Title: Clinical effectiveness and safety of vedolizumab intravenous in real world clinical practice in ulcerative colitis Korean patients: a multicenter postmarketing observational study NCT Number: NCT03535649 Protocol Approve Date: 24 September 2018 Certain information within this protocol has been redacted (ie, specific content is masked irreversibly from view with a black/blue bar) to protect either personally identifiable information (PPD) or company confidential information (CCI). This may include, but is not limited to, redaction of the following: Named persons or organizations associated with the study. Proprietary information, such as scales or coding systems, which are considered confidential information under prior agreements with license holder. Other information as needed to protect confidentiality of Takeda or partners, personal information, or to otherwise protect the integrity of the clinical study. Vedolizumab-5045 Non-Interventional Study Protocol Title: Clinical effectiveness and safety of vedolizumab intravenous in real world clinical practice in ulcerative colitis Korean patients: a multicenter post- marketing observational study Short title: Vedolizumab in ulcerative colitis Korean patients Study ID: Vedolizumab-5045 Sponsor: Takeda Pharmaceuticals Korea Co., Ltd. (Daechi-dong, 12F) 8, Teheran-ro 98-gil, Gangnam-gu, Seoul 06181, Korea Phone: +82 2 3484 0800 Fax: +82 2 3484 0808 Study phase: Medical Affairs, Post-Approval Company Sponsored (Observational) Date of final version 4.1 of protocol: 24 September 2018 (Amendment 4) Proper f Takeda: For non-commercial use only and subject to the applicable Terms of Use Study Protocol Final Ver. 4.1, 24-SEP-2018 Page 1 of 47 9HGROL]XPDE $GPLQLVWUDWLYH,QIRUPDWLRQ &RQWDFWV ,VVXH &RQWDFW $GYHUVHHYHQWVDQGSUHJQDQF\UHSRUWLQJ 7DNHGD.RUHD3KDUPDFRYLJLODQFH7HDP (PDLO'62.5#WDNHGDFRP )D[ 7HO 6WXG\0DQDJHU FRQGXFWRIWKHVWXG\ PPD rms of Use 7ULDO&OLQLFLDQ PHGLFDODGYLFHRQSURWRFROFRPSRXQGDQGPHGLFDO PDQDJHPHQWRISDWLHQWV 5HVSRQVLEOH0HGLFDO2IILFHU FDUULHVRYHUDOOUHVSRQVLELOLW\IRUWKHFRQGXFWRIWKHVWXG\ a Property of Takeda: For non-commercial use only a 6WXG\3URWRFRO)LQDO9HU6(3 3DJHRI 9HGROL]XPDE $SSURYDO 5(35(6(17$7,9(62)7$.('$ 7KLV VWXG\ ZLOO EH FRQGXFWHG ZLWK WKH KLJKHVW UHVSHFW IRU WKH LQGLYLGXDO SDUWLFLSDQWV LQ DFFRUGDQFHZLWKWKHUHTXLUHPHQWVRIWKLVFOLQLFDOVWXG\SURWRFRODQGDOVRLQDFFRUGDQFHZLWK WKHIROORZLQJ x 7KHHWKLFDOSULQFLSOHVWKDWKDYHWKHLURULJLQLQWKH'HFODUDWLRQRI+HOVLQNL x ,QWHUQDWLRQDO &RQIHUHQFH RQ +DUPRQLVDWLRQ ,&+ ( *RRG &OLQLFDO 3UDFWLFHDFWLFH *&3 * &RQVROLGDWHG*XLGHOLQH x *XLGHOLQHVIRU*RRG3KDUPDFRYLJLODQFH3UDFWLFHV *93 x *XLGHOLQHVIRU*RRG3KDUPDFRHSLGHPLRORJ\3UDFWLFHV *33 x $OO DSSOLFDEOH ODZV DQG UHJXODWLRQV LQFOXGLQJ ZLWKRXWRXW OLPLOLPOLPLWDWLRQ GDWD SULYDF\ ODZV FOLQLFDOWULDOGLVFORVXUHODZVDQGUHJXODWLRQV 6,*1$785(6 nly and subject to the applicable Terms of Use PPD Property of 6WXG\3URWRFRO)LQDO9HU6(3 3DJHRI Vedolizumab-5045 INVESTIGATOR SIGNATURE PAGE I confirm that I have read and that I understand this protocol and any other product information provided by the sponsor. I agree to conduct this study in accordance with the requirements of this protocol and also to protect the rights, safety, privacy, and well-being of study patients in accordance with the following: The ethical principles that have their origin in the Declaration of Helsinki. International Conference on Harmonisation, E6 Good Clinical Practice: Consolidated Guideline. All applicable laws and regulations, including, without limitation, data privacy laws and regulations. Regulatory requirements for reporting serious adverse events as defined in this protocol. Signature of Investigator Date <Investigator Name (print or type)> <Investigator’s Title> <Location of Facility (City, State/Provence)> <Location of Facility (Country)> Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use Study Protocol Final Ver. 4.1, 24-SEP-2018 Page 4 of 47 Vedolizumab-5045 STUDY SUMMARY Name of Sponsor(s): Compound/Product [if applicable]: Takeda Korea Vedolizumab Title of Protocol: Clinical effectiveness and safety of vedolizumab intravenous in real world clinical practice in ulcerative colitis Korean patients: a multicenter post-marketing observational study Study Number: Vedolizumab-5045 Phase: 4 (observational) Study Design: This is an observational, multicenter, post-marketing study that will analyze real world data on the effectiveness and safety of vedolizumab intravenous (IV) in South Korean patients presenting ulcerative colitis (UC) and having failed tumor necrosis factor (TNF)-α antagonist therapy (as per the approved label). Patients will be identified from the medical records and enrolled in the study if they meet the inclusion and exclusion criteria. Screening logs of potential patients will be maintained at each of the sites, to record reasons why the patient failed eligibility screening. Both retrospective and prospective patient data will be collected, with prospective data collected for treatment baseline visit (i.e. first date of vedolizumab treatment) and follow up visits. Prospective data will be collected according to each site’s IRB definition (i.e. whether treatment baseline and follow up visits happens post initial IRB submission date, or post initial IRB approval date, etc). The study will collect information on demographics, risk factors, clinical data, laboratory and endoscopic data, previous UC medications and surgeries, UC medications and concomitant treatments at baseline (start of vedolizumab treatment) and follow-up. The safety outcome measures will include: adverse events of special interest (AESIs) (serious infections, opportunistic infections, hepatitis viral infection, gastrointestinal infections, respiratory infections, other clinically significant infections, malignancies, infusion-related reactions, and hepatic injury), serious adverse events (SAEs), and pregnancy outcomes. The data will be abstracted, if available, from the medical charts. Data on pregnancy and pregnancy outcomes will be collected subject to a written informed consent from the patient or the patient’s partner. Primary Objectives: To assess the clinical effectiveness of vedolizumab IV in UC Korean patients by the clinical response at 6 weeks. To assess the safety of vedolizumab IV in UC Korean patients. Secondary Objectives: To assess the clinical effectiveness of vedolizumab IV in UC Korean patients by the clinical response at 14 weeks and clinical remission at 6 and 14 weeks. To assess the clinical effectiveness of vedolizumab IV in UC Korean patients on mucosal healing at 6 and 14 weeks. 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