠺ᛂ 0 1 (0.1%) 0 1 (0.1%) 㛵⠇ᦆയ 1 (0.4%) 1 (0.1%) 0 0 ୗ⫥㦵ᢡ 0 1 (0.1%) 0 0 ⚄⤒ᦆയ 0 1 (0.1%) 0 0 ฎ⨨ᚋୗ⑩ 0 1 (0.1%) 0 0 ฎ⨨ᚋ⾑⭘ 0 1 (0.1%) 0 0 እയᚋ㢁㒊ೃ⩌ 1 (0.4%) 1 (0.1%) 0 0 ⾡ᚋࣞ࢘ࢫ 0 1 (0.1%) 0 0 ฎ⨨ࡼࡿᝏᚰ 0 1 (0.1%) 0 1 (0.1%) ⫘㦵㦵ᢡ 0 1 (0.1%) 0 0 ᘬࡗࡁയ 0 1 (0.1%) 0 0 ⬨ᰕᦆയ 0 1 (0.1%) 0 0 ⬚㦵ᦆയ 0 1 (0.1%) 0 0 ࢫࢺ࣮࣐㒊⅖ 0 1 (0.1%) 0 0 ࢧࣥࣂ࣮ࣥ 0 1 (0.1%) 0 0 ║ࡢ᧿㐣യ 0 1 (0.1%) 0 1 (0.1%) ⭷᩿ 0 1 (0.1%) 0 0 ⭝᩿ 0 1 (0.1%) 0 0 ⇕യ 0 1 (0.1%) 0 0 ṑ∳◚ᢡ 0 1 (0.1%) 0 0 ྛ✀≀㉁ẘᛶ 0 1 (0.1%) 0 0 ྜే 0 1 (0.1%) 0 0 ࿀ྜ㒊ฟ⾑ 1 (0.4%) 0 0 0 ಶ ║ࡢ⇕യ 1 (0.4%) 0 1 (0.4%) 0 ࠎ ᅄ⫥ᦆയ 1 (0.4%) 0 0 0 ࡢヨ ⓶᧿㐣യ 1 (0.4%) 0 0 0 ⮫ᗋ᳨ᰝ 19 (7.9%) 76 (6.6%) 7 (2.9%) 20 (1.7%) 㦂 ࢫࣃࣛࢠࣥ㓟࣑ࣀࢺࣛࣥࢫࣇ࢙࣮ࣛࢮቑຍ 0 8 (0.7%) 0 2 (0.2%) ࡢࡲ య㔜ῶᑡ 3 (1.2%) 8 (0.7%) 0 1 (0.1%) ࣛࢽ࣑ࣥࣀࢺࣛࣥࢫࣇ࢙࣮ࣛࢮቑຍ 0 6 (0.5%) 0 2 (0.2%) ヨ ࡵ ࣊ࣔࢢࣟࣅࣥῶᑡ 1 (0.4%) 6 (0.5%) 0 1 (0.1%) 㦂 )
183
(48 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 All TEAEs Reasonably related TEAEs Placebo a Ustekinumab Placebo a Ustekinumab ⾑୰ࣈࢻ࢘⢾ቑຍ 1 (0.4%) 5 (0.4%) 0 0 ዲ୰⌫ᩘቑຍ 0 5 (0.4%) 0 1 (0.1%) ⾑ᑠᯈᩘቑຍ 0 5 (0.4%) 0 0 ⓑ⾑⌫ᩘቑຍ 1 (0.4%) 5 (0.4%) 0 2 (0.2%)
⾑୰࣒࢝ࣜ࢘ῶᑡ 0 4 (0.3%) 0 0 2.7.6 ⫢ᶵ⬟᳨ᰝ␗ᖖ 5 (2.1%) 4 (0.3%) 3 (1.2%) 2 (0.2%) ࣜࣥࣃ⌫ᩘῶᑡ 0 4 (0.3%) 0 3 (0.3%) ⾑୰ࢡࣞࢳࢽࣥቑຍ 2 (0.8%) 3 (0.3%) 1 (0.4%) 1 (0.1%) ⫢㓝⣲ୖ᪼ 0 3 (0.3%) 0 1 (0.1%) ⾑Ύࣇ࢙ࣜࢳࣥῶᑡ 0 3 (0.3%) 0 0 య㔜ቑຍ 0 3 (0.3%) 0 2 (0.2%) ⾑୰ࣝ࢝ࣜ࣍ࢫࣇࢱ࣮ࢮቑຍ 0 2 (0.2%) 0 0 ⾑୰ࣅࣜࣝࣅࣥቑຍ 0 2 (0.2%) 0 1 (0.1%) ࣐࣊ࢺࢡࣜࢵࢺῶᑡ 2 (0.8%) 2 (0.2%) 0 1 (0.1%) ᚰᢿᩘቑຍ 0 2 (0.2%) 0 2 (0.2%) ࣈࢻ࢘⌫⳦᳨ᰝ㝧ᛶ 0 2 (0.2%) 0 0 ࣅࢱ࣑ࣥ㹂ῶᑡ 0 2 (0.2%) 0 0 ⓑ⾑⌫ᩘῶᑡ 0 2 (0.2%) 0 0 ᢪྜࣅࣜࣝࣅࣥቑຍ 0 1 (0.1%) 0 0 ⾑୰࢝ࣝࢩ࣒࢘ቑຍ 0 1 (0.1%) 0 0 ⾑୰㟁ゎ㉁␗ᖖ 0 1 (0.1%) 0 0 ⾑୰࣐ࢢࢿࢩ࣒࢘ῶᑡ 0 1 (0.1%) 0 0 ⾑୰ࣜࣥῶᑡ 0 1 (0.1%) 0 1 (0.1%) ᣑᙇᮇ⾑ᅽୖ᪼ 0 1 (0.1%) 0 1 (0.1%) ⾑ᅽୖ᪼ 0 1 (0.1%) 0 0 ⾑୰⏥≧⭢่⃭࣍ࣝࣔࣥῶᑡ 0 1 (0.1%) 0 0 య ୖ᪼ 0 1 (0.1%) 0 1 (0.1%) ࢡࣟࢫࢺࣜࢪ᳨࣒࢘ᰝ㝧ᛶ 0 1 (0.1%) 0 1 (0.1%) ࣄࢺங㢌⭘࢘ࣝࢫ᳨ᰝ㝧ᛶ 0 1 (0.1%) 0 1 (0.1%) 㓟⣲㣬ᗘపୗ 0 1 (0.1%) 0 0 Ꮚᐑ㢁㒊ࢫ࣑␗ᖖ 1 (0.4%) 1 (0.1%) 0 0 ࢺࣛࣥࢫ࣑ࢼ࣮ࢮୖ᪼ 0 1 (0.1%) 0 1 (0.1%) ࣅࢱ࣑ࣥ㹀㸯㸰ῶᑡ 0 1 (0.1%) 0 0 ಶ ฟ⾑㛫ᘏ㛗 1 (0.4%) 0 0 0 ࠎ ⾑୰ࣝࣈ࣑ࣥῶᑡ 2 (0.8%) 0 1 (0.4%) 0 ࡢヨ ዲ㓟⌫ᩘቑຍ 1 (0.4%) 0 1 (0.4%) 0 ⮫ᗋ᳨ᰝ␗ᖖ 1 (0.4%) 0 0 0 㦂 ⾑ᑠᯈᩘῶᑡ 1 (0.4%) 0 1 (0.4%) 0 ࡢࡲ ⥲⺮ⓑῶᑡ 1 (0.4%) 0 1 (0.4%) 0 ⢭⚄㞀ᐖ 6 (2.5%) 66 (5.7%) 2 (0.8%) 9 (0.8%) ヨ ࡵ ࠺ࡘ 2 (0.8%) 25 (2.2%) 1 (0.4%) 5 (0.4%) 㦂 )
184
(49 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 All TEAEs Reasonably related TEAEs Placebo a Ustekinumab Placebo a Ustekinumab Ᏻ 1 (0.4%) 12 (1.0%) 0 1 (0.1%) ╀ 2 (0.8%) 12 (1.0%) 0 0 ╧╀㞀ᐖ 1 (0.4%) 5 (0.4%) 1 (0.4%) 1 (0.1%) ⴠࡕ╔ࡁࡢ࡞ࡉ 0 4 (0.3%) 0 1 (0.1%)
㘒≧ែ 0 2 (0.2%) 0 0 2.7.6 ᗁぬ 0 2 (0.2%) 0 1 (0.1%) ࣃࢽࢵࢡⓎస 0 2 (0.2%) 0 0 ␗ᖖ࡞ክ 0 1 (0.1%) 0 0 ὀពḞ㝗ከືᛶ㞀ᐖ 0 1 (0.1%) 0 0 ᴟᛶ㞀ᐖ 0 1 (0.1%) 0 0 ᢚ࠺ࡘẼศ 0 1 (0.1%) 0 0 ゎ㞳ᛶ㞀ᐖ 0 1 (0.1%) 0 0 ่⃭᫆ᛶ 0 1 (0.1%) 0 1 (0.1%) ⢭⚄≧ែኚ 0 1 (0.1%) 0 0 Ẽศືᦂ 0 1 (0.1%) 0 0 ⚄⤒㐣ᩄ 0 1 (0.1%) 0 0 ᚰⓗእയᚋࢫࢺࣞࢫ㞀ᐖ 0 1 (0.1%) 0 0 ࢫࢺࣞࢫ 0 1 (0.1%) 0 0 ⮬ẅᛕ៖ 0 1 (0.1%) 0 0 ࣜࣅࢻ࣮ῶ㏥ 1 (0.4%) 0 0 0 ௦ㅰ࠾ࡼࡧᰤ㣴㞀ᐖ 12 (5.0%) 62 (5.4%) 0 2 (0.2%) ⬺Ỉ 1 (0.4%) 15 (1.3%) 0 0 ప࣒࢝ࣜ࢘⾑ 3 (1.2%) 13 (1.1%) 0 0 㣗ḧῶ㏥ 1 (0.4%) 8 (0.7%) 0 2 (0.2%) ࣅࢱ࣑ࣥ㹂Ḟஈ 2 (0.8%) 6 (0.5%) 0 0 㕲Ḟஈ 1 (0.4%) 5 (0.4%) 0 0 ࣅࢱ࣑ࣥ㹀㸯㸰Ḟஈ 0 4 (0.3%) 0 0 పࣝࣈ࣑ࣥ⾑ 1 (0.4%) 3 (0.3%) 0 0 ③㢼 3 (1.2%) 2 (0.2%) 0 0 㧗⾑⢾ 0 2 (0.2%) 0 0 ᰤ㣴㞀ᐖ 0 2 (0.2%) 0 0 యᾮ㈓␃ 0 1 (0.1%) 0 0 㧗ࢥࣞࢫࢸ࣮ࣟࣝ⾑ 0 1 (0.1%) 0 0 ಶ 㧗⬡⾑ 0 1 (0.1%) 0 0 ࠎ ప࣐ࢢࢿࢩ࣒࢘⾑ 1 (0.4%) 1 (0.1%) 0 0 ࡢヨ పࢼࢺ࣒ࣜ࢘⾑ 0 1 (0.1%) 0 0 పࣜࣥ㓟⾑ 0 1 (0.1%) 0 0 㦂 ⾑ᾮ㔞ῶᑡ 0 1 (0.1%) 0 0 ࡢࡲ ࣅࢱ࣑ࣥ㹀㸴Ḟஈ 1 (0.4%) 1 (0.1%) 0 0 ள㖄Ḟஈ 0 1 (0.1%) 0 0 ヨ ࡵ ⢾ᒀ 1 (0.4%) 0 0 0 㦂 )
185
(50 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 All TEAEs Reasonably related TEAEs Placebo a Ustekinumab Placebo a Ustekinumab ⾑ᾮ࠾ࡼࡧࣜࣥࣃ⣔㞀ᐖ 10 (4.1%) 60 (5.2%) 0 7 (0.6%) ㈋⾑ 5 (2.1%) 25 (2.2%) 0 1 (0.1%) 㕲Ḟஈᛶ㈋⾑ 3 (1.2%) 11 (1.0%) 0 1 (0.1%) ⓑ⾑⌫ῶᑡ 2 (0.8%) 6 (0.5%) 0 1 (0.1%)
ࣜࣥࣃ⌫ῶᑡ 1 (0.4%) 6 (0.5%) 0 2 (0.2%) 2.7.6 ⓑ⾑⌫ቑຍ 0 4 (0.3%) 0 1 (0.1%) ࣜࣥࣃ⠇ 0 3 (0.3%) 0 1 (0.1%) ⾑ᑠᯈቑຍ 0 3 (0.3%) 0 0 ៏ᛶᝈࡢ㈋⾑ 0 1 (0.1%) 0 0 ෆฟ⾑Ⓨ⏕ࡢቑຍഴྥ 0 1 (0.1%) 0 0 ዲ୰⌫ῶᑡ 0 1 (0.1%) 0 0 ⭁⭘ 0 1 (0.1%) 0 0 ≉Ⓨᛶ⾑⭘ 0 1 (0.1%) 0 0 ║㞀ᐖ 13 (5.4%) 51 (4.4%) 2 (0.8%) 7 (0.6%) ║⇱ 1 (0.4%) 5 (0.4%) 1 (0.4%) 0 㟝ど 0 5 (0.4%) 0 4 (0.3%) ║▛⅖ 0 4 (0.3%) 0 0 ║③ 1 (0.4%) 4 (0.3%) 1 (0.4%) 0 ὶᾦቑຍ 0 4 (0.3%) 0 1 (0.1%) 㟠⢏⭘ 0 3 (0.3%) 0 0 ⓑෆ㞀 1 (0.4%) 2 (0.2%) 0 0 ⤖⭷ฟ⾑ 0 2 (0.2%) 0 0 ║่⃭ 0 2 (0.2%) 0 1 (0.1%) ║ࡑ࠺ 1 (0.4%) 2 (0.2%) 0 0 ║㒊⭘⬽ 0 2 (0.2%) 0 0 ගど 0 2 (0.2%) 0 0 ࡪ࠺⭷⅖ 0 2 (0.2%) 0 0 ║⢭⑂ປ 0 1 (0.1%) 0 0 ど 0 1 (0.1%) 0 1 (0.1%) ⤖⭷⾑ 0 1 (0.1%) 0 0 ࣞࣝࢠ࣮ᛶ⤖⭷⅖ 0 1 (0.1%) 0 0 ║▛‵⑈ 0 1 (0.1%) 0 0 ║▛⣚ᩬ 1 (0.4%) 1 (0.1%) 0 0 ಶ ║▛ୗᆶ 0 1 (0.1%) 0 0 ࠎ ⥳ෆ㞀 0 1 (0.1%) 0 1 (0.1%) ࡢヨ 㐲ど 0 1 (0.1%) 0 1 (0.1%) ᙬ⅖ 0 1 (0.1%) 0 0 㦂 㯤ᩬᏍ 0 1 (0.1%) 0 0 ࡢࡲ ║㒊ᛌឤ 0 1 (0.1%) 0 0 ║⾑ 3 (1.2%) 1 (0.1%) 0 0 ヨ ࡵ 㧗║ᅽ 0 1 (0.1%) 0 0 㦂 )
186
(51 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 All TEAEs Reasonably related TEAEs Placebo a Ustekinumab Placebo a Ustekinumab ⪁ど 0 1 (0.1%) 0 1 (0.1%) ▖Ꮝᑕ㞀ᐖ 0 1 (0.1%) 0 0 ▖Ꮝྠ 0 1 (0.1%) 0 1 (0.1%) ⥙⭷᱾ሰ 0 1 (0.1%) 0 0
ᩳど 0 1 (0.1%) 0 1 (0.1%) 2.7.6 どຊపୗ 2 (0.8%) 1 (0.1%) 0 0 ◪Ꮚయᾋ㐟≀ 1 (0.4%) 1 (0.1%) 0 0 ᙬẟᵝయ⅖ 1 (0.4%) 0 0 0 ゅ⭷⅖ 1 (0.4%) 0 0 0 どຊ㞀ᐖ 1 (0.4%) 0 0 0 ⾑⟶㞀ᐖ 4 (1.7%) 37 (3.2%) 1 (0.4%) 10 (0.9%) 㧗⾑ᅽ 1 (0.4%) 10 (0.9%) 0 2 (0.2%) ῝㒊㟼⬦⾑ᰦ 0 7 (0.6%) 0 1 (0.1%) ࡚ࡾ 1 (0.4%) 7 (0.6%) 0 4 (0.3%) ప⾑ᅽ 0 4 (0.3%) 0 0 ₻⣚ 1 (0.4%) 3 (0.3%) 1 (0.4%) 2 (0.2%) ⾑⭘ 0 2 (0.2%) 0 0 ᮎᲈ෭ឤ 0 2 (0.2%) 0 1 (0.1%) ᮏែᛶ㧗⾑ᅽ 0 1 (0.1%) 0 0 ⾑ᰦ 1 (0.4%) 1 (0.1%) 0 0 㟼⬦⒗ 0 1 (0.1%) 0 0 ⭈࠾ࡼࡧᒀ㊰㞀ᐖ 6 (2.5%) 35 (3.0%) 0 1 (0.1%) ⭈⤖▼ 3 (1.2%) 11 (1.0%) 0 0 ᒀᅔ㞴 0 5 (0.4%) 0 0 ⭈③ 0 3 (0.3%) 0 0 ᒀ⟶⤖▼ 0 2 (0.2%) 0 0 㢖ᒀ 2 (0.8%) 2 (0.2%) 0 0 ⺮ⓑᒀ 0 2 (0.2%) 0 1 (0.1%) ⭈ 0 2 (0.2%) 0 0 ⭤⬔②⦰ 0 1 (0.1%) 0 0 ⾑ᒀ 0 1 (0.1%) 0 0 ኻ⚗ 0 1 (0.1%) 0 0 ኪ㛫㢖ᒀ 0 1 (0.1%) 0 0 ಶ ஈᒀ 0 1 (0.1%) 0 0 ࠎ ከᒀ 0 1 (0.1%) 0 0 ࡢヨ ⭈ᄞ⬊ 1 (0.4%) 1 (0.1%) 0 0 ⭈ᶵ⬟㞀ᐖ 0 1 (0.1%) 0 0 㦂 ⭈ᒀ⣽⟶ቯṚ 0 1 (0.1%) 0 0 ࡢࡲ ᒀ㐨⊃✽ 0 1 (0.1%) 0 0 ⭈⮚③ 1 (0.4%) 0 0 0 ヨ ࡵ ⏕Ṫ⣔࠾ࡼࡧஙᡣ㞀ᐖ 12 (5.0%) 29 (2.5%) 0 5 (0.4%) 㦂 )
187
(52 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 All TEAEs Reasonably related TEAEs Placebo a Ustekinumab Placebo a Ustekinumab ༸ᕢᄞ⬊ 1 (0.4%) 6 (0.5%) 0 0 ᭶⤒ᅔ㞴 2 (0.8%) 2 (0.2%) 0 0 ዪᛶ⏕Ṫჾ⒦ 1 (0.4%) 2 (0.2%) 0 0 ࣂࣝࢺࣜࣥᄞ⭘ 1 (0.4%) 1 (0.1%) 0 0
ࣂࣝࢺࣜࣥ⭢⅖ 1 (0.4%) 1 (0.1%) 0 1 (0.1%) 2.7.6 ஙᡣ③ 0 1 (0.1%) 0 1 (0.1%) ஙᡣᅽ③ 0 1 (0.1%) 0 0 Ꮚᐑ㢁㒊ୖ⓶␗ᙧᡂ 0 1 (0.1%) 0 1 (0.1%) ຨ㉳ 0 1 (0.1%) 0 0 ⏕Ṫჾ③ 0 1 (0.1%) 0 0 㛢⤒ᮇ≧ 0 1 (0.1%) 0 0 ᛶჾᾋ⭘ 0 1 (0.1%) 0 0 㝜⒦ 0 1 (0.1%) 0 0 㝜③ 0 1 (0.1%) 0 1 (0.1%) 㛢⤒ᚋฟ⾑ 0 1 (0.1%) 0 0 ᭶⤒๓ೃ⩌ 0 1 (0.1%) 0 0 ฎዪ⭷ᙉ㠎 0 1 (0.1%) 0 0 㝜ᄞᄞ⬊ 0 1 (0.1%) 0 0 ᛶᶵ⬟ 0 1 (0.1%) 0 0 Ꮚᐑ⬺ 0 1 (0.1%) 0 0 ⭐ᄞ⬊ 0 1 (0.1%) 0 0 ⭐Ẽ㡢 0 1 (0.1%) 0 1 (0.1%) ⭐ฟ⾑ 0 1 (0.1%) 0 1 (0.1%) ዪᛶእ㝜㒊₽⒆ 0 1 (0.1%) 0 0 እ㝜⭐⇱ 0 1 (0.1%) 0 0 ↓᭶⤒ 1 (0.4%) 0 0 0 ஙᡣศἪ 1 (0.4%) 0 0 0 ஙᡣ⭘⒗ 1 (0.4%) 0 0 0 ዪᛶஙᡣ 1 (0.4%) 0 0 0 ᭶⤒㐣ከ 2 (0.8%) 0 0 0 ṇᏊᐑฟ⾑ 1 (0.4%) 0 0 0 ⢭ᕢ③ 1 (0.4%) 0 0 0 ᚰ⮚㞀ᐖ 2 (0.8%) 20 (1.7%) 0 3 (0.3%) ಶ 㢖⬦ 0 9 (0.8%) 0 1 (0.1%) ࠎ ື 1 (0.4%) 5 (0.4%) 0 2 (0.2%) ࡢヨ ⊃ᚰ 0 2 (0.2%) 0 0 ᚰᡣ⣽ື 0 2 (0.2%) 0 0 㦂 ᚰ➽ 0 1 (0.1%) 0 0 ࡢࡲ Ὕᛶ㢖⬦ 0 1 (0.1%) 0 0 ᚰᐊᛶᮇእ⦰ 0 1 (0.1%) 0 0 ヨ ࡵ ᚰ⢒ື 1 (0.4%) 0 0 0 㦂 )
188
(53 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 All TEAEs Reasonably related TEAEs Placebo a Ustekinumab Placebo a Ustekinumab ⪥࠾ࡼࡧ㏞㊰㞀ᐖ 4 (1.7%) 19 (1.6%) 0 6 (0.5%) ᅇ㌿ᛶࡵࡲ࠸ 3 (1.2%) 7 (0.6%) 0 3 (0.3%) ⪥③ 0 3 (0.3%) 0 0 ⪥㬆 0 3 (0.3%) 0 2 (0.2%)
⪥⟶ᶵ⬟㞀ᐖ 0 1 (0.1%) 0 0 2.7.6 ⫈ぬ㞀ᐖ 0 1 (0.1%) 0 0 ࣓ࢽ࢚࣮ࣝ 0 1 (0.1%) 0 0 ⪥₃ 0 1 (0.1%) 0 0 㰘⭷㞀ᐖ 0 1 (0.1%) 0 0 㰘⭷✸Ꮝ 0 1 (0.1%) 0 1 (0.1%) ≀㓉࠸ 1 (0.4%) 0 0 0 Ⰻᛶࠊᝏᛶ࠾ࡼࡧヲ⣽᫂ࡢ᪂⏕≀㸦ᄞ⬊࠾ࡼࡧ࣏࣮ࣜࣉࢆྵ ࡴ㸧 7 (2.9%) 19 (1.6%) 1 (0.4%) 2 (0.2%) ⓶ங㢌⭘ 1 (0.4%) 3 (0.3%) 1 (0.4%) 1 (0.1%) ᇶᗏ⣽⬊⒴ 2 (0.8%) 2 (0.2%) 0 0 ⭠⭢⭘ 0 2 (0.2%) 0 0 ࢡࣟࢥࣝࢻࣥ 1 (0.4%) 1 (0.1%) 0 0 ⭤⬔ࡢⰋᛶ᪂⏕≀ 0 1 (0.1%) 0 0 ⓶Ⰻᛶ᪂⏕≀ 0 1 (0.1%) 0 0 ༸ᕢⰋᛶ⭘⒆ 0 1 (0.1%) 0 0 ၚᾮ⭢ࡢⰋᛶ᪂⏕≀ 0 1 (0.1%) 0 0 ࢝ࣝࢳࣀࢻ⭘⒆ 0 1 (0.1%) 0 1 (0.1%) ⾑⟶⭘ 0 1 (0.1%) 0 0 ࢣࣛࢺ࢝ࣥࢺ࣮࣐ 0 1 (0.1%) 0 0 ࣓ࣛࣀࢧࢺᛶẕᩬ 0 1 (0.1%) 0 0 ༸ᕢ⭢⭘ 0 1 (0.1%) 0 0 ⬡₃ᛶゅ 0 1 (0.1%) 0 0 ᑠ⭠⭢⒴ 0 1 (0.1%) 0 1 (0.1%) ⓶᭷Ჲ⣽⬊⒴ 0 1 (0.1%) 0 0 Ꮚᐑᖹ➽⭘ 1 (0.4%) 1 (0.1%) 0 0 ங⭢⥺⥔⭢⭘ 1 (0.4%) 0 0 0 㧊⭷⭘ 1 (0.4%) 0 0 0 ᡥᖹୖ⓶⒴ 1 (0.4%) 0 0 0 ಶ ච⣔㞀ᐖ 5 (2.1%) 17 (1.5%) 0 0 ࠎ Ꮨ⠇ᛶࣞࣝࢠ࣮ 4 (1.7%) 8 (0.7%) 0 0 ࡢヨ ⸆≀㐣ᩄ 1 (0.4%) 3 (0.3%) 0 0 㐣ᩄ 0 2 (0.2%) 0 0 㦂 㸲ᆺ㐣ᩄ 0 2 (0.2%) 0 0 ࡢࡲ ື≀ࣞࣝࢠ࣮ 0 1 (0.1%) 0 0 ་⒪ᶵჾࣞࣝࢠ࣮ 0 1 (0.1%) 0 0 ヨ ࡵ ⫢⫹㐨⣔㞀ᐖ 1 (0.4%) 11 (1.0%) 0 2 (0.2%) 㦂 )
189
(54 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 All TEAEs Reasonably related TEAEs Placebo a Ustekinumab Placebo a Ustekinumab ⫹▼ 0 5 (0.4%) 0 1 (0.1%) ⫹ᄞ⅖ 1 (0.4%) 2 (0.2%) 0 0 ⫹⟶⅖ 0 1 (0.1%) 0 0 ⫢ᄞ⬊ 0 1 (0.1%) 0 0
⫢ᶵ⬟␗ᖖ 0 1 (0.1%) 0 1 (0.1%) 2.7.6 ⬡⫫⫢ 0 1 (0.1%) 0 0 ෆศἪ㞀ᐖ 1 (0.4%) 8 (0.7%) 0 1 (0.1%) ⭈ᶵ⬟ 1 (0.4%) 4 (0.3%) 0 0 ⏥≧⭢ᶵ⬟ஹ㐍 0 1 (0.1%) 0 0 ⏥≧⭢ᶵ⬟పୗ 0 1 (0.1%) 0 0 ⥆Ⓨᛶ⭈⓶㉁ᶵ⬟ 0 1 (0.1%) 0 0 ⏥≧⭢⅖ 0 1 (0.1%) 0 1 (0.1%) ዷፎࠊ⏘〟࠾ࡼࡧ࿘⏘ᮇࡢ≧ែ 2 (0.8%) 5 (0.4%) 0 0 ዷፎ 1 (0.4%) 5 (0.4%) 0 0 ⮬↛ὶ⏘ 1 (0.4%) 0 0 0 ♫⎔ቃ 4 (1.7%) 3 (0.3%) 0 0 ࣃ࣮ࢺࢼ࣮ࡢዷፎ 2 (0.8%) 3 (0.3%) 0 0 ேᕤஙᡣ⏝⪅ 1 (0.4%) 0 0 0 ≀㉁⏝⪅ 1 (0.4%) 0 0 0 እ⛉࠾ࡼࡧෆ⛉ฎ⨨ 0 1 (0.1%) 0 0 ᢤṑ 0 1 (0.1%) 0 0 ඛኳᛶࠊᐙ᪘ᛶ࠾ࡼࡧ㑇ఏᛶ㞀ᐖ 1 (0.4%) 0 0 0 ື⬦ᑤᘚ 1 (0.4%) 0 0 0
a Includes all data for subjects who were in clinical response to placebo IV induction dosing and received placebo SC in this maintenance study, and the data from Week 8 onward for subjects who were in clinical response to ustekinumab IV induction dosing and received placebo SC in this maintenance study. TEAEs=Treatment Emergent Adverse Events [TJPCAE11C.RTF] [CNTO1275\Z_SCS\DBR_2015_07\RE_JPKK\PROD\TJPCAE11C.SAS] 28OCT2015, 23:46
ಶ ࠎ ࡢヨ 㦂 ࡢࡲ ヨ ࡵ 㦂 )
190
(55 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 (2) ୰Ṇ⮳ࡗࡓ᭷ᐖ㇟ࡢヲ⣽㸦44 㐌┠ཪࡣ⏝㔞ㄪ⠇ࡢᐇⅬࡲ࡛㸧
1) 㞟ᅋ ⾲ 2.7.6.4-12 ᅉᯝ㛵ಀࢆၥࢃ࡞࠸ࡍ࡚ࡢ୰Ṇ⮳ࡗࡓ᭷ᐖ㇟㸦ࣛࣥࢲ࣒ᚋ㦂⸆ࡀᢞࡉࢀࡓ⿕㦂⪅㸧
Treatment Study 2.7.6 group after Agent Study Day Maintenance Induction Age Dose Dose of AEa/ MedDRA Treatment treatment Subje (yrs)/ Adjustment/ Prior Duration preferred Infusion Serious Relation to Group group ct ID Sex Study Daya to AE (days) term Verbatim Term Infectionb Reaction AE Severity Study Drug Action Taken Outcome 90 mg SC 130 mg 1008- 2/M 90.0 133/7 ࢡ࣮ࣟࣥ WORSENING No No Y SEVERE NOT DRUG RECOVERED/ q8w IV 10423 mg CROHN'S DISEASE RELATED WITHDRAWN RESOLVED 2202- 3/F 90.0 92/41 ዷፎ PREGNANCY No No N MILD NOT DRUG RECOVERED/ 10534 mg RELATED WITHDRAWN RESOLVED 1049- 4/F 90.0 187/10 ⭠⊃✽ SPLENIC No No Y MILD NOT DRUG RECOVERED/ 20148 mg FLEXURE RELATED WITHDRAWN RESOLVED STENOSIS 6 mg/kg 3314- 2/F 90.0 234/232 ዷፎ PREGNANCY No No N MILD NOT DRUG RECOVERED/ IV 10330 mg RELATED WITHDRAWN RESOLVED 90 mg SC 130 mg 1018- 4/F 0 mg 238/66 ⏥≧⭢⅖ THYROIDITIS No No N MODERATE POSSIBLE DRUG RECOVERED/ q12w IV 10162 WITHDRAWN RESOLVED 1039- 2/F 0 mg 134/Ongoi ࢡ࣮ࣟࣥ MICROPERFORAT Yes No N SEVERE POSSIBLE DRUG NOT 10681 ng ION DUE TO WITHDRAWN RECOVERED/ CROHNS DISEASE NOT RESOLVED 2/F 0 mg ⭠⊃✽ COLONIC No No N SEVERE POSSIBLE DRUG NOT STRICTURE WITHDRAWN RECOVERED/ NOT RESOLVED 2/F 0 mg 135/Ongoi ⭡㒊ឤᰁ INTRA- Yes No Y SEVERE POSSIBLE DRUG NOT ng ABDOMINAL WITHDRAWN RECOVERED/ INFECTION NOT WITHOUT RESOLVED ABSCESS 2406- 4/F 0 mg 132/2 ࢡ࣮ࣟࣥ FLARE CROHN'S No No Y MODERATE NOT DRUG RECOVERED/ 11023 DISEASE RELATED WITHDRAWN RESOLVED WITH SEQUELAE ಶ 4301- 1/M 0 mg 218/6 ࢡ࣮ࣟࣥ CROHN'S DISEASE No No Y MODERATE NOT DRUG RECOVERED/ ࠎ 20660 AGGRAVATION RELATED WITHDRAWN RESOLVED ࡢヨ 6 mg/kg 1018- 5/M 0 mg 141/124 ⒦ NEW LEFT No No N MODERATE NOT DRUG RECOVERED/
IV 10167 PERIANAL RELATED WITHDRAWN RESOLVED 㦂
FISTULA ࡢࡲ 1057- 4/F 90.0 105/Ongoi ⭠⟶⒦ INTESTINAL No No N MODERATE NOT DRUG NOT 10264 mg ng FISTULA RELATED WITHDRAWN RECOVERED/ ヨ ࡵ NOT 㦂
) RESOLVED
191
(56 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 Treatment Study group after Agent Study Day Maintenance Induction Age Dose Dose of AEa/ MedDRA Treatment treatment Subje (yrs)/ Adjustment/ Prior Duration preferred Infusion Serious Relation to Group group ct ID Sex Study Daya to AE (days) term Verbatim Term Infectionb Reaction AE Severity Study Drug Action Taken Outcome 4216- 1/F 90.0 80/Ongoin ⫠㛛⮋⒆ PERIANAL Yes No Y SEVERE NOT DRUG NOT 10754 mg g ABSCESS RELATED WITHDRAWN RECOVERED/
NOT 2.7.6 RESOLVED 1113- 3/F 0 mg 117/3 Ⓨ⑈ RASH RIGHT No No N MILD VERY DRUG RECOVERED/ 10977 UPPER LIKELY WITHDRAWN RESOLVED EXTRIMITY 5615- 3/F 90.0 234/Ongoi ࡏࡘ BOILS IN ARMPIT Yes No N MODERATE VERY DRUG NOT 20818 mg ng AND GROIN LIKELY WITHDRAWN RECOVERED/ NOT RESOLVED 1025- 2/F 0 mg 220/Ongoi ዷፎ PREGNANCY No No N MILD NOT DRUG NOT 21033 ng RELATED WITHDRAWN RECOVERED/ NOT RESOLVED Placebo SC 130 mg 1069- 3/M 0 mg 145/4 ⒦ ANAL FISTULA No No Y SEVERE NOT DRUG RECOVERED/ IV 10230 RELATED WITHDRAWN RESOLVED 4803- 3/M 0 mg 330/13 ⭠✸Ꮝ COLON No No Y SEVERE NOT DRUG RECOVERED/ 10456 PERFORATION RELATED WITHDRAWN RESOLVED 3605- 3/M 0 mg 288/296 ⤖᰾ TUBERCULOSIS Yes No N MILD POSSIBLE DRUG RECOVERED/ 20285 CONFIRMED BY WITHDRAWN RESOLVED CT SCAN AND X- RAY 2704- 4/M 0 mg 276/14 ࢡ࣮ࣟࣥ WORSENING OF No No Y SEVERE NOT DRUG RECOVERED/ 20776 CROHNS DISEASE RELATED WITHDRAWN RESOLVED 6 mg/kg 2711- 3/M 0 mg 128/Ongoi ࢡ࣮ࣟࣥ WORSENING No No Y SEVERE DOUBTFUL DRUG NOT IV 10412 ng CROHN'S DISEASE WITHDRAWN RECOVERED/ NOT RESOLVED 5302- 3/M 0 mg 347/33 ⭠⭤⬔⒦ COLOVESICAL No No Y SEVERE NOT DRUG RECOVERED/ 20191 FISTULA RELATED WITHDRAWN RESOLVED DRAINING FAECES 3429- 2/F 0 mg ዷፎ PREGNANCY No No N SEVERE NOT DRUG RECOVERED/ 20401 RELATED WITHDRAWN RESOLVED ಶ 4002- 5/F 0 mg 243/40 ࢡ࣮ࣟࣥ CROHN DISEASE No No N MILD NOT DRUG RECOVERED/ ࠎ
20467 EXACERBATION RELATED WITHDRAWN RESOLVED ࡢヨ
a Relative to the date of first treatment in maintenance study. 㦂
b Infection as assessed by the investigator. ࡢࡲ Adverse events are coded using MedDRA 17.1. [LPMDASF17A.rtf] [CNTO1275\CRD3003\DBR_CSR\RE_PMDA\lpmdasf17a.sas] 20SEP2016, 21:43 ヨ ࡵ 㦂 )
192
(57 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003
⾲ 2.7.6.4-13 㦂⸆ྜ⌮ⓗ㛵㐃ᛶࡀ࠶ࡿ୰Ṇ⮳ࡗࡓ᭷ᐖ㇟㸦ࣛࣥࢲ࣒ᚋ㦂⸆ࡀᢞࡉࢀࡓ⿕㦂⪅㸧 Treatment Study group after Agent Study Day Maintenance Induction Age Dose Dose of AEa/ MedDRA
Treatment treatment Subje (yrs)/ Adjustment/ Prior to Duration preferred Infusion Serious Relation to 2.7.6 Group group ct ID Sex Study Daya AE (days) term Verbatim Term Infectionb Reaction AE Severity Study Drug Action Taken Outcome 90 mg SC 130 mg 1018- 4/F 0 mg 238/66 ⏥≧⭢⅖ THYROIDITIS No No N MODERATE POSSIBLE DRUG RECOVERED/ q12w IV 10162 WITHDRAWN RESOLVED 1039- 2/F 0 mg 134/Ongoi ࢡ࣮ࣟࣥ MICROPERFORAT Yes No N SEVERE POSSIBLE DRUG NOT 10681 ng ION DUE TO WITHDRAWN RECOVERED/ CROHNS NOT DISEASE RESOLVED 2/F 0 mg ⭠⊃✽ COLONIC No No N SEVERE POSSIBLE DRUG NOT STRICTURE WITHDRAWN RECOVERED/ NOT RESOLVED 2/F 0 mg 135/Ongoi ⭡㒊ឤᰁ INTRA- Yes No Y SEVERE POSSIBLE DRUG NOT ng ABDOMINAL WITHDRAWN RECOVERED/ INFECTION NOT WITHOUT RESOLVED ABSCESS 6 mg/kg 1113- 3/F 0 mg 117/3 Ⓨ⑈ RASH RIGHT No No N MILD VERY DRUG RECOVERED/ IV 10977 UPPER LIKELY WITHDRAWN RESOLVED EXTRIMITY 5615- 3/F 90.0 234/Ongoi ࡏࡘ BOILS IN ARMPIT Yes No N MODERATE VERY DRUG NOT 20818 mg ng AND GROIN LIKELY WITHDRAWN RECOVERED/ NOT RESOLVED Placebo SC 130 mg 3605- 3/M 0 mg 288/296 ⤖᰾ TUBERCULOSIS Yes No N MILD POSSIBLE DRUG RECOVERED/ IV 20285 CONFIRMED BY WITHDRAWN RESOLVED CT SCAN AND X- RAY
a Relative to the date of first treatment in maintenance study. b Infection as assessed by the investigator. Adverse events are coded using MedDRA 17.1. ಶ
[LPMDASF19A.rtf] [CNTO1275\CRD3003\DBR_CSR\RE_PMDA\lpmdasf19a.sas] 20SEP2016, 21:43 ࠎ ࡢヨ 㦂
ࡢࡲ ヨ ࡵ 㦂 )
193
(58 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 2) ᪥ᮏே㞟ᅋ ⾲ 2.7.6.4-14 ୰Ṇ⮳ࡗࡓ᭷ᐖ㇟ཬࡧ㦂⸆ྜ⌮ⓗ㛵㐃ᛶࡀ࠶ࡿ୰Ṇ⮳ࡗࡓ᭷ᐖ㇟ 㸦ࣛࣥࢲ࣒ᚋ㦂⸆ࡀᢞࡉࢀࡓ⿕㦂⪅㸧 Treatment Study 2.7.6 group after Agent Study Day Maintenance Induction Age Dose Dose of AEa/ MedDRA Relation to Treatment treatment (yrs)/ Adjustment/ Prior to Duration preferred Infusion Serious Study Group group Subject ID Sex Study Daya AE (days) term Verbatim Term Infectionb Reaction AE Severity Drug Action Taken Outcome 90 mg SC 6 mg/kg 4216-10754 1/F 90.0 mg 80/Ongoing ⫠㛛⮋⒆ PERIANAL Yes No Y SEVERE NOT DRUG NOT q12w IV ABSCESS RELATED WITHDRAWN RECOVERED/NOT RESOLVED
a Relative to the date of first treatment in maintenance study. b Infection as assessed by the investigator. Adverse events are coded using MedDRA 17.1. [LPMDASF17B.rtf] [CNTO1275\CRD3003\DBR_CSR\RE_PMDA\lpmdasf17b.sas] 20SEP2016, 21:43
ಶ ࠎ ࡢヨ 㦂 ࡢࡲ ヨ ࡵ 㦂 )
194
(59 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 (3) ୰Ṇ⮳ࡗࡓ᭷ᐖ㇟ࡢヲ⣽㸦44 㐌┠ࡲ࡛㸧
1) 㞟ᅋ
2.7.6 ⾲ 2.7.6.4-15 ୰Ṇ⮳ࡗࡓ᭷ᐖ㇟ཬࡧ㦂⸆ྜ⌮ⓗ㛵㐃ᛶࡀ࠶ࡿ୰Ṇ⮳ࡗࡓ᭷ᐖ㇟㸦㦂⸆ࡀᢞࡉࢀࡓ⿕㦂⪅㸧 Study Randomized Treatment Study Day of at Week 0 Maintena group after Agent AEa/ of this nce Induction Age Dose Dose Durati MedDRA maintenance Treatment treatment Subje (yrs)/ Adjustment/ Prior on preferred Infec Infusion Serious Relation to study Group group ct ID Sex Study Daya to AE (days) term Verbatim Term tionb Reaction AE Severity Study Drug Action Taken Outcome Yes Placebo 130 mg 1069- 3/M 0 mg 145/4 ⒦ ANAL FISTULA No No Y SEVERE NOT DRUG RECOVERED/ SC IV 10230 RELATED WITHDRAWN RESOLVED 3314- 3/F 90 mg SC 90.0 ↓ຊ INTENSE No No Y SEVERE PROBABLE DRUG RECOVERED/ 10280 q8w/79 mg ASTHENIA WITHDRAWN RESOLVED 3/F 90 mg SC 90.0 ࠺ࡘ DEPRESSIVE No No Y SEVERE PROBABLE DRUG RECOVERED/ q8w/79 mg SYNDROM WITHDRAWN RESOLVED 4803- 3/M 0 mg 330/1 ⭠✸Ꮝ COLON No No Y SEVERE NOT DRUG RECOVERED/ 10456 3 PERFORATION RELATED WITHDRAWN RESOLVED 3605- 3/M 0 mg 288/2 ⤖᰾ TUBERCULOSIS Yes No N MILD POSSIBLE DRUG RECOVERED/ 20285 96 CONFIRMED BY WITHDRAWN RESOLVED CT SCAN AND X-RAY 2704- 4/M 0 mg 276/1 ࢡ࣮ࣟࣥ WORSENING OF No No Y SEVERE NOT DRUG RECOVERED/ 20776 4 CROHNS RELATED WITHDRAWN RESOLVED DISEASE 6 mg/kg 3404- 4/F 90 mg SC 0 mg 223/3 ࢡ࣮ࣟࣥ WORSENING OF No No Y MODERATE DOUBTFUL DRUG RECOVERED/ IV 10331 q8w/106 9 CROHN'S WITHDRAWN RESOLVED DISEASE 2711- 3/M 0 mg 128/O ࢡ࣮ࣟࣥ WORSENING No No Y SEVERE DOUBTFUL DRUG NOT 10412 ngoin CROHN'S WITHDRAWN RECOVERED/ g DISEASE NOT RESOLVED 5302- 3/M 0 mg 347/3 ⭠⭤⬔⒦ COLOVESICAL No No Y SEVERE NOT DRUG RECOVERED/ 20191 3 FISTULA RELATED WITHDRAWN RESOLVED DRAINING ಶ FAECES ࠎ 3429- 2/F 0 mg ዷፎ PREGNANCY No No N SEVERE NOT DRUG RECOVERED/ ࡢヨ 20401 RELATED WITHDRAWN RESOLVED
4002- 5/F 0 mg 243/4 ࢡ࣮ࣟࣥ CROHN No No N MILD NOT DRUG RECOVERED/ 㦂
20467 0 DISEASE RELATED WITHDRAWN RESOLVED ࡢࡲ EXACERBATION 90 mg SC 130 mg 1018- 4/F 0 mg 238/6 ⏥≧⭢⅖ THYROIDITIS No No N MODERATE POSSIBLE DRUG RECOVERED/ ヨ q12w IV 10162 6 WITHDRAWN RESOLVED ࡵ 㦂 )
195
(60 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 Study Randomized Treatment Study Day of at Week 0 Maintena group after Agent AEa/ of this nce Induction Age Dose Dose Durati MedDRA maintenance Treatment treatment Subje (yrs)/ Adjustment/ Prior on preferred Infec Infusion Serious Relation to study Group group ct ID Sex Study Daya to AE (days) term Verbatim Term tionb Reaction AE Severity Study Drug Action Taken Outcome 4104- 3/F 90 mg SC 0 mg 162/1 ࢡ࣮ࣟࣥ CROHN No No Y SEVERE NOT DRUG RECOVERED/
10647 q8w/51 4 DISEASE RELATED WITHDRAWN RESOLVED 2.7.6 RELAPSE WITH SEQUELAE 1039- 2/F 0 mg 134/O ࢡ࣮ࣟࣥ MICROPERFORA Yes No N SEVERE POSSIBLE DRUG NOT 10681 ngoin TION DUE TO WITHDRAWN RECOVERED/ g CROHNS NOT DISEASE RESOLVED 2/F 0 mg ⭠⊃✽ COLONIC No No N SEVERE POSSIBLE DRUG NOT STRICTURE WITHDRAWN RECOVERED/ NOT RESOLVED 2/F 0 mg 135/O ⭡㒊ឤᰁ INTRA- Yes No Y SEVERE POSSIBLE DRUG NOT ngoin ABDOMINAL WITHDRAWN RECOVERED/ g INFECTION NOT WITHOUT RESOLVED ABSCESS 2406- 4/F 0 mg 132/2 ࢡ࣮ࣟࣥ FLARE CROHN'S No No Y MODERATE NOT DRUG RECOVERED/ 11023 DISEASE RELATED WITHDRAWN RESOLVED WITH SEQUELAE 4301- 1/M 0 mg 218/6 ࢡ࣮ࣟࣥ CROHN'S No No Y MODERATE NOT DRUG RECOVERED/ 20660 DISEASE RELATED WITHDRAWN RESOLVED AGGRAVATION 6 mg/kg 1018- 5/M 0 mg 141/1 ⒦ NEW LEFT No No N MODERATE NOT DRUG RECOVERED/ IV 10167 24 PERIANAL RELATED WITHDRAWN RESOLVED FISTULA 1057- 4/F 90.0 105/O ⭠⟶⒦ INTESTINAL No No N MODERATE NOT DRUG NOT 10264 mg ngoin FISTULA RELATED WITHDRAWN RECOVERED/ g NOT RESOLVED 4201- 3/F 90 mg SC 0 mg 241/1 ⭡⭷⅖ PERITONITIS Yes No Y SEVERE NOT DRUG RECOVERED/ 10360 q8w/133 33 RELATED WITHDRAWN RESOLVED 4216- 1/F 90.0 80/On ⫠㛛⮋⒆ PERIANAL Yes No Y SEVERE NOT DRUG NOT ಶ
10754 mg going ABSCESS RELATED WITHDRAWN RECOVERED/ ࠎ
NOT ࡢヨ RESOLVED
1113- 3/F 0 mg 117/3 Ⓨ⑈ RASH RIGHT No No N MILD VERY DRUG RECOVERED/ 㦂
10977 UPPER LIKELY WITHDRAWN RESOLVED ࡢࡲ EXTRIMITY ヨ ࡵ 㦂 )
196
(61 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 Study Randomized Treatment Study Day of at Week 0 Maintena group after Agent AEa/ of this nce Induction Age Dose Dose Durati MedDRA maintenance Treatment treatment Subje (yrs)/ Adjustment/ Prior on preferred Infec Infusion Serious Relation to study Group group ct ID Sex Study Daya to AE (days) term Verbatim Term tionb Reaction AE Severity Study Drug Action Taken Outcome 5615- 3/F 90.0 234/O ࡏࡘ BOILS IN Yes No N MODERATE VERY DRUG NOT
20818 mg ngoin ARMPIT AND LIKELY WITHDRAWN RECOVERED/ 2.7.6 g GROIN NOT RESOLVED 1025- 2/F 0 mg 220/O ዷፎ PREGNANCY No No N MILD NOT DRUG NOT 21033 ngoin RELATED WITHDRAWN RECOVERED/ g NOT RESOLVED 90 mg SC 130 mg 1008- 2/M 90.0 133/7 ࢡ࣮ࣟࣥ WORSENING No No Y SEVERE NOT DRUG RECOVERED/ q8w IV 10423 mg CROHN'S RELATED WITHDRAWN RESOLVED DISEASE 2202- 3/F 90.0 92/41 ዷፎ PREGNANCY No No N MILD NOT DRUG RECOVERED/ 10534 mg RELATED WITHDRAWN RESOLVED 1049- 4/F 90.0 187/1 ⭠⊃✽ SPLENIC No No Y MILD NOT DRUG RECOVERED/ 20148 mg 0 FLEXURE RELATED WITHDRAWN RESOLVED STENOSIS 4213- 3/M 90 mg SC 0 mg 155/9 ࢡ࣮ࣟࣥ WORSENING OF No No Y SEVERE NOT DRUG RECOVERED/ 20895 q8w/58 8 CROHN'S RELATED WITHDRAWN RESOLVED DISEASE 6 mg/kg 1046- 4/F 90 mg SC 0 mg 162/11 ᄞ⅖ RECTAL No No N MODERATE DOUBTFUL DRUG RECOVERED/ IV 10129 q8w/85 3 BLEEDING DUE WITHDRAWN RESOLVED TO POUCH INFLAMATION 3314- 2/F 90.0 234/2 ዷፎ PREGNANCY No No N MILD NOT DRUG RECOVERED/ 10330 mg 32 RELATED WITHDRAWN RESOLVED No Placebo Placebo 1027- 4/F Placebo 0 mg 247/1 ࢡࣟࢫࢺࣜ C. DIFFICILE Yes No Y SEVERE POSSIBLE DRUG RECOVERED/ SC IV 10490 SC/170 0 ࢪ࣒࣭࢘ࢹ COLITIS WITHDRAWN RESOLVED ࣇࢩࣞ ⭠⅖ 4/F Placebo 0 mg ࢡ࣮ࣟࣥ CROHNS No No Y SEVERE NOT DRUG RECOVERED/ SC/170 PROCTOCOLITIS RELATED WITHDRAWN RESOLVED 5619- 5/M Placebo 0 mg 227/1 ࢡ࣮ࣟࣥ INPATIENT No No Y SEVERE NOT DRUG RECOVERED/
10586 SC/148 3 HOSPITALISATI RELATED WITHDRAWN RESOLVED ಶ ON DUE TO ࠎ CROHNS FLARE ࡢヨ 4803- 3/F 0 mg 223/1 ࢡ࣮ࣟࣥ WORSENING OF No No Y MODERATE NOT DRUG RECOVERED/ 10691 0 CROHN RELATED WITHDRAWN RESOLVED DISEASE 㦂 4211- 2/F /57 0 mg 70/On ࢡ࣮ࣟࣥ WORSENING OF No No N MODERATE NOT DRUG NOT ࡢࡲ 11160 going THE CROHN`S RELATED WITHDRAWN RECOVERED/ DISEASE NOT ヨ ࡵ RESOLVED 㦂 )
197
(62 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 Study Randomized Treatment Study Day of at Week 0 Maintena group after Agent AEa/ of this nce Induction Age Dose Dose Durati MedDRA maintenance Treatment treatment Subje (yrs)/ Adjustment/ Prior on preferred Infec Infusion Serious Relation to study Group group ct ID Sex Study Daya to AE (days) term Verbatim Term tionb Reaction AE Severity Study Drug Action Taken Outcome 3610- 3/F Placebo 0 mg 238/11 ዪᛶ⏕Ṫჾ SIGMOIDEO- No No Y SEVERE NOT DRUG RECOVERED/ 20093 SC/60 6 ⒦ PELVIC FISTULA RELATED WITHDRAWN RESOLVED 2.7.6 WITH SEQUELAE 2708- 3/F 0 mg 247/O 㦵႙ኻ BONE LOSS No No N SEVERE POSSIBLE DRUG NOT 20212 ngoin WITHDRAWN RECOVERED/ g NOT RESOLVED 1008- 7/F Placebo 0 mg ᩬ≧ୣ⑈≧ MACULOPAPUL No No N MODERATE POSSIBLE DRUG NOT 21023 SC/64 ⓶⑈ AR RASH ON WITHDRAWN RECOVERED/ CHEST AND NOT BACK RESOLVED 130 mg Placebo 3610- 2/F 129.6 115/13 ዷፎ PREGNANCY No No N MILD NOT DRUG RECOVERED/ IV IV 10283 mg RELATED WITHDRAWN RESOLVED 1001- 3/F 129.6 66/26 ࢡ࣮ࣟࣥ CROHN'S No No Y SEVERE DOUBTFUL DRUG RECOVERED/ 10406 mg DISEASE FLARE WITHDRAWN RESOLVED 4209- 4/F 0 mg 285/4 ࢡ࣮ࣟࣥ CROHN'S No No Y SEVERE NOT DRUG RECOVERED/ 10427 2 DISEASE RELATED WITHDRAWN RESOLVED AGGRAVATED 4216- 2/M 0 mg 196/O ࢡ࣮ࣟࣥ DETERIORATIO No No Y SEVERE NOT DRUG NOT 10627 ngoin N OF CROHN'S RELATED WITHDRAWN RECOVERED/ g DISEASE NOT RESOLVED 1015- 5/F 0 mg 264/5 ࣈࢻ࢘⌫⳦ STAPHYLOCOC Yes No Y MODERATE PROBABLE DRUG RECOVERED/ 10811 2 ᛶ⫵⅖ CUS AUREUS WITHDRAWN RESOLVED PNEUMONIA 1017- 5/M 129.6 107/O ࢡ࣮ࣟࣥ WORSENING OF No No N MODERATE POSSIBLE DRUG NOT 10876 mg ngoin CROHNS WITHDRAWN RECOVERED/ g NOT RESOLVED 2405- 5/F 129.6 78/On ⭡㒊⮋⒆ ABDOMINAL Yes No N MILD DOUBTFUL DRUG NOT 10944 mg going PARIETAL WITHDRAWN RECOVERED/ ABCESS NOT
RESOLVED ಶ
5/F 129.6 ⭠⟶⓶⒦ ENTERO- No No Y SEVERE DOUBTFUL DRUG RECOVERED/ ࠎ
mg CUTANEOUS WITHDRAWN RESOLVED ࡢヨ FISTULA
2711- 3/M 90.0 137/6 ⭡㒊⮋⒆ ABDOMINAL Yes No Y SEVERE POSSIBLE DRUG RECOVERED/ 㦂
10966 mg 8 ABSCESS WITHDRAWN RESOLVED ࡢࡲ ヨ ࡵ 㦂 )
198
(63 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 Study Randomized Treatment Study Day of at Week 0 Maintena group after Agent AEa/ of this nce Induction Age Dose Dose Durati MedDRA maintenance Treatment treatment Subje (yrs)/ Adjustment/ Prior on preferred Infec Infusion Serious Relation to study Group group ct ID Sex Study Daya to AE (days) term Verbatim Term tionb Reaction AE Severity Study Drug Action Taken Outcome 1067- 5/F 0 mg 200/O ⬺㧊 OTHER No No N MODERATE POSSIBLE DRUG NOT
11019 ngoin DEMYELINATIN WITHDRAWN RECOVERED/ 2.7.6 g G DISEASES OF NOT CENTRAL RESOLVED NERVOUS SYSTEM 4810- 2/F 0 mg 303/9 ࣛࢽࣥ INCREASED No No N MODERATE POSSIBLE DRUG RECOVERED/ 20266 0 ࣑ࣀࢺࣛࣥ ALANINE WITHDRAWN RESOLVED ࢫࣇ࢙࣮ࣛ AMINOTRASFER ASE ࢮቑຍ 3415- 4/M 129.6 㛵⠇③ WORSENING OF No No N SEVERE NOT DRUG RECOVERED/ 20381 mg ARTHRALGIA RELATED WITHDRAWN RESOLVED 3301- 2/F 90.0 129/2 ᑠ⭠㛢ሰ DISTAL SMALL No No Y MODERATE NOT DRUG RECOVERED/ 20481 mg 7 BOWEL RELATED WITHDRAWN RESOLVED OBSTRUCTION 2712- 4/F 0 mg 162/7 ࢡ࣮ࣟࣥ CROHNS FLARE No No Y SEVERE DOUBTFUL DRUG RECOVERED/ 20607 WITHDRAWN RESOLVED 3610- 5/F 129.6 ࢡ࣮ࣟࣥ WORSENING OF No No N MODERATE NOT DRUG NOT 20680 mg CROHN'S RELATED WITHDRAWN RECOVERED/ DISEASE NOT RESOLVED 90 mg SC 130 mg 1053- 4/F 90.0 126/O ࢡ࣮ࣟࣥ WORSENING No No N MODERATE NOT DRUG NOT IV 10175 mg ngoin CROHNS RELATED WITHDRAWN RECOVERED/ g DISEASE NOT RESOLVED 5608- 1/F 90.0 73/30 ⭠⟶⊃✽ BOWEL No No Y SEVERE NOT DRUG RECOVERED/ 10248 mg STRICTURE RELATED WITHDRAWN RESOLVED 5617- 4/F 90.0 65/15 ࡃࡶ⭷ୗฟ SUB No No Y SEVERE DOUBTFUL DRUG RECOVERED/ 10424 mg 3 ⾑ ARACHNOID WITHDRAWN RESOLVED HAEMORRHAGE WITH SEQUELAE 1078- 5/F 90.0 98/15 ⓶᭷Ჲ⣽ SQUAMOUS No No N MODERATE DOUBTFUL DRUG RECOVERED/
10778 mg ⬊⒴ CELL WITHDRAWN RESOLVED ಶ CARCINOMA IN ࠎ SITU LEFT FACE ࡢヨ 5601- 2/F 90.0 110/4 ࢡ࣮ࣟࣥ EXACERBATION No No Y MODERATE NOT DRUG RECOVERED/ 10905 mg OF CHROHN'S RELATED WITHDRAWN RESOLVED DISEASE 㦂 2712- 5/F 90.0 298/2 ᑠ⭠㛢ሰ SMALL BOWEL No No Y SEVERE DOUBTFUL DRUG RECOVERED/ ࡢࡲ 10910 mg 5 OBSTRUCTION WITHDRAWN RESOLVED 1006- 4/M 90.0 226/1 ୗ⑩ INCREASED No No N MODERATE NOT DRUG RECOVERED/ ヨ ࡵ 10974 mg 9 DIARRHEA RELATED WITHDRAWN RESOLVED 㦂 )
199
(64 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 Study Randomized Treatment Study Day of at Week 0 Maintena group after Agent AEa/ of this nce Induction Age Dose Dose Durati MedDRA maintenance Treatment treatment Subje (yrs)/ Adjustment/ Prior on preferred Infec Infusion Serious Relation to study Group group ct ID Sex Study Daya to AE (days) term Verbatim Term tionb Reaction AE Severity Study Drug Action Taken Outcome 2206- 2/F 90.0 72/7 ࢡ࣮ࣟࣥ FLARE OF No No Y SEVERE NOT DRUG RECOVERED/
11016 mg CROHN'S WITH RELATED WITHDRAWN RESOLVED 2.7.6 MOUTH ULCERS 1017- 2/M 90.0 108/O 㹁ᆺ⫢⅖ HEPATITIS C Yes No N MILD NOT DRUG NOT 11103 mg ngoin RELATED WITHDRAWN RECOVERED/ g NOT RESOLVED 3425- 4/M 90.0 131/O 㛵⠇③ ARTHRALGIA No No N SEVERE POSSIBLE DRUG NOT 20103 mg ngoin WITHDRAWN RECOVERED/ g NOT RESOLVED 2704- 2/F 90.0 240/1 ⭠⟶⊃✽ ILEOCOLIC No No Y SEVERE DOUBTFUL DRUG RECOVERED/ 20348 mg 4 STRICTURE WITHDRAWN RESOLVED 5608- 2/F 90.0 312/3 ࢡ࣮ࣟࣥ EXCACERBATIO No No Y SEVERE NOT DRUG RECOVERED/ 20690 mg 0 N OF CROHNS RELATED WITHDRAWN RESOLVED 1068- 2/M 0 mg 227/2 ⑊③ BODY AHCES No No N MODERATE POSSIBLE DRUG RECOVERED/ 20821 6 AFTER WITHDRAWN RESOLVED INJECTION 3314- 3/F 90.0 85/10 ࢡ࣮ࣟࣥ FLARE UP OF No No Y SEVERE NOT DRUG RECOVERED/ 20944 mg CROHN'S RELATED WITHDRAWN RESOLVED DISEASE WITH SEQUELAE 6 mg/kg 3314- 2/F 0 mg 164/2 ࢡ࣮ࣟࣥ SEVERE FLARE No No Y SEVERE NOT DRUG RECOVERED/ IV 10284 7 UP OF CROHN'S RELATED WITHDRAWN RESOLVED DISEASE 3425- 3/F 0 mg 160/3 ࢡ࣮ࣟࣥ WORSENING OF No No Y MODERATE NOT DRUG RECOVERED/ 10566 1 CROHNS RELATED WITHDRAWN RESOLVED DISEASE 1049- 6/M 90.0 101/O ➽ⴎ⦰ᛶഃ AMYOTROPIC No No N SEVERE NOT DRUG NOT 10618 mg ngoin ⣴◳ LATERAL RELATED WITHDRAWN RECOVERED/ g SCLEROSIS NOT RESOLVED 2204- 2/F 90.0 107/1 ࢡ࣮ࣟࣥ EXACERBATION No No Y SEVERE DOUBTFUL DRUG RECOVERED/ 10689 mg 5 OF CROHNS WITHDRAWN RESOLVED ಶ
DISEASE ࠎ
3314- 1/F 90.0 101/1 ࢡ࣮ࣟࣥ WORSENING OF No No Y SEVERE NOT DRUG RECOVERED/ ࡢヨ 10908 mg 88 CROHN'S RELATED WITHDRAWN RESOLVED
DISEASE 㦂
2712- 4/F 90.0 108/1 ᑠ⭠㛢ሰ SMALL BOWEL No No Y SEVERE NOT DRUG RECOVERED/ ࡢࡲ 10955 mg 2 OBSTRUCTION RELATED WITHDRAWN RESOLVED 4202- 2/M 90.0 172/3 ࢡ࣮ࣟࣥ WORSENING OF No No Y MODERATE NOT DRUG RECOVERED/ ヨ 11150 mg 7 CROHNS RELATED WITHDRAWN RESOLVED ࡵ 㦂
) DISEASE
200
(65 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 Study Randomized Treatment Study Day of at Week 0 Maintena group after Agent AEa/ of this nce Induction Age Dose Dose Durati MedDRA maintenance Treatment treatment Subje (yrs)/ Adjustment/ Prior on preferred Infec Infusion Serious Relation to study Group group ct ID Sex Study Daya to AE (days) term Verbatim Term tionb Reaction AE Severity Study Drug Action Taken Outcome 4706- 3/F 90.0 112/22 ࢡ࣮ࣟࣥ FLARE OF No No Y MODERATE NOT DRUG RECOVERED/
20298 mg CROHN'S RELATED WITHDRAWN RESOLVED 2.7.6 DISEASE 3417- 3/F 90.0 247/9 ࢡ࣮ࣟࣥ WORSENING OF No No Y SEVERE DOUBTFUL DRUG RECOVERED/ 20377 mg CROHN'S WITHDRAWN RESOLVED DISEASE 4212- 4/M 90.0 80/10 ࢡ࣮ࣟࣥ WORSENING OF No No Y MODERATE NOT DRUG RECOVERED/ 20536 mg 6 CROHN'S RELATED WITHDRAWN RESOLVED DISEASE 1018- 4/M 90.0 95/On ዲ୰⌫ᩘቑ FURTHER No No N MODERATE DOUBTFUL DRUG NOT 20621 mg going ຍ INCREASE OF WITHDRAWN RECOVERED/ NEUTROPHIL NOT RESOLVED
a Relative to the date of first treatment in maintenance study. b Infection as assessed by the investigator. Adverse events are coded using MedDRA 17.1. [LPMDASF18A.rtf] [CNTO1275\CRD3003\DBR_CSR\RE_PMDA\lpmdasf18a.sas] 20SEP2016, 21:43
ಶ ࠎ ࡢヨ 㦂 ࡢࡲ ヨ ࡵ 㦂 )
201
(66 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 2) ᪥ᮏே㞟ᅋ ⾲ 2.7.6.4-16 ୰Ṇ⮳ࡗࡓ᭷ᐖ㇟ཬࡧ㦂⸆ྜ⌮ⓗ㛵㐃ᛶࡀ࠶ࡿ୰Ṇ⮳ࡗࡓ᭷ᐖ㇟㸦㦂⸆ࡀᢞࡉࢀࡓ⿕㦂⪅㸧 Randomized Inducti Treatment Study Study at Week 0 on Age group after Agent Day of of this Maintenance treatm (yrs) Dose Dose AEa/ MedDRA 2.7.6 maintenance Treatment ent Subje / Adjustment/ Prior Duration preferred Infec Infusion Serious Relation to study Group group ct ID Sex Study Daya to AE (days) term Verbatim Term tionb Reaction AE Severity Study Drug Action Taken Outcome Yes 90 mg SC 6 4201- 3/F 90 mg SC 0 mg 241/133 ⭡⭷⅖ PERITONITIS Yes No Y SEVERE NOT DRUG RECOVERED/ q12w mg/kg 10360 q8w/133 RELATED WITHDRAWN RESOLVED IV 4216- 1/F 90.0 80/Ongoi ⫠㛛⮋⒆ PERIANAL Yes No Y SEVERE NOT DRUG NOT 10754 mg ng ABSCESS RELATED WITHDRAWN RECOVERED/ NOT RESOLVED 90 mg SC 130 4213- 3/ 90 mg SC 0 mg 155/98 ࢡ࣮ࣟࣥ WORSENING No No Y SEVERE NOT DRUG RECOVERED/ q8w mg IV 20895 M q8w/58 OF CROHN'S RELATED WITHDRAWN RESOLVED DISEASE No Placebo SC Placeb 4211- 2/F /57 0 mg 70/Ongoi ࢡ࣮ࣟࣥ WORSENING No No N MODERATE NOT DRUG NOT o IV 11160 ng OF THE RELATED WITHDRAWN RECOVERED/ CROHN`S NOT DISEASE RESOLVED 130 mg IV Placeb 4209- 4/F 0 mg 285/42 ࢡ࣮ࣟࣥ CROHN'S No No Y SEVERE NOT DRUG RECOVERED/ o IV 10427 DISEASE RELATED WITHDRAWN RESOLVED AGGRAVATED 4216- 2/ 0 mg 196/Ong ࢡ࣮ࣟࣥ DETERIORATI No No Y SEVERE NOT DRUG NOT 10627 M oing ON OF RELATED WITHDRAWN RECOVERED/ CROHN'S NOT DISEASE RESOLVED 90 mg SC 6 4202- 2/ 90.0 172/37 ࢡ࣮ࣟࣥ WORSENING No No Y MODERATE NOT DRUG RECOVERED/ mg/kg 11150 M mg OF CROHNS RELATED WITHDRAWN RESOLVED IV DISEASE 4212- 4/ 90.0 80/106 ࢡ࣮ࣟࣥ WORSENING No No Y MODERATE NOT DRUG RECOVERED/ 20536 M mg OF CROHN'S RELATED WITHDRAWN RESOLVED DISEASE
a Relative to the date of first treatment in maintenance study.
b Infection as assessed by the investigator. ಶ
Adverse events are coded using MedDRA 17.1. ࠎ [LPMDASF18B.rtf] [CNTO1275\CRD3003\DBR_CSR\RE_PMDA\lpmdasf18b.sas] 20SEP2016, 21:43 ࡢヨ
㦂 ࡢࡲ
ヨ ࡵ 㦂 )
202
(67 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003
2.7.6.4.3 㔜⠜࡞᭷ᐖ㇟ࡢࢹ࣮ࢱ
(1) 㔜⠜࡞᭷ᐖ㇟ࡢヲ⣽㸦44 㐌┠ཪࡣ⏝㔞ㄪ⠇ࡢᐇⅬࡲ࡛㸧
1) 㞟ᅋ 2.7.6
⾲ 2.7.6.4-17 㔜⠜࡞᭷ᐖ㇟ཬࡧ㦂⸆ྜ⌮ⓗ㛵㐃ᛶࡀ࠶ࡿ㔜⠜࡞᭷ᐖ㇟㸦ࣛࣥࢲ࣒ᚋ㦂⸆ࢆᢞࡉࢀࡓ⿕᳨⪅㸧 Treatment Study Study group after Agent Day of Maintenance Induction Age Dose Dose AEa/ Treatment treatment Subjec (yrs)/ Adjustment/ Prior Duratio MedDRA Infusion Serious Relation to Group group t ID Sex Study Daya to AE n (days) preferred term Verbatim Term Infectionb Reaction AE Severity Study Drug Action Taken Outcome 90 mg SC 130 mg 1015- 4/M 90.0 71/5 ⭠⊃✽ COLONIC No No Y SEVERE NOT DOSE NOT RECOVERED/ q8w IV 10352 mg STRICTURE RELATED CHANGED RESOLVED 1008- 2/M 90.0 100/3 ᑠ⭠㛢ሰ PARTIAL SMALL No No Y MODERATE DOUBTFUL DOSE NOT RECOVERED/ 10423 mg BOWEL CHANGED RESOLVED OBSTRUCTION 2/M 90.0 108/2 ᑠ⭠㛢ሰ PARTIAL SMALL No No Y MODERATE DOUBTFUL DOSE NOT RECOVERED/ mg BOWEL CHANGED RESOLVED OBSTRUCTION 2/M 90.0 133/7 ࢡ࣮ࣟࣥ WORSENING No No Y SEVERE NOT DRUG RECOVERED/ mg CROHN'S DISEASE RELATED WITHDRAWN RESOLVED 3420- 3/F 0 mg 259/65 ࢡ࣮ࣟࣥ FLAIR OF CROHNS No No Y SEVERE NOT DOSE NOT RECOVERED/ 10556 DISEASE RELATED CHANGED RESOLVED 3201- 4/F /121 90.0 107/22 ࢡ࣮ࣟࣥ WORSENING OF No No Y MODERATE NOT DOSE NOT RECOVERED/ 10889 mg CHRON'S DISEASE RELATED CHANGED RESOLVED 4/F /121 0 mg 165/13 ࢡ࣮ࣟࣥ WORSENING OF No No Y MODERATE NOT DOSE NOT RECOVERED/ CHRON'S DISEASE RELATED CHANGED RESOLVED 2704- 3/F 90.0 387/5 ༸ᕢ⭢⭘ BENIGN OVARIAN No No Y SEVERE DOUBTFUL DRUG RECOVERED/ 10988 mg MUCINOUS INTERRUPTED RESOLVED CYSTADENOMA 1049- 4/F 90.0 187/10 ⭠⊃✽ SPLENIC FLEXURE No No Y MILD NOT DRUG RECOVERED/ 20148 mg STENOSIS RELATED WITHDRAWN RESOLVED 6 mg/kg 4112- 4/M 90.0 196/9 ࢡ࣮ࣟࣥ RELAPSE OF No No Y SEVERE NOT DOSE NOT RECOVERED/ IV 10497 mg CROHNS DISEASE RELATED CHANGED RESOLVED ಶ 4212- 3/M /57 90.0 104/9 ⭠㛢ሰ COLONIC No No Y MODERATE DOUBTFUL DOSE NOT RECOVERED/ ࠎ 10505 mg OBSTRUCTION CHANGED RESOLVED ࡢヨ 2712- 2/F /142 90.0 75/26 ∦㢌③ SEVERE MIGRAINE No No Y SEVERE NOT DOSE NOT RECOVERED/
10954 mg HEADACHE RELATED CHANGED RESOLVED 㦂
1043- 3/F /167 0 mg 216/27 ࢘ࣝࢫឤᰁ VIRAL SYNDROME Yes No Y SEVERE POSSIBLE DOSE NOT RECOVERED/ ࡢࡲ 10979 CHANGED RESOLVED 1022- 3/F 90.0 63/3 ⭡③ ABDOMINAL PAIN No No Y MODERATE DOUBTFUL DOSE NOT RECOVERED/ ヨ ࡵ 20641 mg CHANGED RESOLVED 㦂 )
203
(68 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 Treatment Study Study group after Agent Day of Maintenance Induction Age Dose Dose AEa/ Treatment treatment Subjec (yrs)/ Adjustment/ Prior Duratio MedDRA Infusion Serious Relation to Group group t ID Sex Study Daya to AE n (days) preferred term Verbatim Term Infectionb Reaction AE Severity Study Drug Action Taken Outcome 1007- 2/M 90.0 347/2 ⫵⅖ PNEUMONIA Yes No Y SEVERE POSSIBLE DOSE NOT RECOVERED/ 20955 mg CHANGED RESOLVED 1016- 3/M 90.0 177/37 ║ᖏ≧⑁⑈ HERPES ZOSTER Yes No Y MODERATE POSSIBLE DRUG RECOVERED/ 2.7.6 21010 mg KERATOCONJUNCT INTERRUPTED RESOLVED IVITIS 90 mg SC 130 mg 1006- 6/F /163 90.0 160/3 ῝㒊㟼⬦⾑ᰦ DEEP VEIN No No Y SEVERE NOT DOSE NOT RECOVERED/ q12w IV 10085 mg THROMBOSIS RELATED CHANGED RESOLVED 1018- 4/F 0 mg 222/55 ࣞࣝࢠ࣮ᛶ DELAYED No No Y SEVERE DOUBTFUL DRUG RECOVERED/ 10162 ㍺⾑ᛂ ALLERGIC INTERRUPTED RESOLVED REACTION, LIKELY DUE TO IRON INFUSION OR BLOOD TRANSFUSION 1096- 5/M 90.0 96/6 ࢘ࣝࢫᛶ⫶ VIRAL Yes No Y MODERATE NOT DOSE NOT RECOVERED/ 10651 mg ⭠⅖ GASTROENTERITIS RELATED CHANGED RESOLVED 1039- 2/F 0 mg 135/Ong ⭡㒊ឤᰁ INTRA- Yes No Y SEVERE POSSIBLE DRUG NOT 10681 oing ABDOMINAL WITHDRAWN RECOVERED/ INFECTION NOT WITHOUT ABSCESS RESOLVED 2406- 4/F 0 mg 132/2 ࢡ࣮ࣟࣥ FLARE CROHN'S No No Y MODERATE NOT DRUG RECOVERED/ 11023 DISEASE RELATED WITHDRAWN RESOLVED WITH SEQUELAE 2204- 2/M 0 mg 270/3 ᑠ⭠㛢ሰ PARTIAL SMALL No No Y MODERATE POSSIBLE DOSE NOT RECOVERED/ 20144 BOWEL CHANGED RESOLVED OBSTRUCTION 3414- 2/M 90.0 237/10 ᆶ⅖ APPENDICITIS Yes No Y SEVERE DOUBTFUL DOSE NOT RECOVERED/ 20406 mg CHANGED RESOLVED 4301- 1/M 0 mg 218/6 ࢡ࣮ࣟࣥ CROHN'S DISEASE No No Y MODERATE NOT DRUG RECOVERED/ 20660 AGGRAVATION RELATED WITHDRAWN RESOLVED 6 mg/kg 1091- 2/M 90.0 93/4 ⮬ẅᛕ៖ SUICIDAL No No Y SEVERE DOUBTFUL DOSE NOT RECOVERED/ IV 10100 mg IDEATION CHANGED RESOLVED
2/M 90.0 113/73 ࢡ࣮ࣟࣥ WORSENING No No Y SEVERE NOT DOSE NOT RECOVERED/ ಶ mg CROHNS FLARE RELATED CHANGED RESOLVED ࠎ 2/M 90.0 318/7 ࢡ࣮ࣟࣥ WORSENING No No Y SEVERE DOUBTFUL DOSE NOT RECOVERED/ ࡢヨ mg CROHNS FLARE CHANGED RESOLVED 1018- 5/M 0 mg 264/5 ࢡ࣮ࣟࣥ EXARCEBATION OF No No Y SEVERE NOT NOT RECOVERED/ 10167 PERIANALCROHNS RELATED APPLICABLE RESOLVED 㦂 DISEASE ࡢࡲ 2301- 2/F 90.0 157/2 ⫶⭠⅖ GASTROENTERITIS Yes No Y SEVERE NOT DOSE NOT RECOVERED/ 10432 mg RELATED CHANGED RESOLVED ヨ ࡵ 㦂 )
204
(69 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 Treatment Study Study group after Agent Day of Maintenance Induction Age Dose Dose AEa/ Treatment treatment Subjec (yrs)/ Adjustment/ Prior Duratio MedDRA Infusion Serious Relation to Group group t ID Sex Study Daya to AE n (days) preferred term Verbatim Term Infectionb Reaction AE Severity Study Drug Action Taken Outcome 4211- 7/F 0 mg 120/27 ᆶ⅖ APPENDICITIS No No Y SEVERE DOUBTFUL DOSE NOT RECOVERED/ 10438 CHANGED RESOLVED 7/F 0 mg ⳦⾑ BACTEREMIA Yes No Y SEVERE DOUBTFUL DOSE NOT RECOVERED/ 2.7.6 CHANGED RESOLVED 4107- 2/F 90.0 233/8 ࢡ࣮ࣟࣥ CROHN'S DISEASE No No Y MODERATE NOT DOSE NOT RECOVERED/ 10677 mg RELAPSE RELATED CHANGED RESOLVED 4216- 1/F 90.0 80/Ongo ⫠㛛⮋⒆ PERIANAL Yes No Y SEVERE NOT DRUG NOT 10754 mg ing ABSCESS RELATED WITHDRAWN RECOVERED/ NOT RESOLVED 4602- 6/M 90.0 74/40 ⾡ᚋឤᰁ POST-OPERATIVE Yes No Y MODERATE NOT DOSE NOT RECOVERED/ 10902 mg WOUND RELATED CHANGED RESOLVED INFECTION". 6/M 0 mg 217/10 ࢝ࣥࣆࣟࣂࢡ CAMPILOBACTER Yes No Y MODERATE NOT DOSE NOT RECOVERED/ ࢱ࣮⫶⭠⅖ GASTRO ENTERITIS RELATED CHANGED RESOLVED 1005- 6/M 0 mg 362/3 ᮏែᛶ㧗⾑ᅽ PRIMARY No No Y MODERATE DOUBTFUL DOSE NOT RECOVERED/ 20434 IDIOPATHIC CHANGED RESOLVED HYPERTENSION Placebo SC 130 mg 1007- 2/F 0 mg 167/5 ⫵⅖ PNEUMONIA Yes No Y SEVERE DOUBTFUL DOSE NOT RECOVERED/ IV 10134 CHANGED RESOLVED 1069- 3/M 0 mg 145/4 ⒦ ANAL FISTULA No No Y SEVERE NOT DRUG RECOVERED/ 10230 RELATED WITHDRAWN RESOLVED 1013- 3/M 0 mg 195/8 ≀㉁⏝⪅ TRANSIENT No No Y SEVERE NOT DOSE NOT RECOVERED/ 10255 CHEMICAL ABUSE RELATED CHANGED RESOLVED 3312- 4/F /141 0 mg 180/3 㢌③ ACUTE HEADACHE No No Y MODERATE NOT DOSE NOT RECOVERED/ 10374 RELATED CHANGED RESOLVED 4803- 3/M 0 mg 330/13 ⭠✸Ꮝ COLON No No Y SEVERE NOT DRUG RECOVERED/ 10456 PERFORATION RELATED WITHDRAWN RESOLVED 2702- 2/F 0 mg 77/5 ࢡ࣮ࣟࣥ CROHN'S DISEASE No No Y SEVERE NOT NOT RECOVERED/ 10624 FLARE RELATED APPLICABLE RESOLVED WITH SEQUELAE 3306- 2/M 0 mg 333/4 ⒦ ANAL FISTULA No No Y MODERATE NOT DOSE NOT RECOVERED/ 10796 RELATED CHANGED RESOLVED ಶ 4603- 5/F /56 0 mg 106/10 ࢡ࣮ࣟࣥ CROHN'S FLARE No No Y SEVERE POSSIBLE DOSE NOT RECOVERED/ 10805 CHANGED RESOLVED ࠎ 2202- 6/F /183 0 mg 157/216 㛵⠇③ WORSENING OF No No Y SEVERE NOT DRUG RECOVERED/ ࡢヨ 20506 ARTHRALGIA RELATED INTERRUPTED RESOLVED 1049- 6/F /173 0 mg 210/31 ࢡ࣮ࣟࣥ CROHN'S FLARE No No Y SEVERE NOT DOSE NOT RECOVERED/ 㦂
20520 RELATED CHANGED RESOLVED ࡢࡲ 2704- 4/M 0 mg 276/14 ࢡ࣮ࣟࣥ WORSENING OF No No Y SEVERE NOT DRUG RECOVERED/ 20776 CROHNS DISEASE RELATED WITHDRAWN RESOLVED ヨ ࡵ 㦂 )
205
(70 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 Treatment Study Study group after Agent Day of Maintenance Induction Age Dose Dose AEa/ Treatment treatment Subjec (yrs)/ Adjustment/ Prior Duratio MedDRA Infusion Serious Relation to Group group t ID Sex Study Daya to AE n (days) preferred term Verbatim Term Infectionb Reaction AE Severity Study Drug Action Taken Outcome 6 mg/kg 2711- 3/M 0 mg 128/Ong ࢡ࣮ࣟࣥ WORSENING No No Y SEVERE DOUBTFUL DRUG NOT IV 10412 oing CROHN'S DISEASE WITHDRAWN RECOVERED/
NOT 2.7.6 RESOLVED 5609- 4/F 0 mg 261/4 ⫠㛛⮋⒆ PERIANAL Yes No Y MODERATE DOUBTFUL DRUG RECOVERED/ 10637 ABSCESS, NEW INTERRUPTED RESOLVED 1010- 3/F /141 0 mg 187/17 ࢡ࣮ࣟࣥ CROHN FLARE No No Y SEVERE NOT DOSE NOT RECOVERED/ 10794 RELATED CHANGED RESOLVED 2714- 3/F /204 0 mg 166/50 ⥺⥔➽③ EXACERBATION OF No No Y SEVERE DOUBTFUL DOSE NOT RECOVERED/ 10929 FIBROMYALGIA CHANGED RESOLVED 1001- 4/F 0 mg 132/1 㧊⭷⭘ MENINGIOMA No No Y SEVERE DOUBTFUL DOSE NOT RECOVERED/ 11014 CHANGED RESOLVED 5302- 3/M 0 mg 347/33 ⭠⭤⬔⒦ COLOVESICAL No No Y SEVERE NOT DRUG RECOVERED/ 20191 FISTULA DRAINING RELATED WITHDRAWN RESOLVED FAECES 1022- 5/M /168 0 mg 172/2 ⭜㒊⬨ᰕ⟶⊃ LUMBAR SPINAL No No Y MODERATE NOT DOSE NOT RECOVERED/ 20548 ✽ STENOSIS RELATED CHANGED RESOLVED 1120- 6/F 0 mg 357/3 ࢡ࣮ࣟࣥ WORSENING OF No No Y MODERATE NOT DOSE NOT RECOVERED/ 20848 CROHNS RELATED CHANGED RESOLVED 2606- 2/M 0 mg 192/8 ⫵⅖ RIGHT ALVEOLAR Yes No Y MODERATE POSSIBLE DRUG RECOVERED/ 20878 PNEUMONIA INTERRUPTED RESOLVED
a Relative to the date of first treatment in maintenance study. b Infection as assessed by the investigator. Adverse events are coded using MedDRA 17.1. [LPMDASF23A.rtf] [CNTO1275\CRD3003\DBR_CSR\RE_PMDA\lpmdasf23a.sas] 20SEP2016, 21:43
ಶ ࠎ ࡢヨ 㦂 ࡢࡲ ヨ ࡵ 㦂 )
206
(71 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 2) ᪥ᮏே㞟ᅋ ⾲ 2.7.6.4-18 㔜⠜࡞᭷ᐖ㇟ཬࡧ㦂⸆ྜ⌮ⓗ㛵㐃ᛶࡀ࠶ࡿ㔜⠜࡞᭷ᐖ㇟㸦ࣛࣥࢲ࣒ᚋ㦂⸆ࢆᢞࡉࢀࡓ⿕᳨⪅㸧 Study Treatment Agen Inductio group after t Study Day 2.7.6 Maintenanc n Age Dose Dose of AEa/ e Treatment treatment Subject (yrs)/ Adjustment/ Prior Duration MedDRA Infusion Serious Relation to Group group ID Sex Study Daya to AE (days) preferred term Verbatim Term Infectionb Reaction AE Severity Study Drug Action Taken Outcome 90 mg SC 6 mg/kg 4212- 3/M /57 90.0 104/9 ⭠㛢ሰ COLONIC No No Y MODERATE DOUBTFUL DOSE NOT RECOVERED/ q8w IV 10505 mg OBSTRUCTION CHANGED RESOLVED 90 mg SC 6 mg/kg 4211- 7/F 0 mg 120/27 ᆶ⅖ APPENDICITIS No No Y SEVERE DOUBTFUL DOSE NOT RECOVERED/ q12w IV 10438 CHANGED RESOLVED 7/F 0 mg ⳦⾑ BACTEREMIA Yes No Y SEVERE DOUBTFUL DOSE NOT RECOVERED/ CHANGED RESOLVED 4216- 1/F 90.0 80/Ongoing ⫠㛛⮋⒆ PERIANAL Yes No Y SEVERE NOT DRUG NOT 10754 mg ABSCESS RELATED WITHDRAWN RECOVERED/ NOT RESOLVED
a Relative to the date of first treatment in maintenance study. b Infection as assessed by the investigator. Adverse events are coded using MedDRA 17.1. [LPMDASF23B.rtf] [CNTO1275\CRD3003\DBR_CSR\RE_PMDA\lpmdasf23b.sas] 20SEP2016, 21:43
ಶ ࠎ ࡢヨ 㦂 ࡢࡲ ヨ ࡵ 㦂 )
207
(72 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 (2) 㔜⠜࡞᭷ᐖ㇟ࡢヲ⣽㸦44 㐌┠ࡲ࡛㸧
1) 㞟ᅋ ⾲ 2.7.6.4-19 㔜⠜࡞᭷ᐖ㇟ཬࡧ㦂⸆ྜ⌮ⓗ㛵㐃ᛶࡀ࠶ࡿ㔜⠜࡞᭷ᐖ㇟㸦㦂⸆ࢆᢞࡉࢀࡓ⿕᳨⪅㸧
Treatment 2.7.6 group Study Randomized Mainte after Dose Study Day of at Week 0 nance Adjustme Agent AEa/ of this Treatm Induction Age nt/ Dose Durati maintenance ent treatment Subject (yrs)/ Study Prior on MedDRA Infec- Infusion Serious Relation to study Group group ID Sex Daya to AE (days) preferred term Verbatim Term tionb Reaction AE Severity Study Drug Action Taken Outcome Yes Placebo 130 mg 1007- 2/F 0 mg 167/5 ⫵⅖ PNEUMONIA Yes No Y SEVERE DOUBTFUL DOSE NOT RECOVERED/ SC IV 10134 CHANGED RESOLVED 1069- 3/M 0 mg 145/4 ⒦ ANAL FISTULA No No Y SEVERE NOT DRUG RECOVERED/ 10230 RELATED WITHDRAWN RESOLVED 1013- 3/M 0 mg 195/8 ≀㉁⏝⪅ TRANSIENT No No Y SEVERE NOT DOSE NOT RECOVERED/ 10255 CHEMICAL RELATED CHANGED RESOLVED ABUSE 3314- 3/F 90 mg SC 90.0 ↓ຊ INTENSE No No Y SEVERE PROBABLE DRUG RECOVERED/ 10280 q8w/79 mg ASTHENIA WITHDRAWN RESOLVED 3/F 90 mg SC 90.0 ࠺ࡘ DEPRESSIVE No No Y SEVERE PROBABLE DRUG RECOVERED/ q8w/79 mg SYNDROM WITHDRAWN RESOLVED 3312- 4/F /141 0 mg 180/3 㢌③ ACUTE No No Y MODERATE NOT DOSE NOT RECOVERED/ 10374 HEADACHE RELATED CHANGED RESOLVED 4803- 3/M 0 mg 330/13 ⭠✸Ꮝ COLON No No Y SEVERE NOT DRUG RECOVERED/ 10456 PERFORATION RELATED WITHDRAWN RESOLVED 2702- 2/F 0 mg 77/5 ࢡ࣮ࣟࣥ CROHN'S No No Y SEVERE NOT NOT RECOVERED/ 10624 DISEASE FLARE RELATED APPLICABLE RESOLVED WITH SEQUELAE 1089- 4/F 90 mg SC 0 mg 183/12 ࢡ࣮ࣟࣥ CROHN'S FLARE No No Y SEVERE DOUBTFUL DOSE NOT RECOVERED/ 10632 q8w/81 CHANGED RESOLVED 4/F 90 mg SC 0 mg 184/11 ᑠ⭠㛢ሰ PARTIAL SMALL No No Y SEVERE DOUBTFUL DOSE NOT RECOVERED/ q8w/81 BOWEL CHANGED RESOLVED OBSTRUCTION 3306- 5/M 90 mg SC 0 mg 142/8 ࣥࣇ࢚ࣝ INFLUENZA No No Y MODERATE NOT NOT RECOVERED/ ಶ 10727 q8w/85 ࣥࢨ RELATED APPLICABLE RESOLVED ࠎ 3306- 2/M 0 mg 333/4 ⒦ ANAL FISTULA No No Y MODERATE NOT DOSE NOT RECOVERED/ 10796 RELATED CHANGED RESOLVED ࡢヨ 4603- 5/F /56 0 mg 106/10 ࢡ࣮ࣟࣥ CROHN'S FLARE No No Y SEVERE POSSIBLE DOSE NOT RECOVERED/ 10805 CHANGED RESOLVED 㦂 5/F 90 mg SC 90.0 167/83 ࢡ࣮ࣟࣥ WORSENING No No Y SEVERE NOT DOSE NOT RECOVERED/ ࡢࡲ q8w/56 mg CROHNS RELATED CHANGED RESOLVED DISEASE WITH ヨ ࡵ SEQUELAE 㦂 )
208
(73 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 Treatment group Study Randomized Mainte after Dose Study Day of at Week 0 nance Adjustme Agent AEa/ of this Treatm Induction Age nt/ Dose Durati maintenance ent treatment Subject (yrs)/ Study Prior on MedDRA Infec- Infusion Serious Relation to study Group group ID Sex Daya to AE (days) preferred term Verbatim Term tionb Reaction AE Severity Study Drug Action Taken Outcome 2202- 6/F /183 0 mg 157/21 㛵⠇③ WORSENING OF No No Y SEVERE NOT DRUG RECOVERED/ 2.7.6 20506 6 ARTHRALGIA RELATED INTERRUPTED RESOLVED 1049- 6/F /173 0 mg 210/31 ࢡ࣮ࣟࣥ CROHN'S FLARE No No Y SEVERE NOT DOSE NOT RECOVERED/ 20520 RELATED CHANGED RESOLVED 2704- 4/M 0 mg 276/14 ࢡ࣮ࣟࣥ WORSENING OF No No Y SEVERE NOT DRUG RECOVERED/ 20776 CROHNS RELATED WITHDRAWN RESOLVED DISEASE 6 mg/kg 3404- 4/F 90 mg SC 0 mg 223/39 ࢡ࣮ࣟࣥ WORSENING OF No No Y MODERATE DOUBTFUL DRUG RECOVERED/ IV 10331 q8w/106 CROHN'S WITHDRAWN RESOLVED DISEASE 2711- 3/M 0 mg 128/O ࢡ࣮ࣟࣥ WORSENING No No Y SEVERE DOUBTFUL DRUG NOT 10412 ngoing CROHN'S WITHDRAWN RECOVERED/ DISEASE NOT RESOLVED 3428- 2/M 90 mg SC 90.0 250/3 ⭈⤖▼ NEPHROLITHIAS No No Y MODERATE DOUBTFUL DOSE NOT RECOVERED/ 10434 q8w/113 mg IS LEFT CHANGED RESOLVED 5609- 4/F 0 mg 261/4 ⫠㛛⮋⒆ PERIANAL Yes No Y MODERATE DOUBTFUL DRUG RECOVERED/ 10637 ABSCESS, NEW INTERRUPTED RESOLVED 1010- 3/F /141 0 mg 187/17 ࢡ࣮ࣟࣥ CROHN FLARE No No Y SEVERE NOT DOSE NOT RECOVERED/ 10794 RELATED CHANGED RESOLVED 2714- 3/F /204 0 mg 166/50 ⥺⥔➽③ EXACERBATION No No Y SEVERE DOUBTFUL DOSE NOT RECOVERED/ 10929 OF CHANGED RESOLVED FIBROMYALGIA 1001- 4/F 0 mg 132/1 㧊⭷⭘ MENINGIOMA No No Y SEVERE DOUBTFUL DOSE NOT RECOVERED/ 11014 CHANGED RESOLVED 5302- 3/M 0 mg 347/33 ⭠⭤⬔⒦ COLOVESICAL No No Y SEVERE NOT DRUG RECOVERED/ 20191 FISTULA RELATED WITHDRAWN RESOLVED DRAINING FAECES 5104- 5/F 90 mg SC 90.0 171/12 ࢡ࣮ࣟࣥ WORSENING OF No No Y MODERATE NOT DOSE NOT RECOVERED/ 20303 q8w/113 mg CROHN'S RELATED CHANGED RESOLVED DISEASE 1022- 5/M /168 0 mg 172/2 ⭜㒊⬨ᰕ⟶ LUMBAR SPINAL No No Y MODERATE NOT DOSE NOT RECOVERED/ ಶ 20548 ⊃✽ STENOSIS RELATED CHANGED RESOLVED ࠎ 1120- 6/F 0 mg 357/3 ࢡ࣮ࣟࣥ WORSENING OF No No Y MODERATE NOT DOSE NOT RECOVERED/ ࡢヨ 20848 CROHNS RELATED CHANGED RESOLVED 2606- 2/M 0 mg 192/8 ⫵⅖ RIGHT Yes No Y MODERATE POSSIBLE DRUG RECOVERED/ 㦂
20878 ALVEOLAR INTERRUPTED RESOLVED ࡢࡲ PNEUMONIA ヨ ࡵ 㦂 )
209
(74 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 Treatment group Study Randomized Mainte after Dose Study Day of at Week 0 nance Adjustme Agent AEa/ of this Treatm Induction Age nt/ Dose Durati maintenance ent treatment Subject (yrs)/ Study Prior on MedDRA Infec- Infusion Serious Relation to study Group group ID Sex Daya to AE (days) preferred term Verbatim Term tionb Reaction AE Severity Study Drug Action Taken Outcome 90 mg 130 mg 1006- 6/F /163 90.0 160/3 ῝㒊㟼⬦⾑ DEEP VEIN No No Y SEVERE NOT DOSE NOT RECOVERED/ 2.7.6 SC IV 10085 mg ᰦ THROMBOSIS RELATED CHANGED RESOLVED q12w 1018- 4/F 0 mg 222/55 ࣞࣝࢠ࣮ DELAYED No No Y SEVERE DOUBTFUL DRUG RECOVERED/ 10162 ᛶ㍺⾑ᛂ ALLERGIC INTERRUPTED RESOLVED REACTION, LIKELY DUE TO IRON INFUSION OR BLOOD TRANSFUSION 4104- 3/F 90 mg SC 0 mg 162/14 ࢡ࣮ࣟࣥ CROHN DISEASE No No Y SEVERE NOT DRUG RECOVERED/ 10647 q8w/51 RELAPSE RELATED WITHDRAWN RESOLVED WITH SEQUELAE 1096- 5/M 90.0 96/6 ࢘ࣝࢫᛶ VIRAL Yes No Y MODERATE NOT DOSE NOT RECOVERED/ 10651 mg ⫶⭠⅖ GASTROENTERI RELATED CHANGED RESOLVED TIS 1039- 2/F 0 mg 135/O ⭡㒊ឤᰁ INTRA- Yes No Y SEVERE POSSIBLE DRUG NOT 10681 ngoing ABDOMINAL WITHDRAWN RECOVERED/ INFECTION NOT WITHOUT RESOLVED ABSCESS 3415- 5/F 90 mg SC 0 mg 214/5 ⫪ᅇ᪕➽⭝ OUTLET No No Y MODERATE NOT DOSE NOT RECOVERED/ 10880 q8w/45 ᯈೃ⩌ IMPINGEMENT RELATED CHANGED RESOLVED SYNDROME 2406- 4/F 0 mg 132/2 ࢡ࣮ࣟࣥ FLARE CROHN'S No No Y MODERATE NOT DRUG RECOVERED/ 11023 DISEASE RELATED WITHDRAWN RESOLVED WITH SEQUELAE 2204- 2/M 0 mg 270/3 ᑠ⭠㛢ሰ PARTIAL SMALL No No Y MODERATE POSSIBLE DOSE NOT RECOVERED/ 20144 BOWEL CHANGED RESOLVED OBSTRUCTION 3414- 2/M 90.0 237/10 ᆶ⅖ APPENDICITIS Yes No Y SEVERE DOUBTFUL DOSE NOT RECOVERED/ ಶ 20406 mg CHANGED RESOLVED ࠎ
4301- 1/M 0 mg 218/6 ࢡ࣮ࣟࣥ CROHN'S No No Y MODERATE NOT DRUG RECOVERED/ ࡢヨ 20660 DISEASE RELATED WITHDRAWN RESOLVED
AGGRAVATION 㦂
6 mg/kg 1091- 2/M 90.0 93/4 ⮬ẅᛕ៖ SUICIDAL No No Y SEVERE DOUBTFUL DOSE NOT RECOVERED/ ࡢࡲ IV 10100 mg IDEATION CHANGED RESOLVED 2/M 90.0 113/73 WORSENING No No Y SEVERE NOT DOSE NOT RECOVERED/ ࢡ࣮ࣟࣥ ヨ mg CROHNS FLARE RELATED CHANGED RESOLVED ࡵ 㦂 )
210
(75 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 Treatment group Study Randomized Mainte after Dose Study Day of at Week 0 nance Adjustme Agent AEa/ of this Treatm Induction Age nt/ Dose Durati maintenance ent treatment Subject (yrs)/ Study Prior on MedDRA Infec- Infusion Serious Relation to study Group group ID Sex Daya to AE (days) preferred term Verbatim Term tionb Reaction AE Severity Study Drug Action Taken Outcome 2/M 90.0 318/7 ࢡ࣮ࣟࣥ WORSENING No No Y SEVERE DOUBTFUL DOSE NOT RECOVERED/ 2.7.6 mg CROHNS FLARE CHANGED RESOLVED 1018- 5/M 0 mg 264/5 ࢡ࣮ࣟࣥ EXARCEBATION No No Y SEVERE NOT NOT RECOVERED/ 10167 OF RELATED APPLICABLE RESOLVED PERIANALCROH NS DISEASE 4201- 3/F 90 mg SC 0 mg 241/13 ⭡⭷⅖ PERITONITIS Yes No Y SEVERE NOT DRUG RECOVERED/ 10360 q8w/133 3 RELATED WITHDRAWN RESOLVED 3/F 90 mg SC 0 mg 300/26 ⫹ᄞ⅖ CHOLECYSTITIS Yes No Y SEVERE DOUBTFUL NOT RECOVERED/ q8w/133 APPLICABLE RESOLVED 2301- 2/F 90.0 157/2 ⫶⭠⅖ GASTROENTERI Yes No Y SEVERE NOT DOSE NOT RECOVERED/ 10432 mg TIS RELATED CHANGED RESOLVED 4211- 7/F 0 mg 120/27 ᆶ⅖ APPENDICITIS No No Y SEVERE DOUBTFUL DOSE NOT RECOVERED/ 10438 CHANGED RESOLVED 7/F 0 mg ⳦⾑ BACTEREMIA Yes No Y SEVERE DOUBTFUL DOSE NOT RECOVERED/ CHANGED RESOLVED 4107- 2/F 90.0 233/8 ࢡ࣮ࣟࣥ CROHN'S No No Y MODERATE NOT DOSE NOT RECOVERED/ 10677 mg DISEASE RELATED CHANGED RESOLVED RELAPSE 1013- 5/M 90 mg SC 0 mg 210/41 ࢡ࣮ࣟࣥ CROHN'S FLARE, No No Y SEVERE NOT NOT RECOVERED/ 10741 q8w/55 WORSENING RELATED APPLICABLE RESOLVED 5/M 90 mg SC 90.0 299/28 ࢡ࣮ࣟࣥ CROHN'S FLARE, No No Y SEVERE NOT NOT RECOVERED/ q8w/55 mg WORSENING RELATED APPLICABLE RESOLVED 4216- 1/F 90.0 80/On ⫠㛛⮋⒆ PERIANAL Yes No Y SEVERE NOT DRUG NOT 10754 mg going ABSCESS RELATED WITHDRAWN RECOVERED/ NOT RESOLVED 4602- 6/M 90.0 74/40 ⾡ᚋឤᰁ POST- Yes No Y MODERATE NOT DOSE NOT RECOVERED/ 10902 mg OPERATIVE RELATED CHANGED RESOLVED WOUND INFECTION". 6/M 0 mg 217/10 ࢝ࣥࣆࣟࣂ CAMPILOBACTE Yes No Y MODERATE NOT DOSE NOT RECOVERED/ ࢡࢱ࣮⫶⭠ R GASTRO RELATED CHANGED RESOLVED ಶ ࠎ ⅖ ENTERITIS ࡢヨ 5605- 2/F 90 mg SC 90.0 324/3 ࢡ࣮ࣟࣥ CROHN'S No No Y MODERATE NOT DOSE NOT RECOVERED/ 20330 q8w/64 mg EXACERBATION RELATED CHANGED RESOLVED 1005- 6/M 0 mg 362/3 ᮏែᛶ㧗⾑ PRIMARY No No Y MODERATE DOUBTFUL DOSE NOT RECOVERED/ 㦂 20434 ᅽ IDIOPATHIC CHANGED RESOLVED ࡢࡲ HYPERTENSION 90 mg 130 mg 1015- 4/M 90.0 71/5 ⭠⊃✽ COLONIC No No Y SEVERE NOT DOSE NOT RECOVERED/ ヨ ࡵ SC q8w IV 10352 mg STRICTURE RELATED CHANGED RESOLVED 㦂 )
211
(76 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 Treatment group Study Randomized Mainte after Dose Study Day of at Week 0 nance Adjustme Agent AEa/ of this Treatm Induction Age nt/ Dose Durati maintenance ent treatment Subject (yrs)/ Study Prior on MedDRA Infec- Infusion Serious Relation to study Group group ID Sex Daya to AE (days) preferred term Verbatim Term tionb Reaction AE Severity Study Drug Action Taken Outcome 1008- 2/M 90.0 100/3 ᑠ⭠㛢ሰ PARTIAL SMALL No No Y MODERATE DOUBTFUL DOSE NOT RECOVERED/ 2.7.6 10423 mg BOWEL CHANGED RESOLVED OBSTRUCTION 2/M 90.0 108/2 ᑠ⭠㛢ሰ PARTIAL SMALL No No Y MODERATE DOUBTFUL DOSE NOT RECOVERED/ mg BOWEL CHANGED RESOLVED OBSTRUCTION 2/M 90.0 133/7 ࢡ࣮ࣟࣥ WORSENING No No Y SEVERE NOT DRUG RECOVERED/ mg CROHN'S RELATED WITHDRAWN RESOLVED DISEASE 1080- 3/F 90 mg SC 90.0 292/17 ⫵⅖⌫⳦ᛶ PNEUMOCOCCA Yes No Y SEVERE DOUBTFUL DOSE NOT RECOVERED/ 10452 q8w/57 mg ⫵⅖ L PNEUMONIA CHANGED RESOLVED 3420- 3/F 0 mg 259/65 ࢡ࣮ࣟࣥ FLAIR OF No No Y SEVERE NOT DOSE NOT RECOVERED/ 10556 CROHNS RELATED CHANGED RESOLVED DISEASE 3201- 4/F /121 90.0 107/22 ࢡ࣮ࣟࣥ WORSENING OF No No Y MODERATE NOT DOSE NOT RECOVERED/ 10889 mg CHRON'S RELATED CHANGED RESOLVED DISEASE 4/F /121 0 mg 165/13 ࢡ࣮ࣟࣥ WORSENING OF No No Y MODERATE NOT DOSE NOT RECOVERED/ CHRON'S RELATED CHANGED RESOLVED DISEASE 2704- 3/F 90.0 387/5 ༸ᕢ⭢⭘ BENIGN No No Y SEVERE DOUBTFUL DRUG RECOVERED/ 10988 mg OVARIAN INTERRUPTED RESOLVED MUCINOUS CYSTADENOMA 1049- 4/F 90.0 187/10 ⭠⊃✽ SPLENIC No No Y MILD NOT DRUG RECOVERED/ 20148 mg FLEXURE RELATED WITHDRAWN RESOLVED STENOSIS 4213- 3/M 90 mg SC 0 mg 155/98 ࢡ࣮ࣟࣥ WORSENING OF No No Y SEVERE NOT DRUG RECOVERED/ 20895 q8w/58 CROHN'S RELATED WITHDRAWN RESOLVED DISEASE 6 mg/kg 1046- 4/F 90 mg SC 0 mg 220/3 ⫶⭠ฟ⾑ GATROINTESTIN No No Y SEVERE NOT DOSE NOT RECOVERED/ IV 10129 q8w/85 AL BLEED RELATED CHANGED RESOLVED ಶ 2709- 3/M 90 mg SC 90.0 132/32 ࢡ࣮ࣟࣥ SEVERE No No Y SEVERE NOT DOSE NOT RECOVERED/ 10296 q8w/57 mg 5 ABDOMINAL RELATED CHANGED RESOLVED ࠎ PAIN DUE TO ࡢヨ CROHNS DISEASE 㦂
3/M 90 mg SC 90.0 353/10 ࢡ࣮ࣟࣥ CROHNS No No Y SEVERE DOUBTFUL DOSE NOT RECOVERED/ ࡢࡲ q8w/57 mg 4 DISEASE CHANGED RESOLVED ヨ ࡵ 㦂 )
212
(77 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 Treatment group Study Randomized Mainte after Dose Study Day of at Week 0 nance Adjustme Agent AEa/ of this Treatm Induction Age nt/ Dose Durati maintenance ent treatment Subject (yrs)/ Study Prior on MedDRA Infec- Infusion Serious Relation to study Group group ID Sex Daya to AE (days) preferred term Verbatim Term tionb Reaction AE Severity Study Drug Action Taken Outcome 3/M 90 mg SC 90.0 368/11 ⴥᛶ⫵⅖ LEFT LOWER Yes No Y MODERATE NOT DOSE NOT RECOVERED/ 2.7.6 q8w/57 mg 8 LOBE RELATED CHANGED RESOLVED PNEUMONIA 3420- 3/F 90 mg SC 0 mg 274/3 ⭡㒊࣊ࣝࢽ ABDOMINAL No No Y SEVERE NOT NOT RECOVERED/ 10322 q8w/49 WALL HERNIA RELATED APPLICABLE RESOLVED 4112- 4/M 90.0 196/9 ࢡ࣮ࣟࣥ RELAPSE OF No No Y SEVERE NOT DOSE NOT RECOVERED/ 10497 mg CROHNS RELATED CHANGED RESOLVED DISEASE 4212- 3/M /57 90.0 104/9 ⭠㛢ሰ COLONIC No No Y MODERATE DOUBTFUL DOSE NOT RECOVERED/ 10505 mg OBSTRUCTION CHANGED RESOLVED 2712- 2/F /142 90.0 75/26 ∦㢌③ SEVERE No No Y SEVERE NOT DOSE NOT RECOVERED/ 10954 mg MIGRAINE RELATED CHANGED RESOLVED HEADACHE 1043- 3/F /167 0 mg 216/27 ࢘ࣝࢫឤ VIRAL Yes No Y SEVERE POSSIBLE DOSE NOT RECOVERED/ 10979 ᰁ SYNDROME CHANGED RESOLVED 1022- 3/F 90.0 63/3 ⭡③ ABDOMINAL No No Y MODERATE DOUBTFUL DOSE NOT RECOVERED/ 20641 mg PAIN CHANGED RESOLVED 1007- 2/M 90.0 347/2 ⫵⅖ PNEUMONIA Yes No Y SEVERE POSSIBLE DOSE NOT RECOVERED/ 20955 mg CHANGED RESOLVED 1016- 3/M 90.0 177/37 ║ᖏ≧⑁⑈ HERPES ZOSTER Yes No Y MODERATE POSSIBLE DRUG RECOVERED/ 21010 mg KERATOCONJUN INTERRUPTED RESOLVED CTIVITIS No Placebo Placebo 1014- 5/F Placebo 0 mg 209/16 ⫹ᄞ⅖ CHRONIC No No Y SEVERE NOT DOSE NOT RECOVERED/ SC IV 10031 SC/120 ACALCULOUS RELATED CHANGED RESOLVED CHOLECYCTITIS 1011- 3/M Placebo 0 mg 155/4 ࢡ࣮ࣟࣥ CROHNS FLARE No No Y SEVERE NOT DOSE NOT RECOVERED/ 10104 SC/85 RELATED CHANGED RESOLVED 5611- 1/M 0 mg 149/4 ౽⛎ CONTSIPATION No No Y MODERATE NOT DOSE NOT RECOVERED/ 10228 RELATED CHANGED RESOLVED 1007- 4/M /143 0 mg 195/4 ᑠ⭠㛢ሰ SMALL BOWEL No No Y MODERATE DOUBTFUL DOSE NOT RECOVERED/ 10232 OBSTRUCTION CHANGED RESOLVED
5606- 2/M 0 mg 332/36 ⫠㛛⮋⒆ PERIANAL Yes No Y SEVERE DOUBTFUL DOSE NOT RECOVERED/ ಶ
10340 ABSCESS CHANGED RESOLVED ࠎ 1027- 4/F Placebo 0 mg 247/10 C. DIFFICILE Yes No Y SEVERE POSSIBLE DRUG RECOVERED/
ࢡࣟࢫࢺࣜ ࡢヨ 10490 SC/170 ࢪ࣒࣭࢘ࢹ COLITIS WITHDRAWN RESOLVED
ࣇࢩࣞ 㦂
⭠⅖ ࡢࡲ 4/F Placebo 0 mg ࢡ࣮ࣟࣥ CROHNS No No Y SEVERE NOT DRUG RECOVERED/ SC/170 PROCTOCOLITIS RELATED WITHDRAWN RESOLVED ヨ ࡵ 㦂 )
213
(78 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 Treatment group Study Randomized Mainte after Dose Study Day of at Week 0 nance Adjustme Agent AEa/ of this Treatm Induction Age nt/ Dose Durati maintenance ent treatment Subject (yrs)/ Study Prior on MedDRA Infec- Infusion Serious Relation to study Group group ID Sex Daya to AE (days) preferred term Verbatim Term tionb Reaction AE Severity Study Drug Action Taken Outcome 5619- 5/M Placebo 0 mg 227/13 ࢡ࣮ࣟࣥ INPATIENT No No Y SEVERE NOT DRUG RECOVERED/ 2.7.6 10586 SC/148 HOSPITALISATIO RELATED WITHDRAWN RESOLVED N DUE TO CROHNS FLARE 5610- 3/F 0 mg 118/2 ேᕤஙᡣ BILATERAL No No Y MILD NOT DOSE NOT RECOVERED/ 10587 ⏝⪅ BREAST RELATED CHANGED RESOLVED PROSTHETIC IMPLANTS 4803- 3/F 0 mg 223/10 ࢡ࣮ࣟࣥ WORSENING OF No No Y MODERATE NOT DRUG RECOVERED/ 10691 CROHN DISEASE RELATED WITHDRAWN RESOLVED 3419- 4/F 0 mg 315/2 ࿀ྜ㒊ฟ⾑ ILEO-CAECAL No No Y MODERATE NOT DOSE NOT RECOVERED/ 11089 ANASTOMOTIC RELATED CHANGED RESOLVED BLEEDING 2202- 5/M /191 0 mg 228/2 ⫪ᅇ᪕➽⭝ RIGHT SUB No No Y SEVERE NOT DOSE NOT RECOVERED/ 20072 ᯈೃ⩌ ACROMIAL RELATED CHANGED RESOLVED IMPINGEMENT 3610- 3/F Placebo 0 mg 238/11 ዪᛶ⏕Ṫჾ SIGMOIDEO- No No Y SEVERE NOT DRUG RECOVERED/ 20093 SC/60 6 ⒦ PELVIC FISTULA RELATED WITHDRAWN RESOLVED WITH SEQUELAE 2208- 1/M 0 mg 146/3 ࣐࣮࣭ࣟࣜ SUSPECTED No No Y MODERATE NOT DOSE NOT RECOVERED/ 20489 ࣡ࢫೃ MALLORY WEISS RELATED CHANGED RESOLVED ⩌ TEAR 3607- 3/F /175 0 mg 209/8 㰯Ⲗ NASAL POLYPS No No Y SEVERE NOT DOSE NOT RECOVERED/ 20732 RELATED CHANGED RESOLVED 1048- 5/F Placebo 0 mg 186/6 ࢡ࣮ࣟࣥ CROHN'S FLARE No No Y SEVERE NOT DOSE NOT RECOVERED/ 20764 SC/120 RELATED CHANGED RESOLVED 4803- 4/M 0 mg 75/24 ࢡ࣮ࣟࣥ CROHN'S No No Y MODERATE NOT DOSE NOT RECOVERED/ 20770 DISEASE RELATED CHANGED RESOLVED WORSENING 3606- 2/F 0 mg 133/3 ங⭢⥺⥔⭢ BREAST No No Y MILD NOT DOSE NOT RECOVERED/ 20804 FIBROADENOMA RELATED CHANGED RESOLVED ⭘ ಶ
1135- 4/M 0 mg 366/1 ⮬↛ὶ⏘ SPONTANEOUS No No Y SEVERE NOT DOSE NOT RECOVERED/ ࠎ
20958 ABORTION OF RELATED CHANGED RESOLVED ࡢヨ PREGNANT PARTNER 㦂 2718- 3/F Placebo 0 mg 289/35 ⫠ ANAL FISSURE No No Y MODERATE NOT DOSE NOT RECOVERED/ 21022 SC/115 RELATED CHANGED RESOLVED ࡢࡲ 130 mg Placebo 1015- 5/M 0 mg 314/27 ┤⭠⮋⒆ LARGE LEFT Yes No Y SEVERE NOT DOSE NOT RECOVERED/ IV IV 10023 ISCHIORECTAL RELATED CHANGED RESOLVED ヨ ࡵ ABSCESS 㦂 )
214
(79 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 Treatment group Study Randomized Mainte after Dose Study Day of at Week 0 nance Adjustme Agent AEa/ of this Treatm Induction Age nt/ Dose Durati maintenance ent treatment Subject (yrs)/ Study Prior on MedDRA Infec- Infusion Serious Relation to study Group group ID Sex Daya to AE (days) preferred term Verbatim Term tionb Reaction AE Severity Study Drug Action Taken Outcome 5/M 0 mg 316/21 ῝㒊㟼⬦⾑ DEEP VENOUS No No Y SEVERE NOT DOSE NOT RECOVERED/ 2.7.6 ᰦ THROMBOSIS RELATED CHANGED RESOLVED 4107- 2/M 129.6 136/21 ࢡ࣮ࣟࣥ MALNUTRITION No No Y SEVERE NOT DOSE NOT RECOVERED/ 10316 mg AND ANEMIA RELATED CHANGED RESOLVED DUE TO CROHN'S DISEASE RELAPSE 2/M 129.6 234/15 ⭡㒊⒵╔ SUBOCCLUSION No No Y SEVERE NOT NOT RECOVERED/ mg BECAUSE OF RELATED APPLICABLE RESOLVED ADHERENCES 3406- 4/F 129.6 88/5 ⒦ PERIANAL No No Y MODERATE NOT DOSE NOT RECOVERED/ 10338 mg FISTULA RELATED CHANGED RESOLVED 1057- 2/M 129.6 142/3 ࠺ࡘ DEPRESSION No No Y MODERATE NOT DOSE NOT RECOVERED/ 10350 mg EXACERBATION RELATED CHANGED RESOLVED 5609- 2/M 0 mg 263/3 ⫠㛛⮋⒆ PERIANAL Yes No Y MODERATE POSSIBLE DOSE NOT RECOVERED/ 10365 ABSCESS CHANGED RESOLVED 1001- 3/F 129.6 66/26 ࢡ࣮ࣟࣥ CROHN'S No No Y SEVERE DOUBTFUL DRUG RECOVERED/ 10406 mg DISEASE FLARE WITHDRAWN RESOLVED 3314- 2/F 129.6 152/17 ᒀ⟶⤖▼ URETERAL No No Y MODERATE NOT NOT RECOVERED/ 10421 mg LITHIASIS RELATED APPLICABLE RESOLVED 2/F 129.6 185/O ࢡ࣮ࣟࣥ WORSENING OF No No Y MODERATE NOT NOT RECOVERED/ mg ngoing CROHN'S RELATED APPLICABLE RESOLVED DISEASE 2/F 129.6 191/23 ⫢㓝⣲ୖ᪼ ELEVATED No No Y MODERATE NOT NOT RECOVERED/ mg LIVER ENZYMES RELATED APPLICABLE RESOLVED DUE TO CYCLOSPORINE 4209- 4/F 0 mg 285/42 ࢡ࣮ࣟࣥ CROHN'S No No Y SEVERE NOT DRUG RECOVERED/ 10427 DISEASE RELATED WITHDRAWN RESOLVED AGGRAVATED 5604- 3/F 129.6 124/5 ②ᨥ SEIZURES No No Y SEVERE DOUBTFUL NOT RECOVERED/ 10436 mg APPLICABLE RESOLVED ಶ 3415- 3/M 129.6 73/44 ࢡ࣮ࣟࣥ WORSENING OF No No Y MODERATE NOT DOSE NOT RECOVERED/ 10460 mg CROHN'S RELATED CHANGED RESOLVED ࠎ DISEASE ࡢヨ 4808- 2/M 0 mg 356/3 㕲Ḟஈᛶ㈋ IRON No No Y MODERATE NOT DOSE NOT RECOVERED/ 10543 ⾑ DEFICIENCY RELATED CHANGED RESOLVED 㦂 ANAEAMIA ࡢࡲ 3401- 2/F 0 mg 357/12 ⫶⭠⅖ ACCUTE Yes No Y SEVERE NOT DOSE NOT RECOVERED/ 10550 GASTROENTERI RELATED CHANGED RESOLVED ヨ ࡵ TIS 㦂 )
215
(80 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 Treatment group Study Randomized Mainte after Dose Study Day of at Week 0 nance Adjustme Agent AEa/ of this Treatm Induction Age nt/ Dose Durati maintenance ent treatment Subject (yrs)/ Study Prior on MedDRA Infec- Infusion Serious Relation to study Group group ID Sex Daya to AE (days) preferred term Verbatim Term tionb Reaction AE Severity Study Drug Action Taken Outcome 3410- 3/M 129.6 60/43 ᮎᲈᛶᾋ⭘ OEDEMAS IN No No Y SEVERE PROBABLE DOSE NOT RECOVERED/ 2.7.6 10564 mg BOTH ANKLES CHANGED RESOLVED 3/M 129.6 119/21 ࢡ࣮ࣟࣥ WORSENING OF No No Y SEVERE NOT DOSE NOT RECOVERED/ mg CROHN'S RELATED CHANGED RESOLVED DISEASE 4216- 2/M 0 mg 196/O ࢡ࣮ࣟࣥ DETERIORATION No No Y SEVERE NOT DRUG NOT 10627 ngoing OF CROHN'S RELATED WITHDRAWN RECOVERED/ DISEASE NOT RESOLVED 4201- 6/F 0 mg 371/2 ⫠㛛⮋⒆ WORSENING OF Yes No Y MODERATE NOT DOSE NOT RECOVERED/ 10643 PERIANAL RELATED CHANGED RESOLVED ABSCESS 1069- 4/F 129.6 187/78 ࢡ࣮ࣟࣥ CROHN'S FLARE No No Y SEVERE DOUBTFUL DOSE NOT RECOVERED/ 10679 mg CHANGED RESOLVED 3314- 6/M 129.6 145/11 ␗ᙧᡂ LOW AND HIGH No No Y SEVERE DOUBTFUL NOT RECOVERED/ 10738 mg 0 GRADE RECTAL APPLICABLE RESOLVED DYSPLASIA 1064- 2/M 129.6 59/4 ᰤ㣴㞀ᐖ PROTEIN No No Y SEVERE DOUBTFUL DOSE NOT RECOVERED/ 10772 mg CALORIE CHANGED RESOLVED MALNUTRITION 1015- 5/F 0 mg 264/52 ࣈࢻ࢘⌫⳦ STAPHYLOCOCC Yes No Y MODERATE PROBABLE DRUG RECOVERED/ 10811 ᛶ⫵⅖ US AUREUS WITHDRAWN RESOLVED PNEUMONIA 2204- 2/F 0 mg 253/11 ࢡ࣮ࣟࣥ WORSENING OF No No Y SEVERE NOT DOSE NOT RECOVERED/ 10848 3 CROHN'S RELATED CHANGED RESOLVED DISEASE 4603- 2/F 129.6 186/28 ࢡ࣮ࣟࣥ INCREASED No No Y SEVERE NOT NOT RECOVERED/ 10904 mg ACTIVITY RELATED APPLICABLE RESOLVED CROHN'S WITH DISEASE SEQUELAE 4605- 6/M 90.0 214/91 ⭈⤖▼ KIDNEYSTONE No No Y SEVERE DOUBTFUL DOSE NOT RECOVERED/ 10936 mg CHANGED RESOLVED 2405- 5/F 129.6 78/15 ⭠⟶⓶⒦ ENTERO- No No Y SEVERE DOUBTFUL DRUG RECOVERED/ ಶ 10944 mg CUTANEOUS WITHDRAWN RESOLVED ࠎ
FISTULA ࡢヨ 3314- 2/F 129.6 60/11 ⣅ሢ FECAL No No Y MILD DOUBTFUL DOSE NOT RECOVERED/
10962 mg IMPACTION CHANGED RESOLVED 㦂
2711- 3/M 90.0 137/68 ⭡㒊⮋⒆ ABDOMINAL Yes No Y SEVERE POSSIBLE DRUG RECOVERED/ ࡢࡲ 10966 mg ABSCESS WITHDRAWN RESOLVED 1013- 6/M 90.0 250/10 SMALL BOWEL No No Y SEVERE NOT NOT RECOVERED/ ᑠ⭠㛢ሰ ヨ 11005 mg OBSTRUCTION, RELATED APPLICABLE RESOLVED ࡵ 㦂
) ACUTE
216
(81 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 Treatment group Study Randomized Mainte after Dose Study Day of at Week 0 nance Adjustme Agent AEa/ of this Treatm Induction Age nt/ Dose Durati maintenance ent treatment Subject (yrs)/ Study Prior on MedDRA Infec- Infusion Serious Relation to study Group group ID Sex Daya to AE (days) preferred term Verbatim Term tionb Reaction AE Severity Study Drug Action Taken Outcome 6/M 90.0 255/O ᑠ⭠⭢⒴ METASTATIC No No Y SEVERE POSSIBLE NOT NOT 2.7.6 mg ngoing ADENOCARCINO APPLICABLE RECOVERED/ MA OF SMALL NOT BOWEL RESOLVED 6/M 90.0 269/O ᑠ⭠㛢ሰ SMALL BOWEL No No Y SEVERE NOT NOT NOT mg ngoing OBSTRUCTION, RELATED APPLICABLE RECOVERED/ HIGH GRADE NOT RESOLVED 1001- 3/F 129.6 191/9 ࢡࣟࢫࢺࣜ C DIFFICILE Yes No Y SEVERE DOUBTFUL NOT RECOVERED/ 11034 mg ࢪ࣒࣭࢘ࢹ COLITIS APPLICABLE RESOLVED ࣇࢩࣞ ⭠⅖ 1014- 4/F 90.0 119/12 ᰤ㣴㞀ᐖ CHRONIC No No Y MODERATE NOT DOSE NOT RECOVERED/ 11054 mg NUTRITIONAL RELATED CHANGED RESOLVED DEPLETION 2406- 3/F 129.6 111/4 ⣅ሢ FECAL No No Y MODERATE NOT DOSE NOT RECOVERED/ 11079 mg IMPACTION RELATED CHANGED RESOLVED 4213- 4/M 129.6 149/56 ࢡ࣮ࣟࣥ WORSENING OF No No Y SEVERE NOT NOT RECOVERED/ 11139 mg CROHNS RELATED APPLICABLE RESOLVED DISEASE 4201- 2/F 129.6 146/23 ࢡ࣮ࣟࣥ WORSENING OF No No Y SEVERE NOT NOT RECOVERED/ 11141 mg CROHN'S RELATED APPLICABLE RESOLVED DISEASE 1022- 7/F 90.0 299/11 ⬨ᰕ⟶⊃✽ SPINAL No No Y SEVERE NOT DOSE NOT RECOVERED/ 20038 mg 1 STENOSIS RELATED CHANGED RESOLVED 2212- 5/M 129.6 74/2 ⭠㛢ሰ BOWEL No No Y MODERATE DOUBTFUL DOSE NOT RECOVERED/ 20054 mg OBSTRUCTION CHANGED RESOLVED 5/M 90.0 298/1 ⭠㛢ሰ BOWEL No No Y SEVERE DOUBTFUL DOSE NOT RECOVERED/ mg OBSTRUCTION CHANGED RESOLVED 5/M 0 mg 343/2 ⭠㛢ሰ BOWEL No No Y SEVERE DOUBTFUL DOSE NOT RECOVERED/ OBSTRUCTION CHANGED RESOLVED
3610- 4/F 129.6 99/3 ⒦ PERIANAL No No Y MODERATE NOT DOSE NOT RECOVERED/ ಶ
20397 mg FISTULA RELATED CHANGED RESOLVED ࠎ
4/F 90.0 206/3 ⫠㛛⮋⒆ PERIANAL Yes No Y MODERATE NOT DOSE NOT RECOVERED/ ࡢヨ mg ABSCESS RELATED CHANGED RESOLVED
3412- 6/F 129.6 169/3 ᚰᡣ⣽ື ATRIAL No No Y SEVERE NOT NOT RECOVERED/ 㦂 20429 mg FIBRILLATION RELATED APPLICABLE RESOLVED ࡢࡲ PAROXYSMAL 3612- 1/F 129.6 144/6 ㈋⾑ ANAEMIA No No Y MODERATE NOT NOT RECOVERED/ 20469 mg RELATED APPLICABLE RESOLVED ヨ ࡵ 㦂 )
217
(82 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 Treatment group Study Randomized Mainte after Dose Study Day of at Week 0 nance Adjustme Agent AEa/ of this Treatm Induction Age nt/ Dose Durati maintenance ent treatment Subject (yrs)/ Study Prior on MedDRA Infec- Infusion Serious Relation to study Group group ID Sex Daya to AE (days) preferred term Verbatim Term tionb Reaction AE Severity Study Drug Action Taken Outcome 3301- 2/F 90.0 129/27 ᑠ⭠㛢ሰ DISTAL SMALL No No Y MODERATE NOT DRUG RECOVERED/ 2.7.6 20481 mg BOWEL RELATED WITHDRAWN RESOLVED OBSTRUCTION 1006- 2/M 129.6 111/10 ࢡ࣮ࣟࣥ CROHN'S No No Y SEVERE NOT DOSE NOT RECOVERED/ 20484 mg DISEASE FLARE RELATED CHANGED RESOLVED 5307- 3/M 0 mg 327/19 ᛴᛶ㰯⭍ ACUTE Yes No Y MODERATE NOT DOSE NOT RECOVERED/ 20565 ⅖ SINUSITIS RELATED CHANGED RESOLVED 3409- 3/F 129.6 76/2 ⫹ᄞ⅖ CHOLECYSTITIS Yes No Y SEVERE NOT DOSE NOT RECOVERED/ 20602 mg RELATED CHANGED RESOLVED 2712- 4/F 0 mg 162/7 ࢡ࣮ࣟࣥ CROHNS FLARE No No Y SEVERE DOUBTFUL DRUG RECOVERED/ 20607 WITHDRAWN RESOLVED 4302- 3/M 0 mg 323/11 യ SHOULDER No No Y MODERATE NOT DOSE NOT RECOVERED/ 20679 CONTUSION RELATED CHANGED RESOLVED 3/M 0 mg 㠎ᖏ SPRAIN OF THE No No Y MODERATE NOT DOSE NOT RECOVERED/ PELVIS RELATED CHANGED RESOLVED 3/M 0 mg 㠎ᖏ SPRAIN OF THE No No Y MODERATE NOT DOSE NOT RECOVERED/ CERVICAL AND RELATED CHANGED RESOLVED LUMBAR 4217- 4/F 0 mg 168/8 Ꮚᐑᖹ➽ MYOMA UTERI No No Y SEVERE NOT DOSE NOT RECOVERED/ 20711 ⭘ RELATED CHANGED RESOLVED 3412- 5/F 0 mg 200/15 ⭈③ RENAL COLIC No No Y SEVERE DOUBTFUL DOSE NOT RECOVERED/ 20728 CHANGED RESOLVED 4209- 3/M 129.6 127/69 ࢡ࣮ࣟࣥ CROHN'S No No Y MODERATE DOUBTFUL NOT RECOVERED/ 20834 mg DISEASE APPLICABLE RESOLVED AGGRAVATED 3425- 4/F 0 mg 240/7 ┤⭠࿘ᅖ⮋ PERIPROCTITIC Yes No Y MODERATE NOT DOSE NOT RECOVERED/ 20835 ⒆ ABSCESS RELATED CHANGED RESOLVED 5301- 4/F 90.0 144/12 Ẽ⟶ᨭ⅖ BRONCHITIS Yes No Y SEVERE NOT DOSE NOT RECOVERED/ 20943 mg RELATED CHANGED RESOLVED 90 mg 130 mg 1007- 2/F 90.0 103/6 ┤⭠࿘ᅖ⮋ PERIRECTAL Yes No Y MODERATE DOUBTFUL DOSE NOT RECOVERED/ SC IV 10108 mg ⒆ ABSCESS CHANGED RESOLVED 1007- 2/M 90.0 145/3 ᑠ⭠㛢ሰ PARTIAL SMALL No No Y MODERATE DOUBTFUL DOSE NOT RECOVERED/ ಶ 10137 mg BOWEL CHANGED RESOLVED ࠎ
OBSTRUCTION ࡢヨ 1007- 2/F 90.0 88/7 ᑠ⭠⊃✽ PARTIAL SMALL No No Y SEVERE DOUBTFUL DOSE NOT RECOVERED/
10164 mg BOWEL CHANGED RESOLVED 㦂
OBSTRUCTION ࡢࡲ SECONDARY TO ILEOCECAL AND ヨ DISTAL ILEUM ࡵ 㦂
) STRICTURE.
