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Clinical Trial Protocol Protocol ZK-001 Version 3.1, June 5, 2018 Clinical Trial Protocol Safety and Pharmacokinetic Evaluation of Zika Virus Immune Globulin in Healthy Volunteers ZK-001 Version 3.1 June 5, 2018 Emergent BioSolutions Canada Inc. 155 Innovation Dr., Winnipeg, Manitoba R3T 5Y3 CONFIDENTIAL This document is a confidential communication of the Sponsor. Acceptance of this document constitutes an agreement by the recipient that no unpublished information contained within will be published or disclosed without prior written approval, except that this document may be disclosed to the appropriate Ethics Committee and Regulatory Authority under the condition that they keep it confidential. Emergent BioSolutions Canada Inc. Confidential and Proprietary Page 1 of 57 Protocol ZK-001 Version 3.1, June 5, 2018 Safety and Pharmacokinetic Evaluation of Zika Virus Immune Globulin in Healthy Volunteers Protocol ZK-001 Version 3.1 June 5, 2018 Trial Sponsor: Emergent BioSolutions Canada Inc. 155 Innovation Drive Winnipeg, MB, R3T 5Y3, Canada Contract Research Organization (CRO): INC Research 720 King Street West Toronto, ON, M5V 2T3, Canada Tel: 416-963-9338 CRO Reference Laboratory: Dynacare 115 Midair Court Brampton, ON, L6P 5M3, Canada Clinical Trial Scientist: Bojan Drobic, PhD Tel: 204-275-4196 Fax: 204-487-4086 E-mail: [email protected] Emergent BioSolutions Canada Inc. Confidential and Proprietary Page 2 of 57 Protocol ZK-001 Version 3.1, June 5, 2018 Sponsor’s Study Medical Monitor: Hugo Astacio, MD 155 Innovation Drive Winnipeg, MB, R3T 5Y3, Canada Tel: 204-275-4441; Mobile: 204-230-7786 Email: [email protected] Emergent BioSolutions Canada Inc. Confidential and Proprietary Page 3 of 57 Protocol ZK-001 Version 3.1, June 5, 2018 ZK-001 Protocol Synopsis Title Safety and Pharmacokinetic Evaluation of Zika Virus Immune Globulin in Healthy Volunteers Sponsor Emergent BioSolutions Canada Inc. 155 Innovation Drive Winnipeg, MB, R3T 5Y3 Canada Trial Start Q2-Q3 2018 Objectives Primary Objective: • To assess safety of ZIKV-IG in healthy volunteers. Secondary Objective: • To determine pharmacokinetics (PK) of ZIKV-IG in healthy volunteers. Subject Healthy male and non-pregnant female volunteers Population Sample Size 30 subjects Number of Trial The clinical trial will be conducted at a single trial site. Sites Test Product Zika Virus Immune Globulin (Human) (ZIKV-IG) (code name: NP-024), a purified human immunoglobulin preparation containing neutralizing antibodies to Zika virus. ZIKV-IG is supplied as a sterile liquid suitable for intravenous administration to individuals with blood type O+ or O-. Reference Placebo (saline solution), supplied as a sterile liquid suitable for Product intravenous administration. Protocol Design Phase 1, single-center, randomized, double blind, placebo- controlled trial design. Dosage One dose level of ZIKV-IG will be evaluated, along with placebo. Thirty subjects will be randomized to intravenously receive either ZIKV-IG dose (50.0 mL undiluted; n=19) or placebo (50.0 mL; n=11). Dosing of the first six subjects (group 1) will be staggered over three days, wherein two subjects per day will be randomized 1:1 Emergent BioSolutions Canada Inc. Confidential and Proprietary Page 5 of 57 Protocol ZK-001 Version 3.1, June 5, 2018 and dosed at least 3 hours apart (subgroups 1A, 1B, 1C; each subgroup to be dosed at least one day apart). If in the opinion of the principal investigator there are no identified safety concerns after the first six dosed subjects, a group of six subjects (group 2) will be randomized 2:1 and dosed (at least 30 minutes apart) over the course of one day. A safety monitoring committee will be held to evaluate safety (collected up to 72 hours post-dosing) of the first 12 dosed subjects. If there are no safety signals identified, then the remaining 18 subjects will be randomized 2:1 and dosed (at least 30 minutes apart) in three separate groups of six subjects (groups 3, 4, 5) over a period of three days; each group of six subjects will be dosed over the course of one day. Each subject will be followed-up for 85 calendar days post-study treatment administration. Inclusion Criteria 1. Informed consent voluntarily signed by subject. 2. Age: 18–55 years of age. 3. Blood type O+ or O-. 