218
(83 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 Treatment group Study Randomized Mainte after Dose Study Day of at Week 0 nance Adjustme Agent AEa/ of this Treatm Induction Age nt/ Dose Durati maintenance ent treatment Subject (yrs)/ Study Prior on MedDRA Infec- Infusion Serious Relation to study Group group ID Sex Daya to AE (days) preferred term Verbatim Term tionb Reaction AE Severity Study Drug Action Taken Outcome 1007- 3/M 90.0 116/4 ⳦⾑ BACTEREMIA Yes No Y SEVERE POSSIBLE DOSE NOT RECOVERED/ 2.7.6 10176 mg CHANGED RESOLVED 1111- 4/F 90.0 303/7 㠀ᚰ⮚ᛶ⬚ CHEST No No Y MODERATE NOT DOSE NOT RECOVERED/ 10190 mg ③ PAIN(NON RELATED CHANGED RESOLVED CARDIAC) 1107- 2/F 0 mg 136/2 ࣂࣝࢺࣜࣥ BARTHOLIN No No Y MODERATE NOT DOSE NOT RECOVERED/ 10197 ᄞ⭘ CYST RELATED CHANGED RESOLVED 2/F 0 mg 313/4 Ⓨ⇕ FEVER No No Y MODERATE NOT DOSE NOT RECOVERED/ RELATED CHANGED RESOLVED 2/F 90.0 360/2 Ⓨ⇕ FEVER No No Y MODERATE DOUBTFUL DOSE NOT RECOVERED/ mg CHANGED RESOLVED 1111- 2/F 90.0 78/9 ࢡ࣮ࣟࣥ EXACERBATION No No Y SEVERE NOT DOSE NOT RECOVERED/ 10241 mg OF CROHNS RELATED CHANGED RESOLVED DISEASE 1069- 2/M 90.0 100/4 ࣝࢥ࣮ࣝ ALCOHOL No No Y SEVERE NOT DOSE NOT RECOVERED/ 10247 mg ୰ẘ INTOXICATION RELATED CHANGED RESOLVED 5608- 1/F 90.0 73/30 ⭠⟶⊃✽ BOWEL No No Y SEVERE NOT DRUG RECOVERED/ 10248 mg STRICTURE RELATED WITHDRAWN RESOLVED 1068- 4/M 0 mg 175/5 ᑠ⭠㛢ሰ SMALL BOWEL No No Y MODERATE NOT DOSE NOT RECOVERED/ 10399 OBSTRUCTION RELATED CHANGED RESOLVED 1057- 5/M 90.0 126/5 ᑠ⭠㛢ሰ PARTIAL SMALL No No Y SEVERE DOUBTFUL DOSE NOT RECOVERED/ 10407 mg BOWEL CHANGED RESOLVED OBSTRUCTION 5/M 90.0 254/4 ᑠ⭠㛢ሰ SMALL BOWEL No No Y MODERATE NOT DOSE NOT RECOVERED/ mg OBSTRUCTION RELATED CHANGED RESOLVED 5606- 2/M 90.0 178/3 ࢘ࣝࢫឤ VIRAL Yes No Y MODERATE POSSIBLE NOT RECOVERED/ 10411 mg ᰁ INFECTION APPLICABLE RESOLVED 5617- 4/F 90.0 65/153 ࡃࡶ⭷ୗฟ SUB No No Y SEVERE DOUBTFUL DRUG RECOVERED/ 10424 mg ⾑ ARACHNOID WITHDRAWN RESOLVED HAEMORRHAGE WITH SEQUELAE
1058- 6/M 90.0 336/19 ᚰ➽ EXACERBATION No No Y MODERATE DOUBTFUL DOSE NOT RECOVERED/ ಶ
10485 mg OF NON- CHANGED RESOLVED ࠎ
ISCHEMIC ࡢヨ CARDIOMYOPAT
HY 㦂 3404- 3/F 90.0 230/7 DEEP VEIN No No Y MODERATE DOUBTFUL DOSE NOT RECOVERED/
῝㒊㟼⬦⾑ ࡢࡲ 10500 mg ᰦ THROMBOSIS IN CHANGED RESOLVED THE LEFT LEG 3/F 0 mg 254/7 ⫼㒊③ WORSENING OF No No Y MODERATE DOUBTFUL DOSE NOT RECOVERED/ ヨ ࡵ BACK PAIN CHANGED RESOLVED 㦂 )
219
(84 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 Treatment group Study Randomized Mainte after Dose Study Day of at Week 0 nance Adjustme Agent AEa/ of this Treatm Induction Age nt/ Dose Durati maintenance ent treatment Subject (yrs)/ Study Prior on MedDRA Infec- Infusion Serious Relation to study Group group ID Sex Daya to AE (days) preferred term Verbatim Term tionb Reaction AE Severity Study Drug Action Taken Outcome 3/F 0 mg 256/5 ⭡㒊ᛌឤ ABDOMINAL No No Y MODERATE DOUBTFUL DOSE NOT RECOVERED/ 2.7.6 DISCOMFORT CHANGED RESOLVED 1015- 3/F 90.0 121/7 ࢡ࣮ࣟࣥ EXACERBATION No No Y SEVERE NOT DOSE NOT RECOVERED/ 10521 mg OF CROHN'S RELATED CHANGED RESOLVED DISEASE 2711- 5/F 90.0 122/4 ୖ⭎㦵㦵ᢡ COMMINUTED No No Y SEVERE NOT DOSE NOT RECOVERED/ 10523 mg LEFT PROXIMAL RELATED CHANGED RESOLVED HUMERUS FRACTURE 1036- 6/M 0 mg 300/6 ⭠⅖ LEFT SIDE No No Y SEVERE DOUBTFUL NOT RECOVERED/ 10699 COLITIS APPLICABLE RESOLVED WITH SEQUELAE 1009- 3/F 90.0 180/3 ࢡ࣮ࣟࣥ ACUTE CROHN'S No No Y SEVERE NOT NOT RECOVERED/ 10713 mg FLARE RELATED APPLICABLE RESOLVED 1001- 4/M 90.0 345/34 ኚᙧᛶ⬨᳝ WORSENING No No Y SEVERE NOT DOSE NOT RECOVERED/ 10732 mg CERVICAL AND RELATED CHANGED RESOLVED LUMBAR WITH SPONDYLOSIS SEQUELAE 1107- 5/F 90.0 81/12 ࢡ࣮ࣟࣥ CROHN'S FLARE No No Y SEVERE NOT DOSE NOT RECOVERED/ 10766 mg RELATED CHANGED RESOLVED 1107- 2/F 90.0 60/5 ⾑୰㟁ゎ㉁ ELECTROLYTES No No Y MODERATE NOT DOSE NOT RECOVERED/ 10769 mg ␗ᖖ ABNORMALITIE RELATED CHANGED RESOLVED S 4201- 2/M 90.0 108/15 ࢡ࣮ࣟࣥ WORSENING No No Y SEVERE NOT NOT RECOVERED/ 10814 mg 3 CROHN'S RELATED APPLICABLE RESOLVED DISEASE 4203- 2/F 0 mg 310/9 ⇕ᑕ HEATSTROKE No No Y MODERATE DOUBTFUL DOSE NOT RECOVERED/ 10819 CHANGED RESOLVED 4605- 2/M 90.0 59/64 ࢡ࣮ࣟࣥ WORSENING No No Y SEVERE NOT DOSE NOT RECOVERED/ 10842 mg CROHN'S RELATED CHANGED RESOLVED DISEASE WITH SEQUELAE ಶ 1051- 2/M 90.0 92/4 ᑠ⭠㛢ሰ SMALL BOWEL No No Y SEVERE NOT DOSE NOT RECOVERED/ ࠎ
10846 mg OBSTRUCTION RELATED CHANGED RESOLVED ࡢヨ 1009- 3/M 90.0 66/2 ⚄⤒᰿㞀ᐖ RIGHT C7 No No Y MODERATE NOT DOSE NOT RECOVERED/
10894 mg RADICULOPATH RELATED CHANGED RESOLVED 㦂
Y ࡢࡲ 1009- 4/F 90.0 77/7 ࠺ࡘ WORSENING No No Y MODERATE NOT DOSE NOT RECOVERED/ 10895 mg DEPRESSION RELATED CHANGED RESOLVED ヨ ࡵ 㦂 )
220
(85 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 Treatment group Study Randomized Mainte after Dose Study Day of at Week 0 nance Adjustme Agent AEa/ of this Treatm Induction Age nt/ Dose Durati maintenance ent treatment Subject (yrs)/ Study Prior on MedDRA Infec- Infusion Serious Relation to study Group group ID Sex Daya to AE (days) preferred term Verbatim Term tionb Reaction AE Severity Study Drug Action Taken Outcome 5601- 2/F 90.0 110/4 ࢡ࣮ࣟࣥ EXACERBATION No No Y MODERATE NOT DRUG RECOVERED/ 2.7.6 10905 mg OF CHROHN'S RELATED WITHDRAWN RESOLVED DISEASE 2712- 5/F 90.0 298/25 ᑠ⭠㛢ሰ SMALL BOWEL No No Y SEVERE DOUBTFUL DRUG RECOVERED/ 10910 mg OBSTRUCTION WITHDRAWN RESOLVED 5/F 90.0 317/6 ౽㔞ቑຍ INCREASED No No Y SEVERE NOT NOT RECOVERED/ mg ILEOSTOMY RELATED APPLICABLE RESOLVED OUTPUT 2206- 2/F 90.0 72/7 ࢡ࣮ࣟࣥ FLARE OF No No Y SEVERE NOT DRUG RECOVERED/ 11016 mg CROHN'S WITH RELATED WITHDRAWN RESOLVED MOUTH ULCERS 2/F 90.0 161/4 ᑠ⭠㛢ሰ PARTIAL SMALL No No Y SEVERE NOT NOT RECOVERED/ mg BOWEL RELATED APPLICABLE RESOLVED OBSRUCTION 3414- 2/M 90.0 108/6 ࢡ࣮ࣟࣥ ACUTE FLARE No No Y SEVERE NOT DOSE NOT RECOVERED/ 20202 mg OF CROHNS RELATED CHANGED RESOLVED DISEASE WITH SEQUELAE 1019- 3/M 90.0 92/11 ᑠ⭠㛢ሰ DISTAL SMALL No No Y SEVERE NOT DOSE NOT RECOVERED/ 20279 mg BOWEL RELATED CHANGED RESOLVED OBSTRUCTION 3/M 0 mg 211/6 ᑠ⭠㛢ሰ SMALL BOWEL No No Y MODERATE NOT DOSE NOT RECOVERED/ OBSTRUCTION RELATED CHANGED RESOLVED 1015- 3/F 0 mg 328/20 ⫵⅖ PNEUMONIA Yes No Y SEVERE NOT DOSE NOT RECOVERED/ 20305 RELATED CHANGED RESOLVED 2704- 2/F 90.0 240/14 ⭠⟶⊃✽ ILEOCOLIC No No Y SEVERE DOUBTFUL DRUG RECOVERED/ 20348 mg STRICTURE WITHDRAWN RESOLVED 2704- 4/F 90.0 186/6 ῝㒊㟼⬦⾑ DVT No No Y SEVERE DOUBTFUL DOSE NOT RECOVERED/ 20461 mg ᰦ CHANGED RESOLVED WITH SEQUELAE 4/F 90.0 241/6 ⬚㦵ᦆയ BONY TRAUMA No No Y SEVERE NOT DOSE NOT RECOVERED/ mg TO THE RELATED CHANGED RESOLVED ಶ STERNUM ࠎ
1014- 4/M 90.0 128/7 ᑠ⭠㛢ሰ PARTIAL SMALL No No Y SEVERE NOT DOSE NOT RECOVERED/ ࡢヨ 20487 mg BOWEL RELATED CHANGED RESOLVED
OBSTRUCTION 㦂
1068- 4/M 90.0 71/1 ኻ⚄ SYNCOPE No No Y MILD NOT DOSE NOT RECOVERED/ ࡢࡲ 20554 mg RELATED CHANGED RESOLVED 4/M 90.0 135/13 ABDOMINAL Yes No Y MODERATE NOT NOT RECOVERED/ ⭡㒊⮋⒆ ヨ mg 4 ABSCESS RELATED APPLICABLE RESOLVED ࡵ 㦂 )
221
(86 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 Treatment group Study Randomized Mainte after Dose Study Day of at Week 0 nance Adjustme Agent AEa/ of this Treatm Induction Age nt/ Dose Durati maintenance ent treatment Subject (yrs)/ Study Prior on MedDRA Infec- Infusion Serious Relation to study Group group ID Sex Daya to AE (days) preferred term Verbatim Term tionb Reaction AE Severity Study Drug Action Taken Outcome 4/M 90.0 248/21 ࢡ࣮ࣟࣥ WORSENING OF No No Y MODERATE NOT NOT RECOVERED/ 2.7.6 mg CROHN'S RELATED APPLICABLE RESOLVED DISEASE 1031- 4/F 0 mg 178/44 Ꮚᐑ⬺ PROLAPSED No No Y MODERATE NOT DOSE NOT RECOVERED/ 20623 UTERUS RELATED CHANGED RESOLVED 5608- 2/F 90.0 312/30 ࢡ࣮ࣟࣥ EXCACERBATIO No No Y SEVERE NOT DRUG RECOVERED/ 20690 mg N OF CROHNS RELATED WITHDRAWN RESOLVED 1048- 2/M 90.0 118/7 ࢡ࣮ࣟࣥ CROHN'S No No Y MILD DOUBTFUL DOSE NOT RECOVERED/ 20746 mg COLITIS CHANGED RESOLVED 5608- 1/F 90.0 71/83 ࢡ࣮ࣟࣥ WORSENING OF No No Y SEVERE NOT NOT RECOVERED/ 20753 mg CROHN'S RELATED APPLICABLE RESOLVED SYMPTOMS 1096- 5/F 90.0 85/29 ࢡ࣮ࣟࣥ CROHNS FLARE No No Y MODERATE NOT DOSE NOT RECOVERED/ 20803 mg RELATED CHANGED RESOLVED 3603- 2/M 0 mg 220/14 㛵⠇③ PHYSIOTHERAP No No Y MILD NOT DOSE NOT RECOVERED/ 20930 Y DUE TO JOINT RELATED CHANGED RESOLVED PAIN 3314- 3/F 90.0 85/10 ࢡ࣮ࣟࣥ FLARE UP OF No No Y SEVERE NOT DRUG RECOVERED/ 20944 mg CROHN'S RELATED WITHDRAWN RESOLVED DISEASE WITH SEQUELAE 6 mg/kg 1030- 1/F 90.0 108/13 ࢡ࣮ࣟࣥ CROHN'S No No Y MILD DOUBTFUL DOSE NOT RECOVERED/ IV 10016 mg 9 DISEASE CHANGED RESOLVED EXACERBATION 1/F 0 mg 246/4 ࢡ࣮ࣟࣥ ILEAL CROHN'S No No Y MODERATE NOT DOSE NOT RECOVERED/ DISEASE RELATED CHANGED RESOLVED 1009- 3/M 90.0 85/2 ࢡ࣮ࣟࣥ PERIANAL No No Y SEVERE NOT DOSE NOT RECOVERED/ 10084 mg CROHN'S RELATED CHANGED RESOLVED DISEASE 1005- 3/M 0 mg 266/23 ᗁぬ HALLUCINATIO No No Y MODERATE DOUBTFUL DOSE NOT RECOVERED/ 10186 NS CHANGED RESOLVED 3314- 2/F 0 mg 164/27 ࢡ࣮ࣟࣥ SEVERE FLARE No No Y SEVERE NOT DRUG RECOVERED/ 10284 UP OF CROHN'S RELATED WITHDRAWN RESOLVED ಶ DISEASE ࠎ
1009- 1/F 0 mg 156/4 ⫘㌾㦵⅖ INFLAMMATORY No No Y SEVERE NOT DOSE NOT RECOVERED/ ࡢヨ 10333 COSTOCHONDRI RELATED CHANGED RESOLVED
TIS 㦂
5608- 2/F 0 mg 150/7 ⭡③ ABDOMINAL No No Y SEVERE NOT DOSE NOT RECOVERED/ ࡢࡲ 10355 PAIN RELATED CHANGED RESOLVED 2/F 0 mg 276/18 NON-SPECIFIC No No Y SEVERE NOT DOSE NOT RECOVERED/ ⭡③ ヨ ABDOMINAL RELATED CHANGED RESOLVED ࡵ 㦂
) PAIN
222
(87 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 Treatment group Study Randomized Mainte after Dose Study Day of at Week 0 nance Adjustme Agent AEa/ of this Treatm Induction Age nt/ Dose Durati maintenance ent treatment Subject (yrs)/ Study Prior on MedDRA Infec- Infusion Serious Relation to study Group group ID Sex Daya to AE (days) preferred term Verbatim Term tionb Reaction AE Severity Study Drug Action Taken Outcome 1006- 4/M 90.0 343/14 ࿘ᮇᛶྤ CYCLIC No No Y SEVERE DOUBTFUL DOSE NOT RECOVERED/ 2.7.6 10390 mg ೃ⩌ VOMITTING CHANGED RESOLVED SYNDROME 3313- 2/F 90.0 221/8 ࢡ࣮ࣟࣥ CROHN'S No No Y SEVERE NOT NOT RECOVERED/ 10459 mg DISEASE RELATED APPLICABLE RESOLVED WORSENING 1102- 2/F 90.0 171/26 ࢡ࣮ࣟࣥ EXACERBATION No No Y SEVERE NOT NOT RECOVERED/ 10495 mg OF CROHN'S RELATED APPLICABLE RESOLVED DISEASE 3309- 4/F 90.0 69/437 ࢡ࣮ࣟࣥ WORSENING OF No No Y MODERATE NOT DOSE NOT RECOVERED/ 10526 mg CROHN'S RELATED CHANGED RESOLVED DISEASE 1031- 6/F 90.0 67/6 ་⒪ᶵჾ㛵 INFECTION OF Yes No Y MODERATE POSSIBLE DOSE NOT RECOVERED/ 10529 mg 㐃ឤᰁ CENTRAL CHANGED RESOLVED VENOUS CATHETER 6/F 90.0 79/5 ⭈ᒀ⣽⟶ቯ ACUTE No No Y MODERATE DOUBTFUL DOSE NOT RECOVERED/ mg Ṛ TUBULAR CHANGED RESOLVED NECROSIS 5614- 5/M 90.0 157/10 ୗ⑩ INCREASE No No Y MODERATE NOT DOSE NOT RECOVERED/ 10555 mg DIARRHOEA RELATED CHANGED RESOLVED 3425- 3/F 0 mg 160/31 ࢡ࣮ࣟࣥ WORSENING OF No No Y MODERATE NOT DRUG RECOVERED/ 10566 CROHNS RELATED WITHDRAWN RESOLVED DISEASE 2204- 2/F 90.0 107/15 ࢡ࣮ࣟࣥ EXACERBATION No No Y SEVERE DOUBTFUL DRUG RECOVERED/ 10689 mg OF CROHNS WITHDRAWN RESOLVED DISEASE 3401- 4/F 90.0 132/4 ⫶⭠⅖ ACUTE Yes No Y MODERATE NOT NOT RECOVERED/ 10797 mg GASTROENTERI RELATED APPLICABLE RESOLVED TIS 2716- 3/F 90.0 204/6 ࢡ࣮ࣟࣥ CROHN'S No No Y SEVERE NOT DOSE NOT RECOVERED/ 10897 mg DISEASE RELATED CHANGED RESOLVED EXACERBATION ಶ 3314- 1/F 90.0 101/18 ࢡ࣮ࣟࣥ WORSENING OF No No Y SEVERE NOT DRUG RECOVERED/ ࠎ
10908 mg 8 CROHN'S RELATED WITHDRAWN RESOLVED ࡢヨ DISEASE
5608- 4/F 90.0 207/3 ⫠㛛⮋⒆ ABSCESS (ANAL) Yes No Y SEVERE NOT NOT RECOVERED/ 㦂
10945 mg RELATED APPLICABLE RESOLVED ࡢࡲ 2712- 4/F 90.0 108/12 ᑠ⭠㛢ሰ SMALL BOWEL No No Y SEVERE NOT DRUG RECOVERED/ 10955 mg OBSTRUCTION RELATED WITHDRAWN RESOLVED ヨ 4305- 5/F 0 mg 283/14 ILEAL CROHN'S No No Y MODERATE DOUBTFUL DOSE NOT RECOVERED/ ࡵ ࢡ࣮ࣟࣥ 㦂
) 10959 DISEASE CHANGED RESOLVED
223
(88 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 Treatment group Study Randomized Mainte after Dose Study Day of at Week 0 nance Adjustme Agent AEa/ of this Treatm Induction Age nt/ Dose Durati maintenance ent treatment Subject (yrs)/ Study Prior on MedDRA Infec- Infusion Serious Relation to study Group group ID Sex Daya to AE (days) preferred term Verbatim Term tionb Reaction AE Severity Study Drug Action Taken Outcome 4111- 3/M 90.0 146/10 ᑠ⭠㛢ሰ ILEUM BOWEL No No Y SEVERE DOUBTFUL DOSE NOT RECOVERED/ 2.7.6 10983 mg OBSTRUCTION CHANGED RESOLVED 3/M 0 mg 214/2 ฎ⨨ࡼࡿ POST- No No Y SEVERE NOT DOSE NOT RECOVERED/ ⑊③ PROCEDURE RELATED CHANGED RESOLVED PAIN 2203- 4/M 90.0 64/169 ከⓎᛶ㛵⠇ POLY-ARTHRITIS No No Y SEVERE POSSIBLE DOSE NOT RECOVERED/ 11058 mg ⅖ CHANGED RESOLVED WITH SEQUELAE 4307- 3/M 90.0 133/16 ⭠㛢ሰ PARTIAL No No Y MODERATE NOT DOSE NOT RECOVERED/ 11071 mg COLONIC RELATED CHANGED RESOLVED OBSTRUCTION 2712- 5/F 90.0 78/37 ⫠㛛⮋⒆ PERI ANAL Yes No Y MODERATE DOUBTFUL DOSE NOT RECOVERED/ 11118 mg ABSCESS CHANGED RESOLVED 4202- 2/M 90.0 172/37 ࢡ࣮ࣟࣥ WORSENING OF No No Y MODERATE NOT DRUG RECOVERED/ 11150 mg CROHNS RELATED WITHDRAWN RESOLVED DISEASE 4706- 3/F 90.0 112/22 ࢡ࣮ࣟࣥ FLARE OF No No Y MODERATE NOT DRUG RECOVERED/ 20298 mg CROHN'S RELATED WITHDRAWN RESOLVED DISEASE 3417- 3/F 90.0 247/9 ࢡ࣮ࣟࣥ WORSENING OF No No Y SEVERE DOUBTFUL DRUG RECOVERED/ 20377 mg CROHN'S WITHDRAWN RESOLVED DISEASE 4212- 4/M 90.0 80/106 ࢡ࣮ࣟࣥ WORSENING OF No No Y MODERATE NOT DRUG RECOVERED/ 20536 mg CROHN'S RELATED WITHDRAWN RESOLVED DISEASE 4/M 90.0 133/9 ᩋ⾑ SEPSIS Yes No Y SEVERE POSSIBLE NOT RECOVERED/ mg APPLICABLE RESOLVED 4224- 2/F 90.0 293/3 ࢘ࣝࢫᛶ GASTROENTERI Yes No Y MODERATE DOUBTFUL DOSE NOT RECOVERED/ 20826 mg ⫶⭠⅖ TIS VIRAL CHANGED RESOLVED 1025- 5/F 90.0 86/3 㠀ᚰ⮚ᛶ⬚ NON CARDIAC No No Y MODERATE NOT DOSE NOT RECOVERED/ 20836 mg CHEST PAIN RELATED CHANGED RESOLVED
③ ಶ
1107- 3/M 0 mg 166/85 ఏᰁᛶ༢᰾ EBV HEPATITIS Yes No Y MODERATE POSSIBLE DRUG RECOVERED/ ࠎ 20939 INTERRUPTED RESOLVED ⫢⅖ ࡢヨ
a Relative to the date of first treatment in maintenance study. 㦂 b Infection as assessed by the investigator. ࡢࡲ Adverse events are coded using MedDRA 17.1. [LPMDASF24A.rtf] [CNTO1275\CRD3003\DBR_CSR\RE_PMDA\lpmdasf24a.sas] 20SEP2016, 21:43 ヨ ࡵ 㦂 )
224
(89 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 2) ᪥ᮏே㞟ᅋ ⾲ 2.7.6.4-20 㔜⠜࡞᭷ᐖ㇟ཬࡧ㦂⸆ྜ⌮ⓗ㛵㐃ᛶࡀ࠶ࡿ㔜⠜࡞᭷ᐖ㇟㸦㦂⸆ࢆᢞࡉࢀࡓ⿕᳨⪅㸧 Treatment group Study Randomized Mainten after Dose Study Day of 2.7.6 at Week 0 ance Age Adjustme Agent AEa/ of this Treatme Induction (yrs) nt/ Dose Durati MedDRA maintenance nt treatment Subje / Study Prior on preferred Infection Infusion Serious Relation to study Group group ct ID Sex Daya to AE (days) term Verbatim Term b Reaction AE Severity Study Drug Action Taken Outcome Yes 90 mg 6 mg/kg 4201- 3/F 90 mg SC 0 mg 241/13 ⭡⭷⅖ PERITONITIS Yes No Y SEVERE NOT DRUG RECOVERED/ SC IV 10360 q8w/133 3 RELATED WITHDRAWN RESOLVED q12w 3/F 90 mg SC 0 mg 300/26 ⫹ᄞ⅖ CHOLECYSTITIS Yes No Y SEVERE DOUBTFUL NOT RECOVERED/ q8w/133 APPLICABLE RESOLVED 4211- 7/F 0 mg 120/27 ᆶ⅖ APPENDICITIS No No Y SEVERE DOUBTFUL DOSE NOT RECOVERED/ 10438 CHANGED RESOLVED 7/F 0 mg ⳦⾑ BACTEREMIA Yes No Y SEVERE DOUBTFUL DOSE NOT RECOVERED/ CHANGED RESOLVED 4216- 1/F 90.0 80/On ⫠㛛⮋⒆ PERIANAL Yes No Y SEVERE NOT DRUG NOT 10754 mg going ABSCESS RELATED WITHDRAWN RECOVERED/ NOT RESOLVED 90 mg 130 mg 4213- 3/ 90 mg SC 0 mg 155/98 ࢡ࣮ࣟࣥ WORSENING OF No No Y SEVERE NOT DRUG RECOVERED/ SC q8w IV 20895 M q8w/58 CROHN'S RELATED WITHDRAWN RESOLVED DISEASE 6 mg/kg 4212- 3/ /57 90.0 104/9 ⭠㛢ሰ COLONIC No No Y MODERATE DOUBTFUL DOSE NOT RECOVERED/ IV 10505 M mg OBSTRUCTION CHANGED RESOLVED No 130 mg Placebo 4209- 4/F 0 mg 285/42 ࢡ࣮ࣟࣥ CROHN'S No No Y SEVERE NOT DRUG RECOVERED/ IV IV 10427 DISEASE RELATED WITHDRAWN RESOLVED AGGRAVATED 4216- 2/ 0 mg 196/O ࢡ࣮ࣟࣥ DETERIORATIO No No Y SEVERE NOT DRUG NOT 10627 M ngoing N OF CROHN'S RELATED WITHDRAWN RECOVERED/ DISEASE NOT RESOLVED 4201- 6/F 0 mg 371/2 ⫠㛛⮋⒆ WORSENING OF Yes No Y MODERATE NOT DOSE NOT RECOVERED/ 10643 PERIANAL RELATED CHANGED RESOLVED
ABSCESS ಶ
4213- 4/ 129.6 149/56 ࢡ࣮ࣟࣥ WORSENING OF No No Y SEVERE NOT NOT RECOVERED/ ࠎ 11139 M mg CROHNS RELATED APPLICABLE RESOLVED ࡢヨ DISEASE 4201- 2/F 129.6 146/23 ࢡ࣮ࣟࣥ WORSENING OF No No Y SEVERE NOT NOT RECOVERED/ 11141 mg CROHN'S RELATED APPLICABLE RESOLVED 㦂 DISEASE ࡢࡲ 4217- 4/F 0 mg 168/8 Ꮚᐑᖹ➽ MYOMA UTERI No No Y SEVERE NOT DOSE NOT RECOVERED/ 20711 ⭘ RELATED CHANGED RESOLVED ヨ ࡵ 㦂 )
225
(90 ࢘ࢫࢸ࢟ࢾ࣐ࣈ CNTO1275CRD3003 Treatment group Study Randomized Mainten after Dose Study Day of at Week 0 ance Age Adjustme Agent AEa/ of this Treatme Induction (yrs) nt/ Dose Durati MedDRA maintenance nt treatment Subje / Study Prior on preferred Infection Infusion Serious Relation to study Group group ct ID Sex Daya to AE (days) term Verbatim Term b Reaction AE Severity Study Drug Action Taken Outcome
4209- 3/ 129.6 127/69 ࢡ࣮ࣟࣥ CROHN'S No No Y MODERATE DOUBTFUL NOT RECOVERED/ 2.7.6 20834 M mg DISEASE APPLICABLE RESOLVED AGGRAVATED 90 mg 130 mg 4201- 2/ 90.0 108/15 ࢡ࣮ࣟࣥ WORSENING No No Y SEVERE NOT NOT RECOVERED/ SC IV 10814 M mg 3 CROHN'S RELATED APPLICABLE RESOLVED DISEASE 4203- 2/F 0 mg 310/9 ⇕ᑕ HEATSTROKE No No Y MODERATE DOUBTFUL DOSE NOT RECOVERED/ 10819 CHANGED RESOLVED 6 mg/kg 4202- 2/ 90.0 172/37 ࢡ࣮ࣟࣥ WORSENING OF No No Y MODERATE NOT DRUG RECOVERED/ IV 11150 M mg CROHNS RELATED WITHDRAWN RESOLVED DISEASE 4212- 4/ 90.0 80/106 ࢡ࣮ࣟࣥ WORSENING OF No No Y MODERATE NOT DRUG RECOVERED/ 20536 M mg CROHN'S RELATED WITHDRAWN RESOLVED DISEASE 4/ 90.0 133/9 ᩋ⾑ SEPSIS Yes No Y SEVERE POSSIBLE NOT RECOVERED/ M mg APPLICABLE RESOLVED 4224- 2/F 90.0 293/3 ࢘ࣝࢫᛶ GASTROENTERI Yes No Y MODERATE DOUBTFUL DOSE NOT RECOVERED/ 20826 mg ⫶⭠⅖ TIS VIRAL CHANGED RESOLVED
a Relative to the date of first treatment in maintenance study. b Infection as assessed by the investigator. Adverse events are coded using MedDRA 17.1. [LPMDASF24B.rtf] [CNTO1275\CRD3003\DBR_CSR\RE_PMDA\lpmdasf24b.sas] 20SEP2016, 21:43
ಶ ࠎ ࡢヨ 㦂 ࡢࡲ ヨ ࡵ 㦂 )
226 ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
2.7.6.4.3.1 Narratives SAE㸦᪥ᮏேⓎ⌧ࡋࡓ㇟ࡢࡳ㸧㸪㦂⸆ྜ⌮ⓗ㛵㐃ᛶࡀ࠶ࡿ SAE ཬࡧ㔜⠜࡞ឤᰁ ࡢヲ⣽ࢆ⿕㦂⪅ࡈ௨ୗ♧ࡍࠋ
Table of Narratives Subject Death Japanese Related SAE Serious Number infection 4201-10360 X X 4201-10643 X X 4201-10814 X 4201-11141 X 4202-11150 X 4203-10819 X 4209-10427 X 4209-20834 X 4211-10438 X X 4212-10505 X 4212-20536 X X X 4213-11139 X 4213-20895 X 4216-10627 X 4216-10754 X X 4217-20711 X 4224-20826 X X 1007-10176 X X 1007-20955 X X 1013-11005 X 1015-10811 X X 1016-21010 X X 1031-10529 X X 1039-10681 X X 1043-10979 X X 1107-20939 X X 2203-11058 X 2204-20144 X 2606-20878 X X 2711-10966 X X 3314-10280 X 3410-10564 X 4603-10805 X 5606-10411 X X 5609-10365 X X 1001-11034 X 1007-10108 X 1007-10134 X 1015-10023 X 1015-20305 X 1068-20554 X 1080-10452 X
22 7 (91) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
Subject Death Japanese Related SAE Serious Number infection 1096-10651 X 2301-10432 X 2709-10296 X 2712-11118 X 3401-10550 X 3401-10797 X 3409-20602 X 3414-20406 X 3425-20835 X 3610-20397 X 4602-10902 X 5301-20943 X 5307-20565 X 5608-10945 X 5609-10637 X
(1) Subject CNTO1275CRD3003-4201-10360
1) Reason for narrative selection SAE Discontinuation of study agent due to AE Event of interest: Serious infection
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome (Study day I/M) 2013-03-15 ⭡⭷⅖ Y SEVERE/ Y/ DRUG WITHDRAWN/ 2013-07-25 (241/184) (PERITONITIS) NOT RELATED Y RECOVERED/RESOLVED (373/316) 2013-05-13 ⫹ᄞ⅖ Y SEVERE/ Y/ NOT APPLICABLE/ 2013-06-07 (300/243) (CHOLECYSTITIS) DOUBTFUL Y RECOVERED/RESOLVED (325/268)
3) Baseline Demographic Information Age (years): 3 Sex: Female Weight (kg): 63.2 Race: Asian Date of birth: Height (cm): 167.2
4) Induction Treatment Group Induction study: CNTO1275CRD3001 Randomized Treatment Group: Ustekinumab Approximating 6 mg/kg IV Actual Treatment Group: Ustekinumab Approximating 6 mg/kg IV
5) Maintenance Treatment Group Assigned Treatment Group: Randomized subject/Responder to ustekinumab IV induction dosing/ustekinumab 90 mg SC q12w
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2012-07-18 1 Ustekinumab 389.7 mg WEEK 0 MAINTENANCE 2012-09-13 58 Ustekinumab 90 mg WEEK 8 MAINTENANCE 2012-11-07 113 Placebo 0 mg WEEK 12 MAINTENANCE 2012-12-05 141 Ustekinumab 90 mg
22 8 (92) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
Visit Start Date Study Day Actual Treatment Dose WEEK 16 MAINTENANCE 2013-01-04 171 Placebo 0 mg WEEK 20 MAINTENANCE 2013-01-23 190 Ustekinumab 90 mg WEEK 24 MAINTENANCE 2013-02-20 218 Placebo 0 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: Y Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: -
8) Induction Baseline Crohn's Disease History Date of diagnosis: 01JAN1989 Disease duration: 23.55 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪⫠㛛࿘ᅖ
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: PREVIOUS HISTORY Sinus tracts/perforation: NEVER Fistula: NEVER Stricture complications of (CD): CURRENTLY PRESENT
10) Concomitant Crohn's Disease-Related Surgeries Surgery Date Result of lack of efficacy? ࢻࣞࢼ࣮ࢪ-⤒⓶ษ㛤ཬࡧࢻࣞࢼ࣮ࢪ 2013-03-17 Y ேᕤ⫠㛛ࡢタ⨨ 2013-03-17 Y
11) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 0 PREDNISOLONE 10 mg 10 mg WEEK 8 MAINTENANCE PREDNISOLONE 7.5 mg 7.5 mg WEEK 12 MAINTENANCE PREDNISOLONE 5 mg 5 mg WEEK 16 MAINTENANCE PREDNISOLONE 2.5 mg 2.5 mg SAFETY FOLLOW-UP MAINTENANCE PREDNISOLONE 2.5 mg 2.5 mg SAFETY FOLLOW-UP MAINTENANCE HYDROCORTISONE 200 mg - SAFETY FOLLOW-UP MAINTENANCE HYDROCORTISONE 300 mg - SAFETY FOLLOW-UP MAINTENANCE PREDNISOLONE 0 mg 0 mg SAFETY FOLLOW-UP MAINTENANCE HYDROCORTISONE 0 mg - SAFETY FOLLOW-UP MAINTENANCE HYDROCORTISONE 0 mg - SAFETY FOLLOW-UP MAINTENANCE HYDROCORTISONE 0 mg - SAFETY FOLLOW-UP MAINTENANCE HYDROCORTISONE 0 mg - SAFETY FOLLOW-UP MAINTENANCE HYDROCORTISONE 0 mg - SAFETY FOLLOW-UP MAINTENANCE METHYLPREDNISOLONE 0 mg - SAFETY FOLLOW-UP MAINTENANCE PREDNISOLONE 2.5 mg 2.5 mg SAFETY FOLLOW-UP MAINTENANCE HYDROCORTISONE 150 mg - SAFETY FOLLOW-UP MAINTENANCE HYDROCORTISONE 75 mg - SAFETY FOLLOW-UP MAINTENANCE HYDROCORTISONE 0 mg - SAFETY FOLLOW-UP MAINTENANCE HYDROCORTISONE 0 mg - SAFETY FOLLOW-UP MAINTENANCE PREDNISOLONE 0 mg 0 mg SAFETY FOLLOW-UP MAINTENANCE HYDROCORTISONE 200 mg - SAFETY FOLLOW-UP MAINTENANCE HYDROCORTISONE 100 mg - SAFETY FOLLOW-UP MAINTENANCE HYDROCORTISONE 200 mg - SAFETY FOLLOW-UP MAINTENANCE HYDROCORTISONE 100 mg - SAFETY FOLLOW-UP MAINTENANCE HYDROCORTISONE 200 mg -
22 9 (93) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
Visit Drug Dose Prednisone equivalent SAFETY FOLLOW-UP MAINTENANCE METHYLPREDNISOLONE 250 mg -
12) Narrative Text ⿕㦂⪅ࡣ 3 ṓࡢ᪥ᮏேዪᛶ࡛㸪2012 ᖺ 7 ᭶ 18 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏࢆ㟼⬦ෆᢞࡉ ࢀࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏ 90 mg ࢆ q12w ࡛⓶ୗᢞࡍࡿ⩌ࣛࣥࢲ࣒ࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪⭜③㸪᰾㸪 ࣅࢱ࣑ࣥ B ⩌Ḟஈ㸪㐣㛗㐣ከつ๎᭶⤒㸪ᑠ⭠㛢ሰ㸦2007 ᖺ㸧㸪ᅇ⭠ᮎ➃ษ㝖㸦2007 ᖺ㸧ཬࡧ ⫹▼㸦2007 ᖺ㸧࡛࠶ࡗࡓࠋ SAE/Discontinuation of study agent due to AE/Serious infection㸸⭡⭷⅖㸦Day 241㸧 SAE/Serious infection㸸⫹ᄞ⅖㸦Day 300㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2013 ᖺ 3 ᭶ 15 ᪥㧗ᗘࡢୗ⭡㒊③ཬࡧⓎ⇕㸦య 38°C㸧ࡀࡳࡽ ࢀ㸪2013 ᖺ 3 ᭶ 17 ᪥ධ㝔ࡋࡓࠋࢥࣥࣆ࣮ࣗࢱ᩿ᒙᙳ㸦CT㸧ࢫ࢟ࣕࣥ㸦᪥᫂㸧࡛ࡣ㸪S ≧⤖⭠࿘㎶ᙉᗘࡢ⅖ཬࡧ⭠⟶✸Ꮝࡢྍ⬟ᛶࡀㄆࡵࡽࢀࡓࠋᮏ㇟ࡼࡾ㸪㦂⸆ࡢᢞࡀ୰ Ṇࡉࢀࡓࠋྠ᪥ࡢ⮫ᗋ᳨ᰝ್ࡣ㸪C ᛂᛶࡓࢇⓑ㸦CRP㸧⃰ᗘ 21.84 mg/dL㹙ṇᖖ⠊ᅖ㸦NR㸧0- 0.3 mg/dL㹛࡛࠶ࡗࡓࠋୗ⭡㒊③ࡣ࣌ࣥࢱࢰࢩࣥࡀᢞࡉࢀࡓࠋ⿕㦂⪅ࡣ 2013 ᖺ 3 ᭶ 17 ᪥㸪 ษ㝖⾡ཬࡧࢫࢺ࣮࣐㐀タ⾡ࢆཷࡅࡓࠋ┤⭠⒦ཬࡧ㦵┙㒊ࡢ⅖㉳ᅉࡍࡿ㧗ᗘࡢ⒵╔ࡢࡓࡵ㸪ษ 㝖⾡ࡣᅔ㞴ࢆᴟࡵࡓࠋ2013 ᖺ 3 ᭶ 22 ᪥㸪ࢲࢢࣛࢫ❐ࢻࣞࢼ࣮ࢪࢆᐇࡋࡓࠋ2013 ᖺ 3 ᭶ 27 ᪥ ⿕㦂⪅ࡣᾘჾෆ⛉Ჷ⛣㏦ࡉࢀࡓࠋᢠ⏕≀㉁㸪ࣥࣇࣜ࢟ࢩ࣐ࣈཬࡧ୍◪㓟ࢯࢯࣝࣅࢻ ࡼࡿ⒪ࡀᐇࡉࢀࡓࠋ⭡③ࡀᝏࡋ㸪࣌ࣥࢱࢰࢩࣥࡼࡾ⑊③⟶⌮ࡉࢀࡓࠋ2013 ᖺ 4 ᭶ 17 ᪥ ࡢ CT ࢫ࡛࢟ࣕࣥ㸪⫹▼ࡀࡳࡽࢀࡓࠋ2013 ᖺ 4 ᭶ 24 ᪥ࡢ⭠ෆど㙾᳨ᰝ࡛ࡣ㸪⊃✽ࡀࡳࡽࢀࡓ ࡀ᫂ࡽ࡞⒦Ꮝࡣ࡞ࡗࡓࠋ2013 ᖺ 5 ᭶ 7 ᪥ࡢ⮫ᗋ᳨ᰝ್ࡣ㸪ࣝ࢝ࣜ࣍ࢫࣇࢱ࣮ࢮ 475 IU/L 㸦NR 104-338 IU/L㸧㸪ࣛࢽ࣑ࣥࣀࢺࣛࣥࢫࣇ࢙࣮ࣛࢮ 130 IU/L㸦NR<30 IU/L㸧㸪ࢫࣃࣛ ࢠࣥ㓟࣑ࣀࢺࣛࣥࢫࣇ࢙࣮ࣛࢮ 79 IU/L㸦NR <30 IU/L㸧㸪┤᥋ࣅࣜࣝࣅࣥ 0.7 mg/dL㸦NR 0.0- 0.3 mg/dL㸧㸪⥲ࣅࣜࣝࣅࣥ 1.4 mg/dL㸦NR 0.2-1.2 mg/dL㸧㸪CRP ⃰ᗘ 3.51 mg/dL㸦NR 0.00- 0.30 mg/dL㸧࡛࠶ࡗࡓࠋ2013 ᖺ 5 ᭶ 13 ᪥Ⓨ⇕㸦37°C㸧ࡀ࠶ࡾ㸪CRP ⃰ᗘࡣ 3.51 mg/dL ࡛㸪ᚰ ❐㒊③ཬࡧྑᏘ⫘㒊③ࡀㄆࡵࡽࢀࡓࠋ2013 ᖺ 5 ᭶ 13 ᪥ࡢ⭡㒊㉸㡢Ἴ᳨ᰝ࡛ࡣ㸪⫹ᄞ」ᩘࡢ⫹ ▼㸦᭱ 15 mm㸧ࢆక࠺⤖▼ᛶ⫹ᄞ⅖ཬࡧ࿘ᅖ⬡⫫ࡢ࢚ࢥ࣮ࣞ࣋ࣝቑࢆక࠺⫹ᄞቨࡢ⫧ཌࡀࡳ ࡽࢀ㸪៏ᛶ⫹ᄞ⅖ࡀ♧၀ࡉࢀࡓࠋ⿕㦂⪅ࡣ 2013 ᖺ 5 ᭶ 30 ᪥⫹ᄞษ㝖⾡ࢆཷࡅࡓࠋ⌮⤌⧊Ꮫ ⓗᡤぢ࡛ࡣ㸪ࡧࡽࢇ-⏕ᛶኚ㸦erosion-regeneration change㸧ࢆక࠺⢓⭷ࡢⴎ⦰㸪⧄⥔ཬࡧᾋ ⭘ࡼࡿ⫧ཌ㸪ࣟ࢟ࢱࣥࢫ࣮࣭࢟ࢩࣙࣇὝ㐣ᙧᡂཬࡧ⭢➽୪ࡧ㒊ศⓗ࡞⅖ࡀࡳࡽࢀࡓࠋ ࡇࢀࡽࡼࡾ㸪⫹▼㉳ᅉࡍࡿ⫹ᄞ⅖ࡀ♧၀ࡉࢀࡓࠋᝏᛶ⭘⒆ࡢᡤぢࡣ࡞ࡗࡓࠋ⿕㦂⪅ࡣ࣌ ࣥࢱࢰࢩࣥࡼࡿ⒪ࢆཷࡅࡓࠋ2013 ᖺ 6 ᭶ 19 ᪥Ⓨ⇕ࡀⓎ⌧ࡋࡓࠋ୰ᚰ㟼⬦࢝ࢸ࣮ࢸࣝࡀᢤ ཤࡉࢀ㸪2013 ᖺ 6 ᭶ 20 ᪥ᤄ⟶ࡉࢀࡓࠋᢠ⏕≀㉁㸪ࢫࢸࣟࢻ㸪㙠③ཬࡧᨭᣢ⒪ἲࡼࡿ ⒪ࡀᐇࡉࢀࡓࠋ2013 ᖺ 6 ᭶ 28 ᪥㸪⬺ฟࡋࡓࢫࢺ࣮࣐ࢆᡭ࡛ඖᡠࡋࡓࠋ2013 ᖺ 7 ᭶ 23 ᪥ 㸪୰ᚰ㟼⬦࢝ࢸ࣮ࢸࣝࡣᢤཤࡉࢀࡓࠋ2013 ᖺ 7 ᭶ 24 ᪥㸪ࣥࣇࣜ࢟ࢩ࣐ࣈࡢᢞࡀ୰Ṇࡉࢀ㸪 ࢲ࣒࣐ࣜࣈࡀᢞࡉࢀࡓࠋ⿕㦂⪅ࡣ㸪2013 ᖺ 7 ᭶ 25 ᪥㏥㝔ࡋࡓࠋ
23 0 (94) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
13) Other Adverse Events Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2012-08-08 ㈋⾑ MILD/ N/ DOSE NOT CHANGED/ 2012-11-07 (22/.) (ANEMIA) POSSIBLE NA RECOVERED/RESOLVED (113/.) 2012-09-13 㐣㛗㐣ከつ๎᭶⤒ MILD/ N/ DOSE NOT CHANGED/ 2012-10-17 (58/.) (MENOMETRORRHAGIA) NOT NA RECOVERED/RESOLVED (92/.) RELATED 2013-01-05 ༸ᕢⰋᛶ⭘⒆ MILD/ N/ DOSE NOT CHANGED/ Ongoing (172/115) (BENIGN OVARIAN TUMOR) NOT NA NOT RECOVERED/NOT - RELATED RESOLVED 2013-03-15 ⤖⭠⒦ MODERATE/ N/ NOT APPLICABLE/ 2013-04-24 (241/184) (SIGMOID COLON FISTULA) NOT NA RECOVERED/RESOLVED (281/224) RELATED 2013-06-12 㛵⠇③ MILD/ N/ NOT APPLICABLE/ 2013-06-17 (330/273) (GONALGIA) NOT NA RECOVERED/RESOLVED (335/278) RELATED 2013-06-18 ་⒪ᶵჾ㛵㐃ឤᰁ MILD/ Y/ NOT APPLICABLE/ 2013-06-22 (336/279) (INFECTION OF CV NOT Y RECOVERED/RESOLVED (340/283) CATHETER) RELATED
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route FERROUS SULFATE 2012-08-13 2012-12-05 ORAL DIENOGEST 2013-01-23 2013-03-17 ORAL SODIUM BICARBONATE 2013-03-17 2013-03-17 INTRAVENOUS DRIP SUGAMMADEX SODIUM 2013-03-17 2013-03-17 INTRAVENOUS DROPERIDOL 2013-03-17 2013-03-17 INTRAVENOUS ROCURONIUM BROMIDE 2013-03-17 2013-03-17 INTRAVENOUS FAMOTIDINE 2013-03-17 2013-03-17 INTRAVENOUS FENTANYL 2013-03-17 2013-03-17 INTRAVENOUS FENTANYL 2013-03-17 2013-03-22 OTHER OMEPRAZOLE 2013-03-17 2013-03-27 INTRAVENOUS PETHIDINE HYDROCHLORIDE 2013-03-17 2013-03-17 INTRAVENOUS LEVOBUPIVACAINE HYDROCHLORIDE 2013-03-17 2013-03-22 OTHER PROPOFOL 2013-03-17 2013-03-17 INTRAVENOUS FLURBIPROFEN AXETIL 2013-03-17 2013-03-29 INTRAVENOUS SEVOFLURANE 2013-03-17 2013-03-17 RESPIRATORY (INHALATION) DEXTROSE AND SODIUM CHLORIDE INJECTION 2013-03-17 2013-03-18 INTRAVENOUS DRIP CARBOHYDRATES NOS W/POTASSIUM CHLORIDE/SODIUM 2013-03-17 2013-03-18 INTRAVENOUS DRIP PENTAZOCINE 2013-03-17 2013-03-17 INTRAMUSCULAR PRIMAXIN 2013-03-17 2013-03-23 INTRAVENOUS DRIP REMIFENTANIL HYDROCHLORIDE 2013-03-17 2013-03-17 INTRAVENOUS LIDOCAINE 2013-03-17 2013-03-17 OTHER XYLOCAINE-EPINEPHRINE 2013-03-17 2013-03-17 OTHER XYLOCAINE-EPINEPHRINE 2013-03-17 2013-03-17 OTHER AMINO ACIDS NOS W/ELECTROLYTES NOS/GLUCOSE/TH 2013-03-18 2013-03-22 INTRAVENOUS DRIP ALBUMIN HUMAN 2013-03-18 2013-03-19 INTRAVENOUS DRIP INSULIN HUMAN 2013-03-18 2013-03-18 SUBCUTANEOUS SODIUM CHLORIDE 2013-03-18 2013-03-19 INTRAVENOUS DRIP DIENOGEST 2013-03-19 - ORAL BUPIVACAINE 2013-03-20 2013-03-20 OTHER AMINO ACIDS NOS W/CARBOHYDRATES NOS/07403701/ 2013-03-22 2013-05-29 INTRAVENOUS DRIP PENTAZOCINE 2013-03-22 2013-03-31 INTRAMUSCULAR INSULIN HUMAN 2013-03-23 2013-03-23 SUBCUTANEOUS SACCHARATED IRON OXIDE 2013-03-29 2013-04-08 INTRAVENOUS CELECOXIB 2013-03-31 2013-05-01 ORAL PENTAZOCINE 2013-03-31 2013-04-09 INTRAVENOUS
23 1 (95) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
Preferred Term Start Date End Date Route MEROPENEM 2013-04-08 2013-04-13 INTRAVENOUS DRIP PENTAZOCINE 2013-04-15 2013-04-15 INTRAVENOUS FLURBIPROFEN AXETIL 2013-04-17 2013-04-18 INTRAVENOUS GLYCINE MAX SEED OIL 2013-04-22 2013-04-29 INTRAVENOUS DRIP HYOSCINE BUTYLBROMIDE 2013-04-24 2013-04-24 INTRAVENOUS DIAZEPAM 2013-04-24 2013-04-24 INTRAVENOUS PETHIDINE HYDROCHLORIDE 2013-04-24 2013-04-24 INTRAVENOUS PENTAZOCINE 2013-04-24 2013-05-28 INTRAVENOUS FLURBIPROFEN AXETIL 2013-04-29 2013-05-12 INTRAVENOUS HYOSCINE BUTYLBROMIDE 2013-05-01 2013-05-01 INTRAVENOUS DIMETICONE 2013-05-01 2013-05-01 ORAL DIAZEPAM 2013-05-01 2013-05-01 INTRAVENOUS REBAMIPIDE 2013-05-01 - ORAL PRONASE 2013-05-01 2013-05-01 ORAL SODIUM BICARBONATE 2013-05-01 2013-05-01 ORAL LIDOCAINE 2013-05-01 2013-05-01 INTRAVENOUS LIDOCAINE HYDROCHLORIDE 2013-05-01 2013-05-01 ORAL PANTHENOL 2013-05-03 2013-05-07 INTRAVENOUS DRIP CAMOSTAT 2013-05-08 - ORAL PANTETHINE 2013-05-08 2013-05-14 ORAL AMINO ACIDS NOS W/ELECTROLYTES NOS/GLUCOSE/TH 2013-05-10 2013-05-10 INTRAVENOUS DRIP AMINO ACIDS NOS W/ELECTROLYTES NOS/GLUCOSE/TH 2013-05-13 2013-05-15 INTRAVENOUS DRIP SULPERAZON 2013-05-13 2013-05-28 INTRAVENOUS DRIP PENTAZOCINE 2013-05-28 2013-06-07 INTRAMUSCULAR SODIUM BICARBONATE 2013-05-30 2013-05-30 INTRAVENOUS DRIP SUGAMMADEX SODIUM 2013-05-30 2013-05-30 INTRAVENOUS CEFMETAZOLE SODIUM 2013-05-30 2013-06-01 INTRAVENOUS DRIP DROPERIDOL 2013-05-30 2013-05-30 INTRAVENOUS ROCURONIUM BROMIDE 2013-05-30 2013-05-30 INTRAVENOUS FENTANYL 2013-05-30 2013-05-30 INTRAVENOUS FENTANYL 2013-05-30 2013-06-03 OTHER BUPIVACAINE HYDROCHLORIDE 2013-05-30 2013-06-01 OTHER PLAS AMINO 2013-05-30 2013-05-30 INTRAVENOUS DRIP LEVOBUPIVACAINE HYDROCHLORIDE 2013-05-30 2013-06-03 OTHER PROPOFOL 2013-05-30 2013-05-30 INTRAVENOUS FLURBIPROFEN AXETIL 2013-05-30 2013-06-01 INTRAVENOUS SEVOFLURANE 2013-05-30 2013-05-30 RESPIRATORY (INHALATION) DEXTROSE AND SODIUM CHLORIDE INJECTION 2013-05-30 2013-05-30 INTRAVENOUS DRIP CARBOHYDRATES NOS W/POTASSIUM CHLORIDE/SODIUM 2013-05-30 2013-05-31 INTRAVENOUS DRIP REMIFENTANIL HYDROCHLORIDE 2013-05-30 2013-05-30 INTRAVENOUS XYLOCAINE-EPINEPHRINE 2013-05-30 2013-05-30 OTHER LIDOCAINE 2013-05-30 2013-05-30 OTHER XYLOCAINE-EPINEPHRINE 2013-05-30 2013-05-30 OTHER AMINO ACIDS NOS W/ELECTROLYTES NOS/GLUCOSE/TH 2013-05-31 2013-05-31 INTRAVENOUS DRIP AMINO ACIDS NOS W/CARBOHYDRATES NOS/07403701/ 2013-05-31 2013-06-24 INTRAVENOUS DRIP PENTAZOCINE 2013-06-07 - INTRAVENOUS FLURBIPROFEN AXETIL 2013-06-18 2013-06-19 INTRAVENOUS SULPERAZON 2013-06-19 2013-06-21 INTRAVENOUS DRIP CARBOHYDRATES NOS W/POTASSIUM CHLORIDE/SODIUM 2013-06-19 2013-06-19 INTRAVENOUS DRIP FAMOTIDINE 2013-06-22 - ORAL BEPOTASTINE BESILATE 2013-06-22 - ORAL AMINO ACIDS NOS W/ELECTROLYTES NOS/GLUCOSE/TH 2013-06-25 - INTRAVENOUS DRIP
23 2 (96) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
(2) Subject CNTO1275CRD3003-4201-10643
1) Reason for narrative selection SAE Event of interest: Serious infection
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome I/M) 2013-09-24 ⫠㛛⮋⒆ Y MODERATE/ Y/ DOSE NOT CHANGED/ 2013-09-25 (371/317) (WORSENING OF PERIANAL NOT Y RECOVERED/RESOLVED (372/318) ABSCESS) RELATED
3) Baseline Demographic Information Age (years): 6 Sex: Female Weight (kg): 47.4 Race: Asian Date of birth: Height (cm): 162.2
4) Induction Treatment Group Induction study: CNTO1275CRD3001 Randomized Treatment Group: Placebo IV Actual Treatment Group: Placebo IV
5) Maintenance Treatment Group Assigned Treatment Group: Non-randomized subject/Non-responder to placebo IV induction dosing and received ustekinumab in maintenance
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2012-09-19 1 Placebo 0 mg WEEK 0 MAINTENANCE 2012-11-12 55 Placebo 0 mg WEEK 0 MAINTENANCE 2012-11-12 55 Ustekinumab 129.6 mg WEEK 8 MAINTENANCE 2013-01-09 113 Ustekinumab 90 mg WEEK 12 MAINTENANCE 2013-02-07 142 Placebo 0 mg WEEK 16 MAINTENANCE 2013-03-07 170 Placebo 0 mg WEEK 20 MAINTENANCE 2013-04-04 198 Ustekinumab 90 mg WEEK 24 MAINTENANCE 2013-05-02 226 Placebo 0 mg WEEK 28 MAINTENANCE 2013-05-30 254 Placebo 0 mg WEEK 32 MAINTENANCE 2013-06-27 282 Ustekinumab 90 mg WEEK 36 MAINTENANCE 2013-07-24 309 Placebo 0 mg WEEK 40 MAINTENANCE 2013-08-22 338 Placebo 0 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: N Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: Y
8) Induction Baseline Crohn's Disease History Date of diagnosis: 05AUG1999 Disease duration: 13.13 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪⫠㛛࿘ᅖ㸪ᑠ⭠㏆㸭⫶㸭㣗㐨
23 3 (97) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: CURRENTLY PRESENT Stricture complications of (CD): CURRENTLY PRESENT
10) Concomitant Crohn's Disease-Related Surgeries Surgery Date Result of lack of efficacy? ࢻࣞࢼ࣮ࢪ-ࢩ࣮ࢺࣥ␃⨨ 2013-09-24 N
11) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 0 PREDNISOLONE 5 mg 5 mg WEEK 16 MAINTENANCE PREDNISOLONE 2.5 mg 2.5 mg WEEK 20 MAINTENANCE PREDNISOLONE 5 mg 5 mg
12) Narrative Text ⿕㦂⪅ࡣ 6 ṓࡢ᪥ᮏேዪᛶ࡛㸪2012 ᖺ 9 ᭶ 19 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ࣉࣛࢭ࣎ࢆ㟼⬦ෆᢞ ࡉࢀࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡎ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏࢆᢞ ࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪㧗⾑ᅽ࡛࠶ࡗ ࡓࠋ SAE/Serious infection㸸⫠㛛⮋⒆㸦Day 371㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2013 ᖺ 9 ᭶ 24 ᪥⫠㛛࿘ᅖ⮋⒆ࡢ୰➼ᗘࡢᝏࡢࡓࡵධ㝔ࡋ㸪 ྠ᪥㸪ࢩ࣮ࢺࣥ␃⨨⾡ࢆཷࡅࡓࠋࡑࡢࡢ⒪ࡋ࡚㸪ࢪࢡࣟࣇ࢙ࢼࢡ㸪ࢭࣇࢪࢺࣞࣥ㸪ࣆ࣎࢟ ࢩࣝ㸪ࣞࣂ࣑ࣆࢻࡀᢞࡉࢀࡓࠋ2013 ᖺ 9 ᭶ 25 ᪥⫠㛛࿘ᅖ⮋⒆ࡣᾘᩓࡋࡓሗ࿌ࡉࢀ㸪ྠ᪥ ⿕㦂⪅ࡣ㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome (Study day I/M) 2012-10-31 ⓶⅖㻌 MILD/ Y/ DOSE NOT CHANGED/ 2012-11-16 (43/.) (PERIANAL DERMATITIS) POSSIBLE Y RECOVERED/RESOLVED (59/.) 2013-03-07 㰯ဗ㢌⅖㻌 MILD/ Y/ DOSE NOT CHANGED/ 2013-03-18 (170/116) (COMMON COLD) POSSIBLE N RECOVERED/RESOLVED (181/127) 2013-04-04 ㈋⾑㻌 MILD/ N/ DOSE NOT CHANGED/ 2013-10-18 (198/144) (ANEMIA) POSSIBLE NA RECOVERED/RESOLVED (395/341) 2013-04-20 ⫶⭠ฟ⾑㻌 MILD/ N/ DOSE NOT CHANGED/ 2013-04-29 (214/160) (GASTROINTESTINAL BLEEDING) POSSIBLE NA RECOVERED/RESOLVED (223/169) 2013-06-17 ⫶⭠ฟ⾑ MILD/ N/ DOSE NOT CHANGED/ 2013-06-18 (272/218) (GASTROINTESTINAL BLEEDING) POSSIBLE NA RECOVERED/RESOLVED (273/219) 2013-07-21 ⫶⭠ฟ⾑ MILD/ N/ DOSE NOT CHANGED/ 2013-07-25 (306/252) (GASTROINTESTINAL BLEEDING) POSSIBLE NA RECOVERED/RESOLVED (310/256)
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route CIPROFLOXACIN HYDROCHLORIDE 2012-11-01 2012-11-08 ORAL PA 2013-03-07 2013-03-11 ORAL SACCHARATED IRON OXIDE 2013-04-08 2013-05-28 INTRAVENOUS OMEPRAZOLE 2013-04-22 2013-04-24 INTRAVENOUS DRIP SACCHARATED IRON OXIDE 2013-07-24 2013-10-02 INTRAVENOUS CEFDITOREN PIVOXIL 2013-09-25 2013-09-26 ORAL
23 4 (98) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
Preferred Term Start Date End Date Route REBAMIPIDE 2013-09-25 2013-09-26 ORAL DICLOFENAC 2013-09-25 2013-09-25 ORAL
(3) Subject CNTO1275CRD3003-4201-10814
1) Reason for narrative selection SAE 2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome I/M) 2013-02-15 ࢡ࣮ࣟࣥ Y SEVERE/ N/ NOT APPLICABLE/ 2013-07-17 (108/50) (WORSENING CROHN'S NOT NA RECOVERED/RESOLVED (260/202) DISEASE) RELATED
3) Baseline Demographic Information ȋȌǣ ʹ ǣ ȋȌǣ Ͷͷ ǣ ǣ ͳͻͺǦͲͷǦͲͷ ȋ Ȍǣ ͳͷǤͶ
4) Induction Treatment Group Induction study: CNTO1275CRD3001 Randomized Treatment Group: Ustekinumab 130 mg IV Actual Treatment Group: Ustekinumab 130 mg IV 5) Maintenance Treatment Group Assigned Treatment Group: Non-randomized subject/Non-responder to ustekinumab IV induction dosing and received ustekinumab in maintenance 6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2012-10-31 1 Ustekinumab 129.6 mg WEEK 0 MAINTENANCE 2012-12-28 59 Ustekinumab 90 mg WEEK 0 MAINTENANCE 2012-12-28 59 Placebo 0 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: Y Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: - 8) Induction Baseline Crohn's Disease History Date of diagnosis: 19SEP2003 Disease duration: 9.12 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪⫠㛛࿘ᅖ㸪ᑠ⭠㏆㸭⫶㸭㣗㐨
23 5 (99) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: CURRENTLY PRESENT Stricture complications of (CD): CURRENTLY PRESENT 10) Concomitant Crohn's Disease-Related Surgeries Surgery Date Result of lack of efficacy? ேᕤ⫠㛛ࡢタ⨨ 2013-03-26 Y ᅇ⭠ษ㝖 2013-03-26 Y ⤖⭠ษ㝖ཪࡣள 2013-03-26 Y ᑠ⭠ࡢ㢧ᚤ㙾ⓗᣑᙇ⾡ 2013-05-01 Y ᑠ⭠ࡢ㢧ᚤ㙾ⓗᣑᙇ⾡ 2013-05-08 Y ᑠ⭠ࡢ㢧ᚤ㙾ⓗᣑᙇ⾡ 2013-05-24 Y ᅇ⭠ษ㝖 2013-06-24 Y
11) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 0 PREDNISOLONE 1.25 mg 1.25 mg SAFETY FOLLOW-UP MAINTENANCE METHYLPREDNISOLONE 250 mg - SAFETY FOLLOW-UP MAINTENANCE METHYLPREDNISOLONE 0 mg - SAFETY FOLLOW-UP MAINTENANCE HYDROCORTISONE 0 mg - SAFETY FOLLOW-UP MAINTENANCE HYDROCORTISONE 0 mg - SAFETY FOLLOW-UP MAINTENANCE PREDNISOLONE 0 mg 0 mg SAFETY FOLLOW-UP MAINTENANCE PREDNISOLONE 20 mg 20 mg SAFETY FOLLOW-UP MAINTENANCE PREDNISOLONE 15 mg 15 mg SAFETY FOLLOW-UP MAINTENANCE PREDNISOLONE 10 mg 10 mg SAFETY FOLLOW-UP MAINTENANCE PREDNISOLONE 10 mg 10 mg SAFETY FOLLOW-UP MAINTENANCE PREDNISOLONE 7.5 mg 7.5 mg SAFETY FOLLOW-UP MAINTENANCE PREDNISOLONE 5 mg 5 mg SAFETY FOLLOW-UP MAINTENANCE HYDROCORTISONE 200 mg - SAFETY FOLLOW-UP MAINTENANCE HYDROCORTISONE 200 mg -
12) Narrative Text ⿕㦂⪅ࡣ 2 ṓࡢ᪥ᮏே⏨ᛶ࡛㸪2012 ᖺ 10 ᭶ 31 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏࢆ㟼⬦ෆᢞ ࡉࢀࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡎ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏࢆᢞࡉ ࢀࡓࠋ SAE㸸ࢡ࣮ࣟࣥ㸦Day 108㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2013 ᖺ 2 ᭶ 15 ᪥ࢡ࣮ࣟࣥࡢᝏࡢࡓࡵධ㝔ࡋࡓࠋ⭠ୗ㒊 㸦lower intestine㸧ࡢฟ⾑ࡢࡓࡵ㸪ྠ᪥ࡢ࣊ࣔࢢࣟࣅ್ࣥࡣపࡃ㸪7.0 g/dL㹙ṇᖖ⠊ᅖ㸦NR㸧12.6- 16.5 g/dL㹛࡛࠶ࡗࡓࠋ㍺⾑ᚋ≧ែࡣᨵၿࡋ㸪2013 ᖺ 2 ᭶ 17 ᪥ࡢ࣊ࣔࢢࣟࣅ್ࣥࡣ 9.2 g/dL ࡞ࡗࡓࠋ⿕㦂⪅ࡣ㸪2013 ᖺ 2 ᭶ 13 ᪥ࡽ 24 ᪥ࡲ࡛⃰ཌ㉥⾑⌫ 14 ༢ࡀ㍺⾑ࡉࢀࡓࠋ࣓ࢺࢡ ࣟࣉ࣑ࣛࢻ㸪࣌ࣥࢱࢰࢩࣥཬࡧࣃࣥࢸࣀ࣮ࣝࡼࡿ⒪ࢆᐇࡋࡓࠋ2013 ᖺ 3 ᭶ 26 ᪥㸪⭡⭍ 㙾ୗ┤⭠⤖⭠ษ㝖⾡㸪ᑠ⭠ษ㝖⾡ཬࡧ⤖⭠⒦㐀タ⾡ࢆཷࡅࡓࠋ2013 ᖺ 4 ᭶ 17 ᪥㸪X ⥺⏬ീ ࠕࢽ࣮࣎㸦㙾㠃ീ㸧ࠖࡀㄆࡵࡽࢀࡓࠋ2013 ᖺ 4 ᭶ 22 ᪥ࡢᑠ⭠㐀ᙳ࡛ࡣ㸪ษ㝖ᚋࡢᑠ⭠⊃✽㒊 ࡀㄆࡵࡽࢀࡓࠋ2013 ᖺ 5 ᭶ 1 ᪥ཬࡧ 31 ᪥㸪ࢫࢺ࣮࣐ࢆ⤒⏤ࡋࡓࣂ࣮ࣝࣥࡼࡿᑠ⭠ᣑᙇ⾡ ࢆヨࡳࡓࡀ㸪ኻᩋࡋࡓࠋ2013 ᖺ 5 ᭶ 8 ᪥㸪⤒ཱྀࡢࣂ࣮ࣝࣥࡼࡿᑠ⭠ᣑᙇ⾡ࡣᡂຌࡋࡓࡀ㸪 2013 ᖺ 5 ᭶ 24 ᪥ࡣᡂຌ࡛࠶ࡗࡓࠋ2013 ᖺ 6 ᭶ 1 ᪥㸪⿕㦂⪅ࡣ㯮Ⰽ࡞ࡗࡓ⾑౽㸦melena
23 6 (100) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
with black stools㸧ࢆⓎ⌧ࡋ㸪⾑ᅽࡢ㝆ୗ㸦್ࡢሗ࿌࡞ࡋ㸧ཬࡧ࣊ࣔࢢࣟࣅ್ࣥࡢపୗ㸦11.6 g/dL㸧 ࡀࡳࡽࢀࡓࠋ㉥⾑⌫ 4 ༢ࡀ㍺⾑ࡉࢀࡓࠋ2013 ᖺ 6 ᭶ 1 ᪥ࡢࢥࣥࣆ࣮ࣗࢱ᩿ᒙᙳ㸦CT㸧ࢫ࢟ ࡛ࣕࣥࡣ㸪᫂ࡽ࡞✰㸦✸Ꮝ㸧ࡣ࡞ࡗࡓࠋ2013 ᖺ 6 ᭶ 3 ᪥㸪ୖ㒊ෆど㙾᳨ᰝࢆᐇࡋࡓࡀ㸪 ฟ⾑㒊ࡣ☜ㄆ࡛ࡁ࡞ࡗࡓࠋ2013 ᖺ 6 ᭶ 4 ᪥ࡢ࣊ࣔࢢࣟࣅ್ࣥࡣ 9.9 g/dL ࡛࠶ࡗࡓࡀ㸪2013 ᖺ 6 ᭶ 6 ᪥ࡣ 12.3 g/dL ᨵၿࡋࡓࠋ 2013 ᖺ 6 ᭶ 17 ᪥㸪⿕㦂⪅ࡣ 38.7°C ࡢⓎ⇕ࢆⓎ⌧ࡋࡓࠋྠ᪥ࡢ⮫ᗋ᳨ᰝ್ࡣ㸪C ᛂᛶࡓࢇ ⓑ⃰ᗘ 1.37 mg/dL㸦NR 0-0.30 mg/dL㸧㸪ࣛࢽ࣑ࣥࣀࢺࣛࣥࢫࣇ࢙࣮ࣛࢮ 52 IU/L㸦NR 0- 30 IU/L㸧㸪ࣝ࢝ࣜ࣍ࢫࣇࢱ࣮ࢮ 389 IU/L㸦NR 104-338 IU/L㸧࡛࠶ࡗࡓࠋ࢝ࢸ࣮ࢸࣝឤᰁࡀ ࢃࢀࡓࡓࡵ㸪௨๓㸦᪥ᮍሗ࿌㸧ᤄ⟶ࡉࢀࡓ୰ᚰ㟼⬦㸦CV㸧࢝ࢸ࣮ࢸࣝࢆᢤཤࡋࡓࠋ2013 ᖺ 6 ᭶ 18 ᪥㸪CV ࢝ࢸ࣮ࢸࣝࡣᤄ⟶ࡉࢀࡓࠋ2013 ᖺ 6 ᭶ 24 ᪥㸪⿕㦂⪅ࡣᑠ⭠ษ㝖⾡ࢆཷ ࡅࡓࠋ2013 ᖺ 7 ᭶ 1 ᪥ࡢ⮫ᗋ᳨ᰝ࡛ࡢ࣊ࣔࢢࣟࣅ್ࣥࡣ 12.1 g/dL ࡛࠶ࡗࡓࠋ⿕㦂⪅ࡣ㸪2013 ᖺ 7 ᭶ 17 ᪥㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome (Study day I/M) 2012-10-31 ㈋⾑ MODERATE/ N/ NOT APPLICABLE/ 2013-04-02 (1/.) (ANEMIA) DOUBTFUL NA RECOVERED/RESOLVED (154/.) 2012-12-10 㰯ဗ㢌⅖ MILD/ Y/ DOSE NOT CHANGED/ 2012-12-13 (41/.) (COMMON COLD) NOT RELATED Y RECOVERED/RESOLVED (44/.) 2013-01-25 㰯ဗ㢌⅖ MILD/ Y/ DOSE NOT CHANGED/ 2013-01-30 (87/29) (COMMON COLD) NOT RELATED Y RECOVERED/RESOLVED (92/34) 2013-03-18 യ MILD/ N/ NOT APPLICABLE/ Ongoing (139/81) (STEROID CONTUSION) NOT RELATED NA NOT RECOVERED/NOT RESOLVED -
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route FERROUS SULFATE 2012-11-05 2013-02-15 ORAL SACCHARATED IRON OXIDE 2012-11-05 2012-11-05 INTRAVENOUS SACCHARATED IRON OXIDE 2012-11-21 2012-11-21 INTRAVENOUS MOXIFLOXACIN HYDROCHLORIDE 2012-12-12 2012-12-17 ORAL FLURBIPROFEN AXETIL 2012-12-12 2012-12-12 INTRAVENOUS DICLOFENAC 2012-12-12 2012-12-19 ORAL DICLOFENAC 2012-12-28 2013-01-30 ORAL MOXIFLOXACIN HYDROCHLORIDE 2013-01-25 2013-01-30 ORAL AMINO ACIDS NOS W/ELECTROLYTES NOS/GLUCOSE/TH 2013-02-15 2013-02-21 INTRAVENOUS DRIP SACCHARATED IRON OXIDE 2013-02-15 2013-03-25 INTRAVENOUS SULPERAZON 2013-02-15 2013-02-25 INTRAVENOUS DRIP DEXTROSE AND SODIUM CHLORIDE INJECTION 2013-02-15 2013-02-21 INTRAVENOUS DRIP PENTAZOCINE 2013-02-15 2013-03-26 INTRAVENOUS ASPHAGEN 2013-02-15 2013-03-12 INTRAVENOUS VITAMEDIN /00274301/ 2013-02-15 2013-02-21 INTRAVENOUS DRIP HYOSCINE BUTYLBROMIDE 2013-02-19 2013-02-19 INTRAVENOUS DIMETICONE 2013-02-19 2013-02-19 ORAL PRONASE 2013-02-19 2013-02-19 ORAL SODIUM BICARBONATE 2013-02-19 2013-02-19 ORAL LIDOCAINE 2013-02-19 2013-02-19 INTRAVENOUS LIDOCAINE HYDROCHLORIDE 2013-02-19 2013-02-19 ORAL METHYLPREDNISOLONE SODIUM SUCCINATE 2013-02-20 2013-02-22 INTRAVENOUS DRIP HYOSCINE BUTYLBROMIDE 2013-02-22 2013-02-22 INTRAVENOUS AMINO ACIDS NOS W/COPPER/ELECTROLYTES NOS/GLU 2013-02-22 2013-02-24 INTRAVENOUS DRIP DIAZEPAM 2013-02-22 2013-02-22 INTRAVENOUS PETHIDINE HYDROCHLORIDE 2013-02-22 2013-02-22 INTRAVENOUS
23 7 (101) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
Preferred Term Start Date End Date Route AMINO ACIDS NOS W/COPPER/ELECTROLYTES NOS/GLU 2013-02-25 2013-03-25 INTRAVENOUS DRIP GLYCINE MAX SEED OIL 2013-03-09 2013-03-25 INTRAVENOUS DRIP ADAPALENE 2013-03-18 2013-05-06 TOPICAL LEVOBUPIVACAINE HYDROCHLORIDE 2013-03-26 2013-03-28 OTHER SODIUM BICARBONATE 2013-03-26 2013-03-26 INTRAVENOUS DRIP SUGAMMADEX SODIUM 2013-03-26 2013-03-26 INTRAVENOUS DROPERIDOL 2013-03-26 2013-03-26 INTRAVENOUS ROCURONIUM BROMIDE 2013-03-26 2013-03-26 INTRAVENOUS FENTANYL 2013-03-26 2013-03-26 INTRAVENOUS FENTANYL 2013-03-26 2013-03-28 OTHER HESPANDER /00520901/ 2013-03-26 2013-03-26 INTRAVENOUS DRIP PETHIDINE HYDROCHLORIDE 2013-03-26 2013-03-26 INTRAVENOUS PLAS AMINO 2013-03-26 2013-03-26 INTRAVENOUS DRIP PROPOFOL 2013-03-26 2013-03-26 INTRAVENOUS SEVOFLURANE 2013-03-26 2013-03-26 RESPIRATORY (INHALATION) DEXTROSE AND SODIUM CHLORIDE INJECTION 2013-03-26 2013-03-26 INTRAVENOUS DRIP CARBOHYDRATES NOS W/POTASSIUM CHLORIDE/SODIUM 2013-03-26 2013-03-27 INTRAVENOUS DRIP PENTAZOCINE 2013-03-26 2013-04-08 INTRAMUSCULAR REMIFENTANIL HYDROCHLORIDE 2013-03-26 2013-03-26 INTRAVENOUS XYLOCAINE-EPINEPHRINE 2013-03-26 2013-03-26 OTHER LIDOCAINE 2013-03-26 2013-03-26 OTHER XYLOCAINE-EPINEPHRINE 2013-03-26 2013-03-26 OTHER AMINO ACIDS NOS W/ELECTROLYTES NOS/GLUCOSE/TH 2013-03-27 2013-03-28 INTRAVENOUS DRIP FLURBIPROFEN AXETIL 2013-03-27 2013-03-30 INTRAVENOUS AMINO ACIDS NOS W/COPPER/ELECTROLYTES NOS/GLU 2013-03-29 2013-04-15 INTRAVENOUS DRIP PENTAZOCINE 2013-04-03 - ORAL PENTAZOCINE 2013-04-08 2013-05-24 INTRAVENOUS DAIKENCHUTO 2013-04-10 - ORAL PANTHENOL 2013-04-10 2013-04-30 INTRAVENOUS DRIP HYDROXYZINE 2013-04-16 2013-04-17 INTRAVENOUS AMINO ACIDS NOS W/ELECTROLYTES NOS/GLUCOSE/TH 2013-04-16 2013-04-17 INTRAVENOUS DRIP ULTRACET 2013-04-16 - ORAL AMINO ACIDS NOS W/COPPER/ELECTROLYTES NOS/GLU 2013-04-18 2013-05-08 INTRAVENOUS DRIP HYOSCINE BUTYLBROMIDE 2013-05-01 2013-05-01 INTRAVENOUS DIAZEPAM 2013-05-01 2013-05-01 INTRAVENOUS PETHIDINE HYDROCHLORIDE 2013-05-01 2013-05-01 INTRAVENOUS CLINDAMYCIN PHOSPHATE 2013-05-07 - TOPICAL HYDROCORTISON MED TERRAMYCIN 2013-05-07 - TOPICAL FLUMAZENIL 2013-05-08 2013-05-08 INTRAVENOUS HYOSCINE BUTYLBROMIDE 2013-05-08 2013-05-08 INTRAVENOUS MIDAZOLAM 2013-05-08 2013-05-08 INTRAVENOUS DIMETICONE 2013-05-08 2013-05-08 ORAL PETHIDINE HYDROCHLORIDE 2013-05-08 2013-05-08 INTRAVENOUS LIDOCAINE 2013-05-08 2013-05-08 INTRAVENOUS XYLOCAINE-EPINEPHRINE 2013-05-08 2013-05-08 TOPICAL LIDOCAINE HYDROCHLORIDE 2013-05-08 2013-05-08 ORAL GABEXATE MESILATE 2013-05-09 2013-05-14 INTRAVENOUS DRIP CARBOHYDRATES NOS W/POTASSIUM CHLORIDE/SODIUM 2013-05-09 2013-05-14 INTRAVENOUS DRIP AMINO ACIDS NOS W/COPPER/ELECTROLYTES NOS/GLU 2013-05-10 - INTRAVENOUS DRIP HYOSCINE BUTYLBROMIDE 2013-05-24 2013-05-24 INTRAVENOUS MIDAZOLAM MALEATE 2013-05-24 2013-05-24 INTRAVENOUS DIMETICONE 2013-05-24 2013-05-24 ORAL PETHIDINE HYDROCHLORIDE 2013-05-24 2013-05-24 INTRAVENOUS FLURBIPROFEN AXETIL 2013-05-24 2013-05-24 INTRAVENOUS LIDOCAINE 2013-05-24 2013-05-24 INTRAVENOUS LIDOCAINE HYDROCHLORIDE 2013-05-24 2013-05-24 ORAL
23 8 (102) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
(4) Subject CNTO1275CRD3003-4201-11141
1) Reason for narrative selection SAE 2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome I/M) 2013-06-25 ࢡ࣮ࣟࣥ Y SEVERE/ N/ NOT APPLICABLE/ 2013-07-17 (146/90) (WORSENING OF CROHN'S NOT NA RECOVERED/RESOLVED (168/112) DISEASE) RELATED
3) Baseline Demographic Information ȋȌǣ ʹʹ ǣ ȋȌǣ ͷ͵Ǥͺ ǣ ǣ ͳͻͻͲǦͲʹǦͲ ȋ Ȍǣ ͳͷǤʹ
4) Induction Treatment Group Induction study: CNTO1275CRD3001 Randomized Treatment Group: Placebo IV Actual Treatment Group: Placebo IV 5) Maintenance Treatment Group Assigned Treatment Group: Non-randomized subject/Non-responder to placebo IV induction dosing and received ustekinumab in maintenance 6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2013-01-31 1 Placebo 0 mg WEEK 0 MAINTENANCE 2013-03-28 57 Placebo 0 mg WEEK 0 MAINTENANCE 2013-03-28 57 Ustekinumab 129.6 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: Y Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: - 8) Induction Baseline Crohn's Disease History Date of diagnosis: 09APR2005 Disease duration: 7.82 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪⫠㛛࿘ᅖ
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: CURRENTLY PRESENT Stricture complications of (CD): CURRENTLY PRESENT 10) Concomitant Crohn's Disease-Related Surgeries Surgery Date Result of lack of efficacy? ࢻࣞࢼ࣮ࢪ-⤒⓶ษ㛤ཬࡧࢻࣞࢼ࣮ࢪ 2013-06-03 Y
23 9 (103) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
11) Concomitant Steroids Visit Drug Dose Prednisone equivalent SAFETY FOLLOW-UP MAINTENANCE PREDNISOLONE 20 mg 20 mg SAFETY FOLLOW-UP MAINTENANCE PREDNISOLONE 20 mg 20 mg SAFETY FOLLOW-UP MAINTENANCE METHYLPREDNISOLONE 500 mg - SAFETY FOLLOW-UP MAINTENANCE PREDNISOLONE 15 mg 15 mg SAFETY FOLLOW-UP MAINTENANCE PREDNISOLONE 12.5 mg 12.5 mg SAFETY FOLLOW-UP MAINTENANCE PREDNISOLONE 0 mg 0 mg SAFETY FOLLOW-UP MAINTENANCE METHYLPREDNISOLONE 0 mg -
12) Narrative Text ⿕㦂⪅ࡣ 2 ṓࡢ᪥ᮏேዪᛶ࡛㸪2013 ᖺ 1 ᭶ 31 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ࣉࣛࢭ࣎ࢆ㟼⬦ෆᢞ ࡉࢀࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡎ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏࢆᢞ ࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪ࣅࢱ࣑ࣥ B ⩌ Ḟஈཬࡧ⫠㛛࿘ᅖ⓶⅖࡛࠶ࡗࡓࠋ SAE㸸ࢡ࣮ࣟࣥ㸦Day 146㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ㛗ᘬࡃ⭡③㸪ୗ⑩ཬࡧẼࡢࡼ࠺࡞ឤࡌ㸦a sick feeling㸧ࡀ࠶ࡾ㸪 㣗≀ཬࡧỈศࡀᦤྲྀ࡛ࡁ࡞࠸ࡓࡵ㸪2013 ᖺ 6 ᭶ 25 ᪥ධ㝔ࡋࡓࠋ2013 ᖺ 5 ᭶ 23 ᪥㦂⸆ࡢᢞ ࢆ୰Ṇࡋࡓࠋ≧ࡢᨵၿࡀࡳࡽࢀ࡞࠸ࡓࡵ㸪2013 ᖺ 6 ᭶ 24 ᪥ࢲ࣒࣐ࣜࣈࡢᢞ㸦2013 ᖺ 6 ᭶ 10 ᪥ᢞ㛤ጞ㸧ࡶ୰Ṇࡋ㸪ࡑࡢᚋࡣࣉࣞࢻࢽࢰࣟࣥࢆᢞࡋࡓࠋ2013 ᖺ 6 ᭶ 24 ᪥ࡢ⮫ᗋ ᳨ᰝ್ࡣ㸪C ᛂᛶࡓࢇⓑ㸦CRP㸧⃰ᗘ 4.2 mg/dL㹙ṇᖖ⠊ᅖ㸦NR㸧0-0.30 mg/dL㹛㸪࣊ࣔࢢࣟࣅ ࣥ 8.7 g/dL㸦NR 10.6-14.4 g/dL㸧㸪࣐࣊ࢺࢡࣜࢵࢺ 30.1%㸦NR 32.1-42.7%㸧࡛࠶ࡗࡓࠋ࣓ࢳࣝࣉ ࣞࢻࢽࢰࣟࣥ㸪ྵ⢾㓟㕲㸦ࣇ࢙ࢪࣥ㸧ཬࡧࣃࢬࣇࣟ࢟ࢧࢩࣥࡼࡿ⒪ࢆᐇࡋࡓࡀ㸪⭠ෆᢞ 㸦enteral intake㸧ࡣ࡞ࡗࡓࠋ⿕㦂⪅ࡢ≧ࡣᨵၿࡋ㸪2013 ᖺ 7 ᭶ 1 ᪥ࡢ⮫ᗋ᳨ᰝ್ࡣ㸪CRP ⃰ᗘ 0.75 mg/dL㸪࣐࣊ࢺࢡࣜࢵࢺ 31.1%㸪࣊ࣔࢢࣟࣅࣥ 9.3 g/dL ࡛࠶ࡗࡓࠋ⿕㦂⪅ࡣ㸪2013 ᖺ 7 ᭶ 17 ᪥㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2013-02-02 Ⓨ⇕ MILD/ N/ DOSE NOT CHANGED/ 2013-02-04 (3/.) (FEVER) NOT NA RECOVERED/RESOLVED (5/.) RELATED 2013-03-04 ᭶⤒ᅔ㞴 MILD/ N/ DOSE NOT CHANGED/ 2013-03-05 (33/.) (MENSTRUAL PAIN) NOT NA RECOVERED/RESOLVED (34/.) RELATED 2013-03-24 Ⓨ⇕ MILD/ N/ DOSE NOT CHANGED/ 2013-03-25 (53/.) (FEVER) NOT NA RECOVERED/RESOLVED (54/.) RELATED 2013-04-02 ᭶⤒ᅔ㞴 MILD/ N/ DOSE NOT CHANGED/ 2013-04-02 (62/6) (MENSTRUAL PAIN) NOT NA RECOVERED/RESOLVED (62/6) RELATED 2013-05-02 ᭶⤒ᅔ㞴 MILD/ N/ DOSE NOT CHANGED/ 2013-05-02 (92/36) (MENSTRUAL PAIN) NOT NA RECOVERED/RESOLVED (92/36) RELATED 2013-05-23 ㈋⾑ MILD/ N/ NOT APPLICABLE/ 2013-07-29 (113/57) (ANEMIA) NOT NA RECOVERED/RESOLVED (180/124) RELATED 2013-06-01 ⫠㛛⮋⒆ MILD/ Y/ NOT APPLICABLE/ 2013-06-03 (122/66) (WORSENING OF PERIANAL NOT N RECOVERED/RESOLVED (124/68) ABSCESS) RELATED
24 0 (104) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route DICLOFENAC 2013-02-02 2013-02-03 ORAL ACETYLSALICYLIC ACID 2013-03-04 2013-03-05 ORAL DICLOFENAC 2013-03-24 2013-03-24 ORAL ACETYLSALICYLIC ACID 2013-04-02 2013-04-02 ORAL ACETYLSALICYLIC ACID 2013-05-02 2013-05-02 ORAL SACCHARATED IRON OXIDE 2013-05-23 2013-05-23 INTRAVENOUS SACCHARATED IRON OXIDE 2013-06-10 2013-06-10 INTRAVENOUS FERROUS SULFATE 2013-06-24 2013-06-25 ORAL AMINO ACIDS NOS W/ELECTROLYTES NOS/GLUCOSE/TH 2013-06-25 2013-07-04 INTRAVENOUS DRIP SACCHARATED IRON OXIDE 2013-06-25 2013-07-16 INTRAVENOUS HEPARIN SODIUM 2013-06-26 2013-07-04 INTRAVENOUS HYOSCINE BUTYLBROMIDE 2013-06-27 2013-06-28 INTRAVENOUS DIMETICONE 2013-06-27 2013-06-27 ORAL SODIUM PICOSULFATE 2013-06-27 2013-06-27 ORAL POSTERISAN F 2013-06-27 - TOPICAL PRONASE 2013-06-27 2013-06-27 ORAL SODIUM BICARBONATE 2013-06-27 2013-06-27 ORAL LIDOCAINE HYDROCHLORIDE 2013-06-27 2013-06-27 ORAL DIAZEPAM 2013-06-28 2013-06-28 INTRAVENOUS COLYTE /00751601/ 2013-06-28 2013-06-28 ORAL PETHIDINE HYDROCHLORIDE 2013-06-28 2013-06-28 INTRAVENOUS XYLOCAINE-EPINEPHRINE 2013-06-28 2013-06-28 TOPICAL METOCLOPRAMIDE HYDROCHLORIDE 2013-07-01 2013-07-01 INTRAVENOUS SENNOSIDE A+B CALCIUM 2013-07-01 2013-07-02 ORAL FERROUS SULFATE 2013-07-17 2013-07-30 ORAL (5) Subject CNTO1275CRD3003-4202-11150
1) Reason for narrative selection SAE Discontinuation of study agent due to AE 2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome I/M) 2013-08-19 ࢡ࣮ࣟࣥ Y MODERATE/ N/ DRUG WITHDRAWN/ 2013-09-24 (172/120) (WORSENING OF CROHNS NOT NA RECOVERED/RESOLVED (208/156) DISEASE) RELATED
3) Baseline Demographic Information ȋȌǣ ʹͷ ǣ ȋȌǣ ͷǤ ǣ ǣ ͳͻͺǦͲǦͲͳ ȋ Ȍǣ ͳͻǤͷ
4) Induction Treatment Group Induction study: CNTO1275CRD3001 Randomized Treatment Group: Ustekinumab Approximating 6 mg/kg IV Actual Treatment Group: Ustekinumab Approximating 6 mg/kg IV
24 1 (105) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
5) Maintenance Treatment Group Assigned Treatment Group: Non-randomized subject/Non-responder to ustekinumab IV induction dosing and received ustekinumab in maintenance 6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2013-03-01 1 Ustekinumab 389.7 mg WEEK 0 MAINTENANCE 2013-04-22 53 Ustekinumab 90 mg WEEK 0 MAINTENANCE 2013-04-22 53 Placebo 0 mg WEEK 8 MAINTENANCE 2013-06-15 107 Ustekinumab 90 mg WEEK 12 MAINTENANCE 2013-07-11 133 Placebo 0 mg WEEK 16 MAINTENANCE 2013-08-09 162 Ustekinumab 90 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: Y Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: - 8) Induction Baseline Crohn's Disease History Date of diagnosis: 31DEC2007 Disease duration: 5.17 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪⫠㛛࿘ᅖ㸪ᑠ⭠㏆㸭⫶㸭㣗㐨
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: CURRENTLY PRESENT Stricture complications of (CD): NEVER 10) Concomitant Crohn's Disease-Related Surgeries Surgery Date Result of lack of efficacy? ⤖⭠ࡢ㒊ศⓗษ㝖㸦༙⤖⭠ษ㝖࡞㸧 2013-09-04 Y
11) Concomitant Steroids Visit Drug Dose Prednisone equivalent SAFETY FOLLOW-UP MAINTENANCE PREDNISOLONE 20 mg 20 mg SAFETY FOLLOW-UP MAINTENANCE METHYLPREDNISOLONE 125 mg - SAFETY FOLLOW-UP MAINTENANCE PREDNISOLONE 0 mg 0 mg SAFETY FOLLOW-UP MAINTENANCE METHYLPREDNISOLONE 0 mg -
12) Narrative Text ⿕㦂⪅ࡣ 2 ṓࡢ᪥ᮏே⏨ᛶ࡛㸪2013 ᖺ 3 ᭶ 1 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏࢆ㟼⬦ෆᢞࡉ ࢀࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡎ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏࢆᢞࡉࢀ ࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪࠺ࡘཬࡧႚ ↮࡛࠶ࡗࡓࠋ
24 2 (106) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
SAE/Discontinuation of study agent due to AE㸸ࢡ࣮ࣟࣥ㸦Day 172㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2013 ᖺ 8 ᭶ 19 ᪥㸪⭡③ཬࡧୗ⑩ࢆッ࠼ධ㝔ࡋࡓࠋྠ᪥ࡢ⮫ᗋ ᳨ᰝ␗ᖖ್ࡣ㸪C ᛂᛶࡓࢇⓑ⃰ᗘ 0.31 mg/dL㹙ṇᖖ⠊ᅖ㸦NR㸧<0.3 mg/dL㹛࡛࠶ࡗࡓࠋ2013 ᖺ 8 ᭶ 21 ᪥ࡢ᰾☢Ẽඹ㬆⏬ീἲ㸦MRI㸧࡛ࡣ㸪ୗ⾜⤖⭠ᮎ➃ࡽ S ≧⤖⭠ཬࡪ⅖㸪㢧ⴭ࡞ᾋ⭘ ᛶࡢ⫧ཌཬࡧ࿘ᅖࡢ⾑⟶ቑṪ㸪ᑠ⭠ࡢኚ୪ࡧ⭠ෆ⭍⊃✽ࡢᡤぢࡀࡳࡽࢀࡓࠋ2013 ᖺ 8 ᭶ 23 ᪥ࡢ⭠ෆど㙾᳨ᰝཬࡧ࢞ࢫࢺࣟࢢࣛࣇ᳨ࣥᰝ࡛ࡣ㸪ୗ⾜⤖⭠ᮎ➃ࡽ S ≧⤖⭠ࡅ࡚ 5 cm ௨ୖࡢ⣣≧ࡢ⊃✽㸦string-like stenosis㸧ཬࡧ⫠㛛ᇦάືᮇࡢ⦪㉮₽⒆ࡀࡳࡽࢀࡓࠋ2013 ᖺ 8 ᭶ 26 ᪥ࡢ⮫ᗋ᳨ᰝ್ࡣ㸪࣐࣊ࢺࢡࣜࢵࢺ 39.4%㸦NR 40.2-51.5%㸧࡛࠶ࡗࡓࠋ2013 ᖺ 9 ᭶ 4 ᪥ 㸪⿕㦂⪅ࡣ≧ࡢࡳࡽࢀࡿୗ⾜⤖⭠ཬࡧ S ≧⤖⭠ࡢ㒊ศⓗ⤖⭠ษ㝖⾡୪ࡧṇᖖ㒊ศࡢ➃➃࿀ ྜ⾡ࢆཷࡅࡓࠋ⾡ᚋࡣⰋዲᅇࡋ㸪⿕㦂⪅ࡣ 2013 ᖺ 9 ᭶ 24 ᪥㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2013-02-22 㰯ဗ㢌⅖ MILD/ Y/ NOT APPLICABLE/ 2013-02-24 (-7/.) (COMMON COLD) NOT N RECOVERED/RESOLVED (-5/.) RELATED 2013-06-14 㰯ဗ㢌⅖ MILD/ Y/ DOSE NOT CHANGED/ 2013-06-16 (106/54) (COMMON COLD) NOT N RECOVERED/RESOLVED (108/56) RELATED 2013-08-15 ឤᰁᛶ⭠⅖ MODERATE/ Y/ DOSE NOT CHANGED/ 2013-09-24 (168/116) (SUSPECT OF INFECTION POSSIBLE Y RECOVERED/RESOLVED (208/156) ENTERITIS) 2013-10-25 ⶼ㯞⑈ MILD/ N/ NOT APPLICABLE/ 2013-10-26 (239/187) (URTICARIA) NOT NA RECOVERED/RESOLVED (240/188) RELATED
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route CARBOCISTEINE 2013-02-22 2013-02-24 ORAL DEXTROMETHORPHAN HYDROBROMIDE 2013-02-22 2013-02-24 ORAL PARACETAMOL 2013-02-23 2013-02-23 ORAL FOSFOMYCIN CALCIUM 2013-08-16 2013-08-18 ORAL SULPERAZON 2013-08-19 2013-08-26 INTRAVENOUS DRIP CARBOHYDRATES NOS W/POTASSIUM CHLORIDE/SODIUM 2013-08-19 2013-08-26 INTRAVENOUS DRIP METOCLOPRAMIDE HYDROCHLORIDE 2013-08-21 2013-08-21 INTRAVENOUS DRIP MAGNESIUM 2013-09-03 2013-09-03 ORAL PROPOFOL 2013-09-04 2013-09-04 INTRAVENOUS BOLUS ALBUMIN HUMAN 2013-09-04 2013-09-04 INTRAVENOUS DRIP DROPERIDOL 2013-09-04 2013-09-08 SUBCUTANEOUS ROCURONIUM BROMIDE 2013-09-04 2013-09-04 INTRAVENOUS BOLUS FENTANYL 2013-09-04 2013-09-04 INTRAVENOUS BOLUS FLOMOXEF SODIUM 2013-09-04 2013-09-06 INTRAVENOUS DRIP FUROSEMIDE 2013-09-04 2013-09-04 INTRAVENOUS BOLUS BUPRENORPHINE HYDROCHLORIDE 2013-09-04 2013-09-08 SUBCUTANEOUS BUPIVACAINE HYDROCHLORIDE 2013-09-04 2013-09-07 OTHER OMEPRAZOLE 2013-09-04 2013-09-07 INTRAVENOUS BOLUS METOCLOPRAMIDE HYDROCHLORIDE 2013-09-04 2013-09-04 INTRAVENOUS BOLUS FLURBIPROFEN AXETIL 2013-09-04 2013-09-04 INTRAVENOUS DRIP SOLACET F 2013-09-04 2013-09-04 INTRAVENOUS DRIP REMIFENTANIL HYDROCHLORIDE 2013-09-04 2013-09-04 INTRAVENOUS DRIP LYO-DIAMIN 2013-09-05 2013-09-07 INTRAVENOUS BOLUS CARBOHYDRATES NOS W/POTASSIUM CHLORIDE/SODIUM 2013-09-05 2013-09-07 INTRAVENOUS DRIP AMINO ACIDS NOS W/ELECTROLYTES NOS/GLUCOSE/TH 2013-09-08 2013-09-16 INTRAVENOUS DRIP
24 3 (107) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
Preferred Term Start Date End Date Route CEFAZOLIN 2013-09-17 2013-09-19 INTRAVENOUS DRIP STRONG NEO-MINOPHAGEN C 2013-10-25 2013-10-25 INTRAVENOUS BOLUS METHYLPREDNISOLONE SODIUM SUCCINATE 2013-10-25 2013-10-25 INTRAVENOUS DRIP SOLITA-T1 2013-10-25 2013-10-25 INTRAVENOUS DRIP FEXOFENADINE HYDROCHLORIDE 2013-10-26 2013-10-30 ORAL FAMOTIDINE 2013-10-26 2013-10-30 ORAL PREDNISOLONE 2013-10-26 2013-10-28 ORAL
(6) Subject CNTO1275CRD3003-4203-10819
1) Reason for narrative selection SAE 2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome (Study day I/M) 2013-09-06 ⇕ᑕ Y MODERATE/ N/ DOSE NOT CHANGED/ 2013-09-14 (310/254) (HEATSTROKE) DOUBTFUL NA RECOVERED/RESOLVED (318/262)
3) Baseline Demographic Information ȋȌǣ ʹ ǣ ȋȌǣ ͳ ǣ ǣ ͳͻͺͶǦͳʹǦͲͳ ȋ Ȍǣ ͳͲǤʹ
4) Induction Treatment Group Induction study: CNTO1275CRD3001 Randomized Treatment Group: Ustekinumab 130 mg IV Actual Treatment Group: Ustekinumab 130 mg IV 5) Maintenance Treatment Group Assigned Treatment Group: Non-randomized subject/Non-responder to ustekinumab IV induction dosing and received ustekinumab in maintenance 6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2012-11-01 1 Ustekinumab 129.6 mg WEEK 0 MAINTENANCE 2012-12-27 57 Ustekinumab 90 mg WEEK 0 MAINTENANCE 2012-12-27 57 Placebo 0 mg WEEK 8 MAINTENANCE 2013-02-12 104 Ustekinumab 90 mg WEEK 12 MAINTENANCE 2013-03-12 132 Placebo 0 mg WEEK 16 MAINTENANCE 2013-04-11 162 Ustekinumab 90 mg WEEK 20 MAINTENANCE 2013-05-16 197 Placebo 0 mg WEEK 24 MAINTENANCE 2013-06-06 218 Ustekinumab 90 mg WEEK 28 MAINTENANCE 2013-07-04 246 Placebo 0 mg WEEK 32 MAINTENANCE 2013-08-01 274 Ustekinumab 90 mg WEEK 36 MAINTENANCE 2013-08-29 302 Placebo 0 mg WEEK 40 MAINTENANCE 2013-09-26 330 Ustekinumab 90 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: N Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: Y
24 4 (108) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
8) Induction Baseline Crohn's Disease History Date of diagnosis: 02OCT2001 Disease duration: 11.09 years Involved areas: ᅇ⭠ࡢࡳ㸪ᾘ⟶እኚ㸦㛵⠇⅖㸭㛵⠇③㸧
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: NEVER Stricture complications of (CD): PREVIOUS HISTORY 10) Concomitant Crohn's Disease-Related Surgeries None reported 11) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 0 PREDNISOLONE 20 mg 20 mg WEEK 12 MAINTENANCE PREDNISOLONE 15 mg 15 mg WEEK 16 MAINTENANCE PREDNISOLONE 10 mg 10 mg WEEK 20 MAINTENANCE PREDNISOLONE 7.5 mg 7.5 mg WEEK 20 MAINTENANCE PREDNISOLONE 5 mg 5 mg WEEK 28 MAINTENANCE PREDNISOLONE 2.5 mg 2.5 mg
12) Narrative Text ⿕㦂⪅ࡣ 2 ṓࡢ᪥ᮏேዪᛶ࡛㸪2012 ᖺ 11 ᭶ 1 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏࢆ㟼⬦ෆᢞࡉ ࢀࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡎ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏࢆᢞࡉࢀ ࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪ႚ↮࡛࠶ࡗࡓࠋ SAE㸸⇕ᑕ㸦Day 310㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2013 ᖺ 9 ᭶ 6 ᪥㸪⇕ᑕࡢࡓࡵධ㝔ࡋࡓࠋྠ᪥ࡢ⮫ᗋ᳨ᰝ␗ᖖ ್ࡣ㸪ࢡࣞࢳࣥ࢟ࢼ࣮ࢮ 39 IU/L㹙ṇᖖ⠊ᅖ㸦NR㸧40-150 IU/L㹛㸪࣊ࣔࢢࣟࣅࣥ 11.2 g/dL 㸦NR 11.5-15.0 g/dL㸧㸪㕲 26 ȝg/dL㸦NR 40-180 ȝg/dL㸧㸪ங㓟⬺Ỉ⣲㓝⣲ 112 IU/L㸦NR 120- 240 IU/L㸧㸪ᖹᆒ㉥⾑⌫࣊ࣔࢢࣟࣅࣥ 22.4 pg㸦NR 28.0-34.0 pg㸧㸪ᖹᆒ㉥⾑⌫ᐜ✚ 73 fL㸦NR 85- 102 fL㸧㸪⾑ᑠᯈᩘ 38×104/ȝL㸦NR 14-34×104/ȝL㸧㉥⾑⌫ᩘ 544×104/ȝL㸦NR 380-500×104/ȝL㸧㸪 ⥲ࡓࢇⓑ 5.8 g/dL㸦NR 6.7-8.3 g/dL㸧㸪ᒀ⣲㔞㸦urea volume㸧5.0 mg/dL㸦NR 8.0-20.0 mg/dL㸧࡛ ࠶ࡗࡓࠋ2013 ᖺ 9 ᭶ 11 ᪥ࡢᇵ㣴᳨ᰝࡢ⤖ᯝࡣ㸪ཎᛶ⭠⳦㸪⭠⅖ࣅࣈࣜ࢜㸪㯤Ⰽࣈࢻ࢘⌫⳦㸪 Campylobacter jejuni ୪ࡧࢧࣝࣔࢿࣛ⳦✀ཬࡧ㉥⑩⳦✀ࡣ㝜ᛶ࡛࠶ࡗࡓࠋࣈࢻ࢘⢾㸭ሷࢼࢺࣜ ࣒࢘㸭ሷ࣒࢝ࣜ࢘㸭ሷ࢝ࣝࢩ࣒࢘Ỉ≀㸭㓑㓟ࢼࢺ࣒ࣜ࢘Ỉ≀㸦ࣦ࣮ࣥ D ㍺ᾮ㸧㸪ࢫ ࢥࣝࣅࣥ㓟㸪ࣜࣥ㓟ࢳ࣑ࣥࢪࢫࣝࣇࢻ㸭ࣆࣜࢻ࢟ࢩࣥሷ㓟ሷ㸦ࣅࢱ࣓ࢪࣥ㸧㸪ཬࡧࣈࢻ࢘⢾ 㸭ሷࢼࢺ࣒ࣜ࢘㸭ሷ࣒࢝ࣜ࢘㸭㓑㓟ࢼࢺ࣒ࣜ࢘㸦ࢯࣜࢱ-T ㍺ᾮ㸧ࡼࡿ⒪ࡀᐇࡉࢀࡓࠋ ⿕㦂⪅ࡣ㸪2013 ᖺ 9 ᭶ 15 ᪥㏥㝔ࡋࡓࠋ
24 5 (109) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
13) Other Adverse Events Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2012-12-01 ୖ⭡㒊③ MODERATE/ N/ DOSE NOT CHANGED/ 2013-05-11 (31/.) (UPPER ABDOMINAL NOT NA RECOVERED/RESOLVED (192/.) PAIN) RELATED 2012-12-01 ᝏᚰ MODERATE/ N/ DOSE NOT CHANGED/ 2012-12-27 (31/.) (NAUSEA) NOT NA RECOVERED/RESOLVED (57/.) RELATED 2013-02-19 㰯ဗ㢌⅖ MILD/ Y/ DOSE NOT CHANGED/ 2013-03-06 (111/55) (COMMON COLD) NOT N RECOVERED/RESOLVED (126/70) RELATED 2013-08-29 ⬺Ỉ MODERATE/ N/ DOSE NOT CHANGED/ 2013-08-29 (302/246) (DEHYDRATION) DOUBTFUL NA RECOVERED/RESOLVED (302/246) 2013-09-11 㢌③ MILD/ N/ DOSE NOT CHANGED/ Ongoing (315/259) (HEADACHE) DOUBTFUL NA NOT RECOVERED/NOT - RESOLVED 2013-10-08 ࣂࣝࢺࣜࣥ⭢⅖ MODERATE/ Y/ DOSE NOT CHANGED/ 2014-06-13 (342/286) (BARTHOLINITIS) PROBABLE Y RECOVERED/RESOLVED (590/534)
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route CARBOHYDRATES NOS W/POTASSIUM CHLORIDE/SODIUM 2013-08-29 2013-08-29 INTRAVENOUS DRIP VEEN 3G 2013-09-06 2013-09-10 INTRAVENOUS DRIP VEEN D 2013-09-06 2013-09-10 INTRAVENOUS DRIP ASCORBIC ACID 2013-09-06 2013-09-10 INTRAVENOUS DRIP VITAMEDIN INTRAVENOUS 2013-09-06 2013-09-10 INTRAVENOUS DRIP SOLITA-T3 2013-09-07 2013-09-09 INTRAVENOUS DRIP CEFDITOREN PIVOXIL 2013-10-19 2013-10-24 ORAL LOXOPROFEN SODIUM 2013-10-19 2013-11-27 ORAL
(7) Subject CNTO1275CRD3003-4209-10427
1) Reason for narrative selection SAE Discontinuation of study agent due to AE
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome I/M) 2013-05-14 ࢡ࣮ࣟࣥ Y SEVERE/ N/ DRUG WITHDRAWN/ 2013-06-24 (285/224) (CROHN'S DISEASE NOT NA RECOVERED/RESOLVED (326/265) AGGRAVATED) RELATED
3) Baseline Demographic Information Age (years): 4 Sex: Female Weight (kg): 57.6 Race: Asian Date of birth: Height (cm): 167.5
4) Induction Treatment Group Induction study: CNTO1275CRD3001 Randomized Treatment Group: Placebo IV Actual Treatment Group: Placebo IV
24 6 (110) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
5) Maintenance Treatment Group Assigned Treatment Group: Non-randomized subject/Non-responder to placebo IV induction dosing and received ustekinumab in maintenance
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2012-08-03 1 Placebo 0 mg WEEK 0 MAINTENANCE 2012-10-03 62 Ustekinumab 129.6 mg WEEK 0 MAINTENANCE 2012-10-03 62 Placebo 0 mg WEEK 8 MAINTENANCE 2012-11-28 118 Ustekinumab 90 mg WEEK 12 MAINTENANCE 2012-12-28 148 Placebo 0 mg WEEK 16 MAINTENANCE 2013-01-23 174 Placebo 0 mg WEEK 20 MAINTENANCE 2013-02-22 204 Ustekinumab 90 mg WEEK 24 MAINTENANCE 2013-03-15 225 Placebo 0 mg WEEK 28 MAINTENANCE 2013-04-19 260 Placebo 0 mg WEEK 32 MAINTENANCE 2013-05-17 288 Ustekinumab 90 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: Y Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: -
8) Induction Baseline Crohn's Disease History Date of diagnosis: 01APR2010 Disease duration: 2.34 years Involved areas: ᅇ⭠ཬࡧ⤖⭠
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: PREVIOUS HISTORY Sinus tracts/perforation: NEVER Fistula: PREVIOUS HISTORY Stricture complications of (CD): PREVIOUS HISTORY
10) Concomitant Crohn's Disease-Related Surgeries Surgery Date Result of lack of efficacy? 㛤⭡ࡼࡿࢻࣞࢼ࣮ࢪ㸦⭡㒊⮋⒆࡞㸧 2013-06-07 Y ษ㝖-ᅇ┣㒊 2013-06-07 Y
11) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 0 PREDNISOLONE 10 mg 10 mg WEEK 0 BETAMETHASONE 0.75 mg 5 mg WEEK 36 MAINTENANCE METHYLPREDNISOLONE 250 mg - WEEK 36 MAINTENANCE METHYLPREDNISOLONE 500 mg - WEEK 36 MAINTENANCE METHYLPREDNISOLONE 0 mg - WEEK 36 MAINTENANCE METHYLPREDNISOLONE 0 mg - WEEK 36 MAINTENANCE PREDNISOLONE 0 mg 0 mg
24 7 (111) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
12) Narrative Text ⿕㦂⪅ࡣ 4 ṓࡢ᪥ᮏேዪᛶ࡛㸪2012 ᖺ 8 ᭶ 3 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ࣉࣛࢭ࣎ࢆ㟼⬦ෆᢞ ࡉࢀࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡎ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏࢆᢞ ࡉࢀࡓࠋデ⒪グ㘓ࡽࡢ᪤ Ṕࡣ㸪S ≧⤖⭠㏆ࢆྵࡴᅇ┣㒊ษ㝖㸦᪥ᮍሗ࿌㸧࡛࠶ࡗࡓࠋ SAE/Discontinuation of study agent due to AE㸸ࢡ࣮ࣟࣥ㸦Day 285㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ⅖㸪✸Ꮝཬࡧ⮋⒆ᙧᡂࡢ࠸ࢆక࠺άືᮇࡢࢡ࣮ࣟࣥデ᩿ ࡉࢀ 2013 ᖺ 5 ᭶ 24 ᪥ධ㝔ࡋࡓࠋ⿕㦂⪅ࡣ 2013 ᖺ 5 ᭶ 14 ᪥ࡽ⭡③ࢆⓎ⌧ࡋ࡚࠸ࡓࠋ2013 ᖺ 5 ᭶ 20 ᪥ࡢ⭡㒊ࢥࣥࣆ࣮ࣗࢱ᩿ᒙᙳ㸦CT㸧ࢫ࡛࢟ࣕࣥࡣ㸪⭈│ᣑᙇ㸪ᕥ⭈│ᒀ⟶⛣⾜㒊㛢 ሰ㸦࠸㸧㸪ྑ⭈⤖▼㸪ᕥ⬚Ỉ㈓␃㸪ᑡ㔞ࡢ⭡Ỉ㸪㍍ᗘࡢ⭁⭘㸪ᅇ⭠㏆࠾ࡅࡿ࿀ྜ㒊ࡢ⫧ཌ㸪 ⭠㛫⭷ࡢ⬡⫫⤌⧊ࡢ⃰ᗘୖ᪼㸪άືᮇࡢ⅖ᛶኚ୪ࡧᑠ⭠ཬࡧ⭠㛫⭷ࡢ✸Ꮝ㸪⮋⒆ᙧᡂࡀ ࡳࡽࢀࡓࡀ㸪⭡⭍ෆ㐟㞳࢞ࢫࡣ࡞ࡗࡓࠋྠ᪥ࡢ⮫ᗋ᳨ᰝ್ࡣ㸪C ᛂᛶࡓࢇⓑ⃰ᗘ 7.8 mg/dL 㹙ṇᖖ⠊ᅖ㸦NR㸧<0.30 mg/dL㹛㸪࣊ࣔࢢࣟࣅࣥ 11.2 g/dL㸦NR 11.3-15.2 g/dL㸧ཬࡧ࣐࣊ࢺࢡࣜ ࢵࢺ 33.3%㸦NR 34-46%㸧࡛࠶ࡗࡓࠋࣟ࢟ࢯࣉࣟࣇ࢙ࣥ㸪ࢪࢡࣟࣇ࢙ࢼࢡ㸪ࣄࢻࣟ࢟ࢩࢪࣥ㸪ࣇ ࣟࣔ࢟ࢭࣇ㸪ࢢࣜࢭ࣮ࣟࣝ㸭ࣞࢩࢳࣥ㸭⢭〇㇋Ἔ㸪ሷ࣐ࣥ࢞ࣥ㸭◲㓟ள㖄㸦࢚࣓࣑ࣞࣥࢵ ࢡ㸧㸪⥲ྜࣅࢱ࣑ࣥ㸭ࢹ࢟ࢫࢺ࣮ࣟࢫ㸭࣑ࣀ㓟㸭㟁ゎ㉁㸦ࣇࣝ࢝ࣜࢵࢡ 1 ྕཬࡧ 2 ྕ㍺ᾮ㸧㸪 ங㓟ࣜࣥࢤࣝᾮ㸪ࣈࢻ࢘⢾㸭㓑㓟ࣜࣥࢤࣝᾮ㸦ࣦ࣮ࣥ D ㍺ᾮ㸧㸪◪㓟࣒࢝ࣜ࢘㸪࢝ࣝࣂࢰࢡࣟ ࣒ࢫࣝ࣍ࣥ㓟ࢼࢺ࣒ࣜ࢘㸪ࢺࣛࢿ࢟ࢧ࣒㓟㸪࣊ࣔࢥࢢ࣮ࣛࢮ㸪ሷࢼࢺ࣒ࣜ࢘㸭ሷ࣒࢝ࣜ࢘ 㸭ሷ࣐ࢢࢿࢩ࣒࢘㸭ࣈࢻ࢘⢾㸦ࢫࢸ࣐ࣜࣥ 3 ྕ MG ㍺ᾮ㸧ࡼࡿ⒪ࡀᐇࡉࢀࡓࠋ2013 ᖺ 5 ᭶ 29 ᪥ࡢ⭠ෆど㙾᳨ᰝࡢ⤖ᯝ㸪࿀ྜ㒊ࡽᅇ┣㒊ࡢ㛤ཱྀ㒊㸦opening of the ileocecal junction㸧ࡅ࡚άືᮇࡢ⅖ᛶ₽⒆ࡀࡳࡽࢀࡓࠋS ≧⤖⭠άືᮇࡢᑠࡉ࡞₽⒆ཬࡧ」ᩘಶᡤ ⦪㉮₽⒆ࡢ⒕ࡶࡳࡽࢀࡓࠋ⭠ࡢ⊃✽ࡀࡳࡽࢀ㸪ࡉࡽ࡞ࡿ⭠ࡢどㄆࡣࢧࣥࣉࢳ࣮ࣗࣈࡢ␃⨨ ࡀᚲせ࡛࠶ࡾ㸪⭠⒦Ꮝࡢᡤぢࡀሗ࿌ࡉࢀࡓࠋ2013 ᖺ 6 ᭶ 7 ᪥㸪ᅇ┣㒊ࡢษ㝖⾡㸪⮋⒆ࡢὙί ཬࡧࢻࣞࢼ࣮ࢪࡀᐇࡉࢀࡓࠋ⿕㦂⪅ࡣ㸪2013 ᖺ 6 ᭶ 24 ᪥㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome (Study day I/M) 2012-12-27 ⫶㣗㐨㏫ὶᛶᝈ MILD/ N/ DOSE NOT CHANGED/ 2013-05-17 (147/86) (REFLUX ESOPHAGITIS) NOT RELATED NA RECOVERED/RESOLVED (288/227) 2013-03-01 ࢘ࣝࢫឤᰁ MILD/ Y/ DOSE NOT CHANGED/ 2013-03-05 (211/150) (VIRAL INFECTION) NOT RELATED Y RECOVERED/RESOLVED (215/154) 2013-04-14 ୖ⭡㒊③ MILD/ N/ DOSE NOT CHANGED/ 2013-04-16 (255/194) (ABDMINAL PAIN UPPER) NOT RELATED NA RECOVERED/RESOLVED (257/196) 2013-05-20 ⭈⤖▼ MILD/ N/ DOSE NOT CHANGED/ Ongoing (291/230) (CALCULUS RENAL) DOUBTFUL NA NOT RECOVERED/NOT RESOLVED -
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route FAMOTIDINE 2013-01-23 2013-05-17 ORAL CEFCAPENE PIVOXIL HYDROCHLORIDE 2013-03-01 2013-03-04 ORAL LACTOMIN 2013-03-01 2013-03-04 ORAL LOXOPROFEN SODIUM 2013-03-01 2013-03-04 ORAL LANSOPRAZOLE 2013-04-14 2013-04-16 ORAL LOXOPROFEN SODIUM 2013-04-14 2013-04-16 ORAL METHYLPREDNISOLONE SODIUM SUCCINATE 2013-05-20 2013-05-22 INTRAVENOUS FLOMOXEF SODIUM 2013-05-24 2013-05-24 INTRAVENOUS RINGER-LACTATE 2013-05-24 2013-05-24 INTRAVENOUS METHYLPREDNISOLONE SODIUM SUCCINATE 2013-05-24 2013-05-24 INTRAVENOUS
24 8 (112) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
Preferred Term Start Date End Date Route FAMOTIDINE 2013-06-08 2013-06-23 ORAL
(8) Subject CNTO1275CRD3003-4209-20834
1) Reason for narrative selection SAE
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome I/M) 2014-07-23 ࢡ࣮ࣟࣥ Y MODERATE/ N/ NOT APPLICABLE/ 2014-09-29 (127/71) (CROHN'S DISEASE DOUBTFUL NA RECOVERED/RESOLVED (195/139) AGGRAVATED)
3) Baseline Demographic Information Age (years): 3 Sex: Male Weight (kg): 65 Race: Asian Date of birth: Height (cm): 180.7
4) Induction Treatment Group Induction study: CNTO1275CRD3002 Randomized Treatment Group: Placebo IV Actual Treatment Group: Placebo IV
5) Maintenance Treatment Group Assigned Treatment Group: Non-randomized subject/Non-responder to placebo IV induction dosing and received ustekinumab in maintenance
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2014-03-19 1 Placebo 0 mg WEEK 0 MAINTENANCE 2014-05-14 57 Ustekinumab 129.6 mg WEEK 0 MAINTENANCE 2014-05-14 57 Placebo 0 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: Y Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: -
8) Induction Baseline Crohn's Disease History Date of diagnosis: 07APR2010 Disease duration: 3.95 years Involved areas: ⤖⭠ࡢࡳ㸪⫠㛛࿘ᅖ
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: CURRENTLY PRESENT Stricture complications of (CD): CURRENTLY PRESENT
24 9 (113) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
10) Concomitant Crohn's Disease-Related Surgeries Surgery Date Result of lack of efficacy? ேᕤ⫠㛛ࡢタ⨨ 2014-09-09 N ⤖⭠ษ㝖-ཪࡣள 2014-09-09 N
11) Concomitant Steroids None reported
12) Narrative Text ⿕㦂⪅ࡣ 3 ṓࡢ᪥ᮏே⏨ᛶ࡛㸪2014 ᖺ 3 ᭶ 19 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ࣉࣛࢭ࣎ࢆ㟼⬦ෆᢞ ࡉࢀࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡎ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏࢆᢞ ࡉࢀࡓࠋ SAE㸸ࢡ࣮ࣟࣥ㸦Day 127㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2014 ᖺ 8 ᭶ 25 ᪥㸪⫠㛛⊃✽ࡢ⢭ᐦ᳨ᰝཬࡧእ⛉⒪ἲࡢࡓࡵධ 㝔ࡋࡓࠋ2014 ᖺ 7 ᭶ 23 ᪥ࢡ࣮ࣟࣥࡢᝏࡀㄆࡵࡽࢀࡓࠋ᳨ᰝࡢ⤖ᯝ㸪ྑ༙⤖⭠⊃✽ࡀ☜ ㄆࡉࢀࡓࠋ2014 ᖺ 8 ᭶ 28 ᪥ࡢ⭡㒊-㦵┙㒊ࡢࢥࣥࣆ࣮ࣗࢱ᩿ᒙᙳ㸦CT㸧ࢫ࡛࢟ࣕࣥࡣ㸪ᶓ⾜ ⤖⭠ཬࡧ S ≧⤖⭠ࡢ₢⭷ୗᒙ⤌⧊ 2 ࢝ᡤࡢ᫂░࡞ቃ⏺ཬࡧ⫧ཌ㸪⤖⭠ࡢ⊃✽ཬࡧ▷⦰㸪ᶓ⾜ ⤖⭠ࡢ⭠ቨ⫧ཌཬࡧ⤖⭠ഐࣜࣥࣃ⠇⭘⬽ࡢᨵၿ㸪⫹▼୪ࡧ⭁⭘ࡀࡳࡽࢀࡓࠋ2014 ᖺ 9 ᭶ 1 ᪥ࡢ ୖ㒊ᾘ⟶ෆど㙾᳨ᰝࡢ⤖ᯝ㸪ᄇ㛛㒊ࡀⓑⰍࢆᖏࡧ࡚࠾ࡾ㸪⫶㣗㐨㏫ὶᛶᝈࡀࢃࢀࡓࠋ༑ ᣦ⭠๓ቨ₽⒆⒕㸦S2㸧㸪⫶య㒊ࡽ✴❞㒊ࡅ࡚ෆ㒊యከᩘࡢࡧࡽࢇ㸦ᑠᙙୖ㸧 ࡀ⦪⓾యࢆᶓ᩿ࡍࡿࡼ࠺ࡳࡽࢀࡓࠋࡇࢀࡣᡤㅝ㸪➉⠇ᙧࡤࢀࡿࡶࡢ࡛࠶ࡗࡓࠋྠ᪥ࡢෆ ど㙾᳨ᰝ᥇ྲྀࡋࡓ⏕᳨ヨᩱࡢ⌮⤌⧊Ꮫⓗᡤぢ࡛ࡣ㸪ከࡃࡢ៏ᛶࡢ⅖ᛶᾐ₶ཬࡧࡧࡽࢇࢆ క࠺⾲ᒙࡢᾋ⭘୪ࡧᑡᩘࡢ࣊ࣜࢥࣂࢡࢱ࣮࣭ࣆࣟࣜࡀࡳࡽࢀࡓࠋ2014 ᖺ 9 ᭶ 9 ᪥㸪⤖⭠ࡢள ษ㝖⾡ཬࡧᅇ⭠⒦㐀タ⾡ࢆཷࡅࡓࠋ⾡๓ཬࡧ⾡ᚋ௨ୗࢆᢞࡉࢀࡓ㸸ࢭ࣎ࣇࣝࣛࣥ㸪ࣟࢡ ࣟࢽ࣒࢘⮯≀㸪ࢻࣟ࣌ࣜࢻ࣮ࣝ㸪ࣉ࣏ࣟࣇ࢛࣮ࣝ㸪ࣞ࣎ࣈࣆࣂ࢝ࣥሷ㓟ሷ㸪ࢼࣟ࢟ࢯࣥሷ㓟 ሷ㸪ࣜࢻ࢝ࣥሷ㓟ሷ㸪ࣇࣝࣝࣅࣉࣟࣇ࢙ࣥ ࢟ࢭࢳࣝ㸪ࢺࣟࣆࣥ◲㓟ሷ㸪ࢿ࢜ࢫࢳࢢ࣑ࣥ ࣓ࢳࣝ◲㓟ሷ㸪ࣇ࢙ࣥࢱࢽࣝࢡ࢚ࣥ㓟ሷ㸪ࣔࣝࣄࢿሷ㓟ሷ㸪hetastarch㸪ࣇࣟࣔ࢟ࢭࣇࢼࢺ࣒ࣜ࢘㸪 ࣟ࢟ࢯࣉࣟࣇ࢙ࣥࢼࢺ࣒ࣜ࢘㸪㟁ゎ㉁⁐ᾮ㸪ங㓟ࣜࣥࢤࣝᾮ㸪ࢺࣛࢿ࢟ࢧ࣒㓟㸪ࣂࢺࣟ࢟ࢯࣅࣥ㸪 ࢝ࣝࣂࢰࢡ࣒ࣟ㸪ࢫࣝ࣍ࣥ㓟ࢼࢺ࣒ࣜ࢘㸪ሷ㓟࣓ࢺࢡࣟࣉ࣑ࣛࢻ㸪ࣇࣔࢳࢪࣥ㸪㠀⤒ཱྀᰤ 㣴㸪elemeal㸪࣐ࢡࣟࢦ࣮ࣝ㸭ሷ࣒࢝ࣜ࢘㸭Ⅳ㓟Ỉ⣲ࢼࢺ࣒ࣜ࢘㸭ሷࢼࢺ࣒ࣜ࢘㸭◲㓟ࢼࢺࣜ ࣒࢘㸦ࢽࣇࣞࢵࢡ㸧㸪࢚ࣀ࢟ࢧࣃࣜࣥࢼࢺ࣒ࣜ࢘㸪࣊ࣃࣜࣥࢼࢺ࣒ࣜ࢘㸪ࢡ࢚ࣥ㓟➨୍㕲ࢼࢺࣜ ࣒࢘㸪࣓ࢧࣛࢪࣥ㸪ࢡࣟࣝ࣊࢟ࢩࢪࣥࢢࣝࢥࣥ㓟ሷཬࡧ࣏ࣅࢻ࣮ࣥࣚࢻࠋ⾡ᚋࡢᅇࡣⰋዲ࡛࠶ ࡾ㸪⿕㦂⪅ࡣ㸪2014 ᖺ 9 ᭶ 29 ᪥㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome (Study day I/M) 2014-06-23 ⫶⭠⅖ MILD/ Y/ DOSE NOT CHANGED/ 2014-06-27 (97/41) (ACUTE GASTROENTERITIS) DOUBTFUL N RECOVERED/RESOLVED (101/45) 2014-07-23 ⫠㛛⊃✽ MODERATE/ N/ NOT APPLICABLE/ 2014-09-29 (127/71) (ANAL STENOSIS) DOUBTFUL NA RECOVERED/RESOLVED (195/139) 2014-08-28 ⭠⊃✽ MODERATE/ N/ NOT APPLICABLE/ 2014-09-29 (163/107) (RIGHT HEMICOLON STENOSIS) DOUBTFUL NA RECOVERED/RESOLVED (195/139)
14) Concomitant Medications for Adverse Events None reported
25 0 (114) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
(9) Subject CNTO1275CRD3003-4211-10438
1) Reason for narrative selection SAE Event of interest: Serious infection
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome (Study day I/M) 2012-11-15 ᆶ⅖ Y SEVERE/ N/ DOSE NOT CHANGED/ 2012-12-11 (120/66) (APPENDICITIS) DOUBTFUL NA RECOVERED/RESOLVED (146/92) 2012-11-15 ⳦⾑ Y SEVERE/ Y/ DOSE NOT CHANGED/ 2012-12-01 (120/66) (BACTEREMIA) DOUBTFUL Y RECOVERED/RESOLVED (136/82)
3) Baseline Demographic Information Age (years): 7 Sex: Female Weight (kg): 48 Race: Asian Date of birth: Height (cm): 157.5
4) Induction Treatment Group Induction study: CNTO1275CRD3001 Randomized Treatment Group: Ustekinumab Approximating 6 mg/kg IV Actual Treatment Group: Ustekinumab Approximating 6 mg/kg IV
5) Maintenance Treatment Group Assigned Treatment Group: Randomized subject/Responder to ustekinumab IV induction dosing/ustekinumab 90 mg SC q12w
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2012-07-19 1 Ustekinumab 259.2 mg WEEK 0 MAINTENANCE 2012-09-11 55 Ustekinumab 90 mg WEEK 8 MAINTENANCE 2012-11-06 111 Placebo 0 mg WEEK 12 MAINTENANCE 2012-12-11 146 Ustekinumab 90 mg WEEK 16 MAINTENANCE 2013-01-08 174 Placebo 0 mg WEEK 20 MAINTENANCE 2013-02-05 202 Placebo 0 mg WEEK 24 MAINTENANCE 2013-03-05 230 Ustekinumab 90 mg WEEK 28 MAINTENANCE 2013-04-02 258 Placebo 0 mg WEEK 32 MAINTENANCE 2013-04-26 282 Placebo 0 mg WEEK 36 MAINTENANCE 2013-05-21 307 Ustekinumab 90 mg WEEK 40 MAINTENANCE 2013-06-18 335 Placebo 0 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: N Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: Y
8) Induction Baseline Crohn's Disease History Date of diagnosis: 26NOV2008 Disease duration: 3.65 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪ᑠ⭠㏆㸭⫶㸭㣗㐨
25 1 (115) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: NEVER Stricture complications of (CD): NEVER
10) Concomitant Crohn's Disease-Related Surgeries None reported
11) Concomitant Steroids None reported
12) Narrative Text ⿕㦂⪅ࡣ 7 ṓࡢ᪥ᮏேዪᛶ࡛㸪2012 ᖺ 7 ᭶ 19 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏࢆ㟼⬦ෆᢞࡉ ࢀࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏ 90 mg ࢆ q12w ࡛⓶ୗᢞࡍࡿ⩌ࣛࣥࢲ࣒ࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪㕲Ḟஈᛶ㈋⾑㸪 ኚᙧᛶ㛵⠇㸪⭷⅖㸪౽⛎㸪⫧ᛶᚰ➽㸪⭝⅖࡛࠶ࡗࡓࠋ SAE㸸ᆶ⅖㸦Day 120㸧 SAE/Serious Infection㸸⳦⾑㸦Day 120㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2012 ᖺ 11 ᭶ 16 ᪥Ⓨ⇕㸪ྤཬࡧୖ⭡㒊③ࡢࡓࡵධ㝔ࡋࡓࠋᑠ ⭠ࡲ࡛ࡢ㐀ᙳ᳨ᰝ࡛ࡣ㸪ᑠ⭠ෆኚࡣࡳࡽࢀ࡞ࡗࡓࠋ⮫ᗋ᳨ᰝ್ࡣ㸪C ᛂᛶࡓࢇⓑ㸦CRP㸧 ⃰ᗘ 9.5 mg/dL㹙ṇᖖ⠊ᅖ㸦NR㸧<0.20 mg/dL㹛㸪ⓑ⾑⌫ᩘ㸦WBC㸧4.6×103/ȝL㸦NR 3.5-9×103/ȝL㸧 ࡛࠶ࡗࡓࠋ⭡㒊 X ⥺᳨ᰝ࡛ࡣ㸪⭠ෆ࢞ࢫࡢ㈓␃ཬࡧ౽ࡢ㞟ሢࡀࡳࡽࢀࡓࠋ⿕㦂⪅ࡣᢠ⏕≀㉁ 㸦ヲ⣽᫂㸧ࢆᢞࡉࢀࡓࠋ⭡㒊㐀ᙳࢥࣥࣆ࣮ࣗࢱ᩿ᒙᙳ㸦CT㸧ࢫ࡛࢟ࣕࣥࡣ㸪┣⭠ཬࡧ ᆶ⭘⬽ࡀࡳࡽࢀ㸪࿘ᅖ⬡⫫ᵝࡢ㝜ᙳࡀㄆࡵࡽࢀࡓࠋࣂࢱࣝࢧࣥࡣ㸪య 39.5°C㸪⾑ᅽ 123/64 mmHg ࡛࠶ࡗࡓࠋ⭡㒊㐀ᙳ CT ࢫ࢟ࣕࣥ㸦᪥ᮍሗ࿌㸧࡛ࡣ㸪⭠㛢ሰࡀࡳࡽࢀࡓࠋ⭠ࡢᅇ ┣㒊ᾮయ✵Ẽࡀ⁀ࡲࡗࡓ✵Ὕࡀࡳࡽࢀ㸪⮋⒆ࡀࢃࢀࡓࡀ㸪ࡇࡢ✵Ὕ࡛࢞ࢫࡀ⏕⏘ࡉࢀࡓࡢ ⭠ࡘ࡞ࡀࡗ࡚࠸ࡿࡇࡼࡿࡶࡢࡣุ᩿࡛ࡁ࡞ࡗࡓࠋ⫹ᄞᾋ⭘ཬࡧ୧ഃ⭈ᄞ⬊ࡀࡳࡽࢀ ࡓࠋ2012 ᖺ 11 ᭶ 16 ᪥ࡢ⭡㒊㉸㡢Ἴ᳨ᰝ࡛ࡣ㸪ᕥୗ⭡㒊ᾋ㐟≀㸦debris㸧ࢆక࠺⭡Ỉࡀࡳࡽࢀ ࡓࠋ⭡㒊 X ⥺᳨ᰝ࡛ࡣ㸪㐟㞳࢞ࢫࡣࡳࡽࢀ࡞ࡗࡓࠋ⿕㦂⪅ࡢ⭡③ࡣᚎࠎ㍍ῶࡋࡓࡀ㸪Ⓨ⇕ 㸦39.0°C㸧ࡣᣢ⥆ࡋ㸪ࢭࣇࢺࣜ࢟ࢯࣥࢆᢞࡉࢀࡓࠋ2012 ᖺ 11 ᭶ 17 ᪥ࡢ⾑ᾮ᳨ᰝ࡛ࡣ㸪ࢢࣛ ࣒㝜ᛶᱰ⳦㝧ᛶ࡛࠶ࡾ㸪⾑ᾮᇵ㣴᳨ᰝ࡛ࡣ㸪⭠⳦ࡢቑṪࡀࡳࡽࢀࡓࠋࡇࢀࡽࡢ⤖ᯝࡼࡾ㸪⳦⾑ デ᩿ࡉࢀࡓࠋࢭࣇࢺࣜ࢟ࢯࣥࡼࡿ⒪ࡣ⥅⥆ࡋ㸪࣓ࣟ࣌ࢿ࣒ࡼࡿ⒪ࢆ㛤ጞࡋࡓࠋ 2012 ᖺ 11 ᭶ 19 ᪥ࡢ⮫ᗋ᳨ᰝ࡛ࡣ㸪CRP ⃰ᗘ 27 mg/dL㸦༢ཬࡧ⠊ᅖࡢグ㍕࡞ࡋ㸧࡛࠶ࡗࡓࠋ 2012 ᖺ 11 ᭶ 20 ᪥ࡢ⥭ᛴࡢ㐀ᙳ CT ࢫ࡛࢟ࣕࣥࡣ㸪ᅇ┣㒊࿘ᅖࡢ⬡⫫⤌⧊ཬࡧ⭡Ỉࡢቑຍ୪ࡧ ᾮయࡀ⁀ࡲࡗࡓ✵Ὕࡀࡳࡽࢀ㸪࠾ࡑࡽࡃ⮋⒆⪃࠼ࡽࢀࡓࠋᛴᛶࡢ✸Ꮝᛶᆶ⅖デ᩿ࡉࢀࡓࠋ 2012 ᖺ 11 ᭶ 21 ᪥ࡢ⭡㒊㉸㡢Ἴ᳨ᰝ࡛ࡣ㸪ᅇ┣㒊ᾋ㐟≀㸦debris㸧ࢆక࠺⭡Ỉࡀࡳࡽࢀᆶࡢ ✸Ꮝࡢྍ⬟ᛶࡀ♧ࡉࢀࡓࠋ2012 ᖺ 11 ᭶ 26 ᪥ࡢ㉸㡢Ἴࢫ࢟ࣕࣥࡢ㏣㊧ㄪᰝ࡛ࡣ㸪ᅇ┣㒊ࡢ⭡Ỉࡢ ῶᑡࡀࡳࡽࢀ㸪ᆶࡢ⭘⬽ࡣ࡞ࡗࡓࠋCRP ⃰ᗘࡣ 0.8 mg/dL㸪WBC ࡣ 2.6×103/ȝL ࡛࠶ࡗࡓࠋ 2012 ᖺ 11 ᭶ 27 ᪥ࡢ⭠ෆど㙾᳨ᰝ࡛ࡣ㸪ᆶ㛤ཱྀ㒊㸦mouth surrounding the appendix㸧ࡢ⢓⭷ࡢ
25 2 (116) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
Ⓨ㉥ཬࡧ⫧ཌ㸪⅖ࡢ㍍ῶ㸪άືᛶࡢኚࢆకࢃ࡞࠸⅖ᛶ࣏࣮ࣜࣉ㸪ࢡ࣮ࣟࣥࡢᐶゎཬࡧ⤖ ⭠ࡢ₽⒆⒕ࡀࡳࡽࢀ㸪ᅇ⭠ࡢኚࡣάືᛶࢆకࢃ࡞ࡗࡓࠋࢼࢺ࣒ࣜ࢘㸭࣒࢝ࣜ࢘㸭࢝ࣝࢩ࢘ ࣒㸭ሷ≀㸭㓑㓟ሷ㸭ࣈࢻ࢘⢾㸦ࣦ࣮ࣥ D ㍺ᾮ㸧㸪ࣈࢻ࢘⢾ῧຍࢭࢸ࣮ࢺ⥔ᣢᾮ㸦ࣦ࣮ࣥ 3G ㍺ᾮ㸧㸪ࣃࣛࢭࢱ࣮ࣔࣝ㸪࣓ࢧࣛࢪࣥཬࡧ࣌ࣥࢱࢰࢩࣥࡼࡿ⒪ࡀᐇࡉࢀࡓࠋ⿕㦂⪅ࡣ㸪 2012 ᖺ 12 ᭶ 1 ᪥㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome (Study day I/M) 2012-08-25 ⠇㊊ື≀่യ MILD/ N/ DOSE NOT CHANGED/ 2012-08-27 (38/.) (BEE STINGS) NOT RELATED NA RECOVERED/RESOLVED (40/.) 2013-03-05 ⓑ⾑⌫ῶᑡ MILD/ N/ DOSE NOT CHANGED/ 2013-11-12 (230/176) (LEUKOPENIA) NOT RELATED NA RECOVERED/RESOLVED (482/428) 2013-04-19 ࢘ࣝࢫᛶ⫶⭠⅖ MILD/ Y/ DOSE NOT CHANGED/ 2013-04-25 (275/221) (VIRAL ENTERITIS) NOT RELATED Y RECOVERED/RESOLVED (281/227)
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route VALISONE-G 2012-08-26 2012-08-26 TRANSDERMAL BISACODYL 2012-11-16 2012-11-16 RECTAL VEEN 3G 2012-11-16 2012-11-28 INTRAVENOUS VEEN D 2012-11-16 2012-11-28 INTRAVENOUS CEFTRIAXONE SODIUM 2012-11-17 2012-11-18 INTRAVENOUS PHENOXYMETHYLPENICILLIN 2012-11-19 2012-11-26 INTRAVENOUS PENTAZOCINE HYDROCHLORIDE 2012-11-19 2012-11-19 INTRAMUSCULAR PARACETAMOL 2012-11-20 2012-11-20 ORAL MESALAZINE 2013-05-22 - ORAL
(10) Subject CNTO1275CRD3003-4212-10505
1) Reason for narrative selection SAE
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome (Study day I/M) 2012-11-14 ⭠㛢ሰ Y MODERATE/ N/ DOSE NOT CHANGED/ 2012-11-22 (104/44) (COLONIC OBSTRUCTION) DOUBTFUL NA RECOVERED/RESOLVED (112/52)
3) Baseline Demographic Information Age (years): 3 Sex: Male Weight (kg): 68 Race: Asian Date of birth: Height (cm): 169.5
4) Induction Treatment Group Induction study: CNTO1275CRD3001 Randomized Treatment Group: Ustekinumab Approximating 6 mg/kg IV Actual Treatment Group: Ustekinumab Approximating 6 mg/kg IV
5) Maintenance Treatment Group Assigned Treatment Group: Randomized subject/Responder to ustekinumab IV induction dosing/ustekinumab 90 mg SC q8w
25 3 (117) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2012-08-03 1 Ustekinumab 389.7 mg WEEK 0 MAINTENANCE 2012-10-02 61 Ustekinumab 90 mg WEEK 8 MAINTENANCE 2012-11-27 117 Ustekinumab 90 mg WEEK 12 MAINTENANCE 2012-12-21 141 Placebo 0 mg WEEK 16 MAINTENANCE 2013-01-22 173 Ustekinumab 90 mg WEEK 20 MAINTENANCE 2013-02-27 209 Placebo 0 mg WEEK 24 MAINTENANCE 2013-03-19 229 Ustekinumab 90 mg WEEK 28 MAINTENANCE 2013-04-16 257 Placebo 0 mg WEEK 32 MAINTENANCE 2013-05-15 286 Ustekinumab 90 mg WEEK 36 MAINTENANCE 2013-06-12 314 Placebo 0 mg WEEK 40 MAINTENANCE 2013-07-10 342 Ustekinumab 90 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: N Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: Y
8) Induction Baseline Crohn's Disease History Date of diagnosis: 30JUN2005 Disease duration: 7.10 years Involved areas: ⤖⭠ࡢࡳ㸪⫠㛛࿘ᅖ
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: PREVIOUS HISTORY Stricture complications of (CD): CURRENTLY PRESENT
10) Concomitant Crohn's Disease-Related Surgeries None reported
11) Concomitant Steroids None reported
12) Narrative Text ⿕㦂⪅ࡣ 3 ṓࡢ᪥ᮏே⏨ᛶ࡛㸪2012 ᖺ 8 ᭶ 3 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏࢆ㟼⬦ෆᢞࡉ ࢀࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏ 90 mg ࢆ q8w ࡛⓶ୗᢞࡍࡿ⩌ࣛࣥࢲ࣒ࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪╀ཬࡧ㈋ ⾑࡛࠶ࡗࡓࠋ SAE㸸⭠㛢ሰ㸦Day 104㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2012 ᖺ 11 ᭶ 14 ᪥⤖⭠㛢ሰ⥆Ⓨࡋࡓ⭡③ࡼࡾධ㝔ࡋࡓࠋྠ ᪥ࡢ⭡㒊ࢥࣥࣆ࣮ࣗࢱ᩿ᒙᙳࢫ࡛࢟ࣕࣥࡣ㸪ᶓ⾜⤖⭠ࡽୖ⾜⤖⭠ཬࡧᅇ⭠ᮎ➃ᣑᙇ㸪ᕥ⤖ ⭠᭤ཬࡧୗ⾜⤖⭠ࡢෆ⭍⫧ཌཬࡧ⊃✽㸪⌧ࡢ⭠࠾ࡅࡿࢡ࣮ࣟࣥ㉳ᅉࡋࡓ⭠⊃✽୪ࡧ ࣞ࢘ࢫࡀࡳࡽࢀࡓࠋ⮫ᗋ᳨ᰝ್ࡣ㸪C ᛂᛶࡓࢇⓑ⃰ᗘ 0.92 mg/dL㸦2012 ᖺ 11 ᭶ 14 ᪥㸧㸪
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4.17 mg/dL㸦2012 ᖺ 11 ᭶ 15 ᪥㸧㹙ṇᖖ⠊ᅖ㸦NR㸧<0.30 mg/dL㹛㸪Ȗ-ࢢࣝࢱ࣑ࣝࢺࣛࣥࢫࣇ࢙ࣛ ࣮ࢮ 77 IU㸦2012 ᖺ 11 ᭶ 15 ᪥㸧㸦NR 16-73 IU㸧㸪⥲ࡓࢇⓑ 8.4 g/dL㸦2012 ᖺ 11 ᭶ 14 ᪥㸧㸦NR 6.0-8.0 g/dL㸧㸪ⓑ⾑⌫ᩘ 129×102/ȝL㸦2012 ᖺ 11 ᭶ 14 ᪥㸧㸪120×102/ȝL㸦2012 ᖺ 11 ᭶ 15 ᪥㸧 㸦NR 40-90×102/ȝL㸧࡛࠶ࡗࡓࠋ2012 ᖺ 11 ᭶ 15 ᪥ࡢ⣽⳦ᢠཎ᳨ᰝ࡛ࡣ㸪ࢡࣟࢫࢺࣜࢪ࣒࣭࢘ࢹ ࣇࢩࣞ㝧ᛶ࡛࠶ࡗࡓࠋ౽ᇵ㣴᳨ᰝ࡛ࡣ␗ᖖࡣ࡞ࡗࡓࠋ࣌ࣥࢱࢰࢩࣥ㸪ࣜࣥࢤࣝᾮ㸪࣑ࣀ 㓟㸭㟁ゎ㉁⁐ᾮ㸦ࣅ࣮ࣇ࣮ࣜࢻ㸧ࡼࡿ⒪ࢆᐇࡋࡓࠋ2012 ᖺ 11 ᭶ 19 ᪥ࡢୗ㒊ᾘ⟶ෆど㙾 ᳨ᰝ࡛ࡣ㸪⫠㛛ࡽ 10 cm ࡢ┤⭠⊃✽ࡣ࡞ࡗࡓࡀ㸪ࣇࣂ࣮ࢫࢥ࣮ࣉࡣ㏻㐣࡛ࡁ࡞ࡗࡓࠋ ⿕㦂⪅ࡣ㸪2012 ᖺ 11 ᭶ 22 ᪥㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2012-08-08 Ⓨ⇕ MILD/ Y/ DOSE NOT CHANGED/ 2012-08-10 (6/.) (FEVER) DOUBTFUL N RECOVERED/RESOLVED (8/.) 2012-11-16 ᡥ᱈⅖ MILD/ Y/ DOSE NOT CHANGED/ 2012-11-20 (106/46) (TONSILLITIS) NOT Y RECOVERED/RESOLVED (110/50) RELATED 2012-11-17 ࢡࣟࢫࢺࣜࢪ࣒࣭࢘ࢹࣇࢩࣞ⭠⅖ MILD/ Y/ DOSE NOT CHANGED/ 2012-11-27 (107/47) (CLOSTRIDIUM DIFFICILE ASSOCIATED NOT Y RECOVERED/RESOLVED (117/57) DIARRHEA) RELATED
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route PENTAZOCINE HYDROCHLORIDE 2012-11-14 2012-11-14 INTRAMUSCULAR CEFDITOREN PIVOXIL 2012-11-16 2012-11-21 ORAL TRANEXAMIC ACID 2012-11-16 2012-11-21 ORAL METRONIDAZOLE 2012-11-17 2012-11-24 ORAL
(11) Subject CNTO1275CRD3003-4212-20536
1) Reason for narrative selection SAE Discontinuation of study agent due to AE Event of interest: Serious infection
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome I/M) 2013-08-09 ࢡ࣮ࣟࣥ Y MODERATE/ N/ DOSE NOT CHANGED/ 2013-10-17 (3/.) (WORSENING OF CROHN'S NOT NA RECOVERED/RESOLVED (72/.) DISEASE) RELATED 2013-10-25 ࢡ࣮ࣟࣥ Y MODERATE/ N/ DRUG WITHDRAWN/ 2014-02-07 (80/23) (WORSENING OF CROHN'S NOT NA RECOVERED/RESOLVED (185/128) DISEASE) RELATED 2013-12-17 ᩋ⾑ Y SEVERE/ Y/ NOT APPLICABLE/ 2013-12-25 (133/76) (SEPSIS) POSSIBLE Y RECOVERED/RESOLVED (141/84)
3) Other Adverse Events Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome (Study day I/M) 2013-08-09 㢌③ MILD/ N/ DOSE NOT CHANGED/ 2013-10-07 (3/.) (HEADACHE) NOT RELATED NA RECOVERED/RESOLVED (62/.)
25 5 (119) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome (Study day I/M) 2013-08-29 ་⒪ᶵჾ㛵㐃ឤᰁ MILD/ Y/ DOSE NOT CHANGED/ 2013-09-07 (23/.) (CENTRAL LINE INFECTION) NOT RELATED Y RECOVERED/RESOLVED (32/.) 2013-08-31 ཱྀ⭍࣊ࣝ࣌ࢫ MILD/ Y/ DOSE NOT CHANGED/ 2013-09-08 (25/.) (HERPES LABIALIS) POSSIBLE Y RECOVERED/RESOLVED (33/.) 2013-09-03 ࡊ⒔ MILD/ N/ DOSE NOT CHANGED/ 2013-09-08 (28/.) (ACNE) NOT RELATED NA RECOVERED/RESOLVED (33/.) 2013-10-25 ⫠㛛⮋⒆ MODERATE/ Y/ DOSE NOT CHANGED/ 2014-03-26 (80/23) (PERIANAL ABSCESS) DOUBTFUL Y RECOVERED/RESOLVED (232/175) 2013-11-06 㰯ဗ㢌⅖ MILD/ Y/ DOSE NOT CHANGED/ 2013-11-29 (92/35) (COMMON COLD) NOT RELATED N RECOVERED/RESOLVED (115/58) 2013-12-06 ┤⭠⮋⒆ MODERATE/ Y/ DOSE NOT CHANGED/ 2014-01-06 (122/65) (RECTAL ABSCESS) DOUBTFUL Y RECOVERED/RESOLVED (153/96) 2013-12-17 ⣽⳦ᛶ⭠⅖ SEVERE/ Y/ DOSE NOT CHANGED/ 2014-01-04 (133/76) (MRSA ENTEROCOLITIS) DOUBTFUL Y RECOVERED/RESOLVED (151/94) 2013-12-17 ཱྀ⭍࢝ࣥࢪࢲ MILD/ Y/ NOT APPLICABLE/ 2014-01-18 (133/76) (CANDIDA STOMATITIS) DOUBTFUL Y RECOVERED/RESOLVED (165/108) 2013-12-19 ⭈ᶵ⬟㞀ᐖ MILD/ N/ DOSE NOT CHANGED/ 2014-01-25 (135/78) (RENAL IMPAIRMENT) NOT RELATED NA RECOVERED/RESOLVED (172/115) 2013-12-20 တႿ MILD/ N/ NOT APPLICABLE/ 2013-12-29 (136/79) (COUGH) NOT RELATED NA RECOVERED/RESOLVED (145/88) 2014-03 ព㆑ᾘኻ MODERATE/ N/ NOT APPLICABLE/ 2014-03 - (UNCONSCIOUSNESS) NOT RELATED NA RECOVERED/RESOLVED -
4) Baseline Demographic Information Age (years): 4 Sex: Male Weight (kg): 49.8 Race: Asian Date of birth: Height (cm): 169.3
5) Induction Treatment Group Induction study: CNTO1275CRD3002 Randomized Treatment Group: Ustekinumab Approximating 6 mg/kg IV Actual Treatment Group: Ustekinumab Approximating 6 mg/kg IV
6) Maintenance Treatment Group Assigned Treatment Group: Non-randomized subject/Non-responder to ustekinumab IV induction dosing and received ustekinumab in maintenance
7) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2013-08-07 1 Ustekinumab 259.2 mg WEEK 0 MAINTENANCE 2013-10-03 58 Ustekinumab 90 mg WEEK 0 MAINTENANCE 2013-10-03 58 Placebo 0 mg WEEK 8 MAINTENANCE 2013-11-29 115 Ustekinumab 90 mg
8) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: Y Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: -
9) Induction Baseline Crohn's Disease History Date of diagnosis: 01SEP1996 Disease duration: 16.93 years Involved areas: ᅇ⭠ࡢࡳ㸪⫠㛛࿘ᅖ
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10) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: PREVIOUS HISTORY Fistula: CURRENTLY PRESENT Stricture complications of (CD): CURRENTLY PRESENT
11) Concomitant Crohn's Disease-Related Surgeries Surgery Date Result of lack of efficacy? ࢻࣞࢼ࣮ࢪ-⤒⓶ษ㛤ཬࡧࢻࣞࢼ࣮ࢪ 2013-10-25 Y ࢻࣞࢼ࣮ࢪ-⤒⓶ษ㛤ཬࡧࢻࣞࢼ࣮ࢪ 2013-12-19 Y ࢻࣞࢼ࣮ࢪ-⤒⓶ษ㛤ཬࡧࢻࣞࢼ࣮ࢪ 2014-01-26 Y
12) Concomitant Steroids None reported
13) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route DEXTROSE AND SODIUM CHLORIDE INJECTION 2013-08-09 2013-08-11 INTRAVENOUS BLOOD SUBSTITUTES AND PERFUSION SOLUTIONS 2013-08-09 2013-08-09 INTRAVENOUS RED BLOOD CELLS 2013-08-10 2013-08-10 INTRAVENOUS NEOLAMIN 3B /00520001/ 2013-08-10 2013-08-11 INTRAVENOUS ALBUMIN HUMAN 2013-08-10 2013-08-11 INTRAVENOUS OSMOSAL /00501801/ 2013-08-10 2013-08-11 INTRAVENOUS GLYCINE MAX SEED OIL 2013-08-11 2013-08-16 INTRAVENOUS SOLUTIONS FOR PARENTERAL NUTRITION 2013-08-12 2013-08-15 INTRAVENOUS HYDROXYZINE EMBONATE 2013-08-13 2013-08-14 INTRAMUSCULAR AMINO ACIDS NOS W/COPPER/ELECTROLYTES NOS/GLU 2013-08-14 2013-08-14 INTRAVENOUS AMINO ACIDS NOS W/COPPER/ELECTROLYTES NOS/GLU 2013-08-16 2013-09-05 INTRAVENOUS LIDOCAINE HYDROCHLORIDE 2013-08-20 2013-08-20 TOPICAL HYDROXYZINE EMBONATE 2013-08-21 2013-08-22 INTRAMUSCULAR INTRALIPID /00272201/ 2013-08-27 2013-08-29 INTRAVENOUS CEFEPIME HYDROCHLORIDE 2013-08-29 2013-09-02 INTRAVENOUS FLURBIPROFEN AXETIL 2013-08-29 2013-08-29 INTRAVENOUS HYDROXYZINE EMBONATE 2013-08-29 2013-08-30 INTRAMUSCULAR SODIUM CHLORIDE 2013-08-29 2013-09-02 INTRAVENOUS DEXTROSE AND SODIUM CHLORIDE INJECTION 2013-08-29 2013-08-30 INTRAVENOUS METAMIZOLE SODIUM 2013-08-29 2013-08-29 INTRAVENOUS VANCOMYCIN HYDROCHLORIDE 2013-08-29 2013-09-02 INTRAVENOUS VIDARABINE 2013-08-31 2013-09-08 TRANSDERMAL ADAPALENE 2013-09-03 2013-09-08 TRANSDERMAL CEFAZOLIN SODIUM 2013-09-03 2013-09-07 INTRAVENOUS NADIFLOXACIN 2013-09-03 2013-09-08 TRANSDERMAL HYDROXYZINE EMBONATE 2013-09-04 2013-09-04 INTRAMUSCULAR AMINO ACIDS NOS W/ELECTROLYTES NOS/GLUCOSE/TH 2013-09-06 2013-09-11 INTRAVENOUS NUTRIENTS NOS 2013-09-07 2013-09-08 ORAL NUTRIENTS NOS 2013-09-09 2013-09-12 ORAL OSMOSAL /00501801/ 2013-09-12 2013-09-12 INTRAVENOUS NUTRIENTS NOS 2013-09-13 2013-09-14 ORAL NUTRIENTS NOS 2013-09-15 2013-09-30 ORAL DEXTROSE AND SODIUM CHLORIDE INJECTION 2013-09-27 2013-09-27 INTRAVENOUS HYDROXYZINE EMBONATE 2013-09-28 2013-09-30 INTRAMUSCULAR NEOLAMIN 3B /00520001/ 2013-09-28 2013-10-01 INTRAVENOUS OSMOSAL /00501801/ 2013-09-28 2013-10-01 INTRAVENOUS NUTRIENTS NOS 2013-10-01 2013-10-01 ORAL
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Preferred Term Start Date End Date Route NUTRIENTS NOS 2013-10-02 2013-10-02 ORAL NUTRIENTS NOS 2013-10-03 2013-10-06 ORAL HYDROXYZINE EMBONATE 2013-10-07 2013-10-07 INTRAMUSCULAR CEFCAPENE PIVOXIL HYDROCHLORIDE 2013-10-27 2013-10-27 ORAL HYDROXYZINE EMBONATE 2013-10-27 2013-10-27 INTRAMUSCULAR PENTAZOCINE 2013-10-27 2013-10-27 INTRAMUSCULAR HYDROXYZINE EMBONATE 2013-10-30 2013-10-31 INTRAMUSCULAR PENTAZOCINE 2013-10-30 2013-10-31 INTRAMUSCULAR POVIDONE-IODINE 2013-10-30 2013-10-30 INTRAVENOUS LIDOCAINE HYDROCHLORIDE 2013-10-30 2013-10-30 INTRAVENOUS HYDROXYZINE EMBONATE 2013-11-06 2013-11-06 INTRAMUSCULAR PENTAZOCINE 2013-11-06 2013-11-06 INTRAMUSCULAR HYDROXYZINE EMBONATE 2013-11-27 2013-11-27 INTRAMUSCULAR PENTAZOCINE 2013-11-27 2013-11-27 INTRAMUSCULAR HYDROXYZINE EMBONATE 2013-11-29 2013-11-29 INTRAMUSCULAR PENTAZOCINE 2013-11-29 2013-11-29 INTRAMUSCULAR CIPROFLOXACIN HYDROCHLORIDE 2013-12-06 2013-12-08 ORAL HYDROXYZINE EMBONATE 2013-12-06 2013-12-06 INTRAMUSCULAR PENTAZOCINE 2013-12-06 2013-12-06 INTRAMUSCULAR AMINO ACIDS NOS W/ELECTROLYTES NOS/GLUCOSE/TH 2013-12-09 2013-12-17 INTRAVENOUS AMINO ACIDS NOS W/COPPER/ELECTROLYTES NOS/GLU 2013-12-09 2013-12-11 INTRAVENOUS LOXOPROFEN 2013-12-09 2013-12-09 ORAL GLYCINE MAX SEED OIL 2013-12-10 2013-12-11 INTRAVENOUS HYDROXYZINE HYDROCHLORIDE 2013-12-11 2013-12-11 INTRAMUSCULAR CEFTRIAXONE SODIUM 2013-12-11 2013-12-17 INTRAVENOUS LOXOPROFEN 2013-12-11 2013-12-11 ORAL PENTAZOCINE HYDROCHLORIDE 2013-12-11 2013-12-11 INTRAMUSCULAR ALBUMIN HUMAN 2013-12-11 2013-12-11 INTRAVENOUS AMINO ACIDS NOS W/COPPER/ELECTROLYTES NOS/GLU 2013-12-12 2013-12-17 INTRAVENOUS HYDROXYZINE EMBONATE 2013-12-15 2013-12-16 INTRAMUSCULAR PENTAZOCINE 2013-12-15 2013-12-16 INTRAMUSCULAR CEFEPIME HYDROCHLORIDE 2013-12-17 2013-12-19 INTRAVENOUS FLURBIPROFEN AXETIL 2013-12-17 2013-12-18 INTRAVENOUS METRONIDAZOLE 2013-12-17 2014-01-04 ORAL NEOLAMIN 3B /00520001/ 2013-12-17 2013-12-20 INTRAVENOUS ALBUMIN HUMAN 2013-12-17 2013-12-17 INTRAVENOUS DEXTROSE AND SODIUM CHLORIDE INJECTION 2013-12-17 2013-12-24 INTRAVENOUS OSMOSAL /00501801/ 2013-12-17 2013-12-22 INTRAVENOUS METAMIZOLE SODIUM 2013-12-17 2013-12-18 INTRAMUSCULAR VANCOMYCIN HYDROCHLORIDE 2013-12-17 2013-12-18 INTRAVENOUS CASPOFUNGIN ACETATE 2013-12-19 2013-12-24 INTRAVENOUS PLASMA PROTEIN FRACTION (HUMAN) 2013-12-19 2013-12-19 INTRAVENOUS HUSCODE 2013-12-19 2013-12-21 ORAL L-CARBOCYSTEINE 2013-12-19 2013-12-21 ORAL RINGER-LACTATIS 2013-12-19 2013-12-20 INTRAVENOUS MEROPENEM TRIHYDRATE 2013-12-19 2013-12-24 INTRAVENOUS NOREPINEPHRINE 2013-12-19 2013-12-21 INTRAVENOUS TULOBUTEROL 2013-12-19 2014-01-06 TRANSDERMAL TRANEXAMIC ACID 2013-12-19 2013-12-24 ORAL VANCOMYCIN HYDROCHLORIDE 2013-12-19 2014-01-04 ORAL FLURBIPROFEN AXETIL 2013-12-20 2013-12-20 INTRAVENOUS ALBUMIN HUMAN 2013-12-20 2013-12-21 INTRAVENOUS VANCOMYCIN HYDROCHLORIDE 2013-12-20 2013-12-30 INTRAVENOUS POVIDONE-IODINE 2013-12-21 2013-12-25 TOPICAL POLAPREZINC 2013-12-21 2013-12-24 ORAL DEQUALINIUM CHLORIDE 2013-12-21 2013-12-25 ORAL
25 8 (122) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
Preferred Term Start Date End Date Route ZINC OXIDE 2013-12-21 2013-12-31 TRANSDERMAL NEOLAMIN 3B /00520001/ 2013-12-23 2013-12-24 INTRAVENOUS OSMOSAL /00501801/ 2013-12-23 2013-12-25 INTRAVENOUS AMINO ACIDS NOS W/ELECTROLYTES NOS/GLUCOSE/TH 2013-12-25 2014-01-06 INTRAVENOUS AMPHOTERICIN B 2013-12-25 2014-01-18 ORAL AMINO ACIDS NOS W/COPPER/ELECTROLYTES NOS/GLU 2013-12-26 2013-12-26 INTRAVENOUS AMINO ACIDS NOS W/COPPER/ELECTROLYTES NOS/GLU 2013-12-27 2014-01-06 INTRAVENOUS FUROSEMIDE 2013-12-27 2013-12-31 ORAL GLYCINE MAX SEED OIL 2013-12-30 2013-12-31 INTRAVENOUS RED BLOOD CELLS 2014-01-03 2014-01-03 INTRAVENOUS GLYCINE MAX SEED OIL 2014-01-04 2014-01-06 INTRAVENOUS RED BLOOD CELLS 2014-01-08 2014-01-09 INTRAVENOUS AMINO ACIDS NOS W/COPPER/ELECTROLYTES NOS/GLU 2014-01-09 2014-01-30 INTRAVENOUS INFLIXIMAB 2014-01-16 2014-01-16 INTRAVENOUS METAMIZOLE SODIUM 2014-01-17 2014-01-17 INTRAVENOUS NUTRIENTS NOS 2014-01-21 2014-01-23 ORAL AZATHIOPRINE 2014-01-21 - ORAL NUTRIENTS NOS 2014-01-24 2014-01-26 ORAL CEFTRIAXONE 2014-01-25 2014-01-29 INTRAVENOUS HYDROXYZINE EMBONATE 2014-01-25 2014-01-27 INTRAMUSCULAR SODIUM CHLORIDE 2014-01-25 2014-01-29 INTRAVENOUS LOXOPROFEN 2014-01-25 2014-01-25 ORAL PENTAZOCINE 2014-01-25 2014-01-26 INTRAVENOUS DEXTROSE AND SODIUM CHLORIDE INJECTION 2014-01-25 2014-02-02 INTRAVENOUS DEXTROSE AND SODIUM CHLORIDE INJECTION 2014-01-25 2014-02-02 INTRAVENOUS PARACETAMOL 2014-01-27 2014-01-27 ORAL PARACETAMOL 2014-01-29 2014-01-29 ORAL HYDROXYZINE EMBONATE 2014-01-30 2014-01-30 INTRAVENOUS INFLIXIMAB 2014-01-30 2014-01-30 INTRAVENOUS NEOLAMIN 3B /00520001/ 2014-01-31 2014-02-02 INTRAVENOUS OSMOSAL /00501801/ 2014-01-31 2014-02-03 INTRAVENOUS
14) Narrative Text ⿕㦂⪅ࡣ 4 ṓࡢ᪥ᮏே⏨ᛶ࡛㸪2013 ᖺ 8 ᭶ 7 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏ㸦㹼6 mg/kg ⩌㸧 ࢆ㟼⬦ෆᢞࡉࢀࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏ 90 mg ࢆ q8w ࡛⓶ୗᢞࡍࡿ⩌ࣛࣥࢲ࣒ࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪ᅇ⭠⭤⬔⒦Ꮝ ࡼࡿᅇ⭠⒦㐀タཬࡧ⒦Ꮝ㛢㙐㸪✸Ꮝᛶ⭡⭷⅖㸪ᅇ⭠✸Ꮝ㸪ᅇ┣㒊ษ㝖㸪᰾ᡭ⾡㸪ࢩ࣮ࢺࣥ␃ ⨨ࢆక࠺⒦୪ࡧࣥࣇࣜ࢟ࢩ࣐ࣈ㸪ࢲ࣒࣐ࣜࣈཬࡧࢨࢳ࢜ࣉࣜࣥࡼࡿ⒪࡛࠶ࡗࡓࠋ
௨ୗࡣᐶゎᑟධヨ㦂 CNTO1275CRD3002 ࡢ㦂⥲ᣓሗ࿌᭩ࡢ⿕㦂⪅ࡢླྀ㏙࡚ሗ࿌ࡉࢀࡓ ㇟࡛࠶ࡿ㸸 SAE㸸ࢡ࣮ࣟࣥ㸦Day 3㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2013 ᖺ 8 ᭶ 9 ᪥⾑౽ࡢࡓࡵᩆᛴእ᮶ࢆཷデࡋ㸪ࢡ࣮ࣟࣥᝏ ࡢࡓࡵ㸪ධ㝔ࡋࡓࠋྠ᪥ࡑࡢᚋ㸪⿕㦂⪅ࡣ㢌③㸪ᾋືᛶࡵࡲ࠸ཬࡧᝏᚰࢆッ࠼ࡓࠋ⌮Ꮫⓗ᳨ᰝ࡛ ࡣ㸪⭠㞧㡢ࡢቑຍ௨እ㸪᫂ࡽ࡞ᡤぢࡣ࡞ࡗࡓࠋୗ㒊ᾘჾෆど㙾᳨ᰝ࡛ࡣ㸪ᑠࡉ࠸⎔≧ࡢ₽ ⒆ཬࡧ⫠㛛₽⒆ࡢ㐍ᒎࡀㄆࡵࡽࢀࡓࠋ㢌㒊ཬࡧ⬚㒊ࢥࣥࣆ࣮ࣗࢱ᩿ᒙᙳ㸦CT㸧ࢫ࡛࢟ࣕࣥ ࡣ㸪⬻ࡢᒁᡤኚཬࡧ᪂つࡢ⫵ኚࡣ࡞ࡗࡓࠋ⭡㒊 CT ࢫ࡛࢟ࣕࣥࡣ㍍ᗘࡢᑠ⭠ቨ⫧ཌ㸪୪ࡧ ࿀ྜ㒊ཱྀഃࡢᑠ⭠㸪ୖ⾜⤖⭠ཬࡧ S ≧⤖⭠㍍ᗘࡢ⫧ཌཬࡧᣑᙇࡀㄆࡵࡽࢀࡓࠋ
25 9 (123) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
2013 ᖺ 8 ᭶ 10 ᪥ᗘᐇࡋࡓ⭡㒊 CT ᳨ᰝ࡛ࡣ㸪ᅇ┣ษ㝖㒊࿘㎶ࡢ⭠⟶ᾋ⭘ᛶࡢ⫧ཌ ࡀㄆࡵࡽࢀ㸪ࡇࢀࡣࢡ࣮ࣟࣥࡼࡿάືᮇࡢ⅖㉳ᅉࡍࡿ⪃࠼ࡽࢀࡓࠋୖ⾜⤖⭠ࡢᣑᙇࡣ㸪 ๓ᅇࡢ CT ࢫ࢟ࣕࣥ⤖ᯝẚ㍑ࡋ࡚ᨵၿࡋ࡚࠸ࡓࠋ2013 ᖺ 8 ᭶ 20 ᪥ࡢୗ㒊ᾘჾෆど㙾᳨ᰝ ࡛ࡣ㸪࿀ྜ㒊ཱྀഃࡢᑠ⭠ཬࡧ S ≧⤖⭠ࡽ┤⭠㸦⫠㛛⦕ࡽ 15 cm㸧ࡲ࡛ࡢ㒊㸪ࡧࡽࢇ㸪ὸ ࠸₽⒆ཬࡧ⮋ᛶศἪ≀ࡀᩓᅾᛶㄆࡵࡽࢀࡓࠋ2013 ᖺ 9 ᭶ 27 ᪥ࡢᾘჾෆど㙾᳨ᰝ࡛ࡣ㸪ୖ 㒊ᾘ⟶␗ᖖᡤぢࡣ࡞ࡗࡓࡀ㸪ୗ㒊ᾘჾෆど㙾᳨ᰝ࡛ࡣ㸪⭠࿀ྜ㒊ὸ࠸₽⒆ཬࡧ⮋ ᛶศἪ≀ࡀㄆࡵࡽࢀࡓࠋ≧ែࡣࡸࡸᨵၿࡋࡓࡀ㸪S ≧⤖⭠ࡢࡧࡽࢇཬࡧὸ࠸₽⒆ࡣᣢ⥆ࡋࡓࠋ 2013 ᖺ 9 ᭶ 28 ᪥ࡢ⭡㒊 CT ࢫ࡛࢟ࣕࣥࡣ㸪ᅇ┣ษ㝖㒊࿘㎶ࡢ⭠⟶ᾋ⭘ᛶࡢ⫧ཌࡀࡳࡽࢀ㸪 ࢡ࣮ࣟࣥࡢᝏ㸪㦵┙ෆࡢᑠ⭠ᣑᙇࡢ㍍ᗘᝏཬࡧ⭡Ỉ㔞ࡢቑຍ㉳ᅉࡍࡿ⪃࠼ࡽࢀࡓࠋ 2013 ᖺ 8 ᭶ 9 ᪥ࡽ 2013 ᖺ 10 ᭶ 30 ᪥ࡲ࡛ࡢ⮫ᗋ᳨ᰝ್ࡣ௨ୗࡢኚືࡀㄆࡵࡽࢀࡓ㸸ࣛ ࢽ࣑ࣥࣀࢺࣛࣥࢫࣇ࢙࣮ࣛࢮ 49-76 IU/L㹙ṇᖖ⠊ᅖ㸦NR㸧4-44 IU/L㹛㸪Ȗ-ࢢࣝࢱ࣑ࣝࢺࣛࣥࢫ ࣇ࢙࣮ࣛࢮ 115-475 IU/L㸦NR 16-73 IU/L㸧㸪࣐࣊ࢺࢡࣜࢵࢺ 29.8%-37%㸦NR 40%-55%㸧㸪࣊ࣔ ࢢࣟࣅࣥ 8.4-11.3 g/dL㸦NR 14-18 g/dL㸧㸪㉥⾑⌫ᩘ 270-391×104/ȝcL㸦NR 400-570×104/ȝL㸧㸪⥲ ࡓࢇⓑ 3.6-5.8 g/dL㸦NR 6-8 g/dL㸧㸪ⓑ⾑⌫ᩘ 27-80×102/ȝL㸦NR 40-90×102/ȝL㸧ࠋ ⿕㦂⪅ࡣ㸪2013 ᖺ 10 ᭶ 17 ᪥㏥㝔ࡋ㸪ྠ᪥㸪ࢡ࣮ࣟࣥࡢᝏࡣᅇ㸭ᾘᩓࡋࡓሗ࿌ࡉࢀ ࡓࠋ
௨ୗࡣᐶゎ⥔ᣢ⒪ἲ࡛࠶ࡿᮏヨ㦂࡛つᐃࡉࢀࡓሗ࿌ᮇ㛫Ⓨ⌧ࡋࡓ㇟࡛࠶ࡿ㸸 SAE/Discontinuation of study agent due to AE㸸ࢡ࣮ࣟࣥ㸦Day 80㸧 CIOMS ཬࡧ⮫ᗋグ㘓ࡼࡿ㸪⿕㦂⪅ࡣࢡ࣮ࣟࣥࡢ⒪ࡢࡓࡵ㸪2013 ᖺ 12 ᭶ 9 ᪥ධ㝔ࡋ ࡓࠋ⿕㦂⪅ࡣ⒦ࡢᝏࡢࡓࡵ㸪2013 ᖺ 10 ᭶ 25 ᪥㦂ᐇタࡢእ⛉᮶㝔ࡋ࡚࠸ࡓࠋ⑊③ ᑐࡋ㙠③ࢆᢞࡉࢀ㸪⒦㒊ࢻ࣮ࣞࣥࢆᤄධࡋࡓࠋ⒦ࡢ⑊③ࡣ 2013 ᖺ 10 ᭶ 27 ᪥ཬ ࡧ 30 ᪥㧗ᗘ࡞ࡾ㸪⒦㒊ࡢࢻ࣮ࣞࣥࡀ⬺ฟࡋࡓࡓࡵ᮶㝔ࡋࡓࠋ⑊③ᑐࡋ㸪ࣄࢻࣟ࢟ࢩ ࢪࣥ㸦ࢱࣛࢵࢡࢫ-P㸧ཬࡧ࣌ࣥࢱࢰࢩࣥ㸦࣌ࣥࢱࢪࣥ㸧ࡀᢞࡉࢀ㸪ࢻ࣮ࣞࣥࡣᤄධཬࡧᅛ ᐃࡉࢀࡓࠋ2013 ᖺ 10 ᭶ 31 ᪥ࡢデᐹ࡛ࡣ㸪ࢻ࣮ࣞࣥᤄධ㒊ࢆほᐹࡋ㸪ᾘẘࡋࡓࠋ2013 ᖺ 11 ᭶ 6 ᪥⒦㒊ࡢࢻ࣮ࣞࣥࢆほᐹࡋ㸪ホ౯ࡋࡓࠋ⑊③ࡀᣢ⥆ࡋࡓࡓࡵࣄࢻࣟ࢟ࢩࢪࣥཬࡧ࣌ࣥࢱ ࢰࢩࣥࡀᢞࡉࢀ㸪ࢻ࣮ࣞࣥࡣᤄධཬࡧᅛᐃࡉࢀࡓࠋ ⒦ࡢ⑊③ࡀ㧗ᗘ࡞ࡗࡓࡓࡵ㸪2013 ᖺ 12 ᭶ 6 ᪥ CT ࢫ࢟ࣕࣥࢆᐇࡋࡓ⤖ᯝ㸪ࢡ࣮ࣟࣥ ࡢᝏデ᩿ࡉࢀ㸪㦂⸆ࡢᢞࢆᘏᮇࡋࡓࠋ୍᪦ධ㝔ࡋ㸪⭡③㸪Ⓨ⇕ཬࡧ┤⭠⮋⒆㉳ᅉࡋ ࡓ⫠㛛⒦Ꮝ㒊ࡢ⑊③ᑐࡋ࡚㸪ᢠ⏕≀㉁㸦ࢭࣇ࢙ࣆ࣒ሷ㓟ሷ㸪ࣂࣥࢥ࣐ࢩࣥ㸪ࢭࣇࢰࣜࣥࢼ ࢺ࣒ࣜ࢘㸧㸪⤯㣗㸪ࣅ࣮ࣇ࣮ࣜࢻࢆ⏝ࡋࡓ㧗࣮࢝ࣟࣜࡢỈศ⿵⤥㸦mineral injection)㸪࢚ࣝࢿ࢜ ࣃ 1 ྕ㍺ᾮ㸦㠀⤒ཱྀᰤ㣴㸧㸪ࣝࣈ࣑ࣥཬࡧࢭࣇࢺࣜ࢟ࢯࣥࡼࡿ⒪ࡀᐇࡉࢀࡓࠋ 2013 ᖺ 12 ᭶ 16 ᪥ࡲ࡛ entazocine ࡀᢞࡉࢀ㸪2013 ᖺ 12 ᭶ 16 ᪥ࢯࢪࣥࢆᄇ㟝㸦isodine injection㸧ࡉࢀࡓࠋ 㦂⸆ᢞ 18 ᪥ᚋࡢ 2013 ᖺ 12 ᭶ 17 ᪥㸪⿕㦂⪅ࡣ 40°C ࡢⓎ⇕ࢆⓎ⌧ࡋ㸪ᩋ⾑デ᩿ࡉ ࢀࡓ㸦ୗグࡢ SAE㸸ᩋ⾑ࢆཧ↷㸧ࠋྠ᪥㸪ᢠ⏕≀㉁⒪ࡼࡿഇ⭷ᛶᑠ⭠⤖⭠⅖㉳ᅉࡍࡿ ⪃࠼ࡽࢀࡿୗ⑩ࢆⓎ⌧ࡋࡓࠋࡑࡢᚋ㸪࣓ࢺࣟࢽࢲࢰ࣮ࣝ㸦ࣇࣛࢪ࣮ࣝ㸧ࢆᢞࡉࢀࡓࠋ2013 ᖺ 12 ᭶ 19 ᪥㸪┤⭠࿘ᅖ⮋⒆ࡢࡓࡵࢻࣞࢼ࣮ࢪࢆᐇࡋࡓࠋ౽ཬࡧ⮋⒆᳨య㸦abscess matter㸧ࡢ᳨ ᰝ࡛ࡣ㸪࣓ࢳࢩࣜࣥ⪏ᛶ㯤Ⰽࣈࢻ࢘⌫⳦㸦MRSA㸧㝧ᛶ࡛࠶ࡾ㸪MRSA ࡼࡿᑠ⭠⤖⭠⅖ࡀ♧၀
26 0 (124) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
ࡉࢀࡓࠋᑠ⭠⅖ᑐࡋ࡚࣓ࢺࣟࢽࢲࢰ࣮ࣝཬࡧࣂࣥࢥ࣐ࢩࣥሷ㓟ሷࡼࡿ⒪ࡀᐇࡉࢀࡓࠋ ⿕㦂⪅ࡣࡉࡽ㸪ୖグࡢ⸆ࢆᢞࡉࢀࡓࠋ2013 ᖺ 12 ᭶ 19 ᪥ࡢ CT ࢫ࢟ࣕࣥࡢᡤぢ࡛ࡣ㸪㛫㉁ ᛶ⫵⅖ࢆྵࡴឤᰁࡢྍ⬟ᛶཬࡧᕥ⫵ᗏ㒊ᾐ₶ᙳࡀㄆࡵࡽࢀࡓࠋ ࡑࡢᚋࡢᩘ᪥㛫࠾ࡅࡿ⒪࡛ࡣ㸪ᚰ⾑⟶ࡢᏳᐃᛶࢆ⥔ᣢࡋࡘࡘ㸪₯ᅾⓗ࡞ឤᰁࢆ⒪ࡋ࡞ ࡀࡽ⟶⌮ࡉࢀࡓࠋ2013 ᖺ 12 ᭶ 25 ᪥㸪⿕㦂⪅ࡣᚠ⎔ືែࡢᝏࡽᅇࡋࡓࡓࡵ㸪ᩋ⾑ࡣᅇ 㸭ᾘᩓࡋࡓデ᩿ࡉࢀࡓ㸦ୗグࡢ SAE㸸ᩋ⾑ࢆཧ↷㸧ࠋ2013 ᖺ 12 ᭶ 30 ᪥⇕ࡣୗࡀࡾ㸪 ⅖ᛂࡣᨵၿࡉࢀࡓࡀ㸪ୗ⑩ࡣᣢ⥆ࡋࡓࡓࡵ㸪࣓ࢺࣟࢽࢲࢰ࣮ࣝཬࡧࣂࣥࢥ࣐ࢩࣥࡢ⤒ཱྀᢞ ࡢࡳ⥅⥆ࡋࡓࠋ2014 ᖺ 1 ᭶ 3 ᪥ࡢ⾑ᾮ᳨ᰝ࡛ࡣ㸪㈋⾑ࡢ㐍⾜క࠺࣊ࣔࢢࣟࣅࣥప್㸦6.5㸪 ༢ᮍሗ࿌㸧ࡀࡳࡽࢀࡓࠋᩆ῭⒪㸦corrective treatment㸧ࡋ࡚㉥⾑⌫ 2 ༢ࡀ㍺⾑ࡉࢀ㸪࣊ࣔ ࢢࣟࣅ್ࣥࡣ 2014 ᖺ 1 ᭶ 4 ᪥ 8.3 ᨵၿࡋࡓࠋࣂࣥࢥ࣐ࢩࣥࡢ⤒ཱྀᢞࡣ୰Ṇࡉࢀࡓࠋ 2014 ᖺ 1 ᭶ 7 ᪥ࡢẚ㔜ࡣ 1.023㸦NR 1.006-1.022㸪༢ᮍሗ࿌㸧㧗್࡛࠶ࡗࡓࠋ2014 ᖺ 1 ᭶ 9 ᪥㸪࣊ࣔࢢࣟࣅ್ࣥࡣୖ᪼ࡋ࡚࠸࡞ࡗࡓࠋ㉥⾑⌫ࡀࡉࡽ 2 ༢㍺⾑ࡉࢀࡓࠋ2014 ᖺ 1 ᭶ 10 ᪥ࡢᢠ㓟⳦ࡢ᳨ᰝࡣ㝜ᛶ࡛࠶ࡗࡓࡀ㸪ྠ᪥ࡢ୍⯡ࡢ⣽⳦᳨ᰝ࡛㸪⫵⬊ࡢὙίᾮࡽឤᰁᛶཎ⳦ ࡀ᳨ฟࡉࢀࡓࠋ2014 ᖺ 1 ᭶ 16 ᪥ࣥࣇࣜ࢟ࢩ࣐ࣈࢆᢞࡉࢀࡓࠋ 2014 ᖺ 1 ᭶ 25 ᪥ࡢ⭡㒊 CT ࢫ࡛࢟ࣕࣥࡣ㸪࿀ྜ㒊ࡼࡾ๓ࡢᅇ⭠⭠ቨࡢ⫧ཌࡀࡳࡽࢀ㸪௨๓ࡢ ᡭ⾡ᚋࡢᡤぢ㸦2014 ᖺ 1 ᭶ 6 ᪥㸧ྠᵝ࡛࠶ࡗࡓࠋ┤⭠⭠ቨࡢ⫧ཌࡣⱝᖸ㍍ῶࡋࡓࡼ࠺࡛࠶ࡗࡓࠋ ᫂☜࡞⮋⒆ᙧᡂཪࡣ㐟㞳࢞ࢫࡣ࡞ࡃ㸪⭡⭍ෆ⭡Ỉࡣࡳࡽࢀ࡞ࡗࡓࠋデ᩿࡛ࡣ㸪⫠㛛࿘ᅖࡢ⮋ ⒆ࡢቑᝏࡀࢃࢀࡓࠋ 2014 ᖺ 1 ᭶ 26 ᪥㸪┤⭠ࡢ⮋⒆ࡢᇵ㣴᳨ᰝ࡛ࡣ㸪⫵⅖ᱰ⳦ࡀ㝧ᛶ㸦+2㸧࡛࠶ࡾ㸪ȕ-ࣛࢡࢱ࣐ ࣮ࢮࢆ⏘⏕ࡍࡿ MRSA ࡶᑡ㔞᳨ฟࡉࢀࡓࠋ2014 ᖺ 1 ᭶ 28 ᪥⿕㦂⪅ࡢ≧ࡣᏳᐃࡋ㸪⇕ࡀୗࡀ ࡗࡓࡇࡽ㸪2014 ᖺ 1 ᭶ 30 ᪥ࣥࣇࣜ࢟ࢩ࣐ࣈࡀᢞࡉࢀࡓࠋ ⿕㦂⪅ࡣ㸪2014 ᖺ 2 ᭶ 7 ᪥㏥㝔ࡋࡓࠋ SAE㸸ᩋ⾑㸦Day 133㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣࢡ࣮ࣟࣥᝏࡢ⒪ࡢࡓࡵ 2013 ᖺ 12 ᭶ 9 ᪥ධ㝔ࡋࡓࠋ2013 ᖺ 12 ᭶ 17 ᪥㸪ᝏᚰ㸪ྤ㸪ᝏᐮ㸪ᡓុཬࡧព㆑㞀ᐖࡢ≧ࢆక࠺ᩋ⾑デ᩿ࡉࢀࡓࠋࣂ ࢱࣝࢧࣥࡣ௨ୗࡢ࠾ࡾ࡛࠶ࡗࡓ㸸⾑ᅽ ᙜึࡢ 153/95 mmHg ࡽ 60-70/30-40 mmHg పୗ㸪 ᚰᢿᩘ 95 ᢿ/ศ㸪య 39°Cࠋᝏᚰᑐࡋ࡚࣓ࢺࢡࣟࣉ࣑ࣛࢻࡀᢞࡉࢀ㸪ࣝࣈ࣑ࣥ㸪ࢭࣇ࢙ࣆ ࣒ሷ㓟ሷ㸪ࣇࣝࣝࣅࣉࣟࣇ࢙ࣥ ࢟ࢭࢳࣝ㸦ࣟࣆ࢜ࣥ㸧㸪࣓ࢱ࣑ࢰ࣮ࣝࢼࢺ࣒ࣜ࢘Ỉ≀㸦࣓ ࢳࣟࣥ㸧ཬࡧࣂࣥࢥ࣐ࢩࣥࡀᢞࡉࢀࡓࠋⓎ⇕ࡣ 40.3°C ୖ᪼ࡋࡓࠋ2013 ᖺ 12 ᭶ 17 ᪥᥇ ྲྀࡋࡓ౽ࡣ MRSA 㝧ᛶ㸦1+㸧࡛࠶ࡗࡓࠋ2013 ᖺ 12 ᭶ 18 ᪥ࡣ⾑ᅽ 107/67 mmHg㸪య 39.4°C ࡛࠶ࡗࡓࠋⓎ⇕ࡣᣢ⥆ࡋࡓࡀ㸪⅖ᛶ࣐࣮࣮࢝ࡢ್ࡣᨵၿࡋࡘࡘ࠶ࡗࡓࠋ᥇ྲྀࡋࡓ౽ࡣ MRSA ཬࡧ Candida parapsilosis 㝧ᛶ࡛࠶ࡗࡓ㸦ࡑࢀࡒࢀ 3+㸪1+㸧ࠋࢭࣇ࢙ࣆ࣒ሷ㓟ሷ㸪ࣟࣆ࢜ࣥཬࡧ ࣂࣥࢥ࣐ࢩࣥࡢᢞࢆ⥅⥆ࡋࡓࠋ2013 ᖺ 12 ᭶ 19 ᪥ࡢ⦰ᮇ⾑ᅽࡣ౫↛ 70 mmHg ๓ᚋ࡛࠶ࡗ ࡓࠋࣝࣈ࣑ࢿ࣮ࢺࢆᢞࡉࢀࡓࠋ⿕㦂⪅ࡣᝏᐮཬࡧᡓុࡢ⮬ぬ≧ࡀ࠶ࡾ㸪㌟ᛶ⑊③ཬࡧ⑂ ປࢆッ࠼ࡓࠋࣀࣝࢻࣞࢼࣜࣥࡢᢞࢆ㛤ጞࡋࡓࠋ⥲ᢞ㔞ᑐࡋ࡚㸪ண ࡉࢀࡿᒀ㔞ࡣ 500 mL/24 hr㸦NR ᮍሗ࿌㸧ᑡ࡞ࡗࡓࠋ⿕㦂⪅ࡢ⭈ᶵ⬟ࡣⴭࡋࡃᝏࡋ࡚࠸ࡿ⪃࠼ࡽࢀࡓࠋ ࡑࡢᚋ㸪⾑ᅽ 103/52 mmHg㸪ᚰᢿᩘ 107 ᢿ/ศ㸪య 36°C ࡞ࡗࡓࠋ2013 ᖺ 12 ᭶ 19 ᪥᥇ྲྀࡋ ࡓၻ⑱ࡣ㸪MRSA 㝧ᛶ㸦1+㸧࡛࠶ࡗࡓࠋࢡࣟࢫࢺࣜࢪ࣒࣭࢘ࢹࣇࢩࣞᇵ㣴᳨ᰝࡣ㝜ᛶ࡛࠶ࡗ
26 1 (125) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
ࡓࠋ᥇ྲྀࡋࡓ౽ࡣ MRSA 㝧ᛶ㸦3+㸧࡛࠶ࡗࡓࠋࢭࣇ࢙ࣆ࣒ሷ㓟ሷཬࡧࣂࣥࢥ࣐ࢩࣥࡢᢞࢆ ⥅⥆ࡋࡓࠋ࢝ࣥࢧࢲࢫ㸦࢝ࢫ࣏ࣇࣥࢠࣥ㓑㓟ሷ㸧ཬࡧ࣓ࣟ࣌ࢿ࣒ࡢᢞࡶ㛤ጞࡋࡓࠋ 2013 ᖺ 12 ᭶ 20 ᪥㸪⿕㦂⪅ࡢᒀ㔞ࡣቑຍࡋ㸪ࣂࢱࣝࢧࣥࡣᨵၿࡋࡓ㸦ᒀ㔞 800 mL/16 hr㸪 ⾑ᅽ 126/71 mmHg㸪ᚰᢿᩘ 106 ᢿ/ศཬࡧయ 37.7°C㸧ࠋ᥇ྲྀࡋࡓ౽ࡣ MRSA㸪Candida parapsilosis ཬࡧ Candida albicans ࡀ࠸ࡎࢀࡶ㝧ᛶ࡛࠶ࡗࡓ㸦ࡑࢀࡒࢀ 2+㸪2+㸪1+㸧ࠋᒀ᳨ᰝࡢ⤖ ᯝࡣ㝜ᛶ࡛࠶ࡗࡓࠋࣀࣝࢻࣞࢼࣜࣥ㸪࢝ࣥࢧࢲࢫ㸪࣓ࣟ࣌ࢿ࣒㸪ࣂࣥࢥ࣐ࢩࣥཬࡧࣟࣆ࢜ ࣥࡢᢞࢆ⥅⥆ࡋࡓࠋ2013 ᖺ 12 ᭶ 21 ᪥ࡢࣂࢱࣝࢧࣥࡣ㸪⾑ᅽ 112/73 mmHg㸪ᚰᢿᩘ 106 ᢿ /ศཬࡧయ 37.0°C ࡛࠶ࡗࡓࠋࣀࣝࢻࣞࢼࣜࣥࡢᢞࢆ୰Ṇࡋ㸪࢝ࣥࢧࢲࢫ㸪࣓ࣟ࣌ࢿ࣒ཬ ࡧࣂࣥࢥ࣐ࢩࣥࡢᢞࡣ⥅⥆ࡋࡓࠋࡑࡢᚋࡢᩘ᪥㛫࡛⿕㦂⪅ࡢࣂࢱࣝࢧࣥࡣᏳᐃࡋ㸪⇕ࡣ ୗࡀࡗࡓࠋ 2013 ᖺ 12 ᭶ 25 ᪥ࡢࣂࢱࣝࢧࣥࡣ⾑ᅽ 142/90 mmHg㸪ᚰᢿᩘ 75 ᢿ/ศཬࡧయ 37.5°C ࡛࠶ ࡾ㸪ྠ᪥㸪SAE ࡛࠶ࡿᩋ⾑ࡣᾘᩓࡋࡓデ᩿ࡉࢀࡓࠋ
(12) Subject CNTO1275CRD3003-4213-11139
1) Reason for narrative selection SAE
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome I/M) 2013-07-20 ࢡ࣮ࣟࣥ Y SEVERE/ N/ NOT APPLICABLE/ 2013-09-13 (149/85) (WORSENING OF CROHNS NOT NA RECOVERED/RESOLVED (204/140) DISEASE) RELATED
3) Baseline Demographic Information Age (years): 4 Sex: Male Weight (kg): 64.6 Race: Asian Date of birth: Height (cm): 176
4) Induction Treatment Group Induction study: CNTO1275CRD3001 Randomized Treatment Group: Placebo IV Actual Treatment Group: Placebo IV
5) Maintenance Treatment Group Assigned Treatment Group: Non-randomized subject/Non-responder to placebo IV induction dosing and received ustekinumab in maintenance
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2013-02-22 1 Placebo 0 mg WEEK 0 MAINTENANCE 2013-04-27 65 Placebo 0 mg WEEK 0 MAINTENANCE 2013-04-27 65 Ustekinumab 129.6 mg
26 2 (126) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: Y Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: -
8) Induction Baseline Crohn's Disease History Date of diagnosis: 13JUL1991 Disease duration: 21.62 years Involved areas: ⤖⭠ࡢࡳ㸪⫠㛛࿘ᅖ
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: CURRENTLY PRESENT Stricture complications of (CD): PREVIOUS HISTORY
10) Concomitant Crohn's Disease-Related Surgeries Surgery Date Result of lack of efficacy? ⤖⭠ࡢ㒊ศⓗษ㝖㸦༙⤖⭠ษ㝖࡞㸧 2013-08-26 Y
11) Concomitant Steroids Visit Drug Dose Prednisone equivalent SAFETY FOLLOW-UP MAINTENANCE PREDNISOLONE 20 mg - SAFETY FOLLOW-UP MAINTENANCE HYDROCORTISONE 0 mg - SAFETY FOLLOW-UP MAINTENANCE HYDROCORTISONE 0 mg - SAFETY FOLLOW-UP MAINTENANCE PREDNISOLONE 20 mg - SAFETY FOLLOW-UP MAINTENANCE HYDROCORTISONE 100 mg - SAFETY FOLLOW-UP MAINTENANCE HYDROCORTISONE 100 mg - SAFETY FOLLOW-UP MAINTENANCE HYDROCORTISONE 100 mg - SAFETY FOLLOW-UP MAINTENANCE HYDROCORTISONE 50 mg - SAFETY FOLLOW-UP MAINTENANCE PREDNISOLONE 0 mg - SAFETY FOLLOW-UP MAINTENANCE PREDNISOLONE 0 mg - SAFETY FOLLOW-UP MAINTENANCE HYDROCORTISONE 0 mg -
12) Narrative Text ⿕㦂⪅ࡣ 4 ṓࡢ᪥ᮏே⏨ᛶ࡛㸪2013 ᖺ 2 ᭶ 22 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ࣉࣛࢭ࣎ࢆ㟼⬦ෆᢞ ࡉࢀࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡎ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏࢆᢞ ࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪㒊ศⓗ⤖⭠ษ 㝖㸦ୖ⾜⤖⭠㸪2000 ᖺ 5 ᭶ 29 ᪥㸧㸪⫹ᄞษ㝖㸪C ࢳ࣮ࣗࣈ␃⨨㸪༑ᣦ⭠ᘓ㸦2002 ᖺ 8 ᭶ 2 ᪥㸧㸪ࢩ࣮ࢺࣥ␃⨨㸦2006 ᖺ 10 ᭶ 19 ᪥㸧ཬࡧୗ⾜⤖⭠ษ㝖㸦2010 ᖺ 11 ᭶ 18 ᪥㸧࡛࠶ࡗࡓࠋ SAE㸸ࢡ࣮ࣟࣥ㸦Day 149㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2013 ᖺ 8 ᭶ 19 ᪥㸪⭡㒊⭾‶ࡢࡓࡵධ㝔ࡋࡓࠋ⭡㒊⭾‶ࡣ㸪ྑ ୖ⭡㒊ࡢ⭘⬽ཬࡧࡍࡍࡾ㡢ࡢࡼ࠺࡞㸦slurping㸧⭠㞧㡢ࡢ⮬ぬ≧ࡀ࠶ࡗࡓ 2013 ᖺ 7 ᭶ 20 ᪥ࡽ Ⓨ⌧ࡋࡓࠋάືᮇࡢ₽⒆ཬࡧྑୖ㒊࿀ྜ㒊ࡢ⊃✽㉳ᅉࡋࡓ⭠㛢ሰࡢⓎࡢࡓࡵ㸪⭠ᣑᙇ⾡ࡀ⧞ ࡾ㏉ࡉࢀ㸪࿀ྜ㒊ᘓࡀィ⏬ࡉࢀࡓࠋ2013 ᖺ 8 ᭶ 19 ᪥ࡢ⮫ᗋ᳨ᰝ␗ᖖ್ࡣ㸪ࢡࣞࢳࢽࣥ 1.34 mg/dL㹙ṇᖖ⠊ᅖ㸦NR㸧0.61-1.14 mg/dL㹛ཬࡧ C ᛂᛶࡓࢇⓑ⃰ᗘ 0.4 mg/dL
26 3 (127) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
㸦NR<0.3 mg/dL㸧࡛࠶ࡗࡓࠋ2013 ᖺ 8 ᭶ 21 ᪥ࡢ⭡㒊㉸㡢Ἴ᳨ᰝ࡛ࡣ㸪୧⭈⮚ᚤᑠ࡞⤖▼ཬࡧ ྑୗ⭡㒊⭠ቨࡢ⫧ཌࡀࡳࡽࢀࡓࠋ2013 ᖺ 8 ᭶ 22 ᪥ࡢ⭠ෆど㙾᳨ᰝ࡛ࡣ㸪⫠㛛ᇦ㢧ⴭ࡞⅖ ࡀࡳࡽࢀࡓࠋ2013 ᖺ 8 ᭶ 26 ᪥࿀ྜ㒊ᘓ⾡ࡀ⾜ࢃࢀ㸪⤖⭠ࡢ㒊ศⓗษ㝖グ㘓ࡉࢀࡓࠋ⿕ 㦂⪅ࡣ௨ୗࡀᢞࡉࢀࡓ㸸general nutrients㸪ங㓟ࣜࣥࢤࣝᾮ㸪㠀⤒ཱྀᰤ㣴㸪ᰤ㣴⿵⤥㸪ࣇࣟ ࣔ࢟ࢭࣇࢼࢺ࣒ࣜ࢘㸪ࣈࣉࣞࣀࣝࣇࣥሷ㓟ሷ㸪ࣇࣝࣝࣅࣉࣟࣇ࢙ࣥ ࢟ࢭࢳࣝ㸪࢝ࣥࣞࣀ㓟 ࣒࢝ࣜ࢘㸪ࢢࣜࢳࣝࣜࢳࣥ㓟୍ࣥࣔࢽ࣒࢘㸪ࢪ࣓ࢳࢥࣥ㸪࣓ࢺࢡࣟࣉ࣑ࣛࢻ㸪࣓ࢧࣛࢪࣥ㸪ࣄ ࢻࣟࢥࣝࢳࢰࣥࢥࣁࢡ㓟࢚ࢫࢸࣝࢼࢺ࣒ࣜ࢘㸪ࣇ࢙ࢪࣥ㸪ࢨࢳ࢜ࣉࣜࣥ㸪ࣄࢻࣟࢥࣝࢳࢰࣥ㸭 ࢿ࣐࢜ࢩࣥ㸦Hemolex㸧㸪ࢪࣇ࢙ࣥࣄࢻ࣑ࣛࣥ㸪ࣃࣛࢭࢱ࣮ࣔࣝ㸪ࣉࣞࢻࢽࢰࣟࣥ㸪ࣥࣇࣜ ࢟ࢩ࣐ࣈ㸪࣏ࣅࢻ࣮ࣥࣚࢻ㸪Ⅳ㓟Ỉ⣲ࢼࢺ࣒ࣜ࢘㸭ࢼࢺ࣒ࣜ࢘ࢢࣞࢼ࣮ࢺ㸦ࣁࢳࢬࣞ㸧㸪ࢰ ࣝࣆࢹ࣒㸪L-ࢫࣃࣛࢠࣥ㓟࣒࢝ࣜ࢘㸪ࣟ࢟ࢯࣉࣟࣇ࢙ࣥ㸪ࣞࣂ࣑ࣆࢻ㸪ࢣࢺࣉࣟࣇ࢙ࣥῧ㸪 ங㓟⳦㸪ࣇࣟࢭ࣑ࢻ㸪࣒࢝ࣜ࢘㸪࢚ࣂࢫࢳࣥ㸪ࢫࣆࣟࣀࣛࢡࢺࣥࠋ⿕㦂⪅ࡣ㸪2013 ᖺ 9 ᭶ 13 ᪥ ㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2013-09-02 ࣛࢽ࣑ࣥࣀࢺࣛࣥࢫࣇ࢙࣮ࣛࢮቑຍ MODERATE/ N/ NOT APPLICABLE/ 2013-09-28 (193/129) (ELEVATED ALT) NOT NA RECOVERED/RESOLVED (219/155) RELATED 2013-09-02 ࢫࣃࣛࢠࣥ㓟࣑ࣀࢺࣛࣥࢫࣇ࢙࣮ࣛ MODERATE/ N/ NOT APPLICABLE/ 2013-09-12 (193/129) ࢮቑຍ NOT NA RECOVERED/RESOLVED (203/139) (ELEVATED AST) RELATED
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route NUTRIENTS NOS 2013-08-19 2013-08-19 ORAL MINERALS NOS W/VITAMINS NOS 2013-08-23 - ORAL FLOMOXEF SODIUM 2013-08-26 2013-08-28 INTRAVENOUS BUPRENORPHINE HYDROCHLORIDE 2013-08-26 2013-08-26 INTRAVENOUS FLURBIPROFEN AXETIL 2013-08-26 2013-08-26 INTRAVENOUS METOCLOPRAMIDE HYDROCHLORIDE 2013-08-27 2013-08-31 INTRAVENOUS POTASSIUM CANRENOATE 2013-08-27 2013-09-02 INTRAVENOUS HYDROCORTISONE SODIUM SUCCINATE 2013-08-27 2013-08-30 INTRAVENOUS ASPHAGEN 2013-09-04 - INTRAVENOUS
(13) Subject CNTO1275CRD3003-4213-20895
1) Reason for narrative selection SAE Discontinuation of study agent due to AE
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome I/M) 2014-09-13 ࢡ࣮ࣟࣥ Y SEVERE/ N/ DRUG WITHDRAWN/ 2014-12-19 (155/100) (WORSENING OF CROHN'S NOT NA RECOVERED/RESOLVED (252/197) DISEASE) RELATED
26 4 (128) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
3) Baseline Demographic Information Age (years): 3 Sex: Male Weight (kg): 50.8 Race: Asian Date of birth: Height (cm): 176.9
4) Induction Treatment Group Induction study: CNTO1275CRD3002 Randomized Treatment Group: Ustekinumab 130 mg IV Actual Treatment Group: Ustekinumab 130 mg IV
5) Maintenance Treatment Group Assigned Treatment Group: Randomized subject/Responder to ustekinumab IV induction dosing/ustekinumab 90 mg SC q8w
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2014-04-12 1 Ustekinumab 129.6 mg WEEK 0 MAINTENANCE 2014-06-06 56 Ustekinumab 90 mg WEEK 8 MAINTENANCE 2014-08-02 113 Ustekinumab 90 mg WEEK 12 MAINTENANCE 2014-08-30 141 Placebo 0 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: Y Did the subject terminate the study participation before the Week 44 visit?: Y Did subject enter the long-term extension study?: -
8) Induction Baseline Crohn's Disease History Date of diagnosis: 06JUN2001 Disease duration: 12.85 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪⫠㛛࿘ᅖ㸪ᑠ⭠㏆㸭⫶㸭㣗㐨
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: PREVIOUS HISTORY Stricture complications of (CD): CURRENTLY PRESENT
10) Concomitant Crohn's Disease-Related Surgeries None reported
11) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 12 MAINTENANCE PREDNISONE 20 mg -
12) Narrative Text ⿕㦂⪅ࡣ 3 ṓࡢ᪥ᮏே⏨ᛶ࡛㸪2014 ᖺ 4 ᭶ 12 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏࢆ㟼⬦ෆᢞࡉ ࢀࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏ 90 mg ࢆ q8w ࡛⓶ୗᢞࡍࡿ⩌ࣛࣥࢲ࣒ࡉࢀࡓࠋ
26 5 (129) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪࡚ࢇࢇཬࡧ ႚ↮࡛࠶ࡗࡓࠋ SAE/Discontinuation of study agent due to AE㸸ࢡ࣮ࣟࣥ㸦Day 155㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 3 ᪥㛫ᣢ⥆ࡋࡓ⫶③㸪⭡㒊⭾‶ឤཬࡧୗ⑩ࡢࡓࡵ 2014 ᖺ 9 ᭶ 16 ᪥ ධ㝔ࡋࡓࠋ2014 ᖺ 9 ᭶ 16 ᪥㸪⫠㛛⊃✽ࡢࡓࡵࣂ࣮ࣝࣥᣑᙇࡼࡿ⭠ෆど㙾᳨ᰝࢆᐇࡋ ࡓࠋᑠ⭠ഃ」ᩘࡢάືᮇࡢ₽⒆ཬࡧ⫠㛛ᇦ㞳ࡋࡓ⢓⭷ࡀࡳࡽࢀࡓࠋࣈࢻ࢘⢾ຍங㓟ࣜࣥࢤ ࣝᾮ㸦ࢯࣝࣛࢡࢺ D㸧㸪ࣈࢻ࢘⢾㸭㟁ゎ㉁ᾮ㸦ࢯࣝࢹ࣒ 3AG㸧㸪ࣉࣞࢻࢽࢰࣟࣥ㸪ࣈࢻ࢘⢾㸪ྵ ⢾㓟㕲㸪㇋Ἔ㸪ࣈࢻ࢘⢾㸭㟁ゎ㉁㸭࣑ࣀ㓟㸭ࣅࢱ࣑ࣥ B1㸦ࣅ࣮ࣇ࣮ࣜࢻ㸧ࡼࡿ⒪ࡀ ᐇࡉࢀࡓࠋ2014 ᖺ 9 ᭶ 16 ᪥ࡢ⮫ᗋ᳨ᰝ್ࡣ㸪⥲ࡓࢇⓑ 6.6 g/dL㹙ṇᖖ⠊ᅖ㸦NR㸧6.7- 8.2 g/dL㹛㸪C ᛂᛶࡓࢇⓑ⃰ᗘ 2.1 mg/dL㸦NR<0.30 mg/dL㸧㸪࣐࣊ࢺࢡࣜࢵࢺ 38.4%㸦NR 39- 52%㸧࡛࠶ࡗࡓࠋ⿕㦂⪅ࡣ 2014 ᖺ 9 ᭶ 17 ᪥㏥㝔ࡋࡓࠋࢡ࣮ࣟࣥࡢᝏࡼࡾ㸪㦂⸆ࡢᢞ ࢆ୰Ṇࡋࡓࠋ ≧ࡀᣢ⥆ࡋࡓࡓࡵ㸪⿕㦂⪅ࡣ 2014 ᖺ 9 ᭶ 22 ᪥ධ㝔ࡋࡓࠋ2014 ᖺ 9 ᭶ 29 ᪥ࡽ㠀 ⤒ཱྀᰤ㣴ἲࡀ⏝࠸ࡽࢀࡓࠋ2 ᅇࡢ㢛⢏⌫྾╔⒪ἲ㸦G-CAP㸧ࢆཷࡅ㸪2014 ᖺ 9 ᭶ 30 ᪥⭠ෆ ど㙾᳨ᰝࢆཷࡅࡓ㸦᳨ᰝ⤖ᯝࡢሗ࿌࡞ࡋ㸧ࠋ2014 ᖺ 10 ᭶ 1 ᪥㸪ࣥࣇࣜ࢟ࢩ࣐ࣈࢆ 2 ಸࡢ⏝ 㔞㸦10 mg/kg㸧࡛ᢞࡉࢀࡓࠋ2014 ᖺ 10 ᭶ 2 ᪥ࡽࣄࢩࣇ࣮ࢤࣥ C ࡼࡿ⒪ࡀ㛤ጞࡉࢀࡓࠋ 2014 ᖺ 10 ᭶ 7 ᪥ G-CAP ⒪ἲࢆཷࡅࡓࠋ⿕㦂⪅ࡣ 2014 ᖺ 10 ᭶ 8 ᪥㏥㝔ࡋ㸪2014 ᖺ 10 ᭶ 14 ᪥ධ㝔ࡋࡓࠋᑠ⭠ࡢ X ⥺㏱ど᳨ᰝ࡛ࡣ㸪༑ᣦ⭠ࡢୗ⾜㒊✺ฟ㸦᠁ᐊ㸧ཬࡧ┤⭠⊃✽ࡀ ࡳࡽࢀࡓࠋᑠ⭠⭠ࡢ⤖ྜ㒊࡛㸪ഹ࡞⊃✽ࡀࢃࢀࡓࠋ2014 ᖺ 10 ᭶ 15 ᪥ࡢ X ⥺㏱どୗ࡛ ࡢࢲࣈࣝࣂ࣮ࣝࣥᑠ⭠ෆど㙾᳨ᰝ࡛ࡣ㸪ࢡ࣮ࣟࣥࡢάືᮇࡢᡤぢࡣࡳࡽࢀ࡞ࡗࡓࠋ⿕㦂⪅ࡣ 2014 ᖺ 10 ᭶ 16 ᪥㏥㝔ࡋ㸪10 ᭶ 20 ᪥⤖⭠⒦㐀タࡢࡓࡵධ㝔ࡋࡓࠋ2014 ᖺ 10 ᭶ 21 ᪥ཬࡧ 27 ᪥㸪G-CAP ⒪ἲࢆཷࡅࡓࠋ2014 ᖺ 10 ᭶ 29 ᪥㸪⿕㦂⪅ࡣ⭡⭍㙾ୗ࡛┤⭠ษ㝖⾡ࢆཷࡅࡓࠋ ྠ᪥ࡢ X ⥺᳨ᰝ࡛ࡣ㸪ᕥ㦵┙㒊ࢫࢺ࣮࣐ࣃ࢘ࢳྲྀࡾࡅࡽࢀࡓࢡࣜࢵࣉࡀࡳࡽࢀࡓࠋ࣌ࣥࢱ ࢰࢩࣥ㸪ࣄࢻࣟ࢟ࢩࢪࣥ㸪ࣄࢻࣟࢥࣝࢳࢰࣥࢥࣁࢡ㓟࢚ࢫࢸࣝࢼࢺ࣒ࣜ࢘㸪࣓ࢺࢡࣟࣉ࣑ࣛࢻ㸪 ࢚ࣀ࢟ࢧࣃࣜࣥ㸪ࣇࣝࣝࣅࣉࣟࣇ࢙ࣥࡼࡿ⒪ࡀᐇࡉࢀࡓࠋ2014 ᖺ 11 ᭶ 4 ᪥ࡢேᕤ⫠㛛ࢆ ⤒⏤ࡋࡓ㸦trans-artificial-anal㸧㐀ᙳ⏬ീࢫ࢟ࣕࣥཬࡧ X ⥺᳨ᰝ࡛ࡣ㸪␗ᖖࡣ࡞ࡗࡓࠋேᕤ⫠㛛 ࡢᾋ⭘㉳ᅉࡋࡓ⤖⭠ෆࡢᅽຊࢆୗࡆࡿࡓࡵ㸪␃⨨ࢳ࣮ࣗࣈࡣ⥔ᣢࡋࡓࠋ⫠㛛␃⨨ࡋ࡚࠸ࡓࢻ ࣮ࣞࣥ㸦anal channel drain㸧ࡣ 2014 ᖺ 11 ᭶ 5 ᪥㝖ཤࡉࢀ㸪ࣈࢻ࢘⢾ຍங㓟ࣜࣥࢤࣝᾮ㸦ࢯࣝࣛ ࢡࢺ D㸧㸪ࣈࢻ࢘⢾㸭㟁ゎ㉁㸭࣑ࣀ㓟㸭ࣅࢱ࣑ࣥ B1㸦ࣅ࣮ࣇ࣮ࣜࢻ㸧ཬࡧࣉࣞࢻࢽࢰࣟࣥ ࡼࡿ⒪ࢆཷࡅࡓࠋேᕤ⫠㛛ࢆࡋ࡚ࢳ࣮ࣗࣈࢆᤄධ㸦᪥ᮍሗ࿌㸧ࡍࡿ㸪ࢳ࣮ࣗࣈࡢඛ➃ ࡽ⣙ 10 cm ࡢ⨨࡛พࢇࡔࠋ2014 ᖺ 11 ᭶ 10 ᪥ࡢ⭡㒊 X ⥺᳨ᰝ࡛ࡣ㸪࢞ࢫࡢ㈓␃ཬࡧᶓ⾜⤖⭠ࡢ ⭾⬽ࡀࡳࡽࢀࡓࠋேᕤ⫠㛛ࢆࡋ࡚ࢳ࣮ࣗࣈࢆᤄධࡋ㸪ෆᐜ≀ࡀ྾ᘬࡉࢀࡓࠋ⿕㦂⪅ࡢ≧ែࡣᨵ ၿࡋ㸪2014 ᖺ 11 ᭶ 11 ᪥ὶື㣗ࢆ㛤ጞࡋࡓࠋ2014 ᖺ 11 ᭶ 17 ᪥ࡢ X ⥺᳨ᰝ࡛ࡣ㸪ῶᅽࡢࡓࡵ ࡢࢳ࣮ࣗࣈࡢ㛢ሰཪࡣேᕤ⫠㛛࿘㎶ࡢ౽ࡼࡿ㛢ሰࡢ࠸ཬࡧᶓ⾜⤖⭠ࡢ⭾⬽ࢆక࠺࢞ࢫ㈓␃ࡀ ࡳࡽࢀ㸪2014 ᖺ 11 ᭶ 18 ᪥ෆど㙾ୗ࡛྾ᘬࡉࢀࡓࠋ⭠ෆど㙾᳨ᰝ࡛ࡣ㸪⭠⟶ὸ࠸ࡧࡽࢇཬ ࡧேᕤ⫠㛛ᾋ⭘ࡀࡳࡽࢀ㸪౽㛢ሰࡢཎᅉ⪃࠼ࡽࢀࡓࠋ㔞ࡢἾ≧౽ࡢ྾ᘬᚋ㸪≧ࡣᨵၿࡋࡓࠋ 2014 ᖺ 11 ᭶ 25 ᪥⤖⭠ᅛᐃ⾡ࢆᐇࡋ㸪⭠⟶⒵╔ࢆ㞳ࡋࡓࠋ2014 ᖺ 11 ᭶ 26 ᪥ࡢ X ⥺᳨ᰝ ࡛ࡣ㸪⤖⭠᫂☜࢞ࢫࡀㄆࡵࡽࢀࡓࡀ㸪౽ࡼࡿ㛢ሰࡣࡳࡽࢀ࡞ࡗࡓࠋᅇ⭠ࡢ㐀ᙳ⏬ീࢫ࢟ ࡛ࣕࣥࡣ㸪ேᕤ⫠㛛ࢆࡋ࡚ᤄධࡋࡓࢳ࣮ࣗࣈࡡࡌࢀࡀࡳࡽࢀࡓࡓࡵ㸪ࢳ࣮ࣗࣈࢆᢤཤࡋࡓࠋ
26 6 (130) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
2014 ᖺ 12 ᭶ 16 ᪥ࡢ⬚㒊㸪⭡㒊ཬࡧ㦵┙㒊ࡢ㠀㐀ᙳࢥࣥࣆ࣮ࣗࢱ᩿ᒙᙳ㸦CT㸧ࢫ࡛࢟ࣕࣥࡣ㸪 㦵┙⭍ᑡ㔞ࡢ⭡Ỉࡀࡳࡽࢀࡓࠋྠ᪥ࡢ⮫ᗋ᳨ᰝ್ࡣ㸪ࣛࢽ࣑ࣥࣀࢺࣛࣥࢫࣇ࢙࣮ࣛࢮ 154 IU/L㸦NR 9-44 IU/L㸧㸪ࢫࣃࣛࢠࣥ㓟࣑ࣀࢺࣛࣥࢫࣇ࢙࣮ࣛࢮ 51 IU/L㸦NR 13-36 IU/L㸧 ࣝ࢝ࣜ࣍ࢫࣇࢱ࣮ࢮ 882 IU/L㸦NR 130-324 IU/L㸧㸪⾑Ύ࣑࣮ࣛࢮ 166 IU/L㸦NR 40- 125 IU/L㸧࡛࠶ࡗࡓࠋCT ࢫ࢟ࣕࣥཬࡧ⮫ᗋ᳨ᰝࡢ⤖ᯝ㸪ࢡ࣮ࣟࣥཬࡧ⫢ᶵ⬟␗ᖖデ᩿ࡉࢀࡓࠋ ⿕㦂⪅ࡣ㸪2014 ᖺ 12 ᭶ 19 ᪥㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome (Study day I/M) 2014-03-28 Ⓨ⇕ MILD/ N/ NOT APPLICABLE/ 2014-03-29 (-15/.) (FEVER) NOT RELATED NA RECOVERED/RESOLVED (-14/.) 2014-04-17 Ⓨ⇕ MILD/ N/ DOSE NOT CHANGED/ 2014-04-20 (6/.) (FEVER) NOT RELATED NA RECOVERED/RESOLVED (9/.)