4. Body mass index (BMI) of 18–30. • Note: minimum body weight of 50 kg. 5. For female subjects (with male partners) that are not surgically sterilized (e.g., did not undergo hysterectomy, bilateral oophorectomy or tubal ligation), use of an effective method of contraception throughout the trial including: • Using hormonal contraception (oral, injectable or implant) continuously for 3 months prior to screening and willing to continue to use hormonal contraception throughout the entire trial. • Intrauterine device (IUD) inserted at least 1 month prior to screening. • Double barrier type of birth control measure (e.g., condoms, diaphragms, cervical sponge with spermicide). • True abstinence. • For female subjects who are post-menopausal, documented follicle- stimulating hormone (FSH) ≥40 mIU/mL must be obtained. If the FSH is <40 mIU/mL, the subject must agree to use an acceptable form of contraception (see above). • Females of childbearing potential without male sexual partners must be willing to maintain their sexual status as it is throughout the study. Emergent BioSolutions Canada Inc. Confidential and Proprietary Page 6 of 57 Protocol ZK-001 Version 3.1, June 5, 2018 6. For male subjects that have not had a vasectomy, use of a condom with spermicide or true abstinence for the duration of the study. Note: female partners (that are of childbearing potential) of male study subjects (that have not had a vasectomy) should use one of the effective contraception methods (eg, hormonal contraception, IUD or barrier type). Also, male subjects must not donate sperm for the duration of the study. • Males without female sexual partners must be willing to maintain their sexual status as it is throughout the study. 7. Healthy as determined by principal investigator or a qualified designate based on medical history, physical exam, vital signs, urinalysis, blood chemistry and hematology test results at screening. Exclusion 1. Use of any investigational product within the past 30 days. Criteria 2. Use of any investigational product during the study. 3. Individuals with blood type A, B or AB. 4. Recipient of any blood product within the past 12 months. 5. Plasma donation within 7 days or significant blood loss or blood donation within 56 days of baseline. 6. Blood donation at any time during the study. 7. 0 g/L. Females with a hemoglobin level ≤12 8. Males with a hemoglobin level <130 g/L. 9. History of hypersensitivity to blood or plasma products. 10. History of allergy to latex or rubber. 11. History of IgA deficiency. 12. History of hypercoagulable conditions (e.g., deep vein thrombosis or pulmonary embolism). 13. History of myocardial infarction. 14. History of stroke. 15. History of renal impairment/failure. 16. Currently pregnant or lactating or planning to become pregnant during the study. 17. History of flavivirus infection [ZIKV, dengue virus (DENV), West Nile virus (WNV), Japanese encephalitis virus (JEV), Emergent BioSolutions Canada Inc. Confidential and Proprietary Page 7 of 57 Protocol ZK-001 Version 3.1, June 5, 2018 yellow fever virus (YFV)] or vaccination with licensed or investigational flavivirus vaccine. 18. Plans to travel to an area with active flavivirus (e.g., ZIKV and/or DENV) transmission during the study (and up to 10 months after the study drug administration) or has returned from an endemic area with these diseases within 30 days of screening. 19. Positive nucleic acid test (NAT) or serology for ZIKV or positive serology for WNV or DENV. 20. Positive serology test (at screening) for human immunodeficiency virus 1 and 2 (HIV), hepatitis C virus (HCV); positive test for hepatitis B virus (HBV) as determined by HBsAg. 21. History of chronic or acute severe neurologic condition (e.g., diagnosis of Guillain-Barre syndrome, epilepsy, Bell's palsy, meningitis or disease with any focal neurologic deficits). 22. Heavy smokers ( cigarettes a day) or electronic cigarette ≥15 use. 23. History of, or suspected substance abuse problem (including alcohol). 24. Failure of drug (urine) test at screening or baseline. 25. Failure of alcohol (breath) test at screening or baseline. 26. Receipt of a live vaccine within 28 days prior to screening or anticipated receipt of a live vaccine during the study period. 27. Individuals with planned surgical procedures that will occur during the study. 28. An opinion of the investigator that it would be unwise to allow participation of the subject in the study. Assessments Screening (within 35 days prior to Baseline): • Informed consent. • Review of study criteria. • Medical history, complete physical exam, vital signs (temperature, sitting blood pressure, respiratory rate, pulse oximetry and pulse rate), concomitant medications, body weight and height. • Blood type test. Emergent BioSolutions Canada Inc. Confidential and Proprietary Page 8 of 57 Protocol ZK-001 Version 3.1, June 5, 2018 • Electrocardiogram (ECG) assessment. • Hematology, blood chemistry and urinalysis (see Appendix I). • Viral marker testing: serology for HIV, HBV, HCV; ZIKV NAT (serum, urine) and serology for ZIKV, and serology for WNV and DENV. Note: ZIKV IgM serology will be performed by the site’s reference laboratory, while ZIKV IgG serology will be performed by the sponsor-developed non-diagnostic assay. • Serum pregnancy test for all female subjects of child bearing potential and FSH assessment for female subjects who are post-menopausal (defined as being amenorrheic for at least 1 year). • Drug (urine) test. • Alcohol (breath) test. Baseline (Day -1; within 24 hours prior to Day 1): • Review of study criteria. • Complete physical exam, vital signs, body weight. • Hematology, blood chemistry (see Appendix I). • Medical history and concomitant medications. • Viral marker testing: ZIKV NAT (serum, urine) and serology for ZIKV.
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