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route AMINO ACIDS NOS W/ELECTROLYTES NOS/GLUCOSE/TH 2014-09-16 - INTRAVENOUS DRIP SACCHARATED IRON OXIDE 2014-09-16 - INTRAVENOUS DRIP GLUCOSE 2014-09-16 - INTRAVENOUS DRIP GLYCINE MAX SEED OIL 2014-09-16 - INTRAVENOUS DRIP PREDNISOLONE 2014-09-16 - INTRAVENOUS DRIP OSMOSAL /00501801/ 2014-09-16 - INTRAVENOUS DRIP SOLULACT TMR 2014-09-16 - INTRAVENOUS DRIP
(14) Subject CNTO1275CRD3003-4216-10627
1) Reason for narrative selection SAE Discontinuation of study agent due to AE
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome I/M) 2013-03-19 ࢡ࣮ࣟࣥ Y SEVERE/ N/ DRUG WITHDRAWN/ Ongoing (196/141) (DETERIORATION OF CROHN'S NOT NA NOT RECOVERED/NOT - DISEASE) RELATED RESOLVED
3) Baseline Demographic Information Age (years): 2 Sex: Male Weight (kg): 52 Race: Asian Date of birth: Height (cm): 176.4
4) Induction Treatment Group Induction study: CNTO1275CRD3001 Randomized Treatment Group: Placebo IV Actual Treatment Group: Placebo IV
5) Maintenance Treatment Group Assigned Treatment Group: Non-randomized subject/Non-responder to placebo IV induction dosing and received ustekinumab in maintenance
26 7 (131) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2012-09-05 1 Placebo 0 mg WEEK 0 MAINTENANCE 2012-10-30 56 Ustekinumab 129.6 mg WEEK 0 MAINTENANCE 2012-10-30 56 Placebo 0 mg WEEK 8 MAINTENANCE 2012-12-25 112 Ustekinumab 90 mg WEEK 12 MAINTENANCE 2013-01-22 140 Placebo 0 mg WEEK 16 MAINTENANCE 2013-02-19 168 Placebo 0 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: Y Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: -
8) Induction Baseline Crohn's Disease History Date of diagnosis: 18NOV2008 Disease duration: 3.80 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪⫠㛛࿘ᅖ
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: PREVIOUS HISTORY Stricture complications of (CD): NEVER
10) Concomitant Crohn's Disease-Related Surgeries None reported
11) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 0 PREDNISOLONE 10 mg 10 mg WEEK 0 POSTERISAN FORTE 2000 mg - WEEK 20 MAINTENANCE PREDNISOLONE 7.5 mg 7.5 mg SAFETY FOLLOW-UP MAINTENANCE METHYLPREDNISOLONE 125 mg - SAFETY FOLLOW-UP MAINTENANCE HYDROCORTISONE 125 mg - SAFETY FOLLOW-UP MAINTENANCE HYDROCORTISONE 0 mg -
12) Narrative Text ⿕㦂⪅ࡣ 2 ṓࡢ᪥ᮏே⏨ᛶ࡛㸪2012 ᖺ 9 ᭶ 5 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ࣉࣛࢭ࣎ࢆ㟼⬦ෆᢞ ࡉࢀࡓࠋᮏ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡎ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏࢆᢞ ࡉࢀࡓࠋ SAE/Discontinuation of study agent due to AE㸸ࢡ࣮ࣟࣥ㸦Day 196㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2013 ᖺ 3 ᭶ 19 ᪥ࡽⓎ⌧ࡋ࡚࠸ࡓࢡ࣮ࣟࣥࡢᝏࡢࡓࡵ 2013 ᖺ 3 ᭶ 27 ᪥ධ㝔ࡋࡓࠋ㧗ᗘࡢⓎ⇕ཬࡧୗ⑩ࡢ≧ࡀㄆࡵࡽࢀࡓࠋ2013 ᖺ 3 ᭶ 27 ᪥ࡢ⮫ᗋ᳨ᰝ ್ࡣ㸪C ᛂᛶࡓࢇⓑ⃰ᗘ 7.08 mg/dL㹙ṇᖖ⠊ᅖ㸦NR㸧0-0.10 mg/dL㹛㸪࣐࣊ࢺࢡࣜࢵࢺ 26.3% 㸦NR 36-52%㸧㸪࣊ࣔࢢࣟࣅࣥ 9 g/dL㸦NR 14-18 g/dL㸧㸪ࣝࣈ࣑ࣥ 2.4 g/dL㸦NR 4-5 g/dL㸧࡛ ࠶ࡗࡓࠋ2013 ᖺ 3 ᭶ 29 ᪥ࡢୗ㒊ᾘ⟶ෆど㙾᳨ᰝ࡛ࡣ㸪ᾋ⭘ཬࡧᶓ⾜⤖⭠ࡽ S ≧⤖⭠ࡅ ࡚」ᩘࡢ⦪㉮₽⒆㸦circumferentially longitudinal ulcers㸧ࡀࡳࡽࢀࡓࠋ2013 ᖺ 4 ᭶ 1 ᪥ࡢୖ㒊㦵┙
26 8 (132) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
㒊ࢥࣥࣆ࣮ࣗࢱ᩿ᒙᙳࢫ࡛࢟ࣕࣥࡣ㸪ᶓ⾜⤖⭠ࡢ୰ኸࡽ⫠㛛ᇦࡅ࡚⭠ቨ⫧ཌࡢቑᙉࡀࡳ ࡽࢀࡓࠋࣥࣇࣜ࢟ࢩ࣐ࣈ㸪㟁ゎ㉁⁐ᾮ㸪ࣜࣥࢤࣝᾮ㸭ࣈࢻ࢘⢾㸦ࣛࢡࢸࢵࢡ G㸧㸪ࣄࢻࣟࢥࣝ ࢳࢰࣥ㸪ࢪࣇ࢙ࣥࣄࢻ࣑ࣛࣥ㸪dexchlorpheniramine㸪࣊ࣃࣜࣥ㸪࣓ࢳࣝࣉࣞࢻࢽࢰࣟࣥ㸪ࣃࣛࢭ ࢱ࣮ࣔࣝ㸪ᰤ㣴⿵⤥㸦࢚ࣞࣥࢱ࣮ࣝ㸧ࡼࡿ⒪ࡀᐇࡉࢀࡓࠋ⿕㦂⪅ࡣ㸪2013 ᖺ 4 ᭶ 11 ᪥ ㏥㝔ࡋࡓࠋᮏ㇟ࡼࡾ㸪㦂⸆ࡢᢞࢆ୰Ṇࡋࡓࠋ
13) Other Adverse Events Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome (Study day I/M) 2013-04-23 㠎ᖏ MILD/ N/ NOT APPLICABLE/ 2013-05-22 (231/176) (SPRAIN OF THE RIGHT WRIST) NOT RELATED NA RECOVERED/RESOLVED (260/205)
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route MINERALS NOS W/VITAMINS NOS 2013-03-19 - INTRAVENOUS PARACETAMOL 2013-04-09 - ORAL HYDROCORTISONE 2013-04-09 2013-04-09 INTRAVENOUS HEPARIN SODIUM 2013-04-09 2013-04-09 INTRAVENOUS DEXCHLORPHENIRAMINE MALEATE 2013-04-09 2013-04-09 ORAL INFLIXIMAB 2013-04-09 - INTRAVENOUS DIPHENHYDRAMINE 2013-04-09 - ORAL METHYLPREDNISOLONE SODIUM SUCCINATE 2013-04-09 - INTRAVENOUS
(15) Subject CNTO1275CRD3003-4216-10754
1) Reason for narrative selection SAE Discontinuation of study agent due to AE Event of interest: Serious infection
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome I/M) 2013-01-23 ⫠㛛⮋⒆ Y SEVERE/ Y/ DRUG WITHDRAWN/ Ongoing (80/28) (PERIANAL NOT Y NOT RECOVERED/NOT - ABSCESS) RELATED RESOLVED
3) Baseline Demographic Information Age (years): 1 Sex: Female Weight (kg): 41.4 Race: Asian Date of birth: Height (cm): 142.4
4) Induction Treatment Group Induction study: CNTO1275CRD3001 Randomized Treatment Group: Ustekinumab Approximating 6 mg/kg IV Actual Treatment Group: Ustekinumab Approximating 6 mg/kg IV
5) Maintenance Treatment Group Assigned Treatment Group: Randomized subject/Responder to ustekinumab IV induction dosing/ustekinumab 90 mg SC q12w
26 9 (133) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2012-11-05 1 Ustekinumab 259.2 mg WEEK 0 MAINTENANCE 2012-12-27 53 Ustekinumab 90 mg WEEK 8 MAINTENANCE 2013-02-21 109 Placebo 0 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: Y Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: -
8) Induction Baseline Crohn's Disease History Date of diagnosis: 31JAN2006 Disease duration: 6.77 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪ᾘ⟶እኚ㸦ࣇࢱᛶཱྀෆ⅖㸧
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: NEVER Stricture complications of (CD): NEVER
10) Concomitant Crohn's Disease-Related Surgeries Surgery Date Result of lack of efficacy? ࢻࣞࢼ࣮ࢪ-ࢩ࣮ࢺࣥ␃⨨ 2013-02-28 Y
11) Concomitant Steroids Visit Drug Dose Prednisone equivalent SAFETY FOLLOW-UP MAINTENANCE METHYLPREDNISOLONE 125 mg -
12) Narrative Text ⿕㦂⪅ࡣ 1 ṓࡢ᪥ᮏேዪᛶ࡛㸪2012 ᖺ 11 ᭶ 5 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏࢆ㟼⬦ෆᢞࡉ ࢀࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏ 90 mg ࢆ q12w ࡛⓶ୗᢞࡍࡿ⩌ࣛࣥࢲ࣒ࡉࢀࡓࠋ SAE/Discontinuation of study agent due to AE/Serious infection㸸⫠㛛⮋⒆㸦Day 80㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2013 ᖺ 1 ᭶ 23 ᪥⫠㛛࿘ᅖ⭘⬽ࡀⓎ⌧ࡋࡓࠋ2013 ᖺ 2 ᭶ 25 ᪥ Ⓨ⇕ཬࡧ⫠㛛࿘ᅖ⭘⬽ࡢቑᝏࡀㄆࡵࡽࢀ㸪⿕㦂⪅ࡣ 2013 ᖺ 2 ᭶ 26 ᪥ධ㝔ࡋࡓࠋྠ᪥ࡢୖ㒊㦵 ┙ᇦࡢࢥࣥࣆ࣮ࣗࢱ᩿ᒙᙳ㸦CT㸧ࢫ࡛࢟ࣕࣥࡣ㸪⫠㛛ࡢᕥഃ࢝ࣉࢭࣝໟࡲࢀࡓࡼ࠺࡞ 㸦encapsulated㸧⫠㛛࿘ᅖ⮋⒆ࡀࡳࡽࢀࡓࠋྠ᪥ࡢ⮫ᗋ᳨ᰝ್ࡣ㸪C ᛂᛶࡓࢇⓑ⃰ᗘ 10.3 mg/dL 㹙ṇᖖ⠊ᅖ㸦NR㸧<0.10 mg/dL㹛ཬࡧⓑ⾑⌫ᩘ 16.11×103/L㸦NR 3.5-9.0×103/L㸧࡛࠶ࡗࡓࠋ2013 ᖺ 2 ᭶ 28 ᪥㸪ࢩ࣮ࢺࣥἲࡢࡓࡵࡢࢻ࣮ࣞࣥࢆ␃⨨ࡋࡓࠋ6 ࡢ᪉ྥ⫠㸪㦵ࡢ๓࡛㸪㝜 ၁ࡢᕥഃ࠶ࡓࡿ㒊ศ⮋⒆⭍ࡀࡳࡽࢀࡓࠋࡑࡢ㸪ࢭࣇ࢝࣌ࣥ㸪ࢭࣇ࣓ࢱࢰ࣮ࣝ㸪ࢭ࣎ࣇࣝࣛ ࣥ㸪ࣉ࣏ࣟࣇ࢛࣮ࣝ㸪ࣟ࢟ࢯࣉࣟࣇ࢙ࣥ㸪ࣇ࢙ࣥࢱࢽࣝ㸪ࣥࣇࣜ࢟ࢩ࣐ࣈཬࡧࣜࢻ࢝ࣥࡼ ࡿ⒪ࡀᐇࡉࢀࡓࠋࢻࣞࢼ࣮ࢪᚋ㸪2013 ᖺ 3 ᭶ 14 ᪥ࡢୖ㒊㦵┙ᇦࡢ CT ࢫ࡛࢟ࣕࣥࡣ㸪⮋⒆ ⭍ࡢ⦰ᑠࡀࡳࡽࢀࡓࠋ⿕㦂⪅ࡣ㸪2013 ᖺ 3 ᭶ 18 ᪥㏥㝔ࡋࡓࠋ
27 0 (134) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
13) Other Adverse Events Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2012-11-07 እ㝜㒊⅖ MILD/ Y/ DOSE NOT CHANGED/ 2012-11-30 (3/.) (VULVITIS) POSSIBLE Y RECOVERED/RESOLVED (26/.) 2012-11-08 㱘ṑ MILD/ N/ DOSE NOT CHANGED/ 2012-12-14 (4/.) (DENTAL CARIES) NOT NA RECOVERED/RESOLVED (40/.) RELATED 2012-11-12 ୖẼ㐨ឤᰁ MILD/ Y/ DOSE NOT CHANGED/ 2012-12-23 (8/.) (UPPER RESPIRATORY TRACT NOT Y RECOVERED/RESOLVED (49/.) INFECTION) RELATED
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route GENTAMICIN SULFATE 2012-11-07 2012-12-14 TOPICAL PARACETAMOL 2012-11-08 2012-11-08 ORAL GARENOXACIN MESILATE 2012-11-12 2012-11-14 ORAL PA 2012-11-16 2012-12-22 ORAL DEXTROMETHORPHAN HYDROBROMIDE 2012-12-18 2012-12-23 ORAL CEFMETAZOLE SODIUM 2013-02-26 2013-03-07 INTRAVENOUS LOXOPROFEN 2013-02-27 2013-03-03 ORAL FENTANYL 2013-02-28 2013-03-01 INTRAVENOUS LIDOCAINE 2013-02-28 2013-02-28 INTRAVENOUS PROPOFOL 2013-02-28 2013-02-28 INTRAVENOUS SEVOFLURANE 2013-02-28 2013-02-28 OTHER FLURBIPROFEN AXETIL 2013-03-04 2013-03-04 INTRAVENOUS PARACETAMOL 2013-03-15 - ORAL DIPHENHYDRAMINE 2013-03-15 - ORAL METHYLPREDNISOLONE SODIUM SUCCINATE 2013-03-15 - INTRAVENOUS
(16) Subject CNTO1275CRD3003-4217-20711
1) Reason for narrative selection SAE
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome (Study day I/M) 2014-06-09 Ꮚᐑᖹ➽⭘ Y SEVERE/ N/ DOSE NOT CHANGED/ 2014-06-16 (168/112) (MYOMA UTERI) NOT RELATED NA RECOVERED/RESOLVED (175/119)
3) Baseline Demographic Information Age (years): 4 Sex: Female Weight (kg): 49 Race: Asian Date of birth: Height (cm): 161.5
4) Induction Treatment Group Induction study: CNTO1275CRD3002 Randomized Treatment Group: Placebo IV Actual Treatment Group: Placebo IV
5) Maintenance Treatment Group Assigned Treatment Group: Non-randomized subject/Non-responder to placebo IV induction dosing and received ustekinumab in maintenance
27 1 (135) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2013-12-24 1 Placebo 0 mg WEEK 0 MAINTENANCE 2014-02-18 57 Placebo 0 mg WEEK 0 MAINTENANCE 2014-02-18 57 Ustekinumab 129.6 mg WEEK 8 MAINTENANCE 2014-04-15 113 Ustekinumab 90 mg WEEK 12 MAINTENANCE 2014-05-13 141 Placebo 0 mg WEEK 16 MAINTENANCE 2014-06-17 176 Placebo 0 mg WEEK 20 MAINTENANCE 2014-07-08 197 Ustekinumab 90 mg WEEK 24 MAINTENANCE 2014-08-05 225 Placebo 0 mg WEEK 28 MAINTENANCE 2014-09-02 253 Placebo 0 mg WEEK 32 MAINTENANCE 2014-10-07 288 Ustekinumab 90 mg WEEK 36 MAINTENANCE 2014-10-28 309 Placebo 0 mg WEEK 40 MAINTENANCE 2014-12-02 344 Placebo 0 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: N Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: Y
8) Induction Baseline Crohn's Disease History Date of diagnosis: 29MAY2012 Disease duration: 1.57 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪⫠㛛࿘ᅖ㸪ᾘ⟶እኚ㸦㛵⠇⅖㸭㛵⠇③㸪⤖⠇ᛶ⣚ᩬ㸧
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: NEVER Stricture complications of (CD): NEVER
10) Concomitant Crohn's Disease-Related Surgeries None reported
11) Concomitant Steroids None reported
12) Narrative Text ⿕㦂⪅ࡣ 4 ṓࡢ᪥ᮏேዪᛶ࡛㸪2013 ᖺ 12 ᭶ 24 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ࣉࣛࢭ࣎ࢆ㟼⬦ෆ ᢞࡉࢀࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡎ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏࢆᢞ ࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪Ꮚᐑ➽⭘㸪ཱྀ ෆ⅖㸪ⰼ⢊㸪౽⛎㸪IgA ⭈ཬࡧႚ↮࡛࠶ࡗࡓࠋ SAE㸸Ꮚᐑᖹ➽⭘㸦Day 168㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ᭶⤒㐣ከࡢࡓࡵ 2014 ᖺ 6 ᭶ 9 ᪥ධ㝔ࡋࡓࠋᏊᐑ➽⭘ࡢࡓࡵ㸪 2014 ᖺ 6 ᭶ 10 ᪥⭡⭍㙾ࡼࡿ⭐ᘧᏊᐑ㝖⾡㸪ᕥ༸⟶ษ㝖⾡ཬࡧഐ༸ᕢᄞ⬊ษ㝖⾡ࢆᐇࡋ ࡓࠋ⾡ᚋ⿕㦂⪅ࡣ⑊③㸪ᝏᚰཬࡧྤࢆⓎ⌧ࡋࡓࠋ2014 ᖺ 6 ᭶ 11 ᪥ࡢ⮫ᗋ᳨ᰝ್ࡣ㸪C ᛂ
27 2 (136) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
ᛶࡓࢇⓑ⃰ᗘ 1.62 mg/dL㹙ṇᖖ⠊ᅖ㸦NR㸧0.0-0.2 mg/dL㹛㸪࣊ࣔࢢࣟࣅࣥ 9.0 g/dL㸦NR 12- 15 g/dL㸧㸪࣐࣊ࢺࢡࣜࢵࢺ 28.7%㸦NR 35.0-45.0%㸧࡛࠶ࡗࡓࠋ2014 ᖺ 7 ᭶ 16 ᪥ࡢ⌮Ꮫⓗᡤぢ ࡛ࡣ㸪Ꮚᐑయࡢ๓ቨྑഃ 41×12 mm ࡢ᭷ⱼ࣏࣮ࣜࣉ㸪ࣜࣥࣃ⟶ᖹ➽⭘ࢆక࠺◳ᛶ⾑⟶࿘ ᅖ㢮ୖ⓶⣽⬊⭘⒆㸦sclerosing perivascular epitheloid cell tumor㸧㸪᫂☜⥙≧㸦clear reticulum㸧ࡢ ከゅ⣽⬊ཬࡧ▷⣳㗽⣽⬊ࡢ㐣ᙧᡂ୪ࡧ⾑⟶ቨ࠾ࡅࡿ࣏࣮ࣜࣉඛ➃᫂☜࡞ᑠࡉ࠸⬊ᕢ≧ᵓ㐀 ཬࡧ⭘⒆⣽⬊ࡢሢࡀࡳࡽࢀࡓࠋ⭘⒆⣽⬊ࡣ㸪චᰁⰍ࡛ࢹࢫ࣑ࣥᢠయ㝧ᛶ࡛࠶ࡾ㸪HMB-45㸦㒊 ศⓗ㸧㸪melan-A㸪S-100 ࢱࣥࣃࢡ㉁㸪CD10 ཬࡧ cytokeratin AE1/AE3 ᢠయ࡛ࡍ࡚㝧ᛶ࡛࠶ࡗࡓࠋ ⭘⒆⣽⬊ࡣෆ⓶࠾࠸࡚ D2-40 ᢠయࡼࡿචᰁⰍ࡛ࡶ㝧ᛶࢆ♧ࡋ㸪ࣜࣥࣃ⣔⏤᮶࡛࠶ࡿࡇࡀ ♧၀ࡉࢀࡓࠋ⌮Ꮫⓗデ᩿ࡣ㸪ࣜࣥࣃ⟶ᖹ➽⭘㸦Ꮚᐑయ㸧㛵㐃ࡍࡿ◳ᛶ⾑⟶࿘ᅖ㢮ୖ⓶ ⣽⬊⭘⒆㸦PEComa㸧࡛࠶ࡗࡓࠋ࣌ࣥࢱࢰࢩࣥ㸪ࣄࢻࣟ࢟ࢩࢪࣥࣃࣔ㓟ሷ㸪࣓ࢺࢡࣟࣉ࣑ࣛࢻཬ ࡧ◲㓟㕲ࡼࡿ⒪ࡀᐇࡉࢀࡓࠋ⿕㦂⪅ࡣ 37.5°C ࡢⓎ⇕㸦᪥ᮍሗ࿌㸧ࢆⓎ⌧ࡋ㸪ࣟ࢟ࢯࣉ ࣟࣇ࢙ࣥࢼࢺ࣒ࣜ࢘ࢆᢞࡉࢀࡓࠋ2014 ᖺ 6 ᭶ 12 ᪥య ࡣ 36.9°C పୗࡋࡓࠋ⿕㦂⪅ࡣ㸪 2014 ᖺ 6 ᭶ 16 ᪥㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome (Study day I/M) 2014-03-27 ᰾ MODERATE/ N/ DOSE NOT CHANGED/ Ongoing (94/38) (HEMORRHOID) NOT RELATED NA NOT RECOVERED/NOT RESOLVED - 2014-06-08 ⫼㒊③ MILD/ N/ DOSE NOT CHANGED/ 2014-06-17 (167/111) (ACUTE LOW BACK PAIN) NOT RELATED NA RECOVERED/RESOLVED (176/120) 2014-06-10 ᝏᚰ MODERATE/ N/ DOSE NOT CHANGED/ 2014-06-11 (169/113) (NAUSEA) NOT RELATED NA RECOVERED/RESOLVED (170/114) 2014-06-10 ฎ⨨ࡼࡿ⑊③ MODERATE/ N/ DOSE NOT CHANGED/ 2014-06-11 (169/113) (PAIN AFTER SURGERY) NOT RELATED NA RECOVERED/RESOLVED (170/114) 2014-06-10 ྤ MODERATE/ N/ DOSE NOT CHANGED/ 2014-06-11 (169/113) (VOMITTING) NOT RELATED NA RECOVERED/RESOLVED (170/114) 2014-06-11 ㈋⾑ MODERATE/ N/ DOSE NOT CHANGED/ 2014-07-08 (170/114) (ANEMIA) NOT RELATED NA RECOVERED/RESOLVED (197/141) 2014-06-12 㢌③ MILD/ N/ DOSE NOT CHANGED/ 2014-06-13 (171/115) (HEADACHE) NOT RELATED NA RECOVERED/RESOLVED (172/116) 2014-06-12 ➽㦵᱁③ MODERATE/ N/ DOSE NOT CHANGED/ 2014-06-13 (171/115) (SHOULDER PAIN) NOT RELATED NA RECOVERED/RESOLVED (172/116) 2014-06-14 㰯ဗ㢌⅖ MILD/ Y/ DOSE NOT CHANGED/ 2014-06-17 (173/117) (COMMON COLD) NOT RELATED N RECOVERED/RESOLVED (176/120) 2014-06-22 ࡑ࠺ MODERATE/ N/ DOSE NOT CHANGED/ 2014-07-08 (181/125) (ITCHING) NOT RELATED NA RECOVERED/RESOLVED (197/141) 2014-07-11 ᖏ≧⑁⑈ MODERATE/ Y/ DOSE NOT CHANGED/ 2014-07-22 (200/144) (HERPES ZOSTER) POSSIBLE Y RECOVERED/RESOLVED (211/155) 2014-10-12 㰯ဗ㢌⅖ MILD/ Y/ DOSE NOT CHANGED/ 2014-12-02 (293/237) (COMMON COLD) DOUBTFUL N RECOVERED/RESOLVED (344/288) 2014-12-02 㰯⅖ MILD/ N/ DOSE NOT CHANGED/ Ongoing (344/288) (CHRONIC RHINITIS) DOUBTFUL NA NOT RECOVERED/NOT RESOLVED -
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route HYDROXYZINE EMBONATE 2014-06-10 2014-06-10 INTRAMUSCULAR METOCLOPRAMIDE 2014-06-10 2014-06-10 INTRAVENOUS DRIP PENTAZOCINE 2014-06-10 2014-06-10 INTRAMUSCULAR LOXOPROFEN SODIUM 2014-06-11 2014-06-12 ORAL KETOPROFEN 2014-06-12 2014-06-12 TRANSDERMAL DEQUALINIUM CHLORIDE 2014-06-14 2014-06-15 TOPICAL FEXOFENADINE 2014-06-22 2014-06-23 ORAL EBASTINE 2014-06-25 2014-06-29 ORAL
27 3 (137) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
Preferred Term Start Date End Date Route VALACICLOVIR HYDROCHLORIDE 2014-07-11 2014-07-18 ORAL EBASTINE 2014-10-24 2014-11-21 ORAL L-CARBOCYSTEINE 2014-10-24 2014-10-28 ORAL TIPEPIDINE HIBENZATE 2014-10-24 2014-10-28 ORAL EBASTINE 2014-12-03 2014-12-16 ORAL
(17) Subject CNTO1275CRD3003-4224-20826
1) Reason for narrative selection SAE Event of interest: Serious infection
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome I/M) 2014-03-01 ࢡ࣮ࣟࣥ Y MILD/ N/ NOT APPLICABLE/ 2014-03-06 (-11/.) (CROHN'S DISEASE NOT NA RECOVERED/RESOLVED (-6/.) AGGRAVATED) RELATED 2014-12-29 ࢘ࣝࢫᛶ⫶⭠⅖ Y MODERATE/ Y/ DOSE NOT CHANGED/ 2014-12-31 (293/237) (GASTROENTERITIS VIRAL) DOUBTFUL N RECOVERED/RESOLVED (295/239)
3) Baseline Demographic Information Age (years): 2 Sex: Female Weight (kg): 39.8 Race: Asian Date of birth: Height (cm): 153.8
4) Induction Treatment Group Induction study: CNTO1275CRD3002 Randomized Treatment Group: Ustekinumab Approximating 6 mg/kg IV Actual Treatment Group: Ustekinumab Approximating 6 mg/kg IV
5) Maintenance Treatment Group Assigned Treatment Group: Non-randomized subject/Non-responder to ustekinumab IV induction dosing and received ustekinumab in maintenance
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2014-03-12 1 Ustekinumab 259.2 mg WEEK 0 MAINTENANCE 2014-05-07 57 Ustekinumab 90 mg WEEK 0 MAINTENANCE 2014-05-07 57 Placebo 0 mg WEEK 8 MAINTENANCE 2014-07-02 113 Ustekinumab 90 mg WEEK 12 MAINTENANCE 2014-07-30 141 Placebo 0 mg WEEK 16 MAINTENANCE 2014-08-27 169 Ustekinumab 90 mg WEEK 20 MAINTENANCE 2014-09-24 197 Placebo 0 mg WEEK 24 MAINTENANCE 2014-10-15 218 Ustekinumab 90 mg WEEK 28 MAINTENANCE 2014-11-19 253 Placebo 0 mg WEEK 32 MAINTENANCE 2014-12-17 281 Ustekinumab 90 mg WEEK 36 MAINTENANCE 2015-01-14 309 Placebo 0 mg WEEK 40 MAINTENANCE 2015-02-18 344 Ustekinumab 90 mg
27 4 (138) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: N Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: Y
8) Induction Baseline Crohn's Disease History Date of diagnosis: 31AUG2007 Disease duration: 6.53 years Involved areas: ᅇ⭠ࡢࡳ㸪ᾘ⟶እኚ㸦ࣇࢱᛶཱྀෆ⅖㸪㛵⠇⅖㸭㛵⠇③㸧
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: NEVER Stricture complications of (CD): NEVER
10) Concomitant Crohn's Disease-Related Surgeries None reported
11) Concomitant Steroids None reported
12) Narrative Text ⿕㦂⪅ࡣ 2 ṓࡢ᪥ᮏேዪᛶ࡛㸪2014 ᖺ 3 ᭶ 12 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏࢆ㟼⬦ෆᢞࡉ ࢀࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡎ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏࢆᢞࡉࢀ ࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪ᑜᖖᛶⓄ㸪 㕲Ḟஈᛶ㈋⾑㸪⫶⅖㸪⏕⌮③㸪ဗ㢌③㸪ⰼ⢊㸪ႚ↮࡛࠶ࡗࡓࠋ SAE㸸ࢡ࣮ࣟࣥ㸦Day -11㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2014 ᖺ 2 ᭶ 28 ᪥Ⓨ⇕㸦39-40°C㸧ࢆⓎ⌧ࡋ㸪⥆࠸࡚ 2014 ᖺ 3 ᭶ 1 ᪥㛵⠇③ཬࡧ㢌③ࡀⓎ⌧ࡋࡓࠋయ ࡣ 38.8°C ࡛㸪⅖ᛂ್ࡀୖ᪼ࡋ㸪㍍ᗘࡢ⬺Ỉഴྥࡀ࠶ ࡗࡓࠋࢡ࣮ࣟࣥࡢᝏデ᩿ࡉࢀ㸪ྠ᪥ධ㝔ࡋࡓࠋ⿕㦂⪅ࡣ㸪⤯㣗ୗ࡛Ỉศ⿵⤥ࡢධ㝔⟶⌮ ࡉࢀࡓࠋ࣋ࣥࣇ࢛ࢳ࣑ࣥ㸭ࣅࢱ࣑ࣥ B12㸭ࣅࢱ࣑ࣥ B6㸦ࣅࢱ࣓ࢪࣥ㸧㸪ࣃࣛࢭࢱ࣮ࣔࣝ㸪ࢹ ࢝ࣜࢽ࣒࢘ࡼࡿ⒪ࡀᐇࡉࢀࡓࠋ2014 ᖺ 3 ᭶ 3 ᪥㸪⿕㦂⪅ࡢ≧ཬࡧ⅖ᛂࡣᛴ㏿ᨵ ၿࡋ㸪㣗ࢆ㛤ጞࡋࡓࠋ2014 ᖺ 3 ᭶ 6 ᪥ࢡ࣮ࣟࣥࡢᝏࡣᾘᩓࡋࡓሗ࿌ࡉࢀ㸪ྠ᪥⿕㦂⪅ ࡣ㏥㝔ࡋࡓࠋ SAE/Serious infection㸸࢘ࣝࢫᛶ⫶⭠⅖㸦Day 293㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2014 ᖺ 12 ᭶ 29 ᪥Ⓨ⇕㸪⭡③ཬࡧୗ⑩ࢆⓎ⌧ࡋ㸪ྠ᪥ධ㝔ࡋࡓࠋ ឤᰁ⤒㊰ࡣ⿕㦂⪅ࡢᏊ౪ࡽࡼࡿࡶࡢ᥎ ࡉࢀࡓࠋ2014 ᖺ 12 ᭶ 29 ᪥ࡢࣂࢱࣝࢧࣥࡣ㸪 ⾑ᅽ 105/60 mmHg㸪⬦ᢿ 105 ᢿ/ศ㸪య 38°C ࡛࠶ࡗࡓࠋྠ᪥ࡢ⮫ᗋ᳨ᰝ್␗ᖖ್ࡣ㸪C ᛂᛶ ࡓࢇⓑ⃰ᗘ 4.21 mg/dL㹙ṇᖖ⠊ᅖ㸦NR㸧0.1 mg/dL㹛㸪࣐࣊ࢺࢡࣜࢵࢺ 26.5%㸦NR 35.4-49.5%㸧
27 5 (139) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
࡛࠶ࡗࡓࠋ⿵ᾮ㸪࣋ࣥࣇ࢛ࢳ࣑ࣥ㸭ࣅࢱ࣑ࣥ B12㸭ࣅࢱ࣑ࣥ B6㸦ࣅࢱ࣓ࢪࣥ㸧ཬࡧࣇࣔࢳ ࢪࣥ㸦࢞ࢫࢱ࣮㸧ὀᑕࡼࡿ⒪ࡀᐇࡉࢀࡓࠋ⿕㦂⪅ࡣ㸪2014 ᖺ 12 ᭶ 31 ᪥㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome (Study day I/M) 2014-04-26 ୗ⭡㒊③ MILD/ N/ DOSE NOT CHANGED/ 2014-04-26 (46/.) (LOWER ABDOMINAL PAIN) NOT RELATED NA RECOVERED/RESOLVED (46/.) 2014-05-01 㰯ဗ㢌⅖ MILD/ Y/ DOSE NOT CHANGED/ 2014-05-06 (51/.) (COMMON COLD) NOT RELATED Y RECOVERED/RESOLVED (56/.) 2014-06-25 ⪥ୗ⭢⅖ MILD/ Y/ DOSE NOT CHANGED/ 2014-07-30 (106/50) (PAROTITIS) NOT RELATED N RECOVERED/RESOLVED (141/85) 2014-09-24 ⪥ୗ⭢⅖ MILD/ Y/ DOSE NOT CHANGED/ 2014-12-17 (197/141) (PAROTITIS) NOT RELATED N RECOVERED/RESOLVED (281/225) 2014-11-25 㰯ဗ㢌⅖ MILD/ Y/ DOSE NOT CHANGED/ 2014-11-30 (259/203) (COMMON COLD) NOT RELATED Y RECOVERED/RESOLVED (264/208) 2014-12-16 㰯ဗ㢌⅖ MILD/ Y/ DOSE NOT CHANGED/ 2015-01-14 (280/224) (COMMON COLD) NOT RELATED Y RECOVERED/RESOLVED (309/253) 2015-02-06 㰯ဗ㢌⅖ MILD/ Y/ DOSE NOT CHANGED/ 2015-02-07 (332/276) (COMMON COLD) NOT RELATED N RECOVERED/RESOLVED (333/277)
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route VITAMEDIN /00274301/ 2014-03-01 2014-03-03 INTRAVENOUS PARACETAMOL 2014-03-02 2014-03-02 ORAL DEQUALINIUM CHLORIDE 2014-03-02 2014-03-04 ORAL PARACETAMOL 2014-04-26 2014-04-26 ORAL FLUTICASONE FUROATE 2014-05-01 2014-05-01 TOPICAL CEFDITOREN PIVOXIL 2014-05-01 2014-05-06 ORAL BEPOTASTINE BESILATE 2014-05-01 2014-05-06 ORAL LOXOPROFEN SODIUM 2014-06-26 2014-07-02 ORAL LOXOPROFEN SODIUM 2014-09-24 2014-09-25 ORAL CEFDITOREN PIVOXIL 2014-11-25 2014-11-30 ORAL L-CARBOCYSTEINE 2014-11-25 2014-11-30 ORAL LOXOPROFEN SODIUM 2014-12-17 2015-01-06 ORAL PA 2014-12-17 2014-12-23 ORAL CEFDITOREN PIVOXIL 2014-12-24 2014-12-27 ORAL L-CARBOCYSTEINE 2014-12-24 2014-12-27 ORAL FAMOTIDINE 2014-12-29 2014-12-31 INTRAVENOUS VITAMEDIN INTRAVENOUS 2014-12-30 2014-12-31 INTRAVENOUS LOXOPROFEN SODIUM 2015-02-06 2015-02-07 ORAL
(18) Subject CNTO1275CRD3003-1007-10176
1) Reason for narrative selection SAE Event of interest: Serious infection
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome (Study day I/M) 2012-07-29 ⳦⾑ Y SEVERE/ Y/ DOSE NOT CHANGED/ 2012-08-01 (116/62) (BACTEREMIA) POSSIBLE Y RECOVERED/RESOLVED (119/65)
27 6 (140) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
3) Baseline Demographic Information ȋȌǣ ͵Ͷ ǣ ȋȌǣ ͻǤͻ ǣ ǣ ͳͻǦͳͲǦ͵Ͳ ȋ Ȍǣ ͳʹǤ
4) Induction Treatment Group Induction study: CNTO1275CRD3001 Randomized Treatment Group: Ustekinumab 130 mg IV Actual Treatment Group: Ustekinumab 130 mg IV
5) Maintenance Treatment Group Assigned Treatment Group: Non-randomized subject/Non-responder to ustekinumab IV induction dosing and received ustekinumab in maintenance
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2012-04-05 1 Ustekinumab 129.6 mg WEEK 0 MAINTENANCE 2012-05-29 55 Ustekinumab 90 mg WEEK 0 MAINTENANCE 2012-05-29 55 Placebo 0 mg WEEK 8 MAINTENANCE 2012-07-20 107 Ustekinumab 90 mg WEEK 12 MAINTENANCE 2012-08-21 139 Placebo 0 mg WEEK 16 MAINTENANCE 2012-09-18 167 Ustekinumab 90 mg WEEK 20 MAINTENANCE 2012-10-16 195 Placebo 0 mg WEEK 24 MAINTENANCE 2012-11-14 224 Ustekinumab 90 mg WEEK 28 MAINTENANCE 2012-12-12 252 Placebo 0 mg WEEK 32 MAINTENANCE 2013-01-08 279 Ustekinumab 90 mg WEEK 36 MAINTENANCE 2013-02-05 307 Placebo 0 mg WEEK 40 MAINTENANCE 2013-03-05 335 Ustekinumab 90 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: N Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: Y
8) Induction Baseline Crohn's Disease History Date of diagnosis: 30JUN2008 Disease duration: 3.77 years Involved areas: ⤖⭠ࡢࡳ㸪ᾘ⟶እኚ㸦PSC㸧
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: NEVER Stricture complications of (CD): NEVER
10) Concomitant Crohn's Disease-Related Surgeries None reported
11) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 0 PREDNISONE 30 mg 30 mg
27 7 (141) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
Visit Drug Dose Prednisone equivalent WEEK 12 MAINTENANCE HYDROCORTISONE CREAM 1% 1 - WEEK 12 MAINTENANCE HYDROCORTISONE SUPPOSITORIES 25 mg - WEEK 12 MAINTENANCE PREDNISONE 40 mg 40 mg WEEK 12 MAINTENANCE PREDNISONE 35 mg 35 mg WEEK 12 MAINTENANCE HYDROCORTISONE - - WEEK 12 MAINTENANCE PREDNISONE 30 mg 30 mg WEEK 12 MAINTENANCE HYDROCORTISONE 0 mg - WEEK 16 MAINTENANCE PREDNISONE 25 mg 25 mg WEEK 16 MAINTENANCE PREDNISONE 20 mg 20 mg WEEK 20 MAINTENANCE PREDNISONE 15 mg 15 mg WEEK 20 MAINTENANCE PREDNISONE 12.5 mg 12.5 mg WEEK 24 MAINTENANCE PREDNISONE 10 mg 10 mg WEEK 28 MAINTENANCE PREDNISONE 9 mg 9 mg WEEK 28 MAINTENANCE PREDNISONE 8 mg 8 mg WEEK 32 MAINTENANCE PREDNISONE 7 mg 7 mg WEEK 32 MAINTENANCE PREDNISONE 6 mg 6 mg WEEK 36 MAINTENANCE PREDNISONE 5 mg 5 mg WEEK 36 MAINTENANCE PREDNISONE 4 mg 4 mg WEEK 40 MAINTENANCE PREDNISONE 2 mg 2 mg WEEK 40 MAINTENANCE PREDNISONE 3 mg 3 mg WEEK 44 MAINTENANCE PREDNISONE 20 mg 20 mg WEEK 44 MAINTENANCE PREDNISONE 15 mg 15 mg WEEK 44 MAINTENANCE PREDNISONE 1 mg 1 mg WEEK 44 MAINTENANCE PREDNISONE 0 mg 0 mg
12) Narrative Text ⿕㦂⪅ࡣ 3 ṓࡢⓑே⏨ᛶ࡛㸪2012 ᖺ 4 ᭶ 5 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏࢆ㟼⬦ෆᢞࡉࢀ ࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡎ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏࢆᢞࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪Ᏻ㸪㧗⾑ᅽ㸪 ⫧‶㸪୧⭸③㸪㛢ሰᛶ╧╀↓྾ࡢ࠸㸪ࢡࣟࢫࢺࣜࢪ࣒࣭࢘ࢹࣇࢩࣞᛶୗ⑩㸪ᛴᛶ⭈ᶵ ⬟㸪ཎⓎᛶ◳ᛶ⫹⟶⅖㸪ࢡ࣮ࣟࣥࡼࡿ⥆Ⓨᛶ㞀ᐖ㸪ႚ↮㸪࢜࢟ࢩࢥࢻࣥᑐࡍࡿࣞ ࣝࢠ࣮࡛࠶ࡗࡓࠋ SAE/Serious infection㸸⳦⾑㸦Day 116㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣᐮẼࡀቑࡋᝏᐮࢆⓎ⌧ࡋࡓ㸦Ⓨ⌧᪥᫂㸧ࠋ2012 ᖺ 7 ᭶ 29 ᪥㸪 ⿕㦂⪅ࡣ⭡㒊ᛌឤ㸪⭡㒊⭾‶ឤ㸪⭾‶ཬࡧ୧⭸③ࢆⓎ⌧ࡋ㸪ࣝࣉࣛࢰ࣒ࣛཬࡧ࣓࢜ࣉࣛࢰ࣮ ࣝࢆ᭹⏝ࡋࡓࠋ⭡㒊ᛌឤࡣ౽ࡢᚋᨵၿࡋࡓࠋࡑࡢᚋ㸪㌟ᛶ⑊③㸪⑊③㸪ᛰឤཬࡧⓎ⇕ ࢆッ࠼ᩆᛴእ᮶ࢆཷデࡋࡓࠋప⾑ᅽཬࡧ㢖⬦ࡀㄆࡵࡽࢀ㸪ᛴᛶᩋ⾑ࡼࡾධ㝔ࡋࡓࠋప⾑ᅽࡣ ᩋ⾑㸭⭈ᶵ⬟⥆Ⓨࡋࡓࡶࡢ⪃࠼ࡽࢀࡓࠋ2012 ᖺ 7 ᭶ 29 ᪥ࡢ⾑ᾮᇵ㣴᳨ᰝ࡛ࡣࢢࣛ ࣒㝜ᛶᱰ⳦㝧ᛶ࡛࠶ࡾ㸪⫵⅖ᱰ⳦ྠᐃࡉࢀ㸪ࡍ࡚ࡢᢠ⏕≀㉁ឤཷᛶࢆ♧ࡋࡓࠋ⭡㒊㉸㡢Ἴ ᳨ᰝ࡛ࡣ࢚ࢥ࣮㍤ᗘࡀᗈ⠊ᅖࢃࡓࡾୖ᪼ࡋ㸪⫢⮚ࡢ࢚ࢥ࣮⏬ീࢸࢡࢫࢳࣕࡣ⢒㐀࡛㸪㍍ᗘࡢ⫢ ෆ⫹⟶ᣑᙇࢆక࠺⫹ᄞᣑᙇࡀㄆࡵࡽࢀࡓࠋ⭡㒊ཬࡧ㦵┙㒊ࢥࣥࣆ࣮ࣗࢱ᩿ᒙᙳ㸦CT㸧ࢫ࢟ࣕ ࣥࡼࡾ㸪ከⓎᛶᮎᲈ⫹⟶ᣑᙇཬࡧ⫹⟶࿘ᅖࡢቑࡀ☜ㄆࡉࢀ㸪ୖ⾜ᛶ⫹⟶⅖ࡀ♧၀ࡉࢀࡓࠋྠ ᪥ࡢ⮫ᗋ᳨ᰝ್ࡣ㸪ࣅࣜࣝࣅࣥ㸦1.1 mg/dL㸧ཬࡧ⫢ࢺࣛࣥࢫ࣑ࢼ࣮ࢮࢆྵࡵ㸪⯡ⓗ␗ᖖࡣ ࡞ࡗࡓࠋ⒪ࡣ㟼⬦ෆ⿵ᾮ㸪ࢫࢸࣟࢻ㸪ࣀࣝࢻࣞࢼࣜࣥ㸪ࣂࢯࣉࣞࢩࣥཬࡧࣆ࣌ࣛࢩࣜ ࣥ㸭ࢱࢰࣂࢡࢱ࣒㸦ࢰࢩࣥ㸧ࡀ⏝࠸ࡽࢀࡓࠋ⿕㦂⪅ࡢ⾑ᅽࡣ 24 㛫௨ෆᨵၿࡋ㸪⾑⟶స⏝⸆ ࡢᢞࡣ୰Ṇࡉࢀࡓࠋ2012 ᖺ 7 ᭶ 30 ᪥ᐇࡉࢀࡓ⭡㒊᰾☢Ẽඹ㬆⏬ീἲ㸦MRI㸧ࡼࡾ㸪⫢ ෆ⫹⟶ࡢ⊃✽ࡀㄆࡵࡽࢀ㸪≉㸪㛵㐃ࡍࡿⴎ⦰ࡀ࠶ࡿྑⴥࡢ quadrate lobe S6 㡿ᇦཬࡧ S7 㡿ᇦ࡛
27 8 (142) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
㢧ⴭ࡛࠶ࡾ㸪ཎⓎᛶ◳ᛶ⫹⟶⅖ࡀ♧၀ࡉࢀࡓࠋ⫹ᄞࡣ㍍ᗘ⭾ᙇࡋ㸪ワࡲࡾࡼࡿ」ᩘࡢ㝜ᙳ ࡢḞᦆࡀࡳࡽࢀ㸪࠾ࡑࡽࡃ㝯㉳ᛶ㸦tumefactive㸧ࡢ⫹Ἶࢆ♧ࡍീ⪃࠼ࡽࢀࡓࠋ2012 ᖺ 8 ᭶ 1 ᪥㸪 ⿕㦂⪅ࡣࣞ࣎ࣇࣟ࢟ࢧࢩࣥཬࡧ࠸ࡘࡶ᭹⏝ࡋ࡚࠸ࡿ⸆ࢆฎ᪉ࡉࢀ㸪㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2012-07-29 ⫹⟶⅖ SEVERE/ N/ DOSE NOT CHANGED/ 2012-08-01 (116/62) (CHOLANGITIS) DOUBTFUL NA RECOVERED/RESOLVED (119/65) 2012-07-29 ప⾑ᅽ SEVERE/ N/ DOSE NOT CHANGED/ 2012-08-01 (116/62) (ACUTE HYPOTENSION) DOUBTFUL NA RECOVERED/RESOLVED (119/65) 2012-07-29 ⭈ SEVERE/ N/ DOSE NOT CHANGED/ 2012-08-01 (116/62) (RENAL INSUFFICIENCY) DOUBTFUL NA RECOVERED/RESOLVED (119/65) 2012-11 ࡑ࠺ MILD/ N/ DOSE NOT CHANGED/ Ongoing - (ITCHING ON SKIN) DOUBTFUL NA NOT RECOVERED/NOT - RESOLVED 2013-03-20 ⭡③ MODERATE/ N/ DOSE NOT CHANGED/ Ongoing (350/296) (INCREASED ABDOMINAL POSSIBLE NA NOT RECOVERED/NOT - PAIN) RESOLVED 2013-03-20 ౽ᅇᩘቑຍ MODERATE/ N/ DOSE NOT CHANGED/ Ongoing (350/296) (INCREASED BOWEL POSSIBLE NA NOT RECOVERED/NOT - MOVEMENTS) RESOLVED
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route DIPHENHYDRAMINE HYDROCHLORIDE 2012-07-30 2012-07-30 INTRAVENOUS MORPHINE 2012-07-30 2012-07-30 INTRAVENOUS METOCLOPRAMIDE 2012-07-30 2012-07-30 INTRAVENOUS KETOROLAC TROMETHAMINE 2012-07-30 2012-07-30 INTRAVENOUS PARACETAMOL 2012-07-30 2012-07-30 ORAL ONDANSETRON 2012-07-30 2012-07-30 INTRAVENOUS
(19) Subject CNTO1275CRD3003-1007-20955
1) Reason for narrative selection SAE Event of interest: Serious infection
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome (Study day I/M) 2015-04-25 ⫵⅖ Y SEVERE/ Y/ DOSE NOT CHANGED/ 2015-04-26 (347/292) (PNEUMONIA) POSSIBLE Y RECOVERED/RESOLVED (348/293)
3) Baseline Demographic Information Age (years): 2 Sex: Male Weight (kg): 70.8 Race: White Date of birth: Height (cm): 195.6
4) Induction Treatment Group Induction study: CNTO1275CRD3002 Randomized Treatment Group: Ustekinumab Approximating 6 mg/kg IV Actual Treatment Group: Ustekinumab Approximating 6 mg/kg IV
27 9 (143) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
5) Maintenance Treatment Group Assigned Treatment Group: Randomized subject/Responder to ustekinumab IV induction dosing/ustekinumab 90 mg SC q8w
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2014-05-14 1 Ustekinumab 389.7 mg WEEK 0 MAINTENANCE 2014-07-08 56 Ustekinumab 90 mg WEEK 8 MAINTENANCE 2014-08-28 107 Ustekinumab 90 mg WEEK 12 MAINTENANCE 2014-09-25 135 Placebo 0 mg WEEK 16 MAINTENANCE 2014-10-28 168 Ustekinumab 90 mg WEEK 20 MAINTENANCE 2014-11-25 196 Placebo 0 mg WEEK 24 MAINTENANCE 2014-12-23 224 Ustekinumab 90 mg WEEK 28 MAINTENANCE 2015-01-22 254 Placebo 0 mg WEEK 32 MAINTENANCE 2015-02-18 281 Ustekinumab 90 mg WEEK 36 MAINTENANCE 2015-03-18 309 Placebo 0 mg WEEK 40 MAINTENANCE 2015-04-22 344 Ustekinumab 90 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: N Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: Y
8) Induction Baseline Crohn's Disease History Date of diagnosis: 31OCT2005 Disease duration: 8.54 years Involved areas: ⤖⭠ࡢࡳ
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: NEVER Stricture complications of (CD): NEVER
10) Concomitant Crohn's Disease-Related Surgeries None reported
11) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 0 PREDNISONE 20 mg 20 mg WEEK 16 MAINTENANCE PREDNISONE 15 mg 15 mg WEEK 24 MAINTENANCE PREDNISONE 10 mg 10 mg WEEK 28 MAINTENANCE PREDNISONE 5 mg 5 mg WEEK 32 MAINTENANCE PREDNISONE 20 mg 20 mg WEEK 32 MAINTENANCE PREDNISONE 15 mg 15 mg WEEK 32 MAINTENANCE PREDNISONE 2.5 mg 2.5 mg
28 0 (144) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
12) Narrative Text ⿕㦂⪅ࡣ 2 ṓࡢⓑே⏨ᛶ࡛㸪2014 ᖺ 5 ᭶ 14 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏࢆ㟼⬦ෆᢞࡉࢀ ࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏ 90 mg ࢆ q8w ࡛⓶ୗᢞࡍࡿ⩌ࣛࣥࢲ࣒ࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪ࢡࣟࢫࢺࣜࢪ ࣒࣭࢘ࢹࣇࢩࣞឤᰁ㸪ὀពḞ㝗࣭ከືᛶ㞀ᐖཬࡧ⸆ㄏⓎᛶ㦵⢒㧼࡛࠶ࡗࡓࠋᐙ᪘Ṕࡣ㯮 Ⰽ⭘㸦∗㸧ཬࡧ๓❧⭢⒴㸦ẕ᪉ࡢ♽∗㸧࡛࠶ࡗࡓࠋ SAE/Serious infection㸸⫵⅖㸦Day 347㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2015 ᖺ 4 ᭶ 25 ᪥ປసᛶ྾ᅔ㞴ࡢᛴᛶⓎཬࡧ῝྾ࡼࡿ ㍍ᗘࡢ࠺ࡗ⾑ཬࡧᛶတႿࡢᝏࡢࡓࡵධ㝔ࡋࡓࠋ⿕㦂⪅ࡣ 2 㐌㛫ཬࡪⓎ⇕㸪ᝏᐮ㸪⑂ປࢆッ ࠼ࡓࠋ⿕㦂⪅ࡣ 2015 ᖺ 4 ᭶ 17 ᪥ࣈࣛࢪࣝ᪑⾜ࡽᡠࡗࡓᚋ㸪ࢡࣟࢫࢺࣜࢪ࣒࣭࢘ࢹࣇࢩ ࣞឤᰁ⒪ࡢࡓࡵ 2015 ᖺ 4 ᭶ 22 ᪥࣓ࢺࣟࢽࢲࢰ࣮ࣝࡢᢞࢆ㛤ጞࡋ㸪ࢡࣟࢫࢺࣜࢪ࣒࣭࢘ࢹ ࣇࢩࣞឤᰁࡣ㍍ᛌࡋࡘࡘ࠶ࡗࡓࠋ2015 ᖺ 4 ᭶ 25 ᪥ࡢ⌮Ꮫⓗᡤぢࡋ࡚ࡣ㸪య 38.3°C㸪ႍ 㬆ࡢ࡞࠸῝྾ࢆక࠺တႿ㸪㊴③ཬࡧ⭡ቨ㜵ᚚࡢ࡞࠸㍍ᗘࡢୗ⭡㒊ᅽ③ཬࡧ᫂☜࡞⭠㞧㡢ࡀㄆ ࡵࡽࢀࡓࠋྠ᪥ࡢ⬚㒊 X ⥺ീࡣ㸪2015 ᖺ 4 ᭶ 15 ᪥ẚ୧ഃୗⴥ᪂ࡓ࡞ᾐ₶ᙳࡀࡳࡽࢀ㸪ᕷ ୰⫵⅖ࡀ♧၀ࡉࢀࡓࠋ⬚ỈཬࡧẼ⬚ࡣሗ࿌ࡉࢀ࡞ࡗࡓࠋ⏕⌮㣗ሷỈ㸪ࣂࣥࢥ࣐ࢩࣥ㸪ࣞ࣎ࣇ ࣟ࢟ࢧࢩࣥࡼࡿ⒪ࢆཷࡅࡓࠋ⿕㦂⪅ࡣ㸪2015 ᖺ 4 ᭶ 26 ᪥㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2014-05-19 ᰾ MODERATE/ N/ DOSE NOT CHANGED/ Ongoing (6/.) (RIGHT EXTERNAL NOT NA NOT RECOVERED/NOT - HEMERRHOID) RELATED RESOLVED 2015-04-22 ࢡࣟࢫࢺࣜࢪ࣒࣭࢘ࢹࣇࢩࣞ MODERATE/ Y/ DOSE NOT CHANGED/ Ongoing (344/289) ឤᰁ POSSIBLE Y NOT RECOVERED/NOT - (CLOSTRIDIUM DIFFICILE RESOLVED INFECTION)
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route METRONIDAZOLE 2015-04-23 - ORAL LEVOFLOXACIN 2015-04-25 2015-04-25 INTRAVENOUS LEVOFLOXACIN 2015-04-25 2015-05-01 ORAL SODIUM CHLORIDE 2015-04-25 2015-04-25 INTRAVENOUS VANCOMYCIN 2015-04-25 2015-04-25 INTRAVENOUS
(20) Subject CNTO1275CRD3003-1013-11005
1) Reason for narrative selection SAE Event of interest: Malignancy
28 1 (145) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome I/M) 2013-08-24 ᑠ⭠㛢ሰ Y SEVERE/ N/ NOT APPLICABLE/ 2013-09-02 (250/194) (SMALL BOWEL OBSTRUCTION, NOT NA RECOVERED/RESOLVED (259/203) ACUTE) RELATED 2013-08-29 ࢝ࣝࢳࣀࢻ⭘⒆ N MODERATE/ N/ NOT APPLICABLE/ 2013-08-29 (255/199) (CARCINOID TUMOR, POSSIBLE NA RECOVERED/RESOLVED (255/199) INCIDENTAL) 2013-08-29 ᑠ⭠⭢⒴ Y SEVERE/ N/ NOT APPLICABLE/ Ongoing (255/199) (METASTATIC POSSIBLE NA NOT RECOVERED/NOT - ADENOCARCINOMA OF SMALL RESOLVED BOWEL) 2013-09-12 ᑠ⭠㛢ሰ Y SEVERE/ N/ NOT APPLICABLE/ Ongoing (269/213) (SMALL BOWEL OBSTRUCTION, NOT NA NOT RECOVERED/NOT - HIGH GRADE) RELATED RESOLVED
3) Baseline Demographic Information Age (years): 6 Sex: Male Weight (kg): 68 Race: White Date of birth: Height (cm): 166.4
4) Induction Treatment Group Induction study: CNTO1275CRD3001 Randomized Treatment Group: Placebo IV Actual Treatment Group: Placebo IV
5) Maintenance Treatment Group Assigned Treatment Group: Non-randomized subject/Non-responder to placebo IV induction dosing and received ustekinumab in maintenance
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2012-12-18 1 Placebo 0 mg WEEK 0 MAINTENANCE 2013-02-12 57 Placebo 0 mg WEEK 0 MAINTENANCE 2013-02-12 57 Ustekinumab 129.6 mg WEEK 8 MAINTENANCE 2013-04-09 113 Ustekinumab 90 mg WEEK 12 MAINTENANCE 2013-05-07 141 Placebo 0 mg WEEK 16 MAINTENANCE 2013-06-06 171 Placebo 0 mg WEEK 20 MAINTENANCE 2013-07-01 196 Ustekinumab 90 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: Y Did the subject terminate the study participation before the Week 44 visit?: Y Did subject enter the long-term extension study?: -
8) Induction Baseline Crohn's Disease History Date of diagnosis: 30SEP2008 Disease duration: 4.22 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪ᑠ⭠㏆㸭⫶㸭㣗㐨
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER
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Fistula: NEVER Stricture complications of (CD): CURRENTLY PRESENT
10) Concomitant Crohn's Disease-Related Surgeries Surgery Date Result of lack of efficacy? ษ㝖-ᅇ┣㒊 2013-08-29 N
11) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 20 MAINTENANCE BUDESONIDE 9 mg - WEEK 20 MAINTENANCE METHYLPREDNISOLONE 80 mg - WEEK 20 MAINTENANCE METHYLPREDNISOLONE 0 mg - WEEK 20 MAINTENANCE DEXAMETHASONE 8 mg - WEEK 20 MAINTENANCE DEXAMETHASONE 0 mg - WEEK 20 MAINTENANCE HYDROCORTISONE 200 mg - WEEK 20 MAINTENANCE HYDROCORTISONE 0 mg - WEEK 20 MAINTENANCE DEXAMETHASONE 40 mg - WEEK 20 MAINTENANCE DEXAMETHASONE 0 mg -
12) Narrative Text ⿕㦂⪅ࡣ 6 ṓࡢⓑே⏨ᛶ࡛㸪2012 ᖺ 12 ᭶ 18 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ࣉࣛࢭ࣎ࢆ㟼⬦ෆᢞ ࡉࢀࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡎ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏࢆᢞ ࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪Ᏻᐃ⊃ᚰ 㸦2009 ᖺ 12 ᭶ 23 ᪥㸧㸪⬚③㸪ቯཪࡣ㛢ሰࡢ࡞࠸⭡⭍࣊ࣝࢽ㸦㒊≉ᐃ㸧㸪య㔜ῶᑡ㸪 യ㸪⪥㬆㸪⫶㣗㐨㏫ὶᛶᝈ㸪ࢫࢺࣞࢫヨ㦂␗ᖖ㸪ࣅࢱ࣑ࣥ D Ḟஈ㸪㛵⠇⅖㸪㞴⫈㸪ෙື⬦ᛶᚰ ᝈ㸪㧗⬡⾑㸦2012 ᖺ 5 ᭶ 16 ᪥㸧㸪ᚰ➽㸦2012 ᖺ 5 ᭶ 16 ᪥㸧㸪࠺ࡗ⾑ᛶᚰ㸪௨๓ࡢႚ ↮㸪㣧㓇㸪࣓ࣝ࢝ࣉࢺࣉࣜࣥᑐࡍࡿࣞࣝࢠ࣮㸪ᡭ᰿⟶ῶᅽ⾡㸪᰾ᡭ⾡㸪ᕥ๓ୗ⾜ᯞ㸦LAD㸧 ࡢࢫࢸࣥࢺࡼࡿ⤒⓶ⓗෙື⬦ᙧᡂ㸪ࣥࣉࣛࣥࢺࡼࡿⓑෆ㞀ᡭ⾡㸪࣮ࣞࢩࢵࢡᡭ⾡㸪S ≧ ⤖⭠᠁ᐊ⅖㸪⫠㝖ཤ࡛࠶ࡗࡓࠋᐙ᪘Ṕࡣ㸪ⱝᖺᛶෙື⬦ᝈ㸦55 ṓᮍ‶㸧ཬࡧ⒴㸦ᘵ㸧࡛࠶ ࡗࡓࠋ SAE㸸ᑠ⭠㛢ሰ㸦Day 250㸪269㸧 SAE/Malignancy㸸ᑠ⭠⭢⒴㸦Day 255㸧 Maligancy㸸࢝ࣝࢳࣀࢻ⭘⒆㸦Day 255㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2013 ᖺ 8 ᭶ 24 ᪥㸪 4 ᪥㛫ཬࡪ③ᛶ⭡③ཬࡧ⫹Ồྤ 㸦5 ᅇⓎ⌧㸧ࢆッ࠼࡚ධ㝔ࡋࡓࠋ⾑౽ἥࡣ࡞ࡗࡓࠋ⌮Ꮫⓗᡤぢ࡛ࡣ㸪⭠㞧㡢ࡢῶᙅࢆక࠺⭡ 㒊⭾‶ࡀࡳࡽࢀࡓࠋ⭡㒊ཬࡧ㦵┙㒊ࡢࢥࣥࣆ࣮ࣗࢱ᩿ᒙᙳ㸦CT㸧ࢫ࢟ࣕࣥ㸦2013 ᖺ 8 ᭶ 24 ᪥㸧 ࡛ࡣ㸪ྑୗ⭡㒊ᅇ⭠ࢆྵࡴᑠ⭠⊃✽ࡀ 3 ࢝ᡤㄆࡵࡽࢀ㸪ࡑࢀࡒࢀ⫧ཌཬࡧ㐣ᗘࡢ⭠ቨቑࡀ㛵 㐃ࡋࡓ㒊ศⓗ࡞ᑠ⭠㛢ሰ㛵ࡋ࡚࠸ࡿྍ⬟ᛶࡀ࠶ࡾ㸪ࡇࢀࡽࡣࡍ࡚άືᮇࡢ⅖ᛶ⭠ᝈཪ ࡣࢡ࣮ࣟࣥࢆ♧၀ࡍࡿࡶࡢ࡛࠶ࡗࡓࠋ⭠✸Ꮝࡢᚩೃࡣ࡞࠸ࡀ㸪㍍ᗘࡢ⭡Ỉࡀ⭡㒊ཬࡧ㦵┙㒊 ࡳࡽࢀࡓࠋ᠁ᐊ⅖ࢆకࢃ࡞࠸ S ≧⤖⭠᠁ᐊࡀࡳࡽࢀࡓࠋ2013 ᖺ 8 ᭶ 25 ᪥ࡢ CT ࢫ࡛࢟ࣕࣥࡣ㸪 ⭡㒊ᑡ㔞ࡢ㐟㞳ᾮయ㸪ᅇ┣㒊㍍ᗘࡢ⅖ࡀㄆࡵࡽࢀࡓࡀ㸪㛢ሰࡢᚩೃࡣࡳࡽࢀ࡞ࡗࡓࠋ⿕ 㦂⪅ࡢ㏻ᖖࡢ౽ᅇᩘࡣ 1 ᪥ 3 ᅇ࡛࠶ࡿࡀ㸪2014 ᖺ 8 ᭶ 24 ᪥ᑡ㔞ࡢ౽ࡀ 1 ᅇࡢࡳ࠶ࡾ㸪ࡑ ࢀ௨㝆ࡣᨺᒂཬࡧ౽ࡀ࡞࠸ሗ࿌ࡋࡓࠋ㰯⭍⫶྾ᘬࢆ㛤ጞࡍࡿ≧ࡣᨵၿࡋࡓࠋ2013 ᖺ 8 ᭶ 27 ᪥ࡢ⭡㒊 X ⥺᳨ᰝࡢࢥࣥࢺࣛࢫࢺࡣ㸪୰➼ᗘᣑᙇࡋࡓ㏆ཬࡧ୰㛫㒊ࡢ✵⭠ಀ㋟࡛ࡣ୍㈏
28 3 (147) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
ࡋ࡚㏱㐣㸪㐲ᑠ⭠ಀ㋟࡛ࡣ㏱㐣ࢆ♧ࡋ㸪ᑠ⭠୰㛫㒊ࡢ㛢ሰ୍⮴ࡍࡿࡶࡢ࡛࠶ࡗࡓࠋᑠ⭠㐀 ᙳ㸦2013 ᖺ 8 ᭶ 27 ᪥㸧࡛ࡣ㸪ᣑᙇࡋࡓ㏆✵⭠ಀ㋟㸪⫶ཬࡧ༑ᣦ⭠࠾࠸࡚ࢆక࠺㐀ᙳ ࡢ㏻㐣㐜ᘏࡀㄆࡵࡽࢀࡓࠋ2013 ᖺ 8 ᭶ 29 ᪥㸪⿕㦂⪅ࡣᅇ⭠⤖⭠ษ㝖㸦ᅇ⭠ᮎ➃㸪┣⭠ཬࡧ ᆶ㸧ࢆక࠺ヨ㦂㛤⭡ࢆᐇࡋึᮇ࿀ྜࢆᐇࡋࡓࠋᡭ⾡ᡤぢ࡛ࡣ㸪ᅇ⭠ᮎ➃㸪῝࠸⅖ཬ ࡧᙉ࠸⊃✽ࢆక࠺㢧ⴭ࡞ࢡ࣮ࣟࣥࡀࡳࡽࢀࡓࠋᑠ⭠⏕᳨ࡼࡾ㸪⧄⥔⤌⧊∦୰くⓗ࡞⭢⒴ ࡀㄆࡵࡽࢀࡓࠋᅇ⭠┣⭠ᮎ➃⏕᳨ࡼࡾ㸪ᅇ┣ᘚཬࡧᅇ⭠ᮎ➃㸪⭠ቨᒙཬࡧ₢⭷⾲㠃㐩ࡍ ࡿ✸Ꮝࢆక࠺くᛶࡢ༳⎔⣽⬊⒴ࡀㄆࡵࡽࢀࡓࠋ⭘⒆ࡣᑠ⭠₢⭷ཬࡧᆶࡢ⚄⤒࿘ᅖࢆᾐ₶ࡋ࡚ ࠾ࡾ㸪ᚤᑠ࡞✸Ꮝࡀ♧၀ࡉࢀࡓࠋ⭘⒆ࡣ⭠㛫⭷ࡢ࿘㎶࡛ 1 cm ௨ෆᣑࡋ㸪12 ಶ࠶ࡿ⭠㛫⭷ࣜ ࣥࣃ⠇ࡢ࠺ࡕࡢ 9 ಶ㌿⛣ࡋ࡚࠸ࡓࠋࣜࣥࣃ⠇እࡢᣑࡶࡳࡽࢀࡓࠋᑠ⭠᠁ᐊ࡛┤ᚄ⣙ 5 mm ࡢ࢝ࣝࢳࣀࢻ⭘⒆ࡀࡳࡽࢀࡓࠋ⒪ࡣ㙠③⸆㸪ᢠ⏕≀㉁ཬࡧ୍⯡ⓗ࡞ᑐ⒪ἲ⸆ࡀ⏝࠸ࡽࢀ ࡓࠋ2013 ᖺ 9 ᭶ 2 ᪥⿕㦂⪅ࡣ㏥㝔ࡋࡓࠋ ⿕㦂⪅ࡣᾮయࢆྵࡴ㣗≀⪏ᛶཬࡧᡭ⾡௨㝆ࡢ࢞ࢫἥ㢖ᗘῶᑡࡼࡾ㸪2013 ᖺ 9 ᭶ 12 ᪥ ධ㝔ࡋࡓࠋ㰯⭍⫶ࢳ࣮ࣗࣈ␃⨨ࡼࡾ⭠ෆࡢᅽຊࢆῶࡽࡍࡇࡀ࡛ࡁ㸪㠀⤒ཱྀᰤ㣴ἲࡀ㛤ጞ ࡉࢀࡓࠋ⾡ᚋࡢᾋ⭘ࡢ㍍ῶཬࡧ㛢ሰࡀ㍍ῶ࡛ࡁࡿྍ⬟ᛶࡀ࠶ࡿࡓࡵ㸪ࢹ࢟ࢧ࣓ࢱࢰࣥ⒪ἲࢆヨࡳ ࡓࡀኻᩋࡋࡓࠋᑠ⭠㐀ᙳ᳨ᰝ࡛ࡣ㸪㐀ᙳࡀ⤖⭠ෆ 2.5 㛫ࡋ㸪㏻㐣ࡣ㐜ࡃ㸪ᑠ⭠㏆࡛ ୰➼ᗘᣑᩓࡋ࿀ྜ㒊㏆ᩡ㸦narrowing㸧ࡍࡿࡢࡀㄆࡵࡽࢀࡓࠋ㒊ศⓗ࡞㛢ሰࡣᣢ⥆ࡋࡓࡀ㸪 ධ㝔ᮇ㛫ࢆ㏻ࡌ࡚㛫Ḟⓗᨺᒂཬࡧ౽ࡀ࠶ࡗࡓࠋ⿕㦂⪅ࡣᩘ᪥㛫㸪㰯⭍⫶ࢳ࣮ࣗࣈ㝖ཤ⪏࠼ ࡓࡀ㸪ࡑࢀ௨㝆⭡㒊ࡀ⭾ᙇࡋ㸪ྤࡁẼࢆദࡋ㸪ྤࡋࡓࠋ⏬ീࡼࡾ㛢ሰࡀ☜ㄆࡉࢀ㸪㰯⭍⫶ࢳ ࣮ࣗࣈࡀᡠࡉࢀ㸪⤒⓶ⓗෆど㙾ୗ⫶⒦㐀タ⾡㸦PEG㸧ࢳ࣮ࣗࣈࡀᾘჾෆ⛉་ࡼࡗ࡚␃⨨ࡉࢀ ࡓࠋ⿕㦂⪅ࡣ㸪2013 ᖺ 9 ᭶ 24 ᪥㐲㝸㌿⛣ࢆక࠺⤖⭠⒴ࡢࡓࡵ㟁ヰ࡛㦂ྠពࢆ᧔ᅇࡋࡓࠋ⿕ 㦂⪅ࡣ㸪2013 ᖺ 10 ᭶ 2 ᪥㏥㝔ࡋࡓࠋ 2013 ᖺ 10 ᭶ 3 ᪥ࡢ⭠ෆど㙾᳨ᰝࡼࡾ㸪άືᮇࡢᅇ⭠⅖ࡣ࡞࠸ࡀ㸪⊃✽ࡀᣢ⥆ࡋ࡚࠸ࡿࡇ ࡀ☜ㄆࡉࢀࡓࠋᶓ⾜⤖⭠ཬࡧ S ≧⤖⭠㐲 3 mm ࡢ↓ⱼᛶ࣏࣮ࣜࣉࡶࡳࡽࢀࡓࠋᡭ⾡ࡢ ⌮Ꮫⓗ᳨ᰝࡼࡾ㸪㐣ᙧᡂᛶ࣏࣮ࣜࣉࢆక࠺⟶≧⭢⭘࡛࠶ࡿࡇࡀ☜ㄆࡉࢀࡓࠋ㢧ᚤ㙾᳨ᰝࡼ ࡾ㸪᫂░࡞࣏࣮ࣜࣉᵝࡢ㍯㒌ࢆࡋࡓ⤖⭠⢓⭷ࡢ᩿∦ཬࡧࡸࡸ㐣࡞࣒ࢳࣥ⏘ᡂࡀ☜ㄆࡉࢀࡓࠋ ࣇࣜࣝ≧ᵓ㐀ࡣ㐣ᙧᡂᛶ࣏࣮ࣜࣉ≉᭷࡛࠶ࡿࠋ␗ᙧᡂࡢᚩೃࡣ࡞ࡗࡓࠋࡼࡾ῝࠸㡿ᇦࡢษ∦ ࡛ࡣ㸪࣏࣮ࣜࣉࡢ 1 ࡘ㸪ప࠸ Grade ࡢ␗ᙧᡂࡀㄆࡵࡽࢀࡿࡇࡀ᫂ࡽ࡞ࡗࡓࠋ2013 ᖺ 10 ᭶ 8 ᪥㸪⿕㦂⪅ࡣ 5-fluorouracil㸦5-FU㸧ࡼࡿᏛ⒪ἲࢆ㛤ጞࡋࡓࠋ⿕㦂⪅ࡣ⭡③ࡢᝏ ཬࡧ PEG ࢳ࣮ࣗࣈࡽࡢ౽≧ᾮࢆッ࠼㸪2013 ᖺ 10 ᭶ 14 ᪥ධ㝔ࡋࡓࠋ⿕㦂⪅ࡣ㠀ᖖ⾶ᙅ ࡋ㸪៏ᛶࡢᗈỗᛶ⭡③㸪ᝏᚰ㸪Ṍ⾜ཬࡧᒀᅔ㞴୪ࡧ PEG ࢳ࣮ࣗࣈࡢở≀㏫ὶࡀࡳࡽࢀࡓࠋ ⌮Ꮫⓗᡤぢ࡛ࡣࢃࡎᗈ⠊ᛶࡢᅽ③ཬࡧ⭠㞧㡢ࢆక࠺㍍ᗘࡽ୰➼ᗘࡢ⭡㒊⭾‶ࡀࡳࡽࢀࡓࠋ ⬚㒊 X ⥺᳨ᰝ࡛ࡣᮎᲈ✸่୰ᚰ㟼⬦࢝ࢸ࣮ࢸࣝࣛࣥࡀࡳࡽࢀ㸪ᛴᛶᝈࡢᚩೃࡣ࡞ࡗࡓࠋ⭡ 㒊ཬࡧ㦵┙㒊ࡢ CT ࢫ࢟ࣕࣥ㸦2013 ᖺ 10 ᭶ 14 ᪥㸧࡛ࡣ㸪ᑠ⭠ᗈ⠊࡞⫧ཌࡀࡳࡽࢀ㸪⭠㛫⭷࡛ ࡢ stranding ୍⮴ࡍࡿࡶࡢ࡛࠶ࡗࡓࠋ⫢ୗ㡿ᇦ⿕ໟࡉࢀࡓ⭡⭍ෆᾮయ㈓␃ࡀ 1 ࢝ᡤཬࡧࡑࡢ ࡢᑠ⭠㛢ሰࡀ 3 ࢝ᡤ࠶ࡾ㸪ᑠ⭠⅖⥆Ⓨࡋࡓྍ⬟ᛶࡀ࠶ࡗࡓࠋࢡࣟࣝࣉ࣐ࣟࢪࣥሷ㓟ሷ㸪࢜࢟ ࢩࢥࢻࣥ㸪hydromorphone ཬࡧ㠀⤒ཱྀᰤ㣴ࡼࡿ⒪ࢆ⾜ࡗࡓࠋ⿕㦂⪅ࡣⓎ⇕ࡋ㸪࣏࣮ࢺࡢ ᇵ㣴᳨ᰝ࡛ࡣ㸪࣓ࢳࢩࣜࣥ⪏ᛶ㯤Ⰽࣈࢻ࢘⌫⳦㝧ᛶ࡛࠶ࡗࡓࠋࣂࣥࢥ࣐ࢩࣥࡼࡿ⒪ࢆ㛤ጞ ࡋ㸪ࡑࡢᚋࣜࢿࢰࣜࢻษࡾ᭰࠼ࡽࢀࡓࠋ࣏࣮ࢺࡣ㝖ཤࡉࢀࡓࠋ2013 ᖺ 10 ᭶ 17 ᪥㸪ᣔ࠸ᾮᇵ㣴 ࡛㯤Ⰽࣈࢻ࢘⌫⳦ࡢ㔞ቑṪࡀࡳࡽࢀࡓࠋ⾑ᾮᇵ㣴㸦2013 ᖺ 10 ᭶ 17 ᪥㸧ཬࡧᒀᇵ㣴㸦2013 ᖺ
28 4 (148) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
10 ᭶ 18 ᪥㸧࡛ࡣቑṪࡣࡳࡽࢀ࡞ࡗࡓࠋࢢ࣒ࣛᰁⰍ࡛ࡣሢ≧ཬࡧ⌫≧ࡢࢢ࣒ࣛ㝧ᛶ⌫⳦ࡀࡳ ࡽࢀࡓࠋ1 㐌㛫ᚋ㸪⿕㦂⪅ࡢ≧ࡣᨵၿࡋࡓࡓࡵ㸪㏻ᖖ㣗࡞ࡗࡓࠋ2013 ᖺ 10 ᭶ 23 ᪥㸪⿕㦂 ⪅ࡣᏛ⒪ἲࡢ 2 ࢧࢡࣝ┠ࢆ㛤ࡋࡓࠋ⿕㦂⪅ࡣ㸪2013 ᖺ 10 ᭶ 28 ᪥㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2013-01-31 ⪥ឤᰁ MILD/ Y/ DOSE NOT CHANGED/ 2013-02-12 (45/.) (EAR INFECTION) DOUBTFUL Y RECOVERED/RESOLVED (57/.) 2013-02-13 ⪥₃ MILD/ N/ DOSE NOT CHANGED/ 2013-02-20 (58/2) (EAR DRAINAGE) DOUBTFUL NA RECOVERED/RESOLVED (65/9) 2013-06-17 ࢡ࣮ࣟࣥ MODERATE/ N/ DOSE NOT CHANGED/ Ongoing (182/126) (CROHN'S FLARE, NOT NA NOT RECOVERED/NOT - WORSENING) RELATED RESOLVED
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route CEFALEXIN 2013-02-05 2013-02-12 ORAL PSEUDOEPHEDRINE HYDROCHLORIDE 2013-02-13 2013-02-20 ORAL BUDESONIDE 2013-07-11 - ORAL ADALIMUMAB 2013-08-13 2013-09 SUBCUTANEOUS CIPROFLOXACIN 2013-08-20 2013-09-02 ORAL METRONIDAZOLE 2013-08-20 2013-08-30 ORAL HYDROMORPHONE HYDROCHLORIDE 2013-08-24 2013-09-02 INTRAVENOUS DRIP LEVOFLOXACIN 2013-08-24 2013-08-24 INTRAVENOUS DRIP MORPHINE SULFATE 2013-08-24 2013-08-25 INTRAVENOUS BOLUS ONDANSETRON HYDROCHLORIDE 2013-08-24 - ORAL FAMOTIDINE 2013-08-25 2013-09-02 ORAL HEPARIN 2013-08-25 2013-09-02 INTRAMUSCULAR PIP/TAZO 2013-08-25 2013-08-30 INTRAVENOUS DRIP PROMETHAZINE 2013-08-25 2013-08-29 ORAL METHYLPREDNISOLONE SODIUM SUCCINATE 2013-08-26 2013-08-29 INTRAVENOUS PARACETAMOL 2013-08-29 2013-08-30 INTRAVENOUS BOLUS DIPHENHYDRAMINE 2013-08-29 2013-09-01 INTRAVENOUS BOLUS HYDROCORTISONE SODIUM SUCCINATE 2013-08-29 2013-09-01 INTRAVENOUS DRIP NALOXONE 2013-08-29 2013-09-01 INTRAVENOUS BOLUS ROPIVACAINE HYDROCHLORIDE 2013-08-29 2013-09-02 INTRAVENOUS DRIP LORATADINE 2013-08-30 2013-09-02 ORAL OMEPRAZOLE 2013-09 2013-10-04 ORAL POTASSIUM 2013-09-01 - ORAL OXYCODONE HYDROCHLORIDE 2013-09-02 - ORAL HYDROMORPHONE HYDROCHLORIDE 2013-09-12 2013-10-02 INTRAVENOUS MORPHINE SULFATE 2013-09-12 2013-09-12 INTRAVENOUS PROMETHAZINE 2013-09-12 2013-09-12 INTRAVENOUS ALTEPLASE 2013-09-13 2013-10-02 INTRAVENOUS HEPARIN 2013-09-13 - INTRAMUSCULAR PANTOPRAZOLE 2013-09-13 - ORAL INTRALIPID /00272201/ 2013-09-13 - INTRAVENOUS DEXAMETHASONE 2013-09-17 2013-09-29 INTRAVENOUS MAGNESIUM SULFATE 2013-09-20 2013-09-20 INTRAVENOUS PARACETAMOL 2013-09-25 - ORAL PARACETAMOL 2013-09-26 - RECTAL CEFAZOLIN 2013-09-30 2013-09-30 INTRAVENOUS FENTANYL 2013-09-30 2013-09-30 INTRAVENOUS MIDAZOLAM 2013-09-30 2013-09-30 INTRAVENOUS HYDROMORPHONE HYDROCHLORIDE 2013-10-14 2013-10-25 INTRAVENOUS
28 5 (149) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
Preferred Term Start Date End Date Route POTASSIUM CHLORIDE 2013-10-14 2013-10-25 INTRAVENOUS PROMETHAZINE 2013-10-14 2013-10-14 INTRAMUSCULAR SODIUM CHLORIDE 2013-10-14 2013-10-25 ORAL TETRACOSACTIDE 2013-10-15 2013-10-15 INTRAMUSCULAR BISACODYL 2013-10-16 2013-10-25 ORAL CHLORPROMAZINE 2013-10-16 2013-10-18 INTRAVENOUS CEFEPIME HYDROCHLORIDE 2013-10-17 2013-10-18 INTRAVENOUS MAGNESIUM SULFATE 2013-10-17 2013-10-20 INTRAVENOUS VANCOMYCIN 2013-10-17 2013-10-21 INTRAVENOUS CEFAZOLIN 2013-10-18 2013-10-19 INTRAVENOUS DEXAMETHASONE 2013-10-20 2013-10-21 INTRAVENOUS LINEZOLID 2013-10-21 2013-10-24 INTRAVENOUS FLUOROURACIL 2013-10-22 2013-10-24 INTRAVENOUS CALCIUM FOLINATE 2013-10-22 2013-10-22 INTRAVENOUS ALTEPLASE 2013-10-24 2013-10-25 INTRAVENOUS
(21) Subject CNTO1275CRD3003-1015-10811
1) Reason for narrative selection SAE Discontinuation of study agent due to AE Event of interest: Serious infection
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome I/M) 2013-07-29 ࣈࢻ࢘⌫⳦ᛶ⫵⅖ Y MODERATE/ Y/ DRUG WITHDRAWN/ 2013-09-18 (264/207) (STAPHYLOCOCCUS AUREUS PROBABLE Y RECOVERED/RESOLVED (315/258) PNEUMONIA)
3) Baseline Demographic Information Age (years): 5 Sex: Female Weight (kg): 96.4 Race: White Date of birth: Height (cm): 156
4) Induction Treatment Group Induction study: CNTO1275CRD3001 Randomized Treatment Group: Placebo IV Actual Treatment Group: Placebo IV
5) Maintenance Treatment Group Assigned Treatment Group: Non-randomized subject/Non-responder to placebo IV induction dosing and received ustekinumab in maintenance
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2012-11-08 1 Placebo 0 mg WEEK 0 MAINTENANCE 2013-01-04 58 Placebo 0 mg WEEK 0 MAINTENANCE 2013-01-04 58 Ustekinumab 129.6 mg WEEK 8 MAINTENANCE 2013-03-29 142 Ustekinumab 90 mg WEEK 12 MAINTENANCE 2013-04-26 170 Placebo 0 mg WEEK 16 MAINTENANCE 2013-05-15 189 Placebo 0 mg WEEK 20 MAINTENANCE 2013-06-03 208 Ustekinumab 90 mg
28 6 (150) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
Visit Start Date Study Day Actual Treatment Dose WEEK 24 MAINTENANCE 2013-06-21 226 Placebo 0 mg WEEK 28 MAINTENANCE 2013-07-26 261 Placebo 0 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: Y Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: -
8) Induction Baseline Crohn's Disease History Date of diagnosis: 31DEC1981 Disease duration: 30.86 years Involved areas: ⤖⭠ࡢࡳ㸪⫠㛛࿘ᅖ㸪ᾘ⟶እኚ㸦㛵⠇⅖㸭㛵⠇③㸧
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: PREVIOUS HISTORY Stricture complications of (CD): NEVER
10) Concomitant Crohn's Disease-Related Surgeries None reported
11) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 0 BUDESONIDE 9 mg - WEEK 0 HYDROCORTISONE 25 mg - WEEK 0 HYDROCORTISONE 2.5 - WEEK 8 METHYLPREDNISOLONE 80 mg - WEEK 8 METHYLPREDNISOLONE 4 mg 5 mg WEEK 8 METHYLPREDNISOLONE 0 mg - WEEK 8 MAINTENANCE METHYLPREDNISOLONE 4 mg 5 mg WEEK 8 MAINTENANCE METHYLPREDNISOLONE 0 mg 0 mg WEEK 12 MAINTENANCE METHYLPREDNISOLONE 80 mg - WEEK 12 MAINTENANCE METHYLPREDNISOLONE 80 mg - WEEK 12 MAINTENANCE METHYLPREDNISOLONE 80 mg -
12) Narrative Text ⿕㦂⪅ࡣ 5 ṓࡢⓑேዪᛶ࡛㸪2012 ᖺ 11 ᭶ 8 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ࣉࣛࢭ࣎ࢆ㟼⬦ෆᢞ ࡉࢀࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡎ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏࢆᢞࡉ ࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪࠺ࡘ㸪Ᏻ㸪 ╀㸪ᑠᏍ࣊ࣝࢽ㸪᠁ᐊ㸪᰾㸪㛵⠇③㸪៏ᛶᝏᚰ㸪⥺⥔➽③㸪៏ᛶࡪ࠺⭷⅖㸪⫵⅖㸪 ៏ᛶཱྀ⭍ෆ₽⒆㸪ᖏ≧⑁⑈㸪㧗⾑ᅽ㸪⢾ᒀ㸪┤⭠⫠㛛⫠㸪bladder tack㸪៏ᛶ⫠㛛②ᨥ㸪㦵┙ ᗏ➽ຊపୗ㸪㦵┙⬡⫫⭘㸪⫘㌾㦵⅖㸪ୗ⫥㟼Ṇ⬟ೃ⩌㸪ኚᙧᛶ㛵⠇㸪ᮎᲈᛶࢽ࣮ࣗࣟࣃ ࢳ࣮㸪ከⓎᛶ㛵⠇③㸪㍍࠸യ㸪༸⟶⤖⣻㸪⫧‶㸪៏ᛶ⫼㒊③㸪Ꮚᐑฟ㸪㦵┙ᘓࡢ」ྜᡭ⾡㸪 ┤⭠⬺ಟ㸪┤⭠⭼⒦ᡭ⾡㸪⫠㛛⭼⒦ಟ㸦ࢩ࣮ࢺࣥ␃⨨ࢆక࠺㸧㸪ྑᡭ᰿⟶ᡭ⾡㸪᳝㛫ᯈ◚
28 7 (151) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
ᑐࡍࡿ⫼㦵ᡭ⾡ཬࡧ⸆ࣞࣝࢠ࣮㹙ࢫࣆࣜࣥ㸭࢜࢟ࢩࢥࢻࣥሷ㓟ሷ㸦Percodan㸧ཬࡧ࢜࢟ ࢩࢥࢻࣥ㹛࡛࠶ࡗࡓࠋᐙ᪘Ṕࡣ㸪⫵⒴㸦∗㸧࡛࠶ࡗࡓࠋ SAE/Discontinuation of study agent due to AE/Serious infection㸸ࣈࢻ࢘⌫⳦ᛶ⫵⅖㸦Day 264㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ⬺ຊ㸪ᛶတႿࡢᝏཬࡧᜥษࢀࡼࡾ㸪2013 ᖺ 7 ᭶ 29 ᪥ධ㝔 ࡋࡓࠋ⌮Ꮫⓗᡤぢࡋ࡚㸪⫈デࡼࡾ㸪⫵㔝ᚋ㒊ႍ㬆ཬࡧప㡢ᛶ㐃⥆ᛶࣛ㡢ࡀㄆࡵࡽࢀࡓࠋྠ ᪥ࡢࢥࣥࣆ࣮ࣗࢱ᩿ᒙᙳ㸦CT㸧ࢫ࡛࢟ࣕࣥࡣ㸪ྑୖⴥẼ⟶ᨭࡢ⊃✽ࢆక࠺ྑ⫵㛛࿘ᅖ㌾㒊⤌ ⧊ࡢ density mass ࢆㄆࡵ㸪Ẽ⟶ᨭࡣྑୖⴥࡢ⫵⬊ᛶ㝜ᙳࡢ㒊㐃⥆ࡋ࡚࠾ࡾ㸪㛢ሰᚋࡢ↓Ẽ ⫵ཪࡣ⫵⅖ࢆ♧ࡍࡶࡢ᥎ᐃࡉࢀࡓࠋὀ┠ࡍࡁⅬࡋ࡚㸪2013 ᖺ 7 ᭶ 27 ᪥ࡢ CT ື⬦㐀ᙳཬ ࡧࣇࣈࣜࣥ D ࢲ࣐࣮ヨ㦂࡛ࡣ㸪⫵ሰᰦ㝜ᛶ࡛࠶ࡗࡓࠋ⬚㒊 X ⥺᳨ᰝ㸦ᐇ᪥᫂㸧࡛ࡣ㸪 ഹ㛫㝸ࡀቑࡋࡓ⫵㛛࿘ᅖ㸪㛫㉁㸪Ẽ⟶ᨭ࿘ᅖࡢෆഃྑୖ⫵ࡢ⫧ཌࡀㄆࡵࡽࢀ㸪࢘ࣝࢫ ᛶ㛫㉁ᛶ⫵⮚⅖ཪࡣᛂᛶẼ㐨ᝈࡀ♧၀ࡉࢀࡓࠋ2013 ᖺ 8 ᭶ 1 ᪥ᐇࡋࡓẼ⟶ᨭ㙾᳨ᰝ࡛ࡢ ␗ᖖࡋ࡚㸪ྑୖⴥࡢ superior segment ෆ⅖ཬࡧ⊃✽ࢆకࡗࡓ㛢ሰᚋࡢᾐ₶ࡀㄆࡵࡽࢀࡓࠋ ྠ᪥ࡢྑୖẼ⟶ᨭὙίᾮࡢ⣽⬊デࡢ⤖ᯝࡣᝏᛶ⣽⬊㝜ᛶ࡛࠶ࡾ㸪Ⰻᛶࡢୖ⓶⣽⬊ཬࡧ୰➼ᗘࡢዲ ୰⌫ඃࡢΰྜᛶࡢ⅖ࡀㄆࡵࡽࢀࡓࠋྑୖⴥࡢẼ⟶ᨭ⤌⧊ࡢẼ⟶ᨭ㙾⏕᳨࡛ࡣ㸪ᛂᛶ྾⢓ ⭷ཬࡧᒁᡤࡢᐇ㉁ᾋ⭘ࡀㄆࡵࡽࢀࡓࡀ㸪⒴ཬࡧ⫗ⱆ⭘ࡢᚩೃࡣ࡞ࡗࡓࠋ2013 ᖺ 8 ᭶ 2 ᪥㸪Ẽ⟶ ᨭὙίᇵ㣴࡛ࡣ㯤Ⰽࣈࢻ࢘⌫⳦㝧ᛶ㸦୰➼ᗘࡢቑṪ㸧ཬࡧ Į ⁐⾑ᛶࣞࣥࢧ⌫⳦㝧ᛶ㸦㍍ᗘࡢቑṪ㸧 ࡛࠶ࡗࡓࠋ⒪ࡣࣔ࢟ࢩࢩࣜࣥ㸭ࢡࣛࣈࣛࣥ㓟㸦࣮࢜ࢢ࣓ࣥࢳࣥ㸧㸪albuterol㸭ࣉࣛࢺࣟ ࣆ࣒࢘㸦Duoneb㸧ཬࡧヲ⣽᫂ࡢ㙠③⸆ࡀ⏝࠸ࡽࢀࡓࠋ⿕㦂⪅ࡣ㸪2013 ᖺ 8 ᭶ 2 ᪥㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2012-12-27 㛵⠇③ MODERATE/ N/ DOSE NOT CHANGED/ 2013-02-01 (50/.) (WORSENING OF BILATERAL KNEE PAIN) NOT NA RECOVERED/RESOLVED (86/.) RELATED 2013-01-20 యᾮ㈓␃ MODERATE/ N/ DOSE NOT CHANGED/ 2013-01-24 (74/17) (FLUID RETENTION) NOT NA RECOVERED/RESOLVED (78/21) RELATED 2013-02 ෆฟ⾑Ⓨ⏕ࡢቑຍഴྥ(WORSENING OF MODERATE/ N/ DOSE NOT CHANGED/ Ongoing - BRUSING EASILY) NOT NA NOT RECOVERED/NOT - RELATED RESOLVED 2013-02-21 ኚᙧᛶ㛵⠇ MODERATE/ N/ DOSE NOT CHANGED/ 2013-02-28 (106/49) (DEGENERATIVE JOINT DISEASE) NOT NA RECOVERED/RESOLVED (113/56) RELATED 2013-03-01 Ẽ⟶ᨭ⅖ MODERATE/ Y/ DOSE NOT CHANGED/ 2013-03-20 (114/57) (BRONCHITIS) NOT Y RECOVERED/RESOLVED (133/76) RELATED 2013-04-01 ฎ⨨ࡼࡿ⑊③ MODERATE/ N/ DOSE NOT CHANGED/ 2014-01-15 (145/88) (WORSENING BILATERAL KNEE PAIN NOT NA RECOVERED/RESOLVED (434/377) POST BILATERAL UNICONDYLAR KNEE RELATED REPLACEMENT) 2013-05-17 ║③ MODERATE/ N/ DOSE NOT CHANGED/ 2013-05-18 (191/134) (LEFT EYE PAIN) NOT NA RECOVERED/RESOLVED (192/135) RELATED 2013-05-20 ᝏᚰ MODERATE/ N/ DOSE NOT CHANGED/ 2013-05-23 (194/137) (NAUSEA) NOT NA RECOVERED/RESOLVED (197/140) RELATED 2013-05-20 ྤ MODERATE/ N/ DOSE NOT CHANGED/ 2013-05-23 (194/137) (VOMITING) NOT NA RECOVERED/RESOLVED (197/140) RELATED 2013-05-22 ⫠ MODERATE/ N/ DOSE NOT CHANGED/ Ongoing (196/139) (ANAL FISSURE) NOT NA NOT RECOVERED/NOT - RELATED RESOLVED
28 8 (152) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2013-06-10 ⥭ᙇᛶ㢌③ MODERATE/ N/ DOSE NOT CHANGED/ 2013-06-13 (215/158) (TENSION HEADACHE) NOT NA RECOVERED/RESOLVED (218/161) RELATED 2013-06-13 ప࣒࢝ࣜ࢘⾑(HYPOKALEMIA) MILD/ N/ DOSE NOT CHANGED/ 2013-06-13 (218/161) NOT NA RECOVERED/RESOLVED (218/161) RELATED 2013-06-17 Ⓨ⇕ MILD/ N/ DOSE NOT CHANGED/ 2013-06-19 (222/165) (FEVER) NOT NA RECOVERED/RESOLVED (224/167) RELATED 2013-07-25 㛵⠇③ MILD/ N/ DOSE NOT CHANGED/ Ongoing (260/203) (ARTHRALGIA) NOT NA NOT RECOVERED/NOT - RELATED RESOLVED 2013-07-27 ↓Ẽ⫵ MODERATE/ N/ DOSE NOT CHANGED/ 2013-08-02 (262/205) (ATELECTASIS) NOT NA RECOVERED/RESOLVED (268/211) RELATED 2013-07-29 ྾ᅔ㞴 MODERATE/ N/ DOSE NOT CHANGED/ 2013-08-02 (264/207) (SHORTNESS OF BREATH) NOT NA RECOVERED/RESOLVED (268/211) RELATED
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route METHYLPREDNISOLONE ACETATE 2012-12-27 2012-12-27 INTRA-ARTICULAR METHYLPREDNISOLONE 2012-12-30 2013-01-05 ORAL HYDROCHLOROTHIAZIDE 2013-01-20 2013-01-24 ORAL METHYLPREDNISOLONE 2013-02-21 2013-02-27 ORAL AZITHROMYCIN 2013-03-02 2013-03-08 ORAL AZITHROMYCIN 2013-03-12 2013-03-18 ORAL OSELTAMIVIR PHOSPHATE 2013-03-12 2013-03-21 ORAL TUSSICAPS 2013-03-12 - ORAL METHYLPREDNISOLONE ACETATE 2013-04-01 2013-04-01 INTRA-ARTICULAR METHYLPREDNISOLONE ACETATE 2013-04-18 2013-04-18 INTRA-ARTICULAR METHYLPREDNISOLONE ACETATE 2013-04-18 2013-04-18 INTRA-ARTICULAR DIPHENHYDRAMINE HYDROCHLORIDE 2013-05-22 2013-05-22 INTRAVENOUS DIAZEPAM 2013-05-22 - TOPICAL PROMETHAZINE 2013-05-22 2013-05-22 INTRAVENOUS SODIUM CHLORIDE 2013-05-22 2013-05-22 INTRAVENOUS ONDANSETRON 2013-05-22 - ORAL PROCET /01554201/ 2013-06-13 2013-06-13 ORAL POTASSIUM CHLORIDE 2013-06-13 2013-06-13 ORAL SODIUM CHLORIDE 2013-06-13 2013-06-13 INTRAVENOUS MORPHINE 2013-07-29 2013-08-02 INTRAVENOUS PARACETAMOL 2013-07-30 2013-07-30 ORAL DEXTROMETHORPHAN 2013-07-30 2013-08-02 ORAL HYDROCHLOROTHIAZIDE 2013-07-30 2013-08-02 ORAL PROCET /01554201/ 2013-07-30 2013-08-02 ORAL IPRATROPIUM W/SALBUTAMOL 2013-07-31 2013-08-02 RESPIRATORY (INHALATION) AMOXICILLIN 2013-07-31 2013-08-02 ORAL
(22) Subject CNTO1275CRD3003-1016-21010
1) Reason for narrative selection SAE Event of interest: Serious infection
28 9 (153) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome I/M) 2014-12-02 ║ᖏ≧⑁⑈ Y MODERATE/ Y/ DRUG INTERRUPTED/ 2015-01-07 (177/121) (HERPES ZOSTER POSSIBLE Y RECOVERED/RESOLVED (213/157) KERATOCONJUNCTIVITIS)
3) Baseline Demographic Information Age (years): 3 Sex: Male Weight (kg): 78.6 Race: White Date of birth: Height (cm): 180.3
4) Induction Treatment Group Induction study: CNTO1275CRD3002 Randomized Treatment Group: Ustekinumab Approximating 6 mg/kg IV Actual Treatment Group: Ustekinumab Approximating 6 mg/kg IV
5) Maintenance Treatment Group Assigned Treatment Group: Randomized subject/Responder to ustekinumab IV induction dosing/ustekinumab 90 mg SC q8w
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2014-06-09 1 Ustekinumab 389.7 mg WEEK 0 MAINTENANCE 2014-08-04 57 Ustekinumab 90 mg WEEK 8 MAINTENANCE 2014-09-29 113 Ustekinumab 90 mg WEEK 12 MAINTENANCE 2014-10-27 141 Placebo 0 mg WEEK 16 MAINTENANCE 2014-11-24 169 Ustekinumab 90 mg WEEK 24 MAINTENANCE 2015-01-19 225 Ustekinumab 90 mg WEEK 28 MAINTENANCE 2015-02-16 253 Placebo 0 mg WEEK 32 MAINTENANCE 2015-03-16 281 Ustekinumab 90 mg WEEK 36 MAINTENANCE 2015-04-13 309 Placebo 0 mg WEEK 40 MAINTENANCE 2015-05-12 338 Ustekinumab 90 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: N Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: Y
8) Induction Baseline Crohn's Disease History Date of diagnosis: 30JUN2004 Disease duration: 9.94 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪⫠㛛࿘ᅖ㸪ᾘ⟶እኚ㸦㛵⠇⅖㸭㛵⠇③㸧
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: PREVIOUS HISTORY Stricture complications of (CD): NEVER
29 0 (154) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
10) Concomitant Crohn's Disease-Related Surgeries None reported
11) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 20 MAINTENANCE PREDNISOLONE 0.12 mg -
12) Narrative Text ⿕㦂⪅ࡣ 3 ṓࡢⓑே⏨ᛶ࡛㸪2014 ᖺ 6 ᭶ 9 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏࢆ㟼⬦ෆᢞࡉࢀ ࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏ 90 mg ࢆ q8w ࡛⓶ୗᢞࡍࡿ⩌ࣛࣥࢲ࣒ࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪Ỉ①㸪୧ഃே ᕤ⫤㛵⠇⨨㸪㛵⠇⅖㸪ᶵ㣧㓇࡛࠶ࡗࡓࠋ SAE/Serious infection㸸║ᖏ≧⑁⑈㸦Day 177㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2014 ᖺ 12 ᭶ 2 ᪥㸪2 ᪥㛫ࢃࡓࡿྑ║ࡢ⑊③㸪ὶᾦ㸪Ⓨ㉥㸪ⅎ ⇕ឤࢆッ࠼║⛉ࢆཷデࡋࡓࠋ⿕㦂⪅ࡣ㸪ࡇࢀࡽࡢ≧ᑐࡋ࡚ࢸࢺࣛࣄࢻࣟࢰࣜࣥ㸭◲㓟ள㖄㸭 ₶㸦Visine totality㸧ࢆ⏝ࡋࡓࡀ㸪㍍ῶࡋ࡞ࡗࡓࠋ᳨ᰝ࠾࠸࡚㸪ྑ║⤖⭷ࡢᑠ⤖⠇ࡣ ࡞࠸ࡀ୍ⓗ࡞῝ᅾ⾑⟶ࡢ⾑㸦2+㸧ࢆక࠺ᾦᾮᒙࡢయ✚ቑຍࡀㄆࡵࡽࢀࡓࠋึᮇデ᩿ࡣྑ║ࡢ ୍㐣ᛶ࿘ᮇᛶୖᙉ⭷⅖࡛࠶ࡗࡓࠋ⒪ࡣࣉࣞࢻࢽࢰࣟࣥ㓑㓟࢚ࢫࢸࣝⅬ║ࡀ⏝࠸ࡽࢀࡓࠋ 2014 ᖺ 12 ᭶ 3 ᪥㸪⿕㦂⪅ࡣྑ║ࡢ࿘ᅖⓎ⑈ཬࡧᾋ⭘ࢆⓎ⌧ࡋࡓࠋࡑࡢ⩣᪥㸦2014 ᖺ 12 ᭶ 4 ᪥㸧㸪⿕㦂⪅ࡣ⤒㐣ほᐹࡢ᮶㝔㸪ྑ║ࡢ㉥ࡳ③ࡳࡢᣢ⥆ࢆッ࠼ࡓࠋྑ║ࡢ᳨ᰝ࡛ࡣᒓჾ ࡢ V1 ᖏ≧⑁⑈ཬࡧ⤖⭷ࡢ⤖⠇ࡣ࡞࠸ࡀ୍ⓗ࡞῝ᅾ⾑⟶ࡢ⾑㸦2+㸧ࡀㄆࡵࡽࢀࡓࠋゅ⭷࡛ࡣ ㎶⦕ᑠᶞᯞ≧ኚࡀㄆࡵࡽࢀࡓࠋゅ⤖⭷ᖏ≧⑁⑈㸦➨ 6 ⓶⠇㸧デ᩿ࡉࢀࡓࠋ㦂⸆ࡼࡿ ⒪ࡣ㸪ᮏ㇟ࡢࡓࡵ୰᩿ࡉࢀࡓࠋ㏣ຍ⒪ࡋ࡚ࣂࣛࢩࢡࣟࣅࣝࡀฎ᪉ࡉࢀࡓࠋ⤒㐣ほᐹ୰ࡢ 2014 ᖺ 12 ᭶ 11 ᪥㸪ᮏ㇟ࡢ㔜ᗘࡣ⣙ 80%ᨵၿࡋࡓグ㍕ࡉࢀࡓࠋྑ║ࡢ᳨ᰝ࠾࠸࡚㸪ゅ ⭷⾑ࡢ㍍ῶ㸦1+㸧ࡀㄆࡵࡽࢀࡓࠋࡋࡋ㸪⿕㦂⪅ࡣ㛤║ࡀ㞴ࡋࡃ㸪㧥ࡢ⏕࠼㝿ࡢྑᚋࢁ③ࡳ ࡀከᑡ࠶ࡗࡓࠋ2015 ᖺ 1 ᭶ 7 ᪥㸪⿕㦂⪅ࡣゅ⤖⭷ᖏ≧⑁⑈ࡽᅇࡋࡓࠋ
13) Other Adverse Events Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome (Study day I/M) 2014-06-09 Ⓨ⇕ MODERATE/ N/ DOSE NOT CHANGED/ 2014-06-10 (1/.) (ELEVATED TEMPERATURE) NOT RELATED NA RECOVERED/RESOLVED (2/.)
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route PARACETAMOL 2014-06-09 - ORAL PREDNISOLONE ACETATE 2014-12-02 2015-01-07 OPHTHALMIC VALACICLOVIR 2014-12-04 2014-12-11 ORAL
(23) Subject CNTO1275CRD3003-1031-10529
1) Reason for narrative selection SAE Event of interest: Serious infection
29 1 (155) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome I/M) 2012-10-14 ་⒪ᶵჾ㛵㐃ឤᰁ Y MODERATE/ Y/ DOSE NOT CHANGED/ 2012-10-19 (67/11) (INFECTION OF CENTRAL VENOUS POSSIBLE Y RECOVERED/RESOLVED (72/16) CATHETER) 2012-10-26 ⭈ᒀ⣽⟶ቯṚ Y MODERATE/ N/ DOSE NOT CHANGED/ 2012-10-30 (79/23) (ACUTE TUBULAR NECROSIS) DOUBTFUL NA RECOVERED/RESOLVED (83/27)
3) Baseline Demographic Information Age (years): 6 Sex: Female Weight (kg): 81.4 Race: White Date of birth: Height (cm): 164
4) Induction Treatment Group Induction study: CNTO1275CRD3001 Randomized Treatment Group: Ustekinumab Approximating 6 mg/kg IV Actual Treatment Group: Ustekinumab Approximating 6 mg/kg IV
5) Maintenance Treatment Group Assigned Treatment Group: Non-randomized subject/Non-responder to ustekinumab IV induction dosing and received ustekinumab in maintenance
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2012-08-09 1 Ustekinumab 389.7 mg WEEK 0 MAINTENANCE 2012-10-04 57 Ustekinumab 90 mg WEEK 0 MAINTENANCE 2012-10-04 57 Placebo 0 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: Y Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: -
8) Induction Baseline Crohn's Disease History Date of diagnosis: 31JAN2003 Disease duration: 9.52 years Involved areas: ᅇ⭠ࡢࡳ㸪ᾘ⟶እኚ㸦㛵⠇⅖㸭㛵⠇③㸧
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: PREVIOUS HISTORY Sinus tracts/perforation: NEVER Fistula: PREVIOUS HISTORY Stricture complications of (CD): PREVIOUS HISTORY
10) Concomitant Crohn's Disease-Related Surgeries None reported
29 2 (156) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
11) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 0 BUDESONIDE 9 mg - WEEK 0 FLUTICASONE (FLONASE) 0.05 mg -
12) Narrative Text ⿕㦂⪅ࡣ 6 ṓࡢⓑேዪᛶ࡛㸪2012 ᖺ 8 ᭶ 9 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏࢆ㟼⬦ෆᢞࡉࢀ ࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡎ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏࢆᢞࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪ࣂࣥࢥ࣐ࢩ ࣥ⪏ᛶ⭠⌫⳦ឤᰁ㸪࣓ࢳࢩࣜࣥ⪏ᛶ㯤Ⰽࣈࢻ࢘⌫⳦ឤᰁ㸪៏ᛶᝏᚰ㸪ྤཬࡧୗ⑩㸦ࢡ࣮ࣟࣥ ཬࡧᅇ⭠ษ㝖㉳ᅉࡍࡿ㸧㸪៏ᛶ⑊③㸪╧╀㞀ᐖ㸪⒵╔㞳ࢆక࠺ᅇ⭠⤖⭠ษ㝖ࢆྵࡴ」ᩘᅇࡢ ⭠ษ㝖㸦2010 ᖺ 4 ᭶ 26 ᪥㸧㸪ᑠ⭠ෆ⣽⳦㐣ቑṪ㸪⥺⥔➽③㸪㢁᳝㸪⭡㒊₢ᾮ⭘㸦⭡ቨ㸧㸪 ᮎᲈᛶࢽ࣮ࣗࣟࣃࢳ࣮㸦࣓ࢺࢺࣞ࢟ࢧ࣮ࢺཬࡧ࣓ࢺࣟࢽࢲࢰ࣮ࣝ㛵㐃㸧㸪㦵⢒㧼㸪ᆶษ㝖㸪 ⫹ᄞษ㝖㸪Ꮚᐑฟ㸪༸ᕢ㝖㸪㧗⾑ᅽ㸪㐣ཤࡢႚ↮㸪࠺ࡘ㸪⌫ᛶ㈋⾑㸪➽②⦰㸪ᒀ㊰ឤᰁ㸪 ⭈⤖▼㸦ᕥഃ㸧ཬࡧ୧ഃ⭈ᄞ⬊࡛࠶ࡗࡓࠋ௨ୗࡢ⸆ᑐࡍࡿࣞࣝࢠ࣮ࡶ࠶ࡗࡓ㸸ࣔࣝࣄࢿ㸪 ࣇ࢙ࣥࢱࢽࣝ㸪ketorolac㸪meperidine㸪ࣥࣇࣜ࢟ࢩ࣐ࣈ㸪୍㓟❅⣲㸪ࢥࢹࣥཬࡧ࣓ࢺࢺࣞ ࢟ࢧ࣮ࢺࠋ SAE/Serious infection㸸་⒪ᶵჾ㛵㐃ឤᰁ㸦Day 67㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ㣗ḧ႙ኻ㸪➽⫗③㸪⑂ປ㸪⤒ཱྀᦤྲྀ㔞ࡢῶᑡ㸪៏ᛶୗ⑩ཬࡧᒀ ᅔ㞴ཬࡧ୰ᚰ㟼⬦࢝ࢸ࣮ࢸࣝ␃⨨㒊㸦2009 ᖺ 5 ᭶␃⨨㸧ࡢ⑊③ࡀㄆࡵࡽࢀ㸪2012 ᖺ 10 ᭶ 14 ᪥ධ㝔ࡋࡓࠋ⿕㦂⪅ࡣ㸪ࢫࣝࣇ࣓ࢺ࢟ࢧࢰ࣮ࣝ㸭ࢺ࣓ࣜࢺࣉ࣒ࣜཬࡧ㟼⬦ෆ⿵ᾮ㸦࣏࣮ࢺ ࡽࡢ⮬ᕫᢞ㸧ࡼࡿ⒪ࢆཷࡅ࡚࠸ࡓࠋ2012 ᖺ 10 ᭶ 12 ᪥ࡢᒀ᳨ᰝࡣⓑ⾑⌫㸦>182㸧㸪㉥⾑⌫ 㸦11㸧㸪ⓑ⾑⌫࢚ࢫࢸ࣮ࣛࢮ㸦2+㸧㸦ṇᖖ⠊ᅖࡣ᫂㸧࡛࠶ࡗࡓࠋⓎ⇕㸪ⓑ⾑⌫ቑຍ㸪⾑⾜ື ែᏳᐃࡣ࡞ࡗࡓࠋᙜヱ㒊┠❧ࡗࡓ⣚ᩬ㸪⭘⬽ཪࡣࢻࣞࢼ࣮ࢪࡣ࡞ࡗࡓࡀ㸪ゐデ࣏ ࣮ࢺୖഃᅽ③ࡀከᑡㄆࡵࡽࢀࡓࠋᒀᇵ㣴᳨ᰝ࡛ࡣቑṪࡣࡳࡽࢀ࡞ࡗࡓࠋ2012 ᖺ 10 ᭶ 14 ᪥ࡢ ᒀ᳨ᰝ࡛ࡣ㸪ⓑ⾑⌫㸦15㸧࡛࠶ࡗࡓࠋ⒪ࡣ㟼⬦ෆ⿵ᾮ㸪ࣂࣥࢥ࣐ࢩࣥ㸪dilaudid㸪ࣉࣞ࢞ ࣂࣜࣥ㸪ࢫࣝࣇ࣓ࢺ࢟ࢧࢰ࣮ࣝ㸭ࢺ࣓ࣜࢺࣉ࣒ࣜ㸪࣊ࣃࣜࣥ㸪venlaflaxine㸪ࢺࣛࢰࢻࣥཬࡧ࢚ ࢯ࣓ࣉࣛࢰ࣮ࣝࡀ⏝࠸ࡽࢀࡓࠋ2012 ᖺ 10 ᭶ 15 ᪥࢝ࢸ࣮ࢸࣝࡽ᥇ྲྀࡋࡓヨᩱࡢ⾑ᾮᇵ㣴᳨ᰝ ࡢ⤖ᯝࡣ㸪ࢢ࣒ࣛ㝧ᛶ⌫⳦ࡢ㞟ྜయ㸦ࢥࢢ࣮ࣛࢮ㝜ᛶࡢࣈࢻ࢘⌫⳦✀㸪>100 colonies/plate㸧࡛ ࠶ࡾ㸪5 ᪥ᚋᐇࡋࡓᮎᲈ⾑ᇵ㣴᳨ᰝ㸦2012 ᖺ 10 ᭶ 14 ᪥᥇ྲྀ㸧࡛ࡣ㸪ቑṪࡣ࡞ࡗࡓࠋ2012 ᖺ 10 ᭶ 16 ᪥㸪୰ᚰ㟼⬦࢝ࢸ࣮ࢸࣝࡀᢤཤࡉࢀ㸪୍ⓗ㏫ὶ㜵Ṇ࡛ࡁࡿࢺࣜࣉ࣮࣓ࣝࣝࣥ࢝ ࢸ࣮ࢸࣝࢆᕥෆ㢕㟼⬦␃⨨ࡋࡓࠋ⿕㦂⪅ࡣ㸪2012 ᖺ 10 ᭶ 19 ᪥㏥㝔ࡋࡓࠋ SAE㸸⭈ᒀ⣽⟶ቯṚ㸦Day 79㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣᝏᚰཬࡧྤ㸦1 㛫ẖ㸧ࢆッ࠼ 2012 ᖺ 10 ᭶ 26 ᪥ධ㝔ࡋࡓࠋ ๓᪥ࡼࡾ㛵㐃ᛶࡢ࡞࠸ྤ⾑ࡶ࠶ࡗࡓࠋ⿕㦂⪅ࡣ㠀ฟ⾑ᛶࡢୗ⑩㸦1 ᪥ 6㹼12 ᅇ㸧㸪Ⓨờ㸪㌟ ᛶ➽⫗③ཬࡧᛰឤࡶッ࠼ࡓࠋⓎ⇕ཬࡧᝏᐮࡣྰᐃࡋࡓࠋࣂࢱࣝࢧࣥཬࡧ⌮Ꮫⓗ᳨ᰝ࡛ࡣ␗ ᖖࡣࡳࡽࢀ࡞ࡗࡓࠋྠ᪥ࡢ⮫ᗋ᳨ᰝ್ࡣ㸪⾑୰ᒀ⣲❅⣲㸦BUN㸧10 mg/dL㹙ṇᖖ⠊ᅖ㸦NR㸧 7-21 mg/dL㹛㸪ࢡࣞࢳࢽࣥ 1.17 ȝg/dL㸦NR 0.6-1 ȝg/dL㸧㸪ࣂࣥࢥ࣐ࢩࣥ⃰ᗘ 21 ȝg/mL㸦NR 10-20 ȝg/mL㸧㸪⣒⌫యࢁ㐣㔞㸦GFR㸧48.14 mL/min/1.73 m2㸦NR>60 mL/min/1.73 m2㸧㸪࣐ࢢࢿࢩ ࣒࢘ 1.25 mg/dL㸦NR 1.6-2.2 mg/dL㸧㸪࣒࢝ࣜ࢘ 2.7 mmol/L㸦NR 3.5-5.0 mmol/L㸧㸪ࢼࢺ࣒ࣜ࢘
29 3 (157) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
127 mmol/L㸦NR 135-145 mmol/L㸧࡛࠶ࡗࡓࠋᒀ᳨ᰝཬࡧ⬚㒊 X ⥺ࡢ⤖ᯝ␗ᖖࡣࡳࡽࢀ࡞ࡗ ࡓࠋ⭡㒊ࢥࣥࣆ࣮ࣗࢱ᩿ᒙᙳ㸦CT㸧ࢫ࡛࢟ࣕࣥࡣ㸪㞄᥋㒊ᚤ⣽࡞⅖ᛶࡢ stranding ࢆక࠺ ᪂ࡓ࡞ᅇ⭠ᮎ➃ᣢ⥆ᛶࡢ⫧ཌ㸪⬨᳝ᵝࠎ࡞㔜ᗘࡢኚᛶኚཬࡧ⭠㛵⠇୧ഃᛶ◳ࡀㄆ ࡵࡽࢀࡓࠋάືᮇࡢ⅖ᛶ⭠ᝈࡢᚩೃࡣ࡞ࡗࡓࠋᕥୗ⭡㒊ࡢᄞ⬊㸪ᕥഃ⭈⤖▼ཬࡧ୧ഃ⭈ ᄞ⬊ኚࡣ࡞ࡗࡓࠋࣂࣥࢥ࣐ࢩࣥࡢࢺࣛࣇ⃰ᗘࡣ 21 ȝg/mL㸦NR 10-20 ȝg/mL㸧ୖ᪼ࡋࡓࠋ ⒪ࡣ㟼⬦ෆ⿵ᾮ㸪ࣉ࣓ࣟࢱࢪࣥ㸪hydromorphone㸪࢜ࣥࢲࣥࢭࢺࣟࣥ㸪◲㓟࣒࢝ࣜ࢘ཬࡧࣔ ࣝࣄࢿࡀ⏝࠸ࡽࢀࡓࠋࣂࣥࢥ࣐ࢩࣥࡼࡿ⒪ࡣ୰Ṇࡉࢀࡓࠋ2012 ᖺ 10 ᭶ 30 ᪥ࡢ⮫ᗋ᳨ᰝ್ ࡣ BUN10 mg/dL㸪࢝ࣝࢩ࣒࢘ 8.3 mg/dL㸪ࢡࣞࢳࢽࣥ 1.10 ȝg/dL㸪GFR 50.17 mL/min/1.73 m2㸪 ࣐ࢢࢿࢩ࣒࢘ 1.6 mg/dL㸪࣒࢝ࣜ࢘ 4.0 mmol/L ཬࡧࢼࢺ࣒ࣜ࢘ 146 mmol/L ࡛࠶ࡗࡓࠋ⿕㦂⪅ࡣ 2012 ᖺ 10 ᭶ 30 ᪥㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome (Study day I/M) 2012-08-01 ᒀ㊰ឤᰁ MILD/ Y/ NOT APPLICABLE/ 2012-08-17 (-8/.) (URINARY TRACT INFECTION) NOT RELATED Y RECOVERED/RESOLVED (9/.) 2012-08-22 ⻏ᕢ⅖ MODERATE/ Y/ DOSE NOT CHANGED/ 2012-09-04 (14/.) (CELLULITIS) DOUBTFUL Y RECOVERED/RESOLVED (27/.) 2012-10-12 ᒀ㊰ឤᰁ MILD/ Y/ DOSE NOT CHANGED/ 2012-10-16 (65/9) (URINARY TRACT INFECTION) POSSIBLE Y RECOVERED/RESOLVED (69/13) 2012-10-26 ྛ✀≀㉁ẘᛶ MODERATE/ N/ DOSE NOT CHANGED/ 2012-10-30 (79/23) (VANCOMYCIN TOXICITY) NOT RELATED NA RECOVERED/RESOLVED (83/27)
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route LEVOFLOXACIN 2012-08-23 2012-09-07 ORAL BACTRIM 2012-10-13 2012-10-19 ORAL VANCOMYCIN 2012-10-19 2012-10-30 INTRAVENOUS
(24) Subject CNTO1275CRD3003-1039-10681
1) Reason for narrative selection SAE Discontinuation of study agent due to AE Event of interest: Serious infection
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome I/M) 2013-02-20 ࢡ࣮ࣟࣥ(MICROPERFORATION DUE N SEVERE/ Y/ DRUG WITHDRAWN/ Ongoing (134/77) TO CROHNS DISEASE) POSSIBLE Y NOT RECOVERED/NOT - RESOLVED 2013-02-20 ⭠⊃✽ N SEVERE/ N/ DRUG WITHDRAWN/ Ongoing (134/77) (COLONIC STRICTURE) POSSIBLE NA NOT RECOVERED/NOT - RESOLVED 2013-02-21 ⭡㒊ឤᰁ Y SEVERE/ Y/ DRUG WITHDRAWN/ Ongoing (135/78) (INTRA-ABDOMINAL INFECTION POSSIBLE Y NOT RECOVERED/NOT - WITHOUT ABSCESS) RESOLVED
3) Baseline Demographic Information ȋȌǣ ʹ ǣ ȋȌǣ ͷͷǤͷ ǣ ǣ ͳͻͺͷǦͲͷǦͲͶ ȋ Ȍǣ ͳǤ
29 4 (158) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
4) Induction Treatment Group Induction study: CNTO1275CRD3001 Randomized Treatment Group: Ustekinumab 130 mg IV Actual Treatment Group: Ustekinumab 130 mg IV
5) Maintenance Treatment Group Assigned Treatment Group: Randomized subject/Responder to ustekinumab IV induction dosing/ustekinumab 90 mg SC q12w
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2012-10-10 1 Ustekinumab 129.6 mg WEEK 0 MAINTENANCE 2012-12-06 58 Ustekinumab 90 mg WEEK 8 MAINTENANCE 2013-01-31 114 Placebo 0 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: Y Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: -
8) Induction Baseline Crohn's Disease History Date of diagnosis: 20SEP2011 Disease duration: 1.06 years Involved areas: ⤖⭠ࡢࡳ
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: NEVER Stricture complications of (CD): NEVER
10) Concomitant Crohn's Disease-Related Surgeries None reported
11) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 0 PREDNISONE 40 mg 40 mg WEEK 4 MAINTENANCE PREDNISONE 35 mg 35 mg WEEK 4 MAINTENANCE PREDNISONE 30 mg 30 mg WEEK 8 MAINTENANCE PREDNISONE 25 mg 25 mg WEEK 8 MAINTENANCE PREDNISONE 20 mg 20 mg WEEK 8 MAINTENANCE PREDNISONE 15 mg 15 mg WEEK 8 MAINTENANCE PREDNISONE 10 mg 10 mg
12) Narrative Text ⿕㦂⪅ࡣ 2 ṓࡢⓑேዪᛶ࡛㸪2012 ᖺ 10 ᭶ 10 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏࢆ㟼⬦ෆᢞࡉ ࢀࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏ 90 mg ࢆ q12w ࡛⓶ୗᢞࡍࡿ⩌ࣛࣥࢲ࣒ࡉࢀࡓࠋ
29 5 (159) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪ᡥ᱈ฟ㸪ྑ ஙᡣ⭘⒗㝖㸪⬚ࡸࡅ㸪ᝏᚰ㸪ࣅࢱ࣑ࣥ㹂Ḟஈ㸪ࢲ࣒࣐ࣜࣈ⪏࡛࠶ࡗࡓࠋᐙ᪘Ṕࡣࢡ࣮ࣟࣥ 㸦ጜጒ㸧࡛࠶ࡗࡓࠋ Discontinuation of study agent due to AEs㸸ࢡ࣮ࣟࣥ㸦Day 134㸧㸪⭠⊃✽㸦Day 134㸧 SAE/Discontinuation of study agent due to AE/Serious infection㸸⭡㒊ឤᰁ㸦Day 135㸧 2013 ᖺ 2 ᭶ 20 ᪥㸪⿕㦂⪅ࡣࢡ࣮ࣟࣥ㸦ሗ࿌㇟ྡ㸸ࢡ࣮ࣟࣥࡼࡿᚤᑠ✸Ꮝ㸧ཬࡧ ⭠⊃✽㸦ሗ࿌㇟ྡ㸸⤖⭠⊃✽㸧ࢆⓎ⌧ࡋࡓࠋ CIOMS ཬࡧデ⒪㘓ࡼࡿ㸪⿕㦂⪅ࡣ 2013 ᖺ 2 ᭶ 20 ᪥ணᐃࡉࢀ࡚࠸ࡓ⭠ෆど㙾᳨ᰝࢆ ཷࡅࡓࠋ᳨ᰝ⭠⟶๓ฎ⨨㛫ⓗవ⿱ࡀ࡞ࡗࡓࡇཬࡧ S ≧⤖⭠࡛ࡢෆど㙾㏻㐣⬟ࡀグ 㘓ࡉࢀࡓࠋ⿕㦂⪅ࡣ㸪⮬Ꮿ࡛᭱㧗 102°F ࡢⓎ⇕㸪⭡③ཬࡧ㣗ḧῶ㏥ࢆㄆࡵ㸪2013 ᖺ 2 ᭶ 21 ᪥ ධ㝔ࡋࡓࠋ2013 ᖺ 2 ᭶ 21 ᪥ࡢ S ≧⤖⭠⏕᳨࡛ࡣ㸪ᅛ᭷ᒙෆዲ୰⌫ࡀᩓᅾࡍࡿࡇࢆ≉ᚩࡋ ࡓ㍍ᗘࡢάືᮇࡢ៏ᛶ⭠⅖㸪ୖ⓶ୗࡢ⾑⟶࠺ࡗ⾑㸪㝜❐ࡢࡡࡌࢀཬࡧศᒱࢆక࠺₽⒆ཪࡣࡧࡽ ࢇࢆ♧၀ࡍࡿኚࡀࡳࡽࢀࡓࠋ⥭ᛴࡢࢥࣥࣆ࣮ࣗࢱ᩿ᒙᙳ㸦CT㸧ࢫ࢟ࣕࣥ㸦⤖⭠⏬ീ㸧ࡼ ࡾ㸪S ≧⤖⭠᭱㛗 7.5 cm ࡲ࡛ఙ㛗ࡋࡓ㛗࠸༊ᇦࡢ⊃✽㸪㛵㐃ࡍࡿ⭡ቨ⫧ཌ㸦1.7 cm㸧㸪S ≧⤖ ⭠ࡢᚋୗ᪉࢞ࢫࢆྵࡴ」ྜ㈓␃≀㸦㍈᪉ྥ࡛⣙ 6.1×3.6 cm㸧ཬࡧ㦵┙ࡢྑ༙ศ᪂ࡋ࠸⅖ᛶ ኚࡀㄆࡵࡽࢀࡓࠋ⌮Ꮫⓗᡤぢ࡛ࡣ㸪ᕥୖୗ⭡㒊㍍ᗘࡢᅽ③ࡀࡳࡽࢀࡓࠋ2013 ᖺ 2 ᭶ 21 ᪥ࡢ ⮫ᗋ᳨ᰝ࡛ࡣ㸪ⓑ⾑⌫ 10.8㸪࣊ࣔࢢࣟࣅࣥ 10.2㸪࣐࣊ࢺࢡࣜࢵࢺ 33㸦༢ཬࡧṇᖖ⠊ᅖ᫂㸧 ࡛࠶ࡗࡓࠋධ㝔୰㸪ࣇࣞࢢ࣮ࣔࢿࡢྍ⬟ᛶࡀ࠶ࡾ㸪CT ࢞ࢻୗ྾ᘬࢆヨࡳࡓࡀ㸪ᾮయ㈓␃ࡣࡳ ࡽࢀ࡞ࡗࡓࠋ⒪ࡣࢩࣉࣟࣇࣟ࢟ࢧࢩࣥ㸪࣓ࢺࣟࢽࢲࢰ࣮ࣝ㸪prednisone㸪࣓ࢺࢺࣞ࢟ࢧ࣮ ࢺ㸪ࢺ࣐ࣛࢻ࣮ࣝ㸪㟼⬦ෆ⿵ᾮ㸪ࣆ࣌ࣛࢩࣜࣥ㸭ࢱࢰࣂࢡࢱ࣒㸦ࢰࢩࣥ㸧㸪stress-dose ࡢࢫࢸࣟ ࢻཬࡧࣔࣝࣄࢿࡀ⏝࠸ࡽࢀࡓࠋ⿕㦂⪅ࡣ㸪2013 ᖺ 2 ᭶ 26 ᪥㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome (Study day I/M) 2012-12-27 ୖẼ㐨ឤᰁ MILD/ Y/ DOSE NOT CHANGED/ 2013-01-20 (79/22) (UPPER RESPIRATORY INFECTION) NOT RELATED N RECOVERED/RESOLVED (103/46) 2013-01-28 Ⓨ⇕ MODERATE/ Y/ DOSE NOT CHANGED/ 2013-01-29 (111/54) (FEVER) VERY LIKELY N RECOVERED/RESOLVED (112/55)
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route VICKS FORMULA 44M /01056501/ 2012-12-27 - ORAL CHERACOL /00693301/ 2013-01-10 2013-01-10 ORAL TPN /00897001/ 2013-02-24 - INTRAVENOUS CIPROFLOXACIN 2013-02-26 - ORAL METRONIDAZOLE 2013-02-26 - ORAL
(25) Subject CNTO1275CRD3003-1043-10979
1) Reason for narrative selection SAE Event of interest: Serious infection
29 6 (160) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome (Study day I/M) 2013-07-21 ࢘ࣝࢫឤᰁ Y SEVERE/ Y/ DOSE NOT CHANGED/ 2013-08-16 (216/158) (VIRAL SYNDROME) POSSIBLE N RECOVERED/RESOLVED (242/184)
3) Baseline Demographic Information Age (years): 3 Sex: Female Weight (kg): 64.4 Race: White Date of birth: Height (cm): 173
4) Induction Treatment Group Induction study: CNTO1275CRD3001 Randomized Treatment Group: Ustekinumab Approximating 6 mg/kg IV Actual Treatment Group: Ustekinumab Approximating 6 mg/kg IV
5) Maintenance Treatment Group Assigned Treatment Group: Randomized subject/Responder to ustekinumab IV induction dosing/ustekinumab 90 mg SC q8w
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2012-12-18 1 Ustekinumab 389.7 mg WEEK 0 MAINTENANCE 2013-02-14 59 Ustekinumab 90 mg WEEK 8 MAINTENANCE 2013-04-11 115 Ustekinumab 90 mg WEEK 12 MAINTENANCE 2013-05-09 143 Placebo 0 mg WEEK 16 MAINTENANCE 2013-06-06 171 Ustekinumab 90 mg WEEK 20 MAINTENANCE 2013-07-02 197 Placebo 0 mg WEEK 24 MAINTENANCE 2013-07-30 225 Ustekinumab 90 mg WEEK 28 MAINTENANCE 2013-08-29 255 Placebo 0 mg WEEK 32 MAINTENANCE 2013-09-25 282 Ustekinumab 90 mg WEEK 36 MAINTENANCE 2013-10-24 311 Placebo 0 mg WEEK 40 MAINTENANCE 2013-11-25 343 Ustekinumab 90 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: N Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: Y
8) Induction Baseline Crohn's Disease History Date of diagnosis: 31DEC1999 Disease duration: 12.97 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪⫠㛛࿘ᅖ㸪ᑠ⭠㏆㸭⫶㸭㣗㐨
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: NEVER Stricture complications of (CD): PREVIOUS HISTORY
29 7 (161) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
10) Concomitant Crohn's Disease-Related Surgeries None reported
11) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 0 BUDESONIDE 9 mg - WEEK 8 MAINTENANCE BUDESONIDE 6 mg - WEEK 8 MAINTENANCE BUDESONIDE 0 mg -
12) Narrative Text ⿕㦂⪅ࡣ 3 ṓࡢⓑேዪᛶ࡛㸪2012 ᖺ 12 ᭶ 18 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏࢆ㟼⬦ෆᢞࡉ ࢀࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏ 90 mg ࢆ q8w ࡛⓶ୗᢞࡍࡿ⩌ࣛࣥࢲ࣒ࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪S ≧⤖⭠⊃✽㸪 ㈋⾑㸪᰾㸪ᒀ㊰ឤᰁ㸪⫶㣗㐨㏫ὶ㸪②ᨥⓎస㸪⸆➼ᑐࡍࡿࣞࣝࢠ࣮㹙hydromorphone hydrochloride㸦ࡑ࠺㸧㸪ࢡࣟࢼࢮࣃ࣒㸪ሷ㓟࣓ࢺࢡࣟࣉ࣑ࣛࢻ㸦➽◳┤㸧㸪࣓ࢺࣟࢽࢲࢰ࣮ࣝ 㸦ୗ⑩㸧㸪ࣥࣇࣜ࢟ࢩ࣐ࣈ㸦ࢼࣇࣛ࢟ࢩ࣮㸧㸪sulfacetamide sodium㸦ୗ⑩㸧㸪ࣔࣝࣄࢿ㸪 rifaximin㸪ࣉ࣓ࣟࢱࢪࣥ㸦➽◳┤㸧ཬࡧ᥋╔⏝ࢸ࣮ࣉ㹛㸪⤖⭠ள㸦2007 ᖺ 2 ᭶㸧㸪㛤⭡ᡭ⾡ 㸦2007 ᖺ 2 ᭶ཬࡧ 2011 ᖺ 6 ᭶㸧ཬࡧᅇ⭠┤⭠࿀ྜ⾡㸦2011 ᖺ㸧࡛࠶ࡗࡓࠋ SAE/Serious infection㸸࢘ࣝࢫឤᰁ㸦Day 216㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣୗ⭡㒊③㸪⾑ᛶୗ⑩㸦2 㐌㛫๓ࡼࡾ㸧ཬࡧ⑂ປࢆッ࠼㸪2013 ᖺ 8 ᭶ 4 ᪥ධ㝔ࡋࡓࠋ⿕㦂⪅ࡣ௨๓㸪㢌③㸪Ⓨ⑈㸪ဗ㢌③㸪యࡢ③ࡳ㸪တႿ㸪Ⓨ⇕ཬࡧᝏᐮࡀ࠶ ࡾ㸪2013 ᖺ 7 ᭶ 21 ᪥ୖẼ㐨ឤᰁデ᩿ࡉࢀ࡚࠸ࡓࠋ⌮Ꮫⓗᡤぢ࡛ࡣ㸪⭡㒊ࡣ㌾ࡽࡃ⭾‶ࡣ ࡞ࡃ㸪ᕥྑୗ⭡㒊ࡢゐデᑐࡋ࡚⭡ቨ㜵ᚚཪࡣ㊴③ࢆకࢃ࡞࠸ᅽ③ࡀㄆࡵࡽࢀࡓࠋ2013 ᖺ 8 ᭶ 4 ᪥ࡢ⮫ᗋ᳨ᰝ␗ᖖ್ࡣ㸪C ᛂᛶࡓࢇⓑ⃰ᗘ 1.36 mg/dL㹙ṇᖖ⠊ᅖ㸦NR㸧<0.5 mg/dL㹛࡛࠶ࡾ㸪 ྠ᪥ࡢ౽୰࢝ࣝࣉࣟࢸࢡࢳࣥࡣ 1026 ȝg/g㸦NR162.9 ȝg/g㸧࡛࠶ࡗࡓࠋ⒪ࡣሷࢼࢺ࣒ࣜ࢘㸪 ࣜࢻ࢝ࣥ㸪ࢫ࣐ࢺࣜࣉࢱࣥཬࡧ diphenhydramine-zinc acetate cream ࡀ⏝ࡉࢀࡓࠋ2013 ᖺ 8 ᭶ 5 ᪥ࡢ⿕㦂⪅ࡢయ ࡣ 98.8°F ࡛࠶ࡗࡓࠋᅇ⭠ෆど㙾᳨ᰝࡶ S ≧⤖⭠ෆど㙾᳨ᰝࢆᐇࡋࡓ ࡇࢁ㸦ᐇ᪥᫂㸧㸪⫠㛛⟶㒊ࢡ࣮࡛ࣟࣥ࠶ࡿࡇࢆ♧ࡍ⾲ᅾᛶ₽⒆ࡀࡳࡽࢀ㸪࿀ྜ㒊㏆ ࡢᅇ⭠ࡣṇᖖ࡛࠶ࡗࡓࡀ㸪ᅇ⭠⤖⭠࿀ྜ㒊㸦⫠㛛⦕ࡼࡾ 20 cm ௨ෆ㸧⢓⭷ᾋ⭘ཬࡧ₽⒆ࡀㄆࡵ ࡽࢀࡓࠋ࿀ྜ㒊ཬࡧᅇ⭠㐲㒊ࡼࡾ㸪」ᩘࡢ⏕᳨᳨యࢆ᥇ྲྀࡋࡓࠋ┤⭠デ࡛ࡣ㸪⫠㛛ᣓ⣙➽⤖ ⠇ᙧᡂ࠶ࡾᛮࢃࢀࡿ㸦nodularity felt㸧ࢡ࣮ࣟࣥᛶࡢ⫠㛛ᆶ㸦perianal tags㸧ࡀㄆࡵࡽࢀࡓࠋධ 㝔୰㸪⿕㦂⪅ࡣᣢ⥆ࡍࡿ㢌③㸪㢁㒊◳┤ཬࡧ㰯⭍࠺ࡗ⾑ࢆッ࠼ࡓࠋ㌟ᛶࡢࡑ࠺ࢆక࠺ᩬ≧ ᛶ⌫≧⓶⑈ࡀⓎ⌧ࡋࡓࡓࡵ㸪ᑐ⒪ἲࡋ࡚ࣄࢻࣟࢥࣝࢳࢰࣥࢡ࣮࣒ࣜࡼࡿ⒪ࡀ⾜ࢃࢀࡓࠋ 2013 ᖺ 8 ᭶ 7 ᪥ࡢ⿕㦂⪅ࡢࢧࢺ࣓࢞ࣟ࢘ࣝࢫ᳨ᰝࡣ㝜ᛶ࡛࠶ࡗࡓࠋ2013 ᖺ 8 ᭶ 7 ᪥㸪እ⛉ ⌮デ᩿ሗ࿌ࡢ⤖ᯝ࡛㸪࿀ྜ๓㸦pre-anastomotic㸧ࡢᅇ⭠ᚤᑠ࡞㝈ᒁᛶࡢάືᮇࡢᅇ⭠⅖ࡀ☜ㄆ ࡉࢀࡓࠋᅇ⭠ S ≧⤖⭠࿀ྜ㒊࡛ࡣ㸪ᑠ⭠⢓⭷୰➼ᗘࡢ៏ᛶⓗ࡞άືᮇࡢᅇ⭠⅖ཬࡧ₽⒆ࡀㄆࡵ ࡽࢀ㸪⧄⥔⣲ᛶ⮋ᛶᾐฟᾮ㸦fibrinopurulent exudate㸧ࢆక࠺㞳᩿∦ࢆ᭷ࡍࡿ㍍ᗘࡢ៏ᛶⓗ࡞ άືᮇࡢ┤⭠⅖ࡀ㸪₽⒆୍⮴ࡋ࡚ࡳࡽࢀࡓࠋ⒪ࡣሷࢼࢺ࣒ࣜ࢘㸪ࣝࣉࣛࢰ࣒ࣛ㸪 dextrose㸦5%㸧㸪ሷ࣒࢝ࣜ࢘㸪ࢪࣇ࢙ࣥࣄࢻ࣑ࣛࣥ㸪hydromorphone㸪࣊ࣃࣜࣥ㸪norethindrone㸪 ࢜ࣥࢲࣥࢭࢺࣟࣥࡀ⏝ࡉࢀࡓࠋ౽᳨ᰝ࡛ࡣ㸪࢝ࣥࣆࣟࣂࢡࢱ࣮ᢠཎཬࡧ⭠⟶ฟ⾑ᛶ⭠⳦ẘᛶ
29 8 (162) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
ࡣࡶ㝜ᛶ࡛࠶ࡗࡓࠋ౽ᇵ㣴᳨ᰝ࡛ࡣ㸪ࢧࣝࣔࢿࣛ⳦㸪㉥⑩⳦㸪࢚ࣟࣔࢼࢫ⳦ཬࡧࣉࣞࢪ࢜ࣔ ࢼࢫ⳦ࡢྛ⳦✀ࡶ㝜ᛶ࡛࠶ࡗࡓࠋ⿕㦂⪅ࡣ㸪2013 ᖺ 8 ᭶ 9 ᪥㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2013-01-02 Ⓨ⇕ MILD/ N/ DOSE NOT CHANGED/ 2013-01-04 (16/.) (FEVER) NOT NA RECOVERED/RESOLVED (18/.) RELATED 2013-02-07 ୖẼ㐨ឤᰁ MODERATE/ Y/ DOSE NOT CHANGED/ 2013-02-19 (52/.) (UPPER RESPIRATORY INFECTION) NOT N RECOVERED/RESOLVED (64/.) RELATED 2013-02-28 እ㝜⭼┿⳦ឤᰁ MILD/ Y/ DOSE NOT CHANGED/ 2013-03-02 (73/15) (VAGINAL YEAST INFECTION) NOT N RECOVERED/RESOLVED (75/17) RELATED 2013-03-14 ╀ MILD/ N/ DOSE NOT CHANGED/ 2013-04-01 (87/29) (INSOMNIA) NOT NA RECOVERED/RESOLVED (105/47) RELATED 2013-03-14 ᡓ MILD/ N/ DOSE NOT CHANGED/ 2013-04-01 (87/29) (SLIGHT HAND TREMORS TO NOT NA RECOVERED/RESOLVED (105/47) BILATERAL HANDS) RELATED 2013-03-18 㝜㒊࣊ࣝ࣌ࢫ MILD/ Y/ DOSE NOT CHANGED/ 2013-03-23 (91/33) (RASH ON LEFT SIDE OF NOT N RECOVERED/RESOLVED (96/38) ANUS( GENITAL HSV)) RELATED 2013-03-19 ⪥ឤᰁ MODERATE/ Y/ DOSE NOT CHANGED/ 2013-04-01 (92/34) (EAR INFECTION) NOT Y RECOVERED/RESOLVED (105/47) RELATED 2013-03-19 ⑂ປ MILD/ N/ DOSE NOT CHANGED/ 2013-04-01 (92/34) (FATIGUE) NOT NA RECOVERED/RESOLVED (105/47) RELATED 2013-03-19 ከờ MILD/ N/ DOSE NOT CHANGED/ 2013-03-24 (92/34) (SWEATING INCREASED) NOT NA RECOVERED/RESOLVED (97/39) RELATED 2013-03-19 㰯㛢 MODERATE/ Y/ DOSE NOT CHANGED/ 2013-04-01 (92/34) (NASAL CONGESTION) NOT Y RECOVERED/RESOLVED (105/47) RELATED 2013-03-19 ᮎᲈ⭘⬽ MILD/ N/ DOSE NOT CHANGED/ 2013-03-23 (92/34) (BOTH FEET SWOLLEN) NOT NA RECOVERED/RESOLVED (96/38) RELATED 2013-03-19 ᮎᲈ⭘⬽ MILD/ N/ DOSE NOT CHANGED/ 2013-03-23 (92/34) (BOTH HANDS SWOLLEN) NOT NA RECOVERED/RESOLVED (96/38) RELATED 2013-03-19 Ⓨ⇕ MILD/ N/ DOSE NOT CHANGED/ 2013-03-24 (92/34) (FEVER) NOT NA RECOVERED/RESOLVED (97/39) RELATED 2013-03-29 ୖẼ㐨ឤᰁ MODERATE/ Y/ DOSE NOT CHANGED/ 2013-04-01 (102/44) (UPPER RESPIRATORY INFECTION) NOT Y RECOVERED/RESOLVED (105/47) RELATED 2013-05-28 ୖ⭡㒊③ MILD/ N/ DOSE NOT CHANGED/ 2013-06-06 (162/104) (EPIGASTRIC PAIN) DOUBTFUL NA RECOVERED/RESOLVED (171/113) 2013-05-28 ྤ MILD/ N/ DOSE NOT CHANGED/ 2013-07-30 (162/104) (BILE COLOR EMESIS) DOUBTFUL NA RECOVERED/RESOLVED (225/167) 2013-05-29 እ㝜⭼┿⳦ឤᰁ MILD/ Y/ DOSE NOT CHANGED/ 2013-06-01 (163/105) (VAGINAL YEAST INFECTION) POSSIBLE Y RECOVERED/RESOLVED (166/108) 2013-06-24 ᒀ㊰ឤᰁ MODERATE/ Y/ DOSE NOT CHANGED/ 2013-07-02 (189/131) (URINARY TRACT INFECTION) DOUBTFUL Y RECOVERED/RESOLVED (197/139) 2013-06-29 ᾮໟ⅖ MODERATE/ N/ DOSE NOT CHANGED/ 2013-07-30 (194/136) (LEFT ANKLE RETRO ACHILLES DOUBTFUL NA RECOVERED/RESOLVED (225/167) BURSITIS) 2013-06-29 യ MODERATE/ N/ DOSE NOT CHANGED/ 2013-07-30 (194/136) (LEFT FOOT PERFORATION OF DOUBTFUL NA RECOVERED/RESOLVED (225/167) LATERAL ORIGIN OF PLANTAR FASCIA) 2013-06-30 ྤ⾑ MILD/ N/ DOSE NOT CHANGED/ 2013-06-30 (195/137) (BLOOD TINGED EMESIS) DOUBTFUL NA RECOVERED/RESOLVED (195/137)
29 9 (163) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2013-07-21 㰯⭍⅖క࠺㢌③ MILD/ N/ DOSE NOT CHANGED/ 2013-08-09 (216/158) (SINUS PAIN) POSSIBLE NA RECOVERED/RESOLVED (235/177) 2013-07-21 ୖẼ㐨ឤᰁ MODERATE/ Y/ DOSE NOT CHANGED/ 2013-08-09 (216/158) (UPPER RESPIRATORY INFECTION) POSSIBLE N RECOVERED/RESOLVED (235/177) 2013-07-22 Ⓨ⇕ MILD/ N/ DOSE NOT CHANGED/ 2013-07-25 (217/159) (FEVER) POSSIBLE NA RECOVERED/RESOLVED WITH (220/162) SEQUELAE 2013-07-27 ࢡ࣮ࣟࣥ SEVERE/ N/ DOSE NOT CHANGED/ 2013-08-03 (222/164) (CROHN'S DISEASE FLARE) DOUBTFUL NA RECOVERED/RESOLVED (229/171) 2013-07-29 ᰾ MODERATE/ N/ DOSE NOT CHANGED/ 2014-03-31 (224/166) (WORSENING OF HEMORRHOIDS) DOUBTFUL NA RECOVERED/RESOLVED (469/411) 2013-08-04 ៏ᛶᝈࡢ㈋⾑ MILD/ N/ DOSE NOT CHANGED/ Ongoing (230/172) (ANEMIA-CHRONIC DISEASE) DOUBTFUL NA NOT RECOVERED/NOT - RESOLVED 2013-08-04 ࢡ࣮ࣟࣥ SEVERE/ N/ DOSE NOT CHANGED/ 2013-08-16 (230/172) (WORSENING OF CROHN'S DISEASE DOUBTFUL NA RECOVERED/RESOLVED (242/184) FLARE)
2013-08-04 ⾑ᛶୗ⑩ MILD/ N/ DOSE NOT CHANGED/ 2013-08-09 (230/172) (BLOOD DIARRHEA) PROBABLE NA RECOVERED/RESOLVED (235/177) 2013-08-06 㢌③ MILD/ N/ DOSE NOT CHANGED/ 2013-08-09 (232/174) (HEADACHE) DOUBTFUL NA RECOVERED/RESOLVED (235/177) 2013-08-07 ᩬ≧ୣ⑈≧⓶⑈ MILD/ N/ DOSE NOT CHANGED/ 2013-08-10 (233/175) (PRURITIC MACULOPAPULAR RASH DOUBTFUL NA RECOVERED/RESOLVED (236/178) ON TORSO) 2013-09-24 ⓑෆ㞀 MILD/ N/ DOSE NOT CHANGED/ Ongoing (281/223) (BILATERAL CATARACTS) NOT NA NOT RECOVERED/NOT - RELATED RESOLVED 2013-10-19 ⬚㒊ᦆയ MILD/ N/ DOSE NOT CHANGED/ 2013-12-01 (306/248) (BLUNT CHEST TRAUMA RIGHT NOT NA RECOVERED/RESOLVED (349/291) ANTERIOR) RELATED 2013-12-01 ᒀ㊰ឤᰁ MODERATE/ Y/ DOSE NOT CHANGED/ 2013-12-07 (349/291) (UTI) NOT Y RECOVERED/RESOLVED (355/297) RELATED
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route SALBUTAMOL 2013-02-10 2013-02-16 RESPIRATORY (INHALATION) FLUCONAZOLE 2013-02-28 2013-02-28 ORAL AMOXICILLIN 2013-03-24 2013-04-01 ORAL FLUCONAZOLE 2013-05-29 2013-06-01 ORAL NITROFURANTOIN 2013-06-26 2013-07-02 ORAL HYDROMORPHONE HYDROCHLORIDE 2013-08-04 2013-08-09 INTRAVENOUS HYDROMORPHONE HYDROCHLORIDE 2013-10-24 2013-10-24 INTRAMUSCULAR LIDOCAINE 2013-10-24 2013-10-24 TRANSDERMAL LIDOCAINE 2013-10-25 2013-10-25 TRANSDERMAL CIPROFLOXACIN 2013-12-01 2013-12-07 ORAL
(26) Subject CNTO1275CRD3003-1107-20939
1) Reason for narrative selection SAE Event of interest: Serious infection
30 0 (164) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome (Study day I/M) 2014-10-25 ఏᰁᛶ༢᰾⫢⅖ Y MODERATE/ Y/ DRUG INTERRUPTED/ 2015-01-17 (166/108) (EBV HEPATITIS) POSSIBLE Y RECOVERED/RESOLVED (250/192)
3) Baseline Demographic Information ȋȌǣ ͵ͳ ǣ ȋȌǣ ͺͺǤͺ ǣ ǣ ͳͻͺʹǦͲͺǦͳͺ ȋ Ȍǣ ͳͲǤʹ
4) Induction Treatment Group Induction study: CNTO1275CRD3002 Randomized Treatment Group: Ustekinumab Approximating 6 mg/kg IV Actual Treatment Group: Ustekinumab Approximating 6 mg/kg IV
5) Maintenance Treatment Group Assigned Treatment Group: Non-randomized subject/Non-responder to ustekinumab IV induction dosing and received ustekinumab in maintenance
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2014-05-13 1 Ustekinumab 520.2 mg WEEK 0 MAINTENANCE 2014-07-10 59 Ustekinumab 90 mg WEEK 0 MAINTENANCE 2014-07-10 59 Placebo 0 mg WEEK 8 MAINTENANCE 2014-09-08 119 Ustekinumab 90 mg WEEK 12 MAINTENANCE 2014-10-10 151 Placebo 0 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: Y Did the subject terminate the study participation before the Week 44 visit?: Y Did subject enter the long-term extension study?: -
8) Induction Baseline Crohn's Disease History Date of diagnosis: 31DEC2000 Disease duration: 13.37 years Involved areas: ᅇ⭠ཬࡧ⤖⭠
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: NEVER Stricture complications of (CD): PREVIOUS HISTORY
10) Concomitant Crohn's Disease-Related Surgeries None reported
11) Concomitant Steroids None reported
30 1 (165) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
12) Narrative Text ⿕㦂⪅ࡣ 3 ṓࡢⓑே⏨ᛶ࡛㸪2014 ᖺ 5 ᭶ 13 ᪥ᐶゎᑟධ⒪ἲࡋ࡚ᮏࢆ㟼⬦ෆᢞࡉࢀࡓࠋ ⿕㦂⪅ࡣ㸪ᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡎ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏࢆᢞࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪Ⓞ㸪⫶㣗㐨 ㏫ὶᛶᝈ㸪㧗⾑ᅽ㸪⫹▼㸪ᅇ⭠ษ㝖㸪ᆶษ㝖㸪㣧㓇㸦㐌 1 ᮼࡢ࣡ࣥ㸧ཬࡧࢢࣝࢱ࣑ࣥ㓟ࢼ ࢺ࣒ࣜ࢘ᑐࡍࡿࣞࣝࢠ࣮࡛࠶ࡗࡓࠋ SAE/Serious infection㸸ఏᰁᛶ༢᰾⫢⅖ (Day 166) CIOMS ࡼࡿ㸪2014 ᖺ 10 ᭶ 24 ᪥㸪⿕㦂⪅ࡣ⑂ປཬࡧᛰឤࡢ≧ࡀ࠶ࡾ㸪⩣᪥ᝏࡋࡓࠋ ࡲࡓ㸪ᗈ⠊ᛶ➽⫗③㸪တႿཬࡧⓎ⇕㸦᭱㧗 102.7°F㸧ࡶࡳࡽࢀ㸪ࣃࣛࢭࢱ࣮ࣔࣝࢆ᭹⏝ࡋࡓࠋ⿕ 㦂⪅ࡣ㸪ᩆᛴእ᮶㸦ER㸧ࢆཷデࡋࡓࠋ⮫ᗋ᳨ᰝ㸪࢘ࣝࢫ᳨ᰝཬࡧ⬚㒊 X ⥺᳨ᰝࡢ⤖ᯝ␗ᖖ ࡣ࡞ࡃ㸪⿕㦂⪅ࡣᖐᏯࡋࡓࠋⓎ⇕ࡣᣢ⥆ࡋ㸪တႿ㸪ᝏᚰ㸪ᙉ⭷㯤⑇㸪౽ᅇᩘࡢῶᑡ㸦㏻ᖖ 1 ᪥ 6㹼8 ᅇ㸧ཬࡧᗈỗᛶ⭡③㸦ᕥ⬥⭡ཬࡧᕥୗ⭡㒊࡛ࡼࡾᙉ࠸㸧ࡀⓎ⌧ࡋࡓࠋ⿕㦂⪅ࡣ 2014 ᖺ 10 ᭶ 29 ᪥㸪Ⓨ⇕㸪ᕥഃ㢌㒊ࡽᚋ㢌㒊ࡅ࡚ᨺᑕ≧ᗈࡀࡿ㢌③㸪ྑഃ㢌㒊ࡢ㢌③㸦⑊③ࢫࢣ࣮ ࡛ࣝᙉᗘ 7㹼9/10㸧㸪㌟③㸪ᝏᚰ㸪ྤ㸪➽⫗③ཬࡧᬯ〓Ⰽᒀࢆッ࠼㸪ER ࢆཷデࡋࡓࠋࣂࢱ ࣝࢧࣥ␗ᖖࡣ࡞ࡗࡓࠋ⌮Ꮫⓗᡤぢ࡛ࡣ㸪㍍ᗘࡢᙉ⭷㯤⑇ཬࡧ∎ୗ㯤⑇ࢆㄆࡵࡓࠋ⭠㞧㡢ࡣ ⭡㒊య࡛᫂☜࡛࠶ࡾ㸪⫢⭁⭘ࡢᚩೃࡣ࡞ࡗࡓࡀ㸪῝྾ࡼࡾ⭡㒊ᛌឤࡣᝏࡋ㸪⭡㒊 య㍍ᗘࡢ⣸ᩬࢆㄆࡵࡓࠋ⿕㦂⪅ࡣ㸪⢭ᰝཬࡧຍ⒪ࡢࡓࡵ 2014 ᖺ 10 ᭶ 29 ᪥ධ㝔ࡋࡓࠋ 2014 ᖺ 10 ᭶ 29 ᪥ࡢ⮫ᗋ᳨ᰝࡣ㸪⥲ࣅࣜࣝࣅࣥ 7.8 mg/dL㹙ṇᖖ⠊ᅖ㸦NR㸧0.3-1.2 mg/dL㹛㸪 ┤᥋ࣅࣜࣝࣅࣥ 4.9 mg/dL㸦NR 0.1-0.5 mg/dL㸧㸪㛫᥋ࣅࣜࣝࣅࣥ 2.9 mg/dL㸦NR 0.1-0.8 mg/dL㸧㸪 ࢫࣃࣛࢠࣥ㓟࣑ࣀࢺࣛࣥࢫࣇ࢙࣮ࣛࢮ㸦AST㸧136 IU/L㸦NR 14-41 iU/L㸧㸪ࣛࢽ࣑ࣥࣀ ࢺࣛࣥࢫࣇ࢙࣮ࣛࢮ㸦ALT㸧247 IU/L㸦NR 17-63 IU/L㸧㸪ࣝ࢝ࣜ࣍ࢫࣇࢱ࣮ࢮ 158 IU/L㸦NR 32-91 IU/L㸧㸪⾑ᑠᯈᩘ 136㸦NR ཬࡧ༢᫂㸧࡛࠶ࡗࡓࠋ⾑Ύ୰ࢭࢺ࣑ࣀࣇ࢙ࣥࡣ 10 ȝg/mL ᮍ‶࡛࠶ࡗࡓ㸦NR 10-30 ȝg/mL㸧ࠋ⿕㦂⪅ࡢ࢚ࣉࢫࢱ࣭ࣥࣂ࣮࢘ࣝࢫ㸦EBV㸧ࡢ࢘ ࣝࢫ㔞ࡣቑຍࡋ࡚࠸ࡓ㸦EBV IgM>160㸪EBV IgG>31.1㸪␗✀ぶᛶᢠయ౯ 1:8㸧ࠋB ᆺ⫢⅖ 㸦⾲㠃ᢠཎ㸪⾲㠃ᢠయ㸪ࢥᢠయ㸧ཬࡧ A ᆺ㸭C ᆺ⫢⅖ᢠయᑐࡍࡿ⾑ΎᏛⓗ᳨ᰝࡣ㝜ᛶ࡛࠶ࡗ ࡓࠋ࣏࣓࣮ࣜࣛࢮ㐃㙐ᛂ㸦PCR㸧᳨ᰝ࡛ࡣ㸪B ᆺ⫢⅖࢘ࣝࢫཬࡧ C ᆺ⫢⅖࢘ࣝࢫࡣ᳨ฟࡉ ࢀ࡞ࡗࡓࠋ⬚㒊 X ⥺᳨ᰝ࡛ࡣ㸪ഃ㠃ീ࡛⫵ᗏ㒊ᩬ≧ࡢ⫵⬊ᛶ㝜ᙳࡀࢃࢀ㸪⫵⅖ࡀ♧၀ࡉࢀ ࡓࠋ2014 ᖺ 10 ᭶ 29 ᪥ᐇࡋࡓ⭡㒊㉸㡢Ἴ᳨ᰝཬࡧ⭡㒊᰾☢Ẽඹ㬆⏬ീἲ㸦MRI㸧࡛ࡣ㸪⬡⫫ ⫢ࢆక࠺⫢⭁⭘㸪⫢⭘ཬࡧ⫹▼ࡀㄆࡵࡽࢀ㸪⫹ᄞ⅖ࡢᡤぢࡣࡳࡽࢀ࡞ࡗࡓࠋEBV ᑐࡋ ࡚ࡣᨭᣢ⒪ἲࡀ⾜ࢃࢀࡓࠋ⿕㦂⪅ࡣ㸪2014 ᖺ 11 ᭶ 2 ᪥㏥㝔ࡋࡓࠋ 2015 ᖺ 1 ᭶ 17 ᪥ࡢ⮫ᗋ᳨ᰝ࡛ࡣ㸪┤᥋ࣅࣜࣝࣅࣥ 0.2 mg/dL㸪㛫᥋ࣅࣜࣝࣅࣥ 0.8 mg/dL㸪⾑ Ύ⥲ࣅࣜࣝࣅࣥ 1 mg/dL㸪AST 28 IU/L㸪ALT 67 IU/L ࡛࠶ࡗࡓࠋ⮫ᗋࢹ࣮ࢱ࣮࣋ࢫࡼࡿ㸪ᮏ ㇟ࡼࡾ㦂⸆ࡢᢞࡣ୰᩿ࡉࢀ㸪ࡑࡢᚋ㸪㏣㊧⬟࡞ࡗࡓࠋ
13) Other Adverse Events Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2014-04-10 ⣽⳦ᛶ⫶⭠⅖ MODERATE/ Y/ NOT APPLICABLE/ 2014-05-05 (-33/.) (PLESIOMONAS SHIGELLOIDES NOT Y RECOVERED/RESOLVED (-8/.) ENTERITIS) RELATED 2014-05-24 ⫼㒊③ MODERATE/ N/ DOSE NOT CHANGED/ 2014-05-29 (12/.) (BACK PAIN) NOT NA RECOVERED/RESOLVED (17/.) RELATED
30 2 (166) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2014-06-27 ⫼㒊③ MODERATE/ N/ DOSE NOT CHANGED/ Ongoing (46/.) (BACK PAIN) NOT NA NOT RECOVERED/NOT - RELATED RESOLVED 2014-10-01 㰯ဗ㢌⅖ MILD/ Y/ DOSE NOT CHANGED/ 2014-10-05 (142/84) (COMMON COLD) NOT N RECOVERED/RESOLVED (146/88) RELATED 2014-10-31 㢌③ SEVERE/ N/ DRUG INTERRUPTED/ 2014-11-01 (172/114) (SEVERE HEADACHES) POSSIBLE NA RECOVERED/RESOLVED (173/115)
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route CIPROFLOXACIN 2014-04-15 2014-04-30 ORAL PARACETAMOL 2014-05-27 2014-05-29 ORAL DIAZEPAM 2014-05-27 2014-05-29 ORAL TRAMADOL 2014-06-27 - ORAL PARACETAMOL 2014-08-12 2014-08-13 ORAL PARACETAMOL 2014-10-01 2014-10-05 ORAL KETOROLAC 2014-10-29 2014-10-29 INTRAVENOUS METOCLOPRAMIDE 2014-10-29 2014-10-29 INTRAVENOUS ACETYLCYSTEINE 2014-10-29 2014-10-29 INTRAVENOUS ONDANSETRON 2014-10-29 2014-11-01 INTRAVENOUS PIP/TAZO 2014-10-29 2014-10-29 INTRAVENOUS PARACETAMOL 2014-10-31 2014-11-01 ORAL HYDROMORPHONE HYDROCHLORIDE 2014-10-31 2014-11-01 ORAL HEPARIN 2014-10-31 2014-10-31 SUBCUTANEOUS IBUPROFEN 2014-10-31 2014-11-01 ORAL METOCLOPRAMIDE 2014-10-31 2014-10-31 INTRAVENOUS TRAMADOL HYDROCHLORIDE 2014-10-31 2014-11-01 ORAL CYCLOBENZAPRINE 2014-11-02 - ORAL
(27) Subject CNTO1275CRD3003-2203-11058
1) Reason for narrative selection SAE
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome I/M) 2013-02- 㐣ᩄ Y MODERATE/ N/ DOSE NOT CHANGED/ 2013-02-20 18 (ALLERGIC REACTION OF NOT NA RECOVERED/RESOLVED (43/.) (41/.) UNKNOWN CAUSE) RELATED 2013-03- ከⓎᛶ㛵⠇⅖ Y SEVERE/ N/ DOSE NOT CHANGED/ 2013-08-28 13 (POLY-ARTHRITIS) POSSIBLE NA RECOVERED/RESOLVED WITH (232/175) (64/7) SEQUELAE
3) Other Adverse Events None reported
4) Baseline Demographic Information ȋȌǣ Ͷͻ ǣ ȋȌǣ ͳʹͺ ǣ ǣ ͳͻ͵ǦͲ͵Ǧͳͻ ȋ Ȍǣ ͳͺ͵
30 3 (167) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
5) Induction Treatment Group Induction study: CNTO1275CRD3001 Randomized Treatment Group: Ustekinumab Approximating 6 mg/kg IV Actual Treatment Group: Ustekinumab Approximating 6 mg/kg IV
6) Maintenance Treatment Group Assigned Treatment Group: Non-randomized subject/Non-responder to ustekinumab IV induction dosing and received ustekinumab in maintenance
7) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2013-01-09 1 Ustekinumab 520.2 mg WEEK 0 MAINTENANCE 2013-03-07 58 Placebo 0 mg WEEK 0 MAINTENANCE 2013-03-07 58 Ustekinumab 90 mg
8) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: Y Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: -
9) Induction Baseline Crohn's Disease History Date of diagnosis: 31DEC1989 Disease duration: 23.03 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪ᾘ⟶እኚ㸦ࣇࢱᛶཱྀෆ⅖㸪㛵⠇⅖㸭㛵⠇③㸪ᙬ⅖㸭ࡪ ࠺⭷⅖㸧
10) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: NEVER Stricture complications of (CD): NEVER
11) Concomitant Crohn's Disease-Related Surgeries None reported
12) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 4 MAINTENANCE HYDROCORTISONE 100 mg - WEEK 4 MAINTENANCE PREDNISOLONE 40 mg 40 mg WEEK 4 MAINTENANCE PREDNISOLONE 40 mg 40 mg WEEK 4 MAINTENANCE PREDNISOLONE 30 mg 30 mg WEEK 4 MAINTENANCE PREDNISOLONE 25 mg 25 mg WEEK 4 MAINTENANCE PREDNISOLONE 50 mg 50 mg WEEK 4 MAINTENANCE HYDROCORTISONE 0 mg - WEEK 8 MAINTENANCE PREDNISOLONE 20 mg 20 mg WEEK 8 MAINTENANCE PREDNISOLONE 15 mg 15 mg WEEK 8 MAINTENANCE PREDNISOLONE 30 mg 30 mg
30 4 (168) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
13) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route EPINEPHRINE 2013-02-18 2013-02-18 INTRAMUSCULAR PROMETHAZINE 2013-02-18 2013-02-18 INTRAMUSCULAR CETIRIZINE HYDROCHLORIDE 2013-02-18 2013-02-21 ORAL HYDROCORTISONE 2013-03-13 2013-03-20 INTRAVENOUS PANADEINE CO 2013-03-13 2013-03-13 ORAL PETHIDINE 2013-03-13 2013-03-20 INTRAMUSCULAR ENOXAPARIN SODIUM 2013-03-14 2013-03-21 SUBCUTANEOUS PREDNISOLONE 2013-03-20 2013-03-21 ORAL OXYCODONE HYDROCHLORIDE 2013-03-21 2013-03-26 ORAL PREDNISOLONE 2013-03-22 2013-03-26 ORAL FENTANYL 2013-03-26 - TOPICAL PREDNISOLONE 2013-03-27 2013-03-30 ORAL PREDNISOLONE 2013-03-31 2013-04-01 ORAL PREDNISOLONE 2013-04-02 2013-04-02 ORAL PREDNISOLONE 2013-04-03 2013-04-20 ORAL PREDNISOLONE 2013-04-21 2013-04-24 ORAL PREDNISOLONE 2013-04-25 - ORAL
14) Narrative Text ⿕㦂⪅ࡣ 4 ṓࡢⓑே⏨ᛶ࡛㸪2013 ᖺ 1 ᭶ 9 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏ㸦㹼6 mg/kg ⩌㸧ࢆ 㟼⬦ෆᢞࡉࢀࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡎ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏ ࢆᢞࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪⭠ษ㝖㸦1986 ᖺ㸧㸪③㢼㸪㛵⠇③ཬࡧႚ↮㸦1 ᖺ௨ෆ୰Ṇ㸧࡛࠶ࡗࡓࠋ ௨ୗࡣᐶゎᑟධヨ㦂 CNTO1275CRD3001 ࡢ㦂⥲ᣓሗ࿌᭩ࡢ⿕㦂⪅ࡢླྀ㏙࡚ሗ࿌ࡉࢀࡓ ㇟࡛࠶ࡿ㸸 SAE㸸㐣ᩄ㸦Day 41㸧 CIOMS ࡼࡿ㸪2013 ᖺ 2 ᭶ 18 ᪥㸦ᐶゎᑟධ⒪ἲ࡛ࡢᮏᢞ㛤ጞᚋ⣙ 6 㐌㛫㸧㸪⿕㦂⪅ࡣ ㌟ᦋᛶࡢ㉥࠸⭾⑈㸦red pruritic welts㸧ཬࡧཱྀ၁⭘⬽ࢆⓎ⌧ࡋ㸪ᩆᛴ⛉ධ㝔ࡋࡓࠋࢻࣞ ࢼࣜࣥ㸪ࣉ࣓ࣟࢱࢪࣥཬࡧ 2 L ࡢ⏕⌮㣗ሷᾮ㸦IV㸧ࡼࡿ⒪ࡀᐇࡉࢀࡓࠋཎᅉ᫂ࡢࣞࣝ ࢠ࣮ᛂࡀሗ࿌ࡉࢀࡓࠋ⿕㦂⪅ࡣ⒪ຠᯝࡀㄆࡵࡽࢀ㸪ྠ᪥㸪ࢭࢳࣜࢪࣥሷ㓟ሷࢆฎ᪉ࡉࢀ㏥㝔 ࡋࡓࠋᮏ㇟ࡣ 2013 ᖺ 2 ᭶ 20 ᪥ᾘᩓࡋࡓሗ࿌ࡉࢀࡓࠋ㦂ᢸᙜ་ᖌࡣ㸪ᮏ㇟㦂⸆ ࡢᅉᯝ㛵ಀࡘ࠸࡚㛵㐃࡞ࡋ㸦not related㸧ุ᩿ࡋࡓࠋࡑࡢᚋ㸪⿕㦂⪅ࡣ nonresponder ࡋ࡚ᐶ ゎ⥔ᣢヨ㦂⛣⾜ࡋ㸪ࣉࣟࢺࢥ࣮ࣝᚑࡗ࡚ᮏࢆ⓶ୗᢞࡉࢀࡓࠋ ௨ୗࡣᐶゎ⥔ᣢ⒪ἲ࡛࠶ࡿᮏヨ㦂࡛つᐃࡉࢀࡓሗ࿌ᮇ㛫Ⓨ⌧ࡋࡓ㇟࡛࠶ࡿ㸸 SAE㸸ከⓎᛶ㛵⠇⅖㸦Day 64㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ⭸ཬࡧ㊊㛵⠇ࡢ㧗ᗘࡢ㛵⠇③㸪㛵⠇ᾐฟᾮཬࡧ 2013 ᖺ 3 ᭶ 7 ᪥ 㸦ᮏ 90 mg ࢆᢞࡋࡓᐶゎ⥔ᣢヨ㦂 Week 0 ྠ᪥㸧௨㝆ᣢ⥆ࡋ࡚࠸ࡓከⓎᛶ㛵⠇⅖ࡢࡓࡵṌ ⾜⬟࡞ࡾ㸪2013 ᖺ 3 ᭶ 13 ᪥ධ㝔ࡋࡓࠋ ධ㝔㸪⿕㦂⪅ࡣ⭠≧㸪Ⓨ⇕ཬࡧᝏᐮࡣ࡞ࡗࡓࠋྑ⫝㸪ྑ⭸㸪୧㊊㛵⠇ཬࡧ୧ᡭ㤳㸪 ⇕ឤ㸪⬟ື㐠ືཬࡧື㐠ື࡛ࡢ⑊③୪ࡧྍື⠊ᅖࡢῶᑡࡀㄆࡵࡽࢀࡓࠋ2013 ᖺ 3 ᭶ 13 ᪥ࡢ ⮫ᗋ᳨ᰝ࡛ࡣ㸪C ᛂᛶࡓࢇⓑ⃰ᗘ 141 mg/L㸦ṇᖖ⠊ᅖ<5 mg/L㸧࡛࠶ࡗࡓࠋ⒪ࡋ࡚㸪ࢫࢸ
30 5 (169) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
ࣟࢻࡢ㟼⬦ෆᢞ㸪㙠③⸆ཬࡧࢫࢸࣟࢻࡢ㛵⠇ෆὀᑕࡀᐇࡉࢀࡓࠋᮏ㇟ࡣᚋ㑇ࢆక࠺ ࡶࡢࡢ㸪ᅇ㸭ᾘᩓࡋࡓሗ࿌ࡉࢀ㸪⿕㦂⪅ࡣ 2013 ᖺ 3 ᭶ 21 ᪥㏥㝔ࡋࡓࠋ
(28) Subject CNTO1275CRD3003-2204-20144
1) Reason for narrative selection SAE
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome I/M) 2013-05-18 ᑠ⭠㛢ሰ Y MODERATE/ N/ DOSE NOT CHANGED/ 2013-05-20 (270/216) (PARTIAL SMALL BOWEL POSSIBLE NA RECOVERED/RESOLVED (272/218) OBSTRUCTION)
3) Baseline Demographic Information ȋȌǣ ʹͳ ǣ ȋȌǣ ͷͺǤͷ ǣ ǣ ͳͻͻͳǦͲʹǦͳͷ ȋ Ȍǣ ͳͺͳ
4) Induction Treatment Group Induction study: CNTO1275CRD3002 Randomized Treatment Group: Ustekinumab 130 mg IV Actual Treatment Group: Ustekinumab 130 mg IV
5) Maintenance Treatment Group Assigned Treatment Group: Randomized subject/Responder to ustekinumab IV induction dosing/ustekinumab 90 mg SC q12w
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2012-08-22 1 Ustekinumab 129.6 mg WEEK 0 MAINTENANCE 2012-10-15 55 Ustekinumab 90 mg WEEK 8 MAINTENANCE 2012-12-12 113 Placebo 0 mg WEEK 12 MAINTENANCE 2013-01-10 142 Ustekinumab 90 mg WEEK 16 MAINTENANCE 2013-02-04 167 Placebo 0 mg WEEK 20 MAINTENANCE 2013-03-04 195 Placebo 0 mg WEEK 24 MAINTENANCE 2013-04-02 224 Ustekinumab 90 mg WEEK 28 MAINTENANCE 2013-04-29 251 Placebo 0 mg WEEK 32 MAINTENANCE 2013-05-30 282 Placebo 0 mg WEEK 36 MAINTENANCE 2013-06-24 307 Ustekinumab 90 mg WEEK 40 MAINTENANCE 2013-07-22 335 Placebo 0 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: N Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: Y
30 6 (170) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
8) Induction Baseline Crohn's Disease History Date of diagnosis: 31MAY2007 Disease duration: 5.23 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪ᾘ⟶እኚ 㸦㛵⠇⅖㸭㛵⠇③㸧
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: PREVIOUS HISTORY Sinus tracts/perforation: NEVER Fistula: NEVER Stricture complications of (CD): CURRENTLY PRESENT
10) Concomitant Crohn's Disease-Related Surgeries None reported
11) Concomitant Steroids None reported
12) Narrative Text ⿕㦂⪅ࡣ 2 ṓࡢⓑே⏨ᛶ࡛㸪2012 ᖺ 8 ᭶ 22 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏࢆ㟼⬦ෆᢞࡉࢀ ࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏ 90 mg ࢆ q12w ࡛⓶ୗᢞࡍࡿ⩌ࣛࣥࢲ࣒ࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪ᑠ⭠㛢ሰ 㸦2007 ᖺ㸧ཬࡧᅇ⭠ᮎ➃ษ㝖㸦2007 ᖺ㸧࡛࠶ࡗࡓࠋ SAE㸸ᑠ⭠㛢ሰ㸦Day 270㸧 CIOMS ࡼࡿ㸪2013 ᖺ 5 ᭶ 19 ᪥㸪⿕㦂⪅ࡣ㧗ᗘࡢ㛫Ḟᛶୗ⭡㒊③㸪➽②ᨥ㸪౽⛎ཬࡧᝏ ᚰࡢࡓࡵධ㝔ࡋࡓࠋ⌮Ꮫⓗᡤぢ࡛ࡣ㸪⭡ቨ㜵ᚚ㸪⭠㞧㡢ཬࡧ⭡㒊యࡢᡴデࡼࡿᅽ③ࢆㄆࡵ㸪 㦵ୖ㒊࡛㢧ⴭ࡛࠶ࡗࡓࠋ⭡㒊 X ⥺᳨ᰝ࡛ࡣ㸪」ᩘࡢ㙾㠃ീࢆక࠺ከᩘࡢᣑᙇࡋࡓᑠ⭠ಀ㋟ཬࡧ ⤖⭠ᑡ㔞ࡢ࢞ࢫࡀㄆࡵࡽࢀࡓࠋ⭡㒊ࢥࣥࣆ࣮ࣗࢱ᩿ᒙᙳ㸦CT㸧ࢫ࡛࢟ࣕࣥࡣ㸪ᅇ⭠࿀ྜ 㒊㸪ᑠ⭠㐲㍍ᗘᣑᙇࡋࡓಀ㋟㸦᭱ᚄ 33 mm㸧㸪࿀ྜ㒊ཬࡧࡑࡢ㏆ࡢ▷࠸༊ᇦ୰➼ᗘ ࡢ⭠ቨ⫧ཌ㸪⤖⭠ࡽ┤⭠ࡅ࡚౽୰ࡢ࢞ࢫࡀㄆࡵࡽࢀࡓࠋࡇࡢࡇࡽ㸪࿀ྜ㒊࡛ࡢ㒊ศ ⓗ㸭㛢ሰཬࡧᝈࡢ⇞ࡀ♧၀ࡉࢀࡓࠋ⮫ᗋ᳨ᰝ್␗ᖖ್ࡣㄆࡵࡽࢀ࡞ࡗࡓࠋࣇ࢙ࣥࢱ ࢽࣝ㸪pantoprazole㸪࣊ࣃࣜࣥ㸪࣓ࢺࢡࣟࣉ࣑ࣛࢻ㸪࢜ࣥࢲࣥࢭࢺࣟࣥࡼࡿ⒪ࡀᐇࡉࢀࡓࠋ ⿕㦂⪅ࡣ㸪2013 ᖺ 5 ᭶ 20 ᪥㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2012-11 ୖẼ㐨ឤᰁ MILD/ Y/ DOSE NOT CHANGED/ 2012-11-15 - (URTI) DOUBTFUL N RECOVERED/RESOLVED (86/32) 2013-01-10 㛵⠇③ MILD/ N/ DOSE NOT CHANGED/ Ongoing (142/88) (INTERMITTENT KNEE PAIN) DOUBTFUL NA NOT RECOVERED/NOT - RESOLVED 2013-06-30 ⓶┿⳦ឤᰁ MILD/ Y/ DOSE NOT CHANGED/ 2014-08-19 (313/259) (GROIN FUNGAL INFECTION) POSSIBLE N RECOVERED/RESOLVED (728/674)
30 7 (171) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2013-07-31 တႿ MILD/ N/ DOSE NOT CHANGED/ Ongoing (344/290) (INTERMITTENT DRY DOUBTFUL NA NOT RECOVERED/NOT - COUGH) RESOLVED
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route FENTANYL 2013-05-19 2013-05-19 INTRAVENOUS HEPARIN 2013-05-19 2013-05-20 SUBCUTANEOUS METOCLOPRAMIDE 2013-05-19 2013-05-19 INTRAVENOUS MORPHINE 2013-05-19 2013-05-19 INTRAVENOUS ONDANSETRON 2013-05-19 2013-05-19 INTRAVENOUS PANTOPRAZOLE SODIUM SESQUIHYDRATE 2013-05-19 2013-05-20 ORAL KETOCONAZOLE 2013-07-15 2013-08-19 TOPICAL
(29) Subject CNTO1275CRD3003-2606-20878
1) Reason for narrative selection SAE Event of interest: Serious infection
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome I/M) 2014-10-22 ⫵⅖ Y MODERATE/ Y/ DRUG INTERRUPTED/ 2014-10-29 (192/136) (RIGHT ALVEOLAR POSSIBLE Y RECOVERED/RESOLVED (199/143) PNEUMONIA)
3) Baseline Demographic Information ȋȌǣ ʹ͵ ǣ ȋȌǣ ͳʹ͵ ǣ ǣ ͳͻͻͲǦͲǦͲͻ ȋ Ȍǣ ͳͺͷ
4) Induction Treatment Group Induction study: CNTO1275CRD3002 Randomized Treatment Group: Ustekinumab Approximating 6 mg/kg IV Actual Treatment Group: Ustekinumab Approximating 6 mg/kg IV
5) Maintenance Treatment Group Assigned Treatment Group: Randomized subject/Responder to ustekinumab IV induction dosing/placebo SC
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2014-04-14 1 Ustekinumab 520.2 mg WEEK 0 MAINTENANCE 2014-06-09 57 Placebo 0 mg WEEK 8 MAINTENANCE 2014-08-07 116 Placebo 0 mg WEEK 12 MAINTENANCE 2014-08-25 134 Placebo 0 mg WEEK 16 MAINTENANCE 2014-10-02 172 Placebo 0 mg WEEK 20 MAINTENANCE 2014-11-13 214 Placebo 0 mg WEEK 24 MAINTENANCE 2014-12-01 232 Placebo 0 mg WEEK 28 MAINTENANCE 2014-12-18 249 Placebo 0 mg WEEK 32 MAINTENANCE 2015-01-22 284 Placebo 0 mg
30 8 (172) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
Visit Start Date Study Day Actual Treatment Dose WEEK 36 MAINTENANCE 2015-02-23 316 Placebo 0 mg WEEK 40 MAINTENANCE 2015-03-23 344 Placebo 0 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: N Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: Y
8) Induction Baseline Crohn's Disease History Date of diagnosis: 31AUG2007 Disease duration: 6.62 years Involved areas: ⤖⭠ࡢࡳ㸪⫠㛛࿘ᅖ
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: CURRENTLY PRESENT Stricture complications of (CD): NEVER
10) Concomitant Crohn's Disease-Related Surgeries None reported
11) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 20 MAINTENANCE METHYLPREDNISOLONE 20 mg - WEEK 20 MAINTENANCE METHYLPREDNISOLONE 0 mg -
12) Narrative Text ⿕㦂⪅ࡣ 2 ṓࡢⓑே⏨ᛶ࡛㸪2014 ᖺ 4 ᭶ 14 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏࢆ㟼⬦ෆᢞࡉࢀ ࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ࣉࣛࢭ࣎ࢆ⓶ୗᢞ ࡍࡿ⩌ࣛࣥࢲ࣒ࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪ႚ↮࡛࠶ࡗࡓࠋ SAE/Serious infection㸸⫵⅖㸦Day 192㸧 CIOMS ࡼࡿ㸪2014 ᖺ 10 ᭶ 22 ᪥㸪⿕㦂⪅⬺ຊ㸪⬚㒊㔜ᅽឤ㸪ᑡ㔞ࡢၻ⑱ࢆక࠺တႿ③㸪 Ⓨ⇕㸪ᝏᐮ㸪㔞Ⓨờ㸪⑂ປཬࡧ྾ᅔ㞴ࡀࡳࡽࢀࡓࠋ⌮Ꮫⓗᡤぢ࡛ࡣ㸪㢖྾㸪྾ᅔ㞴㸪⓶ ⓑ㸪⯉ⱏ㸪ࢃࡎ࡞‵ᛶࣛ㡢ࢆక࠺ࡀṇᖖ࡞྾ࣃࢱ࣮ࣥ㸪ᚰ㡢ࡣ᫂░࡛࠶ࡿࡀᚰᢿືࣜࢬ ࣒ࡢຍ㏿ᛂࡀㄆࡵࡽࢀ㸪⭡㒊ཬࡧᅄ⫥ࡣṇᖖ࡛࠶ࡗࡓࠋྠ᪥㸦2014 ᖺ 10 ᭶ 22 ᪥㸧㸪X ⥺᳨ᰝ ࡼࡾ㸪⿕㦂⪅ࡣྑ⫵⬊ᛶ⫵⅖デ᩿ࡉࢀධ㝔ࡋࡓࠋ⾑ᾮ࢞ࢫศᯒ࡛ࡣ㸪㓟⣲ศᅽ㸦59㸪༢ཬ ࡧṇᖖ⠊ᅖ᫂㸧ཬࡧ㓟⣲㣬ᗘ㸦90.4㸪༢ཬࡧṇᖖ⠊ᅖ᫂㸧ࢆ㝖ࡁ␗ᖖࡣㄆࡵࡽࢀ࡞ࡗ ࡓࠋࢡࣛࣜࢫ࣐ࣟࢩࣥ㸪࣑࢝ࢩࣥ㸪methylprednisone ཬࡧ⏕⌮㣗ሷỈⅬࡼࡿ⒪ࡀᐇ ࡉࢀࡓࠋ2014 ᖺ 10 ᭶ 29 ᪥㸪⿕㦂⪅ࡣⰋዲ࡞㌟≧ែ࡛㏥㝔ࡋࡓࠋ
30 9 (173) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
13) Other Adverse Events Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome (Study day I/M) 2014-07-07 㛵⠇⅖ MILD/ N/ DOSE NOT CHANGED/ 2014-07-07 (85/29) (ARTHRITIS) NOT RELATED NA RECOVERED/RESOLVED (85/29)
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route AMIKACIN 2014-10-22 2014-10-29 INTRAVENOUS CLARITHROMYCIN 2014-10-22 2014-10-29 INTRAVENOUS METHYLPREDNISOLONE 2014-10-22 2014-10-29 INTRAVENOUS
(30) Subject CNTO1275CRD3003-2711-10966
1) Reason for narrative selection SAE Discontinuation of study agent due to AE Event of interest: Serious infection
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome (Study day I/M) 2013-05-02 ⭡㒊⮋⒆ Y SEVERE/ Y/ DRUG WITHDRAWN/ 2013-07-08 (137/81) (ABDOMINAL ABSCESS) POSSIBLE Y RECOVERED/RESOLVED (204/148)
3) Baseline Demographic Information ȋȌǣ ͵Ͳ ǣ ȋȌǣ ͻͶǤͶ ǣ ǣ ͳͻͺʹǦͲǦʹͲ ȋ Ȍǣ ͳͺʹǤͷ
4) Induction Treatment Group Induction study: CNTO1275CRD3001 Randomized Treatment Group: Placebo IV Actual Treatment Group: Placebo IV
5) Maintenance Treatment Group Assigned Treatment Group: Non-randomized subject/Non-responder to placebo IV induction dosing and received ustekinumab in maintenance
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2012-12-17 1 Placebo 0 mg WEEK 0 MAINTENANCE 2013-02-11 57 Placebo 0 mg WEEK 0 MAINTENANCE 2013-02-11 57 Ustekinumab 129.6 mg WEEK 8 MAINTENANCE 2013-04-08 113 Ustekinumab 90 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: Y Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: -
31 0 (174) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
8) Induction Baseline Crohn's Disease History Date of diagnosis: 31JUL2010 Disease duration: 2.38 years Involved areas: ᅇ⭠ཬࡧ⤖⭠
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: PREVIOUS HISTORY Sinus tracts/perforation: PREVIOUS HISTORY Fistula: PREVIOUS HISTORY Stricture complications of (CD): NEVER
10) Concomitant Crohn's Disease-Related Surgeries Surgery Date Result of lack of efficacy? ࡑࡢษ㛤ཬࡧ⮋⒆ࢻࣞࢼ࣮ࢪ 2013-05-03 N ࡑࡢษ㛤ཬࡧ⮋⒆ࢻࣞࢼ࣮ࢪ 2013-05-24 N ⤖⭠ษ㝖̺ཪࡣள 2013-07-19 N
11) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 0 PREDNISONE 15 mg 15 mg WEEK 12 MAINTENANCE PREDNISONE 10 mg 10 mg WEEK 12 MAINTENANCE PREDNISONE 7.5 mg 7.5 mg WEEK 12 MAINTENANCE PREDNISONE 5 mg 5 mg WEEK 12 MAINTENANCE PREDNISONE 2.5 mg 2.5 mg SAFETY FOLLOW-UP MAINTENANCE HYDROCORTISONE 50 mg - SAFETY FOLLOW-UP MAINTENANCE HYDROCORTISONE 0 mg -
12) Narrative Text ⿕㦂⪅ࡣ 3 ṓࡢⓑே⏨ᛶ࡛㸪2012 ᖺ 12 ᭶ 17 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ࣉࣛࢭ࣎ࢆ㟼⬦ෆᢞ ࡉࢀࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡎ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏࢆᢞ ࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪₽⒆ᛶ⭠⅖ 㸦2010 ᖺ௨㝆㸧㸪⭡⭍ෆ⮋⒆ࡼࡿᅇ⭠㒊ษ㝖⾡㸦2010 ᖺ 7 ᭶㸧㸪ᛶࢡࣟࢫࢺࣜࢪ࣒࢘ឤ ᰁ㸪Edwardsiella ឤᰁ㸪ᛶᖏ≧⑁⑈㸪ྑୖ⫥ࡢ㟼⬦ෆᢞ㒊㛵㐃ࡋࡓ㟼⬦⅖㛵ಀࡍࡿ ῝㒊㟼⬦⾑ᰦ㸪ࣈࢻ࢘⌫⳦ᛶẟໟ⅖㸪㕲Ḟஈᛶ㈋⾑㸪㰯⭍⅖㸪ᑠ⭠✸Ꮝཬࡧᑠ⭠⮋⒆㸦2010 ᖺ 6 ᭶ 16 ᪥㸧ཬࡧᏳ࡛࠶ࡗࡓࠋ SAE/Discontinuation of study agent due to AE/Serious infection㸸⭡㒊⮋⒆㸦Day 137㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2 ࢝᭶㛫ᣢ⥆ࡋ࡚࠸ࡿᕥഃ⭡③ࡢቑᙉ㸪㛫Ḟ⇕㸪౽ᅇᩘࡢኚ ཬࡧపᰤ㣴≧ែࢆ๓᪥ッ࠼㸪2013 ᖺ 5 ᭶ 2 ᪥ධ㝔ࡋࡓࠋධ㝔ࡲ࡛ࡢᩘ࢝᭶㛫࡛㸪⿕㦂⪅ࡢయ 㔜ࡣ 6 kg ῶᑡࡋࡓሗ࿌ࡉࢀࡓࠋ2013 ᖺ 5 ᭶ 2 ᪥ࡢ⭡㒊ཬࡧ㦵┙㒊ࡢࢥࣥࣆ࣮ࣗࢱ᩿ᒙᙳ 㸦CT㸧ࢫ࡛࢟ࣕࣥࡣ㸪ୗ⾜⤖⭠࿘ᛶࡢ⭠ቨ⫧ཌࡀㄆࡵࡽࢀ㸪άືᮇࡢࢡ୍࣮ࣟࣥ⮴ࡍ ࡿᗈ⠊࡞⤖⭠࿘ᅖࡢ⅖ᛶኚࢆకࡗ࡚࠸ࡓࠋࡲࡓ㸪⭡⭍ෆ⮋⒆୍⮴ࡍࡿ 2 ࡘࡢᾮయ㈓␃ࡀ ㄆࡵࡽࢀࡓࠋࡑࡢ࠺ࡕ 1 ࡘࡣᕥ୰⭡㒊ࡢୗ⾜⤖⭠ഃ᪉㸪ࡶ࠺ 1 ࡘࡣୗ⾜⤖⭠୰㛫ࡢᚋ᪉⨨ ࡋ㸪⭠⟶እ࢞ࢫ㸦extra luminal air㸧ࡢẼἻࢆྵࢇ࡛࠸ࡓࠋ2013 ᖺ 5 ᭶ 3 ᪥ࡢ⮫ᗋ᳨ᰝ್ࡣ㸪ⓑ⾑ ⌫ᩘ 12.3×109/L㹙ṇᖖ⠊ᅖ㸦NR㸧4-11×109/L㹛㸪ዲ୰⌫ᩘ 10.2×109/L㸦NR 2-8×109/L㸧࡛࠶ࡗࡓࠋ
31 1 (175) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
2013 ᖺ 5 ᭶ 3 ᪥㸪ᕥ⫘㦵ୗ⨨ࡍࡿ⮋⒆ᑐࡋ࡚ CT ࢞ࢻୗ⤒⓶ⓗࢻࣞࢼ࣮ࢪࡀᐇࡉࢀ ࡓࠋࣃࣛࢭࢱ࣮ࣔࣝ㸪ࢩࣉࣟࣇࣟ࢟ࢧࢩࣥཬࡧ࣓ࢺࣟࢽࢲࢰ࣮ࣝࡼࡿ⒪ࡀᐇࡉࢀࡓࠋ2013 ᖺ 5 ᭶ 7 ᪥ࡢ⭡㒊ཬࡧ㦵┙㒊㉸㡢Ἴ᳨ᰝ࡛ࡣ㸪」ᩘࡢ㝈ᒁᛶ✸Ꮝࢆ♧၀ࡍࡿእほࢆ᭷ࡍࡿᕥ༙⤖ ⭠㛵㐃ࡍࡿ㧗ᗘࡢ⅖ᛶኚཬࡧ 2 ࡘࡢಶูࡢ⅖ᛶ⭘⒗ࡢᏑᅾࡀ☜ㄆࡉࢀࡓࠋᕥ⤖⭠ഐ⁁ ࡢࢻ࣮ࣞࣥᤄධࡼࡾ㸪⅖ᛶ⭘⒗ࡢ⮋Ồᡂศࡣእぢⓗࡣᾘᩓࡋࡓࠋ⅖ᛶ⭘⒗῝㒊୰ኸࡣ㸪 ṧᏑࡋࡓᚤ㔞ࡢ⮋Ồ㈓␃ࡀࡳࡽࢀࡓࠋ⿕㦂⪅ࡣ㸪2013 ᖺ 5 ᭶ 8 ᪥㏥㝔ࡋࡓࠋ 2013 ᖺ 5 ᭶ 22 ᪥ࡢ⮫ᗋ᳨ᰝ್ࡣ㸪C ᛂᛶࡓࢇⓑ㸦CRP㸧⃰ᗘ 125.8 mg/L㸦NR 0-8 mg/L㸧㸪 ⓑ⾑⌫ᩘ 12.5×109/L ཬࡧዲ୰⌫ᩘ 9.8×109/L ࡛࠶ࡗࡓࠋ⿕㦂⪅ࡣ㸪4 ᪥㛫Ⓨ⇕ࡀᣢ⥆ࡋࡓࡓࡵ㸪 2013 ᖺ 5 ᭶ 23 ᪥ධ㝔ࡋࡓࠋྠ᪥ࡢ㉸㡢Ἴ᳨ᰝ࡛ࡣ㸪1 ࡘࡢ⮋⒆ࡢቑࡀㄆࡵࡽࢀࡓࠋ๓ᅇධ 㝔␃⨨ࡋࡓ⤒⓶ࢻ࣮ࣞࣥࡣ㸪ᗫᾮ㔞ࡀῶᑡࡋ࡚࠸ࡓࡓࡵᢤཤࡉࢀࡓࠋࢻ࣮ࣞࣥࡣ㸪2013 ᖺ 5 ᭶ 24 ᪥ᤄධࡉࢀࡓࠋ࣓ࢺࣟࢽࢲࢰ࣮ࣝ㸪ࣆ࣌ࣛࢩࣜࣥ㸪ࣔ࢟ࢩࢩࣜࣥ㸪ࣞ࣎ࣇࣟ࢟ࢧࢩ ࣥ㸪ࢭࣇࢰࣜࣥࢼࢺ࣒ࣜ࢘㸪hydromorphone ཬࡧ iron sucrose ࡼࡿ㏣ຍ⒪ࡀᐇࡉࢀࡓࠋ 2013 ᖺ 5 ᭶ 25 ᪥ࡢᇵ㣴᳨ᰝ࡛ࡣ㸪࣒࣍ࢸࣜࢩࣥཬࡧࣇࣝࢥࢼࢰ࣮ࣝឤཷᛶࡢᚤ㔞ࡢ Candida lusitanie ࡀ᳨ฟࡉࢀࡓࠋ2013 ᖺ 5 ᭶ 27 ᪥ࡢ⿕㦂⪅ࡢ CRP ⃰ᗘࡣ 11.9 mg/L ࡛࠶ࡗࡓࠋ2013 ᖺ 5 ᭶ 29 ᪥ࡢ S ≧⤖⭠ෆど㙾᳨ᰝ࡛ࡣ㸪⅖ࡣᐶゎࡋ࡚࠸ࡓࠋ⿕㦂⪅ࡣ㸪2013 ᖺ 5 ᭶ 30 ᪥㏥㝔ࡋ ࡓࠋ2013 ᖺ 7 ᭶ 8 ᪥㸪㏣㊧ㄪᰝࡢࡓࡵࡢ⭡㒊ཬࡧ㦵┙㒊 CT ࢫ࡛࢟ࣕࣥ㸪⅖ࡣ᫂ࡽᨵၿࡋ ࡚࠸ࡓࡀ㸪๓ᅇࡢ CT ࢫ࢟ࣕࣥẚ㍑ࡍࡿ㸪ᴟࡵ࡚ⴭ᫂࡞⅖ᛶኚࡀㄆࡵࡽࢀࡓࠋ๓ᅇㄆࡵ ࡽࢀࡓୗ⾜⤖⭠ୖ㠃㞄᥋ࡋࡓ⮋⒆ࡣᨵၿ㸭ᾘᩓࡋ࡚࠸ࡓࠋ 2013 ᖺ 7 ᭶ 19 ᪥㸪⿕㦂⪅ࡣᅇ⭠┤⭠࿀ྜࢆక࠺⥭ᛴ⤖⭠㝖ࡢࡓࡵධ㝔ࡋࡓࠋ⭡ቨཬࡧ ࢺࣛࢶ㠌ᖏ㒊ࡽྑ⤖⭠ࢆྵࡴ᥋ྜ㒊ࡲ࡛ࡢ⭠ቨ㛫ࡳࡽࢀࡓ୰➼ᗘ⒵╔ࡣษ㝖ࡋࡓࠋᕥഃ⤖ ⭠ࢆ㝖ࡁ㸪⤖⭠ࡢ≧ែࡣᝏࡃ࡞ࡗࡓࡀ㸪ᕥഃ⤖⭠ࡣᴟࡵ࡚Ⰿࡀ࡞ࡃ㸪⥺⥔ࡀㄆࡵࡽࢀࡓࠋ⤖ ⭠⤌⧊∦ࡢ⌮Ꮫⓗ᳨ᰝ࡛ࡣ㸪㧗ᗘࡢࢡ࣮ࣟࣥࡼࡃ୍⮴ࡍࡿ≉ᚩࡀࡳࡽࢀࡓࠋࡲࡓ㸪⚄⤒㐣 ᙧᡂཬࡧ⥺⥔㛵㐃ࡢ࠶ࡿᒙᛶ⅖ࡀㄆࡵࡽࢀࡓࠋ⅖ࡣ㸪ᛴᛶཬࡧ៏ᛶࡢ୧᪉ࡀࡳࡽࢀ㸪 㝜❐⮋⒆㸪⤖⭠⭠ቨ⮋⒆㸪⤖⭠࿘ᅖࡢ⮋⒆ᙧᡂ㛵㐃ࡍࡿ⁁₽⒆ཬࡧᛴᛶ⭡⭷⅖ࢆకࡗ࡚࠸ࡓࠋ ⭠ቨཬࡧࣜࣥࣃ⠇⫗ⱆ⭘ࡀ」ᩘㄆࡵࡽࢀ㸪ࢡ࣮ࣟࣥࡢ༳㇟ࢆᙉࡃࡋࡓࠋ⿕㦂⪅ࡣ㸪2013 ᖺ 7 ᭶ 26 ᪥㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2013-01-28 ㈋⾑ MODERATE/ N/ DOSE NOT CHANGED/ Ongoing (43/.) (WORSENING ANEMIA) POSSIBLE NA NOT RECOVERED/NOT - RESOLVED 2013-04-09 ⭡③ MILD/ N/ DOSE NOT CHANGED/ 2013-05-08 (114/58) (LEFT SIDED ABDOMINAL POSSIBLE NA RECOVERED/RESOLVED (143/87) PAIN) 2013-04-15 ᐷờ MODERATE/ N/ DOSE NOT CHANGED/ 2013-05-05 (120/64) (NIGHT SWEATS) POSSIBLE NA RECOVERED/RESOLVED (140/84) 2013-04-28 Ⓨ⇕ MODERATE/ N/ DOSE NOT CHANGED/ 2013-04-28 (133/77) (PYREXIA) POSSIBLE NA RECOVERED/RESOLVED (133/77) 2013-05-02 ࢡ࣮ࣟࣥ MODERATE/ N/ DOSE NOT CHANGED/ 2013-05-08 (137/81) (CROHN'S DISEASE NOT NA RECOVERED/RESOLVED (143/87) WORSENING) RELATED
31 2 (176) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route SACCHARATED IRON OXIDE 2013-02-07 - INTRAVENOUS PARACETAMOL 2013-04-09 2013-05-08 ORAL CIPROFLOXACIN 2013-05-02 2013-05-02 ORAL METRONIDAZOLE 2013-05-02 2013-05-02 ORAL CIPROFLOXACIN 2013-05-03 - INTRAVENOUS METRONIDAZOLE 2013-05-03 2013-05-08 INTRAVENOUS METRONIDAZOLE 2013-05-09 - ORAL
(31) Subject CNTO1275CRD3003-3314-10280
1) Reason for narrative selection SAE Discontinuation of study agent due to AE
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome (Study day I/M) 2012-11 ↓ຊ Y SEVERE/ N/ DRUG WITHDRAWN/ 2012-12-11 - (INTENSE ASTHENIA) PROBABLE NA RECOVERED/RESOLVED (181/125) 2012-11 ࠺ࡘ Y SEVERE/ N/ DRUG WITHDRAWN/ 2012-12-11 - (DEPRESSIVE SYNDROM) PROBABLE NA RECOVERED/RESOLVED (181/125)
3) Baseline Demographic Information ȋȌǣ ͵͵ ǣ ȋȌǣ ͷͺ ǣ ǣ ͳͻͻǦͲ͵Ǧʹ ȋ Ȍǣ ͳͲ
4) Induction Treatment Group Induction study: CNTO1275CRD3001 Randomized Treatment Group: Ustekinumab 130 mg IV Actual Treatment Group: Ustekinumab 130 mg IV
5) Maintenance Treatment Group Assigned Treatment Group: Randomized subject/Responder to ustekinumab IV induction dosing/placebo SC
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2012-06-14 1 Ustekinumab 129.6 mg WEEK 0 MAINTENANCE 2012-08-09 57 Placebo 0 mg WEEK 8 MAINTENANCE 2012-10-09 118 Placebo 0 mg WEEK 12 MAINTENANCE 2012-10-26 135 Ustekinumab 90 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: Y Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: -
31 3 (177) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
8) Induction Baseline Crohn's Disease History Date of diagnosis: 31DEC1995 Disease duration: 16.46 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪⫠㛛࿘ᅖ㸪ᑠ⭠㏆㸭⫶㸭㣗㐨㸪ᾘ⟶እኚ㸦㛵⠇⅖㸭㛵⠇ ③㸧
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: NEVER Stricture complications of (CD): NEVER
10) Concomitant Crohn's Disease-Related Surgeries None reported
11) Concomitant Steroids None reported
12) Narrative Text ⿕㦂⪅ࡣ 3 ṓࡢⓑேዪᛶ࡛㸪2012 ᖺ 6 ᭶ 14 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏࢆ㟼⬦ෆᢞࡉࢀ ࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ࣉࣛࢭ࣎ࢆ⓶ୗᢞ ࡍࡿ⩌ࣛࣥࢲ࣒ࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪ᆶษ㝖㸪⫹ ᄞษ㝖㸦2000 ᖺ㸧㸪ࢲࢢࣛࢫ❐ษ㝖㸦douglasectomy㸧㸦⭼࣊ࣝࢽ⒪ཬࡧ┤⭠ᅛᐃ⾡ࡢࡓࡵ㸪 2007 ᖺ 8 ᭶ 13 ᪥㸧㸪ࣥࣇ࢚ࣝࣥࢨೃ⩌㸪ႚ↮㸪࣓ࢺࢺࣞ࢟ࢧ࣮ࢺᑐࡍࡿࣞࣝࢠ࣮㸪⫢ ⣽⬊⼥ゎ㸪Ⓞᛶኚ㸪↓ຊ㸪㛵⠇③ᑐࡍࡿࣥࣇࣜ࢟ࢩ࣐ࣈᢞཬࡧⓄᛶኚᑐࡍࡿ ࢲ࣒࣐ࣜࣈᢞ࡛࠶ࡗࡓࠋࡲࡓ㸪᪩ᮅࡽᑵᐷࡲ࡛ᣢ⥆ࡍࡿ㛵⠇③ࡀ࠶ࡗࡓࡀ㸪ኪ㛫ぬ㓰ࡣ࡞ ࡗࡓࠋ SAE㸸↓ຊཬࡧ࠺ࡘ㸦November 2012㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ㸪ᢚ࠺ࡘࡢ≉ᚩ㸪↓ឤ㸪ᝒယ㸪ᬯ࠸ᛮ⪃ཬࡧ⑂ປࡢ᪂ࡓ࡞⢭⚄ ≧ࡀ࠶ࡾ㸪2012 ᖺ 11 ᭶ 29 ᪥ධ㝔ࡋࡓࠋ⿕㦂⪅ࡢ 1 ࢝᭶㛫ࡢ㌟≧ែࡢኚࡋ࡚㸪2 kg ࡢ య㔜ῶᑡཬࡧᙉ࠸↓ຊࡀㄆࡵࡽࢀࡓࠋ᪥ᖖⓗ࡞ೃᛶࡢࢣ࣮ࢽࢵࣄೃ⩌㸪1 ᪥ 5 ᅇࡢୗ⑩ཬ ࡧ༗๓୰ࡢᝏᚰ࣭ྤࡀሗ࿌ࡉࢀࡓࠋ⭡㒊ࡢ⌮Ꮫⓗᡤぢ࡛ࡣ㸪ᕥഃཬࡧୖ⭡㒊ࡣ่⃭ᐜ᫆ ᛂࡋ㸪ྑ⭠㦵❐⭘⒗ࡀࢃࢀࡓࠋ⿕㦂⪅ࡣ➽⫗③ࡀࡳࡽࢀࡓࡀ㸪ᮅࡢࡇࢃࡤࡾࡣ࡞ࡗࡓࠋ ゐデ࡚⭜᳝ L3㸪L4㸪L5 ཬࡧ⬚᳝ T2 ⑊③ࢆㄆࡵ㸪ࡲࡓ㸪⬨᳝◳┤㸦stiff spine㸧ࡀㄆࡵࡽ ࢀࡓࠋㄆ▱ᶵ⬟᳨ᰝ࡛ࡣ㸪↓ຊ㸪㍍ᗘࡢ↓ឤ㸪ぬ㓰㞀ᐖࡢ࡞࠸Ⰻዲ࡞ぢᙜ㆑㸪ゝㄒὶᬸᛶ㞀 ᐖ୪ࡧὀពຊཬࡧ㞟୰ຊ㞀ᐖࡀㄆࡵࡽࢀࡓࠋࣟࣥ࣋ࣝࢢヨ㦂ࡢ⤖ᯝ㸪㌟యືᦂࡀࡳࡽࢀ㸪ࣟࣥ ࣋ࣝࢢᚩೃࡣ㝧ᛶ࡛࠶ࡗࡓࠋࡇࡢࡇࡣ㸪ഃᛶ㸦lateralization㸧ࡢ࡞࠸Ᏻᐃ࡞Ṍ⾜ࡼࡾ☜ㄆ ࡉࢀࡓࠋ๓ᗞ᳨ᰝ࡛ࡣ␗ᖖࡣ࡞ࡗࡓࠋࣅࢱ࣑ࣥ B12 ᐃ㔞ヨ㦂࡛ࡣ㸪ࣅࢱ࣑ࣥḞஈࡀㄆࡵࡽࢀ ࡓ㸦0.14 ng/mL㸧ࠋ⚄⤒Ꮫⓗ᳨ᰝࡢᡤぢ࡛ࡣ㸪⫝㢌㒊㢌③㸪࠸ࡃࡘࡢពⓗ㘒ㄒཬࡧⓎㄒὶᬸ ᛶࡢపୗࡀㄆࡵࡽࢀࡓࠋ⿕㦂⪅ࡣ㸪2012 ᖺ 12 ᭶ 3 ᪥㏥㝔ࡋࡓࠋ↓ຊཬࡧ࠺ࡘࡼࡾ㸪 㦂⸆ᢞࡣ୰Ṇࡉࢀࡓࠋ
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13) Other Adverse Events Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2012-07-01 ྤ MILD/ N/ DOSE NOT CHANGED/ Ongoing (18/.) (INTERMITENT VOMITING) NOT NA NOT RECOVERED/NOT - RELATED RESOLVED 2012-09-03 㰯ဗ㢌⅖ MILD/ Y/ DOSE NOT CHANGED/ 2012-09-10 (82/26) (COMMON COLD) NOT N RECOVERED/RESOLVED (89/33) RELATED 2012-10-16 ྤ MILD/ N/ DOSE NOT CHANGED/ 2012-10-16 (125/69) (VOMITING) NOT NA RECOVERED/RESOLVED (125/69) RELATED 2012-10-26 㛵⠇③ MILD/ N/ DOSE NOT CHANGED/ Ongoing (135/79) (ARTHRALGIA) NOT NA NOT RECOVERED/NOT - RELATED RESOLVED 2012-10-27 㛵⠇③ SEVERE/ N/ DOSE NOT CHANGED/ Ongoing (136/80) (DIFFUSE JOINT PAIN) POSSIBLE NA NOT RECOVERED/NOT - RESOLVED 2012-10-27 ⓶ᒁ㠃 MILD/ N/ DOSE NOT CHANGED/ 2012-12-11 (136/80) (ERYTHEMATOUS PLAQUE OF PROBABLE NA RECOVERED/RESOLVED (181/125) THE SCALP)
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route PARACETAMOL 2012-09-04 2012-09-05 ORAL TRAMADOL HYDROCHLORIDE 2012-11-29 2012-12 INTRAVENOUS
(32) Subject CNTO1275CRD3003-3410-10564
1) Reason for narrative selection SAE
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome I/M) 2012-11-12 ᮎᲈᛶᾋ⭘ Y SEVERE/ N/ DOSE NOT CHANGED/ 2012-12-24 (60/4) (OEDEMAS IN BOTH ANKLES) PROBABLE NA RECOVERED/RESOLVED (102/46) 2013-01-10 ࢡ࣮ࣟࣥ Y SEVERE/ N/ DOSE NOT CHANGED/ 2013-01-30 (119/63) (WORSENING OF CROHN'S NOT NA RECOVERED/RESOLVED (139/83) DISEASE) RELATED
3) Baseline Demographic Information ȋȌǣ ͵͵ ǣ ȋȌǣ ͻͷ ǣ ǣ ͳͻͻǦͲͳǦͲͳ ȋ Ȍǣ ͳͷ
4) Induction Treatment Group Induction study: CNTO1275CRD3001 Randomized Treatment Group: Placebo IV Actual Treatment Group: Placebo IV
5) Maintenance Treatment Group Assigned Treatment Group: Non-randomized subject/Non-responder to placebo IV induction dosing and received ustekinumab in maintenance
31 5 (179) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2012-09-14 1 Placebo 0 mg WEEK 0 MAINTENANCE 2012-11-09 57 Ustekinumab 129.6 mg WEEK 0 MAINTENANCE 2012-11-09 57 Placebo 0 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: Y Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: -
8) Induction Baseline Crohn's Disease History Date of diagnosis: 31DEC1992 Disease duration: 19.71 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪⫠㛛࿘ᅖ㸪ᾘ⟶እኚ㸦㛵⠇⅖㸭㛵⠇③㸧
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: PREVIOUS HISTORY Stricture complications of (CD): PREVIOUS HISTORY
10) Concomitant Crohn's Disease-Related Surgeries Surgery Date Result of lack of efficacy? DUE TO STENOSIS OF ILEORECTOSTOMY PATIENT WAS RESECTED AND END 2013-01-18 N ILEOSTOMA WAS PLACED
11) Concomitant Steroids None reported
12) Narrative Text ⿕㦂⪅ࡣ 3 ṓࡢⓑே⏨ᛶ࡛㸪2012 ᖺ 9 ᭶ 14 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ࣉࣛࢭ࣎ࢆ㟼⬦ෆᢞ ࡉࢀࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡎ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏࢆᢞࡉ ࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪ႚ↮㸪㛫Ḟᛶ 㢌③㸪ᛴᛶ⭈㸪ᅇ⭠ S ≧⤖⭠࿀ྜ⾡ࢆక࠺⤖⭠ษ㝖㸦2000 ᖺ㸧㸪⅖ᛶᅇ⭠⊃✽㸦2008 ᖺ 3 ᭶㸧㸪ளࣞ࢘ࢫ≧㸪⮬Ⓨⓗ࡞య㔜ῶᑡ㸦3 ࢝᭶㛫࡛ 16 kg㸧㸪ᅇ⭠⒦Ꮝ㸦⫶ᅇ⭠ཬࡧᅇ⭠⤖ ⭠㸧㸪⭤⬔㡬㒊ࡢ⭡⭷⿕そ⾡ࢆక࠺ᑠ⭠㒊ศษ㝖୪ࡧከⓎᛶᑠ⭠⊃✽ᑐࡍࡿᅇ⭠┤⭠࿀ྜ⾡ 㸦2005 ᖺ㸧࡛࠶ࡗࡓࠋ SAE㸸ᮎᲈᛶᾋ⭘㸦Day 60㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ㸪2012 ᖺ 11 ᭶ 12 ᪥ࡼࡾ୧㊊㛵⠇ᾋ⭘ཬࡧ⅖ࡀࡳࡽࢀ㸪2012 ᖺ 11 ᭶ 22 ᪥ධ㝔ࡋࡓࠋ⫵ኚ㸦๓ᅇࡢ⬚㒊 X ⥺᳨ᰝ࡚ㄆࡵࡽࢀࡓ㸧ࡢྍ⬟ᛶࢆྰᐃࡍࡿࡓ ࡵ㸪2012 ᖺ 11 ᭶ 22 ᪥⬚㒊ࢥࣥࣆ࣮ࣗࢱ᩿ᒙᙳࢫ࢟ࣕࣥࢆᐇࡋࡓࡇࢁ㸪⫵ᡤぢ␗ᖖࡣ ࡞ࡗࡓࠋ⌮Ꮫⓗᡤぢ࡛ࡣ㸪㊊㛵⠇࿘ᅖࡢ㌾⤌⧊Ⓨ㉥ཬࡧ ឤࢆక࠺ⴭ᫂࡞⭘⬽㸦ᕥ㊊ࡼࡾྑ ㊊࡛ᙉ࠸㸧ࡀࡳࡽࢀ㸪୧㊊⬦ᢿࡣゐ▱ྍ⬟࡛࠶ࡾ㸪⓶⇱ࡀㄆࡵࡽࢀࡓࠋ⿕㦂⪅ࡣ 1 ᪥ 15 ᅇ
31 6 (180) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
ࡢỈᵝ౽ࡀ࠶ࡾ㸪ධ㝔๓ࡢ 3 㐌㛫Ⓨ⇕ࡀ࠶ࡗࡓッ࠼ࡓࠋ2012 ᖺ 11 ᭶ 29 ᪥ᐇࡋࡓୗ⫥ࡢ ᰾☢Ẽඹ㬆⏬ീἲ㸦MRI㸧࡛ࡣ㸪⭣㒊⓶ୗ⬡⫫⤌⧊ⴭ᫂࡞ᾋ⭘ࢆㄆࡵ㸪ྑഃ࡛㢧ⴭ࡛࠶ࡾ㸪 ㊊⫼㒊ࡲ࡛ཬࢇ࡛࠸ࡓࠋ㛵⠇⭍ኚࡣ࡞ࡃ㸪ᕥྑ㛵⠇⅖ࡣ㝖እࡉࢀࡓࠋX ⥺᳨ᰝ࡛㸪2 ࡘࡢᖹ 㠃࠾࠸࡚㸪ᕥྑ㊊㛵⠇ୖ㒊ࡣ㸪⮫ᗋⓗព⩏ࡢ࠶ࡿ㏥⾜ᛶኚཪࡣ⬺⮻㸭ள⬺⮻ࡣㄆࡵࡽࢀ࡞ ࡗࡓࠋ2012 ᖺ 11 ᭶ 26 ᪥ࡢ C ᛂᛶࡓࢇⓑ㸦CRP㸧⃰ᗘࡣ㸪199 mg/L㹙ṇᖖ⠊ᅖ㸦NR㸧 <5 mg/L㹛࡛࠶ࡗࡓࠋ2012 ᖺ 12 ᭶ 3 ᪥ᐇࡋࡓ౽୰ࡢࢡࣟࢫࢺࣜࢪ࣒࣭࢘ࢹࣇࢩࣞẘ⣲᳨ ᰝࡣ㝜ᛶ࡛࠶ࡗࡓࠋ2012 ᖺ 12 ᭶ 5 ᪥ࡢデᐹ࡛ࡣ㸪ᾋ⭘ࡢ⮬↛㏥⾜ࡀㄆࡵࡽࢀࡓࠋࣥࣆࢩࣜࣥ 㸭ࢫࣝࣂࢡࢱ࣒㸦Unacid㸧㸪ࣈࣉࣟࣇ࢙ࣥ㸪ࢰࣝࣆࢹ࣒㓇▼㓟ሷ㸪ᅛᐃ⾡㸪Lapaset bandages㸪 ᣙୖ㸪෭༷ཬࡧ࣓ࣔࢱࢰࣥࣇࣛࣥ࢝ࣝ࣎ࣥ㓟࢚ࢫࢸࣝࡼࡿ⒪ࡀᐇࡉࢀࡓࠋ⿕㦂⪅ࡣ㸪2012 ᖺ 12 ᭶ 7 ᪥㏥㝔ࡋࡓࠋ SAE㸸ࢡ࣮ࣟࣥ㸦Day 119㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ㣗ᦤྲྀࡣ↓㛵㐃ࡢ㛫Ḟᛶ⭡③ࡀ࠶ࡾ㸪1 ᪥ 0㹼12 ᅇࡢ㠀ฟ⾑ᛶ Ỉᵝ౽ࡀࡳࡽࢀࡓࡓࡵ㸪2013 ᖺ 1 ᭶ 7 ᪥ධ㝔ࡋࡓࠋ⌮Ꮫⓗᡤぢ࡛ࡣ㸪␗ᖖࡣ࡞ࡗࡓࠋྠ᪥ࡢ ୖ⭡㒊㉸㡢Ἴ᳨ᰝ࡛ࡣ㸪ᗈ⠊࡞㩭⣚Ⰽࡢ⅖ᛂ୍⮴ࡋ࡚㸪ᒙᵓ㐀ࡢ࡞႙ኻ㸪10 cm ௨ୖ ࢃࡓࡿᴟᗘࡢቨ⫧ཌཬࡧᗈ⠊࡞⾑ࡀࡳࡽࢀࡓࠋ⣙ 3 cm ࡢ⊃㒊⥆ࡁ㸪ࣃ࣮࣡ࢻࢵࣉ࣮ࣛἲ ࡼࡿࢫ࡛࢟ࣕࣥࡣ㸪࿘ᅖቨ⫧ཌཬࡧᒙᵓ㐀ᾘኻࢆక࠺⾑ࡀࡳࡽࢀࡓࠋ࿀ྜ㒊㸦⅖㉳ ᅉࡋࡓኚࡀࡳࡽࢀࡓ㸧࠾ࡅࡿ⽸ືࡣㄆࡵࡽࢀࡎ㸪⊃✽ࡀᶵ⬟ⓗ㛵㐃ࡀ࠶ࡿᛮࢃࢀࡓࠋ 2013 ᖺ 1 ᭶ 10 ᪥㸪⿕㦂⪅ࡣ⮫ᗋⓗཬࡧᨺᑕ⥺Ꮫⓗ≧ࡀࡳࡽࢀࡿᶵᲔⓗ㸦ள㸧ࣞ࢘ࢫࢆⓎ ⌧ࡋࡓࠋ㧗ᗘࡢ⭡③㸪ࡁ࡞⭠㞧㡢ཬࡧ⭡㒊༢⣧ X ⥺᳨ᰝ࡛౫↛ࡳࡽࢀࡿ standing loops ࢆకࡗ ࡚࠸ࡓࠋಖᏑ⒪ἲୗ࡛㸪ᩘ㛫௨ෆ≧ࡣᨵၿࡋࡓࠋ2013 ᖺ 1 ᭶ 11 ᪥ࡢ౽ᇵ㣴᳨ᰝ࡛ࡣ㸪ࢧ ࣝࣔࢿࣛ㸪㉥⑩⳦㸪࢚ࣝࢩࢽཬࡧ࢝ࣥࣆࣟࣂࢡࢱ࣮ࡢቑṪࡣㄆࡵࡎ㸪ࢡࣟࢫࢺࣜࢪ࣒࢘ᑐࡍ ࡿ᳨ᰝࡶ㝜ᛶ࡛࠶ࡗࡓࠋ2013 ᖺ 1 ᭶ 15 ᪥ࡢ⭡㒊 MRI ࡛ࡣ㸪ᗈ࠸⠊ᅖࢃࡓࡾ࿀ྜ㒊㩭⣚Ⰽࡢ ࢡ࣮ࣟࣥࡢᚩೃࡀࡳࡽࢀ㸪ࢃࡎ imbibing and surrounding fluid ࢆకࡗ࡚࠸ࡓࠋࡲࡓ㸪௨ୗࡢ ᡤぢࡀㄆࡵࡽࢀࡓ㸸┤⭠⅖άᛶࢆక࠺༊ᇦᛶኚ㸪ᑠ⭠ࢡ࣮ࣟࣥࡢ༊ᇦᛶኚ࡞ࡋ㸪ྑ ⫠㛛࿘ᅖ㒊ᩬⅬ≧ಙྕࡢቑຍ㸪」ᩘࡢᛂᛶࡢ⭠㛫⭷ࣜࣥࣃ⠇㸪⮫ᗋⓗព⩏ࡢ࡞࠸㔞ࡢ㐟㞳⭡ ⭍ෆᾮ㸪⫢⮚ཬࡧᕥ⭈ᑠᄞ⬊ࠋ┤⭠デ࡛ࡣ㸪⫠㛛⦕ࡼࡾ 4 cm ㏆⊃✽ࢆㄆࡵ㸪ᡭᣦࡢ㏻㐣 ࡣྍ⬟࡛࠶ࡗࡓࠋ⊃✽๓ᣑᙇࡼࡾ㸪⊃✽➃ࡽ⣙ 15 cm ࡲ࡛┤⭠ෆど㙾ࡢ㏻㐣ࡀྍ⬟࡞ࡗ ࡓࠋ2013 ᖺ 1 ᭶ 18 ᪥㸪ᅇ⭠┤⭠࿀ྜ㒊ࢆศ㞳ࡋ㸪ᅇ⭠ᮎ➃࡛ࢫࢺ࣮࣐ࢆ㐀タࡋࡓࠋࢭࣇࣟ࢟ ࢩ࣒ཬࡧ࣓ࢺࣟࢽࢲࢰ࣮ࣝࡼࡿ㏣ຍ⒪ࡀᐇࡉࢀࡓࠋࡲࡓ㸪⾡ᚋ③ᑐࡋ㸪mebeverine ཬࡧ ࣓ࢱ࣑ࢰ࣮ࣝࢼࢺ࣒ࣜ࢘ࡀᢞࡉࢀࡓࠋ2013 ᖺ 1 ᭶ 21 ᪥ࡢ⌮Ꮫⓗ᳨ᰝ࡛ࡣ㸪ᗈ⠊ᅖࣇࣞࢢ ࣮ࣔࢿᛶࡢ៏ᛶࡢ㩭⣚Ⰽࡢ⅖ࡀㄆࡵࡽࢀࡓࡀ㸪␗ᙧᡂཬࡧᝏᛶ⭘⒆ࡣ࡞ࡗࡓࠋ⾡ᚋ㸪⿕㦂 ⪅ࡣ⭠ࢺࢽ࣮ཬࡧࢫࢺ࣮࣐ഐ⮋⒆ࢆⓎ⌧ࡋࡓࠋ2013 ᖺ 1 ᭶ 22 ᪥ࡢ⿕㦂⪅ࡢ CRP ⃰ᗘࡣ 102 mg/L㸪ⓑ⾑⌫ᩘࡣ 7.63/nL ࡛࠶ࡗࡓࠋ⿕㦂⪅ࡣ㸪2013 ᖺ 1 ᭶ 30 ᪥㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2012-11 㛵⠇③ MILD/ N/ DOSE NOT CHANGED/ Ongoing - (ARTHRALGIA) NOT NA NOT RECOVERED/NOT - RELATED RESOLVED 2012-11-22 ⾑⟶⭘ MILD/ N/ DOSE NOT CHANGED/ Ongoing (70/14) (HAEMANGIOMA) NOT NA NOT RECOVERED/NOT - RELATED RESOLVED
31 7 (181) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2012-11-22 ⭁⭘ MILD/ N/ DOSE NOT CHANGED/ Ongoing (70/14) (SPLENOMEGALIA) NOT NA NOT RECOVERED/NOT - RELATED RESOLVED 2012-12-07 ࢫࣃࣛࢠࣥ㓟࣑ࣀࢺࣛࣥࢫࣇ࢙ MILD/ N/ DOSE NOT CHANGED/ 2013-01-07 (85/29) ࣮ࣛࢮቑຍ DOUBTFUL NA RECOVERED/RESOLVED (116/60) (INCREASED AST) 2012-12-23 ᝏᚰ MILD/ N/ DOSE NOT CHANGED/ 2012-12-23 (101/45) (NAUSEA) NOT NA RECOVERED/RESOLVED (101/45) RELATED 2012-12-30 ᝏᚰ MILD/ N/ DOSE NOT CHANGED/ 2012-12-30 (108/52) (NAUSEA) NOT NA RECOVERED/RESOLVED (108/52) RELATED 2013-01 㯞⑷ᛶࣞ࢘ࢫ MILD/ N/ DOSE NOT CHANGED/ 2013-01 - (POST OP INTESTINAL ATONY) NOT NA RECOVERED/RESOLVED - RELATED 2013-01 ஈᒀ MODERATE/ N/ DOSE NOT CHANGED/ 2013-01 - (OLIGUIA) NOT NA RECOVERED/RESOLVED - RELATED 2013-01 ࢫࢺ࣮࣐㒊⭘⒆ MODERATE/ Y/ DOSE NOT CHANGED/ Ongoing - (POSTSURGERY PARASTOMAL NOT Y NOT RECOVERED/NOT - ABSCESS) RELATED RESOLVED 2013-01-15 ⫢ᄞ⬊ MILD/ N/ DOSE NOT CHANGED/ Ongoing (124/68) (SMALL LIVER CYST LEFT) NOT NA NOT RECOVERED/NOT - RELATED RESOLVED 2013-01-15 ⭈ᄞ⬊ MILD/ N/ DOSE NOT CHANGED/ Ongoing (124/68) (SMALL KIDNEY CYST LEFT) NOT NA NOT RECOVERED/NOT - RELATED RESOLVED 2013-01-18 ⾡ᚋ㈋⾑ SEVERE/ N/ DOSE NOT CHANGED/ 2013-01-29 (127/71) (POST OP ANAEMIA) NOT NA RECOVERED/RESOLVED (138/82) RELATED 2013-01-31 ࣥࣇ࢚ࣝࣥࢨ MODERATE/ Y/ DOSE NOT CHANGED/ 2013-02-06 (140/84) (INFLUENZA) NOT N RECOVERED/RESOLVED (146/90) RELATED
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route IBUPROFEN 2012-11-26 2012-12-04 ORAL SULTAMICILLIN TOSILATE 2012-11-26 2012-12-05 INTRAVENOUS ZOLPIDEM TARTRATE 2012-11-28 2012-12-06 ORAL CEFUROXIME 2013-01 2013-01 INTRAVENOUS INVESTIGATIONAL DRUG 2013-01 2013-01 INTRAVENOUS LOPERAMIDE HYDROCHLORIDE 2013-01 2013-04 ORAL METRONIDAZOLE 2013-01 2013-01 INTRAVENOUS
(33) Subject CNTO1275CRD3003-4603-10805
1) Reason for narrative selection SAE
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome I/M) 2013-02-12 ࢡ࣮ࣟࣥ(CROHN'S Y SEVERE/ N/ DOSE NOT CHANGED/ 2013-02-21 (106/48) FLARE) POSSIBLE NA RECOVERED/RESOLVED (115/57) 2013-04-14 ࢡ࣮ࣟࣥ Y SEVERE/ N/ DOSE NOT CHANGED/ 2013-07-05 (167/109) (WORSENING CROHNS NOT NA RECOVERED/RESOLVED WITH (249/191) DISEASE) RELATED SEQUELAE
31 8 (182) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
3) Baseline Demographic Information Age (years): 5 Sex: Female Weight (kg): 71.2 Race: White Date of birth: - Height (cm): 185
4) Induction Treatment Group Induction study: CNTO1275CRD3001 Randomized Treatment Group: Ustekinumab 130 mg IV Actual Treatment Group: Ustekinumab 130 mg IV
5) Maintenance Treatment Group Assigned Treatment Group: Randomized subject/Responder to ustekinumab IV induction dosing/placebo SC
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2012-10-30 1 Ustekinumab 129.6 mg WEEK 0 MAINTENANCE 2012-12-27 59 Placebo 0 mg WEEK 8 MAINTENANCE 2013-02-20 114 Ustekinumab 90 mg WEEK 12 MAINTENANCE 2013-03-20 142 Placebo 0 mg WEEK 16 MAINTENANCE 2013-04-08 161 Ustekinumab 90 mg WEEK 20 MAINTENANCE 2013-05-13 196 Placebo 0 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: Y Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: -
8) Induction Baseline Crohn's Disease History Date of diagnosis: 03DEC2001 Disease duration: 10.91 years Involved areas: ᅇ⭠ཬࡧ⤖⭠
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: NEVER Stricture complications of (CD): NEVER
10) Concomitant Crohn's Disease-Related Surgeries Surgery Date Result of lack of efficacy? ேᕤ⫠㛛ࡢタ⨨ 2013-06-17 Y ᅇ⭠⒦㐀タࡢ⿵ṇ 2013-06-25 N
11) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 0 PREDNISONE 10 mg 10 mg WEEK 4 MAINTENANCE PREDNISONE 7.5 mg 7.5 mg WEEK 4 MAINTENANCE PREDNISONE 5 mg 5 mg SAFETY FOLLOW-UP MAINTENANCE PREDNISONE 40 mg 40 mg
31 9 (183) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
12) Narrative Text ⿕㦂⪅ࡣ 5 ṓࡢⓑேዪᛶ࡛㸪2012 ᖺ 10 ᭶ 30 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏࢆ㟼⬦ෆᢞࡉ ࢀࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ࣉࣛࢭ࣎ࢆ⓶ୗᢞ ࡍࡿ⩌ࣛࣥࢲ࣒ࡉࢀࡓࠋ⿕㦂⪅ࡣࡑࡢᚋ㸪week 8 ᮏ 90 mg ࢆ q8w ࡛⓶ୗᢞࡍࡿࡼ ࠺⏝㔞ㄪ⠇ࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪╀㸪 ࡓࢇⓑᒀ㸪ࢫࢸ࣮ࢪ 3 ࡢ៏ᛶ⭈ᶵ⬟㸪⭡⭍㙾ୗ⫹ᄞษ㝖㸦2011 ᖺ 3 ᭶ 25 ᪥㸧㸪ᅇ⭠⒦㐀 タ㸪ೃᛶ⫹▼㸪ႚ↮ཬࡧ⸆ࣞࣝࢠ࣮㹙࣓ࢧࣛࢪࣥ㸦㛫㉁ᛶ⭈⅖㸧ཬࡧ࣓ࣝ࢝ࣉࢺࣉࣜࣥ 㸦⮅⅖㸧㹛࡛࠶ࡗࡓࠋ SAE㸸ࢡ࣮ࣟࣥ㸦Day 106㸧 CIOMS ཬࡧṔࡼࡿ㸪 2013 ᖺ 2 ᭶ 12 ᪥㸪⿕㦂⪅ࡣ 2 㐌㛫⥅⥆ࡍࡿᝏᚰཬࡧ⭡③㸪ྤ㸪 㣗ḧ႙ኻࢆッ࠼ධ㝔ࡋࡓࠋ⿕㦂⪅ࡣ 1 ᪥ 5㹼10 ᅇࡢ⢓⾑ᛶ࡛ࡣ࡞࠸ࡀⷧ࠸Ỉᵝ౽ཬࡧ⮬Ꮿ࡛ࡢⓎ ⇕㸦38.4°C㸧ࡶッ࠼ࡓࠋ⮫ᗋ᳨ᰝ್㸦ᐇ᪥᫂㸧ࡣ C ᛂᛶࡓࢇⓑ㸦CRP㸧⃰ᗘ 147 mg/L㸪⣒ ⌫యࢁ㐣㔞㸦GFR㸧33 mL/min/1.73 m2㹙ṇᖖ⠊ᅖ㸦NR㸧᫂㹛࡛࠶ࡗࡓࠋᒀỿ´ࡣᚤ㔞ࡢࡓࢇⓑ 㝧ᛶཬࡧᚤ㔞ࡢ࣊ࣔࢢࣟࣅࣥ㝧ᛶ࡛࠶ࡗࡓࠋⓑ⾑⌫ࡣࡳࡽࢀࡎ㸪ள◪㓟ሷࡣ㝜ᛶ࡛࠶ࡗࡓࠋ౽ᇵ 㣴᳨ᰝ࡛ࡣቑṪࡣㄆࡵࡽࢀࡎ㸪ࢡࣟࢫࢺࣜࢪ࣒࢘㝜ᛶ࡛࠶ࡗࡓࠋ⭡㒊㉸㡢Ἴࢫ࡛࢟ࣕࣥࡣ㸪Ỉ⭈ ࡢᚩೃࡣ࡞ࡃ㸪ኚࡢ࡞࠸ᑠࡉࡃ echo-rich ࡞⭈⮚ീ࡛࠶ࡗࡓࠋ⿕㦂⪅ࡢ౽୰࢝ࣝࣉࣟࢸࢡࢳ ࣥ⃰ᗘࡣୖ᪼ࡋ࡚࠸ࡓࠋෆど㙾᳨ᰝᡤぢ࡛ࡣ㸪㍍ᗘࡽ୰➼ᗘࡢ⤖⭠ࡢ⅖ࡀ♧၀ࡉࢀ㸪⌮⤌ ⧊Ꮫⓗ☜ㄆࡉࢀࡓࠋ⒪ࡣ㸪ࢳ࣑ࣥⅬ㸪࣒࢝ࣜ࢘ࢆῧຍࡋࡓ⏕⌮㣗ሷỈⅬཬࡧ⤒⭠ᰤ 㣴ἲࡀ⏝࠸ࡽࢀࡓࠋ⿕㦂⪅ࡣ㸪2013 ᖺ 2 ᭶ 21 ᪥㏥㝔ࡋࡓࠋ SAE㸸ࢡ࣮ࣟࣥ㸦Day 167㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2013 ᖺ 4 ᭶ 14 ᪥⭡③㸪㣗ḧ႙ኻ㸪ᝏᚰཬࡧ⬺Ỉࡼࡾධ㝔ࡋ ࡓࠋ⿕㦂⪅ࡣ⭡③ࡢቑᙉ㸪1 ᪥ 8 ᅇࡢ౽㸪5 ᪥㛫ࢃࡓࡿ㣗≀ᦤྲྀࡢῶᑡཬࡧ⤖⭠ࢡ࣮ࣟࣥ ࡢᝏࡀㄆࡵࡽࢀࡓࠋ⌮Ꮫⓗ᳨ᰝ࡛ࡣ㸪⿕㦂⪅ࡣ୰➼ᗘࡢ≧࡛㸪⢓⭷ࡣ⇱ࡋ㸪య ࡣ 38.8°C ࡛࠶ࡗࡓࠋ⭡㒊ࡣᰂ㌾࡛ṇᖖ࡞⽸ືࡀ࠶ࡾ㸪ࡸࡸ hypertympanic ࡛㸪ゐ▱ྍ⬟࡞␗ᖖ࡞ ᢠࡣ࡞ࡗࡓࠋ⮫ᗋ᳨ᰝ್ࡣ㸪CRP ⃰ᗘ 142 mg/L㸦NR<8 mg/L㸧㸪ࢡࣞࢳࢽࣥ 210 ȝmol/L 㸦NR 49-90 ȝmol/L㸧㸪᥎⟬⣒⌫యࢁ㐣㔞㸦eGFR㸧21 ȝmol/L/min㸦NR>60 ȝmol/L/min㸧࡛࠶ࡗࡓࠋ ධ㝔୰㸪⿕㦂⪅ࡣ⤒⭠ࢳ࣮ࣗࣈᰤ㣴ࢆཷࡅ㸪ࣜࢩࣀࣉࣜࣝ㸪ࢺ࣐ࣛࢻ࣮ࣝ㸪࢜ࣥࢲࣥࢭࢺࣟࣥ㸪 ࣃࣛࢭࢱ࣮ࣔࣝཬࡧሷ࢝ࣝࢩ࣒࢘ࡼࡿ⒪ࢆཷࡅࡓࠋ2013 ᖺ 4 ᭶ 15 ᪥ࡢ┤⭠ S ≧⤖⭠㙾᳨ ᰝ࡛ࡣ㸪」ᩘࡢ₽⒆ࢆక࠺༊ᇦᛶࡢ┤⭠ S ≧⤖⭠⅖ࡀㄆࡵࡽࢀࡓࠋ⿕㦂⪅ࡣ㸪2013 ᖺ 4 ᭶ 17 ᪥ ㏥㝔ࡋࡓࠋ ⿕㦂⪅ࡣ 2013 ᖺ 6 ᭶ 14 ᪥⭡③ࡢቑᙉ㸪Ⓨ⇕ཬࡧ⢓ᾮࢆక࠺Ỉᵝ౽ࡢࡓࡵධ㝔ࡋࡓࠋ⿕㦂 ⪅ࡣᩘ᪥㛫ࢃࡓࡿ⤒ཱྀᦤྲྀⰋࡼࡾయ㔜ࡀ 2 㐌㛫࡛ 3 kg ῶᑡࡋࡓࠋ⭡㒊 X ⥺ീ࡛ࡣ㸪ୗ⾜ ⤖⭠ẕᣦᅽീࢆక࠺ⴭࡋ࠸ࣁ࢘ࢫࢺࣛࡢῶᑡࢆㄆࡵ㸪⭠⅖ࡀ♧၀ࡉࢀࡓࠋ┣⭠ࡣୖ⾜⤖⭠ ཬࡧᶓ⾜⤖⭠ྠᵝ⭾ᙇࡋ࡚࠸ࡓࠋ2013 ᖺ 6 ᭶ 15 ᪥ࡢ⮫ᗋ᳨ᰝ್ࡣ㸪CRP ⃰ᗘ 43 mg/L㸪࣊ ࣔࢢࣟࣅࣥ 4.8 mmol/L ࡛࠶ࡗࡓࠋ⒪ࡣ nadoparin㸪piritramide㸪ࣉࣞࢻࢽࢰࣟࣥ㸪ࢺ࣐ࣛࢻ࣮ ࣝ㸪ࣃࣛࢭࢱ࣮ࣔࣝ㸪࢜ࣥࢲࣥࢭࢺࣟࣥࡀ⏝࠸ࡽࢀࡓࠋ⿕㦂⪅ࡣ㸪2013 ᖺ 6 ᭶ 16 ᪥⭡⭍㙾ୗ ࡛Ꮝᘧ㸦࣮ࣝࣉᘧ㸧ᅇ⭠⒦㐀タ⾡ࢆཷࡅࡓࠋ⒪ࡣ phytomedadione㸪acenocoumarol㸪zinc sulphate heptahydrate㸭ࣅࢱ࣑ࣥ㸭ᚤ㔞ඖ⣲㸪ࣉࣞࢻࢽࢰࣟࣥ㸪ሷ࣒࢝ࣜ࢘㸪ᚤ㔞ඖ⣲㸪⥲ྜࣅ
32 0 (184) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
ࢱ࣑ࣥ㸪ࢳ࣑ࣥཬࡧ࣊ࣃࣜࣥࡀ⏝࠸ࡽࢀࡓࠋ2013 ᖺ 6 ᭶ 19 ᪥㸪⿕㦂⪅ࡢⓑ⾑⌫ᩘࡀቑຍ ࡋ㸪ෆ࣊ࣝࢽཪࡣ⮋⒆ࡀࢃࢀࡓࠋ2013 ᖺ 6 ᭶ 21 ᪥ࡢ⭡㒊ࢥࣥࣆ࣮ࣗࢱ᩿ᒙᙳࢫ࡛࢟ࣕࣥ ࡣ㸪ᒁᡤⓗ࡞⬡⫫⤌⧊ࡢ࣊ࣝࢽࢆక࠺➽⭷ࡢ⨨࡛ࡢ㛢ሰᇶ࡙ࡃᑠ⭠ࣞ࢘ࢫ㸪ᶓ⾜⤖⭠࡛ ࡢ⭠ቨ⫧ཌῶᑡཬࡧୖ⾜⤖⭠࡛௨๓ࡼࡾㄆࡵࡽࢀ࡚࠸ࡓỗ⭠⅖ࡀㄆࡵࡽࢀࡓࠋ⿕㦂⪅ࡣ㸪2013 ᖺ 6 ᭶ 25 ᪥ᅇ⭠⒦㐀タࡢ⿵ṇᡭ⾡ࢆཷࡅࡓࠋ⿕㦂⪅ࡣ㸪㠀⤒ཱྀᰤ㣴ࢆཷࡅࡓࠋධ㝔୰㸪 ⒪⏝㔞ࡢ nadroparin ࡢᢞ୰⫠㛛ฟ⾑ࢆッ࠼ࡓࠋ⃰ཌ㉥⾑⌫ 2 ༢ࢆᢞࡉࢀ㸪ᢠจᅛ ࡼࡿ⒪ࡣ୰Ṇࡉࢀࡓࠋ⿕㦂⪅ࡣ㸪2013 ᖺ 7 ᭶ 5 ᪥㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2013-04-19 ῝㒊㟼⬦⾑ᰦ SEVERE/ N/ DOSE NOT CHANGED/ 2013-05-06 (172/114) (DEEP VEIN THROMBOSIS RIGHT NOT NA RECOVERED/RESOLVED (189/131) LEG) RELATED 2013-05-16 ⫶㣗㐨㏫ὶᛶᝈ MILD/ N/ DOSE NOT CHANGED/ 2013-06-08 (199/141) (ESOPHAGAL REFLUX) NOT NA RECOVERED/RESOLVED (222/164) RELATED
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route ONDANSETRON 2013-04-08 - ORAL ACENOCOUMAROL 2013-04-19 - ORAL NADROPARIN CALCIUM 2013-04-19 2013-07-02 SUBCUTANEOUS POTASSIUM CHLORIDE 2013-04-19 2013-04-20 INTRAVENOUS DRIP METOCLOPRAMIDE 2013-05-13 - ORAL OMEPRAZOLE 2013-05-16 2013-06-08 ORAL PARACETAMOL 2013-06-14 - ORAL MIDAZOLAM 2013-06-14 2013-06-15 ORAL PIRITRAMIDE 2013-06-16 2013-06-18 SUBCUTANEOUS
(34) Subject CNTO1275CRD3003-5606-10411
1) Reason for narrative selection SAE Event of interest: Serious infection
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome (Study day I/M) 2013-01-16 ࢘ࣝࢫឤᰁ Y MODERATE/ Y/ NOT APPLICABLE/ 2013-01-18 (178/122) (VIRAL INFECTION) POSSIBLE Y RECOVERED/RESOLVED (180/124)
3) Baseline Demographic Information ȋȌǣ ʹ ǣ ȋȌǣ ǤͶ ǣ ǣ ͳͻͺǦͲͳǦͳͳ ȋ Ȍǣ ͳͺ
4) Induction Treatment Group Induction study: CNTO1275CRD3001 Randomized Treatment Group: Ustekinumab 130 mg IV Actual Treatment Group: Ustekinumab 130 mg IV
32 1 (185) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
5) Maintenance Treatment Group Assigned Treatment Group: Non-randomized subject/Non-responder to ustekinumab IV induction dosing and received ustekinumab in maintenance
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2012-07-23 1 Ustekinumab 129.6 mg WEEK 0 MAINTENANCE 2012-09-17 57 Ustekinumab 90 mg WEEK 0 MAINTENANCE 2012-09-17 57 Placebo 0 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: Y Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: -
8) Induction Baseline Crohn's Disease History Date of diagnosis: 30NOV2008 Disease duration: 3.65 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪ᾘ⟶እኚ㸦㛵⠇⅖㸭㛵⠇③㸧
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: PREVIOUS HISTORY Fistula: CURRENTLY PRESENT Stricture complications of (CD): NEVER
10) Concomitant Crohn's Disease-Related Surgeries None reported
11) Concomitant Steroids Visit Drug Dose Prednisone equivalent SAFETY FOLLOW-UP MAINTENANCE HYDROCORTISONE 100 mg -
12) Narrative Text ⿕㦂⪅ࡣ 2 ṓࡢⓑே⏨ᛶ࡛㸪2012 ᖺ 7 ᭶ 23 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏࢆ㟼⬦ෆᢞࡉࢀ ࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡎ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏࢆᢞࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣᯤⲡ⇕࡛࠶ࡗࡓࠋ SAE/Serious infection㸸࢘ࣝࢫឤᰁ㸦Day 178㸧 CIOMS ࡼࡿ㸪2013 ᖺ 9 ᭶ 17 ᪥㸪⿕㦂⪅ࡣ㦂⸆ࡢ᭱⤊ᢞࢆཷࡅ㸪Ᏻᛶࡢ㏣㊧ㄪᰝ ୰࡛࠶ࡗࡓࠋ2013 ᖺ 1 ᭶ 9 ᪥㸪⿕㦂⪅ࡣࢨࢳ࢜ࣉࣜࣥཬࡧࣥࣇࣜ࢟ࢩ࣐ࣈࢆᢞࡉࢀࡓࠋ ⿕㦂⪅ࡣࡑࡢᚋ 2013 ᖺ 1 ᭶ 16 ᪥㸪㢡③ࢆక࠺Ⓨ⇕㸪⬚㒊⤠ᢋឤ㸪ᝏᚰཬࡧࡑ࠺ࢆⓎ⌧ࡋ ࡓࠋ⿕㦂⪅ࡣ㢡ࢆ㛤ࡅࡿࡇࡀ࡛ࡁࡎ㸪ᒀኻ⚗ࢆక࠺⾑⟶㏞㉮⚄⤒ᛶ⬺ࡀㄆࡵࡽࢀࡓࠋ⿕㦂⪅ ࡣ㸪≧Ⓨ⌧ࡢ 24 㛫ᚋ㸦⾑⟶㏞㉮⚄⤒ᛶ⬺ࢆ⮬Ꮿ࡛Ⓨ⌧ࡋࡓ 5 㛫ᚋ㸧ᩆᛴ་⒪㒊㛛ࢆ ཷデࡋ㸪㛵⠇③ཬࡧⓎ⇕ࡢࡓࡵධ㝔ࡋࡓࠋ⿕㦂⪅ࡣ㸪㢕㒊ゐ▱ྍ⬟࡞ࣜࣥࣃ⠇ཬࡧ᫂ࡽ࡞ 㢦㠃⭘⬽ࡀㄆࡵࡽࢀࡓࡀ㸪⩈᫂ࡣ࡞ࡗࡓࠋ2013 ᖺ 1 ᭶ 16 ᪥㸪⿕㦂⪅ࡢⓑ⾑⌫ᩘࡣ 16.9×109/L㹙ṇᖖ⠊ᅖ㸦NR㸧4.2-11.2×109/L㹛࡛࠶ࡗࡓࠋ⬚㒊ཬࡧ⭡㒊 X ⥺ീࡣṇᖖ࡛࠶ࡗࡓࠋ
32 2 (186) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
᰾☢Ẽඹ㬆⏬ീἲ࡛ࡣኚࢆㄆࡵࡎ㸪ഃ㢌ୗ㢡㛵⠇ࡣṇᖖ࡛࠶ࡾ㸪㍍ᗘࡢ㰯⭍⢓⭷ᝈࡀㄆࡵ ࡽࢀࡓࠋ⭜᳝✸่࡛ࡣ␗ᖖࡀ࡞ࡗࡓࠋ⾑ᾮ㸪⬻⬨㧊ᾮཬࡧ┿⳦ᇵ㣴᳨ᰝࡢ⤖ᯝࡣ㝜ᛶ࡛࠶ࡾ㸪 ࢘ࣝࢫࡢ࣏࣓࣮ࣜࣛࢮ㐃㙐ᛂࡶྠᵝ㝜ᛶ࡛࠶ࡗࡓࠋ⒪ࡣ㸪㟼⬦ෆ⿵ᾮ㸪࣋ࣥࢪࣝ࣌ࢽ ࢩࣜࣥ㸪࣓ࢺࣟࢽࢲࢰ࣮ࣝ㸪ࢩࢡࣟࣅࣝཬࡧ㙠③⸆ࡀ⏝࠸ࡽࢀࡓࠋ⿕㦂⪅ࡣ㸪2013 ᖺ 1 ᭶ 18 ᪥㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2012-08-20 㛵⠇③ MODERATE/ N/ DOSE NOT CHANGED/ Ongoing (29/.) (RIGHT HIP PAIN) NOT NA NOT RECOVERED/NOT - RELATED RESOLVED 2012-09-17 㢌③ MILD/ N/ DOSE NOT CHANGED/ 2012-09-18 (57/1) (HEADACHE) PROBABLE NA RECOVERED/RESOLVED (58/2) 2012-09-21 ⫠㛛࿘ᅖ③ MILD/ N/ DOSE NOT CHANGED/ 2012-10-05 (61/5) (PERIANAL PAIN) DOUBTFUL NA RECOVERED/RESOLVED (75/19) 2012-09-21 ┤⭠ฟ⾑ MILD/ N/ DOSE NOT CHANGED/ 2012-10-05 (61/5) (RECTAL BLEEDING) DOUBTFUL NA RECOVERED/RESOLVED (75/19) 2012-10-02 ➽᩿ MODERATE/ N/ DOSE NOT CHANGED/ 2012-11-22 (72/16) (LEFT LEG MUSCLE TEAR) NOT NA RECOVERED/RESOLVED (123/67) RELATED 2012-10-20 㢌③ MILD/ N/ DOSE NOT CHANGED/ 2013-03-01 (90/34) (HEADACHE) DOUBTFUL NA RECOVERED/RESOLVED (222/166) 2012-10-20 ࡑ࠺ MILD/ N/ DOSE NOT CHANGED/ 2013-04-01 (90/34) (ITCHY ELBOWS) POSSIBLE NA RECOVERED/RESOLVED (253/197) 2012-10-20 ⓶⬺ MODERATE/ N/ DOSE NOT CHANGED/ 2013-04-01 (90/34) (DESQUAMATING PALMAR POSSIBLE NA RECOVERED/RESOLVED (253/197) SURFACE) 2013-01-16 ኻ⚄ MODERATE/ N/ NOT APPLICABLE/ 2013-01-16 (178/122) (SYNCOPE VASOVAGAL) POSSIBLE NA RECOVERED/RESOLVED (178/122)
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route PARACETAMOL 2012-10-10 2012-10-10 ORAL NEUTROGENA /04014001/ 2012-10-20 - TOPICAL BENZYLPENICILLIN POTASSIUM 2013-01-16 2013-01-18 INTRAVENOUS CODEINE PHOSPHATE 2013-01-16 2013-01-16 ORAL CYCLIZINE 2013-01-16 2013-01-16 INTRAVENOUS DIAZEPAM 2013-01-16 2013-01-16 ORAL GENERAL NUTRIENTS 2013-01-16 2013-01-17 ORAL METRONIDAZOLE 2013-01-16 2013-01-18 INTRAVENOUS DRIP PARACETAMOL 2013-01-16 2013-01-18 ORAL TRAMADOL 2013-01-16 2013-01-16 INTRAVENOUS ACICLOVIR SODIUM 2013-01-17 2013-01-18 INTRAVENOUS
(35) Subject CNTO1275CRD3003-5609-10365
1) Reason for narrative selection SAE Event of interest: Serious infection
32 3 (187) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome (Study day I/M) 2013-03-23 ⫠㛛⮋⒆ Y MODERATE/ Y/ DOSE NOT CHANGED/ 2013-03-25 (263/205) (PERIANAL ABSCESS) POSSIBLE Y RECOVERED/RESOLVED (265/207)
3) Baseline Demographic Information ȋȌǣ ʹ͵ ǣ ȋȌǣ ͺͲ ǣ ǣ ͳͻͺͻǦͲͶǦͲͷ ȋ Ȍǣ ͳ
4) Induction Treatment Group Induction study: CNTO1275CRD3001 Randomized Treatment Group: Placebo IV Actual Treatment Group: Placebo IV
5) Maintenance Treatment Group Assigned Treatment Group: Non-randomized subject/Non-responder to placebo IV induction dosing and received ustekinumab in maintenance
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2012-07-04 1 Placebo 0 mg WEEK 0 MAINTENANCE 2012-08-31 59 Placebo 0 mg WEEK 0 MAINTENANCE 2012-08-31 59 Ustekinumab 129.6 mg WEEK 8 MAINTENANCE 2012-10-26 115 Ustekinumab 90 mg WEEK 12 MAINTENANCE 2012-11-23 143 Placebo 0 mg WEEK 16 MAINTENANCE 2012-12-19 169 Placebo 0 mg WEEK 20 MAINTENANCE 2013-01-18 199 Ustekinumab 90 mg WEEK 24 MAINTENANCE 2013-02-20 232 Placebo 0 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: Y Did the subject terminate the study participation before the Week 44 visit?: Y Did subject enter the long-term extension study?: -
8) Induction Baseline Crohn's Disease History Date of diagnosis: 31MAR2008 Disease duration: 4.26 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪ᑠ⭠㏆㸭⫶㸭㣗㐨㸪ᾘ⟶እኚ㸦㛵⠇⅖㸭㛵⠇③㸧
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: NEVER Stricture complications of (CD): NEVER
10) Concomitant Crohn's Disease-Related Surgeries Surgery Date Result of lack of efficacy? ࡑࡢࡢษ㛤ཬࡧ⮋⒆ࢻࣞࢼ࣮ࢪ 2013-03-23 Y
32 4 (188) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
11) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 20 MAINTENANCE BUDESONIDE 9 mg - WEEK 24 MAINTENANCE BUDESONIDE 9 mg - WEEK 24 MAINTENANCE BUDESONIDE 6 mg - WEEK 24 MAINTENANCE BUDESONIDE 3 mg -
12) Narrative Text ⿕㦂⪅ࡣ 2 ṓࡢⓑே⏨ᛶ࡛㸪2012 ᖺ 7 ᭶ 4 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ࣉࣛࢭ࣎ࢆ㟼⬦ෆᢞ ࡉࢀࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡎ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏࢆᢞࡉ ࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣᯤⲡ⇕࡛࠶ࡗࡓࠋ SAE/Serious infection㸸⫠㛛⮋⒆㸦Day 263㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2013 ᖺ 3 ᭶ 23 ᪥⫠㛛࿘ᅖ③ཬࡧᅽ③ࢆッ࠼ධ㝔ࡋࡓࠋ2013 ᖺ 3 ᭶ 16 ᪥ࡢ᰾☢Ẽඹ㬆⏬ീἲ࡛ࡣ㸪ࡧࡲࢇᛶࡢᣓ⣙➽ෆᾋ⭘ཬࡧᚋ᪉ࡢ⅖ࡀㄆࡵࡽࢀ㸪ࢡ࣮ࣟ ࣥࡢ≧୍⮴ࡋ࡚࠸ࡓࠋࡲࡓ㸪ᕥ⮌㒊ࡢ⓶ྥࡗ࡚ࡶ⮋ࢆฟࡋࡑ࠺࡞ 2.5 cm ࡢ⮋ ⒆ཬࡧ┤⭠ቨ⫧ཌཬࡧᾋ⭘ࡀㄆࡵࡽࢀ㸪┤⭠⅖ࡀ♧၀ࡉࢀࡓࠋ2013 ᖺ 5 ᭶ 23 ᪥ࡢ⮫ᗋ᳨ᰝ್ࡣ㸪 C ᛂᛶࡓࢇⓑ⃰ᗘ 27.4 mg/L㹙ṇᖖ⠊ᅖ㸦NR㸧0-5 mg/L㹛࡛㸪࣓ࢳࢩࣜࣥ⪏ᛶ㯤Ⰽࣈࢻ࢘⌫⳦ ࡢᇵ㣴᳨ᰝࡣ㝜ᛶ࡛࠶ࡗࡓࠋྠ᪥ࡢ⭠ෆど㙾᳨ᰝ࡛ࡣ㸪㍍ᗘࡢ┤⭠⅖ཬࡧ⫠㛛࿘ᅖ⮋⒆ࡀㄆࡵ ࡽࢀ㸪ษ㛤ཬࡧ⮋ࡉࢀࡓࠋ⤌⧊Ꮫⓗ᳨ᰝ࡛ࡣᑠ⭠ཬࡧ⭠ᩘಶࡢ⫗ⱆ⭘ࡀㄆࡵࡽࢀࡓࠋᴫࡋ ࡚≉ᚩࡣ㸪㢧ⴭ࡞άືᮇࡢ⅖ࢆకࢃ࡞࠸ࢡ୍࣮ࣟࣥ⮴ࡋ࡚࠸ࡓࠋ␗ᙧᡂཬࡧᝏᛶ⭘⒆ࡢᚩ ೃࡣ࡞ࡗࡓࠋ⿕㦂⪅ࡣ㸪ࣇ࢙ࣥࢱࢽࣝ㸪ࢲࣝࢸࣃࣜࣥ㸪ࣃࣛࢭࢱ࣮ࣔࣝ㸪ࢭࣇࣟ࢟ࢩ࣒㸪࣓ࢺ ࣟࢽࢲࢰ࣮ࣝ㸪ࢩࣉࣟࣇࣟ࢟ࢧࢩࣥ㸪Hartmann's compound sodium lactate㸪㟼⬦ෆ⿵ᾮ㸪ࢡ࢚ࣥ㓟 ࣐ࢢࢿࢩ࣒࢘㸪ࢭࣥࣀࢩࢻࡼࡿ⒪ࡶཷࡅࡓࠋ⿕㦂⪅ࡣ㸪2013 ᖺ 3 ᭶ 25 ᪥㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2012-09-01 ౽⛎ SEVERE/ N/ DOSE NOT CHANGED/ 2012-09-13 (60/2) (PROXIMAL CONSTIPATION - RIGHT NOT NA RECOVERED/RESOLVED (72/14) SIDE OF THE BOWEL) RELATED 2012-12-15 ౽⛎ MILD/ N/ DOSE NOT CHANGED/ 2013-01-18 (165/107) (CONSTIPATION) NOT NA RECOVERED/RESOLVED (199/141) RELATED 2012-12-19 ⭡㒊⭾‶ MODERATE/ N/ DOSE NOT CHANGED/ 2013-01-18 (169/111) (ABDOMINAL BLOATING) NOT NA RECOVERED/RESOLVED (199/141) RELATED 2012-12-19 ⭡㒊⭾‶ MILD/ N/ DOSE NOT CHANGED/ 2013-01-18 (169/111) (ABDOMINAL GAS) NOT NA RECOVERED/RESOLVED (199/141) RELATED 2013-01-04 㣗ḧῶ㏥ MILD/ N/ DOSE NOT CHANGED/ 2013-01-18 (185/127) (DECREASE APPETITE) DOUBTFUL NA RECOVERED/RESOLVED (199/141) 2013-01-04 ᝏᚰ MILD/ N/ DOSE NOT CHANGED/ 2013-01-18 (185/127) (NAUSEA) DOUBTFUL NA RECOVERED/RESOLVED (199/141) 2013-01-20 Ꮨ⠇ᛶࣞࣝࢠ࣮ MILD/ N/ DOSE NOT CHANGED/ 2013-01-26 (201/143) (HAY FEVER) DOUBTFUL NA RECOVERED/RESOLVED (207/149)
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route MACROGOL 3350 2012-12-15 - ORAL CETIRIZINE 2013-01-20 2013-01-26 ORAL
32 5 (189) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
(36) Subject CNTO1275CRD3003-1001-11034
1) Reason for narrative selection SAE Event of interest: Serious infection
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome I/M) 2013-07-11 ࢡࣟࢫࢺࣜࢪ࣒࣭࢘ࢹࣇࢩࣞ Y SEVERE/ Y/ NOT APPLICABLE/ 2013-07-19 (191/134) ⭠⅖ DOUBTFUL Y RECOVERED/RESOLVED (199/142) (C DIFFICILE COLITIS)
3) Baseline Demographic Information Age (years): 3 Sex: Female Weight (kg): 64 Race: White Date of birth: Height (cm): 161.3
4) Induction Treatment Group Induction study: CNTO1275CRD3001 Randomized Treatment Group: Placebo IV Actual Treatment Group: Placebo IV
5) Maintenance Treatment Group Assigned Treatment Group: Non-randomized subject/Non-responder to placebo IV induction dosing and received ustekinumab in maintenance
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2013-01-02 1 Placebo 0 mg WEEK 0 MAINTENANCE 2013-02-28 58 Ustekinumab 129.6 mg WEEK 0 MAINTENANCE 2013-02-28 58 Placebo 0 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: Y Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: -
8) Induction Baseline Crohn's Disease History Date of diagnosis: 01JUL1992 Disease duration: 20.51 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪ᑠ⭠㏆㸭⫶㸭㣗㐨㸪ᾘ⟶እኚ㸦㛵⠇⅖㸭㛵⠇③㸧
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: CURRENTLY PRESENT Stricture complications of (CD): PREVIOUS HISTORY
32 6 (190) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
10) Concomitant Crohn's Disease-Related Surgeries None reported
11) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 0 PREDNISONE 30 mg 30 mg WEEK 4 MAINTENANCE METHYLPREDNISOLONE 16 mg 20 mg WEEK 4 MAINTENANCE METHYLPREDNISOLONE 12 mg 15 mg WEEK 4 MAINTENANCE METHYLPREDNISOLONE 4 mg 5 mg WEEK 4 MAINTENANCE METHYLPREDNISOLONE 24 mg 30 mg WEEK 4 MAINTENANCE METHYLPREDNISOLONE 8 mg 10 mg WEEK 4 MAINTENANCE METHYLPREDNISOLONE 20 mg 25 mg WEEK 8 MAINTENANCE METHYLPREDNISOLONE 24 mg 30 mg WEEK 8 MAINTENANCE METHYLPREDNISOLONE 24 mg 30 mg WEEK 8 MAINTENANCE METHYLPREDNISOLONE 20 mg 25 mg WEEK 8 MAINTENANCE METHYLPREDNISOLONE 16 mg 20 mg WEEK 8 MAINTENANCE METHYLPREDNISOLONE 12 mg 15 mg WEEK 8 MAINTENANCE METHYLPREDNISOLONE 8 mg 10 mg WEEK 8 MAINTENANCE METHYLPREDNISOLONE 4 mg 5 mg WEEK 8 MAINTENANCE METHYLPREDNISOLONE 8 mg 10 mg WEEK 8 MAINTENANCE METHYLPREDNISOLONE 16 mg 20 mg WEEK 8 MAINTENANCE METHYLPREDNISOLONE 80 mg - SAFETY FOLLOW-UP MAINTENANCE PREDNISONE 40 mg 40 mg SAFETY FOLLOW-UP MAINTENANCE PREDNISONE 30 mg 30 mg SAFETY FOLLOW-UP MAINTENANCE PREDNISONE 27.5 mg 27.5 mg
12) Narrative Text ⿕㦂⪅ࡣ 3 ṓࡢⓑேዪᛶ࡛㸪2013 ᖺ 1 ᭶ 2 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ࣉࣛࢭ࣎ࢆ㟼⬦ෆᢞ ࡉࢀࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡎ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏࢆᢞࡉ ࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪∦㢌③㸪㢌③㸪 ៏ᛶ⫼㒊③㸪㢖⬦㸪࠺ࡘ㸪⫶㣗㐨㏫ὶᛶᝈ㸪⫠㛛࿘ᅖࡢ⓶⅖㸦rectal dermatitis㸧㸪ႍᜥ㸪 ‵⑈㸪╀㸪ᝏᚰ㸪⫠㸪ᙉ┤ᛶ⬨᳝⅖㸪ࢡࣟࢫࢺࣜࢪ࣒࣭࢘ࢹࣇࢩࣞ⭠⅖㸦2012 ᖺ㸧㸪 ⫹ᄞษ㝖㸪㕲Ḟஈᛶ㈋⾑㸪⭈⤖▼㸪○▼㸪ỗ⾑⌫ῶᑡ㸦6-࣓ࣝ࢝ࣉࢺࣉࣜࣥࢆཎᅉࡍࡿ㸧㸪 ᅇ⭠㒊ศษ㝖㸪Ⓞ㸪⤖⭠ྑ༙ษ㝖ཬࡧࣅࢱ࣑ࣥ B12 Ḟஈ࡛࠶ࡗࡓࠋࡲࡓ㸪⿕㦂⪅ࡣࣥࣇࣜ ࢟ࢩ࣐ࣈ㸪tixocortol㸪6-࣓ࣝ࢝ࣉࢺࣉࣜࣥ㸪ࢼࣉࣟ࢟ࢭࣥཬࡧ࣌ࢽࢩࣜࣥᑐࡍࡿ⸆≀ࣞࣝࢠ ࣮୪ࡧ࣓ࢺࣟࢽࢲࢰ࣮ࣝᑐࡍࡿ⪏ᛶࡀ࠶ࡗࡓࠋ SAE/Serious infection㸸ࢡࣟࢫࢺࣜࢪ࣒࣭࢘ࢹࣇࢩࣞ⭠⅖㸦Day 191㸧 CIOMS ࡼࡿ㸪2013 ᖺ 7 ᭶ 13 ᪥㸪⿕㦂⪅ࡣࢡ࣮ࣟࣥࡢᝏ㸪⭡③㸪ୗ⑩ཬࡧ⬺Ỉࡼࡾ㸪 ධ㝔ࡋࡓࠋ⿕㦂⪅ࡣ 1 ᪥㏻ᖖ 5 ࡽ 6 ᅇࡢ౽ࡀ࠶ࡾ㸪౽ࡢ⣙༙ศࡀ⾑౽࡛࠶ࡗࡓࡓࡵ㸪≧ࡀ ᝏࡋࡓッ࠼ࡓࠋࡉࡽ㸪⭡③ࡢᝏ㸪㔞ࡢୗ⑩㸦1 ᪥ 8㹼10 ᅇ㸧㸪⬺ຊ㸪⑂ປཬࡧᗈỗᛶ ࡢ㛵⠇③ࡀㄆࡵࡽࢀࡓࠋࡲࡓ㸪⿕㦂⪅ࡣࡇࢀࡽࡢ≧ࢆࢡ࣮ࣟࣥࡢᝏࡀཎᅉ࡛࠶ࡿ⪃࠼㸪 ⒪ࡢࡓࡵ prednisone ࢆ 40 mg/᪥ቑ㔞ࡋࡓࠋ2013 ᖺ 7 ᭶ 13 ᪥ࡢ౽᳨ᰝ࡛ࡣᐤ⏕ࡸᐤ⏕༸ ࡣ᳨ฟࡉࢀ࡞ࡗࡓࡀ㸪ࢡࣟࢫࢺࣜࢪ࣒࣭࢘ࢹࣇࢩࣞẘ⣲᳨ᰝࡣ᫂░࡛㸪ẘ⣲ B 㑇ఏᏊࡀ ᳨ฟࡉࢀࡓࠋ2013 ᖺ 7 ᭶ 16 ᪥ࡢ᰾☢Ẽඹ㬆⏬ീἲ࡛ࡣ㸪⭠ቨࡢ⫧ཌⱝࡋࡃࡣቑᙉ㸪⒦Ꮝᙧᡂ㸪 ཪࡣ⮋⒆ᙧᡂࡣ࡞ࡃ㸪⫢⮚㸪⮅⮚㸪⭁⮚ཬࡧ⭈⮚␗ᖖ࡞ಙྕᙉᗘࢆ♧ࡍ㡿ᇦࡣㄆࡵࡽࢀࡎ㸪㦵 ┙ෆࡢ⭘⒗ࡸᾮయ㈓␃ࡶ࡞ࡗࡓࠋ⿕㦂⪅ࡣࣂࣥࢥ࣐ࢩࣥᛂࢆ♧ࡋ㸪ࡲࡓ㸪
32 7 (191) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
hydromorphone hydrochloride㸪㟼⬦ෆ⿵ᾮ㸪ࢫࢸࣟࢻࡢῶ㸪ࣉࣟࢡࣟࣝ࣌ࣛࢪࣥ㸪࢜ࣥࢲࣥ ࢭࢺࣟࣥ㸪ࢫࢡࣛࣝࣇ࣮ࢺཬࡧ࣓࢜ࣉࣛࢰ࣮ࣝࡼࡿ⒪ࡀ⾜ࢃࢀࡓࠋ⿕㦂⪅ࡣ㸪2013 ᖺ 7 ᭶ 19 ᪥㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2012-12-10 㢌③ SEVERE/ N/ NOT APPLICABLE/ 2012-12-11 (-23/.) (WORSENING HEADACHES) NOT NA RECOVERED/RESOLVED (-22/.) RELATED 2012-12-11 ⓶ᛂ MODERATE/ N/ NOT APPLICABLE/ 2012-12-11 (-22/.) (LOCAL SKIN REACTION TO NOT NA RECOVERED/RESOLVED (-22/.) IANESTHESIA) RELATED 2012-12-15 ⭡③ MODERATE/ N/ NOT APPLICABLE/ 2013-03-20 (-18/.) (WORSENING ABDOMINAL NOT NA RECOVERED/RESOLVED (78/.) CRAMPS) RELATED 2012-12-15 㣗ḧῶ㏥ MODERATE/ N/ NOT APPLICABLE/ 2013-03-18 (-18/.) (LOSS OF APPETITE) NOT NA RECOVERED/RESOLVED (76/.) RELATED 2012-12-15 ᛰឤ MODERATE/ N/ NOT APPLICABLE/ 2013-03-18 (-18/.) (MALAISE) NOT NA RECOVERED/RESOLVED (76/.) RELATED 2012-12-23 ⓶⅖ SEVERE/ N/ NOT APPLICABLE/ 2013-02-04 (-10/.) (WORSEMING ANAL NOT NA RECOVERED/RESOLVED (34/.) DERMATITIS) RELATED 2012-12-30 ║่⃭ MODERATE/ N/ NOT APPLICABLE/ 2013-01-12 (-3/.) (BURNING EYES) NOT NA RECOVERED/RESOLVED WITH (11/.) RELATED SEQUELAE 2013-01-07 ⫠㛛࿘ᅖ③ MODERATE/ N/ DOSE NOT CHANGED/ 2013-03-18 (6/.) (INTERNAL RECTAL PAIN) DOUBTFUL NA RECOVERED/RESOLVED (76/.) 2013-01-10 ⓶⅖ MODERATE/ N/ DOSE NOT CHANGED/ Ongoing (9/.) (ANAL DERMATITIS) POSSIBLE NA NOT RECOVERED/NOT RESOLVED - 2013-01-13 ║③ MILD/ N/ DOSE NOT CHANGED/ 2013-01-28 (12/.) (PAIN IN EYES) POSSIBLE NA RECOVERED/RESOLVED (27/.) 2013-01-20 ⫼㒊③ SEVERE/ N/ DOSE NOT CHANGED/ Ongoing (19/.) (WORSENING BACK PAIN) NOT NA NOT RECOVERED/NOT RESOLVED - RELATED 2013-01-23 ⾑୰࣒࢝ࣜ࢘ቑຍ MILD/ N/ DOSE NOT CHANGED/ 2013-02-01 (22/.) (ELEVATED POTASSIUM) DOUBTFUL NA RECOVERED/RESOLVED (31/.) 2013-01-23 ⾑ᑠᯈᩘቑຍ MILD/ N/ DOSE NOT CHANGED/ 2013-02-01 (22/.) (ELEVATED PLATELETS) DOUBTFUL NA RECOVERED/RESOLVED (31/.) 2013-02-08 ⑂ປ SEVERE/ N/ DOSE NOT CHANGED/ Ongoing (38/.) (WORSENING FATIGUE) POSSIBLE NA NOT RECOVERED/NOT RESOLVED - 2013-02-08 ⑊③ MILD/ N/ DOSE NOT CHANGED/ 2013-03-18 (38/.) (BODY ACHES) DOUBTFUL NA RECOVERED/RESOLVED (76/.) 2013-02-19 㢌③ MODERATE/ N/ DOSE NOT CHANGED/ 2013-03-15 (49/.) (WORSENING HEADACHES) POSSIBLE NA RECOVERED/RESOLVED (73/.) 2013-02-19 ᝏᚰ MODERATE/ N/ DOSE NOT CHANGED/ 2013-03-15 (49/.) (WORSENING NAUSEA) DOUBTFUL NA RECOVERED/RESOLVED (73/.) 2013-03-15 ༸ᕢᄞ⬊ MILD/ N/ DOSE NOT CHANGED/ Ongoing (73/16) (OVARIAN CYST) DOUBTFUL NA NOT RECOVERED/NOT RESOLVED - 2013-03-19 ᛰឤ MILD/ N/ DOSE NOT CHANGED/ 2013-03-28 (77/20) (MALAISE) NOT NA RECOVERED/RESOLVED (86/29) RELATED 2013-04-01 㛵⠇③ SEVERE/ N/ DOSE NOT CHANGED/ Ongoing (90/33) (RIGHT KNEE PAIN) POSSIBLE NA NOT RECOVERED/NOT RESOLVED - 2013-04-09 㛵⠇③ SEVERE/ N/ DOSE NOT CHANGED/ Ongoing (98/41) (RIGHT ANKLE PAIN) POSSIBLE NA NOT RECOVERED/NOT RESOLVED - 2013-05-26 ࢡ࣮ࣟࣥ MODERATE/ N/ DOSE NOT CHANGED/ 2013-06-10 (145/88) (WORSENING CROHN'S NOT NA RECOVERED/RESOLVED (160/103) DISEASE) RELATED
32 8 (192) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2013-07-05 ⭡③ MODERATE/ N/ DOSE NOT CHANGED/ 2013-07-10 (185/128) (CRAMPING ABDOMINAL DOUBTFUL NA RECOVERED/RESOLVED (190/133) PAIN) 2013-07-06 ୗ⑩ MODERATE/ N/ DOSE NOT CHANGED/ 2013-07-23 (186/129) (WORSENING DIARRHEA) POSSIBLE NA RECOVERED/RESOLVED (203/146) 2013-07-07 ∦㢌③ SEVERE/ N/ DOSE NOT CHANGED/ Ongoing (187/130) (WORSENING MIGRAINE DOUBTFUL NA NOT RECOVERED/NOT RESOLVED - HEADACHE) 2013-07-10 ╀ MODERATE/ N/ DOSE NOT CHANGED/ Ongoing (190/133) (INSOMINIA) DOUBTFUL NA NOT RECOVERED/NOT RESOLVED - 2013-07-15 ⾑Ύࣇ࢙ࣜࢳࣥῶᑡ MODERATE/ N/ DOSE NOT CHANGED/ 2013-07-16 (195/138) (DECREASED FERRITIN) DOUBTFUL NA RECOVERED/RESOLVED (196/139)
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route LIDOCAINE 2012-12-10 - OTHER NUTRIENTS NOS 2012-12-27 2013-03-01 ORAL CICLOSPORIN 2013-01-03 2013-01-29 OPHTHALMIC LIDOCAINE 2013-01-23 2013-01-23 SUBCUTANEOUS LIDOCAINE 2013-03-12 2013-03-12 INTRA-ARTICULAR TIZANIDINE HYDROCHLORIDE 2013-03-12 2013-03-14 ORAL HYDROMORPHONE HYDROCHLORIDE 2013-03-13 2013-03-15 ORAL OXYCODONE 2013-03-15 2013-04-02 ORAL DIAZEPAM 2013-03-15 - ORAL METHYLPREDNISOLONE 2013-03-21 2013-03-21 ORAL METHYLPREDNISOLONE 2013-03-22 2013-03-22 ORAL METHYLPREDNISOLONE 2013-03-23 2013-03-23 ORAL METHYLPREDNISOLONE 2013-03-24 2013-03-24 ORAL METHYLPREDNISOLONE 2013-03-25 2013-03-25 ORAL METHYLPREDNISOLONE 2013-03-26 2013-03-26 ORAL METHYLPREDNISOLONE 2013-03-27 2013-03-27 ORAL METHYLPREDNISOLONE 2013-03-28 2013-03-28 ORAL METHYLPREDNISOLONE 2013-03-29 2013-03-29 ORAL METHYLPREDNISOLONE 2013-03-30 2013-03-30 ORAL METHYLPREDNISOLONE 2013-03-31 2013-03-31 ORAL METHYLPREDNISOLONE 2013-04-01 2013-04-01 ORAL METHYLPREDNISOLONE ACETATE 2013-04-03 2013-04-03 INTRA-ARTICULAR OXYCODONE 2013-04-03 - ORAL METHYLPREDNISOLONE 2013-04-04 2013-04-11 ORAL METHYLPREDNISOLONE 2013-04-12 2013-04-18 ORAL METHYLPREDNISOLONE 2013-04-19 2013-04-25 ORAL DESOXIMETASONE 2013-06-10 - TOPICAL OXYCODONE HYDROCHLORIDE 2013-07-12 - ORAL VANCOMYCIN 2013-07-13 2013-07-18 ORAL VANCOMYCIN 2013-07-19 2013-07-28 ORAL
(37) Subject CNTO1275CRD3003-1007-10108
1) Reason for narrative selection SAE Event of interest: Serious infection
32 9 (193) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome (Study day I/M) 2012-06-16 ┤⭠࿘ᅖ⮋⒆ Y MODERATE/ Y/ DOSE NOT CHANGED/ 2012-06-21 (103/45) (PERIRECTAL ABSCESS) DOUBTFUL Y RECOVERED/RESOLVED (108/50)
3) Baseline Demographic Information Age (years): 2 Sex: Female Weight (kg): 55.5 Race: White Date of birth: Height (cm): 163.8
4) Induction Treatment Group Induction study: CNTO1275CRD3001 Randomized Treatment Group: Ustekinumab 130 mg IV Actual Treatment Group: Ustekinumab 130 mg IV
5) Maintenance Treatment Group Assigned Treatment Group: Non-randomized subject/Non-responder to ustekinumab IV induction dosing and received ustekinumab in maintenance
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2012-03-06 1 Ustekinumab 129.6 mg WEEK 0 MAINTENANCE 2012-05-03 59 Ustekinumab 90 mg WEEK 0 MAINTENANCE 2012-05-03 59 Placebo 0 mg WEEK 8 MAINTENANCE 2012-07-05 122 Ustekinumab 90 mg WEEK 12 MAINTENANCE 2012-07-31 148 Placebo 0 mg WEEK 16 MAINTENANCE 2012-08-20 168 Ustekinumab 90 mg WEEK 20 MAINTENANCE 2012-09-20 199 Placebo 0 mg WEEK 24 MAINTENANCE 2012-10-15 224 Ustekinumab 90 mg WEEK 28 MAINTENANCE 2012-11-13 253 Placebo 0 mg WEEK 32 MAINTENANCE 2012-12-11 281 Ustekinumab 90 mg WEEK 36 MAINTENANCE 2013-01-02 303 Placebo 0 mg WEEK 40 MAINTENANCE 2013-02-01 333 Ustekinumab 90 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: N Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: -
8) Induction Baseline Crohn's Disease History Date of diagnosis: 08SEP2008 Disease duration: 3.49 years Involved areas: ⤖⭠ࡢࡳ
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: NEVER Stricture complications of (CD): NEVER
33 0 (194) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
10) Concomitant Crohn's Disease-Related Surgeries None reported
11) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 0 PREDNISONE 20 mg 20 mg WEEK 4 MAINTENANCE PREDNISONE 17.5 mg 17.5 mg WEEK 4 MAINTENANCE PREDNISONE 15 mg 15 mg WEEK 4 MAINTENANCE PREDNISONE 12.5 mg 12.5 mg WEEK 8 MAINTENANCE PREDNISONE 20 mg - WEEK 8 MAINTENANCE PREDNISONE 12.5 mg 12.5 mg WEEK 8 MAINTENANCE PREDNISONE 0 mg - WEEK 8 MAINTENANCE PREDNISONE 0 mg 0 mg WEEK 16 MAINTENANCE PREDNISONE 10 mg 10 mg WEEK 16 MAINTENANCE PREDNISONE 7.5 mg 7.5 mg WEEK 16 MAINTENANCE PREDNISONE 5 mg 5 mg WEEK 20 MAINTENANCE PREDNISONE 2.5 mg 2.5 mg WEEK 20 MAINTENANCE PREDNISONE 0 mg 0 mg
12) Narrative Text ⿕㦂⪅ࡣ 2 ṓࡢⓑேዪᛶ࡛㸪2012 ᖺ 3 ᭶ 6 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏࢆ㟼⬦ෆᢞࡉࢀ ࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡎ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏࢆᢞࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪ࢨࢳ࢜ࣉࣜ ࣥᑐࡍࡿ⸆≀ࣞࣝࢠ࣮࡛࠶ࡗࡓࠋ SAE/Serious infection㸸┤⭠࿘ᅖ⮋⒆㸦Day 103㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2012 ᖺ 6 ᭶ 16 ᪥㔜ᗘࡢ⃭ࡋ࠸㸪㗦ࡃ่ࡍࡼ࠺࡞⭡③ཬࡧ┤⭠ ③ࢆッ࠼㸪ᩆᛴእ᮶ࢆཷデࡋࡓࠋࡑࡢࡢ≧ࡋ࡚㸪ኻ⚄㸪┤⭠࿘ᅖᛌឤ㸪๓᪥ 24 㛫ࡢ ౽㔞ࡢῶᑡ㸪㍍ᗘࡢᝏᐮ㸪㍍ᗘࡢ㢌③㸪ᝏᚰཬࡧྤࡀ࠶ࡗࡓࠋࡲࡓ㸪⿕㦂⪅ࡣࢺࣞࡢỈ⾑ ࡀᑡࡋΰࡌࡗ࡚࠸ࡓࡀ㸪᫂ࡽ࡞⮋౽࡛ࡣ࡞ࡗࡓሗ࿌ࡋࡓࠋ⿕㦂⪅ࡣ⮬ศ࡛ࣇ࢙ࢽࣞࣇࣜࣥ ᆘ⸆ࢆ⏝࠸࡚⒪ࡋ㸪prednisone ࡢ㔞ࢆῶࡋࡓࠋ⌮Ꮫⓗᡤぢ࡛ࡣ㸪㍍ᗘࡢ⭡㒊ᅽ③ࡀ࠶ࡾ㸪 㦵ୖ㒊ࡢᅽ③ࡀ᭱ࡶᙉࡗࡓࠋⓎ⇕ࡣ࡞ࡃ㸪㍍ᗘࡢ㧗⾑ᅽ㸦152/109 mmHg㸧ཬࡧ㢖⬦㸦1 ศ㛫࡛ 99 ᢿ㸧ࡀㄆࡵࡽࢀࡓࡀ㸪ࣂࢱࣝࢧࣥࡣᏳᐃࡋ࡚࠸ࡓࠋࢥࣥࣆ࣮ࣗࢱ᩿ᒙᙳ㸦CT㸧ࢫ࢟ࣕ ࡛ࣥࡣ㸪⣙ 5.5cm ࡢ┤⭠࿘ᅖ⮋⒆ࡀ☜ㄆࡉࢀࡓࠋ⒪ࡣ⏕⌮㣗ሷỈ㸪hydromorphone㸪࢜ࣥࢲ ࣥࢭࢺࣟࣥཬࡧࣆ࣌ࣛࢩࣜࣥ㸭ࢱࢰࣂࢡࢱ࣒㸦ࢰࢩࣥ㸧ࡀ⏝ࡉࢀࡓࠋ୍⯡እ⛉ࡼࡿ⟶⌮ࡀᚲ せࡉࢀࡓࡓࡵධ㝔ࡋ㸪ᗈᇦᢠ⏕≀㉁ཬࡧ stress-dose ࡢࢫࢸࣟࢻࡼࡿ⒪ࡀ⾜ࢃࢀࡓࠋ2012 ᖺ 6 ᭶ 17 ᪥㸪┤⭠࿘ᅖ⮋⒆ࡢ⮋ᡭ⾡ࡀ⾜ࢃࢀࡓࠋstress-dose ࡢࢫࢸࣟࢻࡼࡿ⒪ࢆᩘ᪥㛫 ⥅⥆ࡋ㸪ࡑࡢᚋ prednisone ࡼࡿ⒪⛣⾜ࡋࡓࠋ2012 ᖺ 6 ᭶ 19 ᪥㸪ணእࡢ⑊③≧ࡀ ࠶ࡾ㸪ࣆࢵࢢࢸ࣮ࣝ࢝ࢸ࣮ࢸࣝࢆ⤒㝜ⓗᤄධࡋ㸪࣓ࢺࣟࢽࢲࢰ࣮ࣝࡼࡿ⒪ࢆ㛤ጞࡋ㸪 prednisone ࡢ⏝㔞ࢆ࣮࣋ࢫࣛࣥࡢ⏝㔞ࡲ࡛ῶࡋࡓࠋ⿕㦂⪅ࡣ㸪2012 ᖺ 6 ᭶ 21 ᪥㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2012-05-07 Ⓨ⑈ MILD/ N/ DOSE NOT CHANGED/ 2012-05 (63/5) (RASH ON ELBOWS AND BACK OF DOUBTFUL NA RECOVERED/RESOLVED - KNEES)
33 1 (195) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route HYDROMORPHONE HYDROCHLORIDE 2012-06-16 2012-06-19 INTRAVENOUS ONDANSETRON 2012-06-16 2012-06-16 INTRAVENOUS PIP/TAZO 2012-06-16 2012-06-16 INTRAVENOUS PREDNISONE 2012-06-17 2012-06-21 INTRAVENOUS METRONIDAZOLE 2012-06-19 2012-06-26 ORAL (38) Subject CNTO1275CRD3003-1007-10134
1) Reason for narrative selection SAE Event of interest: Serious infection
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome (Study day I/M) 2012-09-05 ⫵⅖ Y SEVERE/ Y/ DOSE NOT CHANGED/ 2012-09-09 (167/111) (PNEUMONIA) DOUBTFUL Y RECOVERED/RESOLVED (171/115)
3) Baseline Demographic Information ȋȌǣ ʹ ǣ ȋȌǣ ͶǤͺ ǣ ǣ ͳͻͺͶǦͳʹǦ͵ͳ ȋ Ȍǣ ͳͲ
4) Induction Treatment Group Induction study: CNTO1275CRD3001 Randomized Treatment Group: Ustekinumab 130 mg IV Actual Treatment Group: Ustekinumab 130 mg IV
5) Maintenance Treatment Group Assigned Treatment Group: Randomized subject/Responder to ustekinumab IV induction dosing/placebo SC
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2012-03-23 1 Ustekinumab 129.6 mg WEEK 0 MAINTENANCE 2012-05-18 57 Placebo 0 mg WEEK 8 MAINTENANCE 2012-07-10 110 Placebo 0 mg WEEK 12 MAINTENANCE 2012-08-10 141 Placebo 0 mg WEEK 16 MAINTENANCE 2012-09-17 179 Placebo 0 mg WEEK 20 MAINTENANCE 2012-10-15 207 Placebo 0 mg WEEK 24 MAINTENANCE 2012-11-08 231 Placebo 0 mg WEEK 28 MAINTENANCE 2012-11-30 253 Placebo 0 mg WEEK 32 MAINTENANCE 2012-12-28 281 Placebo 0 mg WEEK 36 MAINTENANCE 2013-01-25 309 Placebo 0 mg WEEK 40 MAINTENANCE 2013-02-22 337 Placebo 0 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: N Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: Y
33 2 (196) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
8) Induction Baseline Crohn's Disease History Date of diagnosis: 31DEC2005 Disease duration: 6.23 years Involved areas: ⤖⭠ࡢࡳ㸪ᑠ⭠㏆㸭⫶㸭㣗㐨㸪ᾘ⟶እኚ㸦ࣇࢱᛶཱྀෆ⅖㸪㛵⠇⅖㸭㛵 ⠇③㸧
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: NEVER Stricture complications of (CD): NEVER
10) Concomitant Crohn's Disease-Related Surgeries None reported
11) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 0 PREDNISONE 5 mg 5 mg WEEK 4 MAINTENANCE PREDNISONE 5 mg 5 mg WEEK 4 MAINTENANCE PREDNISONE 2.5 mg 2.5 mg WEEK 4 MAINTENANCE PREDNISONE 0 mg 0 mg
12) Narrative Text ⿕㦂⪅ࡣ 2 ṓࡢⓑேዪᛶ࡛㸪2012 ᖺ 3 ᭶ 23 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏࢆ㟼⬦ෆᢞࡉࢀ ࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ࣉࣛࢭ࣎ࢆ⓶ୗᢞ ࡍࡿ⩌ࣛࣥࢲ࣒ࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪⫠㸪⭠⅖㸪 ㈋⾑㸪⫵⅖㸦2006 ᖺ㸧㸪࠺ࡘ㸪㐣ཤࡢႚ↮㸪ࢪࢫ࣐ࣟࢩࣥཬࡧࣥࣇࣜ࢟ࢩ࣐ࣈᑐࡍࡿ ࣞࣝࢠ࣮ཬࡧ᰾ษ㝖㸦2006 ᖺ㸧࡛࠶ࡗࡓࠋᐙ᪘Ṕࡣ₽⒆ᛶ⭠⅖࡛࠶ࡗࡓࠋ SAE/Serious infection㸸⫵⅖㸦Day 167㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2012 ᖺ 9 ᭶ 5 ᪥ 2 ᪥㛫ࢃࡓࡿⓎ⇕㸦103.6°F㸧㸪ᛶတႿ㸪 ㌟ᛶ➽⫗③ཬࡧ㌟ᛶ⑂ປࢆッ࠼㸪ᩆᛴእ᮶㸦ER㸧ࢆཷデࡋࡓࠋတႿ㛵㐃ࡍࡿᝏᚰཬࡧྤ ࡶッ࠼ࡓࠋER ࡛ࡢ⌮Ꮫⓗ᳨ᰝ࡛ࡣ㸪⫈デ࡛ࡢࣛ㡢ཬࡧప㡢ᛶ㐃⥆ᛶࣛ㡢ࡀ㢧ⴭ࡛࠶ࡗࡓࠋࣂ ࢱࣝࢧࣥኚࡣㄆࡵࡽࢀ࡞ࡗࡓࠋER ࠾࠸࡚㸪⿕㦂⪅ࡣ⏕⌮㣗ሷỈ㸦㟼⬦ෆᢞ㸧㸪࢜ ࣥࢲࣥࢭࢺࣟࣥ㸪hydromorphone hydrochloride㸪ࣉ࣓ࣟࢱࢪࣥ㸪ࢻ࢟ࢩࢧࢡࣜࣥཬࡧࢭࣇࢺࣜ ࢟ࢯࣥࢆᢞࡉࢀࡓࠋྠ᪥ࡢ⭡㒊 X ⥺ീ࡛ࡣ㸪ᣑᙇࡢ࡞࠸ᑠ⭠ಀ㋟ཬࡧ⭠ಀ㋟ࡢ⮳ࡿᡤ࡛୰ ➼㔞ࡢ࢞ࢫࡀㄆࡵࡽࢀ㸪⬚㒊 X ⥺ീ࡛ࡣ㸪ྑୗⴥᚋഃ㒊ࡢᐇ㉁㝜ᙳ᫂░࡞㡿ᇦࡀㄆࡵࡽࢀࡓࠋ 2012 ᖺ 9 ᭶ 6 ᪥㸪⿕㦂⪅ࡣ᭦࡞ࡿ⒪ࡢࡓࡵධ㝔ࡋࡓࠋࣞ࣎ࣇࣟ࢟ࢧࢩࣥຍ࠼ࢭࣇࢺࣜ࢟ ࢯࣥཬࡧࢻ࢟ࢩࢧࢡࣜࣥࡼࡿ⒪ࡶ⥅⥆ࡋࡓࠋᡴデࡼࡾ㸪៏ᛶࡢᕥഃ⭡㒊③ཬࡧᕥ⫘㦵⬨ ᰕゅᅽ③ࡶㄆࡵࡽࢀࡓࠋ2012 ᖺ 9 ᭶ 7 ᪥ࡢ⮫ᗋ᳨ᰝ್ࡣ㸪⾑୰ᒀ⣲❅⣲<2 ȝg/dL㹙ṇᖖ⠊ᅖ 㸦NR㸧7-17 ȝg/dL㹛㸪C ᛂᛶࡓࢇⓑ⃰ᗘ 16.9 mg/dL㸦NR<9 mg/dL㸧㸪ࢡࣞࢳࢽࣥ 0.49 mg/dL 㸦NR 0.52-1.04 mg/dL㸧ཬࡧⓑ⾑⌫ᩘ 6.8×103/ȝL㸦NR ᫂㸧࡛࠶ࡗࡓࠋྠ᪥ࡢ⭡㒊ཬࡧ㦵┙㒊ࡢ ࢥࣥࣆ࣮ࣗࢱ᩿ᒙᙳ㸦CT㸧ࢫ࡛࢟ࣕࣥࡣ㸪┤⭠㸪S ≧⤖⭠ཬࡧୗ⾜⤖⭠ཬࡪ㍍ᗘ࡛ᗈ⠊࡞⭠
33 3 (197) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
ቨ⫧ཌࡀㄆࡵࡽࢀ㸪៏ᛶࡢࢡ࣮ࣟࣥࡀ♧၀ࡉࢀࡓࠋࡲࡓ㸪ᕥୗⴥࡢᚋᗏ㒊⃰࠸ᩬ≧ࡢᾐ₶ᙳ ࡀㄆࡵࡽࢀ㸪⫵⅖୍⮴ࡋ࡚࠸ࡓࠋ㏣ຍࡢᡤぢࡋ࡚ࡣ㸪㦵┙ rim enhancement ཪࡣᑠ⬊ᙧᡂ ࡢ࡞࠸㐟㞳ᾮయࡀㄆࡵࡽࢀ㸪༸㛵㐃ࡍࡿ⏕⌮Ꮫⓗ࡞ཎᅉཪࡣ₯ᅾⓗ࡞⅖࡛࠶ࡿྍ⬟ᛶࡀ♧ ၀ࡉࢀࡓࠋ୧⭈⮚ࡣṇᖖ࡛࠶ࡾỈ⭈ࡣ࡞ࡗࡓࠋᒀ᳨ᰝ࡛ࡣ㸪ⓑ⾑⌫࢚ࢫࢸ࣮ࣛࢮ㸪ⓑ⾑⌫ 㸦10-30/hpf㸧㸪㉥⾑⌫㸦5-10/hpf㸧ཬࡧ⣽⳦㸦2+㸧ࡀㄆࡵࡽࢀࡓࠋᒀཬࡧ⾑ᾮᇵ㣴᳨ᰝ㸪౽᳨ᰝ ୪ࡧ࣏࣓࣮ࣜࣛࢮ㐃㙐ᛂ㸦PCR㸧ࡢ⤖ᯝࡣ࠸ࡎࢀࡶ㝜ᛶ࡛࠶ࡾ㸪ࣞࣥࢧ⌫⳦ࡢ㎿㏿ヨ㦂㸭ᇵ 㣴᳨ᰝཬࡧࢡࣟࢫࢺࣜࢪ࣒࣭࢘ࢹࣇࢩࣞẘ⣲ࡢ PCR ౽᳨ᰝࡢ⤖ᯝࡶྠᵝ࡛࠶ࡗࡓࠋዷፎ᳨ ᰝࡣ㝜ᛶ࡛࠶ࡗࡓࠋ2012 ᖺ 9 ᭶ 9 ᪥㸪⿕㦂⪅⾑ᛶୗ⑩ཬࡧᕥୗ⭡㒊③ࢆక࠺⤖⭠ࢡ࣮ࣟࣥ ࡢ㍍ᗘ⇞ࡀㄆࡵࡽࢀࡓࡇࡀሗ࿌ࡉࢀࡓࡀ㸪ධ㝔୰ኚࡋࡓཪࡣᝏࡋࡓࡣุ᩿ࡉࢀ࡞ ࡗࡓࠋ⿕㦂⪅ࡣ㸪2012 ᖺ 9 ᭶ 9 ᪥㏥㝔ࡋࡓࠋ㏥㝔㸪ࣞ࣎ࣇࣟ࢟ࢧࢩࣥ㸪ࢢࣇ࢙ࢿࢩࣥ㸪 albuterol㸪citalopram㸪ࢺ࣐ࣛࢻ࣮ࣝ㸪ࢨࢳ࢜ࣉࣜࣥཬࡧ balsalazide ࢆฎ᪉ࡉࢀࡓࠋ
13) Other Adverse Events Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2012-03-23 ⑂ປ MODERATE/ N/ DOSE NOT CHANGED/ 2012-04-06 (1/.) (WORSENING FATIGUE) DOUBTFUL NA RECOVERED/RESOLVED (15/.) 2012-03-24 ᝏᚰ(WORSENING NAUSEA) MODERATE/ N/ DOSE NOT CHANGED/ 2012-03-30 (2/.) DOUBTFUL NA RECOVERED/RESOLVED (8/.) 2012-03-26 ⓶㞀ᐖ MILD/ N/ DOSE NOT CHANGED/ 2012-04-20 (4/.) (RED BUMPS ON FACE- DOUBTFUL NA RECOVERED/RESOLVED (29/.) OTHER/UNKNOWN) 2012-04-06 ㌟ᛶࡑ࠺ MILD/ N/ DOSE NOT CHANGED/ 2012-04 (15/.) (WHOLE BODY PURITIS) POSSIBLE NA RECOVERED/RESOLVED - 2012-04-07 እ㝜⭐┿⳦ឤᰁ MILD/ Y/ DOSE NOT CHANGED/ 2012-04-08 (16/.) (VAGINAL YEAST INFECTION) POSSIBLE Y RECOVERED/RESOLVED (17/.) 2012-05-15 ኻ⚗ MODERATE/ N/ DOSE NOT CHANGED/ 2012-05-20 (54/.) (INCONTINENCE) DOUBTFUL NA RECOVERED/RESOLVED (59/.) 2012-05-19 ⬺ẟ MODERATE/ N/ DOSE NOT CHANGED/ Ongoing (58/2) (ALOPECIA) DOUBTFUL NA NOT RECOVERED/NOT - RESOLVED 2012-05-19 㢦㠃ᾋ⭘ MODERATE/ N/ DOSE NOT CHANGED/ 2012-05-20 (58/2) (FACIAL EDEMA) DOUBTFUL NA RECOVERED/RESOLVED (59/3) 2012-07-23 ➽㦵᱁◳┤ MODERATE/ N/ DOSE NOT CHANGED/ Ongoing (123/67) (LEG STIFFNESS) DOUBTFUL NA NOT RECOVERED/NOT - RESOLVED 2012-08-03 㰯ฟ⾑ MILD/ N/ DOSE NOT CHANGED/ Ongoing (134/78) (NOSE BLEEDS) DOUBTFUL NA NOT RECOVERED/NOT - RESOLVED 2012-08-03 ཱྀ⭍ෆ₽⒆ᙧᡂ MODERATE/ N/ DOSE NOT CHANGED/ Ongoing (134/78) (WORSENING MOUTH ULCERS) DOUBTFUL NA NOT RECOVERED/NOT - RESOLVED 2012-08-06 ⫘㌾㦵⅖ MODERATE/ N/ DOSE NOT CHANGED/ Ongoing (137/81) (COSTOCHONDRITIS) DOUBTFUL NA NOT RECOVERED/NOT - RESOLVED 2012-08-06 ⥙≧⓶ᩬ MILD/ N/ DOSE NOT CHANGED/ Ongoing (137/81) (LEVIDO RETICULARIS) DOUBTFUL NA NOT RECOVERED/NOT - RESOLVED 2012-08-08 ║⾑ MILD/ N/ DOSE NOT CHANGED/ 2012-08-09 (139/83) (EYE REDNESS) DOUBTFUL NA RECOVERED/RESOLVED (140/84) 2012-08-13 ⬚㒊ᛌឤ MILD/ N/ DOSE NOT CHANGED/ Ongoing (144/88) (CHEST HEAVINESS) DOUBTFUL NA NOT RECOVERED/NOT - RESOLVED 2013-01-22 ࢡࣟࢥࣝࢻࣥ MILD/ N/ DOSE NOT CHANGED/ 2014-04-18 (306/250) (SKIN TAGS) DOUBTFUL NA RECOVERED/RESOLVED (757/701) 2013-02-27 ୖẼ㐨ឤᰁ MODERATE/ Y/ DOSE NOT CHANGED/ 2013-03-22 (342/286) (UPPER RESPIRATORY TRACT POSSIBLE N RECOVERED/RESOLVED (365/309) INFECTION)
33 4 (198) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route DIPHENHYDRAMINE HYDROCHLORIDE 2012-07-10 - ORAL SALBUTAMOL 2012-09 - RESPIRATORY (INHALATION) GUAIFENESIN 2012-09 - ORAL CEFTRIAXONE 2012-09-05 2012-09-05 INTRAVENOUS HYDROMORPHONE HYDROCHLORIDE 2012-09-05 2012-09-05 INTRAVENOUS DOXYCYCLINE 2012-09-05 2012-09-05 ORAL PROMETHAZINE 2012-09-05 2012-09-05 INTRAVENOUS ONDANSETRON 2012-09-05 2012-09-05 INTRAVENOUS LEVOFLOXACIN 2012-09-06 - ORAL BENZONATATE 2013-03-04 2013-03-11 ORAL LEVOFLOXACIN 2013-03-04 2013-03-11 ORAL
(39) Subject CNTO1275CRD3003-1015-10023
1) Reason for narrative selection SAE Event of interest: Serious infection
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome I/M) 2012-07-18 ┤⭠⮋⒆ Y SEVERE/ Y/ DOSE NOT CHANGED/ 2012-08-13 (314/258) (LARGE LEFT ISCHIORECTAL NOT Y RECOVERED/RESOLVED (340/284) ABSCESS) RELATED 2012-07-20 ῝㒊㟼⬦⾑ᰦ Y SEVERE/ N/ DOSE NOT CHANGED/ 2012-08-09 (316/260) (DEEP VENOUS THROMBOSIS) NOT NA RECOVERED/RESOLVED (336/280) RELATED
3) Baseline Demographic Information ȋȌǣ ͷͶ ǣ ȋȌǣ ͻǤͳ ǣ ǣ ͳͻͷǦͲͻǦͳͲ ȋ Ȍǣ ͳͲ
4) Induction Treatment Group Induction study: CNTO1275CRD3001 Randomized Treatment Group: Placebo IV Actual Treatment Group: Placebo IV
5) Maintenance Treatment Group Assigned Treatment Group: Non-randomized subject/Non-responder to placebo IV induction dosing and received ustekinumab in maintenance
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2011-09-09 1 Placebo 0 mg WEEK 0 MAINTENANCE 2011-11-04 57 Ustekinumab 130 mg WEEK 0 MAINTENANCE 2011-11-04 57 Placebo 0 mg WEEK 8 MAINTENANCE 2012-01-06 120 Ustekinumab 90 mg WEEK 12 MAINTENANCE 2012-01-27 141 Placebo 0 mg WEEK 16 MAINTENANCE 2012-02-28 173 Placebo 0 mg WEEK 20 MAINTENANCE 2012-03-23 197 Ustekinumab 90 mg WEEK 24 MAINTENANCE 2012-04-23 228 Placebo 0 mg
33 5 (199) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
Visit Start Date Study Day Actual Treatment Dose WEEK 28 MAINTENANCE 2012-05-18 253 Placebo 0 mg WEEK 32 MAINTENANCE 2012-06-15 281 Ustekinumab 90 mg WEEK 36 MAINTENANCE 2012-07-13 309 Placebo 0 mg WEEK 40 MAINTENANCE 2012-08-13 340 Placebo 0 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: N Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: Y
8) Induction Baseline Crohn's Disease History Date of diagnosis: 26SEP2000 Disease duration: 10.95 years Involved areas: ⤖⭠ࡢࡳ㸪⫠㛛࿘ᅖ
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: PREVIOUS HISTORY Stricture complications of (CD): PREVIOUS HISTORY
10) Concomitant Crohn's Disease-Related Surgeries Surgery Date Result of lack of efficacy? DRAINAGE - PERCUTANEOUS INCISION AND DRAINAGE 2012-07-18 Y
11) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 0 PREDNISONE 10 mg 10 mg WEEK 16 MAINTENANCE PREDNISONE 5 mg 5 mg WEEK 20 MAINTENANCE PREDNISONE 2.5 mg 2.5 mg WEEK 20 MAINTENANCE PREDNISONE 10 mg 10 mg WEEK 24 MAINTENANCE PREDNISONE 5 mg 5 mg WEEK 28 MAINTENANCE PREDNISONE 2.5 mg 2.5 mg
12) Narrative Text ⿕㦂⪅ࡣ 5 ṓࡢⓑே⏨ᛶ࡛㸪2011 ᖺ 9 ᭶ 9 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ࣉࣛࢭ࣎ࢆ㟼⬦ෆᢞ ࡉࢀࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡎ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏࢆᢞࡉ ࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪㦵ῶᑡ 㸦2002㸧㸪៏ᛶୗ⫥⭘⬽㸦2005㸧㸪ᖏ≧⑁⑈㸦2003㸧㸪㟼⬦࠺ࡗ⾑㸦2005㸧㸪ྑୗ⫥῝㒊㟼⬦⾑ ᰦ㸦2010 ᖺ 4 ᭶㸧㸪⤖⭠࣏࣮ࣜࣉ㸦2000 ᖺ 9 ᭶㸧㸪㛵⠇⅖㸦1992㸧㸪⻏ᕢ⅖㸦2011 ᖺ 2 ᭶㸧㸪 ⭡ቨ࣊ࣝࢽ㸦2011 ᖺ㸧㸪Ꮨ⠇ᛶࣞࣝࢠ࣮㸦1997 ᖺ㸧㸪┤⭠࿘ᅖ⮋⒆㸦1991 ᖺ 3 ᭶㸪2009 ᖺ 10 ᭶㸧㸪៏ᛶ㈋⾑㸦1991 ᖺ 2 ᭶㸧㸪⫶㣗㐨㏫ὶᛶᝈ㸦2006 ᖺ㸧㸪ᮎᲈ⾑⟶ᝈ㸪㙐㦵㦵ᢡ 㸦2012 ᖺ 7 ᭶㸧㸪ᡥ᱈ฟཬࡧᶵ㣧㓇࡛࠶ࡗࡓࠋ⿕㦂⪅ࡣ௨๓㸪ࣞ࣎ࣇࣟ࢟ࢧࢩࣥ᭹⏝⸆ ≀ࣞࣝࢠ࣮ࢆⓎ⌧ࡋࡓࠋᐙ᪘Ṕࡣ༸ᕢ⒴㸪⢾ᒀཬࡧ㏱ᯒ㸦ẕ㸧࡛࠶ࡗࡓࠋ2009 ᖺ 7 ᭶ࡢ௨๓ ࡢデ᩿࡛ࡣάືᮇࡢࢡ࣮ࣟࣥデ᩿ࡉࢀ㸪⫠㛛࿘ᅖࡢኚ㸪ᕥഃ⤖⭠⊃✽㸪ഇᛶ࣏࣮ࣜࣉᙧᡂ
33 6 (200) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
ཬࡧ㐲ᶓ⾜⤖⭠ಀ㋟⤖⠇ᛶ㡿ᇦࢆకࡗ࡚࠸ࡓࠋ2010 ᖺ 10 ᭶㸪⭠ෆど㙾᳨ᰝࡼࡾάື ᮇࡢ⤖⭠ࢡ࣮ࣟࣥཬࡧ⫠㛛࿘ᅖࡢኚࡀุ᫂ࡋࡓࠋ SAE/Serious infection㸸┤⭠⮋⒆㸦Day 314㸧 SAE㸸῝㒊㟼⬦⾑ᰦ㸦Day 316㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ㸪2012 ᖺ 7 ᭶ 15 ᪥㸪2 ᪥㛫ࢃࡓࡿ┤⭠③ࡢᝏ୪ࡧయࡢ③ ࡳཬࡧᝏᐮ㸦య 㸸⣙ 102°F㸪ࢭࢺ࣑ࣀࣇ࢙ࣥࡼࡾ⒪㸧ࡀ࠶ࡾ㸪2012 ᖺ 7 ᭶ 18 ᪥ධ 㝔ࡋࡓࠋ⿕㦂⪅ࡣ㸪2012 ᖺ 2 ᭶ 13 ᪥௨㝆 4 ࣏ࣥࢻయ㔜ῶᑡࡋࡓࡇࢆッ࠼ࡓࠋ㌾౽ཬࡧỈᵝ౽ ࡀ 1 ᪥ 4 ᅇ࠶ࡿࡇࡶッ࠼ࡓࡀ㸪┤⭠ฟ⾑㸪⭡③㸪ᐷờ㸪㛵⠇③ࡘ࠸࡚ࡣྰᐃࡋࡓࠋ2 ᖺ௨ୖ ┤⭠࿘ᅖࡢၥ㢟ࡣ࡞ࡃ㸪㠀ࢫࢸࣟࢻᛶᢠ⅖⸆ࡣ⏝ࡋ࡚࠸࡞ࡗࡓࠋࣂࢱࣝࢧࣥ␗ᖖ ࡣ࡞ࡗࡓࠋ ┤⭠᳨ᰝࡼࡾ㸪⮋Ồࡢฟࢆక࠺◳⤖ࡀㄆࡵࡽࢀࡓࡀ㸪⮋⒆ࡢ⨨ࢆ✺ࡁṆࡵࡿࡇࡣ࡛ࡁ ࡞ࡗࡓࠋ⿕㦂⪅ࡣⴭࡋ࠸㈋⾑≧ែ࡛࠶ࡗࡓࠋ⿕㦂⪅ࡣᕥᆘ㦵┤⭠⮋⒆ࡢࢻࣞࢼ࣮ࢪࢆཷࡅࡓࠋ ᐇࡉࢀࡓᇵ㣴᳨ᰝࡢ⤖ᯝࡣᥦ౪ࡉࢀ࡞ࡗࡓࠋᡭ⾡ᚋࡢデ᩿ࡣ㸪ᣲ➽ୖ᪉ᣑࡋ๓᪉ཬࡧᕥ ᚋഃ᪉ࡢ⒦Ꮝ㸦࠾ࡑࡽࡃᣓ⣙➽㈏㏻㸧ࢆ᭷ࡍࡿᆘ㦵┤⭠⮋⒆ཬࡧ┤⭠⊃✽࡛࠶ࡗࡓࠋ⒪ࡣ ࣓ࢺࣟࢽࢲࢰ࣮ࣝ㸪ࢭࣇࢰࣜࣥ㸪ࢫࣝࣇ࣓ࢺ࢟ࢧࢰ࣮ࣝ㸪ࣞ࣎ࣇࣟ࢟ࢧࢩࣥ㸪 hydromorphone㸪࢜ࣥࢲࣥࢭࢺࣟࣥ㸪㟼⬦ෆ⿵ᾮ㸪ࣔࣝࣄࢿཬࡧࢭࢺ࣑ࣀࣇ࢙ࣥ㸭 hydrocodone ࡀ⏝࠸ࡽࢀࡓࠋ ධ㝔୰㸪⿕㦂⪅ࡣᕥୗ⫥③ࢆⓎ⌧ࡋࡓࠋ2012 ᖺ 7 ᭶ 20 ᪥ࡢࢻࢵࣉ࣮ࣛ㉸㡢Ἴ᳨ᰝ࡛ࡣ㸪ᕥୗ ⫥ࡢ῝㒊㟼⬦⣔ᗈ⠊ࡘ࡞⾑ᰦࡀㄆࡵࡽࢀ㸪⥲⭣㟼⬦ࣞ࣋ࣝࡲ࡛ཬࢇ࡛࠸ࡓࠋྠ᪥ࡢ ⮫ᗋ᳨ᰝ್ࡣ㸪࣊ࣔࢢࣟࣅࣥ 8.4㸪ⓑ⾑⌫ᩘ 4.01㸪⾑ᑠᯈᩘ 128㹙༢ཬࡧṇᖖ⠊ᅖ㸦NR㸧᫂㹛 ࡛࠶ࡗࡓࠋྠ᪥㸪㙠㟼ୗ࡛ୗ㟼⬦ࣇࣝࢱ࣮ࡀᤄධࡉࢀࡓࠋ⿕㦂⪅ࡣ㸪࣊ࣃࣜࣥⅬ㸪࣡ࣝࣇ ࣜࣥཬࡧ 1 ༢㍺⾑ࡼࡿ⒪ࢆཷࡅࡓࠋ㦂ᢸᙜ་ᖌࡣ㸪⿕㦂⪅ࡢ⾑ᑠᯈῶᑡࡣ῝㒊㟼⬦ ⾑ᰦࡼࡿࡶࡢุ᩿ࡋࡓࠋ2012 ᖺ 7 ᭶ 21 ᪥ࡢ⮫ᗋ᳨ᰝ್㸦᳨ᰝ㸧ࡣ㸪࣊ࣔࢢࣟࣅࣥ 7.8㸪 ⓑ⾑⌫ᩘ 7.8㸦ᮍ⇍㢛⢏⌫ࢆక࠺㸧㸪ዲ୰⌫ 92.2%ཬࡧ⾑ᑠᯈᩘ 154㸦༢ཬࡧ NR ᫂㸧࡛࠶ࡗ ࡓࠋ2012 ᖺ 7 ᭶ 23 ᪥ࡢ౽᳨ᰝࡣ㸪ࢡࣟࢫࢺࣜࢪ࣒࣭࢘ࢹࣇࢩࣞᢠཎཬࡧẘ⣲ࡶ㝜ᛶ࡛ ࠶ࡗࡓࠋ ⿕㦂⪅ࡢ┤⭠ࡢയࡣⴭࡋࡃᨵၿࡋ㸪ṇᖖ౽࡞ࡾጞࡵࡓࠋ2012 ᖺ 7 ᭶ 28 ᪥ࡢ⮫ᗋ᳨ᰝ್ࡣ㸪 ࣊ࣔࢢࣟࣅࣥ 8.8 g/dL㸦NR 14.0-18.0 g/dL㸧㸪ⓑ⾑⌫ᩘ 5.8㸪⾑ᑠᯈᩘ 142㸦༢᫂㸧࡛࠶ࡾ㸪 2012 ᖺ 7 ᭶ 30 ᪥ࡢ್ࡣ㸪࣊ࣔࢢࣟࣅࣥ 8.6 g/dL㸪ࣉࣟࢺࣟࣥࣅࣥ㛫 29.9 s㸦NR 9.5-12.4 s㸧㸪 ᅜ㝿ᶆ‽ẚ 2.7 ࡛࠶ࡗࡓࠋ⿕㦂⪅ࡣ㸪2012 ᖺ 7 ᭶ 30 ᪥㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2011-12-01 ⻏ᕢ⅖ MODERATE/ Y/ DOSE NOT CHANGED/ 2011-12-19 (84/28) (SKIN CELLULITIS LEFT ANKLE) NOT Y RECOVERED/RESOLVED (102/46) RELATED 2011-12-15 ⏥≧⭢ᶵ⬟పୗ MILD/ N/ DOSE NOT CHANGED/ Ongoing (98/42) (HYPOTHROIDISM) NOT NA NOT RECOVERED/NOT - RELATED RESOLVED 2012-01-07 ࣊ࣔࢢࣟࣅࣥῶᑡ(LOW MODERATE/ N/ DOSE NOT CHANGED/ 2012-01-27 (121/65) HEMOGLOBIN) NOT NA RECOVERED/RESOLVED (141/85) RELATED
33 7 (201) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2012-02-16 ⓶ឤᰁ MODERATE/ Y/ DOSE NOT CHANGED/ 2012-02-26 (161/105) (SKIN INFECTION) NOT Y RECOVERED/RESOLVED (171/115) RELATED 2012-07-02 㙐㦵㦵ᢡ MODERATE/ N/ DOSE NOT CHANGED/ 2012-09-07 (298/242) (FX LEFT CLAVICLE) NOT NA RECOVERED/RESOLVED (365/309) RELATED 2012-08-13 ⬺Ỉ MODERATE/ N/ DOSE NOT CHANGED/ 2012-08-13 (340/284) (DEHYDRATION) NOT NA RECOVERED/RESOLVED (340/284) RELATED 2012-09-06 㛵⠇⅖ MILD/ N/ DOSE NOT CHANGED/ 2012-10-05 (364/308) (WORSENING OF ARTHRITIS) NOT NA RECOVERED/RESOLVED (393/337) RELATED
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route AUGMENTIN /00756801/ 2011-12-05 2011-12-19 ORAL LEVOTHYROXINE 2011-12-16 - ORAL IRON 2012-01-10 - ORAL BACTRIM 2012-02-16 2012-02-25 ORAL PROCET /01554201/ 2012-07-02 - ORAL CEFAZOLIN SODIUM 2012-07-18 2012-07-18 INTRAVENOUS HYDROMORPHONE 2012-07-18 - INTRAVENOUS HYDROMORPHONE 2012-07-18 2012-07-18 INTRAVENOUS RINGER-LACTATE 2012-07-18 2012-07-19 INTRAVENOUS LEVOFLOXACIN 2012-07-18 2012-07-23 INTRAVENOUS METRONIDAZOLE 2012-07-18 2012-07-23 INTRAVENOUS VICODIN 2012-07-18 2012-07-24 ORAL PARACETAMOL 2012-07-18 2012-07-18 INTRAVENOUS SULFAMETHOXAZOLE 2012-07-18 2012-07-30 ORAL ONDANSETRON 2012-07-18 2012-07-30 INTRAVENOUS HEPARIN 2012-07-20 2012-07-20 INTRAVENOUS HEPARIN 2012-07-20 2012-07-30 INTRAVENOUS LEVOFLOXACIN 2012-07-24 2012-07-29 ORAL METRONIDAZOLE 2012-07-24 2012-07-30 ORAL WARFARIN 2012-07-27 2012-07-29 ORAL WARFARIN SODIUM 2012-07-30 - ORAL METRONIDAZOLE 2012-08-01 2012-08-17 ORAL SODIUM CHLORIDE 2012-08-13 2012-08-13 INTRAVENOUS
(40) Subject CNTO1275CRD3003-1015-20305
1) Reason for narrative selection SAE Event of interest: Serious infection
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome (Study day I/M) 2013-12-25 ⫵⅖ Y SEVERE/ Y/ DOSE NOT CHANGED/ 2014-01-13 (328/269) (PNEUMONIA) NOT RELATED Y RECOVERED/RESOLVED (347/288)
3) Baseline Demographic Information ȋȌǣ ͵͵ ǣ ȋȌǣ ͳͶͻǤͷ ǣ ǣ ͳͻͻǦͲͻǦͳͺ ȋ Ȍǣ ͳͷ
33 8 (202) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
4) Induction Treatment Group Induction study: CNTO1275CRD3002 Randomized Treatment Group: Ustekinumab 130 mg IV Actual Treatment Group: Ustekinumab 130 mg IV
5) Maintenance Treatment Group Assigned Treatment Group: Non-randomized subject/Non-responder to ustekinumab IV induction dosing and received ustekinumab in maintenance
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2013-02-01 1 Ustekinumab 129.6 mg WEEK 0 MAINTENANCE 2013-04-01 60 Ustekinumab 90 mg WEEK 0 MAINTENANCE 2013-04-01 60 Placebo 0 mg WEEK 8 MAINTENANCE 2013-06-05 125 Ustekinumab 90 mg WEEK 12 MAINTENANCE 2013-06-28 148 Placebo 0 mg WEEK 16 MAINTENANCE 2013-07-19 169 Ustekinumab 90 mg WEEK 20 MAINTENANCE 2013-08-21 202 Placebo 0 mg WEEK 24 MAINTENANCE 2013-09-17 229 Ustekinumab 90 mg WEEK 28 MAINTENANCE 2013-10-16 258 Placebo 0 mg WEEK 32 MAINTENANCE 2013-11-12 285 Ustekinumab 90 mg WEEK 36 MAINTENANCE 2013-12-19 322 Placebo 0 mg WEEK 40 MAINTENANCE 2014-01-16 350 Ustekinumab 90 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: N Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: Y
8) Induction Baseline Crohn's Disease History Date of diagnosis: 10JUL2012 Disease duration: 0.57 years Involved areas: ᅇ⭠ࡢࡳ㸪ᾘ⟶እኚ㸦㛵⠇⅖㸭㛵⠇③㸧
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: NEVER Stricture complications of (CD): NEVER
10) Concomitant Crohn's Disease-Related Surgeries None reported
11) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 12 MAINTENANCE HYDROCORTISONE 25 mg - WEEK 12 MAINTENANCE HYDROCORTISONE 0 mg - WEEK 36 MAINTENANCE PREDNISONE - -
33 9 (203) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
12) Narrative Text ⿕㦂⪅ࡣ 3 ṓࡢ㯮ேཪࡣࣇࣜ࢝⣔࣓ࣜ࢝ேዪᛶ࡛㸪2013 ᖺ 2 ᭶ 1 ᪥㸪ᐶゎᑟධ⒪ἲ ࡋ࡚ᮏࢆ㟼⬦ෆᢞࡉࢀࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡎ㸪ᐶゎ⥔ᣢ⒪ ἲࡋ࡚ᮏࢆᢞࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪⤖⠇ᛶ⣚ᩬ㸪 㧗⾑ᅽ㸪ႍᜥ㸪῝㒊㟼⬦⾑ᰦ㸦DVT㸧㸪㛵⠇࣐ࣜ࢘ࢳ㸪ⓗ⫧‶㸪Ꮚᐑฟ㸪ᡥ᱈ฟ㸪ᖇ⋤ ษ㛤㸪ஙᡣ⏕᳨㸪ᕥ༸ᕢ㝖࡛࠶ࡗࡓࠋ௨ୗࡢ≀㉁ᑐࡍࡿࣞࣝࢠ࣮ࡶ࠶ࡗࡓ㸸ࣂࢼࢼ㸪 Sclavo test PPD㸦⢭〇ࢶ࣋ࣝࢡࣜࣥ protein derivative㸧ཬࡧ࢚ࢫࢺࣟࢤࣥᵝ≀㉁ࠋᐙ᪘Ṕࡣෙື⬦ ᝈ㸪⬻⾑⟶Ⓨసཬࡧ㛵⠇⅖࡛࠶ࡗࡓࠋ SAE/Serious infection㸸⫵⅖㸦Day 328㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2013 ᖺ 12 ᭶ 26 ᪥တႿ㸪ဗႃ③㸪Ṍ⾜୰ࡢ⬚③㸪ປసࡢᜥษ ࢀࡀ 1 ᪥ᣢ⥆ࡋࡓࡓࡵධ㝔ࡋࡓࠋႤኌ㛵㐃ࡋࡓⓎ⇕ཬࡧᝏᐮࡶッ࠼ࡓࠋ୧ୗ⫥㍍ᗘࡢ⭘⬽ࡀ ㄆࡵࡽࢀࡓࠋࣂࢱࣝࢧࣥࡣయ 38.7°C㸪ᚰᢿᩘ 62 ᢿ/ศ㸪྾ᩘ 20 ᅇ/ศ㸪⾑ᅽ 156/90 mmHg㸪㓟⣲㣬ᗘ 100%㸦ᐊෆ✵Ẽ྾㸧࡛࠶ࡗࡓࠋࣞࣥࢧ⌫⳦ᢠཎ㸪ࣥࣇ࢚ࣝࣥ ࢨࢫࢡ࣮ࣜࢽࣥࢢཬࡧ⾑ᾮணഛᇵ㣴ࡢ⤖ᯝࡣ㝜ᛶ࡛࠶ࡗࡓࠋ2013 ᖺ 12 ᭶ 29 ᪥ࡢ⬚㒊ࢥࣥࣆ࣮ࣗ ࢱ᩿ᒙᙳ㸦CT㸧⾑⟶㐀ᙳᅗࡼࡾ㸪ᗈ⠊࡞ᕥྑୗⴥࡢ⫵⅖ࡀㄆࡵࡽࢀ㸪ᆺࡢ୰ᯡᆺ⫵ሰᰦ ࡢᚩೃࡣ࡞ࡗࡓࠋ⬚㒊 CT ࢫ࢟ࣕࣥ㸦ᐇ᪥᫂㸧࡛ࡣ㸪୧⫵ୗⴥࡢ㒊ศከⓎᛶࡢ⫵ᾐ ₶ࡀㄆࡵࡽࢀࡓࠋ2013 ᖺ 12 ᭶ 31 ᪥ࡢ⬚㒊 X ⥺ീ࡛ࡣ㸪࠶ࡲࡾᣑᙇࡋ࡚࠸࡞࠸⫵㸪㍍ᗘࡢᕥᇶ ᗏ㒊ࡢ↓Ẽ⫵ཪࡣ⫘㦵ᶓ㝸⭷ゅ㕌㛵㐃ࡍࡿᾐ₶ࡀㄆࡵࡽࢀ㸪ᑠ㔞ࡢᕥ⬚Ỉཪࡣ⬚⭷ᛂࡢᚩ ೃࡀ♧၀ࡉࢀࡓࠋ⬚㒊㠀㐀ᙳ CT ࢫ࢟ࣕࣥ㸦2013 ᖺ 12 ᭶ 31 ᪥㸧ࡼࡾ㸪ᗈ⠊ᅖࡢ⫵⬊ᛶ㝜ᙳ 㸦airspace opacities㸧ࡢⴭࡋ࠸ᨵၿ㸦2013 ᖺ 12 ᭶ 29 ᪥ࡢࢫ࢟ࣕࣥẚ㍑㸧ࡀㄆࡵࡽࢀࡓࠋඖࠎ㸪 ᕥྑୖⴥ㝜ᙳࡣ࡞ࡗࡓࠋᕥྑୗⴥ࠾࠸࡚ṧࡿ㝜ᙳࡣ᭱ᑠ࡞ࡗࡓࠋ⫵ᑠ⯉ࡢᾐ₶ࡣ㒊ศ ࡀᾘኻࡋࡓࠋᕥୖⴥ┤ᚄ 4 mm ࡢᑠᆺ࡛ᮎᲈᛶࡢ⤖⠇㝜ᙳࡀㄆࡵࡽࢀ㸪୧ഃ⬚Ỉࡢ㊧ࢆకࡗ ࡚࠸ࡓࠋ┤ᚄ 10 mm ௨ୗࡢከⓎᛶࡢ⦪㝸ࣜࣥࣃ⠇ࡀㄆࡵࡽࢀ㸪㍍ᗘࡢᕥᚰᐊᣑࢆకࡗ࡚࠸ࡓࠋ ᚰᄞᾮࡢᚩೃࡣ࡞ࡗࡓࠋ୧ഃᛶ⫵⅖ࡣ┦ᙜᨵၿࡋ࡚࠸ࡿ༳㇟࡛࠶ࡗࡓࠋ⒪ࡣ㟼⬦ෆ⿵ᾮ㸪 ࣆ࣌ࣛࢩࣜࣥ㸭ࢱࢰࣂࢡࢱ࣒㸦ࢰࢩࣥ㸧㸪ࣞ࣎ࣇࣟ࢟ࢧࢩࣥ㸪DVT ࡢண㜵⸆㸪⫶㣗㐨㏫ὶᛶ ᝈࡢண㜵⸆ࡀ⏝࠸ࡽࢀࡓࠋචᢚไࡼࡿ⒪ࡣぢྜࢃࡉࢀࡓࠋ⿕㦂⪅ࡢ⮫ᗋ≧ែࡣᨵၿࡋ㸪 2014 ᖺ 1 ᭶ 3 ᪥㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2013-03-04 Ꮨ⠇ᛶࣞࣝࢠ࣮ MILD/ N/ DOSE NOT CHANGED/ Ongoing (32/.) (SEASONAL ALLERGIES) NOT NA NOT RECOVERED/NOT - RELATED RESOLVED 2013-06 㛵⠇③ MILD/ N/ DOSE NOT CHANGED/ 2013-06-05 - (JOINT PAIN) NOT NA RECOVERED/RESOLVED (125/66) RELATED 2013-06-14 ᰾ MODERATE/ N/ DOSE NOT CHANGED/ 2013-06-21 (134/75) (HEMORRHOID) NOT NA RECOVERED/RESOLVED (141/82) RELATED 2013-08-08 ࡑ࠺ᛶ⓶⑈ MODERATE/ N/ DOSE NOT CHANGED/ 2013-08-19 (189/130) (RAISED ITCHY RASH FACE AND NOT NA RECOVERED/RESOLVED (200/141) TORSO) RELATED 2013-08-13 㛵⠇③ MODERATE/ N/ DOSE NOT CHANGED/ 2013-08-20 (194/135) (JOINT PAIN) NOT NA RECOVERED/RESOLVED (201/142) RELATED
34 0 (204) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2013-09-15 㛵⠇③ MODERATE/ N/ DOSE NOT CHANGED/ Ongoing (227/168) (JOINT PAIN) NOT NA NOT RECOVERED/NOT - RELATED RESOLVED 2013-09-16 ⣽⳦ᛶ⭐⅖ MODERATE/ Y/ DOSE NOT CHANGED/ 2013-09-24 (228/169) (VAGINAL BACTERIAL INFECTION) NOT N RECOVERED/RESOLVED (236/177) RELATED 2013-10-01 ⤖⠇ᛶ⣚ᩬ MODERATE/ N/ DOSE NOT CHANGED/ 2014-01 (243/184) (ERYTHEMA NODOSUM) NOT NA RECOVERED/RESOLVED - RELATED 2013-10-02 ୖ⭡㒊③ MODERATE/ N/ DOSE NOT CHANGED/ Ongoing (244/185) (UPPER ABDOMINAL PAIN) NOT NA NOT RECOVERED/NOT - RELATED RESOLVED 2013-10-02 ᝏᚰ MODERATE/ N/ DOSE NOT CHANGED/ Ongoing (244/185) (INTERMITTENT NAUSEA) NOT NA NOT RECOVERED/NOT - RELATED RESOLVED 2013-10-02 ྤ MODERATE/ N/ DOSE NOT CHANGED/ Ongoing (244/185) (INTERMITTENT VOMITING) NOT NA NOT RECOVERED/NOT - RELATED RESOLVED 2013-11-04 ༸ᕢᄞ⬊ MILD/ N/ DOSE NOT CHANGED/ Ongoing (277/218) (COMPLEX CYST RIGHT OVARY) NOT NA NOT RECOVERED/NOT - RELATED RESOLVED 2013-11-26 ༙᭶ᯈᦆയ MODERATE/ N/ DOSE NOT CHANGED/ 2013-12 (299/240) (LEFT KNEE TORN MENSICUS) NOT NA RECOVERED/RESOLVED - RELATED 2013-12-25 ႍᜥ MODERATE/ N/ DOSE NOT CHANGED/ 2014-01-03 (328/269) (EXACERBATION OF ASTHMA) NOT NA RECOVERED/RESOLVED (337/278) RELATED 2013-12-27 ⫶㣗㐨㏫ὶᛶᝈ MODERATE/ N/ DOSE NOT CHANGED/ 2014-01-03 (330/271) (GASTROESOPHAGEAL REFLUX) NOT NA RECOVERED/RESOLVED (337/278) RELATED 2014-01-15 ⫠ MODERATE/ N/ DOSE NOT CHANGED/ 2014-02-17 (349/290) (ANAL FISSURE) NOT NA RECOVERED/RESOLVED (382/323) RELATED
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route DIPHENHYDRAMINE HYDROCHLORIDE 2013-03-04 - ORAL HYDROCORTISONE ACETATE 2013-06-14 2013-06-20 RECTAL METRONIDAZOLE 2013-09-16 - TOPICAL CORTISONE 2013-11-26 2013-11-26 INTRA-ARTICULAR ACETYLSALICYLIC ACID 2013-12-26 2013-12-26 ORAL LEVOFLOXACIN 2013-12-26 2013-12-26 INTRAVENOUS MORPHINE 2013-12-26 2013-12-26 INTRAVENOUS SODIUM CHLORIDE 2013-12-26 2013-12-29 INTRAVENOUS PARACETAMOL 2013-12-26 2013-12-26 ORAL ONDANSETRON 2013-12-26 2013-12-26 INTRAVENOUS IPRATROPIUM W/SALBUTAMOL 2013-12-27 2013-12-31 RESPIRATORY (INHALATION) ALUMINIUM W/MAGNESIUM/SIMETICONE 2013-12-27 2013-12-27 ORAL HEPARIN 2013-12-27 2014-01-03 SUBCUTANEOUS VICODIN 2013-12-27 2013-12-27 ORAL VICODIN 2013-12-27 2013-12-30 ORAL PANTOPRAZOLE SODIUM SESQUIHYDRATE 2013-12-27 2014-01-03 INTRAVENOUS PARACETAMOL 2013-12-27 2013-12-30 ORAL POTASSIUM CHLORIDE 2013-12-28 2013-12-30 ORAL PIP/TAZO 2013-12-29 2014-01-03 INTRAVENOUS TUSSIONEX PENNKINETIC 2014-01-03 2014-01-03 ORAL AUGMENTIN /00756801/ 2014-01-04 2014-01-12 ORAL
34 1 (205) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
(41) Subject CNTO1275CRD3003-1068-20554
1) Reason for narrative selection SAE Event of interest: Serious infection
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome I/M) 2013-11-19 ኻ⚄ Y MILD/ N/ DOSE NOT CHANGED/ 2013-11-19 (71/15) (SYNCOPE) NOT NA RECOVERED/RESOLVED (71/15) RELATED 2014-01-22 ⭡㒊⮋⒆ Y MODERATE/ Y/ NOT APPLICABLE/ 2014-06-04 (135/79) (ABDOMINAL ABSCESS) NOT Y RECOVERED/RESOLVED (268/212) RELATED 2014-05-15 ࢡ࣮ࣟࣥ Y MODERATE/ N/ NOT APPLICABLE/ 2014-06-04 (248/192) (WORSENING OF CROHN'S NOT NA RECOVERED/RESOLVED (268/212) DISEASE) RELATED
3) Baseline Demographic Information Age (years): 4 Sex: Male Weight (kg): 66.2 Race: White Date of birth: Height (cm): 186.7
4) Induction Treatment Group Induction study: CNTO1275CRD3002 Randomized Treatment Group: Ustekinumab 130 mg IV Actual Treatment Group: Ustekinumab 130 mg IV
5) Maintenance Treatment Group Assigned Treatment Group: Non-randomized subject/Non-responder to ustekinumab IV induction dosing and received ustekinumab in maintenance
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2013-09-10 1 Ustekinumab 129.6 mg WEEK 0 MAINTENANCE 2013-11-05 57 Ustekinumab 90 mg WEEK 0 MAINTENANCE 2013-11-05 57 Placebo 0 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: Y Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: -
8) Induction Baseline Crohn's Disease History Date of diagnosis: 06DEC2011 Disease duration: 1.77 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪⫠㛛࿘ᅖ㸪ᑠ⭠㏆㸭⫶㸭㣗㐨
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER
34 2 (206) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
Fistula: PREVIOUS HISTORY Stricture complications of (CD): PREVIOUS HISTORY
10) Concomitant Crohn's Disease-Related Surgeries Surgery Date Result of lack of efficacy? ⤖⭠ࡢ㒊ศⓗษ㝖㸦༙⤖⭠ษ㝖࡞㸧 2014-05-15 Y
11) Concomitant Steroids None reported
12) Narrative Text ⿕㦂⪅ࡣ 4 ṓࡢⓑே⏨ᛶ࡛㸪2013 ᖺ 9 ᭶ 10 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏࢆ㟼⬦ෆᢞࡉࢀ ࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡎ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏࢆᢞࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪Ꮨ⠇ᛶࣞࣝ ࢠ࣮㸪៏ᛶపࣝࣈ࣑ࣥ⾑㸪୧ୗ⫥ᾋ⭘㸪៏ᛶ㈋⾑㸪ᡭ⾡ࡼࡿ⒦Ꮝ㝖ཤ㸪ᡥ᱈ฟ㸪⫼㒊ᡭ ⾡㸪⭸ᡭ⾡㸪ࢥࣥࣃ࣮ࢺ࣓ࣥࢺೃ⩌ཬࡧ⭡③࡛࠶ࡗࡓࠋᐙ᪘Ṕࡣ⤖⭠࣏࣮ࣜࣉ㸦∗㸧ཬࡧ⭠ ⅖㸦ẕ㸧࡛࠶ࡗࡓࠋ SAE㸸ኻ⚄㸦Day 71㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣព㆑ࢆᾘኻ㸪㌿ಽࡋ㸪ᩆᛴ⒪ᐊ㸦ER㸧ᦙ㏦ࡉࢀ㸪ࡑࡢᚋࣇࣟ ࢭ࣑ࢻࡢ⏝㔞ቑຍ㉳ᅉࡍࡿయᾮ㔞ῶᑡࡢࡓࡵ㸪2013 ᖺ 11 ᭶ 19 ᪥ධ㝔ࡋࡓࠋ⿕㦂⪅ࡣྑ║ ❐ࡢയཬࡧ║▛⓶ୗฟ⾑ࡀㄆࡵࡽࢀࡓࠋࡲࡓ㸪㐣ཤ 1 㐌㛫㸪㢌㒊ࡩࡽࡩࡽឤཬࡧᾋືᛶࡵࡲ ࠸ࢆక࠺ 2 ᅇࡢኻ⚄Ⓨస㸪1 ᪥ 12㹼17 ᅇࡢࡺࡿ࠸㌾౽㸦ᮇ㛫᫂㸧ཬࡧᐮ෭⪏ࡶッ࠼ࡓࠋ⿕ 㦂⪅ࡣ㸪⾑⟶㏞㉮⚄⤒ᛶኻ⚄デ᩿ࡉࢀࡓࠋ⾑ᅽࡣ 99/57 mmHg ࡛࠶ࡗࡓࠋ2013 ᖺ 11 ᭶ 19 ᪥ࡢ ⮫ᗋ᳨ᰝ್ࡣ㸪࣊ࣔࢢࣟࣅࣥ 8.1 g/dL㸪ࣝࣈ࣑ࣥ 1.6 g/dL㸪⥲ࡓࢇⓑ 4.1 g/dL㸪ࢼࢺ࣒ࣜ࢘ 131 mmol/L㸪࣒࢝ࣜ࢘ 3.2 mmol/L㸪⾑୰ᒀ⣲❅⣲ 13 mg/dL㸪ࢡࣞࢳࢽࣥ 0.88 mg/dL㸦ṇᖖ⠊ᅖ ᫂㸧࡛࠶ࡗࡓࠋ⿕㦂⪅ࡢ₯⾑᳨ᰝࡣ㝧ᛶ࡛࠶ࡗࡓࡀ㸪άືᛶฟ⾑ࡢᚩೃࡣㄆࡵࡽࢀ࡞ࡗࡓࠋ 㢌㒊ࢥࣥࣆ࣮ࣗࢱ᩿ᒙᙳ㸦CT㸧ࢫ࡛࢟ࣕࣥࡣ㸪㰯㦵㦵ᢡࡀㄆࡵࡽࢀࡓࡀ㸪ᛴᛶ㢌ෆฟ⾑ࡣ ࡞ࡗࡓࠋᚰ㟁ᅗ࡛ࡣ㸪ṇᖖ㛫㝸ࡢὝㄪᚊ㸪ṇᖖ㍈ࡀㄆࡵࡽࢀ㸪ᛴᛶࡢ⾑ᛶኚࡣ࡞ࡗࡓࠋ ࣝࣈ࣑ࣥཬࡧ㟁ゎ㉁ࡼࡿ⒪ࡶཷࡅࡓࠋྠ᪥㸪ኻ⚄ࡣᅇࡋࡓሗ࿌ࡉࢀࡓࠋ2013 ᖺ 11 ᭶ 20 ᪥㸪㕲㛵㐃ヨ㦂㸦㕲⃰ᗘ㸪㕲⤖ྜ⬟ཬࡧࣇ࢙ࣜࢳࣥ㸧ࡣ㕲Ḟஈᛶ㈋⾑ཬࡧ㈓ⶶ㕲ࡢపୗ୍ ⮴ࡋࡓࠋ1 ༢ࡢ㉥⾑⌫ࡢ㍺⾑ᚋ㸪⿕㦂⪅ࡣᏳᐃࡋࡓ≧ែ࡛㏥㝔ࡋࡓࠋ SAE/Serious infection㸸⭡㒊⮋⒆㸦Day 135㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2014 ᖺ 1 ᭶ 22 ᪥㸪CT ࢫ࢟ࣕࣥᇶ࡙ࡁ⫢⮚ୗ㒊⮋⒆デ᩿ࡉ ࢀࡓࠋCT ࢫ࢟ࣕࣥࡣ㸪⭡㒊②ᨥࡑࢀ㛵㐃ࡍࡿဗႃ③㸪㣗ḧཬࡧࡋࡷࡗࡃࡾࡀ 10 ᪥㛫ㄆ ࡵࡽࢀࡓࡓࡵ⾜ࢃࢀࡓࠋ2014 ᖺ 1 ᭶ 23 ᪥㸪⿕㦂⪅ࡣ ER ࢆཷデࡋ㸪ྑୖ⭡㒊③ࡢቑᙉ㸦ᙉᗘ 4/10㸧㸪యࡢ③ࡳ㸪ᝏᐮ㸪ᝏᚰ㸪⬺ຊ㸪Ⴔ╀ཬࡧ៏ᛶୗ⑩ࢆッ࠼ධ㝔ࡋࡓࠋ⿕㦂⪅ࡣ㸪ER ཷデ ௨๓ࡽࣟࣛࢱࢪࣥࢆ᭹⏝ࡋ࡚࠸ࡿࡇࢆ࿌ࡆࡓࠋ⌮Ꮫⓗ᳨ᰝ࡛ࡣ㸪㧗ᗘᰤ㣴㞀ᐖཬࡧᾘ⪖ࡀㄆ ࡵࡽࢀࡓࠋࡲࡓ㸪⭡㒊ࡢᅄ༙㒊ࡍ࡚࡛⭠㞧㡢ࡀㄆࡵࡽࢀ㸪ྑୖ⭡㒊ࡢ⭡ቨ㜵ᚚཬࡧ⃭ࡋ࠸ᅽ③ ཬࡧୗ⫥⭘⬽ࡀㄆࡵࡽࢀࡓࠋ2014 ᖺ 1 ᭶ 23 ᪥ࡢ⭡㒊ཬࡧ㦵┙㒊ࡢ㐀ᙳ CT ࢫ࡛࢟ࣕࣥࡣ㸪ྑୖ ⭡㒊⫢ୗᇦ㸪16 mm ࡢ ring-enhancing ࡀࡳࡽࢀࡿᾮయ㸭Ẽయࢆྵࡴ㈓␃≀ࡀㄆࡵࡽࢀࡿࡶ 㸪ᑠ⭠ಀ㋟ཬࡧ⭠ಀ㋟⮋⒆ᙧᡂࡀ☜ㄆࡉࢀ㸪₯ᅾⓗ࡞ᚤᑠ✸Ꮝࡀࢃࢀࡓࠋࡲࡓ㸪ྑ⫢㟼 ⬦ࡢᚋ༊ᯞࡢ⾑ᰦ୪ࡧᗈ⠊࡞⭠㛫⭷ᾋ⭘ཬࡧᑠ㔞ࡢ⭡Ỉࡀ⭡㒊ཬࡧ㦵┙㒊ࡢ ring
34 3 (207) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
enhancement ࢆక࠺㡿ᇦㄆࡵࡽࢀ㸪᪩ᮇࡢᑠ⬊ᙧᡂࡀ♧၀ࡉࢀࡓࠋCT ࢫ࢟ࣕࣥᡤぢࡼࡾ㸪ά ືᮇࡢࢡ࣮ࣟࣥ࠾ࡅࡿ␗ᖖ࡞ᾋ⭘ᛶཬࡧ⅖ᛶࡢ⭠ࡢ≧ែ⥆Ⓨࡋࡓ㸪㸭㒊ศᶵ⬟ⓗ 㛢ሰࡀ♧၀ࡉࢀࡓࠋ᰾☢Ẽඹ㬆⏬ീἲ࡛ࡣ㸪⮋⒆ࡢᝏཬࡧ⭡⭍ෆ࢞ࢫࡀㄆࡵࡽࢀࡓࠋ2014 ᖺ 1 ᭶ 24 ᪥㸪ᮎᲈ✸่୰ᚰ㟼⬦࢝ࢸ࣮ࢸࣝ㸦PICC㸧ࣛࣥࡀᤄධࡉࢀࡓࠋCT ࢞ࢻୗ࡛ࢻ࣮ࣞࣥ ࡀ␃⨨ࡉࢀ㸪ᾮయࡣฟࡉࢀࡓࠋ྾ᘬࡋࡓᾮయࡢᇵ㣴᳨ᰝࡼࡾ㸪࢚ࣥࢸࣟࢥࢵ࢝ࢫ✀ཬࡧ⥳Ⰽ ࣞࣥࢧ⌫⳦ࢢ࣮ࣝࣉࡢⴭࡋ࠸ቑṪࡀ☜ㄆࡉࢀࡓࠋࢡࣛࣈࢩ࢚࣭ࣛ࢜࢟ࢩࢺ࢝ࡢ㍍ᗘࡢቑṪࡶㄆࡵ ࡽࢀࡓࠋ⾑ᾮᇵ㣴ศᯒࡼࡾ㸪ዲẼᛶ⣽⳦ཬࡧ᎘Ẽᛶ⣽⳦ࡀㄆࡵࡽࢀࡓࠋ2014 ᖺ 1 ᭶ 26 ᪥ࡢ⮫ ᗋ᳨ᰝ್ࡣ㸪࣊ࣔࢢࣟࣅࣥ 6.6-8.4 g/dL㸪ⓑ⾑⌫ᩘ 15.5㸦༢᫂㸧࡛࠶ࡗࡓࠋ2014 ᖺ 1 ᭶ 27 ᪥ ࡢ⭡㒊ཬࡧ㦵┙㒊㐀ᙳ CT ࢫ࡛࢟ࣕࣥࡣ㸪⿕㦂⪅ࡢ⫢࿘ᅖ⮋⒆ࡢⴭࡋ࠸ῶᅽ㸦decompression㸧ࡀ ㄆࡵࡽࢀ㸪࣮ࣝࣉ≧࢝ࢸ࣮ࢸࣝ⤖⭠ࡀࡣࡾࡘࡁ㸪⭤⬔ࡢୖ⿕ໟࡉࢀࡓ㈓␃≀ࡀࡳࡽࢀࡓࠋ ⤖⭠ཬࡧᅇ⭠ᮎ➃㒊࡛ࡢኚࡣ㸪⅖ᛶ⭠ᝈࢆ♧၀ࡍࡿࡶࡢ࡛࠶ࡗࡓࠋ⿕㦂⪅ࡣ㟼⬦ෆ⿵ᾮ㸪 ࣥࢫࣜࣥ ࢫࣃࣝࢺ㸪࢜࢟ࢩࢥࢻࣥ㸭ࣃࣛࢭࢱ࣮ࣔࣝ㸦Percocet㸧㸪ࢡࣟࣝࣉ࣐ࣟࢪࣥ㸪ࣂࣛ ࢩࢡࣟࣅࣝ㸪࢜ࣥࢲࣥࢭࢺࣟࣥ㸪ࢼࢫࢱࢳࣥ㸪ࣆ࣌ࣛࢩࣜࣥ㸭ࢱࢰࣂࢡࢱ࣒㸦㟼⬦ෆᢞ㸧㸪 hydromorphone㸪ࣟࣛࢮࣃ࣒㸪ࣞ࣎ࣇࣟ࢟ࢧࢩࣥཬࡧ࣓ࢺࣟࢽࢲࢰ࣮ࣝࡼࡿ⒪ࢆཷࡅࡓࠋ⭡ ⭍ෆ⮋⒆ࡣ㸪ཎᝈ࡛࠶ࡿࢡ࣮ࣟࣥ⥆Ⓨࡋࡓࡶࡢሗ࿌ࡉࢀࡓࠋ⭡㒊⮋⒆ࡢཎᅉࡋ࡚ࡣ㸪 ዲẼᛶཪࡣ᎘Ẽᛶ⳦⩌ࡀΰࡌࡾྜࡗࡓ」ᩘ⳦ឤᰁཪࡣᚤᑠ✸Ꮝࡢ࠸ࡎࢀࡀࢃࢀࡓࠋ 2014 ᖺ 1 ᭶ 30 ᪥㸪⿕㦂⪅ࡣヨ㦂㛤⭡ࢆཷࡅ㸪ᅇ⭠⒦ቑタཬࡧࣁࣝࢺ࣐ࣥ❐㛢㙐ࢆక࠺ᅇ⤖ ⭠ษ㝖ཬࡧ⭡㒊⮋⒆ࡢษ㛤ཬࡧ⮋ࡢᡭ⾡ࢆཷࡅࡓࠋᡭ⾡ᑐࡍࡿ⿕㦂⪅ࡢㄆᐜᛶࡣⰋዲ࡛࠶ࡗ ࡓࠋᡭ⾡ᚋࡢデ᩿ࡣ㸪⭡㒊⮋⒆㸪ᅇ⭠ࢡ࣮ࣟࣥཬࡧ⤖⭠ࢡ࣮࡛ࣟࣥ࠶ࡗࡓࠋ2014 ᖺ 2 ᭶ 6 ᪥ ࡢ⭡㒊ཬࡧ㦵┙㒊 CT ࢫ࢟ࣕࣥ㸦᳨ᰝ㸧࡛ࡣ㸪ᆺࡘᮎᲈᛶࡢ rim-enhancing ࡢࡳࡽࢀࡿᾮయ ㈓␃≀ࡢⓎ⌧ࡀุ᫂ࡋ㸪ྑഃ⭡㒊㞟ྜࡋྑഃ㦵┙㒊᪉ྥᗈࡀࡗࡓ࢞ࢫᛶࡢᕢ⩌ࢆకࡗ ࡚࠾ࡾ㸪⮋⒆୍⮴ࡋ࡚࠸ࡓࠋྑഃỈ⭈ཬࡧỈᒀ⟶ࡀ㛫㝸ࢆ⨨࠸࡚Ⓨ⌧ࡋ㸪ୖὶࡢ㛢ሰࡢཎ ᅉ࡞ࡗ࡚࠸ࡓࠋࡲࡓ㸪┣⭠ཬࡧ S ≧⤖⭠ࡢⴭࡋ࠸⭠ቨ⫧ཌࡀㄆࡵࡽࢀࡓࠋྑ⫢ⴥࡣᆒ୍࡞ ₤ὶࡀㄆࡵࡽࢀ㸪ྑ୰⫢㟼⬦㞄᥋ࡋ࡚ఙᒎࡋ࡚࠸ࡿ㸪࠾ࡑࡽࡃ⤖ྜࡋ࡚࠸ࡿྍ⬟ᛶࡢ࠶ࡿ⟶ ≧ࡢ㝜ᙳḞᦆࡀࡳࡽࢀࡓࠋࡇࡢᡤぢࡀ㸪ᑠ㟼⬦⾑ᰦཪࡣ⫹⟶ᣑᙇࢆ⾲ࡋ࡚࠸ࡿࡣ࡛᫂࠶ࡿࠋ ࡧࡲࢇᛶࡢ㔜㌟ᾋ⭘ཬࡧ㢧ⴭ࡞άືᛶ⭡㒊ࣜࣥࣃ⠇ࡶㄆࡵࡽࢀࡓࠋ⿕㦂⪅ࡣ 2014 ᖺ 2 ᭶ 7 ᪥㸪CT ࢞ࢻୗ⭡⭍ෆᾮࢻࣞࢼ࣮ࢪࢆཷࡅࡓࠋᐇᚋࡢ⿕㦂⪅ࡢ≧ែࡣᏳᐃࡋ࡚࠸ࡓࠋ2014 ᖺ 2 ᭶ 14 ᪥ࡢ⮫ᗋ᳨ᰝ್ࡣ㸪⥲ࡓࢇⓑ 6.1 g/dL㸪ࣝࣈ࣑ࣥ 2 g/dL㸪࣊ࣔࢢࣟࣅࣥ 8.3 g/dL㸪࣊ ࣐ࢺࢡࣜࢵࢺ 27.6%㸪⾑ᑠᯈᩘ 555×103/mm3 ࡛࠶ࡗࡓࠋ⿕㦂⪅ࡣ㸪2014 ᖺ 2 ᭶ 14 ᪥㏥㝔ࡋࡓࠋ SAE㸸Worsening of Crohn's disease㸦Day 248㸧 ⿕㦂⪅ࡣ㸪⭠⟶✸Ꮝࡢ࠸ཬࡧ⫢⮚ୗ㒊⮋⒆ࡢࡓࡵࡢᡭ⾡ࢆཷࡅ࡚࠾ࡾ㸪ᅇࡣᅇ⭠⒦㛢㙐ࢆ క࠺㑅ᢥⓗᶓ⾜⤖⭠ษ㝖ࡢࡓࡵ㸪2014 ᖺ 5 ᭶ 15 ᪥ධ㝔ࡋࡓࠋ⭡㒊ࡢ⌮Ꮫⓗ᳨ᰝ࡛ࡣ㸪ᡴデ ࡼࡾ⭡㒊㕌㔜ࡀㄆࡵࡽࢀࡓࡀ㸪⭡ቨ㜵ᚚ㸪㊴③ཪࡣゐ▱⭘⒗ࡣ࡞ࡗࡓࠋ⭡㒊ࡢデᐹࡣṇᖖ࡛ ࠶ࡗࡓࠋࢫࢺ࣮࣐ࡣࣆࣥࢡⰍ࡛ᶵ⬟ࡋ࡚㸦viable㸧࠾ࡾ㸪⭡㒊ࡢയࡣ⒵ࡋ࡚࠸ࡓࠋ⿕㦂⪅ࡣ 1 ᪥ᙜࡓࡾ 15 ᅇ௨ୖࡢ౽ࡀ࠶ࡿッ࠼ࡓࠋ⿕㦂⪅ࡣព㆑Ύ࡛᫂㸪ぢᙜ㆑ࡣಖࡓࢀ㸪ᛴᛶࡢⱞ⬻ ࡣ࡞ࡃ㸪ၥ㢟࡞ࡃᅇࡋ࡚࠾ࡾ㸪2014 ᖺ 5 ᭶ 21 ᪥㏥㝔ࡋࡓࠋ㏥㝔ࣃࣛࢭࢱ࣮ࣔࣝ㸭࢜࢟ ࢩࢥࢻࣥ㸦Percocet㸧㸪ࣇ࢙ࣥࢱࢽࣝ㸪ࣇࣝࢥࢼࢰ࣮ࣝ㸪࢞ࣂ࣌ࣥࢳࣥ㸪࢞ࣥࢩࢡࣟࣅࣝ㸪 pantoprazole ཬࡧࣂࣛࢩࢡࣟࣅࣝࢆฎ᪉ࡉࢀࡓࠋ 2014 ᖺ 6 ᭶ 4 ᪥㸪⭡㒊⮋⒆ཬࡧࢡ࣮ࣟࣥࡢᝏࡢྛ㇟ࡣ㸪ᅇ㸭ᾘᩓࡋࡓሗ࿌ࡉࢀࡓࠋ
34 4 (208) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
13) Other Adverse Events Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2013-10-04 ᮎᲈᛶᾋ⭘ MODERATE/ N/ DOSE NOT CHANGED/ 2014-03-06 (25/.) (2+ BILATERAL ANKLE NOT NA RECOVERED/RESOLVED (178/.) EDEMA) RELATED 2013-11-19 ㈋⾑ MODERATE/ N/ DOSE NOT CHANGED/ 2013-11-22 (71/15) (WORSENING OF ANEMIA) NOT NA RECOVERED/RESOLVED (74/18) RELATED 2013-11-19 ప࣒࢝ࣜ࢘⾑ MILD/ N/ DOSE NOT CHANGED/ 2013-11-20 (71/15) (HYPOKALEMIA) NOT NA RECOVERED/RESOLVED (72/16) RELATED 2013-11-19 పࢼࢺ࣒ࣜ࢘⾑ MILD/ N/ DOSE NOT CHANGED/ 2013-11-20 (71/15) (HYPONATREMIA) NOT NA RECOVERED/RESOLVED (72/16) RELATED 2013-11-19 യ MODERATE/ N/ DOSE NOT CHANGED/ 2013-12-04 (71/15) (LEFT FACIAL LACERATION) NOT NA RECOVERED/RESOLVED (86/30) RELATED 2014-06-02 ⫵⅖ MILD/ Y/ DOSE NOT CHANGED/ Ongoing (266/210) (PNEUMONIA) NOT N NOT RECOVERED/NOT - RELATED RESOLVED
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route FUROSEMIDE 2013-10-04 2013-11-04 ORAL ALBUMIN HUMAN 2013-11-19 2013-11-19 INTRAVENOUS DRIP LIDOCAINE 2013-11-19 2013-11-19 OTHER SODIUM CHLORIDE 2013-11-19 2013-11-19 INTRAVENOUS BOLUS SODIUM CHLORIDE 2013-11-19 2013-11-20 INTRAVENOUS DRIP POTASSIUM CHLORIDE 2013-11-19 2013-11-19 ORAL KETOROLAC TROMETHAMINE 2013-11-19 2013-11-19 INTRAVENOUS PROCET /01554201/ 2013-11-20 2014-01-23 ORAL RED BLOOD CELLS 2013-11-20 2013-11-20 INTRAVENOUS LORAZEPAM 2014-01-23 2014-01-23 ORAL DEXTROSE AND SODIUM CHLORIDE INJECTION 2014-01-23 2014-02-02 INTRAVENOUS DRIP METRONIDAZOLE 2014-01-23 2014-01-23 INTRAVENOUS DRIP HYDROMORPHONE 2014-01-23 2014-02-06 INTRAVENOUS LEVOFLOXACIN 2014-01-23 2014-01-23 INTRAVENOUS DRIP MEROPENEM TRIHYDRATE 2014-01-23 2014-01-26 INTRAVENOUS DRIP SODIUM CHLORIDE 2014-01-23 2014-01-23 INTRAVENOUS BOLUS SODIUM CHLORIDE 2014-01-23 2014-02-14 INTRAVENOUS CHLORPROMAZINE 2014-01-23 2014-01-23 INTRAMUSCULAR INSULIN ASPART 2014-01-25 2014-02-14 SUBCUTANEOUS NYSTATIN 2014-01-26 2014-02-14 ORAL OXYCOCET 2014-01-27 - ORAL PIP/TAZO 2014-01-27 2014-02-04 INTRAVENOUS DRIP PARACETAMOL 2014-01-30 2014-01-31 INTRAVENOUS HYDROMORPHONE HYDROCHLORIDE 2014-01-30 2014-02-03 INTRAVENOUS EPHEDRINE 2014-01-30 2014-01-30 INTRAVENOUS FENTANYL 2014-01-30 2014-01-30 INTRAVENOUS KETAMINE 2014-01-30 2014-02-03 INTRAVENOUS DRIP FLEBOBAG RING LACT 2014-01-30 2014-01-30 INTRAVENOUS DRIP PHENYLEPHRINE 2014-01-30 2014-01-30 INTRAVENOUS PROPOFOL 2014-01-30 2014-01-30 INTRAVENOUS PANTOPRAZOLE SODIUM SESQUIHYDRATE 2014-01-30 2014-02-14 INTRAVENOUS ROCURONIUM 2014-01-30 2014-01-30 INTRAVENOUS ALVIMOPAN 2014-01-31 2014-02-02 ORAL ENOXAPARIN SODIUM 2014-01-31 2014-02-14 SUBCUTANEOUS GABAPENTIN 2014-02-04 - ORAL
34 5 (209) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
Preferred Term Start Date End Date Route FUROSEMIDE 2014-02-04 2014-02-04 INTRAVENOUS AMOXICILLIN 2014-02-05 - ORAL CIPROFLOXACIN 2014-02-05 - ORAL FENTANYL 2014-02-05 - TOPICAL LIPIDS NOS 2014-02-05 2014-05-14 INTRAVENOUS HYDROMORPHONE 2014-02-06 2014-02-14 ORAL PIP/TAZO 2014-02-06 2014-02-13 INTRAVENOUS RED BLOOD CELLS 2014-02-07 2014-02-07 INTRAVENOUS AMOXICILLIN 2014-02-13 2014-02-27 ORAL CIPROFLOXACIN 2014-02-13 2014-02-27 ORAL OMEPRAZOLE 2014-02-15 - ORAL CEFOXITIN 2014-05-15 2014-05-15 INTRAVENOUS HYDROMORPHONE HYDROCHLORIDE 2014-05-15 2014-05-15 INTRAVENOUS FENTANYL 2014-05-15 2014-05-15 INTRAVENOUS FLEBOBAG RING LACT 2014-05-15 2014-05-15 INTRAVENOUS LIDOCAINE 2014-05-15 2014-05-15 INTRAVENOUS PARACETAMOL 2014-05-15 2014-05-15 INTRAVENOUS PHENYLEPHRINE 2014-05-15 2014-05-15 INTRAVENOUS PROPOFOL 2014-05-15 2014-05-15 INTRAVENOUS ROCURONIUM 2014-05-15 2014-05-15 INTRAVENOUS ONDANSETRON 2014-05-15 2014-05-15 INTRAVENOUS DEXTROSE AND SODIUM CHLORIDE INJECTION 2014-05-16 2014-05-23 INTRAVENOUS HYDROMORPHONE HYDROCHLORIDE 2014-05-16 2014-05-22 INTRAVENOUS ENOXAPARIN SODIUM 2014-05-16 2014-05-22 SUBCUTANEOUS SOLUTIONS FOR PARENTERAL NUTRITION 2014-05-16 2014-05-23 INTRAVENOUS INTRALIPID /00272201/ 2014-05-19 2014-05-23 INTRAVENOUS PARACETAMOL 2014-05-19 2014-05-21 ORAL OXYCOCET 2014-05-20 2014-05-23 ORAL
(42) Subject CNTO1275CRD3003-1080-10452
1) Reason for narrative selection SAE Event of interest: Serious infection
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome I/M) 2013-05-07 ⫵⅖⌫⳦ᛶ⫵⅖(PNEUMOCOCCAL Y SEVERE/ Y/ DOSE NOT CHANGED/ 2013-05-23 (292/238) PNEUMONIA) DOUBTFUL Y RECOVERED/RESOLVED (308/254)
3) Baseline Demographic Information ȋȌǣ ͵ͷ ǣ ȋȌǣ ͷͷǤ͵ ǣ ǣ ͳͻǦͲ͵ǦͲͷ ȋ Ȍǣ ͳͲǤʹ
4) Induction Treatment Group Induction study: CNTO1275CRD3001 Randomized Treatment Group: Ustekinumab 130 mg IV Actual Treatment Group: Ustekinumab 130 mg IV
34 6 (210) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
5) Maintenance Treatment Group Assigned Treatment Group: Randomized subject/Responder to ustekinumab IV induction dosing/ustekinumab 90 mg SC q8w
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2012-07-20 1 Ustekinumab 129.6 mg WEEK 0 MAINTENANCE 2012-09-12 55 Ustekinumab 90 mg WEEK 8 MAINTENANCE 2012-11-07 111 Ustekinumab 90 mg WEEK 12 MAINTENANCE 2012-12-07 141 Placebo 0 mg WEEK 16 MAINTENANCE 2013-01-02 167 Ustekinumab 90 mg WEEK 20 MAINTENANCE 2013-02-05 201 Placebo 0 mg WEEK 24 MAINTENANCE 2013-02-28 224 Ustekinumab 90 mg WEEK 28 MAINTENANCE 2013-04-02 257 Placebo 0 mg WEEK 32 MAINTENANCE 2013-04-23 278 Ustekinumab 90 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: Y Did the subject terminate the study participation before the Week 44 visit?: Y Did subject enter the long-term extension study?: -
8) Induction Baseline Crohn's Disease History Date of diagnosis: 05MAR1998 Disease duration: 14.38 years Involved areas: ⤖⭠ࡢࡳ㸪⫠㛛࿘ᅖ
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: NEVER Stricture complications of (CD): NEVER
10) Concomitant Crohn's Disease-Related Surgeries None reported
11) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 32 MAINTENANCE DEXAMETHASONE 1 -
12) Narrative Text ⿕㦂⪅ࡣ 3 ṓࡢⓑேዪᛶ࡛㸪2012 ᖺ 7 ᭶ 20 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏࢆ㟼⬦ෆᢞࡉࢀ ࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏ 90 mg ࢆ q8w ࡛⓶ୗᢞࡍࡿ⩌ࣛࣥࢲ࣒ࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪㧗⾑ᅽ㸪ཱྀ⭍ ࢝ࣥࢪࢲࡢⓎཬࡧႚ↮㸦16 ṓࡽ 1 ᪥ 1 ⟽㸧࡛࠶ࡗࡓࠋ SAE/Serious infection㸸⫵⅖⌫⳦ᛶ⫵⅖㸦Day 292㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ㸪3㹼5 ᪥㛫⥆ࡃᝏᚰཬࡧྤࡢᝏ㸪⾑⑱ࢆక࠺‵ᛶတႿ㸪ᝏᐮ ࢆక࠺Ⓨ⇕㸦102°F㸧ཬࡧ 1 㐌㛫⥆ࡃᜥษࢀࢆッ࠼㸪2013 ᖺ 5 ᭶ 8 ᪥ධ㝔ࡋࡓࠋࣂࢱࣝࢧ
34 7 (211) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
ࣥࡣ㸪⾑ᅽ 79/49 mmHg㸪ᚰᢿᩘ 49 ᢿ/ศ㸪య 97.1°F ࡛࠶ࡗࡓࠋ⾑ᾮ࢞ࢫศᯒࡣ㸪⾑ᾮ pH 7.23 㹙ṇᖖ⠊ᅖ㸦NR㸧7.38-7.44㹛㸪㓟⣲ศᅽ 22 mmHg㸪㓟Ⅳ⣲ศᅽ 59 mmHg㸦NR 35-
45 mmHg㸧㸪HCO3 25 mEq/L㸦NR 24-26 mEq/L㸧࡛࠶ࡗࡓࠋᩆᛴ⒪ᐊ࡛⏕⌮㣗ሷỈࡢᛴ㏿㟼⬦ ෆᢞᚋ㸪⿕㦂⪅ࡣ⇕ࡀୗࡀࡾ㸪⾑ᅽࡣ 110/80 mmHg ୖ᪼ࡋࡓࠋ⮫ᗋ᳨ᰝ␗ᖖ್㸦2013 ᖺ 5 ᭶ 7 ᪥㸧ࡣ㸪⾑୰ᒀ⣲❅⣲ 35 ȝg/dL㸦NR 7-18 ȝg/dL㸧㸪C ᛂᛶࡓࢇⓑ⃰ᗘ>380.0 mg/L㸦NR ᫂㸧㸪ࢡࣞࢳࢽࣥ 1.71 mg/dL㸦NR 0.70-1.20 mg/dL㸧ཬࡧⓑ⾑⌫ᩘ 17.5×103/mm3㸦NR 4.9- 11.0×103/mm3㸧࡛࠶ࡗࡓࠋ2013 ᖺ 5 ᭶ 7 ᪥ࡢ⬚㒊ཬࡧ⭡㒊ࢥࣥࣆ࣮ࣗࢱ᩿ᒙᙳ㸦CT㸧ࢫ࢟ࣕࣥ ࡛ࡣ㸪⫵⅖୍⮴ࡍࡿീ㸪㠀㛢ሰᛶᕥ⭈⤖▼㸪ࢡ୍࣮ࣟࣥ⮴ࡍࡿከᩘࡢ⭠ቨ⫧ཌ༊ᇦࡀㄆ ࡵࡽࢀ㸪⫵ᗏ୰ᚰ㒊ࡢ⫵⬊ᛶ㝜ᙳཬࡧ⫵ฟ⾑ࡀࢃࢀࡿീࡶㄆࡵࡽࢀࡓࠋ⾑ΎᏛⓗ᳨ᰝࡣ㸪ࢫ ࣌ࣝࢠࣝࢫ IgG ཬࡧ IgA 㝧ᛶ࡛࠶ࡾ㸪௨๓࢝ࣅ᭚㟢ࡋ࡚࠸ࡓࡇࡀ♧၀ࡉࢀࡓࠋ⫵⅖ࣞࣥࢧ⌫ ⳦ࡶ㝧ᛶ࡛࠶ࡗࡓࠋ2013 ᖺ 5 ᭶ 8 ᪥ࡢ࣏࣓࣮ࣜࣛࢮ㐃㙐ᛂ᳨ᰝ࡛ࡣ㸪ࣛࣀ࢘ࣝࢫ㝧ᛶ࡛࠶ ࡗࡓࠋྠ᪥ࡢၻ⑱ࡢࢢ࣒ࣛᰁⰍ࡛ࡣ㸪௬ᛶ⳦⣒ࢆక࠺㓝ẕ㸪ⓑ⾑⌫㸪ࢢ࣒ࣛ㝧ᛶ⌫⳦ཬࡧࢢ࣒ࣛ 㝧ᛶᱰ⳦ࡀㄆࡵࡽࢀࡓࠋデᐹ㬾ཱྀ⒔ࡶㄆࡵࡽࢀࡓࠋ⤒⬚ቨᚰ࢚ࢥ࣮ᅗ࡛ࡣ㸪55%-65%ࡢᕥᐊ 㥑ฟ⋡࡛࠶ࡾ㸪ኚᛶൔᖗᘚᝈࡀㄆࡵࡽࢀࡓࠋධ㝔ࡢ⾑ᾮᇵ㣴᳨ᰝ࡛ࡣ㸪㯤Ⰽࣈࢻ࢘⌫⳦㝧ᛶ ࡛࠶ࡗࡓࡀ㸪᳨ᰝࡣ㝜ᛶ࡛࠶ࡗࡓࠋ⒪ࡣࣞ࣎ࣇࣟ࢟ࢧࢩࣥ㸪nafcillin㸪ࣂࣥࢥ࣐ࢩࣥ㸪 ࣆ࣌ࣛࢩࣜࣥ㸭ࢱࢰࣂࢡࢱ࣒㸦ࢰࢩࣥ㸧㸪ࢩࣉࣟࣇࣟ࢟ࢧࢩࣥ㸪ࣇࣝࢥࢼࢰ࣮ࣝ㸪࣓࢜ࣉࣛࢰ࣮ ࣝཬࡧ࢚ࣀ࢟ࢧࣃࣜࣥࡀ⏝࠸ࡽࢀ㸪⥅⥆ⓗ࡞ࣃࣝࢫ࢜࢟ࢩ࣓ࢺ࣮ࣜཬࡧࢸ࣓ࣞࢺ࣮ࣜࡼࡾࣔࢽ ࢱࣜࣥࢢࡉࢀࡓࠋ2013 ᖺ 5 ᭶ 15 ᪥㸪ࢡࣞࢳࢽࣥࡣ 0.59 mg/dL㸦NR 0.70-1.20 mg/dL㸧పୗ ࡋࡓࠋ⿕㦂⪅ࡣ㸪2013 ᖺ 5 ᭶ 15 ᪥㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2012-08-26 တႿ MILD/ N/ DOSE NOT CHANGED/ Ongoing (38/.) (COUGH) NOT NA NOT RECOVERED/NOT - RELATED RESOLVED 2012-10-28 ࢘ࣝࢫᛶ⫶⭠⅖ MILD/ Y/ DOSE NOT CHANGED/ 2012-10-29 (101/47) (VIRAL GASTROENTERITIS) POSSIBLE N RECOVERED/RESOLVED (102/48) 2013-02-15 ࢘ࣝࢫᛶ⫶⭠⅖ MILD/ Y/ DOSE NOT CHANGED/ 2013-02-16 (211/157) (VIRAL GASTROENTERITIS) DOUBTFUL N RECOVERED/RESOLVED (212/158) 2013-02-17 ࡊ⒔ MILD/ N/ DOSE NOT CHANGED/ 2013-05-15 (213/159) (ACNE) DOUBTFUL NA RECOVERED/RESOLVED (300/246) 2013-04-19 ⤖⭷⅖ MILD/ Y/ DOSE NOT CHANGED/ 2013-04-26 (274/220) (CONJUNCTIVITIS - RIGHT NOT Y RECOVERED/RESOLVED (281/227) EYE) RELATED 2013-04-23 ⤖⭷⅖ MILD/ Y/ DOSE NOT CHANGED/ 2013-04-26 (278/224) (CONJUNCTIVITIS - LEFT NOT Y RECOVERED/RESOLVED (281/227) EYE) RELATED 2013-05-08 ཱྀ⭍࢝ࣥࢪࢲ MILD/ Y/ DOSE NOT CHANGED/ 2013-05-22 (293/239) (ORAL CANDIDIASIS) DOUBTFUL Y RECOVERED/RESOLVED (307/253)
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route DEXACIDIN OPHTHALMIC 2013-04-19 2013-04-26 OPHTHALMIC CIPROFLOXACIN HYDROCHLORIDE 2013-05-07 2013-05-08 ORAL NICOTINE 2013-05-07 2013-05-15 TOPICAL SODIUM CHLORIDE 2013-05-07 2013-05-15 INTRAVENOUS SODIUM CHLORIDE 2013-05-07 2013-05-08 INTRAVENOUS VANCOMYCIN 2013-05-07 2013-05-07 INTRAVENOUS PIP/TAZO 2013-05-07 2013-05-08 INTRAVENOUS
34 8 (212) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
Preferred Term Start Date End Date Route CIPROFLOXACIN 2013-05-08 2013-05-15 INTRAVENOUS VANCOMYCIN 2013-05-08 2013-05-10 INTRAVENOUS ENOXAPARIN SODIUM 2013-05-09 2013-05-15 SUBCUTANEOUS FLUCONAZOLE 2013-05-09 2013-05-22 ORAL OMEPRAZOLE 2013-05-09 2013-05-15 ORAL PNEUMOCOCCAL VACCINE 2013-05-09 2013-05-09 INTRAMUSCULAR POTASSIUM CHLORIDE 2013-05-09 2013-05-09 ORAL GADOTERIDOL 2013-05-10 2013-05-10 INTRAVENOUS LEVOFLOXACIN 2013-05-10 2013-05-15 ORAL NAFCILLIN SODIUM 2013-05-10 2013-05-22 INTRAVENOUS POTASSIUM CHLORIDE 2013-05-10 2013-05-15 ORAL BACITRACIN 2013-05-12 2013-05-12 TOPICAL LIDOCAINE 2013-05-12 2013-05-12 SUBCUTANEOUS PROMETHAZINE HYDROCHLORIDE 2013-05-12 2013-05-15 ORAL
(43) Subject CNTO1275CRD3003-1096-10651
1) Reason for narrative selection SAE Event of interest: Serious infection
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome (Study day I/M) 2012-12-24 ࢘ࣝࢫᛶ⫶⭠⅖ Y MODERATE/ Y/ DOSE NOT CHANGED/ 2012-12-29 (96/40) (VIRAL GASTROENTERITIS) NOT RELATED Y RECOVERED/RESOLVED (101/45)
3) Baseline Demographic Information ȋȌǣ ͷ ǣ ȋȌǣ ͳʹͳǤͳ ǣ ǣ ͳͻͷͷǦͲǦʹͷ ȋ Ȍǣ ͳʹǤ
4) Induction Treatment Group Induction study: CNTO1275CRD3001 Randomized Treatment Group: Ustekinumab 130 mg IV Actual Treatment Group: Ustekinumab 130 mg IV
5) Maintenance Treatment Group Assigned Treatment Group: Randomized subject/Responder to ustekinumab IV induction dosing/ustekinumab 90 mg SC q12w
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2012-09-20 1 Ustekinumab 129.6 mg WEEK 0 MAINTENANCE 2012-11-15 57 Ustekinumab 90 mg WEEK 8 MAINTENANCE 2013-01-10 113 Placebo 0 mg WEEK 12 MAINTENANCE 2013-02-11 145 Ustekinumab 90 mg WEEK 16 MAINTENANCE 2013-03-11 173 Placebo 0 mg WEEK 20 MAINTENANCE 2013-04-08 201 Placebo 0 mg WEEK 24 MAINTENANCE 2013-05-06 229 Ustekinumab 90 mg WEEK 28 MAINTENANCE 2013-06-03 257 Placebo 0 mg WEEK 32 MAINTENANCE 2013-07-08 292 Placebo 0 mg WEEK 36 MAINTENANCE 2013-08-05 320 Ustekinumab 90 mg
34 9 (213) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
Visit Start Date Study Day Actual Treatment Dose WEEK 40 MAINTENANCE 2013-08-26 341 Placebo 0 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: N Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: Y
8) Induction Baseline Crohn's Disease History Date of diagnosis: 31DEC2007 Disease duration: 4.73 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪⫠㛛࿘ᅖ
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: NEVER Stricture complications of (CD): PREVIOUS HISTORY
10) Concomitant Crohn's Disease-Related Surgeries None reported
11) Concomitant Steroids None reported
12) Narrative Text ⿕㦂⪅ࡣ 5 ṓࡢⓑே⏨ᛶ࡛㸪2012 ᖺ 9 ᭶ 20 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏࢆ㟼⬦ෆᢞࡉࢀ ࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏ 90 mg ࢆ q12w ࡛⓶ୗᢞࡍࡿ⩌ࣛࣥࢲ࣒ࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪㧗⬡⾑㸪㧗 ⾑ᅽ㸪↓ೃᛶὝೃ⩌㸪ᮎᮇࡢኚᙧᛶ⭸㛵⠇㸪᠁ᐊᛶᝈ㸪࣮࣌ࢫ࣓࣮࣮࢝␃⨨㸦ึ ᅇ㸸16 ᖺ๓㸪2 ᅇ┠㸸2011 ᖺ㸧㸪デ᩿ⓗ⭡⭍㙾᳨ᰝ㸦18 ṓ㸧㸪ᆶษ㝖㸪ẟᕢᄞ⬊㝖ཤ㸪㐣 ཤࡢႚ↮㸦1996 ᖺ୰Ṇ㸧ཬࡧࡲࢀ࡞㣧㓇࡛࠶ࡗࡓࠋᐙ᪘Ṕࡣ㸪ෙື⬦ᝈ࡛࠶ࡗࡓࠋ SAE/Serious infection㸸࢘ࣝࢫᛶ⫶⭠⅖㸦Day 96㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ㸪1 ᪥⥆࠸ࡓᝏᚰཬࡧྤ㸪⬺ຊ㸪㣗ḧ႙ኻ㸪⭡㒊ᛌឤཬࡧ」ᩘ ᅇཬࡪᣢ⥆ᛶࡢỈᵝ౽ࢆッ࠼࡚ᩆᛴᦙ㏦ࡉࢀࡓᚋ㸪2012 ᖺ 12 ᭶ 24 ᪥ධ㝔ࡋࡓࠋᅄ⫥㠀ᅽ ᛶࡢ㸦nonpitting㸧ᾋ⭘㸪ྑᡭᕥᡭࡼࡾࡶᙉ࠸⭘⬽ࡀㄆࡵࡽࢀ㸪⭘⬽ࡣᩘ࢝᭶㛫ᣢ⥆ࡋ࡚࠸ࡓࠋ ࢥࣥࣆ࣮ࣗࢱ᩿ᒙᙳࢫ࡛࢟ࣕࣥࡣ㸪ᛴᛶ⅖ᛂ㐣⛬ࡢ࡞࠸ࢡ࣮ࣟࣥࢆక࠺ S ≧⤖⭠ཬࡧ┤ ⭠ࡢኚ㸪⫢⮚ࡢ⬡⫫ᾐ₶㸪ᶓ⾜⤖⭠ࡢ᠁ᐊཬࡧ 8 mm ࡢ☜ᐃ࡞ྑ⭈ୖᴟࡢኚ㸦Ỉ⭈࡞ ࡋ㸧ࡀㄆࡵࡽࢀࡓࠋ2012 ᖺ 12 ᭶ 25 ᪥㸪ෆど㙾᳨ᰝࡼࡾ࢘ࣝࢫᛶ⫶⭠⅖ࡀ♧၀ࡉࢀࡓࠋ౽ ᇵ㣴ཬࡧ౽᳨ᰝ࡛ࡣ㸪ࢡࣟࢫࢺࣜࢪ࣒࣭࢘ࢹࣇࢩࣞࢆྵࡵ࡚㝜ᛶ࡛࠶ࡗࡓࠋ⿕㦂⪅ࡣ㟼⬦ෆ ⿵ᾮ㸪࢜ࣥࢲࣥࢭࢺࣟࣥཬࡧࢩࣉࣟࣇࣟ࢟ࢧࢩࣥࡼࡿ⒪ࢆཷࡅ㸪2012 ᖺ 12 ᭶ 29 ᪥㏥㝔ࡋ ࡓࠋ
35 0 (214) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
13) Other Adverse Events None reported
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route CIPROFLOXACIN 2012-12-25 2012-12-29 INTRAVENOUS DRIP
(44) Subject CNTO1275CRD3003-2301-10432
1) Reason for narrative selection SAE Event of interest: Serious infection
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome (Study day I/M) 2013-01-16 ⫶⭠⅖ Y SEVERE/ Y/ DOSE NOT CHANGED/ 2013-01-17 (157/100) (GASTROENTERITIS) NOT RELATED N RECOVERED/RESOLVED (158/101)
3) Baseline Demographic Information ȋȌǣ ʹʹ ǣ ȋȌǣ ͶͺǤ͵ ǣ ǣ ͳͻͻͲǦͲͳǦͲͳ ȋ Ȍǣ ͳͳ
4) Induction Treatment Group Induction study: CNTO1275CRD3001 Randomized Treatment Group: Ustekinumab Approximating 6 mg/kg IV Actual Treatment Group: Ustekinumab Approximating 6 mg/kg IV
5) Maintenance Treatment Group Assigned Treatment Group: Randomized subject/Responder to ustekinumab IV induction dosing/ustekinumab 90 mg SC q12w
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2012-08-13 1 Ustekinumab 259.2 mg WEEK 0 MAINTENANCE 2012-10-09 58 Ustekinumab 90 mg WEEK 8 MAINTENANCE 2012-12-05 115 Placebo 0 mg WEEK 12 MAINTENANCE 2013-01-09 150 Ustekinumab 90 mg WEEK 16 MAINTENANCE 2013-01-30 171 Placebo 0 mg WEEK 20 MAINTENANCE 2013-02-27 199 Placebo 0 mg WEEK 24 MAINTENANCE 2013-03-27 227 Ustekinumab 90 mg WEEK 28 MAINTENANCE 2013-04-24 255 Placebo 0 mg WEEK 32 MAINTENANCE 2013-05-22 283 Placebo 0 mg WEEK 36 MAINTENANCE 2013-06-19 311 Ustekinumab 90 mg WEEK 40 MAINTENANCE 2013-07-17 339 Placebo 0 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: N Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: Y
35 1 (215) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
8) Induction Baseline Crohn's Disease History Date of diagnosis: 30NOV2009 Disease duration: 2.70 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪ᾘ⟶እኚ㸦㛵⠇⅖㸭㛵⠇③㸧
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: CURRENTLY PRESENT Stricture complications of (CD): CURRENTLY PRESENT
10) Concomitant Crohn's Disease-Related Surgeries None reported
11) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 36 MAINTENANCE SCHERIPROCT - -
12) Narrative Text ⿕㦂⪅ࡣ 2 ṓࡢⓑேዪᛶ࡛㸪2012 ᖺ 8 ᭶ 13 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏࢆ㟼⬦ෆᢞࡉࢀ ࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏ 90 mg ࢆ q12w ࡛⓶ୗᢞࡍࡿ⩌ࣛࣥࢲ࣒ࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪㕲Ḟஈᛶ㈋⾑㸪 㝜၁⮋⒆㸪ᅇ⤖⭠⅖ཬࡧࢨࢳ࢜ࣉࣜࣥᑐࡍࡿࣞࣝࢠ࣮࡛࠶ࡗࡓࠋ SAE/Serious infection㸸⫶⭠⅖㸦Day 157㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ㸪ୗ⑩ཬࡧⓎ⇕ࡢ࡞࠸⭡㒊③ࢆッ࠼㸪ᛴᛶ⫶⭠⅖ࡢࡓࡵ 2013 ᖺ 1 ᭶ 16 ᪥ධ㝔ࡋࡓࠋX ⥺⏬ീ㸦ྠ᪥㸧࡛ࡣ㸪⤖⭠ᕥഃ౽ࡀㄆࡵࡽࢀࡓࠋ㐟㞳࢞ࢫࡢᚩೃࡣ࡞ ࡗࡓࠋྠ᪥ࡢ⭡㒊㉸㡢Ἴ᳨ᰝ࡛ࡣ㸪ᅇ┣ᘚ㸪S ≧⤖⭠㐲㸪S ≧⤖⭠㏆㸪ᶓ⾜⤖⭠ᕥഃ㸪ᶓ ⾜⤖⭠୰ኸ㸪ᶓ⾜⤖⭠ྑഃཬࡧᅇ⭠࡛ࡣṇᖖ࡞⭠⟶ቨࡢཌࡉ㸦<3 mm㸧࡛࠶ࡾ㸪⭡Ỉࡣㄆࡵࡽࢀ ࡞ࡗࡓࠋ౽ᇵ㣴᳨ᰝࡣ㝜ᛶ࡛࠶ࡗࡓࠋ⒪ࡣ hyoscine butylbromide㸪࣓ࢺࢡࣟࣉ࣑ࣛࢻཬࡧ ࢫࢥ࣏࣑ࣛࣥࡀ⏝࠸ࡽࢀࡓࠋ⿕㦂⪅ࡣ㸪2013 ᖺ 1 ᭶ 17 ᪥㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2012-10-19 㕲Ḟஈ MILD/ N/ DOSE NOT CHANGED/ 2012-12-03 (68/11) (IRON DEFFICIENCY) NOT NA RECOVERED/RESOLVED (113/56) RELATED 2013-01-30 ⭡③ MILD/ N/ DOSE NOT CHANGED/ 2013-03-27 (171/114) (ABDOMINAL PAIN) NOT NA RECOVERED/RESOLVED (227/170) RELATED 2013-03 Ⓨ⑈ MILD/ N/ DOSE NOT CHANGED/ 2013-06-19 - (EXANTHEMA) NOT NA RECOVERED/RESOLVED (311/254) RELATED 2013-04-23 ⭡③ MILD/ N/ DOSE NOT CHANGED/ Ongoing (254/197) (INTERMITTENT ABDOMINAL NOT NA NOT RECOVERED/NOT - PAIN) RELATED RESOLVED 2013-05-19 㣗ḧῶ㏥ MILD/ N/ DOSE NOT CHANGED/ 2013-06-19 (280/223) (LOSS OF APPETITE) NOT NA RECOVERED/RESOLVED (311/254) RELATED
35 2 (216) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route AKTIFERRIN /00631201/ 2012-10-19 2012-12-03 ORAL HYOSCINE BUTYLBROMIDE 2013-01-16 2013-01-16 INTRAVENOUS METOCLOPRAMIDE 2013-01-16 2013-01-16 INTRAVENOUS MORPHINE HYDROCHLORIDE 2013-01-16 2013-01-16 INTRAVENOUS TRAVOCORT 2013-03 - TOPICAL PARACETAMOL 2013-07-02 - ORAL
(45) Subject CNTO1275CRD3003-2709-10296
1) Reason for narrative selection SAE Event of interest: Serious infection
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome I/M) 2012-11-05 ࢡ࣮ࣟࣥ Y SEVERE/ N/ DOSE NOT CHANGED/ 2013-09-25 (132/75) (SEVERE ABDOMINAL PAIN DUE NOT NA RECOVERED/RESOLVED (456/399) TO CROHNS DISEASE) RELATED 2013-06-14 ࢡ࣮ࣟࣥ Y SEVERE/ N/ DOSE NOT CHANGED/ 2013-09-25 (353/296) (CROHNS DISEASE) DOUBTFUL NA RECOVERED/RESOLVED (456/399) 2013-06-29 ⴥᛶ⫵⅖ Y MODERATE/ Y/ DOSE NOT CHANGED/ 2013-10-24 (368/311) (LEFT LOWER LOBE PNEUMONIA) NOT N RECOVERED/RESOLVED (485/428) RELATED
3) Baseline Demographic Information Age (years): 3 Sex: Male Weight (kg): 72.3 Race: White Date of birth: Height (cm): 192.5
4) Induction Treatment Group Induction study: CNTO1275CRD3001 Randomized Treatment Group: Ustekinumab Approximating 6 mg/kg IV Actual Treatment Group: Ustekinumab Approximating 6 mg/kg IV
5) Maintenance Treatment Group Assigned Treatment Group: Randomized subject/Responder to ustekinumab IV induction dosing/ustekinumab 90 mg SC q8w
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2012-06-27 1 Ustekinumab 389.7 mg WEEK 0 MAINTENANCE 2012-08-23 58 Ustekinumab 90 mg WEEK 8 MAINTENANCE 2012-10-18 114 Ustekinumab 90 mg WEEK 12 MAINTENANCE 2012-11-15 142 Placebo 0 mg WEEK 16 MAINTENANCE 2012-12-17 174 Ustekinumab 90 mg WEEK 20 MAINTENANCE 2013-01-10 198 Placebo 0 mg WEEK 24 MAINTENANCE 2013-02-07 226 Ustekinumab 90 mg WEEK 28 MAINTENANCE 2013-03-07 254 Placebo 0 mg WEEK 32 MAINTENANCE 2013-04-03 281 Ustekinumab 90 mg WEEK 36 MAINTENANCE 2013-05-02 310 Placebo 0 mg WEEK 40 MAINTENANCE 2013-05-30 338 Ustekinumab 90 mg
35 3 (217) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: N Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: Y
8) Induction Baseline Crohn's Disease History Date of diagnosis: 19OCT1999 Disease duration: 12.69 years Involved areas: ᅇ⭠ࡢࡳ㸪ᑠ⭠㏆㸭⫶㸭㣗㐨㸪ᾘ⟶እኚ㸦PSC㸧
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: PREVIOUS HISTORY Sinus tracts/perforation: NEVER Fistula: NEVER Stricture complications of (CD): PREVIOUS HISTORY
10) Concomitant Crohn's Disease-Related Surgeries Surgery Date Result of lack of efficacy? ⾑⭘㝖ཤ㸦⊃✽ᙧᡂ㒊࠾ࡅࡿ㸪ᑠ⭠₃ฟᚋ㸧 2013-06-19 N ヨ㦂㛤⭡㸪ᑠ⭠⥺⥔ᛶ⊃✽ษ㝖 2013-06-25 N
11) Concomitant Steroids None reported
12) Narrative Text ⿕㦂⪅ࡣ 3 ṓࡢⓑே⏨ᛶ࡛㸪2012 ᖺ 6 ᭶ 27 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏࢆ㟼⬦ෆᢞࡉࢀ ࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏ 90 mg ࢆ q8w ࡛⓶ୗᢞࡍࡿ⩌ࣛࣥࢲ࣒ࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪Ᏻ㸪╧╀㞀 ᐖ㸪៏ᛶୗ⑩㸪ษ㝖⾡㸦5 ᅇ㸧㸪⫠ཬࡧ⫹ᄞษ㝖࡛࠶ࡗࡓࠋ⿕㦂⪅ࡢᐙ᪘Ṕࡣ㸪ෙື⬦ᛶᝈ ࡛࠶ࡗࡓࠋ SAEs㸸ࢡ࣮ࣟࣥ㸦Day 132㸪Day 353㸧 SAE/Serious Infection㸸ⴥᛶ⫵⅖㸦Day 368㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2012 ᖺ 11 ᭶ 5 ᪥ᩆᛴእ᮶ࢆཷデࡋ㸪㧗ᗘࡢ⭡③ࢆッ࠼ࡓ㸦⑊ ③ࢫࢣ࣮࡛ࣝᙉᗘ 10/10㸧ࠋࡲࡓ㸪2012 ᖺ 11 ᭶ 4 ᪥ࡢ౽ᅇᩘࡣ 14 ᅇ㸪11 ᭶ 5 ᪥ࡣ 3 ᅇ࡛࠶ࡗ ࡓ㸦ᅇᩘቑຍ㸪⾑౽࡞ࡋ㸧ࠋ⒪ࡣ㸪ketorolac㸪ࢩࣉࣟࣇࣟ࢟ࢧࢩࣥ㸪࣓ࢺࣟࢽࢲࢰ࣮ࣝཬࡧ Ύὶື㣗㸦clear liquid㸧ࡀ⏝ࡉࢀࡓࠋ㏥㝔ࡣ㸪ketorolac ࡀฎ᪉ࡉࢀࡓࠋ⿕㦂⪅ࡣ 2013 ᖺ 2 ᭶ 6 ᪥⭡③ࡢᣢ⥆ࢆッ࠼㸪⑊③ࢫࢣ࣮ࣝࡢᙉᗘࢆ 4/10 ホ౯ࡋࡓࠋ2013 ᖺ 5 ᭶ 1 ᪥㸪⿕㦂 ⪅ࡣ⭡③ࡢᝏ㸦ᙉᗘ 10/10㸧ࢆッ࠼ᩆᛴᦙ㏦ࡉࢀࡓࠋ⤊ኪྤࡀ࠶ࡾ㸪ୗ⑩ࡀᣢ⥆ࡋ࡚࠸ࡿ ッ࠼ࡓࡀ㸪⾑౽ཬࡧⓎ⇕ࡣ࡞ࡗࡓࠋ⿕㦂⪅ࡣᛌឤࡀࡳࡽࢀ㸪ࣂࢱࣝࢧࣥࡣ㸪⾑ᅽ 122/85 mmHg㸪ᚰᢿᩘ 74 ᢿ/ศ㸪྾ᩘ 35 ᅇ/ศ࡛࠶ࡗࡓࠋ⭡㒊ࡢデᐹ࡛ࡣ㸪య⭡ቨ㜵ᚚࢆ క࠺᫂ࡽ࡞ᅽ③ࡀㄆࡵࡽࢀࡓࠋ
35 4 (218) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
⿕㦂⪅ࡣ㸪ᝏᚰ㛵㐃ࡍࡿ㧗ᗘࡢ⭡③ࡀ 3 ᪥㛫ᣢ⥆ࡋ࡚࠾ࡾ㸪2013 ᖺ 6 ᭶ 19 ᪥ධ㝔ࡋࡓࠋ ⿕㦂⪅ࡣ㸪౽ᛶ≧ࡣḟ➨ᾮ≧࡞ࡾ㸪㣗ᦤྲྀⰋ࡞ࡾ㸦┤㏆ 10 ᪥ࡽ 2 㐌㛫ࡢ㛫㸧㸪┤ ㏆ 1 ࢝᭶㛫࡛ 20 ࣏ࣥࢻࡢయ㔜ቑຍ୪ࡧ⭡㒊⭾‶ཬࡧ⭘⬽ࢆッ࠼ࡓࠋᾋືᛶࡵࡲ࠸㸪㟝どࡶッ ࠼ࡓࡀ㸪Ⓨ⇕ཬࡧᝏᐮࡣྰᐃࡋࡓࠋ⿕㦂⪅ࡣ㸪㧗ᗘࡢ⭡③㸪ྤཬࡧୗ⑩ࡼࡾᩆᛴᦙ㏦ࡉࢀ ⒪ࡋࡓ 2013 ᖺ 5 ᭶ 1 ᪥ࢆྵࡵ㸪ධ㝔๓ࡢ 4 ࢝᭶㛫㸪⭡③ࢆホ౯ࡉࢀ࡚࠸ࡓࠋࣔࣝࣄࢿࢆᢞ ࡉࢀࡓࡀ㸪⭡③ࡣ㍍ῶࡋ࡞ࡗࡓࠋC ᛂᛶࡓࢇⓑ⃰ᗘࡣ 8.3 mg/L㹙ṇᖖ⠊ᅖ㸦NR㸧<5 mg/L㹛 ࡛࠶ࡗࡓࠋ⭡㒊㉸㡢Ἴ᳨ᰝ㸦2013 ᖺ 5 ᭶ 1 ᪥㸧࡛ࡣ㸪⤖⭠య」ᩘࡢ㙾㠃ീࢆక࠺୰➼ᗘ㔞ࡢ ࢞ࢫ㸪ᕥ⭡㒊୰ኸ㙾㠃ീࢆక࠺Ꮩ❧ᛶࡢᣑᙇࡋࡓ✵⭠ಀ㋟ࡀㄆࡵࡽࢀࡓ㸦ᑠ⭠㏆ࢡ࣮ࣟࣥ 㛵㐃ࡍࡿ⊃✽ࡀᏑᅾࡋ࡚࠸ࡓࡇ㉳ᅉࡍࡿ⪃࠼ࡽࢀࡿ㸧ࡀ㸪㐟㞳࢞ࢫࡢᚩೃࡣ࡞ࡗࡓࠋ ⭡㒊ཬࡧ㦵┙㒊ࢥࣥࣆ࣮ࣗࢱ᩿ᒙᙳ㸦CT㸧ࢫ࡛࢟ࣕࣥࡣ㸪ᑠ⭠㏆㛢ሰ㸭ᑠ༊⏬ࡢ⊃✽ ⥆Ⓨࡍࡿᣑᙇࡀㄆࡵࡽࢀ㸪៏ᛶⓗ࡞ࡶࡢ⪃࠼ࡽࢀࡓࡀ㸪άືᮇࡢ⅖ࡢᚩೃࡣ࡞ࡗࡓࠋ⒪ ࡣ㸪ketorolac tromethamine ࡀ⏝ࡉࢀࡓࠋ⿕㦂⪅ࡣ㸪┤㏆࡛ࡣ㸪2013 ᖺ 6 ᭶ 17 ᪥ᩆᛴእ᮶ ࢆཷデࡋ࡚࠸ࡓࠋX ⥺㏱どୗ࡛ࡢᑠ⭠ࡢࣂ࣮ࣝࣥᣑᙇ⾡ࢆ⾜ࡋࡓ㸦᪥᫂㸧ࡇࢁ㸪ᑠ⭠ࡢ ୍㒊ࡀࣂ࣮ࣝࣥᣑᙇ㒊ศⓗ㏱᫂ࡋ࡚࠸ࡓࠋ2013 ᖺ 6 ᭶ 19 ᪥ࡢ⌮Ꮫⓗᡤぢ࡛ࡣ㸪⭡㒊 ⭾‶ࡣ࡞ࡃ㸪ᅽ③ࡣᕥୗ⭡㒊㸪ᕥ㦵ୖ㒊ཬࡧᕥ⬥⭡㝈ᒁࡋ࡚࠸ࡓࠋࡲࡓ㸪ᅽ③㒊⭡ቨ㜵 ᚚࡣ࡞ࡗࡓࡀ㸪㊴③ཬࡧ⭠㞧㡢ῶᙅࢆㄆࡵࡓࠋ㠀⤒ཱྀᰤ㣴㸦TPN㸧ࢆ┠ⓗࡋ㸪୰ᚰ㟼 ⬦࢝ࢸ࣮ࢸࣝ㸦central line㸧ࢆ␃⨨ࡋࡓࠋ⭡㒊 X ⥺᳨ᰝ࡛ࡣ㸪⭠⟶ࡢ࢞ࢫീ␗ᖖࡣ࡞ࡃ㸪㐟㞳 ࢞ࢫࡣㄆࡵ࡞ࡗࡓࠋ⭡㒊ཬࡧ㦵┙㒊 CT ࢫ࢟ࣕࣥ㸦2013 ᖺ 6 ᭶ 18 ᪥㸧࡛ࡣ㸪✵⭠ࡢື⬦⒗ᛶ ᣑᙇࡀࡳࡽࢀࡿᑠ⭠ᑠ⭠࿀ྜ㒊㏆ࡢ༑ᣦ⭠ཬࡧ✵⭠࡛ᣑᙇࡀㄆࡵࡽࢀࡓࠋ⭠㛢ሰཬࡧάືᮇ ࡢ⅖ᛶ⭠ᝈࢆ♧၀ࡍࡿᚩೃࡣ࡞ࡗࡓࠋ⿕㦂⪅ࡣ 2013 ᖺ 6 ᭶ 19 ᪥㸪ᑠ⭠ษ㝖ࡢᚋ㸪⊃✽ ᙧᡂ⾡ࢆཷࡅࡓࠋ㝜ᅽ㛢㙐⒪ἲࢆ⏝࠸㸪⣙ 1.5-2 L ࡢ⾑⭘ࡢ㝖ཤࢆ⾜ࡗࡓࠋୗ⭡ቨ⾑⟶ࡼࡾฟ ⾑ࡀࡳࡽࢀࡓࡓࡵ↝ⅎࡋ㸪3 ࡘࡢᑠ⭠ษ㛤ࡣ⦭ྜࡼࡾ㛢㙐ࡋࡓࠋ⊃✽ᙧᡂ⾡㒊࠾ࡅࡿ₃ ฟ⥆ࡁ㸪ࡉࡽ࡞ࡿษ㝖⾡ࢆཷࡅࡓࠋ2013 ᖺ 6 ᭶ 25 ᪥ヨ㦂㛤⭡ࢆཷࡅ㸪ᑠ⭠⥺⥔ᛶ⊃✽ษ㝖㸪 ᑠ⊃✽ᙧᡂ⾡ཬࡧ⧄⥔ᖏ㸦fibrotic band㸧ࡢ₢⭷➽ᒙศ㞳ࢆ⾜ࡗࡓࠋ⌮Ꮫ᳨ᰝ࡛ࡣ㸪₽⒆ࢆక࠺ 㒊ࡢᅛ᭷➽ᒙ㢧ⴭ࡞⫧୪ࡧ⢓⭷ୗᒙ⥺⥔ཬࡧ៏ᛶ⅖ࡀㄆࡵࡽࢀࡓࠋ⿕㦂⪅ࡣ㸪⾡ ๓࣊ࣃࣜࣥඹ ertapenem ࢆᢞࡉࢀࡓࠋ 2013 ᖺ 6 ᭶ 29 ᪥ࡢ⬚㒊 X ⥺᳨ᰝ࡛㸪ᕥୗⴥࡢ⫵⅖ࡢⓎ⌧ࡀ☜ㄆࡉࢀ㸪ධ㝔ᮇ㛫ࡀᘏ㛗ࡉࢀࡓࠋ 2013 ᖺ 6 ᭶ 30 ᪥ࡢ⭡㒊 X ⥺᳨ᰝ࡛㸪⭡㒊୰ኸከ㔞ࡢ࢞ࢫࡀࡳࡽࢀ㸪㒊ศⓗ࡞ᑠ⭠㛢ሰཪࡣࢡ ࣮ࣟࣥ㉳ᅉࡍࡿ⪃࠼ࡽࢀࡿ㧗ᗘࡢ⭠ಀ㋟ᣑᙇࡀㄆࡵࡽࢀࡓࠋ⭡㒊ཬࡧ㦵┙㒊 CT ࢫ࢟ࣕࣥ ࡛ࡣ㸪⭠⟶ࡢ࢞ࢫീࡣṇᖖ࡛࠶ࡾ㸪㛢ሰࡢᚩೃࡣࡳࡽࢀ࡞ࡗࡓࡀ㸪⭡⭍ෆෆ⮚✸Ꮝ㸦㒊 ᫂㸧୍⮴ࡍࡿከ㔞ࡢ࢞ࢫཬࡧᾮయ㈓␃ࢆㄆࡵࡓࠋ2013 ᖺ 7 ᭶ 1 ᪥ࡢ⬚㒊 X ⥺᳨ᰝ࡛㸪ᕥୗⴥ ㍍ᗘࡢ⫵⅖㸪2013 ᖺ 7 ᭶ 2 ᪥ࡣᕥ⫵ᇶᗏ㒊ࡢ↓Ẽ⫵ࢆㄆࡵࡓࡀ㸪2013 ᖺ 7 ᭶ 3 ᪥ࡢ᳨ᰝ࡛ࡣ㸪 ឤᰁཪࡣỈศ㐣㈇Ⲵ㛵㐃ࡍࡿ⪃࠼ࡽࢀࡿ୧⫵ࡢ୰➼ᗘࡢẼ⭍◳ࡢ㐍⾜ࡀࡳࡽࢀࡓ௨๓ࡢ ᳨ᰝ⤖ᯝࡽࡣ㸪ࡁ࡞ኚࡀࡳࡽࢀࡓࠋ⒪ࡣ⏕⌮㣗ሷᾮ㸪ࣇ࢙ࣥࢱࢽࣝ㸪pantoprazole㸪ࣆ ࣌ࣛࢩࣜࣥ㸭ࢱࢰࣂࢡࢱ࣒ཬࡧࣟࣛࢮࣃ࣒ࡀ⏝ࡉࢀࡓࠋ⿕㦂⪅ࡣ㸪2013 ᖺ 7 ᭶ 12 ᪥㏥㝔ࡋ ࡓࠋ⿕㦂⪅ࡣ 2013 ᖺ 7 ᭶ 13 ᪥㸪ᛴᛶ⭡③ཬࡧᝏᚰࡢࡓࡵධ㝔ࡋࡓࠋึᅇࡢ⬚㒊 X ⥺᳨ᰝ࡛ ࡣ㸪⫵Ỉ⭘ࡀ♧၀ࡉࢀࡓࠋධ㝔୰㸪⿕㦂⪅ࡣ⭠ෆ࢞ࢫࡢฟࡀ࠶ࡾ㸪ᗈᇦᢠ⏕≀㉁ࡢᢞࢆ㛤ጞ ࡉࢀࡓࠋࡲࡓ㸪Ⓨ⇕㸪ప㓟⣲≧ែ㸪㯤⑇ཬࡧ㐣Ẽࡀࡳࡽࢀ㸪୧║ࡣࡃࡰࢇ࡛࠸ࡓࠋࡲࡓ㸪㢕㟼 ⬦࠺ࡗ⾑ࡣࡳࡽࢀࡎ㸪㊊ᾋ⭘ࡢᚩೃࡣ࡞ࡗࡓࠋ⿕㦂⪅ࡢᒀ㔞ࡣṇᖖ࡛࠶ࡾ㸪TPN ࡀ㐺⏝ࡉ
35 5 (219) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
ࢀࡓࠋ2013 ᖺ 7 ᭶ 16 ᪥㸪㦵┙ṇ୰㒊ࡢᕥഃ⭡㒊㈓␃≀ࢆㄆࡵࡓࠋ㈓␃≀ᑐࡋ㸪X ⥺㏱どୗ ࡛㉸㡢Ἴࢆ⏝࠸࡚ࢭࣝࢹ࣮ࣥ࢞ἲࡼࡿࢻࣞࢼ࣮ࢪࢆ⾜࠸㸪20 cc ࡢῐ㯤Ⰽࡢᾮయࢆฟࡋࡓࠋ ᛴᛶࡢྜేࡣ࡞ࡃ㸪㈓␃≀ࡣฟࡉࢀࡓࠋ2013 ᖺ 7 ᭶ 16 ᪥ࡢ⬚㒊 X ⥺᳨ᰝ࡛ࡣ㸪୧⫵ ࠾࠸࡚㸪㛫㉁୰➼ᗘቑཬࡧẼ⭍ࡢኚࡀㄆࡵࡽࢀࡓࠋࡲࡓ㸪୧⫵ᑡ㔞ࡢ⬚Ỉࢆㄆࡵ㸪ᚰ ⮚ࡢࡁࡉࡣṇᖖ⠊ᅖࡢୖ㝈࡛࠶ࡗࡓࠋᇵ㣴᳨ᰝ࡛ࡣࣂࣥࢥ࣐ࢩࣥ⪏ᛶ⭠⌫⳦ࡀ㝧ᛶ࡛࠶ࡾ㸪 ࣜࢿࢰࣜࢻࡼࡿ⒪ཬࡧࢤࣥࢱ࣐ࢩࣥࡼࡿ▷ᮇ⒪ࡀ⾜ࢃࢀࡓࠋࣆ࣌ࣛࢩࣜࣥ㸭ࢱࢰࣂࢡ ࢱ࣒ࡼࡿ⒪ࢆ⥅⥆ࡋ㸪ࢻ࣮ࣞࣥࢆ␃⨨ࡋࡓࠋ⿕㦂⪅ࡣ㸪2013 ᖺ 7 ᭶ 26 ᪥㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2013-07-15 ⫼㒊③ MILD/ N/ DOSE NOT CHANGED/ 2013-11-15 (384/327) (MID-BACK PAIN (CONSTANT ACHE)) NOT NA RECOVERED/RESOLVED (507/450) RELATED 2013-07-16 ⫶࿀ྜ㒊₃ฟ MILD/ N/ DOSE NOT CHANGED/ 2013-07-16 (385/328) (SMALL BOWEL ANASTOMATIC LEAK) NOT NA RECOVERED/RESOLVED (385/328) RELATED 2013-07-16 ฎ⨨ᚋ⾑⭘ MILD/ N/ DOSE NOT CHANGED/ 2013-07-16 (385/328) (POST OPERATIVE ABDOMINAL NOT NA RECOVERED/RESOLVED (385/328) HEMATOMA) RELATED
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route KETOROLAC TROMETHAMINE 2012-11-05 2012-11-05 INTRAVENOUS KETOROLAC TROMETHAMINE 2012-11-05 2012-11-05 ORAL DIMENHYDRINATE 2013-05-01 2013-05-01 INTRAVENOUS MORPHINE 2013-05-01 2013-05-01 INTRAVENOUS SODIUM CHLORIDE 2013-05-01 2013-05-01 INTRAVENOUS KETOROLAC TROMETHAMINE 2013-05-01 2013-05-01 INTRAVENOUS TETRACYCLINE 2013-08-04 2013-08-10 ORAL SOLPADEINE /00154101/ 2013-08-04 - ORAL
(46) Subject CNTO1275CRD3003-2712-11118
1) Reason for narrative selection SAE Event of interest: Serious infection
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome (Study day I/M) 2013-03-20 ⫠㛛⮋⒆ Y MODERATE/ Y/ DOSE NOT CHANGED/ 2013-04-25 (78/21) (PERI ANAL ABSCESS) DOUBTFUL Y RECOVERED/RESOLVED (114/57)
3) Baseline Demographic Information ȋȌǣ ͷ͵ ǣ ȋȌǣ ͳͳ ǣ ǣ ͳͻͷͻǦͲͷǦʹ ȋ Ȍǣ ͳͲǤͺ
4) Induction Treatment Group Induction study: CNTO1275CRD3001 Randomized Treatment Group: Ustekinumab Approximating 6 mg/kg IV Actual Treatment Group: Ustekinumab Approximating 6 mg/kg IV
35 6 (220) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
5) Maintenance Treatment Group Assigned Treatment Group: Non-randomized subject/Non-responder to ustekinumab IV induction dosing and received ustekinumab in maintenance
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2013-01-02 1 Ustekinumab 520.2 mg WEEK 0 MAINTENANCE 2013-02-28 58 Ustekinumab 90 mg WEEK 0 MAINTENANCE 2013-02-28 58 Placebo 0 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: Y Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: -
8) Induction Baseline Crohn's Disease History Date of diagnosis: 31DEC1991 Disease duration: 21.01 years Involved areas: ᅇ⭠ࡢࡳ㸪⫠㛛࿘ᅖ㸪ᑠ⭠㏆㸭⫶㸭㣗㐨㸪ᾘ⟶እኚ㸦㛵⠇⅖㸭㛵⠇③㸧
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: PREVIOUS HISTORY Sinus tracts/perforation: NEVER Fistula: PREVIOUS HISTORY Stricture complications of (CD): CURRENTLY PRESENT
10) Concomitant Crohn's Disease-Related Surgeries None reported
11) Concomitant Steroids Visit Drug Dose Prednisone equivalent SAFETY FOLLOW-UP MAINTENANCE BUDESONIDE 3 mg -
12) Narrative Text ⿕㦂⪅ࡣ 5 ṓࡢⓑேዪᛶ࡛㸪2013 ᖺ 1 ᭶ 2 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏࢆ㟼⬦ෆᢞࡉࢀ ࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡎ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏࢆᢞࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪ᮎᲈ⾑⟶ᝈ㸪 ཱྀෆ⇱㸪Ᏻ㸪࠺ࡘ㸪⫠㛛࿘ᅖ⮋⒆㸦2 ᅇ㸪እ⛉ⓗࢻࣞࢼ࣮ࢪࢆせࡋࡓࡶࡢ㸧㸪⭠ษ㝖㸦⭠ ㅖ㒊ࡢษ㝖ࢆక࠺」ᩘᅇࡢ㛤⭡⾡㸧㸪࢚ࣥࢸࣟࢥࢵ࢝ࢫឤᰁ㸪ⓗ⫧‶㸪⊃✽㸦」ᩘᅇࡢࣂࣝ ࣮ࣥᣑᙇ⾡㸧㸪⭡ቨ࣊ࣝࢽཬࡧႚ↮࡛࠶ࡗࡓࠋ SAE/Serious Infection㸸⫠㛛⮋⒆㸦Day 78㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ㸪ᕥ⮌㒊ᛌឤࡢቑᙉࡢࡓࡵ 2013 ᖺ 3 ᭶ 20 ᪥ᾘჾ⛉ࢡࣜࢽ ࢵࢡࢆཷデࡋ㸪ࢩࣉࣟࣇࣟ࢟ࢧࢩࣥཬࡧࢡࣜࣥࢲ࣐ࢩࣥࢆฎ᪉ࡉࢀࡓࠋ⑊③ࡀᝏࡋ㸪⿕㦂⪅ ࡣ 2013 ᖺ 3 ᭶ 25 ᪥ᩆᛴᦙ㏦ࡉࢀࡓࠋ㧗ᗘࡢ⑊③ࡢࡓࡵ⌮Ꮫⓗ᳨ᰝࡣ㝈ᐃⓗ࡛࠶ࡗࡓࡀ㸪⮬↛ ⬺⫠ࡋࡓᛮࢃࢀࡿ┤⭠ࡢᕥഃ◳㒊ࡀㄆࡵࡽࢀࡓࠋྠ᪥㸪⿕㦂⪅ࡣධ㝔ࡋࡓࠋ⩣᪥㸪㯞 㓉ୗ᳨࡚ᰝࢆᐇࡋࡓࡇࢁ㸪᫂ࡽ࡞ internal tract ཬࡧ⒦Ꮝࡢᚩೃࡣ࡞ࡃ㸪⫠㛛࿘ᅖ⮋⒆ࡢ
35 7 (221) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
ࢻࣞࢼ࣮ࢪࢆᐇࡋࡓࠋࢻࣞࢼ࣮ࢪᚋ㸪ᗙᾎ୰ࢆ㝖ࡁ㸪㒊ࢆ⤊ኪ⿕そࡋࡓࠋ⒪ࡣ㸪ᢠ⏕≀ ㉁ཬࡧ ketorolac ࡀ⏝ࡉࢀࡓࠋ⿕㦂⪅ࡣ㸪2013 ᖺ 3 ᭶ 27 ᪥㏥㝔ࡋࡓࠋ
13) Other Adverse Events None reported
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route CIPROFLOXACIN 2013-03-22 2013-04-30 ORAL METRONIDAZOLE 2013-03-22 2013-04-30 ORAL
(47) Subject CNTO1275CRD3003-3401-10550
1) Reason for narrative selection SAE Event of interest: Serious infection
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome I/M) 2013-08-18 ⫶⭠⅖ Y SEVERE/ Y/ DOSE NOT CHANGED/ 2013-08-29 (357/300) (ACCUTE NOT N RECOVERED/RESOLVED (368/311) GASTROENTERITIS) RELATED
3) Baseline Demographic Information ȋȌǣ ʹ ǣ ȋȌǣ ͷǤͺ ǣ ǣ ͳͻͺͷǦͲͳǦͲͳ ȋ Ȍǣ ͳʹ
4) Induction Treatment Group Induction study: CNTO1275CRD3001 Randomized Treatment Group: Placebo IV Actual Treatment Group: Placebo IV
5) Maintenance Treatment Group Assigned Treatment Group: Non-randomized subject/Non-responder to placebo IV induction dosing and received ustekinumab in maintenance
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2012-08-27 1 Placebo 0 mg WEEK 0 MAINTENANCE 2012-10-23 58 Placebo 0 mg WEEK 0 MAINTENANCE 2012-10-23 58 Ustekinumab 129.6 mg WEEK 8 MAINTENANCE 2012-12-18 114 Ustekinumab 90 mg WEEK 12 MAINTENANCE 2013-01-22 149 Placebo 0 mg WEEK 16 MAINTENANCE 2013-02-19 177 Placebo 0 mg WEEK 20 MAINTENANCE 2013-03-12 198 Ustekinumab 90 mg WEEK 24 MAINTENANCE 2013-04-09 226 Placebo 0 mg WEEK 28 MAINTENANCE 2013-05-14 261 Placebo 0 mg WEEK 32 MAINTENANCE 2013-06-11 289 Ustekinumab 90 mg WEEK 36 MAINTENANCE 2013-07-02 310 Placebo 0 mg WEEK 40 MAINTENANCE 2013-07-30 338 Placebo 0 mg
35 8 (222) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: N Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: Y
8) Induction Baseline Crohn's Disease History Date of diagnosis: 01MAY2004 Disease duration: 8.33 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪⫠㛛࿘ᅖ㸪ᾘ⟶እኚ㸦㛵⠇⅖㸭㛵⠇③㸧
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: PREVIOUS HISTORY Sinus tracts/perforation: NEVER Fistula: CURRENTLY PRESENT Stricture complications of (CD): NEVER
10) Concomitant Crohn's Disease-Related Surgeries None reported
11) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 0 PREDNISOLONE 20 mg 20 mg WEEK 24 MAINTENANCE PREDNISOLONE 15 mg 15 mg WEEK 24 MAINTENANCE PREDNISOLONE 10 mg 10 mg WEEK 28 MAINTENANCE PREDNISOLONE 7.5 mg 7.5 mg WEEK 28 MAINTENANCE PREDNISOLONE 5 mg 5 mg WEEK 32 MAINTENANCE PREDNISOLONE 2.5 mg 2.5 mg WEEK 32 MAINTENANCE HYDROCORTISONE 10 mg 2.5 mg WEEK 32 MAINTENANCE PREDNISOLONE 0 mg 0 mg WEEK 44 MAINTENANCE PREDNISOLONE 60 mg - WEEK 44 MAINTENANCE PREDNISOLONE 0 mg - WEEK 44 MAINTENANCE HYDROCORTISONE 0 mg 0 mg WEEK 44 MAINTENANCE HYDROCORTISONE 10 mg 2.5 mg
12) Narrative Text ⿕㦂⪅ࡣ 2 ṓࡢⓑேዪᛶ࡛㸪2012 ᖺ 8 ᭶ 27 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ࣉࣛࢭ࣎ࢆ㟼⬦ෆᢞ ࡉࢀࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡎ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏࢆᢞࡉ ࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪㦵⢒㧼㸪⬨ ᳝㛵⠇⅖㸪ႚ↮㸪᰾ษ㝖㸦2005 ᖺ㸧㸪ᅇ┣㒊ษ㝖㸦2011 ᖺ 5 ᭶ 11 ᪥㸧୪ࡧ repositioning of the ileoascendostomy ཬࡧ⒵╔㞳⾡㸦2012 ᖺ 3 ᭶ 1 ᪥㸧࡛࠶ࡗࡓࠋ SAE/Serious infection㸸⫶⭠⅖㸦Day 357㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣỈᛶୗ⑩㸦1 ᪥ 20 ᅇࡲ࡛ࡢᑡ㔞ࡢ⾑ᾮࢆక࠺౽㸧㸪ྑ⭡③㸪ᝏᚰ ཬࡧྤࡀ࠶ࡾ㸪2013 ᖺ 8 ᭶ 18 ᪥ᩆᛴᦙ㏦ࡉࢀࡓࠋୗ⑩ࡼࡿయᾮ㔞పୗࡀㄆࡵࡽࢀࡓࡓࡵ㸪 ධ㝔ࡋࡓࠋ⌮Ꮫⓗᡤぢ࡛ࡣ㸪⭡㒊⒵⒕ཬࡧྑ⭡㒊⭡ቨ㜵ᚚࢆకࢃ࡞࠸ᅽ③ࢆㄆࡵࡓࡀ㸪 ࡑࡢࡢ␗ᖖࡣ࡞ࡗࡓࠋྠ᪥㸦2013 ᖺ 8 ᭶ 18 ᪥㸧ࡢ C ᛂᛶࡓࢇⓑ㸦CRP㸧⃰ᗘࡣ 36.4 mg/L 㹙ṇᖖ⠊ᅖ㸦NR㸧<7.5 mg/L㹛࡛࠶ࡗࡓࠋ2013 ᖺ 8 ᭶ 20 ᪥ࡢ⭡㒊㉸㡢Ἴ᳨ᰝ࡛ࡣ㸪␗ᖖࡣ࡞
35 9 (223) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
ࡗࡓࠋࣉࣞࢻࢽࢰࣟࣥཬࡧⅬࡼࡿ⒪ࡀ⾜ࢃࢀࡓࠋධ㝔୰⿕㦂⪅ࡢ⮫ᗋ≧ࡣᨵၿࡋࡓࠋ ⿕㦂⪅ࡣ 2013 ᖺ 8 ᭶ 21 ᪥㏥㝔ࡋࡓࡀ㸪Ỉᛶୗ⑩ཬࡧᝏᚰࡀᣢ⥆ࡋ࡚࠾ࡾ㸪2013 ᖺ 8 ᭶ 22 ᪥ ࡾࡘࡅࡢᾘჾෆ⛉་㝔ධ㝔ࡋࡓࠋ2013 ᖺ 8 ᭶ 22 ᪥ࡢ⭡㒊㉸㡢Ἴ᳨ᰝ࡛ࡣ␗ᖖᡤぢ ࡣ࡞ࡗࡓࠋ⒪ࡣ㸪ሷ࣒࢝ࣜ࢘ཬࡧࣉࣞࢻࢽࢰࣟࣥࡀ⏝ࡉࢀࡓࠋ2013 ᖺ 8 ᭶ 23 ᪥ࡢ CRP ⃰ᗘࡣ 19.4 mg/L㸪࣒࢝ࣜ࢘ࡣ 3.39 mmol/L㸦NR 3.3-4.5 mmol/L㸧࡛࠶ࡗࡓࠋୗ⑩㸪⭡③㸪 ㌟≧ែࡣᨵၿࡋ㸪⤒ཱྀᦤྲྀࡀྍ⬟࡞ࡗࡓࡓࡵ㸪⿕㦂⪅ࡣ 2013 ᖺ 8 ᭶ 23 ᪥㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome (Study day I/M) 2012-11-13 㰯ဗ㢌⅖ MILD/ Y/ DOSE NOT CHANGED/ 2013-01-22 (79/22) (COMMON COLD) POSSIBLE N RECOVERED/RESOLVED (149/92) 2013-02-19 㕲Ḟஈᛶ㈋⾑ MILD/ N/ DOSE NOT CHANGED/ Ongoing (177/120) (IRON DEFICIENCY ANEMIA) POSSIBLE NA NOT RECOVERED/NOT RESOLVED - 2013-04-07 㰯ဗ㢌⅖ MILD/ Y/ DOSE NOT CHANGED/ 2013-04 (224/167) (COMMON COLD) POSSIBLE N RECOVERED/RESOLVED -
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route FERRIC CARBOXYMALTOSE 2013-02-26 2013-02-26 INTRAVENOUS FERRIC CARBOXYMALTOSE 2013-06-14 2013-06-14 INTRAVENOUS FERRIC CARBOXYMALTOSE 2013-07-30 2013-07-30 INTRAVENOUS HYOSCINE BUTYLBROMIDE 2013-08-18 2013-08-21 ORAL METOCLOPRAMIDE 2013-08-18 2013-08-21 ORAL METAMIZOLE SODIUM 2013-08-18 2013-08-21 ORAL PREDNISOLONE 2013-08-20 2013-08-21 INTRAVENOUS POTASSIUM CHLORIDE 2013-08-22 2013-08-23 ORAL
(48) Subject CNTO1275CRD3003-3401-10797
1) Reason for narrative selection SAE Event of interest: Serious infection
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome (Study day I/M) 2013-03-12 ⫶⭠⅖ Y MODERATE/ Y/ NOT APPLICABLE/ 2013-03-15 (132/76) (ACUTE GASTROENTERITIS) NOT RELATED N RECOVERED/RESOLVED (135/79)
3) Baseline Demographic Information ȋȌǣ Ͷͷ ǣ ȋȌǣ ͻǤ͵ ǣ ǣ ͳͻǦͲͳǦͲͳ ȋ Ȍǣ ͳ͵
4) Induction Treatment Group Induction study: CNTO1275CRD3001 Randomized Treatment Group: Ustekinumab Approximating 6 mg/kg IV Actual Treatment Group: Ustekinumab Approximating 6 mg/kg IV
5) Maintenance Treatment Group Assigned Treatment Group: Non-randomized subject/Non-responder to ustekinumab IV induction dosing and received ustekinumab in maintenance
36 0 (224) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2012-11-01 1 Ustekinumab 389.7 mg WEEK 0 MAINTENANCE 2012-12-27 57 Placebo 0 mg WEEK 0 MAINTENANCE 2012-12-27 57 Ustekinumab 90 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: Y Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: -
8) Induction Baseline Crohn's Disease History Date of diagnosis: 30SEP1991 Disease duration: 21.09 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪ᾘ⟶እኚ㸦㛵⠇⅖㸭㛵⠇③㸧
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: PREVIOUS HISTORY Sinus tracts/perforation: NEVER Fistula: PREVIOUS HISTORY Stricture complications of (CD): PREVIOUS HISTORY
10) Concomitant Crohn's Disease-Related Surgeries None reported
11) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 0 BUDESONIDE 9 mg -
12) Narrative Text ⿕㦂⪅ࡣ 4 ṓࡢⓑேዪᛶ࡛㸪2012 ᖺ 11 ᭶ 1 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏࢆ㟼⬦ෆᢞࡉࢀ ࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡎ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏࢆᢞࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪㦵⢒㧼㸪⏥ ≧⭢ᶵ⬟పୗ㸪⫶₽⒆㸪㣧㓇㸪㦵ῶᑡ㸪ࣅࢱ࣑ࣥ 12 Ḟஈ㸪║⇱㸪ື⬦ᛶ㧗⾑ᅽ㸪⫹ᄞ ษ㝖ᚋ≧ែ㸪ᡥ᱈ฟ㸪༙⤖⭠ษ㝖㸦1995 ᖺ㸧㸪➃ࠎ࿀ྜࡢ࿀ྜ㒊⊃✽ษ㝖㸦ᅇ⭠ᶓ⾜⤖⭠࿀ྜ ⾡㸪2004 ᖺ 3 ᭶㸧㸪ᑠ㦵┙㒊ࡢឤᰁᛶ⾑⭘ࡼࡿ㛤⭡⾡㸦2004 ᖺ 3 ᭶㸧㸪᪂ࡓ࡞ᅇ⭠ᮎ➃ษ 㝖㸪࿀ྜ㒊ษ㝖㸪ᅇ⭠ᶓ⾜⤖⭠࿀ྜ⾡㸦2011 ᖺ㸧୪ࡧࣥࣇࣜ࢟ࢩ࣐ࣈ㸪ࢲ࣒࣐ࣜࣈ㸪ᢠ⏕ ≀㉁㸦ヲ⣽᫂㸧ཬࡧ㙠③⸆ᑐࡍࡿࣞࣝࢠ࣮࡛࠶ࡗࡓࠋ SAE/Serious infection㸸⫶⭠⅖㸦Day 132㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ㢖Ⓨࡍࡿྤ㸪୰⭡㒊ࡢᛌឤࡢቑᝏཬࡧỈᛶୗ⑩㸦1 ᪥ 5 ᅇࡲ࡛㸧 ࡀ࠶ࡾ㸪2013 ᖺ 3 ᭶ 12 ᪥ධ㝔ࡋࡓࠋධ㝔㸪⿕㦂⪅ࡣ㌟≧ែࡀపୗࡋ࡚࠾ࡾ㸪⑊③ࡢࡓࡵ ືసࡀ⦆៏࡛࠶ࡗࡓࠋ⭡㒊デᐹ࡛ࡣ㸪ᗈỗᛶࡢᅽ③ࢆㄆࡵࡓࡀ㸪➽ᛶ㜵ᚚࡣ࡞ࡃ㸪⫈デ࡛ࡣ⭡㒊 ࡢᅄ༙㒊ࡍ࡚࡛⽸ື㡢ࡀ☜ㄆࡉࢀࡓࠋ⮫ᗋ᳨ᰝ್㸦2013 ᖺ 3 ᭶ 12 ᪥㸧ࡣ㸪ⓑ⾑⌫ᩘ 20.9 Gpt/L㹙ṇᖖ⠊ᅖ㸦NR㸧3.8-9.8 Gpt/L㹛ཬࡧ C ᛂᛶࡓࢇⓑ㸦CRP㸧⃰ᗘ 6.0 mg/L 㸦NR<5.0 mg/L㸧࡛࠶ࡗࡓࠋ⭡㒊 X ⥺᳨ᰝ㸦2013 ᖺ 3 ᭶ 13 ᪥㸧࡛ࡣ㸪✸Ꮝཬࡧ㏻㐣㞀ᐖࡢᚩೃ
36 1 (225) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
ࡣ࡞ࡗࡓࠋྠ᪥ࡢ౽ᇵ㣴᳨ᰝ࡛ࡣ㸪ཎᛶ⭠ෆ⣽⳦㸦ࢡࣟࢫࢺࣜࢪ࣒࣭࢘ࢹࣇࢩࣞ㸧ཬࡧ ཎᛶ࢘ࣝࢫ㸦ࢹࣀ࢘ࣝࢫ㸪ࣟࢱ࢘ࣝࢫ㸪norvo virus㸧ࡣㄆࡵࡽࢀࡎ㸪㢧ᚤ㙾ࡼࡿᐤ ⏕༸ࡶㄆࡵࡽࢀ࡞ࡗࡓࠋ⿕㦂⪅ࡣ≧ࡀⴭ᫂ᨵၿࡋࡓ㏙㸪౽ᅇᩘࡶῶᑡࡋࡓ㸦1 ᪥ 1 ᅇ㸪Ἶ≧౽┦ᙜ㸧ࠋ2013 ᖺ 3 ᭶ 14 ᪥ࡢ⭡㒊㉸㡢Ἴ᳨ᰝ࡛ࡣ㸪␗ᖖࡣ࡞ࡗࡓࠋྠ᪥ࡢ CRP ⃰ᗘࡣ 8.2 mg/L ࡛࠶ࡗࡓࠋ⿕㦂⪅ࡣ㸪2013 ᖺ 3 ᭶ 15 ᪥㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome (Study day I/M) 2012-11-28 㰯ဗ㢌⅖ MILD/ Y/ DOSE NOT CHANGED/ 2013-02-26 (28/.) (COMMON COLD) POSSIBLE N RECOVERED/RESOLVED (118/.) 2012-12-11 ⫼㒊③ MILD/ N/ DOSE NOT CHANGED/ 2013-02-25 (41/.) (BACK PAIN) NOT RELATED NA RECOVERED/RESOLVED (117/.) 2013-01-15 ㏞㊰⅖ MILD/ Y/ DOSE NOT CHANGED/ 2013-02-26 (76/20) (OTITIS INTERNA) POSSIBLE Y RECOVERED/RESOLVED (118/62) 2013-01-30 ∦㢌③ MODERATE/ N/ DOSE NOT CHANGED/ 2013-02-01 (91/35) (MIGRAINE) NOT RELATED NA RECOVERED/RESOLVED (93/37)
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route ROXITHROMYCIN 2013-01-28 2013-02-03 ORAL PHENAZONE 2013-01-30 2013-01-31 ORAL
(49) Subject CNTO1275CRD3003-3409-20602
1) Reason for narrative selection SAE Event of interest: Serious infection
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome (Study day I/M) 2014-01-14 ⫹ᄞ⅖ Y SEVERE/ Y/ DOSE NOT CHANGED/ 2014-01-15 (76/23) (CHOLECYSTITIS) NOT RELATED Y RECOVERED/RESOLVED (77/24)
3) Baseline Demographic Information ȋȌǣ ͵ͳ ǣ ȋȌǣ ͳͲ͵ ǣ ǣ ͳͻͺʹǦͲͳǦͲͳ ȋ Ȍǣ ͳʹ
4) Induction Treatment Group Induction study: CNTO1275CRD3002 Randomized Treatment Group: Placebo IV Actual Treatment Group: Placebo IV
5) Maintenance Treatment Group Assigned Treatment Group: Non-randomized subject/Non-responder to placebo IV induction dosing and received ustekinumab in maintenance
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2013-10-31 1 Placebo 0 mg WEEK 0 MAINTENANCE 2013-12-23 54 Placebo 0 mg
36 2 (226) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
Visit Start Date Study Day Actual Treatment Dose WEEK 0 MAINTENANCE 2013-12-23 54 Ustekinumab 129.6 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: Y Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: -
8) Induction Baseline Crohn's Disease History Date of diagnosis: 01MAY2000 Disease duration: 13.50 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪ᑠ⭠㏆㸭⫶㸭㣗㐨
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: PREVIOUS HISTORY Sinus tracts/perforation: NEVER Fistula: PREVIOUS HISTORY Stricture complications of (CD): PREVIOUS HISTORY
10) Concomitant Crohn's Disease-Related Surgeries None reported
11) Concomitant Steroids None reported
12) Narrative Text ⿕㦂⪅ࡣ 3 ṓࡢⓑேዪᛶ࡛㸪2013 ᖺ 10 ᭶ 31 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ࣉࣛࢭ࣎ࢆ㟼⬦ෆᢞ ࡉࢀࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡎ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏࢆᢞ ࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪Ⓞ㸪ᅇ┣㒊 ษ㝖㸪࣎ࢹ࣭࣐ࢫ࣭ࣥࢹࢵࢡࢫቑຍཬࡧႚ↮࡛࠶ࡗࡓࠋ SAE/Serious Infection㸸⫹ᄞ⅖㸦Day 76㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2014 ᖺ 1 ᭶ 14 ᪥ྑୖ⭡㒊③ࢆⓎ⌧ࡋࡓࠋ⭡㒊㉸㡢Ἴ᳨ᰝ 㸦2014 ᖺ 1 ᭶ 14 ᪥㸧࡛ࡣ㸪3 ᒙᵓ㐀ࢆ࿊ࡍ⫹ᄞቨ⫧ཌࡢቑཬࡧ࣐࣮ࣇ࣮ᚩೃࡢ㝧ᛶࡀㄆࡵ ࡽࢀࡿᛴᛶ⫹ᄞ⅖࡛࠶ࡿࡇࡀุ᫂ࡋࡓࠋྠ᪥㸪⿕㦂⪅ࡣධ㝔ࡋ㸪⭡⭍㙾ୗ⫹ᄞษ㝖⾡ࢆཷࡅࡓࠋ ⒪ࡣ㸪ࢱࢰࣂࢡࢱ࣒㸪࣓ࢱ࣑ࢰ࣮ࣝ㸪࣓ࣟ࣌ࢿ࣒㸪࢚ࣀ࢟ࢧࣃࣜࣥཬࡧࣥࣈࣟ࢟ࢯ࣮ࣝࡀ ⏝ࡉࢀࡓࠋ⾡ᚋ⤒㐣࡛ࡣྜేࡣ࡞ࡃ㸪ᤄධࡉࢀ࡚࠸ࡓ Robinson drain ࡣ⾡ᚋ 2 ᪥┠ᢤཤࡉ ࢀࡓࠋ⫹ᄞ⅖ࡣ 2014 ᖺ 1 ᭶ 15 ᪥ᾘᩓࡋࡓሗ࿌ࡉࢀ㸪⿕㦂⪅ࡣ 2014 ᖺ 1 ᭶ 20 ᪥㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome (Study day I/M) 2014-01-15 ྜే MODERATE/ N/ DOSE NOT CHANGED/ 2014-01-23 (77/24) (PAIN DUE TO WOUND HEALING) NOT RELATED NA RECOVERED/RESOLVED (85/32) 2014-01-22 ᒀ㊰ឤᰁ MODERATE/ Y/ DOSE NOT CHANGED/ 2014-01-25 (84/31) (URINARY TRACT INFECTION) DOUBTFUL Y RECOVERED/RESOLVED (87/34) 2014-02-25 㰯ဗ㢌⅖ MODERATE/ Y/ DOSE NOT CHANGED/ 2014-03-02 (118/65) (COMMON COLD) POSSIBLE Y RECOVERED/RESOLVED (123/70)
36 3 (227) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome (Study day I/M) 2014-05-02 ࣥࣇ࢚ࣝࣥࢨ MODERATE/ Y/ DOSE NOT CHANGED/ 2014-05-09 (184/131) (INFLUENZA) NOT RELATED Y RECOVERED/RESOLVED (191/138)
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route ENOXAPARIN SODIUM 2014-01-14 2014-01-20 SUBCUTANEOUS MEROPENEM TRIHYDRATE 2014-01-14 2014-01-19 INTRAVENOUS METAMIZOLE MAGNESIUM 2014-01-14 2014-01-19 ORAL AMBROXOL 2014-01-15 2014-01-19 ORAL TRAMADOL HYDROCHLORIDE 2014-01-19 2014-01-23 ORAL CIPROFLOXACIN 2014-01-23 2014-01-25 ORAL CLARITHROMYCIN 2014-02-27 2014-03-02 ORAL ROXITHROMYCIN 2014-05-05 2014-05-09 ORAL
(50) Subject CNTO1275CRD3003-3414-20406
1) Reason for narrative selection SAE Event of interest: Serious infection
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome (Study day I/M) 2013-12-28 ᆶ⅖ Y SEVERE/ Y/ DOSE NOT CHANGED/ 2014-01-06 (237/178) (APPENDICITIS) DOUBTFUL Y RECOVERED/RESOLVED (246/187)
3) Baseline Demographic Information Age (years): 2 Sex: Male Weight (kg): 87.6 Race: White Date of birth: Height (cm): 182
4) Induction Treatment Group Induction study: CNTO1275CRD3002 Randomized Treatment Group: Ustekinumab 130 mg IV Actual Treatment Group: Ustekinumab 130 mg IV
5) Maintenance Treatment Group Assigned Treatment Group: Randomized subject/Responder to ustekinumab IV induction dosing/ustekinumab 90 mg SC q12w
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2013-05-06 1 Ustekinumab 129.6 mg WEEK 0 MAINTENANCE 2013-07-04 60 Ustekinumab 90 mg WEEK 8 MAINTENANCE 2013-09-10 128 Placebo 0 mg WEEK 12 MAINTENANCE 2013-10-08 156 Ustekinumab 90 mg WEEK 16 MAINTENANCE 2013-10-25 173 Placebo 0 mg WEEK 20 MAINTENANCE 2013-11-25 204 Placebo 0 mg WEEK 24 MAINTENANCE 2013-12-18 227 Ustekinumab 90 mg WEEK 28 MAINTENANCE 2014-01-10 250 Placebo 0 mg WEEK 32 MAINTENANCE 2014-02-13 284 Placebo 0 mg WEEK 36 MAINTENANCE 2014-03-31 330 Ustekinumab 90 mg WEEK 40 MAINTENANCE 2014-04-17 347 Placebo 0 mg
36 4 (228) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: N Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: Y
8) Induction Baseline Crohn's Disease History Date of diagnosis: 28FEB2009 Disease duration: 4.19 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪ᾘ⟶እኚ㸦㛵⠇⅖㸭㛵⠇③㸧
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: NEVER Stricture complications of (CD): PREVIOUS HISTORY
10) Concomitant Crohn's Disease-Related Surgeries None reported
11) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 20 MAINTENANCE PREDNISONE 40 mg 40 mg WEEK 20 MAINTENANCE PREDNISONE 35 mg 35 mg WEEK 20 MAINTENANCE PREDNISONE 30 mg 30 mg WEEK 20 MAINTENANCE PREDNISONE 25 mg 25 mg WEEK 20 MAINTENANCE PREDNISONE 20 mg 20 mg WEEK 24 MAINTENANCE PREDNISONE 15 mg 15 mg WEEK 24 MAINTENANCE PREDNISONE 10 mg 10 mg WEEK 24 MAINTENANCE PREDNISONE 5 mg 5 mg WEEK 28 MAINTENANCE PREDNISONE 0 mg 0 mg WEEK 32 MAINTENANCE PREDNISONE 30 mg 30 mg WEEK 36 MAINTENANCE PREDNISONE 15 mg 15 mg WEEK 36 MAINTENANCE PREDNISONE 30 mg 30 mg WEEK 36 MAINTENANCE PREDNISONE 25 mg 25 mg WEEK 36 MAINTENANCE PREDNISONE 25 mg 25 mg WEEK 36 MAINTENANCE PREDNISONE 20 mg 20 mg WEEK 40 MAINTENANCE PREDNISONE 22.5 mg 22.5 mg WEEK 40 MAINTENANCE PREDNISONE 20 mg 20 mg WEEK 44 MAINTENANCE PREDNISONE 17.5 mg 17.5 mg WEEK 44 MAINTENANCE PREDNISONE 15 mg 15 mg WEEK 44 MAINTENANCE PREDNISONE 12.5 mg 12.5 mg WEEK 44 MAINTENANCE PREDNISONE 10 mg 10 mg
12) Narrative Text ⿕㦂⪅ࡣ 2 ṓࡢⓑே⏨ᛶ࡛㸪2013 ᖺ 5 ᭶ 6 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏࢆ㟼⬦ෆᢞࡉࢀ ࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏ 90 mg ࢆ q12w ࡛⓶ୗᢞࡍࡿ⩌ࣛࣥࢲ࣒ࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪ྑୗ⭡㒊③ཬ ࡧႚ↮࡛࠶ࡗࡓࠋ
36 5 (229) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
SAE/Serious Infection㸸ᆶ⅖㸦Day 237㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ㸪2013 ᖺ 12 ᭶ 28 ᪥ྑ⭡㒊③ࢆⓎ⌧ࡋࡓࠋ2014 ᖺ 1 ᭶ 4 ᪥㸪⑊ ③ࡀቑᝏࡋ㸪࿘ᅖཬࡧྑୗ⭡㒊㞟୰ࡋ࡚࠸ࡓࠋ㣗ḧ㸪ᝏᚰཬࡧྤࡶࡳࡽࢀࡓࠋ⌮Ꮫⓗ ᡤぢ࡛ࡣ㸪ྑୗ⭡㒊ᅽ③ࡢᚩೃࡣ࡞ࡗࡓࠋ⭡㒊 X ⥺᳨ᰝ࡛ࡣ㸪▷࠸㙾㠃ീࡀㄆࡵࡽࢀ㸪୰ኸ ཬࡧᕥഃ⭡㒊࡛ᑠ⭠ಀ㋟ࡢᣑᙇࡣࡳࡽࢀࡎ㸪⭡⭍ෆẼయཪࡣᾮయࡣㄆࡵࡽࢀ࡞ࡗࡓࠋ2014 ᖺ 1 ᭶ 5 ᪥ࡢ⭡㒊ཬࡧ㦵┙㒊ࢥࣥࣆ࣮ࣗࢱ᩿ᒙᙳࢫ࡛࢟ࣕࣥࡣ㸪ᆶ࿘ᅖ⮋⒆ᙧᡂࢆక࠺ᛴᛶ ᆶ⅖ࡀ♧၀ࡉࢀ㸪⊃✽ࢆ♧၀ࡍࡿ⊃ᑠࡋࡓᅇ⭠㐲㒊㸦3 cm㸧ࡀࡳࡽࢀࡓࠋࡲࡓ㸪࠾ࡑࡽࡃ ᛂᛶࣜࣥࣃ⠇㉳ᅉࡍࡿ㸪᫂░࡞┣⭠ෆഃ㌾㒊⤌⧊ࡢቑࡀࡳࡽࢀࡓࠋ⢭ᰝཬࡧຍ⒪ࢆ┠ⓗ ࡋ㸪⿕㦂⪅ࡣྠ᪥㸦2014 ᖺ 1 ᭶ 5 ᪥㸧ධ㝔ࡋࡓࠋ⿕㦂⪅ࡣ㸪㠀ᡭ⾡ⓗ⒪ἲࡢ㐺⏝ᝈ⪅⪃࠼ ࡽࢀ㸪ࢩࣉࣟࣇࣟ࢟ࢧࢩࣥ㸪࣓ࢺࣟࢽࢲࢰ࣮ࣝ㸪㙠③ཬࡧไྤ㸦ヲ⣽᫂㸧୪ࡧ㟼⬦ෆ⿵ ᾮࡢᢞࢆཷࡅࡓࠋ⒪ࡀዌຠࡋ㸪⿕㦂⪅ࡣ 2014 ᖺ 1 ᭶ 6 ᪥㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome (Study day I/M) 2014-01-10 ⓶┿⳦ឤᰁ MILD/ Y/ DOSE NOT CHANGED/ 2014-02-13 (250/191) (FUNGAL INFECTION TO FINGERS) POSSIBLE N RECOVERED/RESOLVED (284/225) 2014-05-01 ୖẼ㐨ឤᰁ MILD/ Y/ DOSE NOT CHANGED/ 2014-05-05 (361/302) (UPPER RESPIRATORY INFECTION) NOT RELATED N RECOVERED/RESOLVED (365/306)
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route CIPROFLOXACIN 2014-01-05 2014-01-17 ORAL METRONIDAZOLE 2014-01-05 2014-01-17 ORAL CLOTRIMAZOLE 2014-01-10 2014-01-24 TOPICAL
(51) Subject CNTO1275CRD3003-3425-20835
1) Reason for narrative selection SAE
Event of interest: Serious infection 2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome (Study day I/M) 2014-11-25 ┤⭠࿘ᅖ⮋⒆ Y MODERATE/ Y/ DOSE NOT CHANGED/ 2014-12-01 (240/184) (PERIPROCTITIC ABSCESS) NOT RELATED Y RECOVERED/RESOLVED (246/190)
3) Baseline Demographic Information ȋȌǣ Ͷ͵ ǣ ȋȌǣ ͺͳǤ ǣ ǣ ͳͻͳǦͲͳǦͲͳ ȋ Ȍǣ ͳͳ
4) Induction Treatment Group Induction study: CNTO1275CRD3002 Randomized Treatment Group: Placebo IV Actual Treatment Group: Placebo IV
36 6 (230) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
5) Maintenance Treatment Group Assigned Treatment Group: Non-randomized subject/Non-responder to placebo IV induction dosing and received ustekinumab in maintenance
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2014-03-31 1 Placebo 0 mg WEEK 0 MAINTENANCE 2014-05-26 57 Placebo 0 mg WEEK 0 MAINTENANCE 2014-05-26 57 Ustekinumab 129.6 mg WEEK 8 MAINTENANCE 2014-07-17 109 Ustekinumab 90 mg WEEK 12 MAINTENANCE 2014-08-11 134 Placebo 0 mg WEEK 16 MAINTENANCE 2014-09-08 162 Placebo 0 mg WEEK 20 MAINTENANCE 2014-10-13 197 Ustekinumab 90 mg WEEK 24 MAINTENANCE 2014-11-10 225 Placebo 0 mg WEEK 28 MAINTENANCE 2014-12-15 260 Placebo 0 mg WEEK 32 MAINTENANCE 2015-01-12 288 Ustekinumab 90 mg WEEK 36 MAINTENANCE 2015-01-26 302 Placebo 0 mg WEEK 40 MAINTENANCE 2015-03-02 337 Placebo 0 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: N Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: Y
8) Induction Baseline Crohn's Disease History Date of diagnosis: 31DEC1991 Disease duration: 22.25 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪⫠㛛࿘ᅖ㸪ᑠ⭠㏆㸭⫶㸭㣗㐨㸪ᾘ⟶እኚ㸦㛵⠇⅖㸭㛵⠇ ③㸧
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: CURRENTLY PRESENT Stricture complications of (CD): NEVER
10) Concomitant Crohn's Disease-Related Surgeries Surgery Date Result of lack of efficacy? ࡑࡢࡢษ㛤ཬࡧ⮋⒆ࢻࣞࢼ࣮ࢪ 2014-12-01 N
11) Concomitant Steroids None reported
12) Narrative Text ⿕㦂⪅ࡣ 4 ṓࡢⓑேዪᛶ࡛㸪2014 ᖺ 3 ᭶ 31 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ࣉࣛࢭ࣎ࢆ㟼⬦ෆᢞ ࡉࢀࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡎ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏࢆᢞࡉ ࢀࡓࠋ
36 7 (231) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪₽⒆㸪㧗⾑ᅽ ཬࡧ㧗Ᏻື⬦⅖࡛࠶ࡗࡓࠋධᡭࡉࢀࡓデ⒪グ㘓ࡼࢀࡤ㸪⿕㦂⪅ࡣ 2013 ᖺ 11 ᭶ 2 ᪥㸪⒦⟶ ⣒ࡢࢻ࣮ࣞࣥࢆ⏝࠸ࡓ⮋⒆ษ㝖⾡ࢆཷࡅ࡚࠸ࡓࠋ SAE/Serious Infection㸸┤⭠࿘ᅖ⮋⒆㸦Day 240㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2014 ᖺ 11 ᭶ 25 ᪥㸪ྑ⮌㒊ࡢ⑊③ཬࡧⓎ㉥ࢆⓎ⌧ࡋࡓࠋ㉸㡢Ἴ ᳨ᰝ࡛⫠㛛࿘ᅖ⮋⒆ࡀㄆࡵࡽࢀࡓࠋ⿕㦂⪅ࡣ㸪⣒࡛ࢻࣞࢼ࣮ࢪ୰ࡢ⫠㛛࿘ᅖ⮋⒆ࡀ⮬↛✸Ꮝࡋࡓ ࡓࡵ㸪ᩆᛴእ᮶ࢆཷデࡋࡓࠋ⿕㦂⪅ࡣ 2014 ᖺ 12 ᭶ 1 ᪥ධ㝔ࡋ㸪⮋⒆ษ㝖ཬࡧࢻࣞࢼ࣮ࢪ⏝ࡢ ⣒ࡢࢆཷࡅࡓࠋ⿕㦂⪅ࡣ㸪࣓ࢺࣟࢽࢲࢰ࣮ࣝཬࡧࢩࣉࣟࣇࣟ࢟ࢧࢩࣥࡢᢞࢆཷࡅࡓࠋ┤⭠ ࿘ᅖ⮋⒆ࡣ 2014 ᖺ 12 ᭶ 1 ᪥ᾘᩓࡋࡓሗ࿌ࡉࢀ㸪⿕㦂⪅ࡣ⩣᪥㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2014-03-10 ➽⥭ᙇ MODERATE/ N/ NOT APPLICABLE/ Ongoing (-21/.) (TENSION OF NECK NOT NA NOT RECOVERED/NOT - (INTERMITTEND)) RELATED RESOLVED 2014-03-18 㰯ဗ㢌⅖ MODERATE/ Y/ NOT APPLICABLE/ 2014-03-29 (-13/.) (COMMON COLD) NOT N RECOVERED/RESOLVED (-2/.) RELATED 2014-04-04 㢡③ MODERATE/ N/ DOSE NOT CHANGED/ 2014-04-04 (5/.) (JAW PAIN) NOT NA RECOVERED/RESOLVED (5/.) RELATED 2014-05-03 ṑ⫗⅖ MILD/ Y/ DOSE NOT CHANGED/ 2014-05-09 (34/.) (GINGIVITIS) NOT N RECOVERED/RESOLVED (40/.) RELATED 2014-08-25 ᨺᒂ MILD/ N/ DOSE NOT CHANGED/ Ongoing (148/92) (FLATULENCE) NOT NA NOT RECOVERED/NOT - RELATED RESOLVED 2014-09 Ẽศືᦂ MILD/ N/ DOSE NOT CHANGED/ Ongoing - (MOOD SWINGS) NOT NA NOT RECOVERED/NOT - RELATED RESOLVED 2014-09-03 ṑ③ MODERATE/ N/ DOSE NOT CHANGED/ 2014-09-03 (157/101) (TOOTHACHE) NOT NA RECOVERED/RESOLVED (157/101) RELATED 2014-09-13 ⬺ẟ MILD/ N/ DOSE NOT CHANGED/ Ongoing (167/111) (ALOPECIA) NOT NA NOT RECOVERED/NOT - RELATED RESOLVED 2014-10-06 ୖ⭡㒊③ MILD/ N/ DOSE NOT CHANGED/ 2014-11-09 (190/134) (GASTRIC PAIN) NOT NA RECOVERED/RESOLVED (224/168) RELATED 2014-11-03 ཱྀ⭍࣊ࣝ࣌ࢫ MODERATE/ Y/ DOSE NOT CHANGED/ 2014-11-07 (218/162) (HERPES LABIALIS) POSSIBLE N RECOVERED/RESOLVED (222/166) 2014-11-25 ཱྀ⭍࣊ࣝ࣌ࢫ MILD/ Y/ DOSE NOT CHANGED/ 2014-12-11 (240/184) (HERPES LABIALIS) POSSIBLE N RECOVERED/RESOLVED (256/200) 2014-12-15 㕲Ḟஈ MODERATE/ N/ DOSE NOT CHANGED/ Ongoing (260/204) (IRON DEFICIENCY) NOT NA NOT RECOVERED/NOT - RELATED RESOLVED 2015-02-15 㰯ဗ㢌⅖ MODERATE/ Y/ DOSE NOT CHANGED/ 2015-02-21 (322/266) (COMMON COLD) POSSIBLE N RECOVERED/RESOLVED (328/272) 2015-03-27 ⪥③ MILD/ N/ DOSE NOT CHANGED/ 2015-03-29 (362/306) (EARACHE) NOT NA RECOVERED/RESOLVED (364/308) RELATED 2015-03-27 ཱྀ⭍ဗ㢌③ MILD/ Y/ DOSE NOT CHANGED/ 2015-03-29 (362/306) (SORE THROAT) NOT N RECOVERED/RESOLVED (364/308) RELATED 2015-03-28 ཱྀ⭍࣊ࣝ࣌ࢫ MILD/ Y/ DOSE NOT CHANGED/ 2015-04-05 (363/307) (HERPES LABIALIS) POSSIBLE N RECOVERED/RESOLVED (371/315)
36 8 (232) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route HOMEOPATICS NOS 2014-03-19 2014-03-29 ORAL IBUPROFEN 2014-04-04 2014-04-04 ORAL IBUPROFEN 2014-05-03 2014-05-03 ORAL CHLORHEXIDINE GLUCONATE 2014-05-06 2014-05-06 OTHER IBUPROFEN 2014-09-03 2014-09-03 ORAL ACICLOVIR 2014-11-03 2014-11-07 TOPICAL CIPROFLOXACIN 2014-11-26 2014-12-06 ORAL METRONIDAZOLE 2014-11-26 2014-12-06 ORAL FERROUS GLYCINE SULFATE 2015-01-13 2015-01-26 ORAL HOMEOPATHIC PREPARATION 2015-02-15 2015-02-21 ORAL
(52) Subject CNTO1275CRD3003-3610-20397
1) Reason for narrative selection SAE Event of interest: Serious infection
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome (Study day I/M) 2013-05-08 ⫠㛛⮋⒆ Y MODERATE/ Y/ DOSE NOT CHANGED/ 2013-05-13 (21/.) (PERIANAL ABSCESS) NOT RELATED Y RECOVERED/RESOLVED (26/.) 2013-07-25 ⒦ Y MODERATE/ N/ DOSE NOT CHANGED/ 2013-07-27 (99/42) (PERIANAL FISTULA) NOT RELATED NA RECOVERED/RESOLVED (101/44) 2013-11-09 ⫠㛛⮋⒆ Y MODERATE/ Y/ DOSE NOT CHANGED/ 2013-11-11 (206/149) (PERIANAL ABSCESS) NOT RELATED Y RECOVERED/RESOLVED (208/151)
3) Baseline Demographic Information ȋȌǣͶ͵ ǣ ȋȌǣ͵ ǣ ǣͳͻͲǦͲͳǦͲͳ ȋ Ȍǣͳͺ
4) Induction Treatment Group Induction study: CNTO1275CRD3002 Randomized Treatment Group: Placebo IV Actual Treatment Group: Placebo IV
5) Maintenance Treatment Group Assigned Treatment Group: Non-randomized subject/Non-responder to placebo IV induction dosing and received ustekinumab in maintenance
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2013-04-18 1 Placebo 0 mg WEEK 0 MAINTENANCE 2013-06-14 58 Ustekinumab 129.6 mg WEEK 0 MAINTENANCE 2013-06-14 58 Placebo 0 mg WEEK 8 MAINTENANCE 2013-08-08 113 Ustekinumab 90 mg WEEK 12 MAINTENANCE 2013-09-05 141 Placebo 0 mg WEEK 16 MAINTENANCE 2013-10-03 169 Placebo 0 mg WEEK 20 MAINTENANCE 2013-10-31 197 Ustekinumab 90 mg WEEK 24 MAINTENANCE 2013-11-27 224 Placebo 0 mg WEEK 28 MAINTENANCE 2013-12-30 257 Placebo 0 mg
36 9 (233) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
Visit Start Date Study Day Actual Treatment Dose WEEK 32 MAINTENANCE 2014-01-24 282 Ustekinumab 90 mg WEEK 36 MAINTENANCE 2014-02-21 310 Placebo 0 mg WEEK 40 MAINTENANCE 2014-03-24 341 Placebo 0 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: N Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: Y
8) Induction Baseline Crohn's Disease History Date of diagnosis: 25MAR1998 Disease duration: 15.07 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪ᾘ⟶እኚ㸦㛵⠇⅖㸭㛵⠇③㸧
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: PREVIOUS HISTORY Stricture complications of (CD): PREVIOUS HISTORY
10) Concomitant Crohn's Disease-Related Surgeries Surgery Date Result of lack of efficacy? ࢻࣞࢼ࣮ࢪ-⤒⓶ษ㛤ཬࡧࢻࣞࢼ࣮ࢪ 2013-05-08 N ࢻࣞࢼ࣮ࢪ-ࢩ࣮ࢺࣥ␃⨨ 2013-11-25 N
11) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 0 METHYLPREDNISOLONE 8 mg 10 mg WEEK 8 MAINTENANCE METHYLPREDNISOLONE 6 mg 7.5 mg WEEK 8 MAINTENANCE METHYLPREDNISOLONE 4 mg 5 mg WEEK 24 MAINTENANCE METHYLPREDNISOLONE 4 mg 5 mg WEEK 24 MAINTENANCE METHYLPREDNISOLONE 0 mg 0 mg
12) Narrative Text ⿕㦂⪅ࡣ 4 ṓࡢⓑேዪᛶ࡛㸪2013 ᖺ 4 ᭶ 18 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ࣉࣛࢭ࣎ࢆ㟼⬦ෆᢞ ࡉࢀࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡎ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏࢆᢞࡉ ࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪⫶㣗㐨㏫ὶᛶ ᝈ㸪㧗⾑ᅽ㸪ႚ↮㸪aminophenazone ཬࡧ࣌ࢽࢩࣜࣥᑐࡍࡿࣞࣝࢠ࣮࡛࠶ࡗࡓࠋ SAE/Serious Infection㸸⫠㛛⮋⒆㸦Day 21㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ㝜၁እ㒊㞄᥋ࡍࡿ⫠㛛࿘ᅖ⮋⒆ࡀࡳࡽࢀ㸪2013 ᖺ 5 ᭶ 8 ᪥ධ 㝔ࡋࡓࠋධ㝔ᙜ᪥㸪⫠㛛࿘ᅖ⮋⒆ࡢษ㛤ཬࡧࢻࣞࢼ࣮ࢪࢆ⾜ࡋ㸪⢓⛻ᛶࡢ⮋Ồࢆฟࡋࡓࠋ ⒪ࡣ㸪࣓ࢧࣛࢪࣥ㸪pantoprazole㸪ࣅࢯࣉ࣮ࣟࣟࣝ㸪࣓ࢳࣝࣉࣞࢻࢽࢰࣟࣥ㸪ࢪࢡࣟࣇ࢙ࢼࢡ㸪 ࢚ࣀ࢟ࢧࣃࣜࣥཬࡧ aminophenazone ࡀ⏝ࡉࢀࡓࠋ⿕㦂⪅ࡣ㸪2013 ᖺ 5 ᭶ 13 ᪥㏥㝔ࡋࡓࠋ
37 0 (234) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
SAE㸸⒦㸦Day 99㸧 CIOMS ࡼࡿ㸪2013 ᖺ 5 ᭶ࡢ⫠㛛࿘ᅖ⮋⒆ࡢษ㛤ཬࡧࢻࣞࢼ࣮ࢪᚋṧᏑࡋࡓ⒦ࡢࡓࡵ㸪 ⿕㦂⪅ࡣ 2013 ᖺ 7 ᭶ 25 ᪥ධ㝔ࡋࡓࠋ⮋⒆ࡣㄆࡵࡽࢀ࡞ࡗࡓࡀ㸪ࣄ࣏ࢡࣛࢸࢫἲࡼࡿ⒦ ฟ⾡ࢆᐇࡋ㸪⾡㒊ࢻ࣮ࣞࣥࢆ␃⨨ࡋࡓࠋ⒪ࡣ㸪ࢰࣝࣆࢹ࣒㓇▼㓟ሷ㸪࣑ࢲࢰ࣒ࣛ㸪 ங㓟ࣜࣥࢤࣝᾮࡀ⏝ࡉࢀࡓࠋ⿕㦂⪅ࡣ㸪2013 ᖺ 7 ᭶ 27 ᪥㏥㝔ࡋࡓࠋ SAE/Serious Infection㸸⫠㛛⮋⒆㸦Day 206㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2 ᪥㛫Ⓨ⇕ࡀᣢ⥆ࡋ࡚࠾ࡾ㸪⫠㛛࿘ᅖ⮋⒆ࡢࡓࡵ 2013 ᖺ 11 ᭶ 9 ᪥ ධ㝔ࡋࡓࠋゐデ࡛㸪ᕥ㝜၁እ㒊㞄᥋ࡍࡿ᮰≧ࡢᐇᛶ⭘⒗ࢆㄆࡵࡓࠋྠ᪥㸦2013 ᖺ 11 ᭶ 9 ᪥㸧㸪㝜ษ㛤ཬࡧࢻࣞࢼ࣮ࢪࢆ⾜ࡋ㸪ከ㔞ࡢ⮋Ồࢆฟࡋࡓࠋ⒪ࡣ㸪ࢩࣉࣟࣇࣟ࢟ࢧࢩ ࣥ㸪࢚ࣀ࢟ࢧࣃࣜࣥ㸪࣓ࢺࣟࢽࢲࢰ࣮ࣝ㸪mesalamine㸪pantoprazole㸪ࣅࢯࣉ࣮ࣟࣟࣝཬࡧ࣓ࢳࣝ ࣉࣞࢻࢽࢰࣟࣥࡀ⏝ࡉࢀࡓࠋ⿕㦂⪅ࡣ㸪2013 ᖺ 11 ᭶ 11 ᪥㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2013-05-31 Ẽ⟶ᨭ⅖ MILD/ Y/ DOSE NOT CHANGED/ 2013-06-02 (44/.) (BRONCHITIS) NOT Y RECOVERED/RESOLVED (46/.) RELATED 2013-10-24 ࢡ࣮ࣟࣥ MILD/ N/ DOSE NOT CHANGED/ 2013-11-14 (190/133) (WORSENING OF CROHN'S NOT NA RECOVERED/RESOLVED (211/154) DISEASE) RELATED 2014-01-18 ࢘ࣝࢫᛶ⫶⭠⅖ MILD/ Y/ DOSE NOT CHANGED/ 2014-01-23 (276/219) (VIRAL GASTROENTERITIS) NOT Y RECOVERED/RESOLVED (281/224) RELATED
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route ZOLPIDEM 2013-05-08 2013-05-08 ORAL CEFUROXIME 2013-05-31 2013-06-02 ORAL ZOLPIDEM TARTRATE 2013-07-24 2013-07-24 ORAL MIDAZOLAM 2013-07-25 2013-07-25 ORAL RINGER /06419601/ 2013-07-25 2013-07-25 INTRAVENOUS MESALAZINE 2013-07-31 - RECTAL RIFAXIMIN 2013-10-31 2013-11-05 ORAL CIPROFLOXACIN 2013-11-09 2013-11-11 INTRAVENOUS METRONIDAZOLE 2013-11-09 2013-11-11 INTRAVENOUS CIPROFLOXACIN 2013-11-11 2013-11-13 ORAL METRONIDAZOLE 2013-11-11 2013-11-13 ORAL METRONIDAZOLE 2014-01-19 2014-01-31 ORAL
(53) Subject CNTO1275CRD3003-4602-10902
1) Reason for narrative selection SAE Event of interest: Serious infection
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome I/M) 2013-01-07 ⫹⟶⅖ Y MODERATE/ Y/ DOSE NOT CHANGED/ 2013-02-15 (33/.) (CHOLANGITIS) POSSIBLE Y RECOVERED/RESOLVED (72/.)
37 1 (235) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome I/M) 2013-02-17 ⾡ᚋឤᰁ Y MODERATE/ Y/ DOSE NOT CHANGED/ 2013-03-28 (74/18) (POST-OPERATIVE WOUND NOT N RECOVERED/RESOLVED (113/57) INFECTION".) RELATED 2013-07-10 ࢝ࣥࣆࣟࣂࢡࢱ࣮⫶⭠⅖ Y MODERATE/ Y/ DOSE NOT CHANGED/ 2013-07-19 (217/161) (CAMPILOBACTER GASTRO NOT Y RECOVERED/RESOLVED (226/170) ENTERITIS) RELATED
3) Other Adverse Events Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2012-12-06 ⇕ឤ MILD/ N/ DOSE NOT CHANGED/ Ongoing (1/.) (WARM FEET) PROBABLE NA NOT RECOVERED/NOT - RESOLVED 2013-01-11 ⬡⫫౽ MILD/ N/ DOSE NOT CHANGED/ 2013-02-11 (37/.) (STEATORHOE) DOUBTFUL NA RECOVERED/RESOLVED (68/.) 2013-04-15 ␗ᖖ࡞ክ MILD/ N/ DOSE NOT CHANGED/ Ongoing (131/75) (LIVELY DREAMS) DOUBTFUL NA NOT RECOVERED/NOT - RESOLVED 2013-04-19 ᚰᡣ⣽ື MILD/ N/ DOSE NOT CHANGED/ Ongoing (135/79) (ATRIAL FIBRILLATION) NOT NA NOT RECOVERED/NOT - RELATED RESOLVED 2013-04-22 ୗ⑩ MODERATE/ N/ DOSE NOT CHANGED/ 2013-04-30 (138/82) (DIARRHEA) DOUBTFUL NA RECOVERED/RESOLVED (146/90) 2013-11-17 Ẽ㐨ឤᰁ MILD/ Y/ DOSE NOT CHANGED/ 2013-11-22 (347/291) (MILD AIRWAY DOUBTFUL N RECOVERED/RESOLVED (352/296) INFECTION)
4) Baseline Demographic Information ȋȌǣ ͷ ǣ ȋȌǣ ͷǤͺ ǣ ǣ Ǧ ȋ Ȍǣ ͳͶ
5) Induction Treatment Group Induction study: CNTO1275CRD3001 Randomized Treatment Group: Ustekinumab Approximating 6 mg/kg IV Actual Treatment Group: Ustekinumab Approximating 6 mg/kg IV
6) Maintenance Treatment Group Assigned Treatment Group: Randomized subject/Responder to ustekinumab IV induction dosing/ustekinumab 90 mg SC q12w
7) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2012-12-06 1 Ustekinumab 389.7 mg WEEK 0 MAINTENANCE 2013-01-31 57 Ustekinumab 90 mg WEEK 8 MAINTENANCE 2013-03-28 113 Placebo 0 mg WEEK 12 MAINTENANCE 2013-04-25 141 Ustekinumab 90 mg WEEK 16 MAINTENANCE 2013-05-23 169 Placebo 0 mg WEEK 20 MAINTENANCE 2013-06-20 197 Placebo 0 mg WEEK 24 MAINTENANCE 2013-07-25 232 Ustekinumab 90 mg WEEK 28 MAINTENANCE 2013-08-15 253 Placebo 0 mg WEEK 32 MAINTENANCE 2013-09-19 288 Placebo 0 mg WEEK 36 MAINTENANCE 2013-10-15 314 Ustekinumab 90 mg WEEK 40 MAINTENANCE 2013-11-05 335 Placebo 0 mg
37 2 (236) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
8) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: N Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: Y
9) Induction Baseline Crohn's Disease History Date of diagnosis: 31DEC1960 Disease duration: 51.93 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪⫠㛛࿘ᅖ
10) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: PREVIOUS HISTORY Stricture complications of (CD): PREVIOUS HISTORY
11) Concomitant Crohn's Disease-Related Surgeries None reported
12) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 0 BUDESONIDE 9 mg - WEEK 0 FLUTICASON 27.5 - WEEK 4 MAINTENANCE HYDROCORTISONE 200 mg - WEEK 4 MAINTENANCE HYDROCORTISONE 50 mg - WEEK 4 MAINTENANCE HYDROCORTISONE 0 mg - WEEK 4 MAINTENANCE HYDROCORTISONE 0 mg - WEEK 24 MAINTENANCE BUDESONIDE 6 mg - WEEK 24 MAINTENANCE BUDESONIDE 9 mg - WEEK 24 MAINTENANCE HYDROCORTISONE 100 mg - WEEK 24 MAINTENANCE HYDROCORTISONE 0 mg - WEEK 36 MAINTENANCE BUDESONIDE 7 mg - WEEK 40 MAINTENANCE BUDESONIDE 3.5 mg - WEEK 44 MAINTENANCE BUDESONIDE 6 mg -
13) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route AMOXICILLIN W/CLAVULANATE POTASSIUM 2013-01-08 2013-01-09 INTRAVENOUS HYDROCORTISONE 2013-02-11 2013-02-15 INTRAVENOUS NADROPARIN CALCIUM 2013-02-11 2013-02-11 SUBCUTANEOUS AMOXICILLIN W/CLAVULANATE POTASSIUM 2013-02-12 2013-02-12 INTRAVENOUS OXYCODONE HYDROCHLORIDE 2013-02-14 2013-02-18 ORAL TRAMADOL 2013-02-14 2013-02-14 ORAL MACROGOL 2013-02-17 2013-02-18 ORAL NADROPARIN CALCIUM 2013-02-17 2013-02-21 SUBCUTANEOUS
14) Narrative Text ⿕㦂⪅ࡣ 6 ṓࡢⓑே⏨ᛶ࡛㸪2012 ᖺ 12 ᭶ 6 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏ㸦㹼6 mg/kg ⩌㸧 ࢆ㟼⬦ෆᢞࡉࢀࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏ 90 mg ࢆ q12w ࡛⓶ୗᢞࡍࡿ⩌ࣛࣥࢲ࣒ࡉࢀࡓࠋ
37 3 (237) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪⭡③㸪⭡ቨ࣊ ࣝࢽ㸪㐣ᩄ㸦ໟᖏ㸧㸪㧗⾑ᅽ㸪⭠ษ㝖ཬࡧ」ᩘᅇࡢᡭ⾡㹙ࢡ࣮ࣟࣥ㛵㐃㸪⮋⒆ཬࡧ⒦Ꮝࡢ ࡓࡵ㸪ᅇ┣㒊ษ㝖ཬࡧ」ᩘᅇࡢ᪂ࡓ࡞ᅇ⭠ᮎ➃㒊ษ㝖㸦ṧᏑᑠ⭠ࡣ 180 cm㸧㹛࡛࠶ࡗࡓࠋ
௨ୗࡣᐶゎᑟධヨ㦂 CNTO1275CRD3001 ࡢ㦂⥲ᣓሗ࿌᭩ࡢ⿕㦂⪅ࡢླྀ㏙࡚ሗ࿌ࡉࢀࡓ ㇟࡛࠶ࡿ㸸 SAE/Serious infection㸸⫹⟶⅖㸦Day 33㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ๓᪥ࡽ⥆ࡃⓎ⇕ࡢࡓࡵ 2013 ᖺ 1 ᭶ 8 ᪥ධ㝔ࡋࡓࠋ⭡㒊㉸㡢Ἴ ᳨ᰝ࡛ࡣ㸪⤖▼ཬࡧ⫹Ἶࢆక࠺⫹ᄞᣑᙇ୪ࡧ⫹⟶୰ኸࡢᣑᙇࡀࡳࡽࢀࡓࠋෆど㙾ⓗ㏫⾜ᛶ⫹㐨 ⮅⟶ᙳ࡛ࡣ㸪⥲⫹⟶ᣑᙇཬࡧ⫹▼ࡀࡳࡽࢀࡓࠋᣓ⣙➽ษ㛤ཬࡧࣂ࣮ࣝࣥࡼࡿ⫹Ἶ㝖ཤࢆ㸪 ྜేࢆⓎࡍࡿࡇ࡞ࡃᐇࡋࡓࠋࣔ࢟ࢩࢩࣜࣥ㸭ࢡࣛࣈࣛࣥ㓟ࢆᢞࡉࢀࡓࠋ⿕㦂⪅ࡣ 2013 ᖺ 1 ᭶ 11 ᪥㏥㝔ࡋࡓࡀ㸪2013 ᖺ 2 ᭶ 11 ᪥ධ㝔ࡋ㸪2013 ᖺ 2 ᭶ 12 ᪥㛤⭡⫹ᄞฟ ⾡ࢆཷࡅࡓࠋ⫹ᄞࡢ⌮Ꮫⓗᡤぢ࡛ࡣ㸪⫹▼ཬࡧ៏ᛶ⫹ᄞ⅖ࡀㄆࡵࡽࢀ㸪άືᮇࡢ⅖ཬࡧ␗ ᙧᡂࡣ࡞ࡗࡓࠋචࢢࣟࣈࣜࣥ G4 ࡣ㝜ᛶ࡛࠶ࡾ㸪⮬ᕫචᛶࡢ⫹ᄞ⅖ࡣ♧၀ࡉࢀ࡞ࡗࡓࠋ 2013 ᖺ 2 ᭶ 15 ᪥⫹⟶⅖ࡣᾘᩓࡋࡓሗ࿌ࡉࢀ㸪ྠ᪥⿕㦂⪅ࡣ㏥㝔ࡋࡓࠋ
௨ୗࡣᐶゎ⥔ᣢ⒪ἲ࡛࠶ࡿᮏヨ㦂࡛つᐃࡉࢀࡓሗ࿌ᮇ㛫Ⓨ⌧ࡋࡓ㇟࡛࠶ࡿ㸸 SAE/Serious Infection㸸⾡ᚋឤᰁ㸦Day 74㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ㸪⫹ᄞษ㝖⾡ᚋࡢⓎ㉥ཬࡧ⑊③୪ࡧྑୖ⭡㒊ࡢ⭘⬽ࡀㄆࡵࡽ ࢀ㸪⾡ᚋឤᰁࡼࡾ㸪2013 ᖺ 2 ᭶ 17 ᪥ධ㝔ࡋࡓࠋ⿕㦂⪅ࡣ㸪2013 ᖺ 2 ᭶ 12 ᪥⫹ᄞษ㝖⾡ ࢆཷࡅࡓࡀ㸦ୖ㏙㸧㸪⒵╔ࡼࡾᗈ⠊ᅖࡢษ㛤ࡀᚲせ࡛࠶ࡗࡓࡓࡵ㸪ᡭ⾡ 8㹼10 㛫ࢆせࡋࡓࠋ デᐹ࡛ࡣ⭡㒊ࡣᰂࡽࡃ㸪ྑୖ⭡㒊ࡢ⾡ᚋ㒊ࡢゐデ࡛ࡣ⑊③ࢆకࡗࡓࠋഃ㒊࡛㸪Ⓨ㉥ࡀᙉ ࡃ࡞ࡗࡓࠋ⾡ᚋ࿘ᅖࡢゐデ࡛ࡣ㸪⓶ࡀࢃࡎ◳ࡃឤࡌࡽࢀࡓࡀ㸪Ⓨ㉥ཪࡣ ឤࡣㄆࡵ࡞ ࡗࡓࠋ⿕㦂⪅ࡢయ ࡣ 36.7°C ࡛࠶ࡗࡓࠋ⭡㒊㉸㡢Ἴ᳨ᰝ࡛ࡣ㸪⾡ᚋ⤒㐣ࡢᡤぢࡋ࡚㸪⫹ᄞ ࢞ࢫࢆྵࡴᾮయീཬࡧᾋ㐟≀ࡀㄆࡵࡽࢀࡓࠋ 2013 ᖺ 2 ᭶ 19 ᪥ࡢ㉸㡢Ἴ᳨ᰝ࡛ࡣ㸪⫹ᄞᗋࡢ⨨ࡢ⓶ୗ㸪๓ᅇࡢ㉸㡢Ἴ᳨ᰝ࡛ࡶࡳࡽࢀࡓ ᾮయ㈓␃ࡀㄆࡵࡽࢀࡓࠋᾮࢆ┠ⓗࡋ࡚㒊ࢆษ㛤ࡋ㸪ከ㔞ࡢ⮋Ồࢆฟࡋࡓࠋ㒊ࡢᇵ㣴᳨ ᰝࡣ⾜࡞ࢃࡎ㸪ᢠ⏕≀㉁ࡣᢞࡋ࡞ࡗࡓࠋ2012 ᖺ 2 ᭶ 17 ᪥ࡢ⥲ࣅࣜࣝࣅࣥࡣ㸪19 ȝmol/L㸦ṇ ᖖ⠊ᅖ᫂㸧࡛࠶ࡗࡓࠋ ⿕㦂⪅ࡣ㸪2013 ᖺ 2 ᭶ 20 ᪥㏥㝔ࡋࡓࠋᮏ㇟ࡣ㸪2013 ᖺ 3 ᭶ 28 ᪥ᅇ㸭ᾘᩓࡋࡓࠋ SAE/Serious Infection㸸࢝ࣥࣆࣟࣂࢡࢱ࣮⫶⭠⅖㸦Day 217㸧 CIOMS ࡼࡿ㸪2013 ᖺ 7 ᭶ 10 ᪥㸪⿕㦂⪅ࡣ 39°C ࡢⓎ⇕㸪ᝏᐮ㸪ୗ⭡㒊③㸪ୗ⑩ཬࡧᛴᛶ ⭈ᶵ⬟ࡼࡾධ㝔ࡋࡓࠋᒀ᳨ᰝ࡛ࡣ㸪␗ᖖࡣ࡞ࡗࡓࠋ2013 ᖺ 7 ᭶ 11 ᪥ࡢ⭡㒊㉸㡢Ἴ᳨ᰝ ࡛ࡣ㸪ᾮయ࡛‶ࡓࡉࢀࡓᑠ⭠ಀ㋟ཬࡧ⭠ቨ⭘⬽ࡀㄆࡵࡽࢀࡓࠋ᳨ᰝീࡣ㸪ࢡ࣮ࣟࣥࡢᅇ⭠⅖ ୍⮴ࡋࡓࠋ ⮫ᗋ᳨ᰝ್ࡣ௨ୗࡢ࠾ࡾ࡛࠶ࡗࡓ㸸⥲ࣅࣜࣝࣅࣥ 60 ȝmol/L㸦2013 ᖺ 7 ᭶ 11 ᪥㸧ཬࡧ 41 ȝmol/L㸦2013 ᖺ 7 ᭶ 12 ᪥㸧㸪⾑ᾮᇵ㣴࡛ࡣዲẼᛶཪࡣ᎘Ẽᛶࡢ⣽⳦ࢆㄆࡵࡎ㸦2013 ᖺ 7 ᭶ 11 ᪥㸧㸪C ᛂᛶࡓࢇⓑ⃰ᗘ 92 mg/L㸦2013 ᖺ 7 ᭶ 11 ᪥㸧ཬࡧ 8.2 mg/L㸦2013 ᖺ 7 ᭶ 15 ᪥㸧㸪 ࢡࣞࢳࢽࣥ 158 ȝmol/L㸦2013 ᖺ 7 ᭶ 11 ᪥㸧ཬࡧ 128 ȝmol/L㸦2013 ᖺ 7 ᭶ 17 ᪥㸧㸪⣒⌫యℐ㐣
37 4 (238) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
⋡ 38 mL/min㸦2013 ᖺ 7 ᭶ 11 ᪥㸧ཬࡧ 49 mL/min㸦2013 ᖺ 7 ᭶ 18 ᪥㸧ࠋ2013 ᖺ 7 ᭶ 11 ᪥ࡢ⾑ ᾮᇵ㣴࡛ࡣዲẼᛶཪࡣ᎘Ẽᛶࡢ⣽⳦ࢆㄆࡵࡎ㸪౽ᇵ㣴᳨ᰝ࡛ࡣ㸪ࢡࣟࢫࢺࣜࢪ࣒࣭࢘ࢹࣇࢩ ࣞࡣ㝜ᛶ࡛࠶ࡗࡓࠋ⭠ෆࡢཎ⳦ࢆ᳨ฟࡍࡿ࣐ࣝࢳࣉࣞࢵࢡࢫ PCR ᳨ᰝ࡛ࡣ㸪ࢧࣝࣔࢿࣛ㸪㉥ ⑩⳦㸭⭠⟶ධᛶ⭠⳦ࡣ㝜ᛶ࡛࠶ࡾ㸪ᚿ㈡ẘ⣲⏘⏕⭠⳦ࡶ㝜ᛶ࡛࠶ࡗࡓࡀ㸪Campylobacter jejuni ࡣ㝧ᛶ࡛࠶ࡗࡓࠋ ධ㝔୰㸪ࢪࢫ࣐ࣟࢩࣥ㸪㟼⬦ෆ⿵ᾮ㸪nadroparin㸪ሷ࣒࢝ࣜ࢘㸪temazepam㸪ࣈࢹࢯࢽࢻ㸪 ࣓ࢺࣟࢽࢲࢰ࣮ࣝ㸪ࣄࢻࣟࢥࣝࢳࢰࣥ㸪cefuroxine㸪Ⅳ㓟࢝ࣝࢩ࣒࢘㸭ࣅࢱ࣑ࣥ D㸪࢚ࢯ࣓ࣉࣛ ࢰ࣮ࣝཬࡧ࣓ࢺࣉ࣮ࣟࣟࣝࡼࡿ⒪ࡀᐇࡉࢀࡓࠋ⿕㦂⪅ࡣ㸪2013 ᖺ 7 ᭶ 19 ᪥Ᏻᐃࡋࡓ≧ ែ࡛㏥㝔ࡋ㸪ࢪࢫ࣐ࣟࢩࣥࡼࡿ⒪ࡣ⥅⥆ࡋࡓࠋ
(54) Subject CNTO1275CRD3003-5301-20943
1) Reason for narrative selection SAE Event of interest: Serious infection
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome (Study day I/M) 2014-09-25 Ẽ⟶ᨭ⅖ Y SEVERE/ Y/ DOSE NOT CHANGED/ 2014-10-06 (144/88) (BRONCHITIS) NOT RELATED Y RECOVERED/RESOLVED (155/99)
3) Baseline Demographic Information ȋȌǣ Ͷͺ ǣ ȋȌǣ ͶͺǤ ǣ ǣ ͳͻͷǦͳʹǦͲͳ ȋ Ȍǣ ͳͳ
4) Induction Treatment Group Induction study: CNTO1275CRD3002 Randomized Treatment Group: Placebo IV Actual Treatment Group: Placebo IV
5) Maintenance Treatment Group Assigned Treatment Group: Non-randomized subject/Non-responder to placebo IV induction dosing and received ustekinumab in maintenance
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2014-05-05 1 Placebo 0 mg WEEK 0 MAINTENANCE 2014-06-30 57 Placebo 0 mg WEEK 0 MAINTENANCE 2014-06-30 57 Ustekinumab 129.6 mg WEEK 8 MAINTENANCE 2014-08-25 113 Ustekinumab 90 mg WEEK 12 MAINTENANCE 2014-09-29 148 Placebo 0 mg WEEK 16 MAINTENANCE 2014-10-20 169 Placebo 0 mg WEEK 20 MAINTENANCE 2014-11-24 204 Ustekinumab 90 mg WEEK 24 MAINTENANCE 2014-12-19 229 Placebo 0 mg WEEK 28 MAINTENANCE 2015-01-12 253 Placebo 0 mg WEEK 32 MAINTENANCE 2015-02-06 278 Ustekinumab 90 mg WEEK 36 MAINTENANCE 2015-03-16 316 Placebo 0 mg WEEK 40 MAINTENANCE 2015-04-13 344 Placebo 0 mg
37 5 (239) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: N Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: Y
8) Induction Baseline Crohn's Disease History Date of diagnosis: 23AUG2005 Disease duration: 8.70 years Involved areas: ᅇ⭠ࡢࡳ㸪ᾘ⟶እኚ㸦㛵⠇⅖㸭㛵⠇③㸧
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: NEVER
Stricture complications of (CD): NEVER 10) Concomitant Crohn's Disease-Related Surgeries None reported
11) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 12 MAINTENANCE OMNAIR 0.05 mg - WEEK 12 MAINTENANCE HYDROCORTISONE 400 mg - WEEK 12 MAINTENANCE BUDESONIDE 0.25 mg - WEEK 16 MAINTENANCE PREDNISONE 50 mg 50 mg WEEK 16 MAINTENANCE HYDROCORTISONE 0 mg - WEEK 16 MAINTENANCE PREDNISONE 0 mg 0 mg WEEK 16 MAINTENANCE BUDESONIDE 0 mg - WEEK 16 MAINTENANCE OMNAIR 0 mg - WEEK 16 MAINTENANCE BUDESONIDE 2 mg - WEEK 16 MAINTENANCE BUDESONIDE 0 mg - WEEK 28 MAINTENANCE PREDNISONE 10 mg 10 mg WEEK 32 MAINTENANCE PREDNISONE 0 mg 0 mg
12) Narrative Text ⿕㦂⪅ࡣ 4 ṓࡢⓑேዪᛶ࡛㸪2014 ᖺ 5 ᭶ 5 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ࣉࣛࢭ࣎ࢆ㟼⬦ෆᢞ ࡉࢀࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡎ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏࢆᢞࡉ ࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪ࢨࢳ࢜ࣉࣜ ࣥࡼࡿ⥅⥆⒪࡛࠶ࡗࡓࠋ SAE/Serious Infection㸸Ẽ⟶ᨭ⅖㸦Day 144㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ‵ᛶတႿཬࡧ㰯㛢ࡀ 3 㐌㛫ᣢ⥆ࡋ࡚࠾ࡾ㸪Ẽ⟶ᨭ⅖ࡢࡓࡵ㸪2014 ᖺ 9 ᭶ 25 ᪥ධ㝔ࡋࡓࠋእ᮶࡛ࡢᢠ⏕≀㉁ࡼࡿ⒪ࡣຠᯝ༑ศ࡛࠶ࡗࡓࠋ2014 ᖺ 9 ᭶ 26 ᪥ ࡢ㢧ᚤ㙾ⓗၻ⑱᳨ᰝ࡛ࡣ㸪పಸ⋡ど㔝࡛ 25 ಶ௨ୖࡢ⮋⣽⬊ཬࡧ 10 ࡽ 25 ಶࡢᡥᖹୖ⓶⣽⬊ࡀ ࡳࡽࢀࡓࠋከᩘࡢᖖᅾ⣽⳦ྀࡀㄆࡵࡽࢀ㸪ᢠ㓟⳦ࡣ㝜ᛶ࡛࠶ࡗࡓࠋ2014 ᖺ 9 ᭶ 30 ᪥ࡢ⾑ᾮᇵ㣴 ᳨ᰝ࡛ࡣ㸪ዲẼᛶ⣽⳦ཬࡧ᎘Ẽᛶ⣽⳦ࡶ㝜ᛶ࡛࠶ࡗࡓࠋࣔ࢟ࢩࣇࣟ࢟ࢧࢩࣥሷ㓟ሷ㸪ࣄࢻࣟ ࢥࣝࢳࢰࣥ㸪ࣔࣥࢸࣝ࢝ࢫࢺࢼࢺ࣒ࣜ࢘㸪ࢭࢳࣝࢩࢫࢸࣥ㸪ࢭࢺ࣑ࣀࣇ࢙ࣥ㸭࢝ࣇ࢙
37 6 (240) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
ࣥ㸭ࢥࢹࣥࣜࣥ㓟ሷ㸭meprobamate㸦Stilpane㸧㸪xylometazoline㸪ࢩࢡࣞࢯࢽࢻ㸪ࣈࢹࢯࢽࢻ㸪 ࢹ࢟ࢫࢺ࣓ࣟࢺࣝࣇࣥ㸪྾ධ㸪⌮Ꮫ⒪ἲࡼࡿ⒪ࡀ⾜ࢃࢀࡓࠋ⒪ࡀዌຠࡋ㸪⿕㦂⪅ࡣ 2014 ᖺ 9 ᭶ 28 ᪥㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2014-05-05 㰯ဗ㢌⅖ MILD/ Y/ DOSE NOT CHANGED/ 2014-05-11 (1/.) (COMMON COLD) NOT N RECOVERED/RESOLVED (7/.) RELATED 2014-05-05 ኻ⚄ᑍ๓ࡢ≧ែ MODERATE/ N/ DRUG INTERRUPTED/ 2014-05-05 (1/.) (VASO-VAGAL EPISODE) NOT NA RECOVERED/RESOLVED (1/.) RELATED 2014-09-12 Ẽ⟶ᨭ⅖ MODERATE/ Y/ DOSE NOT CHANGED/ 2014-09-25 (131/75) (BRONCHITIS) NOT Y RECOVERED/RESOLVED (144/88) RELATED 2014-12-19 㛵⠇⅖ SEVERE/ N/ DOSE NOT CHANGED/ 2015-01-22 (229/173) (WORSENING OF ARTHRITIS) NOT NA RECOVERED/RESOLVED (263/207) RELATED 2015-03-25 ⬡₃ᛶゅ MODERATE/ N/ DOSE NOT CHANGED/ 2015-03-25 (325/269) (REMOVAL OF BASAL CELL DOUBTFUL NA RECOVERED/RESOLVED (325/269) PAPILOMA)
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route CO-TYLENOL /00446801/ 2014-05-08 2014-05-08 ORAL CEFUROXIME AXETIL 2014-09-13 2014-09-18 ORAL CEFUROXIME 2014-09-18 2014-09-22 ORAL MOXIFLOXACIN HYDROCHLORIDE 2014-09-25 2014-09-28 INTRAVENOUS DRIP HYDROCORTISONE SODIUM SUCCINATE 2014-09-25 2014-09-28 INTRAVENOUS SUPRAGESIC /01152401/ 2014-09-25 2014-09-25 ORAL ACETYLCYSTEINE 2014-09-26 2014-09-28 ORAL BROMHEXINE HYDROCHLORIDE 2014-09-26 2014-09-28 RESPIRATORY (INHALATION) DESLORATADINE 2014-09-26 2014-09-27 ORAL CICLESONIDE 2014-09-26 2014-10-11 NASAL XYLOMETAZOLINE HYDROCHLORIDE 2014-09-26 2014-10-11 NASAL BUDESONIDE 2014-09-26 2014-09-28 RESPIRATORY (INHALATION) MONTELUKAST SODIUM 2014-09-26 2014-10-05 ORAL MOXIFLOXACIN HYDROCHLORIDE 2014-09-29 2014-10-01 ORAL MONTELUKAST SODIUM 2014-09-29 2014-10-05 ORAL BUDESONIDE W/FORMOTEROL FUMARATE 2014-09-29 2014-10-11 RESPIRATORY (INHALATION) PREDNISONE 2014-12-24 2015-01-22 ORAL
(55) Subject CNTO1275CRD3003-5307-20565
1) Reason for narrative selection SAE Event of interest: Serious infection
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome (Study day I/M) 2014-08-08 ᛴᛶ㰯⭍⅖ Y MODERATE/ Y/ DOSE NOT CHANGED/ 2014-08-26 (327/271) (ACUTE SINUSITIS) NOT RELATED Y RECOVERED/RESOLVED (345/289)
37 7 (241) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
3) Baseline Demographic Information ȋȌǣ ͵ͷ ǣ ȋȌǣ ͺͷǤͻ ǣ ǣ ͳͻǦͳͳǦʹ ȋ Ȍǣ ͳͻͷ
4) Induction Treatment Group Induction study: CNTO1275CRD3002 Randomized Treatment Group: Placebo IV Actual Treatment Group: Placebo IV
5) Maintenance Treatment Group Assigned Treatment Group: Non-randomized subject/Non-responder to placebo IV induction dosing and received ustekinumab in maintenance
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2013-09-16 1 Placebo 0 mg WEEK 0 MAINTENANCE 2013-11-11 57 Placebo 0 mg WEEK 0 MAINTENANCE 2013-11-11 57 Ustekinumab 129.6 mg WEEK 8 MAINTENANCE 2014-01-15 122 Ustekinumab 90 mg WEEK 12 MAINTENANCE 2014-02-05 143 Placebo 0 mg WEEK 16 MAINTENANCE 2014-03-03 169 Placebo 0 mg WEEK 20 MAINTENANCE 2014-04-02 199 Ustekinumab 90 mg WEEK 24 MAINTENANCE 2014-04-30 227 Placebo 0 mg WEEK 28 MAINTENANCE 2014-05-28 255 Placebo 0 mg WEEK 32 MAINTENANCE 2014-06-25 283 Ustekinumab 90 mg WEEK 36 MAINTENANCE 2014-07-23 311 Placebo 0 mg WEEK 40 MAINTENANCE 2014-08-20 339 Placebo 0 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: N Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: Y
8) Induction Baseline Crohn's Disease History Date of diagnosis: 30NOV2007 Disease duration: 5.80 years Involved areas: ᅇ⭠ࡢࡳ
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: NEVER Stricture complications of (CD): NEVER
10) Concomitant Crohn's Disease-Related Surgeries None reported
11) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 0 BUDESONIDE 6 mg -
37 8 (242) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
Visit Drug Dose Prednisone equivalent WEEK 12 MAINTENANCE BUDESONIDE 3 mg - WEEK 16 MAINTENANCE BUDESONIDE 0 mg - WEEK 40 MAINTENANCE MOMETASONE 1 - WEEK 40 MAINTENANCE METHYLPREDNISOLONE 100 mg - WEEK 40 MAINTENANCE METHYLPREDNISOLONE 0 mg -
12) Narrative Text ⿕㦂⪅ࡣ 3 ṓࡢⓑே⏨ᛶ࡛㸪2013 ᖺ 9 ᭶ 16 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ࣉࣛࢭ࣎ࢆ㟼⬦ෆᢞ ࡉࢀࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡎ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏࢆᢞࡉ ࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪㰯⭍⅖㸪ႚ ↮㸪ෆど㙾ୗ㰯⭍ᡭ⾡㸪㰯୰㝸ᙧᡂ㸪㰯⏥ษ㝖㸦2012 ᖺ㸧࡛࠶ࡗࡓࠋ SAE/Serious Infection㸸ᛴᛶ㰯⭍⅖㸦Day 327㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣဗႃ③㸪㰯⭍⅖㸪ᕥ๓㢌Ὕ㒊ࡢ③ࡳ㸪ୖẼ㐨≧ཬࡧᚤ⇕ࡀ࠶ ࡾ㸪2014 ᖺ 8 ᭶ 8 ᪥ධ㝔ࡋࡓࠋྠ᪥ࡢ⮫ᗋ᳨ᰝ␗ᖖ್ࡣ㸪⾑Ύࢡࣞࢳࢽࣥ 106 ȝmol/L㹙ṇᖖ ⠊ᅖ㸦NR㸧59-104 ȝmol/L㹛㸪⣒⌫యℐ㐣⋡㸦GFR㸧68 mL/min㸦NR>90 mL/min㸧㸪C ᛂᛶࡓࢇ ⓑ⃰ᗘ 9.8 mg/L㸦NR<5.0 mg/L㸧ཬࡧ⾑ᑠᯈᩘ 120×109/L㸦NR 14-420×109/L㸧࡛࠶ࡗࡓࠋ㍍ᗘࡢ GFR ῶᑡ㹙68 mL/min㸦NR>90 mL/min㸧㹛ࡣ⬺Ỉ⥆Ⓨࡋࡓࡶࡢ࡛࠶ࡾ㸪㍍ᗘࡢ⾑ᑠᯈᩘῶᑡ 㹙120×109/L㸦NR 14-420×109/L㸧㹛ࡣឤᰁ⥆Ⓨࡋࡓࡶࡢ⪃࠼ࡽࢀࡓࠋࢥࣥࣆ࣮ࣗࢱ᩿ᒙᙳ ࢫ࡛࢟ࣕࣥࡣ㸪⠠㦵Ὕཬࡧྑ๓⠠㦵㒊㸪ࢃࡎ㝜ᙳࡀㄆࡵࡽࢀࡓࠋ⮫ᗋⓗࡣ㸪㧗⢓ᗘ࡛㏱ ᫂࡞ᚋ㰯₃ཬࡧኌ㛛࣭ႃ㢌ࡢ⣚ᩬࢆㄆࡵࡓࡀ㸪㰯⭍άືᛶឤᰁࡢᚩೃࡣ࡞ࡃ㸪࢘ࣝࢫᛶឤ ᰁཪࡣࣥࣇ࢚ࣝࣥࢨ୍⮴ࡋࡓࠋ⒪ࡣ㸪ࣔ࢟ࢩࣇࣟ࢟ࢧࢩࣥሷ㓟ሷ㸪࣓ࣔࢱࢰࣥ㸪࢜࢟ࢩ ࣓ࢱࢰࣜࣥሷ㓟ሷཬࡧ࣓ࢳࣝࣉࣞࢻࢽࢰࣟࣥࡀ⏝ࡉࢀࡓࠋ⿕㦂⪅ࡣ㸪2014 ᖺ 8 ᭶ 10 ᪥㏥㝔 ࡋࡓࠋ
13) Other Adverse Events Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome (Study day I/M) 2014-02-13 㰯⭍⅖ MILD/ Y/ DOSE NOT CHANGED/ 2014-02-14 (151/95) (SINUSITIS) NOT RELATED Y RECOVERED/RESOLVED (152/96) 2014-08-07 㰯⭍⅖ MILD/ Y/ DOSE NOT CHANGED/ 2014-08-08 (326/270) (SINUSITIS) NOT RELATED Y RECOVERED/RESOLVED (327/271)
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route AUGMENTIN /00756801/ 2014-02-13 2014-02-14 ORAL MOXIFLOXACIN HYDROCHLORIDE 2014-08-07 2014-08-18 ORAL OXYMETAZOLINE HYDROCHLORIDE 2014-08-07 2014-08-26 NASAL MOMETASONE FUROATE 2014-08-07 - NASAL METHYLPREDNISOLONE 2014-08-08 2014-08-10 INTRAVENOUS DRIP
(56) Subject CNTO1275CRD3003-5608-10945
1) Reason for narrative selection SAE Event of interest: Serious infection
37 9 (243) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome (Study day I/M) 2013-06-27 ⫠㛛⮋⒆ Y SEVERE/ Y/ NOT APPLICABLE/ 2013-06-29 (207/151) (ABSCESS (ANAL)) NOT RELATED N RECOVERED/RESOLVED (209/153)
3) Baseline Demographic Information ȋȌǣ ͶͶ ǣ ȋȌǣ ͻ ǣ ǣ ͳͻͺǦͲ͵ǦͲͻ ȋ Ȍǣ ͳʹǤͷ
4) Induction Treatment Group Induction study: CNTO1275CRD3001 Randomized Treatment Group: Ustekinumab Approximating 6 mg/kg IV Actual Treatment Group: Ustekinumab Approximating 6 mg/kg IV
5) Maintenance Treatment Group Assigned Treatment Group: Non-randomized subject/Non-responder to ustekinumab IV induction dosing and received ustekinumab in maintenance
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2012-12-03 1 Ustekinumab 389.7 mg WEEK 0 MAINTENANCE 2013-01-28 57 Ustekinumab 90 mg WEEK 0 MAINTENANCE 2013-01-28 57 Placebo 0 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: Y Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: -
8) Induction Baseline Crohn's Disease History Date of diagnosis: 05JUL1990 Disease duration: 22.42 years Involved areas: ᅇ⭠ཬࡧ⤖⭠㸪⫠㛛࿘ᅖ㸪ᑠ⭠㏆㸭⫶㸭㣗㐨㸪ᾘ⟶እኚ㸦㛵⠇⅖㸭㛵⠇ ③㸧
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: NEVER Stricture complications of (CD): PREVIOUS HISTORY
10) Concomitant Crohn's Disease-Related Surgeries Surgery Date Result of lack of efficacy? ࢻࣞࢼ࣮ࢪ-ࢩ࣮ࢺࣥ␃⨨ 2013-05-18 Y ࢻࣞࢼ࣮ࢪ-⤒⓶ษ㛤ཬࡧࢻࣞࢼ࣮ࢪ 2013-06-28 Y
11) Concomitant Steroids Visit Drug Dose Prednisone equivalent SAFETY FOLLOW-UP MAINTENANCE DEXAMETHASONE 6 mg -
38 0 (244) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
Visit Drug Dose Prednisone equivalent SAFETY FOLLOW-UP MAINTENANCE DEXAMETHASONE 4 mg - SAFETY FOLLOW-UP MAINTENANCE DEXAMETHASONE 0 mg - SAFETY FOLLOW-UP MAINTENANCE DEXAMETHASONE 0 mg -
12) Narrative Text ⿕㦂⪅ࡣ 4 ṓࡢⓑேዪᛶ࡛㸪2012 ᖺ 12 ᭶ 3 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏࢆ㟼⬦ෆᢞࡉࢀ ࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀࡎ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ᮏࢆᢞࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪ႍᜥ㸪㐣ᩄᛶ ⭠ೃ⩌ཬࡧႚ↮࡛࠶ࡗࡓࠋ SAE/Serious Infection㸸⫠㛛⮋⒆㸦Day 207㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ㸪⫠㛛࿘ᅖࡢ⑊③ࡀቑᙉࡋṌ⾜ᅔ㞴࡞ࡗࡓࡓࡵ㸪2013 ᖺ 6 ᭶ 27 ᪥ධ㝔ࡋࡓࠋ⫠㛛⮋⒆ࡣ㸪2012 ᖺ 12 ᭶ 11 ᪥ࡼࡾᣢ⥆ࡋ࡚࠸ࡓࠋ2013 ᖺ 6 ᭶ 28 ᪥ࡢ࣓ࢳࢩࣜ ࣥ⪏ᛶ㯤Ⰽࣈࢻ࢘⌫⳦ࡢࢫࢡ࣮ࣜࢽࣥࢢ᳨ᰝࡣ㝜ᛶ࡛࠶ࡾ㸪୰㛫ᒀ᳨యࡢ㢧ᚤ㙾᳨ᰝ࡛ࡣ␗ᖖࡣ ࡞ࡃ㸪⫠㛛⮋⒆デ᩿ࡉࢀࡓࠋ⒪ࡣ㸪ࢹ࢟ࢧ࣓ࢱࢰࣥ㸪࢚ࣇ࢙ࢻࣜࣥ㸪ࣔࣝࣄࢿ㸪࢜ࣥࢲࣥ ࢭࢺࣟࣥ㸪ங㓟ࣜࣥࢤࣝᾮ㸪ࢩࣉࣟࣇࣟ࢟ࢧࢩࣥ㸪ࢲࣝࢸࣃࣜࣥ㸪࣓ࢺࣟࢽࢲࢰ࣮ࣝ㸪࣓ࢧࣛࢪ ࣥ㸪ࣇ࢙ࣥࢱࢽࣝཬࡧࣉ࣏ࣟࣇ࢛࣮ࣝࡀ⏝ࡉࢀࡓࠋ⿕㦂⪅ࡣ㸪2013 ᖺ 6 ᭶ 28 ᪥㯞㓉ୗ࡛⫠ 㛛࿘ᅖ⮋⒆ࡢࢻࣞࢼ࣮ࢪཬࡧࢩ࣮ࢺࣥ␃⨨ࢆ⾜ࡉࢀࡓࠋ⫠㛛ᣲ➽ࡢୖ㒊ࡣ Ꮡࡉࢀ㸪✵Ὕࡣࡳ ࡽࢀࡎ㸪⮋ࢆకࢃ࡞࠸◳⤌⧊ࡢࡳࡀほᐹࡉࢀࡓࠋ⿕㦂⪅ࡣ㸪2013 ᖺ 6 ᭶ 29 ᪥㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date End date (Study Preferred Term Intensity/ Inf/ Action Taken/ (Study day day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2012-11- 㛵⠇③ MILD/ N/ NOT APPLICABLE/ Ongoing 23 (ARTHRALGIA) NOT NA NOT RECOVERED/NOT - (-10/.) RELATED RESOLVED 2012-12- ⫠㛛⮋⒆ MODERATE/ Y/ DOSE NOT CHANGED/ 2013-06- 11 (ABSCESS (ANAL)) NOT Y RECOVERED/RESOLVED WITH 26 (9/.) RELATED SEQUELAE (206/.) 2012-12- ࡚ࡾ MILD/ N/ DOSE NOT CHANGED/ Ongoing 20 (WORSENING OF HOT FLUSHES) NOT NA NOT RECOVERED/NOT - (18/.) RELATED RESOLVED 2013-01- ࣜࣥࣃ⠇ MILD/ N/ DOSE NOT CHANGED/ Ongoing 27 (PREAURICULAR GLAND & NOT NA NOT RECOVERED/NOT - (56/.) SUBMANDIBULAR LYMPH NODE RELATED RESOLVED ENLARGED) 2013-01- ࡚ࡾ MILD/ N/ DOSE NOT CHANGED/ 2013-01- 28 (HOT FLUSH (DURING IV INFUSION OF POSSIBLE NA RECOVERED/RESOLVED 28 (57/1) STUDY DRUG)) (57/1) 2013-02- ཱྀ⭍ෆ₽⒆ᙧᡂ MILD/ N/ DOSE NOT CHANGED/ 2013-03- 13 (MOUTH ULCERS) NOT NA RECOVERED/RESOLVED 04 (73/17) RELATED (92/36)
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route CIPROFLOXACIN 2012-12-12 2013-01-09 ORAL METRONIDAZOLE 2012-12-12 2013-01-09 ORAL ERYTHROMYCIN 2013-06-20 - ORAL METRONIDAZOLE 2013-06-27 2013-07-24 ORAL CIPROFLOXACIN 2013-06-28 2013-07-24 ORAL
38 1 (245) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
(57) Subject CNTO1275CRD3003-5609-10637
1) Reason for narrative selection SAE Event of interest: Serious infection
2) Deaths, SAEs, Discontinuations due to AEs, and Other Events of Interest Start date Preferred Term Intensity/ Inf/ Action Taken/ End date (Study day I/M) (Verbatim Term) SAE Relatedness Trt? Outcome (Study day I/M) 2013-05-29 ⫠㛛⮋⒆ Y MODERATE/ Y/ DRUG INTERRUPTED/ 2013-06-01 (261/195) (PERIANAL ABSCESS, NEW) DOUBTFUL Y RECOVERED/RESOLVED (264/198)
3) Baseline Demographic Information ȋȌǣ ͶͶ ǣ ȋȌǣ ͷͷǤ ǣ ǣ ͳͻͺǦͲͶǦʹͲ ȋ Ȍǣ ͳͶ
4) Induction Treatment Group Induction study: CNTO1275CRD3001 Randomized Treatment Group: Ustekinumab Approximating 6 mg/kg IV Actual Treatment Group: Ustekinumab Approximating 6 mg/kg IV
5) Maintenance Treatment Group Assigned Treatment Group: Randomized subject/Responder to ustekinumab IV induction dosing/placebo SC
6) Treatment Received Visit Start Date Study Day Actual Treatment Dose WEEK 0 2012-09-11 1 Ustekinumab 389.7 mg WEEK 0 MAINTENANCE 2012-11-16 67 Placebo 0 mg WEEK 8 MAINTENANCE 2013-01-11 123 Placebo 0 mg WEEK 12 MAINTENANCE 2013-02-08 151 Placebo 0 mg WEEK 16 MAINTENANCE 2013-03-07 178 Placebo 0 mg WEEK 20 MAINTENANCE 2013-04-03 205 Placebo 0 mg WEEK 24 MAINTENANCE 2013-05-01 233 Placebo 0 mg WEEK 28 MAINTENANCE 2013-06-10 273 Placebo 0 mg WEEK 32 MAINTENANCE 2013-07-03 296 Placebo 0 mg WEEK 36 MAINTENANCE 2013-07-29 322 Placebo 0 mg WEEK 40 MAINTENANCE 2013-08-22 346 Placebo 0 mg
7) Maintenance Disposition Did the subject discontinue the study agent before the Week 44 visit?: N Did the subject terminate the study participation before the Week 44 visit?: N Did subject enter the long-term extension study?: Y
8) Induction Baseline Crohn's Disease History Date of diagnosis: 28FEB1995 Disease duration: 17.54 years Involved areas: ⤖⭠ࡢࡳ㸪⫠㛛࿘ᅖ
38 2 (246) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
9) Crohn's Disease Complications Before Induction Baseline Intra-abdominal abscess: NEVER Sinus tracts/perforation: NEVER Fistula: CURRENTLY PRESENT Stricture complications of (CD): CURRENTLY PRESENT
10) Concomitant Crohn's Disease-Related Surgeries Surgery Date Result of lack of efficacy? ࢻࣞࢼ࣮ࢪ-⤒⓶ษ㛤ཬࡧࢻࣞࢼ࣮ࢪ 2013-06-01 Y ࢻࣞࢼ࣮ࢪ-ࢩ࣮ࢺࣥ␃⨨ 2013-06-01 Y
11) Concomitant Steroids Visit Drug Dose Prednisone equivalent WEEK 28 MAINTENANCE DEXAMETHASONE 4 mg - WEEK 28 MAINTENANCE DEXAMETHASONE 0 mg -
12) Narrative Text ⿕㦂⪅ࡣ 4 ṓࡢⓑேዪᛶ࡛㸪2012 ᖺ 9 ᭶ 11 ᪥㸪ᐶゎᑟධ⒪ἲࡋ࡚ᮏࢆ㟼⬦ෆᢞࡉࢀ ࡓࠋ⿕㦂⪅ࡣᐶゎᑟධ⒪ἲ࡛ clinical response ࡀᚓࡽࢀ㸪ᐶゎ⥔ᣢ⒪ἲࡋ࡚ࣉࣛࢭ࣎ࢆ⓶ୗᢞ ࡍࡿ⩌ࣛࣥࢲ࣒ࡉࢀࡓࠋ ୖグࡢ୍ぴ⾲࡛ࡣ♧ࡉࢀ࡚࠸࡞࠸ࡀ㸪CIOMS ࡛ሗ࿌ࡉࢀࡓࡑࡢࡢ᪤ Ṕࡣ㸪⫠㛛࿘ᅖ⮋⒆ ཬࡧࣥࣇࣜ࢟ࢩ࣐ࣈᑐࡍࡿࣞࣝࢠ࣮࡛࠶ࡗࡓࠋ SAE/Serious Infection㸸⫠㛛⮋⒆㸦Day 261㸧 CIOMS ࡼࡿ㸪⿕㦂⪅ࡣ 2013 ᖺ 5 ᭶ 29 ᪥⫠㛛࿘ᅖ③࡛እ᮶デ⒪ᡤࢆཷデࡋ㸪⫠㛛࿘ᅖ ⮋⒆デ᩿ࡉࢀࡓᚋ㸪2013 ᖺ 5 ᭶ 31 ᪥ධ㝔ࡋࡓࠋྠ᪥ࡢ᰾☢Ẽඹ㬆⏬ീἲ࡛ࡣ㸪⫠㛛⭼⒦ୗ 㒊ࡢࢩ࣮ࢺࣥ㸪ᗈ⠊ᅖཬࡪᣓ⣙➽㛫ࡢ⮋㸪ᕥୗᣓ⣙➽ࢆ㈏㏻ࡍࡿ᪂ࡓ࡞⒦⟶ཬࡧࡶ⮋ Ồࢆฟࡋࡑ࠺࡞ᕥ⮌㒊⮋⒆ࢆㄆࡵࡓࠋ⒪ࡣ࣓ࢺࣟࢽࢲࢰ࣮ࣝࡀ⏝ࡉࢀࡓࠋ2013 ᖺ 6 ᭶ 1 ᪥㸪㯞㓉ୗ᳨࡚ᰝࢆᐇࡋࡓࡇࢁ㸪ࢩ࣮ࢺࣥࢆ␃⨨ࡋࡓ⫠㛛⭼⒦㸪ྂ࠸⒦Ꮝ 2 ࡘࡢ㛤ཱྀ 㒊ࢆ᭷ࡍࡿ᪂ࡋ࠸⒦Ꮝཬࡧᆘ㦵⫠㛛❐⮋⒆ࡀㄆࡵࡽࢀ㸪⮋⒆ᑐࡋ࡚ษ㛤ཬࡧ⮋ࢆ⾜ࡗࡓࠋ ࡲࡓ㸪ࢩ࣮ࢺࣥཬࡧ 2 ࡘࡢ᪂ࡋ࠸⒦Ꮝᑐࡋ࡚᪂ࡓࢩ࣮ࢺࣥࢆ␃⨨ࡋࡓࠋྠ᪥ࡢ࣓ࢳࢩࣜ ࣥ⪏ᛶ㯤Ⰽࣈࢻ࢘⌫⳦ࡢ㎿㏿ࢫࢡ࣮ࣜࢽࣥࢢ᳨ᰝࡣ㝜ᛶ࡛࠶ࡗࡓࠋྠ᪥㸦2013 ᖺ 6 ᭶ 1 ᪥㸧㸪⿕ 㦂⪅ࡣ⫠㛛࿘ᅖ⮋⒆ࡽᅇࡋ㸪2013 ᖺ 6 ᭶ 2 ᪥㏥㝔ࡋࡓࠋ
13) Other Adverse Events Start date End date (Study day Preferred Term Intensity/ Inf/ Action Taken/ (Study day I/M) (Verbatim Term) Relatedness Trt? Outcome I/M) 2012-10-20 ⫠㛛⮋⒆ MODERATE/ Y/ DOSE NOT CHANGED/ 2012-11-16 (40/.) (PERIANAL ABSCESS) NOT Y RECOVERED/RESOLVED (67/.) RELATED 2013-01-14 Ⓨ⇕ MILD/ N/ DOSE NOT CHANGED/ 2013-01-15 (126/60) (MILD TEMPERATURE) NOT NA RECOVERED/RESOLVED (127/61) RELATED 2013-03-07 ౽⛎ MILD/ N/ DOSE NOT CHANGED/ 2013-04-03 (178/112) (CONSTIPATION) DOUBTFUL NA RECOVERED/RESOLVED (205/139) 2013-03-15 ࣇࢱᛶཱྀෆ⅖ MILD/ N/ DOSE NOT CHANGED/ 2013-04-07 (186/120) (APTHOUS ULCERS IN MOUTH) DOUBTFUL NA RECOVERED/RESOLVED (209/143) 2013-06-24 ࣥࣇ࢚ࣝࣥࢨᵝᝈ MILD/ N/ DOSE NOT CHANGED/ 2013-06-25 (287/221) (FLU-LIKE SYMPTOMS (FLUSHING AND NOT NA RECOVERED/RESOLVED (288/222) SHIVERING)) RELATED
38 3 (247) ࢘ࢫࢸ࢟ࢾ࣐ࣈ 2.7.6 ಶࠎࡢヨ㦂ࡢࡲࡵ CNTO1275CRD3003 ヨ㦂
14) Concomitant Medications for Adverse Events Preferred Term Start Date End Date Route METRONIDAZOLE 2013-05-29 2013-06-07 ORAL PARACETAMOL 2013-05-29 2013-06-04 ORAL DICLOFENAC 2013-05-31 2013-06-02 ORAL
38 4 (248) ࠙ࠬ࠹ࠠࡑࡉ 2.7.6 ޘߩ⹜㛎ߩ߹ߣ C0379T07 ⹜㛎
2.7.6.5 ᶏᄖ⥃ᐥ╙ IIa ⋧⹜㛎㧔C0379T07 ⹜㛎㧘ෳ⠨⾗ᢱ㧦5.3.5.1.4㧕
2.7.6.5.1 ⷐ
(1) ᴦ㛎ታᣉ⸘↹ᦠ⇟ภ C0379T07
(2) ᴦ㛎ߩᮡ㗴 ਛ╬∝߆ࠄ㊀∝ߩᵴേᦼࠢࡠࡦ∛ᖚ⠪ࠍኻ⽎ߣߒߚ㧘ࠗࡦ࠲ࡠࠗࠠࡦ㧔IL㧕-12p40 ߦኻߔ ࠆࡅ࠻ဳࡕࡁࠢࡠ࠽࡞᛫㨇࠙ࠬ࠹ࠠࡑࡉ㧔એਅ㧘ᧄ㧕㨉ߩ╙ IIa ⋧㧘ᄙᣉ⸳ห㧘ࡦ ࠳ࡓൻ⹜㛎
(3) ᴦ㛎⽿છකᏧ
(4) ᴦ㛎ታᣉක≮ᯏ㑐 62 ᣉ⸳㧔☨࿖ 55 ᣉ⸳㧘ࠞ࠽࠳ 6 ᣉ⸳㧘ࡌ࡞ࠡ1 ᣉ⸳㧕
(5) ᢥ₂㧔ᒁ↪ᢥ₂㧕 Sandborn WJ, Feagan BG, Fedorak RN, Scherl E, Fleisher MR, Katz S, et al; Ustekinumab Crohn’s Disease Study Group. A randomized trial of Ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with moderate-to-severe Crohn’s disease. Gastroenterology. 2008;135(4):1130-41.
(6) ᴦ㛎ታᣉᦼ㑆 2004 ᐕ 5 ᣣ㨪2006 ᐕ 10 ᣣ
(7) 㐿⊒ߩ⋧ ╙ IIa ⋧
(8) ⋡⊛ ਥ⋡⊛ 1. 5-ࠕࡒࡁࠨ࠴࡞㉄㧔5-ASA㧕ൻว‛㧘᛫↢‛⾰㧘ࠦ࡞࠴ࠦࠬ࠹ࡠࠗ࠼߮㧛ߪ∉⺞▵ ⮎ߦࠃࠆᴦ≮ࠍฃߌߚߦ߽߆߆ࠊࠄߕᜬ⛯ߔࠆ㧘ਛ╬∝߆ࠄ㊀∝ߩᵴേᦼࠢࡠࡦ∛ 㨇Crohn’s Disease Activity Index㧔CDAI㧕ࠬࠦࠕ߇ 220 એ 450 એਅ㨉ᖚ⠪ࠍኻ⽎ߣߒߡ㧘 ࠢࡠࡦ∛ߩᓽ߮∝⁁ߩ✭ߦ߅ߌࠆᧄߩലᕈࠍ⹏ଔߔࠆޕ
2. ࠢࡠࡦ∛ᖚ⠪ࠍኻ⽎ߣߒߡ㧘ᧄߩ⊹ਅᛩਈᤨ߮㕒⣂ౝᛩਈᤨߩోᕈࠍ⹏ଔߔࠆޕ
38 5 (1) ࠙ࠬ࠹ࠠࡑࡉ 2.7.6 ޘߩ⹜㛎ߩ߹ߣ C0379T07 ⹜㛎
ᰴ⋡⊛ 1. ᧄ⹜㛎એ㒠ߩ⥃ᐥ㐿⊒ߢ↪ࠆᧄߩᛩਈ⚻〝㧔⊹ਅᛩਈߪ㕒⣂ౝᛩਈ㧕ࠍㆬᛯߔࠆޕ
2. ☨࿖ᷝઃᢥᦠߦⷙቯߐࠇߡࠆࠢࡠࡦ∛ߦኻߔࠆᦨᄢᛚ↪㊂߮↪ᴺߩࠗࡦࡈࠠࠪ ࡑࡉᛩਈࠍฃߌߚ߇㧘ലᨐਇචಽߪലᨐࠍ␜ߒߚ߽ߩߩߘߩᓟലᨐ߇ᶖᄬߒߚᖚ⠪ࠍኻ ⽎ߣߒߡ㧘ࠢࡠࡦ∛ߩᓽ߮∝⁁ߩ✭ߦ߅ߌࠆᧄߩലᕈࠍ⹏ଔߔࠆޕ
3. ᧄߩ⊹ਅᛩਈᤨ߮㕒⣂ౝᛩਈᤨߩ⮎‛േᘒࠍ⹏ଔߔࠆޕ
4. ᧄߩኡ⸃ዉലᨐࠍ⹏ଔߔࠆޕ
(9) ᴦ㛎ᣇᴺ ᧄ⹜㛎ߪ㧘6 ㅳ㑆એᜬ⛯ߔࠆਛ╬∝߆ࠄ㊀∝ߩᵴേᦼࠢࡠࡦ∛ᖚ⠪ߪ≪ሹဳࠢࡠࡦ∛ ᖚ⠪ࠍኻ⽎ߣߒߚ㧘ᧄ㧔2 ↪㊂㧕ߩᄙᣉ⸳ห㧘ࡦ࠳ࡓൻ⹜㛎ߢߞߚޕߔߴߡߩⵍ㛎⠪ߢ㧘 ࡌࠬࠗࡦᤨߩ CDAI ࠬࠦࠕ߇ 220 એ 450 એਅߢࠆߎߣߣߒߚޕᧄ⹜㛎ߢߪ㧘એਅߩ 2 ߟ ߩⵍ㛎⠪㓸࿅ࠍኻ⽎ߦ⹏ଔߒߚޕ · 㓸࿅ 1㧦5-ASA ൻว‛㧘᛫↢‛⾰㧘ࠦ࡞࠴ࠦࠬ࠹ࡠࠗ࠼߮㧛ߪ∉⺞▵⮎㨇᛫ TNF 㧔⣲≌უᱫ࿃ሶ㧕⮎ࠍ㨉ߦࠃࠆᴦ≮ࠍฃߌߚߦ߽߆߆ࠊࠄߕലᨐ߇ᓧࠄࠇߥ߆ߞߚᖚ ⠪ߦኻߒߡ㧘⋤ᬌਅߢᴦ㛎⮎ࠍᛩਈ
· 㓸࿅ 2㧦☨࿖ᷝઃᢥᦠߦⷙቯߐࠇߡࠆࠢࡠࡦ∛ߦኻߔࠆᦨᄢᛚ↪㊂߮↪ᴺߩࠗࡦ ࡈࠠࠪࡑࡉᛩਈࠍฃߌߚ߇㧘ലᨐਇචಽߪലᨐࠍ␜ߒߚ߽ߩߩߘߩᓟലᨐ߇ᶖᄬߒߚ ᖚ⠪ߦኻߒߡ㧘㕖⋤ᬌਅߢᧄࠍᛩਈ
㓸࿅ 1 ߩⵍ㛎⠪ߪࡌࠬࠗࡦᤨߦએਅߩ 4 ⟲ߩߕࠇ߆ߦࡦ࠳ࡓൻߐࠇߚޕ · 0㧘1㧘2 ߮ 3 ㅳ⋡ߦࡊࡏࠍ⊹ਅᛩਈߒ㧘8㧘9㧘10 ߮ 11 ㅳ⋡ߦᧄ 90 mg ࠍ⊹ਅᛩ ਈߔࠆޕ
· 0㧘1㧘2 ߮ 3 ㅳ⋡ߦᧄ 90 mg ࠍ⊹ਅᛩਈߒ㧘8㧘9㧘10 ߮ 11 ㅳ⋡ߦࡊࡏࠍ⊹ਅᛩ ਈߔࠆޕ
· 0 ㅳ⋡ߦࡊࡏࠍ㕒⣂ౝᛩਈߒ㧘8 ㅳ⋡ߦᧄ 4.5 mg/kg ࠍ㕒⣂ౝᛩਈߔࠆޕ
· 0 ㅳ⋡ߦᧄ 4.5 mg/kg ࠍ㕒⣂ౝᛩਈߒ㧘8 ㅳ⋡ߦࡊࡏࠍ㕒⣂ౝᛩਈߔࠆޕ
㓸࿅ 2 ߩⵍ㛎⠪ߪࡌࠬࠗࡦᤨߦએਅߩ 2 ⟲ߩߕࠇ߆ߦࡦ࠳ࡓൻߐࠇߚޕ · 0㧘1㧘2 ߮ 3 ㅳ⋡ߦᧄ 90 mg ࠍ⊹ਅᛩਈߔࠆޕ
· 0 ㅳ⋡ߦᧄ 4.5 mg/kg ࠍ㕒⣂ౝᛩਈߔࠆޕ
38 6 (2) ࠙ࠬ࠹ࠠࡑࡉ 2.7.6 ޘߩ⹜㛎ߩ߹ߣ C0379T07 ⹜㛎
(10) ⵍ㛎⠪ᢙ㧔⸘↹ᤨ߮⸃ᨆᤨ㧕 ⸘↹ᤨ 㓸࿅ 1㧦100 㧘㓸࿅ 2㧦20 ⸃ᨆᤨ 㓸࿅ 1㧦104 㧘㓸࿅ 2㧦27
(11) ⸻ᢿ߮ਥߥㆬᛯၮḰ ᧄ⹜㛎ߩኻ⽎ߪ㧘18 ᱦએߢ 6 ㅳ㑆એᜬ⛯ߔࠆਛ╬∝߆ࠄ㊀∝ߩᵴേᦼࠢࡠࡦ∛ᖚ⠪ߢ ߞߚ㧔ޟᴦ㛎ᣇᴺޠෳᾖ㧕ޕਥ⸃ᨆኻ⽎㓸࿅㧔㓸࿅ 1㧕߮ᰴ⸃ᨆኻ⽎㓸࿅㧔㓸࿅ 2㧕ߪ㧘 ޟᴦ㛎ᣇᴺޠߦቯ⟵ߒߚޕ
(12) ⵍ㛎⮎㧘↪㊂߮ᛩਈᣇᴺ㧘ࡠ࠶࠻⇟ภ 㓸࿅ 1 ߮㓸࿅ 2 ߩߔߴߡߩⵍ㛎⠪ߦ㧘ᧄ㨇࠙ࠬ࠹ࠠࡑࡉ㧔ㆮવሶ⚵឵߃㧕㨉90 mg ߩ⊹ ਅᛩਈߪᧄ 4.5 mg/kg ߩ㕒⣂ౝᛩਈࠍⴕߞߚޕⵍ㛎⮎ߣߒߡᧄ 90 mg ࠍߔࠆή⩶ߩ⊕ ⦡ಓ⚿ੇ῎☳ᧃࠍలႯߒߚࡃࠗࠕ࡞㧔ࡠ࠶࠻⇟ภ㧦 㧕߇ଏ⛎ߐࠇߚޕ
(13) ኻᾖ⮎㧘↪㊂߮ᛩਈᣇᴺ㧘ࡠ࠶࠻⇟ภ ኻᾖ⮎ߣߒߡࡊࡏߢࠆή⩶ߩ⊕⦡ಓ⚿ੇ῎☳ᧃࠍలႯߒߚࡃࠗࠕ࡞㧔ࡠ࠶࠻⇟ภ㧦 㧕߇ଏ⛎ߐࠇߚޕ
(14) ᛩਈᦼ㑆 54 ㅳ㑆㧔ⷰኤᦼ㑆ࠍ㧕
(15) ⹏ଔ㗄⋡ ലᕈߩਥ⸃ᨆ߮৻ㇱߩᰴ⸃ᨆߢߪ㧘ࡦ࠳ࡓൻߐࠇߚߔߴߡߩⵍ㛎⠪ࠍኻ⽎ߣߒߚޕ ᰴ⸃ᨆߢߪ㧘ࡦ࠳ࡓൻߐࠇߚߔߴߡߩⵍ㛎⠪ߪ⹏ଔน⢻ߥ᷹ቯ୯߇ᓧࠄࠇߚㇱಽ㓸࿅ࠍኻ⽎ ߣߒߚޕߥ߅㧘ലᕈ⸃ᨆߪ㧘ታ㓙ߩᛩਈߦ㑐ଥߥߊࡦ࠳ࡓൻߐࠇߚᛩਈ⟲ߦၮߠ߈⸃ᨆߒߚޕ ోᕈߩ⹏ଔߪ㧘ᴦ㛎⮎ࠍ l ࿁એᛩਈߐࠇߚⵍ㛎⠪ࠍኻ⽎ߣߒߚޕߥ߅㧘ోᕈߪ㧘ታ㓙ߩ ᛩਈߦၮߠ߈⸃ᨆߒߚޕ
⮎‛േᘒ ⮎‛േᘒߪ㧘54 ㅳ⋡߹ߢߩⴊᷡਛ࠙ࠬ࠹ࠠࡑࡉỚᐲߦࠃࠅ⹏ଔߒߚޕ⮎‛േᘒࡄࡔ࠲ࠍ ⵍ㛎⠪ߏߣߦផቯߒ㧘㓸࿅ 1 ߢߪ⊹ਅᛩਈ⟲߮㕒⣂ౝᛩਈ⟲ߦߟߡⷐ⚂ߒߚޕ
⮎ജቇ ⴊᷡਛࡃࠗࠝࡑࠞߦߟߡߪⴊᶧᬌࠍ㧘⚦⢩ࡃࠗࠝࡑࠞߦߟߡߪ৻ㇱߩᴦ㛎ታᣉ ᣉ⸳ߢታᣉߒߚౝⷞ㏜ᬌᩏߢᓧࠄࠇߚ↢ᬌᬌࠍ↪ߡ⹏ଔߒߚޕ
38 7 (3) ࠙ࠬ࠹ࠠࡑࡉ 2.7.6 ޘߩ⹜㛎ߩ߹ߣ C0379T07 ⹜㛎
∉ේᕈ ᛫࠙ࠬ࠹ࠠࡑࡉ᛫ߪ㧘54 ㅳ⋡߹ߢߩⴊᷡᬌࠍ↪ߡ⹏ଔߒߚޕ
ലᕈ ਥⷐ⹏ଔ㗄⋡ߪ㧘㓸࿅ 1 ߦ߅ߌࠆ 8 ㅳ⋡ߩ clinical response㧔CDAI ࠬࠦࠕ߇ࡌࠬࠗࡦᤨࠃ ࠅ 25%એ߆ߟ 70 ࡐࠗࡦ࠻એᷫዋ㧕ߢߞߚޕ ߘߩઁߩലᕈ⹏ଔ㗄⋡ߪ㧘᧪㒮ᣣߏߣߩ clinical response㧘clinical remission㧔CDAI ࠬࠦࠕ߇ 150 ࡐࠗࡦ࠻ᧂḩ㧕㧘100-point response㧔CDAI ࠬࠦࠕ߇ࡌࠬࠗࡦᤨࠃࠅ 100 ࡐࠗࡦ࠻એᷫ ዋ㧕㧘clinical response ߮ clinical remission ߩᜬ⛯㧘∳ሹߩ⹏ଔ㧘☼⤑ᴦ≹㧘᧪㒮ᣣߏߣߩ Perianal Disease Activity Index㧔PDAI㧕߮ Inflammatory Bowel Disease Questionnaire㧔IBDQ㧕㧘C ᔕᕈߚࠎ⊕㧔CRP㧕㧘ਗ߮ߦ Crohn’s Disease Endoscopic Index of Severity㧔CDEIS㧕ߢߞߚޕ CDAI ࠬࠦࠕߦߟߡߪ㧘⮎‛േᘒࡄࡔ࠲ߣߩ㑐ㅪᕈ߽⸃ᨆߒߚޕ
ోᕈ ోᕈߪ㧘ᛩਈ⟲㧔ታ㓙ߩᛩਈߦၮߠߊ㧕ߏߣߦኂ⽎ߩ⊒ഀว߮⒳㘃ࠍ⹏ଔߒߚޕ㊀ ◊ߥኂ⽎㧔SAE㧕㧘ᴦ㛎⮎ߣวℂ⊛ߦ㑐ㅪᕈ߇ࠆኂ⽎㧘㜞ᐲߩኂ⽎㧘ᴦ㛎⮎ߩᛩ ਈਛᱛߦ⥋ߞߚኂ⽎㧘⥃ᐥ⊛ߦ㊀ⷐߥኂ⽎ࠍ⊒ߒߚⵍ㛎⠪ᢙ߮⊒ഀวࠍᛩਈ⟲ߏ ߣߦⷐ⚂ߒߚޕ㗼⪺ߥ⥃ᐥᬌᩏ⇣Ᏹ୯߇ႎ๔ߐࠇߚⵍ㛎⠪ᢙ߮ഀวࠍᛩਈ⟲ߏߣߦⷐ⚂ߒߚޕ
(16) ⛔⸘ᚻᴺ ੱญ⛔⸘ቇ⊛․ᕈ߮ࡌࠬࠗࡦᤨߩ∔ᖚ․ᕈ㧔ࠢࡠࡦ∛ߦኻߔࠆ૬↪⮎ࠍ㧕ࠍᛩਈ ⟲ߏߣߦⷐ⚂ߒߚޕ⸥ㅀ⛔⸘㊂ߣߒߡ㧘ㅪ⛯ᄌᢙߪᐔဋ୯㧘ਛᄩ୯㧘ᮡḰᏅ㧘▸࿐㧘྾ಽ▸ ࿐╬㧘ࠞ࠹ࠧᄌᢙߪ⸘ᢙ୯߮ഀวߦࠃࠅⷐ⚂ߒߚޕ2 ୯ᄌᢙ㧔clinical response ߇ᓧࠄࠇߚ ⵍ㛎⠪ߩഀว╬㧕ߩ⸃ᨆߦߪ Fisher ߩ⋥ធ⏕₸ᬌቯ㧘ጀᄌᢙࠍࠆ⸃ᨆߦߪ Cochran Mantel Haenszel ߩࠞࠗੑਸ਼ᬌቯࠍ↪ߚޕߔߴߡߩ⛔⸘ቇ⊛ߥᬌቯߪ㧘ਔᗧ᳓Ḱ 0.05 ߢታᣉߒߚޕ ᰴ⸃ᨆߢߪ㧘ฬ⋡ߩ p ୯ࠍ▚ߒߚޕ࠺࠲ߩⷐ⚂ߦߪ࿑ࠍ↪ߚޕߔߴߡߩലᕈ⸃ᨆ ߪ㧘․ߦᜰቯߩߥ㒢ࠅ㧘intent to treat ߩขᛒߦࠃࠅታᣉߒߚޕߒߚ߇ߞߡ㧘ታ㓙ߩᛩਈߦ㑐 ଥߥߊ㧘ࡦ࠳ࡓൻߐࠇߚᛩਈ⟲ߦၮߠ߈⸃ᨆߒߚޕਥ⸃ᨆߪ㧘ਔᗧ᳓Ḱ 0.05 ߦࠃࠆ Cochran Mantel Haenszel ߩࠞࠗੑਸ਼ᬌቯࠍ↪ߡታᣉߒߚޕ
(17) ⚿ᨐ ᴦ㛎ኻ⽎㓸࿅ ਥ⸃ᨆኻ⽎㓸࿅㧔㓸࿅ 1㧕ߩੱญ⛔⸘ቇ⊛․ᕈߪ㧘ᐕ㦂ߩਛᄩ୯߇㕒⣂ౝᛩਈ⟲ߣᲧセߒߡ⊹ ਅᛩਈ⟲ߢૐ߆ߞߚߎߣࠍ㒰߈㧘ࡦ࠳ࡓൻߐࠇߚᛩਈ⟲㑆ߢో⥸⊛ߦห᭽ߢߞߚޕᐕ㦂ߩਛ ᄩ୯ߪ 41 ᱦߢࠅ㧘↵ᕈߩഀว߇ࠊߕ߆ߦ㜞ߊ㧘߹ߚ⊕ੱ߇ᄢㇱಽࠍභߡߚޕࠢࡠࡦ∛ ⟕ᖚᦼ㑆ߩਛᄩ୯ߪ⚂ 9.7 ᐕߢߞߚޕ
38 8 (4) ࠙ࠬ࠹ࠠࡑࡉ 2.7.6 ޘߩ⹜㛎ߩ߹ߣ C0379T07 ⹜㛎
⮎‛േᘒ ᧄ⹜㛎ߩត⚝⊛⸃ᨆ߆ࠄᓧࠄࠇߚ⮎‛േᘒߩ⚿ᨐࠍએਅߦ␜ߔޕ · ᧄ 90 mg ߩㅳ 1 ࿁⊹ਅᛩਈࠍ 4 ࿁ฃߌߚⵍ㛎⠪ߣᲧセߒߡ㧘ᧄ 4.5 mg/kg ࠍන࿁㕒⣂ౝ ᛩਈߐࠇߚⵍ㛎⠪ߦ߅ߡ㧘ᛩਈᓟ 3 ㅳ⋡߹ߢⴊᷡਛ࠙ࠬ࠹ࠠࡑࡉỚᐲ߇㜞߆ߞߚޕߒ ߆ߒ㧘ᛩਈᓟ 4 ㅳ⋡એ㒠ߪ㧘㕒⣂ౝᛩਈࠍฃߌߚⵍ㛎⠪ߣᲧセߒߡ㧘⊹ਅᛩਈࠍฃߌߚⵍ 㛎⠪ߦ߅ߡⴊᷡਛ࠙ࠬ࠹ࠠࡑࡉỚᐲߩਛᄩ୯ߪ㧘߿߿㜞୯ࠍ␜ߒߚޕ
· 㓸࿅ 1 ߮㓸࿅ 2 ߩ⊹ਅᛩਈ⟲ߦ߅ߌࠆඨᷫᦼ㧔T1/2㧕ߩਛᄩ୯ߪ㧘ߘࠇߙࠇ⚂ 25 ᣣ߮
⚂ 23 ᣣߢߞߚޕ߹ߚ㧘㓸࿅ 1 ߮㓸࿅ 2 ߩ㕒⣂ౝᛩਈ⟲ߦ߅ߌࠆ T1/2 ߩਛᄩ୯ߪ㧘ߘࠇ ߙࠇ⚂ 23 ᣣ߮⚂ 17 ᣣߢߞߚޕ
· ᧄߩ⊹ਅᛩਈࠍฃߌߚⵍ㛎⠪ߦ߅ߌࠆᦑ㔺㊂ߪ㧘㊀ߩᓇ㗀ࠍฃߌࠆߎߣ߇␜ໂߐࠇߚޕ ห↪㊂ࠍᛩਈߒߚ႐ว㧘㊀߇シⵍ㛎⠪ߣᲧセߒߡ㊀ⵍ㛎⠪ߢߪᦑ㔺㊂߇ዋߥ߆ߞߚޕ
· ᧄߩ⊹ਅᛩਈߪ㕒⣂ౝᛩਈࠍฃߌߚⵍ㛎⠪ߢߪ㧘Cmax ୯ߣᛩਈᓟ 8 ㅳ⋡ߦ᷹ቯߒߚ CDAI ࠬࠦࠕߩ㑆ߦᱜߩ⋧㑐㑐ଥ߇ࠄࠇߚޕ
⮎ജቇ ᧄ⹜㛎ߩត⚝⊛⸃ᨆ߆ࠄᓧࠄࠇߚ⮎ജቇߩ⚿ᨐࠍએਅߦ␜ߔޕ · 㓸࿅ 1 ߦ߅ߡ㧘ᧄᛩਈߦࠃࠆࡃࠗࠝࡑࠞߩᄌൻࠍࡊࡏߣᲧセߒߚޕߘߩ⚿ᨐ㧘 ᧄߩන࿁㕒⣂ౝᛩਈᓟ 1㧘4 ߮ 8 ㅳ⋡ߩⴊᷡਛἻ∝ࡑࠞỚᐲߪ㧘ࡊࡏ⟲ߣᲧセ ߒߡૐਅߒߚޕ߹ߚ㧘ᧄߩ⊹ਅᛩਈ⟲ߢ߽ห᭽ߩᄌൻ߇ߺࠄࠇߚ߇㧘ߘߩ⊒ᤨᦼߪ㕒 ⣂ౝᛩਈ⟲ߣᲧセߒߡㆃ߆ߞߚޕ
· 㓸࿅ 2 ߦ߅ߌࠆฦⴊᷡਛࡃࠗࠝࡑࠞỚᐲߩᄌൻߪ㧘㓸࿅ l ߢߺࠄࠇߚᄌൻߣో⥸⊛ߦห ᭽ߢߞߚޕ
· ᧄᛩਈᓟߩ⮎ജቇࡑࠞߩ⊒㊂ߩᄌൻߪ㧘ᧄߦࠃࠆᴦ≮߇ࠢࡠࡦ∛ߩἻ∝ㆊ⒟ ࠍ⺞▵ߔࠆߣ߁⺑ࠍⵣઃߌࠆ߽ߩߢߞߚޕ
ലᕈ 㓸࿅ l㨇5-ASA ൻว‛㧘᛫↢‛⾰㧘ࠦ࡞࠴ࠦࠬ࠹ࡠࠗ࠼߮㧛ߪ∉⺞▵⮎㧔᛫ TNF ⮎ࠍ 㧕ߦࠃࠆᴦ≮ࠍฃߌߚߦ߽߆߆ࠊࠄߕലᨐ߇ᓧࠄࠇߥ߆ߞߚ㧘ਛ╬∝߆ࠄ㊀∝ߩᵴേᦼࠢࡠ ࡦ∛ᖚ⠪㨉ߢߪ㧘ᧄߩ⊹ਅᛩਈߪ㕒⣂ౝᛩਈߦࠃࠅએਅߩ⚿ᨐ߇ᓧࠄࠇߚޕ · ਥⷐ⹏ଔ㗄⋡ߢࠆ 8 ㅳ⋡ߦ clinical response ߇ᓧࠄࠇߚⵍ㛎⠪ߩഀวߪ㧘⊹ਅᛩਈߣ㕒⣂ ౝᛩਈࠍ૬วߒߚࡊࡏ⟲㧔એਅ㧘ࡊࡏ૬ว⟲㧕㧔39.6%㧕ߣᲧセߒߡ㧘⊹ਅᛩਈߣ 㕒⣂ౝᛩਈࠍ૬วߒߚᧄ⟲㧔એਅ㧘ᧄ૬ว⟲㧕㧔49.0%㧕ߢ㜞߆ߞߚ߇㧘⛔⸘ቇ⊛ߦ ᗧߥᏅߪࠄࠇߥ߆ߞߚ㧔p=0.337㧕ޕ
· 8 ㅳ⋡એ೨ߩ⹏ଔᤨὐߦ clinical response ߇ᓧࠄࠇߚⵍ㛎⠪ߩഀวߪ㧘ᧄ૬ว⟲ߢߪ 4 ㅳ ⋡߮ 6 ㅳ⋡߇ߣ߽ߦ 52.9%㧘ࡊࡏ૬ว⟲ߢߪ 4 ㅳ⋡߮ 6 ㅳ⋡߇ߣ߽ߦ 30.2%ߢࠅ㧘 ⟲㑆ߩᏅߪ 8 ㅳ⋡㧔ᧄ૬ว⟲㧦49.0%㧘ࡊࡏ૬ว⟲㧦39.6%㧕ߣᲧセߒߡᄢ߈߆ߞߚޕ
38 9 (5) ࠙ࠬ࠹ࠠࡑࡉ 2.7.6 ޘߩ⹜㛎ߩ߹ߣ C0379T07 ⹜㛎
· ᛩਈ⚻〝ߩ 8 ㅳ⋡ߦ clinical response ߇ᓧࠄࠇߚⵍ㛎⠪ߩഀวߪ㧘⊹ਅᛩਈߢߪᧄ⟲ߣ ࡊࡏ⟲ߢห⒟ᐲߢߞߚ߇㧘㕒⣂ౝᛩਈߢߪࡊࡏ⟲㧔29.6%㧕ߣᲧセߒߡᧄ⟲ 㧔50%㧕ߢ㜞߆ߞߚޕ
· ㆊߦࠗࡦࡈࠠࠪࡑࡉߩᛩਈ⚻㛎߇ࠆⵍ㛎⠪ߩㇱಽ㓸࿅㧔47.1%㧕ߢߪ㧘8 ㅳ⋡ߦ clinical response ߇ᓧࠄࠇߚⵍ㛎⠪ߩഀวߪ㧘ࡊࡏ૬ว⟲㧔25.9%㧕ߣᲧセߒߡᧄ૬ว ⟲㧔59.1%㧕ߢᗧߦ㜞߆ߞߚ㧔p=0.022㧕ޕ
· ᰴ⹏ଔ㗄⋡ߢࠆ 8 ㅳ⋡ߦ 100-point response ߇ᓧࠄࠇߚⵍ㛎⠪ߩഀวߢߩᧄ૬ว⟲ 㧔49.0%㧕ߣࡊࡏ૬ว⟲㧔30.2%㧕ߩᏅ㧔p=0.052㧕ߪ㧘ਥⷐ⹏ଔ㗄⋡ߢࠆ clinical response㧔CDAI ࠬࠦࠕ߇ࡌࠬࠗࡦᤨࠃࠅ 25%એ߆ߟ 70 ࡐࠗࡦ࠻એᷫዋ㧕߇ᓧࠄࠇ ߚⵍ㛎⠪ߩഀวߢߺࠄࠇߚᏅߣᲧセߒߡᄢ߈߆ߞߚޕ
· 8 ㅳ⋡ߦ clinical remission ߇ᓧࠄࠇߚⵍ㛎⠪㧔CDAI ࠬࠦࠕ߇ 150 ࡐࠗࡦ࠻ᧂḩ㧕ߩഀวߪ㧘 ࡊࡏ૬ว⟲㧔17.0%㧕ߣᲧセߒߡᧄ૬ว⟲㧔25.5%㧕ߢ㜞߆ߞߚޕ
㓸࿅ 2㧔☨࿖ᷝઃᢥᦠߦⷙቯߐࠇߡࠆࠗࡦࡈࠠࠪࡑࡉᴦ≮ߢലᨐਇචಽߪലᨐࠍ␜ߒߚ ߽ߩߩߘߩᓟലᨐ߇ᶖᄬߒߚ㧘ਛ╬∝߆ࠄ㊀∝ߩᵴേᦼࠢࡠࡦ∛ᖚ⠪㧕ߢߪ㧘ᧄߩ⊹ਅᛩਈ ߪ㕒⣂ౝᛩਈߦࠃࠅએਅߩ⚿ᨐ߇ᓧࠄࠇߚޕ · 8 ㅳ⋡ߦ clinical response㧔CDAI ࠬࠦࠕ߇ࡌࠬࠗࡦᤨࠃࠅ 25%એ߆ߟ 70 ࡐࠗࡦ࠻એ ᷫዋ㧕߇ᓧࠄࠇߚⵍ㛎⠪ߩഀวߪ㧘ᧄ૬ว⟲ߢߪ 48.1%ߢߞߚޕ
· ᛩਈ⚻〝ߩ 8 ㅳ⋡ߦ clinical response ߇ᓧࠄࠇߚⵍ㛎⠪ߩഀวߪ㧘ᧄߩ⊹ਅᛩਈ⟲ 㧔42.9%㧕ߣᲧセߒߡ㕒⣂ౝᛩਈ⟲㧔53.8%㧕ߢ㜞߆ߞߚޕ
· 100-point response ߇ᓧࠄࠇߚⵍ㛎⠪ߩഀวߪ㧘8 ㅳ⋡ߢߪ⚂ 37%ߢߞߚޕ
· 8 ㅳ⋡ߦ clinical remission ߇ᓧࠄࠇߚⵍ㛎⠪ߩഀวߪ⚂ 30%ߢߞߚޕ
㓸࿅ 1 ߮㓸࿅ 2 ߦ߅ߡ㧘એਅߩ⚿ᨐ߇ᓧࠄࠇߚޕ
· ᧄߩ⊹ਅᛩਈߪ㕒⣂ౝᛩਈࠍฃߌߚⵍ㛎⠪ߢ㧘ᧄߩ⮎‛േᘒߣᔕ㧘ߔߥࠊߜ Cmax ୯ߣ CDAI ࠬࠦࠕߦᱜߩ⋧㑐㑐ଥ߇ࠄࠇߚޕ․ߦ㧘ᧄߩೋ࿁ᛩਈᓟ 8 ㅳ⋡ߦ᷹ቯߒ
ߚ CDAI ࠬࠦࠕߩਛᄩ୯ߦࠃࠆᡷༀߩ⒟ᐲߪ㧘Cmax ୯߇㜞ⵍ㛎⠪㓸࿅ߢᦨ߽㜞߆ߞߚޕ
ోᕈ 㓸࿅ 1 ߮㓸࿅ 2 ߣ߽ߦ㧘ᧄߩᔋኈᕈߪో⥸⊛ߦ⦟ᅢߢߞߚޕోᕈߩ⸃ᨆ⚿ᨐࠍએਅߦ ␜ߔޕ · 㓸࿅ 1 ߩ 8 ㅳ⋡߹ߢߩᦼ㑆㧔ᧄ⹜㛎ߩࡊࡏኻᾖᦼ㑆㧕ߢߪ㧘ኂ⽎ߩ⊒ഀวߪᧄ ૬ว⟲ߣࡊࡏ૬ว⟲ߢห⒟ᐲߢߞߚޕ
· ᧄߩೋ࿁ᛩਈ߆ࠄ 28 ㅳ⋡߹ߢߩኂ⽎ߩ⊒ഀวߪ㧘㓸࿅ 1 ߣ㓸࿅ 2 ߢห⒟ᐲߢߞ ߚޕ
39 0 (6) ࠙ࠬ࠹ࠠࡑࡉ 2.7.6 ޘߩ⹜㛎ߩ߹ߣ C0379T07 ⹜㛎
· 㓸࿅ 1 ߮㓸࿅ 2 ߩ 28 ㅳ⋡߹ߢߩኂ⽎ߩ⊒ഀวߪ㧘ᧄߩ⊹ਅᛩਈࠍฃߌߚⵍ㛎⠪ ߣ㕒⣂ౝᛩਈࠍฃߌߚⵍ㛎⠪ߢห⒟ᐲߢߞߚޕ
· ࿕ቯ↪㊂ߩᴦ㛎⮎ᛩਈࠍฃߌߚ⊹ਅᛩਈ⟲ߩⵍ㛎⠪ߢߪ㧘ࡌࠬࠗࡦᤨߩ㊀߇㊀ⵍ 㛎⠪ߢኂ⽎ߩ⊒ഀว߇ૐะ߇ࠄࠇߚޕ
· SAE ߩ⊒ߪ߹ࠇߢࠅ㧘ߘߩ߶ߣࠎߤ߇ࠢࡠࡦ∛ߦ㑐ㅪߒߚ⽎ߢߞߚޕ
ᵈ⋡ߔߴ߈ኂ⽎ · ᗵᨴ∝ߩ⊒ഀวߪ㧘ᧄ⟲ߣࡊࡏ⟲ߣߩ㑆ߢห⒟ᐲߢߞߚޕ
· 2 ઙߩ㊀◊ߥᗵᨴ∝㧔⒳ᕈࡅࠬ࠻ࡊࠬࡑ∝߮ᗵᨴᕈ⢗⣺Ἳ㧕߇ႎ๔ߐࠇ㧘ߕࠇ߽ 㓸࿅ 2 ߢߩ⊒ߢߞߚޕ⚿ᩭߩ⊒ߪࠄࠇߥ߆ߞߚޕ
· ᵈㇱᔕߩ⊒ߪ߹ࠇߢߞߚޕ
· ోりᕈㆊᢅᔕߪႎ๔ߐࠇߥ߆ߞߚޕ
· 㗼⪺ߥ⥃ᐥᬌᩏ⇣Ᏹ୯ߪ߹ࠇߢߞߚޕ
⚿⺰ 㓸࿅ 1㧦 5-ASA ൻว‛㧘᛫↢‛⾰㧘ࠦ࡞࠴ࠦࠬ࠹ࡠࠗ࠼߮㧛ߪ∉⺞▵⮎㧔᛫ TNF ⮎ࠍ㧕ߦ ࠃࠆᴦ≮ࠍฃߌߚߦ߽߆߆ࠊࠄߕലᨐ߇ᓧࠄࠇߥ߆ߞߚ㧘ਛ╬∝߆ࠄ㊀∝ߩᵴേᦼࠢࡠࡦ∛ᖚ ⠪㧔㓸࿅ 1㧕ߦ߅ߡ㧘એਅߩ⚿⺰߇ᓧࠄࠇߚޕ · ਥⷐ⹏ଔ㗄⋡ߢࠆ 8 ㅳ⋡ߦ clinical response ߇ᓧࠄࠇߚⵍ㛎⠪ߩഀวߪ㧘ࡊࡏ૬ว⟲ ߣᲧセߒߡᧄ૬ว⟲ߢ㜞߆ߞߚ߇㧘⛔⸘ቇ⊛ߦᗧߥᏅߪࠄࠇߥ߆ߞߚޕ
· 8 ㅳ⋡એ೨ߩ⹏ଔᤨὐߢ clinical response ߇ᓧࠄࠇߚⵍ㛎⠪ߩഀวߦ߅ߌࠆᧄ૬ว⟲ߣࡊ ࡏ૬ว⟲ߣߩᏅߪ㧘8 ㅳ⋡ߦ߅ߌࠆ⟲㑆ᏅߣᲧセߒߡᄢ߈߆ߞߚޕ
· ᛩਈ⚻〝ߩ 8 ㅳ⋡ߦ clinical response ߇ᓧࠄࠇߚⵍ㛎⠪ߩഀวߪ㧘⊹ਅᛩਈߢߪᧄ⟲ߣ ࡊࡏ⟲ߢห⒟ᐲߢߞߚ߇㧘㕒⣂ౝᛩਈߢߪࡊࡏ⟲ߣᲧセߒߡᧄ⟲ߢ㜞߆ߞߚޕ
· ㆊߦࠗࡦࡈࠠࠪࡑࡉߩᛩਈ⚻㛎߇ࠆⵍ㛎⠪ߩㇱಽ㓸࿅ߢߪ㧘8 ㅳ⋡ߦ clinical response ߇ᓧࠄࠇߚⵍ㛎⠪ߩഀวߪ㧘ࡊࡏ૬ว⟲ߣᲧセߒߡᧄ૬ว⟲ߢᗧߦ㜞߆ߞߚޕߎ ߩᚲߣ৻⥌ߒߡ㧘ࡌࠬࠗࡦᤨߩ∔ᖚᵴേᕈ㧔CDAI ࠬࠦࠕ㧕㧘ࠦ࡞࠴ࠦࠬ࠹ࡠࠗ࠼ ߮∉⺞▵⮎ߩ೨ᴦ≮ᱧ㧘ਗ߮ߦ೨ᴦ≮ߢߩ᛫ TNF ⮎ߩᦑ㔺⁁ᴫ߆ࠄ್ᢿߐࠇߚ㊀∝ᐲ߇ ࠃࠅ㜞ᖚ⠪ߦ߅ߡ㧘ᧄᛩਈߦࠃࠆో⊛ߥࡌࡀࡈࠖ࠶࠻߇ࠃࠅ⏕ߢߞߚޕ
· ᰴ⹏ଔ㗄⋡ߢࠆ 8 ㅳ⋡ߦ 100-point response ߇ᓧࠄࠇߚⵍ㛎⠪ߩഀวߦ߅ߌࠆᧄ૬ว ⟲ߣࡊࡏ૬ว⟲ߩᏅߪ㧘ਥⷐ⹏ଔ㗄⋡ߢࠆ clinical response㧔CDAI ࠬࠦࠕ߇ࡌࠬ ࠗࡦᤨࠃࠅ 25%એ߆ߟ 70 ࡐࠗࡦ࠻એᷫዋ㧕߇ᓧࠄࠇߚⵍ㛎⠪ߩഀวߢߺࠄࠇߚᏅߣᲧ セߒߡᄢ߈߆ߞߚޕ
39 1 (7) ࠙ࠬ࠹ࠠࡑࡉ 2.7.6 ޘߩ⹜㛎ߩ߹ߣ C0379T07 ⹜㛎
· ⵍ㛎⠪ߪዋᢙߢߞߚ߇㧘㊀߇シⵍ㛎⠪ߢߪࠃࠅᄢ߈ߥലᨐ߇ᓧࠄࠇߡࠆߎߣ߆ࠄ㧘 ᧄߩ⊹ਅᛩਈߦࠃࠆ response ߇ᓧࠄࠇߚⵍ㛎⠪ߩഀวߪࡌࠬࠗࡦᤨߩ㊀ߩᓇ㗀ࠍ ฃߌࠆ߽ߩߣ⠨߃ࠄࠇߚޕ
㓸࿅ 2㧦 ☨࿖ᷝઃᢥᦠߦⷙቯߐࠇߡࠆࠗࡦࡈࠠࠪࡑࡉᴦ≮ߢലᨐਇචಽߪലᨐࠍ␜ߒߚ߽ߩߩߘ ߩᓟലᨐ߇ᶖᄬߒߚ㧘ਛ╬∝߆ࠄ㊀∝ߩᵴേᦼࠢࡠࡦ∛ᖚ⠪㧔㓸࿅ 2㧕ߦ߅ߡ㧘એਅߩ⚿⺰ ߇ᓧࠄࠇߚޕ · ᧄߩ⊹ਅᛩਈߪ㕒⣂ౝᛩਈߩ⚿ᨐ㧘ᧄ૬ว⟲ߦ߅ߌࠆ 8 ㅳ⋡ߦ clinical response 㧔CDAI ࠬࠦࠕ߇ࡌࠬࠗࡦᤨࠃࠅ 25%એ߆ߟ 70 ࡐࠗࡦ࠻એᷫዋ㧕߇ᓧࠄࠇߚⵍ㛎 ⠪ߩഀวߪ㧘㓸࿅ l ߦ߅ߌࠆഀวߣห⒟ᐲߢߞߚޕ
ో㧦 㓸࿅ 1 ߮㓸࿅ 2 ߦ߅ߡ㧘એਅߩ⚿⺰߇ᓧࠄࠇߚޕ · ᧄ⹜㛎એ㒠ߩ⥃ᐥ㐿⊒ߢ↪ࠆᛩਈ⚻〝ࠍᬌ⸛ߔࠆ㓙ߦ㧘ᧄߦࠃࠅ clinical response ߇ᓧ ࠄࠇߚⵍ㛎⠪ߩഀว߇⊹ਅᛩਈ߮㕒⣂ౝᛩਈߢ߶߷ห᭽ߢߞߚ⚿ᨐߪᵈ⋡ߦ୯ߔࠆ߽ ߩߢࠆޕᦝߦ㧘ోᕈߩࡊࡠࡈࠔࠗ࡞ߦ㑐ߒߡ߽㧘2 ߟߩᛩਈ⚻〝ߩ㑆ߦࠄ߆ߥᏅ⇣ ߪߺࠄࠇߥ߆ߞߚޕ৻ᣇ㧘ࡊࡏߦࠃࠆ response ߇ᓧࠄࠇߚⵍ㛎⠪ߩഀวߪ৻⽾ߒߡૐ ߊ㧘߹ߚ⊹ਅᛩਈߣᲧセߒߡ㕒⣂ౝᛩਈߢߪࠃࠅㅦ߿߆ߦⴊᷡਛࡃࠗࠝࡑࠞߦᓇ㗀ࠍ ਈ߃ߚߎߣߪ㧘ᧄ⹜㛎એ㒠ߩ⥃ᐥ㐿⊒ߦ߅ߌࠆኡ⸃ዉ≮ᴺߣߒߡ㕒⣂ౝᛩਈߩ↪ࠍᡰ ᜬߔࠆ߽ߩߢߞߚޕ
· 㓸࿅ 1 ߮㓸࿅ 2 ߣ߽ߦ㧘ᧄߩᔋኈᕈߪో⥸⊛ߦ⦟ᅢߢߞߚޕᧄ⹜㛎ߩࡊࡏኻᾖ ᦼ㑆ߢߪ㧘ኂ⽎ߩ⊒ഀวߪࡊࡏ૬ว⟲ߣᧄ૬ว⟲ߢห⒟ᐲߢࠅ㧘߹ߚᧄ ߩ⊹ਅᛩਈߣ㕒⣂ౝᛩਈߢࠄ߆ߥᏅ⇣ߪߺࠄࠇߥ߆ߞߚޕ
39 2 (8) ࠙ࠬ࠹ࠠࡑࡉ 2.7.6 ޘߩ⹜㛎ߩ߹ߣ C0743T26 ⹜㛎
2.7.6.6 ᶏᄖ⥃ᐥ╙ IIb ⋧⹜㛎㧔C0743T26 ⹜㛎㧘ෳ⠨⾗ᢱ㧦5.3.5.1.5㧕
2.7.6.6.1 ⷐ
(1) ᴦ㛎ታᣉ⸘↹ᦠ⇟ภ C0743T26
(2) ᴦ㛎ߩᮡ㗴 ㆊߦ᛫ TNF ⮎ᴦ≮ࠍฃߌߚਛ╬∝߆ࠄ㊀∝ߩᵴേᦼࠢࡠࡦ∛ᖚ⠪ࠍኻ⽎ߣߒߡ࠙ࠬ࠹ࠠ ࡑࡉ㧔એਅ㧘ᧄ㧕ߩലᕈ߮ోᕈࠍ⹏ଔߔࠆ㧘╙ IIb ⋧㧘ᄙᣉ⸳ห㧘ࡦ࠳ࡓൻ㧘ੑ ㊀⋤ᬌ㧘ࡊࡏኻᾖ㧘ਗⴕ⟲㑆Ყセ⹜㛎
(3) ᴦ㛎⽿છකᏧ
(4) ᴦ㛎ታᣉක≮ᯏ㑐 153 ᣉ⸳㧔ർ☨㧘࡛ࡠ࠶ࡄ߮ࠝࠬ࠻ࠕ㧕
(5) ᢥ₂㧔ᒁ↪ᢥ₂㧕 Sandborn WJ, Gasink C, Gao LL, Blank MA, Johanns J, Guzzo C, et al. Ustekinumab induction and maintenance therapy in refractory Crohn's disease. N Engl J Med. 2012;367(16):1519-28.
(6) ᴦ㛎ታᣉᦼ㑆 2008 ᐕ 10 ᣣ㨪2010 ᐕ 12 ᣣ
(7) 㐿⊒ߩ⋧ ╙ IIb ⋧
(8) ⋡⊛ ਥ⋡⊛ ࠢࡠࡦ∛ᴦ≮ߦኻߒߡᛚߐࠇߚ↪ᴺ↪㊂ߩ 1 એߩ᛫ TNF㧔⣲≌უᱫ࿃ሶ㧕⮎ᴦ≮ࠍ ฃߌߚ߇㧘৻ᰴήലߢߞߚ߆㧘ೋᦼߦലᨐࠍ␜ߒߚ߽ߩߩߘߩᓟലᨐ߇ᶖᄬߒߚᖚ⠪㧘ߪߎ ࠇࠄߩᴦ≮ߦኻߒߡᔋኈᕈ߇ߥ㧘ਛ╬∝߆ࠄ㊀∝ߩᵴേᦼࠢࡠࡦ∛ᖚ⠪ߦ߅ߡ㧘ᧄߦࠃ ࠆ clinical response ߩዉߦ߅ߌࠆലᕈ߮ోᕈࠍ⹏ଔߔࠆޕ clinical response㧦Crohn’s Disease Activity Index㧔CDAI㧕ࠬࠦࠕߩࡌࠬࠗࡦ߆ࠄߩ 100 ࡐ ࠗࡦ࠻એߩᷫዋ㧔ࡌࠬࠗࡦߩ CDAI ࠬࠦࠕ߇ 220 એ 248 એਅߩⵍ㛎⠪ߦߟߡߪ㧘 CDAI ࠬࠦࠕ߇ 150 ࡐࠗࡦ࠻ᧂḩࠍ㆐ᚑߒߡߚ႐ว㧘clinical response ߇ᓧࠄࠇߚߣߺߥߔ㧕
39 3 㧔1㧕 ࠙ࠬ࠹ࠠࡑࡉ 2.7.6 ޘߩ⹜㛎ߩ߹ߣ C0743T26 ⹜㛎
ᰴ⋡⊛ Clinical remission㧘≪ሹߩ⹏ଔ㧘߮☼⤑ᴦ≹ߦ߅ߌࠆᧄߩലᕈࠍ⹏ଔߔࠆޕᧄ⹜㛎એ㒠 ߩ⥃ᐥ㐿⊒ߩߚ㧘ኡ⸃⛽ᜬ≮ᴺߩ↪㊂ߩㆬᛯߩⵣઃߌߣߥࠆ࠺࠲ࠍᓧࠆޕᧄߩ⮎‛േᘒ ߮⮎ജቇ⊛․ᕈࠍᬌ⸛ߔࠆޕᧄߩ clinical response ㆃᑧߦ㑐ߔࠆലᕈࠍ⹏ଔߔࠆޕ clinical remission㧦CDAI ࠬࠦࠕ߇ 150 ࡐࠗࡦ࠻ᧂḩ
(9) ᴦ㛎ᣇᴺ ᧄ⹜㛎ߪ㧘ࡦ࠳ࡓൻ㧘ੑ㊀⋤ᬌ㧘ࡊࡏኻᾖ㧘ਗⴕ⟲㑆㧘↪㊂⸳ቯ㧘╙ IIb ⋧⹜㛎ߢߞ ߚޕߔߴߡߩⵍ㛎⠪ࠍ 0 ㅳ⋡ߦࡦ࠳ࡓൻߒ㧘ኡ⸃ዉᦼߩᛩਈߣߒߡࡊࡏ㧘ᧄ 1㧘3 ߪ 6 mg/kg ࠍ㕒⣂ౝᛩਈ㧔IV㧕ߒߚޕ6 ㅳ⋡ߦਥⷐ⹏ଔ㗄⋡ߢࠆ clinical response ࠍ⹏ଔߒߚޕ0 ㅳ⋡ߦኡ⸃ዉ≮ᴺߢᧄߦഀࠅઃߌࠄࠇߚⵍ㛎⠪ࠍ㧘6 ㅳ⋡ߩ clinical response ߦၮߠ߈㧘8 ㅳ ⋡ߦౣࡦ࠳ࡓൻߒ㧘ኡ⸃⛽ᜬᦼߩᛩਈߣߒߡ 8 ㅳ⋡߮ 16 ㅳ⋡ߦᧄ㧔90 mg㧕ߪࡊࡏ ࠍ⊹ਅᛩਈ㧔SC㧕ߒߚޕᧄߦࠃࠆኡ⸃ዉ≮ᴺߩ responder ߣ non-responder ࠍޘߦౣࡦ࠳ ࡓൻߒߚޕኡ⸃ዉ≮ᴺߢࡊࡏࠍ㕒⣂ౝᛩਈߐࠇߚⵍ㛎⠪ߩ߁ߜ㧘responder ߦߪࡊࡏ㧘 non-responder ߦߪᧄࠍߘࠇߙࠇኡ⸃⛽ᜬᦼߩ 8 ㅳ⋡㧔270 mg㧕߮ 16 ㅳ⋡㧔90 mg㧕ߦ⊹ਅᛩ ਈߒߚޕ 6 ㅳ⋡ߩ clinical response ߩήߦ߆߆ࠊࠄߕ㧘ߕࠇߩᛩਈ⟲ߢ߽ห৻ߩోᕈ߮ലᕈߩ ⹏ଔࠍታᣉߒ㧘⹜㛎ࠍ⛮⛯ߔࠆߎߣߣߒߚޕోᕈ߮ലᕈߩ⹏ଔߪ㧘36 ㅳ⋡߹ߢታᣉߒߚޕ ߔߴߡߩⵍ㛎⠪߇ 6 ㅳ⋡ߩ᧪㒮ࠍቢੌᓟ㧘ਛ㑆⸃ᨆ㧔ࠢࡠࡦ∛ࠍኻ⽎ߣߒߚᧄߩ╙ III ⋧ ⹜㛎ߢ↪ࠆ㧘ኡ⸃ዉᦼߩᛩਈ㊂ߩㆬᛯߩߚ㧕ࠍታᣉߒߚޕਥ⸃ᨆߢߪ㧘╙৻⒳ߩㆊ⺋ߩ᳓ Ḱ㧔0.05㧕ߦߟߡߩ⺞ᢛߪⴕࠊߥ߆ߞߚޕ߹ߚ㧘ߔߴߡߩⵍ㛎⠪߇ 22 ㅳ⋡ߩ᧪㒮ࠍቢੌߒߚᓟ ߦ߽㧘ਛ㑆⸃ᨆ㧔ࠢࡠࡦ∛ࠍኻ⽎ߣߒߚᧄߩ╙ III ⋧⹜㛎ߢ↪ࠆ㧘ኡ⸃⛽ᜬᦼߩ↪ᴺ↪ ㊂ߩㆬᛯߩߚ㧕ࠍታᣉߒߚޕᴦ㛎ᦼ㑆ࠍㅢߒߡ㧘⁛┙࠺࠲ࡕ࠾࠲ࡦࠣᆔຬળ㧔DMC㧕ߦ ࠃࠅోᕈ࠺࠲߇㕖⋤ᬌਅߢࡕ࠾࠲ࡦࠣߐࠇߚޕ
(10) ⵍ㛎⠪ᢙ㧔⸘↹ᤨ߮⸃ᨆᤨ㧕 ⸘↹ᤨ ⚂ 170 ᣉ⸳ߩታᣉක≮ᯏ㑐ߢ⚂ 500 ⸃ᨆᤨ 153 ᣉ⸳ߩታᣉක≮ᯏ㑐ߢ 526 ߇ࡦ࠳ࡓൻߐࠇ㧘ో 526 ߇ലᕈ⸃ᨆኻ⽎㓸࿅߮ో ᕈ⸃ᨆኻ⽎㓸࿅ߣߥߞߚޕ߹ߚ㧘ኡ⸃ዉᦼߦᧄࠍ 1 ࿁એᛩਈߐࠇߚ 394 ߇⮎‛േᘒ⸃ᨆ ኻ⽎㓸࿅ߣߥߞߚޕ
(11) ⸻ᢿ߮ਥߥㆬᛯၮḰ 18 ᱦએߩ㧘ਛ╬∝߆ࠄ㊀∝ߩᵴേᦼࠢࡠࡦ∛㧔CDAI ࠬࠦࠕ߇ 220 એ 450 એਅ㧕ߦ 3 ࠞ એ⟕ᖚߒߡ߅ࠅ㧘X ✢ᬌᩏ߮㧛ߪౝⷞ㏜ᬌᩏߢᄢ⣺Ἳ㧘࿁⣺Ἳ㧘ߪ࿁⚿⣺Ἳ߇⏕ߐ ࠇ㧘ࠢࡠࡦ∛ᴦ≮ࠍ⋡⊛ߣߒ㧘ᛚߐࠇߚ↪ᴺ↪㊂ߢࠗࡦࡈࠠࠪࡑࡉ㧘ࠕ࠳ࡓࡑࡉ⧯ߒ ߊߪ certolizumab pegol ࠍㆊߦᛩਈߐࠇߚ߇㧘৻ᰴήലߢߞߚ߆㧘ೋᦼߦലᨐࠍ␜ߒߚ߽ߩߩ
39 4 㧔2㧕 ࠙ࠬ࠹ࠠࡑࡉ 2.7.6 ޘߩ⹜㛎ߩ߹ߣ C0743T26 ⹜㛎
ߘߩᓟലᨐ߇ᶖᄬߒߚᖚ⠪㧘ߪߎࠇࠄߩ⮎ߦኻߒߡᔋኈᕈ߇ߥ߆ߞߚᖚ⠪ࠍኻ⽎ߣߒߚޕ߹ ߚ㧘૬↪⮎ߩᛩਈ⁁ᴫ߇৻ቯߢࠅ㧘ࠬࠢ࠾ࡦࠣᤨߩ⥃ᐥᬌᩏ⚿ᨐ㧘ਗ߮ߦ⚿ᩭߩᣢᓔᱧ ߮ᬌᩏ⚿ᨐ߇ㆬᛯၮḰߦว⥌ߔࠆᖚ⠪ࠍኻ⽎ߣߒߚޕ
(12) ⵍ㛎⮎㧘↪㊂߮ᛩਈᣇᴺ㧘ࡠ࠶࠻⇟ภ ࠙ࠬ࠹ࠠࡑࡉ㕒ᵈ↪㧔1㧘3 ߪ 6 mg/kg㧕ߪ㧘ή⩶ṁᶧ߇లႯߐࠇߚන࿁ᛩਈ↪ߩࡃࠗ ࠕ࡞߇ଏ⛎ߐࠇߚ㧔ࡠ࠶࠻⇟ภ㧦 㧘 㧘 㧘 㧕ޕ࠙ࠬ࠹ࠠࡑࡉ⊹ਅᵈ ↪ߪ㧘ή⩶ṁᶧ߇లႯߐࠇߚන࿁ᛩਈ↪ߩࡊࡈࠖ࡞࠼ࠪࡦࠫ㨇1 mL ਛߦ࠙ࠬ࠹ࠠ ࡑࡉ㧔ㆮવሶ⚵឵߃㧕90 mg ࠍ㨉߇ଏ⛎ߐࠇߚ㧔ࡠ࠶࠻⇟ภ㧦 㧘 㧘 㧕ޕ
(13) ኻᾖ⮎㧘↪㊂߮ᛩਈᣇᴺ㧘ࡠ࠶࠻⇟ภ ⊹ਅᛩਈ↪ࡊࡏߪ㧘න࿁ᛩਈ↪ߩࡊࡈࠖ࡞࠼ࠪࡦࠫ߇ଏ⛎ߐࠇߚ㧔ࡠ࠶࠻⇟ภ㧦 㧘㧘㧕ޕ
(14) ᛩਈᦼ㑆 ߔߴߡߩⵍ㛎⠪ߪ㧘0 ㅳ⋡ߦࡦ࠳ࡓൻߐࠇ㧘ኡ⸃ዉ≮ᴺߣߒߡࡊࡏ㧘⧯ߒߊߪᧄ 1㧘 3 ߪ 6 mg/kg ߇㕒⣂ౝᛩਈߐࠇߚޕ6 ㅳ⋡ߦਥⷐ⹏ଔ㗄⋡ߢࠆ clinical response ࠍ⹏ଔߒߚޕ0 ㅳ⋡ߦኡ⸃ዉ≮ᴺߢᧄߦഀࠅઃߌࠄࠇߚⵍ㛎⠪ࠍ㧘6 ㅳ⋡ߩ clinical response ߦၮߠ߈ 8 ㅳ⋡ ߦౣࡦ࠳ࡓൻߒ㧘ኡ⸃⛽ᜬᦼߩᛩਈߣߒߡ 8 ㅳ⋡߮ 16 ㅳ⋡ߦᧄ㧔90 mg㧕ߪࡊࡏࠍ ⊹ਅᛩਈߒߚޕౣࡦ࠳ࡓൻߪ㧘ᧄߦࠃࠆኡ⸃ዉ≮ᴺߩ responder ߣ non-responder ߢޘߦ ታᣉߒߚޕኡ⸃ዉ≮ᴺߢࡊࡏࠍ㕒⣂ౝᛩਈߐࠇߚⵍ㛎⠪ߩ߁ߜ㧘responder ߦߪࡊࡏࠍ ኡ⸃⛽ᜬᦼߢࠆ 8 ㅳ⋡߮ 16 ㅳ⋡ߦ㧘non-responder ߦߪᧄࠍ 8 ㅳ⋡㧔270 mg㧕߮ 16 ㅳ⋡ 㧔90 mg㧕ߦߘࠇߙࠇ⊹ਅᛩਈߒߚޕ
(15) ⹏ଔ㗄⋡ ⮎‛േᘒ ⴊᷡਛ࠙ࠬ࠹ࠠࡑࡉỚᐲ ∉ේᕈ ᛫࠙ࠬ࠹ࠠࡑࡉ᛫ ⮎ജቇ ⴊᷡਛ⮎ജቇࡑࠞ㧘ᧃ᪳ⴊਛࡔ࠶ࡦࠫࡖࡏᩭ㉄㧔mRNA㧕ߩ⊒߮ోⴊਛ࠺ࠝࠠ ࠪࡏᩭ㉄㧔DNA㧕ߩ⸃ᨆ ലᕈ CDAI ࠬࠦࠕ㧘ࠦ࡞࠴ࠦࠬ࠹ࡠࠗ࠼≮ᴺਛᱛߩน⢻ᕈ㧘C ᔕᕈߚࠎ⊕㧔CRP㧕㧘ଢਛࠢ࠻ ࡈࠚࡦ߮ଢਛࠞ࡞ࡊࡠ࠹ࠢ࠴ࡦ㧘≪ሹߩ⹏ଔ㧘უ∓ᕈ⤥⊹∝ߩ⹏ଔ㧘ਗ߮ߦᄢ⣺ౝⷞ㏜ᬌᩏ ᖚ⠪ႎ๔ࠕ࠙࠻ࠞࡓ Inflammatory Bowel Disease Questionnaire㧔IBDQ㧕㧘ࠫࠚࡦࠠࡦࠬ⌧⌁⹏ଔ⾰㧔JSEQ㧕
39 5 㧔3㧕 ࠙ࠬ࠹ࠠࡑࡉ 2.7.6 ޘߩ⹜㛎ߩ߹ߣ C0743T26 ⹜㛎
ක≮⚻ᷣቇ ක≮⾗Ḯߩ↪ ోᕈ ኂ⽎㧘㊀◊ߥኂ⽎㧔SAE㧕㧘ࡃࠗ࠲࡞ࠨࠗࡦ㧘ࠗࡦࡈࡘ࡚ࠫࡦࠕ࡚ࠢࠪࡦ߮ᵈ ㇱᔕ㧘ⴊᶧቇ⊛ᬌᩏ߮ⴊᶧ↢ൻቇᬌᩏࡄࡔ࠲㧘ℂቇ⊛ᚲ㧘ਗ߮ߦ 12 ⺃ዉᔃ㔚࿑
(16) ⛔⸘ᚻᴺ ࡦ࠳ࡓൻߐࠇߚߔߴߡߩⵍ㛎⠪ߦߟߡ㧘ੱญ⛔⸘ቇ⊛․ᕈ߮ࡌࠬࠗࡦᤨߩ∔ᖚ․ᕈ ࠍⷐ⚂ߒߚޕ6 ㅳ⋡ߦ clinical response ߇ᓧࠄࠇߚⵍ㛎⠪ߩഀว㧔ਥⷐ⹏ଔ㗄⋡㧕ࠍ▚ߒ㧘ᛩਈ ⟲㑆㧔ᧄ 6 mg/kg ⟲ኻࡊࡏ⟲㧘ᧄ 3 mg/kg ⟲ኻࡊࡏ⟲㧘ᧄ 1 mg/kg ⟲ኻࡊࡏ ⟲㧕ߢᲧセࠍⴕߞߚޕ⟲㑆Ყセߪ㧘᛫ TNF ⮎ᴦ≮ߩೋᦼᴦ≮ߩലᨐ㧔㧛ή㧕ࠍጀ࿃ሶߣߒ㧘 ਔᗧ᳓Ḱ 0.05 ߣߒߚ Cochran Mantel Haenszel ߩࠞࠗੑਸ਼ᬌቯࠍ↪ߚޕ╙৻⒳ߩㆊ⺋ߩ᳓Ḱ ࠍਔ 0.05 ߦࠦࡦ࠻ࡠ࡞ߔࠆߚ㧘࿕ቯ㗅ᐨᴺߦࠃࠅ⸃ᨆࠍⴕߞߚޕᧄ⹜㛎ߢߪ㧘ᧄߩᦨ㜞 ↪㊂㧔6 mg/kg㧕ߢᗧᏅ߇ࠄࠇߚ႐วߦ㧘ઁߩᧄ↪㊂㧔3 mg/kg ߮ 1 mg/kg㧕ߩ⚿ᨐߦ ߆߆ࠊࠄߕᗧߣ್ᢿߔࠆߎߣߣߒߚޕਥⷐߥᰴ⹏ଔ㗄⋡ߢࠆ 6 ㅳ⋡ߩ clinical remission㧘4 ㅳ⋡ߩ clinical response㧘߮ᧄߦࠃࠆኡ⸃ዉ≮ᴺߢ clinical response ߇ᓧࠄࠇߚⵍ㛎⠪ߦ߅ߌ ࠆ 22 ㅳ⋡ߩ clinical remission ߦߟߡ߽㧘ోߩ╙৻⒳ߩㆊ⺋ߩ᳓Ḱࠍਔ 0.05 ߦࠦࡦ࠻ࡠ࡞ ߔࠆߚ㧘࿕ቯ㗅ᐨᴺߦࠃࠅ⸃ᨆࠍⴕߞߚޕਥⷐ⹏ଔ㗄⋡ߢᗧᏅ߇ࠄࠇߚ႐วߪ 6 ㅳ⋡ߩ clinical remission ߩ㧘6 ㅳ⋡ߩ clinical remission ߢᗧᏅ߇ࠄࠇߚ႐วߪ 4 ㅳ⋡ߩ clinical response ߩᬌቯࠍⴕ߁ߎߣߣߒ㧘22 ㅳ⋡ߩ clinical remission ߦߟߡ߽ਥⷐ⹏ଔ㗄⋡ߢᗧᏅ߇ ࠄࠇߚ႐วߦᬌቯࠍⴕ߁ߎߣߣߒߚޕߘߩઁߩᰴ⹏ଔ㗄⋡ߩ⸃ᨆߢߪ㧘ᄙ㊀ᕈߩ⺞ᢛࠍⴕ ࠊߕ⛔⸘ቇ⊛ߦᗧ߆ߤ߁߆ߩ್ᢿߪฬ⋡ߩ p ୯ߦၮߠߡⴕߞߚޕ ਥ⸃ᨆߪ㧘ේೣ intent to treat ߩขᛒߦࠃࠅታᣉߒߚޕߒߚ߇ߞߡ㧘ฦᛩਈ⟲ߦࡦ࠳ࡓߦഀ ࠅઃߌࠄࠇߚฦⵍ㛎⠪ߩലᕈ࠺࠲ߪ㧘ታ㓙ߦᛩਈߐࠇߚᛩਈ⟲ߢߪߥߊഀࠅઃߌࠄࠇߚᛩਈ ⟲ߢ⸃ᨆߐࠇߚޕ ోᕈߪ㧘ኂ⽎ߩ⊒ഀว߮⒳㘃㧘ਗ߮ߦⴊᶧቇ⊛ᬌᩏ߮ⴊᶧ↢ൻቇᬌᩏࡄࡔ࠲ ߩࡌࠬࠗࡦ߆ࠄߩᄌൻ㊂ࠍⷐ⚂ߒߚޕోᕈߩ⹏ଔߪ㧘ᧄ⹜㛎ߢᴦ㛎⮎㧔ⷙቯᛩਈ㊂ߩߔߴ ߡߢ߽৻ㇱߢ߽⦟㧕ࠍ 1 ࿁એᛩਈߐࠇߚⵍ㛎⠪ࠍኻ⽎ߣߒߚޕ
(17) ⚿ᨐ ᴦ㛎ኻ⽎㓸࿅ ኡ⸃ዉᦼߢߪ㧘526 ߩⵍ㛎⠪߇㕒⣂ౝᛩਈߦࠃࠆᧄ 1㧘3 ߪ 6 mg/kg ⟲⧯ߒߊߪࡊ ࡏ⟲ߦ㧘1㧦1㧦1㧦1 ߩഀวߢࡦ࠳ࡓߦഀࠅઃߌࠄࠇߚޕߎߩ߁ߜ㧘49 㧔9.3%㧕߇ᴦ㛎⮎ߩ ᛩਈࠍਛᱛߒߚޕਛᱛℂ↱ߪ㧘ㆊඨᢙߩⵍ㛎⠪߇㧘ലᨐਇචಽߪࠢࡠࡦ∛ߩኂ⽎ߢࠅ㧘 17 ߪߘߩઁ㧔หᗧ᠗࿁㧘᧪㒮ࠦࡦࡊࠗࠕࡦࠬਇ⦟㧘ㆬᛯ㧛㒰ᄖၮḰ㆑╬㧕ߦಽ㘃ߐࠇߚޕ 477 㧔90.7%㧕ߪᧄ⹜㛎ࠍਛᱛߒߥ߆ߞߚޕ ኡ⸃⛽ᜬᦼߢߪ㧘ᧄߩ㕒⣂ౝᛩਈߦࠃࠆ responder ࠍᧄ SC ⟲㧔72 㧕ߪࡊࡏ SC ⟲ 㧔73 㧕ߦ㧘ᧄߩ㕒⣂ౝᛩਈߦࠃࠆ non-responder ࠍᧄ SC ⟲㧔109 㧕ߪࡊࡏ SC ⟲ 㧔110 㧕ߦࡦ࠳ࡓߦഀࠅઃߌߚޕ߹ߚ㧘ࡊࡏߩ㕒⣂ౝᛩਈߦࠃࠆ responder ࠍࡊࡏ
39 6 㧔4㧕 ࠙ࠬ࠹ࠠࡑࡉ 2.7.6 ޘߩ⹜㛎ߩ߹ߣ C0743T26 ⹜㛎
SC ⟲㧔28 㧕ߦ㧘non-responder ࠍᧄ 270/90 mg SC ⟲㧔85 㧕ߦഀࠅઃߌߚޕኡ⸃⛽ᜬᦼߢߪ㧘 63 㧔13.2%㧕ߩⵍ㛎⠪߇ᴦ㛎⮎ߩᛩਈࠍਛᱛߒߚޕᴦ㛎⮎ߩᛩਈࠍਛᱛߒߚⵍ㛎⠪ߪ㧘ᧄ SC ⟲ߣᲧセߒߡࡊࡏ SC ⟲ߢᄙߊ㧘ᦨ߽ᄙਛᱛℂ↱ߪലᨐਇචಽ߮ኂ⽎㧔ᄢㇱಽߪ ࠢࡠࡦ∛ߩኂ⽎㧕ߢߞߚޕ336 㧔70.4%㧕ߪᧄ⹜㛎ࠍਛᱛߒߥ߆ߞߚޕ ኡ⸃ዉᦼߦࡦ࠳ࡓൻߐࠇߚ 526 ߩ߁ߜ㧘309 㧔58.7%㧕ߪᅚᕈߢࠅ㧘490 㧔93.2%㧕 ߪ⊕ੱߢߞߚޕᐕ㦂ߩਛᄩ୯ߪ 38.0 ᱦ㧘㊀ߩਛᄩ୯ߪ 69.0 kg ߢߞߚޕࡌࠬࠗࡦᤨߩ ੱญ⛔⸘ቇ⊛․ᕈߪ㧘ኡ⸃ዉᦼߩ 4 ᛩਈ⟲߮ኡ⸃⛽ᜬᦼߩฦᛩਈ⟲ߢో⥸⊛ߦห᭽ߢߞߚޕ ࡌࠬࠗࡦᤨߩ∔ᖚ․ᕈߪ㧘ᣢሽᴦ≮ߦ㔍ᴦᕈߩਛ╬∝߆ࠄ㊀∝ߩࠢࡠࡦ∛ᖚ⠪㓸࿅ࠍઍ ߔࠆ߽ߩߢߞߚޕࠢࡠࡦ∛ߩ⟕ᖚᦼ㑆ߩਛᄩ୯ߪ 10.34 ᐕ㧘CDAI ࠬࠦࠕߩਛᄩ୯ߪ 316.0㧘 IBDQ ࠬࠦࠕߩਛᄩ୯ߪ 116.0 ߢߞߚޕ∔ᖚ․ᕈߪኡ⸃ዉᦼߩ 4 ᛩਈ⟲ߢో⥸⊛ߦห᭽ߢ ࠅ㧘ኡ⸃⛽ᜬᦼߩࡊࡏ SC ⟲߮ᧄ SC ⟲ߢ߽ห᭽ߢߞߚޕࡌࠬࠗࡦᤨߦ㧘⚂ 50% ߩⵍ㛎⠪߇ࠦ࡞࠴ࠦࠬ࠹ࡠࠗ࠼ࠍᛩਈߐࠇߡߚޕ ᦨೋߦࡦ࠳ࡓൻߐࠇߚ 526 ో߇㧘ᴦ㛎⮎ࠍ 1 ࿁એᛩਈߐࠇߚޕ
ലᕈ · ᧄߦࠃࠆ clinical response ߩኡ⸃ዉ
· 6 ㅳ⋡ߦ clinical response ߇ᓧࠄࠇߚⵍ㛎⠪ߩഀว㧔ਥⷐ⹏ଔ㗄⋡㧕ߪ㧘ࡊࡏ⟲ 㧔23.5%㧕ߣᲧセߒߡᧄ 6 mg/kg ⟲㧔39.7%㧕ߢᗧߦ㜞߆ߞߚ㧔p=0.005㧕ޕ6 ㅳ⋡ߦ clinical response ߇ᓧࠄࠇߚⵍ㛎⠪ߩഀวߪ㧘ᧄ 1 mg/kg ⟲߮ 3 mg/kg ⟲ߢߘࠇߙࠇ 36.6%߮ 34.1%ߢߞߚޕ
· ᧄߦࠃࠆ clinical response ߩኡ⸃ዉߦኻߔࠆലᨐߪ㧘ㇱಽ㓸࿅ߦ߅ߌࠆ⸃ᨆߢ߽߅߅ ߨ৻⽾ߒߡߚޕ
· ౕ⊛ߦߪ㧘᛫ TNF ⮎ᴦ≮ߢ৻ᰴήലߢߞߚⵍ㛎⠪㓸࿅㧔৻ᰴήല㧕㧘ೋᦼߦ ലᨐࠍ␜ߒߚ߽ߩߩߘߩᓟലᨐ߇ᶖᄬߒߚⵍ㛎⠪㓸࿅㧔ੑᰴήല㧕㧘߮᛫ TNF ⮎ߦኻߔࠆᔋኈᕈߩߥⵍ㛎⠪㓸࿅ߦ߅ߡ㧘ⵍ㛎⠪ోߢߺࠄࠇߚ clinical response ߣ৻⥌ߔࠆ⚿ᨐߢߞߚޕ
· 8 ㅳ⋡ߦ clinical response ߇ᓧࠄࠇߚⵍ㛎⠪ߩഀวߪ㧘6 ㅳ⋡ߩഀวߣᲧセߒߡᧄ 6 mg/kg ⟲ߢ㜞ߊ㧘߹ߚᧄ 1 mg/kg ⟲߮ 3 mg/kg ⟲ߢߪૐ߆ߞߚߎߣ߆ࠄ㧘↪㊂ᔕ ᕈ߇␜ໂߐࠇߚޕ
· 6 ㅳ⋡ߦ clinical remission ߇ᓧࠄࠇߚⵍ㛎⠪ߩഀวߢߪ㧘ᛩਈ⟲㑆ߢᗧᏅߪࠄࠇߥ߆ ߞߚޕ
· 8 ㅳ⋡ߦ clinical remission ߇ᓧࠄࠇߚⵍ㛎⠪ߩഀวߪ㧘6 ㅳ⋡ߣᲧセߒߡ㜞߆ߞߚޕ․ߦ㧘 ᧄ 6 mg/kg ⟲ߢ㜞ߊ㧘8 ㅳ⋡ߢߪ 18.3%߮ 6 ㅳ⋡ߢߪ 12.2%ߢߞߚޕ
· 6 ㅳ⋡ߩ≪ሹᔕߩഀวߪ㧘ᧄ 6 mg/kg ⟲ߢߪઁߩᛩਈ⟲ߣᲧセߒߡ㜞ߊ㧘47.1%ߢ ߞߚޕᧄ 1 mg/kg ⟲㧘3 mg/kg ⟲߮ࡊࡏ⟲ߩഀวߪ㧘ߘࠇߙࠇ 15.8%㧘10.0%߮ 21.4%ߢߞߚޕ
39 7 㧔5㧕 ࠙ࠬ࠹ࠠࡑࡉ 2.7.6 ޘߩ⹜㛎ߩ߹ߣ C0743T26 ⹜㛎
· 6 ㅳ⋡ߦ߅ߡ㧘CDAI ࠬࠦࠕߩૐਅ㧘IBDQ ࠬࠦࠕߩᡷༀ㧘CRP ߩᱜᏱൻ㧘ଢਛࠢ࠻ࡈ ࠚࡦ߮ଢਛࠞ࡞ࡊࡠ࠹ࠢ࠴ࡦߩᷫዋߩ⒟ᐲߪ㧘ࡊࡏ⟲ߣᲧセߒߡߔߴߡߩᧄ⟲ ߢᄢ߈ߊ㧘ᧄ 6 mg/kg ⟲ߢߪࡊࡏ⟲ߣߩᗧᏅ߇ࠄࠇߚޕ
· ࡌࠬࠗࡦᤨߦ∛ᄌㇱࠍߔࠆⵍ㛎⠪㓸࿅ߢߪ㧘6 ㅳ⋡ߩ☼⤑ᴦ≹ߩഀวߪ㧘ࡊ ࡏ⟲㧔11.1%㧕ߣᲧセߒߡᧄ IV ૬ว⟲㧔19.5%㧕ߢ㜞߆ߞߚޕᧄߩ 3 ⟲ߢߪ☼⤑ᴦ≹ ߩഀวߪห⒟ᐲߢߞߚޕ
· ኡ⸃⛽ᜬᦼ㧦ᧄߦࠃࠆኡ⸃ዉ≮ᴺߩ responder ߣߒߡౣࡦ࠳ࡓൻߐࠇߚⵍ㛎⠪ߢߪ㧘 ᧄߦࠃࠅ clinical remission ߮ clinical response ߇⛽ᜬߐࠇߚޕ
· 22 ㅳ⋡ߩ clinical remission ߇ᓧࠄࠇߚⵍ㛎⠪ߩഀวߪ㧘ࡊࡏ SC ⟲㧔27.4%㧕ߣᲧセ ߒߡ㧘ᧄ SC ⟲㧔41.7%㧕ߢᗧߦ㜞߆ߞߚ㧔p=0.029㧕ޕ
· 22 ㅳ⋡ߩ clinical response ߇ᓧࠄࠇߚⵍ㛎⠪ߩഀวߪ㧘ࡊࡏ SC ⟲㧔42.5%㧕ߣᲧセ ߒߡ㧘ᧄ SC ⟲㧔69.4%㧕ߢᗧߦ㜞߆ߞߚ㧔p<0.001㧕ޕ
· ᧄߦࠃࠆኡ⸃ዉ≮ᴺߩ responder ߩ߁ߜ㧘ᧄ SC ⟲ߦࡦ࠳ࡓഀࠅઃߌߐࠇߚ ⵍ㛎⠪ߢߪ㧘22 ㅳ⋡ߩ clinical response ߇ᓧࠄࠇߚⵍ㛎⠪ߩഀวߦኡ⸃ዉᦼߩᛩਈ ㊂ߦࠃࠆᄢ߈ߥ㆑ߪߺࠄࠇߥ߆ߞߚޕߒ߆ߒ㧘ࡊࡏ SC ⟲ߦࡦ࠳ࡓഀࠅઃ ߌߐࠇߚⵍ㛎⠪ߢߪ㧘ኡ⸃ዉᦼߩᛩਈ㊂߇ዋߥ߆ߞߚⵍ㛎⠪ߦ߅ߡ clinical response ߇ᓧࠄࠇߚⵍ㛎⠪ߩഀว߇ᣧᦼߦᷫዋߒߚޕ
· 22 ㅳ⋡߹ߢ clinical response ࠍ⛽ᜬߒߡߚⵍ㛎⠪ߩഀวߪ㧘ࡊࡏ SC ⟲㧔32.9%㧕 ߣᲧセߒߡ㧘ᧄ SC ⟲㧔55.6%㧕ߢᗧߦ㜞߆ߞߚ㧔p=0.005㧕ޕ
· 6 ㅳ⋡ߦ clinical remission ߇ᓧࠄࠇߚⵍ㛎⠪ߩ߁ߜ㧘22 ㅳ⋡ߦ clinical remission ࠍ⛽ᜬߒ ߡߚⵍ㛎⠪ߩഀวߪ㧘ᧄ SC ⟲ߢ 78.6%߮ࡊࡏ SC ⟲ߢ 53.3%ߢߞߚ 㧔p=0.056㧕ޕ
· ߘߩઁߩലᕈ⹏ଔ㗄⋡㧔IBDQ ࠬࠦࠕ㧘CRP㧘CDAI ࠬࠦࠕ㧘ଢਛࠢ࠻ࡈࠚࡦ߮ ଢਛࠞ࡞ࡊࡠ࠹ࠢ࠴ࡦ㧕ߩ᷹ቯ⚿ᨐ߽㧘ㅀߩ⚿ᨐࠍᡰᜬߔࠆ߽ߩߢߞߚޕ
· non-responder ߦ߅ߡ㧘ᧄߦࠃࠆㅊടᴦ≮߇ലߢࠆߣߩࠛࡆ࠺ࡦࠬߪᓧࠄࠇߥ߆ ߞߚޕ
· ࡊࡏߦࠃࠆኡ⸃ዉ≮ᴺߩ non-responder ߩ߁ߜ㧘8 ㅳ⋡ߦᧄ 270 mg ߩ⊹ਅᛩਈ ࠍฃߌߚⵍ㛎⠪ߢߪ㧘8 ㅳᓟߦ clinical response ߮ clinical remission ߇ᓧࠄࠇߚⵍ㛎⠪ ߩഀวߪ㧘㕒⣂ౝᛩਈߦࠃࠆኡ⸃ዉ≮ᴺߢࠄࠇߚ⚿ᨐߣ߅߅ߨ৻⥌ߒߚ߇㧘ኻ ᾖ⟲ࠍ⸳ቯߒߥ߆ߞߚߚ⸃㉼ߪ࿎㔍ߢࠆޕ
⮎‛േᘒ߮∉ේᕈ · ᧄ 1㧘3 ߪ 6 mg/kg ߩන࿁㕒⣂ౝᛩਈᓟ㧘ⴊᷡਛ࠙ࠬ࠹ࠠࡑࡉỚᐲߦ↪㊂Ყᕈ߇ ࠄࠇߚޕ0 ㅳ⋡ߩᛩਈ 1 ᤨ㑆ᓟߦ߅ߌࠆⴊᷡਛ࠙ࠬ࠹ࠠࡑࡉỚᐲߩਛᄩ୯ߪ㧘ᧄ 1㧘 3 ߮ 6 mg/kg ⟲ߢߘࠇߙࠇ 24.3㧘71.6 ߮ 144.1 ȝg/mL ߢߞߚޕኡ⸃ዉ⚳ੌᤨ㧔8 ㅳ
39 8 㧔6㧕 ࠙ࠬ࠹ࠠࡑࡉ 2.7.6 ޘߩ⹜㛎ߩ߹ߣ C0743T26 ⹜㛎
⋡㧕ߩⴊᷡਛ࠙ࠬ࠹ࠠࡑࡉỚᐲߩਛᄩ୯ߪ㧘ᧄ 1㧘3 ߮ 6 mg/kg ⟲ߢߘࠇߙࠇ 0.8㧘 3.1 ߮ 7.0 ȝg/mL ߢߞߚޕⴊᷡਛ࠙ࠬ࠹ࠠࡑࡉỚᐲߪ㧘߶ߣࠎߤߩⵍ㛎⠪ߢ 8 ㅳ⋡߹ ߢᬌน⢻ߢࠅ㧘8 ㅳ⋡ߦ߅ߡ࠙ࠬ࠹ࠠࡑࡉỚᐲ߇ቯ㊂ਅ㒢ᧂḩߢߞߚⵍ㛎⠪ߩ ഀวߪ㧘ᦨૐ↪㊂ߢࠆ 1 mg/kg ⟲ߢᦨ߽㜞߆ߞߚ㧔10.3%㧕ޕ
· 㕒⣂ౝᛩਈߒߚᧄߩኡ⸃ዉᦼߩ↪㊂ߦ㑐ଥߥߊ㧘ኡ⸃⛽ᜬᦼߦᧄ 90 mg ߩ⊹ਅᛩਈ ࠍฃߌߚⵍ㛎⠪ߢߪ㧘ኡ⸃⛽ᜬᛩਈ㐿ᆎᓟ⚂ 12 ㅳᓟߦߪห⒟ᐲߩⴊᷡਛ࠙ࠬ࠹ࠠࡑࡉỚ ᐲࠍ␜ߒߚޕ
· 22 ㅳ⋡㧔16 ㅳ⋡ߩᦨ⚳⊹ਅᛩਈߩ 6 ㅳᓟ㧕ߦ߅ߡ㧘ࡊࡏ SC ⟲ߩⵍ㛎⠪ߣߪ⇣ߥࠅ㧘 ᧄ SC ⟲ߩⵍ㛎⠪ߢߪ㧘ⴊᷡਛ࠙ࠬ࠹ࠠࡑࡉỚᐲߩ⛽ᜬ߇␜ߐࠇߚޕ
· ᛫࠙ࠬ࠹ࠠࡑࡉ᛫⹏ଔ↪ߩᬌ߇ᓧࠄࠇߚᧄᛩਈⵍ㛎⠪ 427 ߩ߁ߜ㧘3 㧔0.7%㧕 ߪ 36 ㅳ⋡ߩᦨ⚳᧪㒮ᣣ߹ߢߦ᛫࠙ࠬ࠹ࠠࡑࡉ᛫߇㓁ᕈߣߥߞߚޕߎࠇࠄߩߕࠇߩⵍ 㛎⠪߽㧘᛫ଔߪૐ߆ߞߚ㧔1:10 ߆ࠄ 1:80㧕ޕ߹ߚ㧘ਛ᛫߽㓁ᕈߢߞߚޕ
ᖚ⠪ႎ๔ࠕ࠙࠻ࠞࡓ · ᧄ 1㧘3 ߮ 6 mg/kg ࠍ㕒⣂ౝᛩਈߒߚߣ߈ߩ㧘6 ㅳ⋡ߩ IBDQ ࠬࠦࠕߦ߅ߌࠆࡌࠬ ࠗࡦ߆ࠄߩᡷༀߩᐔဋ୯ߪߘࠇߙࠇ 19.9㧘22.7 ߮ 24.8 ߢࠅ㧘ࡊࡏ⟲ߩ 11.8 ߣᲧセ ߒߡ⛔⸘ቇ⊛ߦᗧߦ㜞߆ߞߚ㧔ߕࠇ߽ p<0.05㧕ޕ
· 6 ㅳ⋡ߩ IBDQ ࠬࠦࠕ߇ࡌࠬࠗࡦ߆ࠄ 16 ࡐࠗࡦ࠻એᡷༀߒߚⵍ㛎⠪ߩഀวߪ㧘ᧄ 1㧘3 ߮ 6 mg/kg ⟲ߢߘࠇߙࠇ 45.0%㧘47.7%߮ 54.7%ߢࠅ㧘ࡊࡏ⟲ߩ 33.1%ߣᲧ セߒߡ㜞߆ߞߚޕ
· 6 ㅳ⋡ߩᧄߦࠃࠆ responder ߢߪ㧘22 ㅳ⋡ߩ IBDQ ࠬࠦࠕߩᐔဋ୯ߪࡊࡏ SC ⟲ߣᲧ セߒߡᧄ SC ⟲ߢᗧߦ㜞߆ߞߚޕ
· 6 ㅳ⋡ߩᧄߦࠃࠆ responder ߢߪ㧘22 ㅳ⋡ߩ IBDQ dimension ࠬࠦࠕߩᐔဋ୯ߪࡊࡏ SC ⟲ߣᲧセߒߡᧄ SC ⟲ߢᗧߦ㜞߆ߞߚ㧔ߕࠇ߽ p<0.05㧕ޕ
· Responder ߣߒߡౣࡦ࠳ࡓൻߐࠇߚⵍ㛎⠪ߩ߁ߜ㧘22 ㅳ⋡ߩ IBDQ ࠬࠦࠕ߇ࡌࠬࠗࡦ ߆ࠄ 16 ࡐࠗࡦ࠻એᡷༀߒߚⵍ㛎⠪ߩഀวߪ㧘ࡊࡏ SC ⟲㧔44.9%㧕ߣᲧセߒߡᧄ SC ⟲㧔68.1%㧕ߢᗧߦ㜞߆ߞߚ㧔p=0.005㧕ޕ
· Responder ߣߒߡౣࡦ࠳ࡓൻߐࠄࠇ㧘6 ㅳ⋡ߩ IBDQ ࠬࠦࠕ߇ࡌࠬࠗࡦ߆ࠄ 16 ࡐࠗࡦ ࠻એᡷༀߒߚⵍ㛎⠪ߩ߁ߜ㧘22 ㅳ⋡ߩ IBDQ ࠬࠦࠕߢ߽ 16 ࡐࠗࡦ࠻એߩᡷༀࠍ⛽ᜬߒ ߚⵍ㛎⠪ߩഀวߪ㧘ᧄ SC ⟲ߢ 71.9%߮ࡊࡏ SC ⟲ߢ 54.9%ߢߞߚޕ36 ㅳ⋡ߩ IBDQ ࠬࠦࠕߢ 16 ࡐࠗࡦ࠻એߩᡷༀࠍ⛽ᜬߒߚⵍ㛎⠪ߩഀวߪ㧘ᧄ SC ⟲ߢ 43.9%߮ ࡊࡏ SC ⟲ߢ 27.5%ߢߞߚޕ
ක≮⚻ᷣቇ · 6 ㅳ⋡ߩ↢↥ᕈߪ㧘ኡ⸃ዉᦼߩߕࠇߩᧄ⟲ߢ߽㧘ࡊࡏ⟲ߣᲧセߒߡᗧߥᡷༀ ߇ߺࠄࠇߚ㧔ߕࠇߩᧄ⟲߽ࡊࡏ⟲ߣߩᲧセߢ p<0.05㧕ޕ
39 9 㧔7㧕 ࠙ࠬ࠹ࠠࡑࡉ 2.7.6 ޘߩ⹜㛎ߩ߹ߣ C0743T26 ⹜㛎
· 6 ㅳ⋡߹ߢߩࠢࡠࡦ∛ߦ㑐ㅪߔࠆ㒮ߪ㧘ࡊࡏ⟲ߣᲧセߒߡᧄ 1 mg/kg ⟲߮ᧄ ૬ว⟲ߢߪᗧߦᷫዋߒߚ㧔ߕࠇߩᧄ⟲߽ࡊࡏ⟲ߣߩᲧセߢ p<0.05㧕ޕ৻ᣇ㧘 ᧄ 3 mg/kg ⟲߮ 6 mg/kg ⟲ߢߪ㧘ࡊࡏ⟲ߣᲧセߒߡᗧߥᏅߪߺࠄࠇߥ߆ߞߚޕ
· 6 ㅳ⋡߹ߢߩࠢࡠࡦ∛ߦ㑐ㅪߔࠆᄖ⑼ಣ⟎ߦߟߡ㧘ߕࠇߩᧄ⟲߽ࡊࡏ⟲ߣᲧ セߒߡ․╩ߔߴ߈㆑ߪߺࠄࠇߥ߆ߞߚޕ
· ኡ⸃⛽ᜬᦼߩߕࠇߩᛩਈ⟲߽㧘22 ㅳ⋡߮ 36 ㅳ⋡ߩ↢↥ᕈߣ 6 ㅳ⋡ߩ↢↥ᕈߢ․╩ߔߴ ߈㆑ߪߺࠄࠇߥ߆ߞߚޕ
ోᕈ ኂ⽎߮ SAE㧔ኡ⸃ዉᦼ㧕 · 8 ㅳ⋡߹ߢߩᧄ 1㧘3 ߮ 6 mg/kg ߩ㕒⣂ౝᛩਈߩᔋኈᕈߪ⦟ᅢߢࠅ㧘ోᕈࡊࡠࡈࠔ ࠗ࡞ߪࡊࡏߣ߶߷ห᭽ߢߞߚޕ
· 8 ㅳ⋡߹ߢߩኡ⸃ዉᦼߢߪ㧘ߕࠇߩᛩਈ⟲ߢ߽ SAE ߩ⊒ߪ߹ࠇߢߞߚޕࠢࡠࡦ ∛ࠍ㒰߈㧘ߕࠇߩᧄ⟲ߢ߽ 2 એߦ⊒ߒߚ SAE ߪߥ߆ߞߚޕ
· ᗵᨴ∝ࠍ⊒ߒߚⵍ㛎⠪ߩഀวߪ㧘8 ㅳ⋡߹ߢߪߔߴߡߩᛩਈ⟲ߢห⒟ᐲߢߞߚޕ㊀◊ ߥᗵᨴ∝ߪ㧘ᧄ 1 mg/kg ⟲㧘3 mg/kg ⟲߮ࡊࡏ⟲ߣᲧセߒߡᧄ 6 mg/kg ⟲ߢᄙߊ ႎ๔ߐࠇߚޕ
· ࠗࡦࡈࡘ࡚ࠫࡦࠕ࡚ࠢࠪࡦߩ⊒ߪ߹ࠇߢࠅ㧘ߕࠇ߽㕖㊀◊ߢ㧘⊒ഀวߪߔߴ ߡߩᛩਈ⟲ߢห⒟ᐲߢߞߚޕ
ኂ⽎߮ SAE㧔ኡ⸃⛽ᜬᦼ㧕 · Responder ߮ non-responder ߣߒߡౣࡦ࠳ࡓൻߐࠇߚⵍ㛎⠪ߢߪ㧘ᧄࠍ⊹ਅᛩਈߒߚ ߣ߈ߩᔋኈᕈߪ⦟ᅢߢࠅ㧘ోᕈࡊࡠࡈࠔࠗ࡞ߪࡊࡏࠍ⊹ਅᛩਈߒߚߣ߈ߣห᭽ߢ ߞߚޕ
· ᧄࠍ 8 ㅳ⋡ߦ 270 mg㧘⛯ߌߡ 16 ㅳ⋡ߦ 90 mg ࠍ⊹ਅᛩਈߔࠆ↪ᴺ↪㊂ߦ߅ߡ߽㧘ᔋ ኈᕈߪ⦟ᅢߢߞߚޕ
· SAE ߩ⊒ഀวߪ㧘ᧄ SC ⟲ߣࡊࡏ SC ⟲ߢห⒟ᐲߢߞߚޕེቭᄢಽ㘃߇ޟ⢗⣺ 㓚ኂޠߩ SAE ߢߪ㧘․ߦࠢࡠࡦ∛߇ᛩਈ⟲ోߢᦨ߽ᄙߊࠄࠇߚޕኡ⸃⛽ᜬᦼߦႎ ๔ߐࠇߚེቭᄢಽ㘃߇ޟ⢗⣺㓚ኂޠએᄖߩ SAE ߢ㧘ߕࠇߩᛩਈ⟲ߢ߽ 2 એߦ⊒ ߒߚ SAE ߪߥ߆ߞߚޕ
· ᱫ㧘㊀◊ߥᣣᗵᨴ∝㧘ߪ⚿ᩭߪߥ߆ߞߚޕ⊹⤏ߩၮᐩ⚦⢩≸߇ 1 ߦࠄࠇߚޕ
· ኡ⸃⛽ᜬᦼߢႎ๔ߐࠇߚᗵᨴ∝ࠍ⊒ߒߚⵍ㛎⠪ߩഀวߪ㧘ߔߴߡߩᛩਈ⟲ߢห⒟ᐲߢ ߞߚޕ㊀◊ߥᗵᨴ∝ߩ⊒ߪ߹ࠇߢࠅ㧘⊒ഀวߪߔߴߡߩᛩਈ⟲ߢห⒟ᐲߢߞߚޕ
· ਥⷐᔃⴊ▤ࠗࡌࡦ࠻ߪߥ߆ߞߚޕ
· ᵈㇱᔕߩ⊒ߪ߹ࠇߢࠅ㧘ߕࠇ߽㕖㊀◊ߢ㧘⊒ഀวߪߔߴߡߩᛩਈ⟲ߢห⒟ ᐲߢߞߚޕ
40 0 㧔8㧕 ࠙ࠬ࠹ࠠࡑࡉ 2.7.6 ޘߩ⹜㛎ߩ߹ߣ C0743T26 ⹜㛎
⥃ᐥᬌᩏ⚿ᨐ · ኡ⸃ዉᦼ߮ኡ⸃⛽ᜬᦼߣ߽ߦ㧘ᢙߩⵍ㛎⠪ߢⴊᶧቇ⊛ᬌᩏ୯ߦ㗼⪺ߥ⇣Ᏹᄌേ߇ ࠄࠇߚޕᦨ߽ࠃߊࠄࠇߚᄌേߪ㧘ࡊࡏ⟲ߢߩࡦࡄᢙᷫዋߢߞߚޕ
· ኡ⸃ዉᦼߢႎ๔ߐࠇߚⴊᶧ↢ൻቇᬌᩏ୯ߩ㗼⪺ߥ⇣Ᏹᄌേߩ߁ߜ㧘ߕࠇߩᛩਈ⟲ߢ߽ 2 એߦห৻ⵍ㛎⠪ߢⶄᢙ࿁ࠄࠇߚᄌേߪߥ߆ߞߚޕኡ⸃⛽ᜬᦼߢߪ㧘ࡦ㉄Ⴎᷫ ዋ߇ᧄ SC ૬ว⟲ߢ 2 ߦⶄᢙ࿁ࠄࠇߚޕ
⚿⺰ ᧄ⹜㛎ߢߪ㧘ㆊߦ᛫ TNF ⮎ᴦ≮߇ήലߢߞߚਛ╬∝߆ࠄ㊀∝ߩࠢࡠࡦ∛ᖚ⠪ߦ߅ߡ㧘 ⥃ᐥ⊛ߦ㊀ⷐߥࠛࡆ࠺ࡦࠬ߇ᓧࠄࠇߚޕᧄߪ㧘clinical response ߩኡ⸃ዉ߮ኡ⸃⛽ᜬߦല ߢߞߚޕ․ߦ㧘36 ㅳ㑆ߩᧄ⹜㛎ߦ߅ߡ㧘0 ㅳ⋡ߦᧄ 1㧘3 ߪ 6 mg/kg ࠍ㕒⣂ౝᛩਈߒ㧘⛯ ߡ 8 ㅳ⋡߮ 16 ㅳ⋡ߦᧄ 90 mg ࠍ⊹ਅᛩਈߒߚⵍ㛎⠪ߢലᕈ߇ࠄࠇߚޕ
· ᧄߦࠃࠆ clinical response ߩኡ⸃ዉ
· 6 ㅳ⋡ߦ clinical response ߇ᓧࠄࠇߚⵍ㛎⠪ߩഀวߪ㧘ࡊࡏ⟲㧔23.5%㧕ߣᲧセߒߡ ᧄ 6 mg/kg ⟲㧔39.7%㧕ߢᗧߦ㜞߆ߞߚ㧔p=0.005㧕ޕ6 ㅳ⋡ߦ clinical response ߇ᓧ ࠄࠇߚⵍ㛎⠪ߩഀวߪ㧘ᧄ 1 mg/kg ⟲߮ 3 mg/kg ⟲ߢߘࠇߙࠇ 36.6%߮ 34.1%ߢ ߞߚޕ
· ᧄߦࠃࠆ clinical response ߩኡ⸃ዉߦኻߔࠆലᨐߪ㧘᛫ TNF ⮎ᴦ≮ߢ৻ᰴήല ߮ੑᰴήല㧘ਗ߮ߦ᛫ TNF ⮎ߦኻߔࠆᔋኈᕈߩߥⵍ㛎⠪ߩㇱಽ㓸࿅ߢ߽߅߅ߨ ৻⽾ߒߡߚޕ
· 8 ㅳ⋡ߦ clinical response ߇ᓧࠄࠇߚⵍ㛎⠪ߩഀวߪ㧘6 ㅳ⋡ߩഀวߣᲧセߒߡᧄ 6 mg/kg ⟲ߢ㜞ߊ㧘߹ߚᧄ 1 mg/kg ⟲߮ 3 mg/kg ⟲ߢߪૐ߆ߞߚߎߣ߆ࠄ㧘↪㊂ᔕ ᕈ߇␜ໂߐࠇߚޕ
· 6 ㅳ⋡ߦ clinical remission ߇ᓧࠄࠇߚⵍ㛎⠪ߩഀวߢߪ㧘ᛩਈ⟲㑆ߢᗧᏅߪࠄࠇߥ߆ ߞߚޕ
· ߘߩઁߩലᕈ⹏ଔ㗄⋡㧔IBDQ ࠬࠦࠕ㧘CRP㧘CDAI ࠬࠦࠕ㧘≪ሹߩ⹏ଔ㧘ଢਛࠢ࠻ࡈ ࠚࡦ߮ଢਛࠞ࡞ࡊࡠ࠹ࠢ࠴ࡦ㧕ߩ᷹ቯ⚿ᨐ߽㧘ㅀߩ⚿ᨐࠍᡰᜬߔࠆ߽ߩߢߞߚޕ
· ᧄߦࠃࠆኡ⸃ዉ≮ᴺߩ responder ߣߒߡౣࡦ࠳ࡓൻߐࠇߚⵍ㛎⠪ߢߪ㧘ᧄߩ⊹ਅᛩ ਈߦࠃࠅ clinical remission ߮ clinical response ߇⛽ᜬߐࠇߚޕ
· 22 ㅳ⋡ߦ clinical remission ߮ clinical response ߇ᓧࠄࠇߚⵍ㛎⠪ߩഀวߪ㧘ࡊࡏ SC ⟲ߣᲧセߒߡᧄ SC ⟲ߢᗧߦ㜞߆ߞߚޕ
· 6 ㅳ⋡ߦ clinical remission ߇ᓧࠄࠇߚⵍ㛎⠪ߩ߁ߜ㧘22 ㅳ⋡ߦ clinical remission ࠍ⛽ᜬߒ ߡߚⵍ㛎⠪ߩഀวߪ㧘ࡊࡏ SC ⟲ߣᲧセߒߡᧄ SC ⟲ߢ㜞߆ߞߚޕ
40 1 㧔9㧕 ࠙ࠬ࠹ࠠࡑࡉ 2.7.6 ޘߩ⹜㛎ߩ߹ߣ C0743T26 ⹜㛎
· ᧄ⹜㛎ߢኻ⽎ߣߒߚⵍ㛎⠪㓸࿅ߦ߅ߡᧄߩᔋኈᕈߪ߅߅ߨ⦟ᅢߢࠅ㧘ోᕈࡊࡠ ࡈࠔࠗ࡞ߪઁߩㆡᔕ∝ߢႎ๔ߐࠇߚ߽ߩߣห᭽ߢߞߚޕ
· 8 ㅳ⋡ߢߩ㕒⣂ౝᛩਈᤨߩోᕈߪ㧘ᧄߣࡊࡏߢห᭽ߢߞߚޕ
· ኡ⸃⛽ᜬᦼߦ߅ߡᧄࠍ⊹ਅᛩਈߒߚߣ߈ߩᔋኈᕈߪ⦟ᅢߢࠅ㧘ోᕈࡊࡠࡈࠔࠗ ࡞ߪࡊࡏ SC ⟲ߣห᭽ߢߞߚޕ
· ᗵᨴ∝ࠍ⊒ߒߚⵍ㛎⠪ߩഀวߪ㧘8 ㅳ⋡߹ߢ߮ኡ⸃⛽ᜬᦼߦ߅ߡ㧘ߔߴߡߩᧄ ⟲߮ࡊࡏ⟲ߢห⒟ᐲߢߞߚޕኡ⸃ዉᦼߢߪ㧘㊀◊ߥᗵᨴ∝ߪᧄ 6 mg/kg ⟲ ߢᄙߊႎ๔ߐࠇߚޕኡ⸃⛽ᜬᦼߢߪ㧘㊀◊ߥᗵᨴ∝ߩ⊒ߪ߹ࠇߢࠅ㧘⊒ഀวߪߔ ߴߡߩᛩਈ⟲ߢห⒟ᐲߢߞߚޕ
· ᱫ㧘㊀◊ߥᣣᗵᨴ∝㧘ߪ⚿ᩭߪߥ߆ߞߚޕ⊹⤏ߩၮᐩ⚦⢩≸߇ 1 ߦࠄࠇ ߚޕਥⷐᔃⴊ▤ࠗࡌࡦ࠻ߪߥ߆ߞߚޕ
· ࠗࡦࡈࡘ࡚ࠫࡦࠕ࡚ࠢࠪࡦ߮ᵈㇱᔕߩ⊒ߪ߹ࠇߢࠅ㧘ߕࠇ߽㕖㊀◊ ߢ㧘⊒ഀวߪߔߴߡߩᛩਈ⟲ߢห⒟ᐲߢߞߚޕ
· ᧄࠍᛩਈߐࠇߚⵍ㛎⠪ߩ߁ߜ㧘36 ㅳ⋡ߩᦨ⚳᧪㒮ᣣ߹ߢߦ᛫࠙ࠬ࠹ࠠࡑࡉ᛫߇ 㓁ᕈߣ್ቯߐࠇߚⵍ㛎⠪ߪ㧘3 ߢߞߚޕ
40 2 㧔10㧕