Clinical trial NCT04804540
Conditions: Ulcerative Colitis Crohn Disease
Keywords: Drug Therapy
Sponsor: Takeda
Start date: 2021-12-08; Completion date: 2024-02-02
Enrollment: 150 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Vedolizumab is a medicine that helps to reduce inflammation and pain in the digestive system. In this study, people with ulcerative colitis or Crohn's disease will be treated with vedolizumab. The main aim of the study is to check for side effects from vedolizumab.

At the first visit, the study doctor will check who can take part. Participants will receive vedolizumab slowly through a vein (infusion). Participants will regularly visit the clinic for up to 46 weeks for more infusions of Vedolizumab. During these visits, the study doctor will check if there are any side effects from this treatment.

Participants will visit the clinic for a final check-up up to 16 weeks after their final infusion of Vedolizumab. Clinic staff will arrange a phone call 6 months after their final infusion of Vedolizumab for a further check-up.

Detailed description:
The drug being tested in this study is called vedolizumab. Vedolizumab is being tested to treat people who have active UC or CD.

The study will enroll approximately 150 patients. Participants will be assigned to the vedolizumab treatment group.

•Vedolizumab 300 mg

Vedolizumab 300 mg IV infusion will be administered once in Weeks 0, 2, 6 and 10 (CD-participants who have not shown a response can receive a dose at Week 10) during induction phase and in Weeks 14, 22, 30, 38 and 46 during maintenance phase.

This multicentre trial will be conducted in India. The overall time to participate in this study is 74 weeks. Participants will make multiple visits to the clinic, and will be contacted by telephone plus a final visit after receiving their last dose of drug for a follow-up assessment.

Arms: arm 1: Vedolizumab 300 mg IV infusion will be administered once in Weeks 0, 2 and 6 during induction phase and in Weeks 14, 22, 30, 38 and 46 during maintenance phase.
Interventions: intervention 1: Vedolizumab IV
Intervention descriptions: intervention 1: Vedolizumab IV infusion

Protocol documents:
Prot_000.pdf: 
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PROTOCOL 
A Multicenter, Single-arm, Open-label, Phase 4 Study to Evaluate the Safety and Efficacy of 
Vedolizumab in Indian Patients With Ulcerative Colitis and Crohn’s Disease 
Vedolizumab to treat Ulcerative Colitis and Crohn’s Disease 
Sponsor: 
Takeda Biopharmaceuticals India Pvt. Ltd. 
6th Floor, Building 8,  
Tower C, DLF Cyber City,  
Gurgaon 122002, Haryana, India 
Study Number: 
Vedolizumab-4020 
IND Number: 
Not Applicable 
Compound: 
Vedolizumab 
Date: 
09 November 2022 
Version Number: 4.0 
Amendment History: 
Date 
Amendment Number 
Region 
24 May 2018 
Initial version 
India 
19 October 2019 
01 
India 
09 October 2020 
02 
India 
30 March 2021 
03 
India 
09 November 
04 
India 
CONFIDENTIAL PROPERTY OF TAKEDA 
This document is a confidential communication of Takeda. Acceptance of this document constitutes the agreement by 
the recipient that no information contained herein will be published or disclosed without written authorization from 
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Takeda except to the extent necessary to obtain informed consent from those persons to whom the drug may be 
administered. Furthermore, the information is only meant for review and compliance by the recipient, his or her staff, 
and applicable institutional review committee and regulatory agencies to enable conduct of the study. 
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1.0 
ADMINISTRATIVE INFORMATION 
1.1 
Contacts 
A separate contact information list will be provided to each site. 
 General advice on protocol procedures should be obtained through the monitor assigned to the study 
site. Information on service providers is given below and relevant guidelines provided to the site. 
Contact Type/Role 
India Contact 
Serious adverse event and pregnancy reporting 
Cognizant 
Email address: eupv@tgrd.com 
Fax number: +1-224 554 1052 
Takeda Medical Monitor 
Dr 
 
 
6th Floor, Building No – 8, Tower – C 
DLF Cyber City, DLF Phase – II, Gurgaon 
Haryana, India  
  
Takeda Responsible Medical Director 
Dr 
  
 
6th Floor, Building No – 8, Tower – C 
DLF Cyber City, DLF Phase – II, Gurgaon 
Haryana, India 
  
Project Management 
Dr 
 
 
6th Floor, Building No – 8, Tower – C 
DLF Cyber City, DLF Phase – II, Gurgaon 
Haryana, India, 
  
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1.2 
Approval  
REPRESENTATIVES OF TAKEDA  
This study will be conducted with the highest respect for the individual participants in accordance 
with the requirements of this study protocol and also in accordance with the following: 
• The ethical principles that have their origin in the Declaration of Helsinki. 
• International Council For Harmonisation E6 Good Clinical Practice: Consolidated Guideline. 
• All applicable laws and regulations, including, without limitation, data privacy laws, clinical 
trial disclosure laws, and regulations. 
SIGNATURES 
The signature of the responsible Takeda medical officer (and other signatories, as applicable) can 
be found on the signature page. 
 
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INVESTIGATOR AGREEMENT  
I confirm that I have read and that I understand this protocol, package insert 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 Council For Harmonisation, E6 Good Clinical Practice: Consolidated Guideline. 
• All applicable laws and regulations as per latest New Drugs and Clinical Trials Rule 2019, 
including, without limitation, data privacy laws and regulations. 
• Regulatory requirements for reporting serious adverse events defined in Section 10.2 of this 
protocol. 
• Terms outlined in the study site agreement. 
• Responsibilities of the Investigator Appendix B. 
I further authorize that my personal information may be processed and transferred in accordance 
with the uses contemplated in Appendix D of this protocol. 
Signature of Investigator 
Date 
Investigator Name (print or type)  
 
 
Investigator’s Title 
 
 
Location of Facility (City, State/Provence) 
 
 
Location of Facility (Country) 
 
 
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TABLE OF CONTENTS 
1.0 
ADMINISTRATIVE INFORMATION .........................................................................3 
1.1 
Contacts ..................................................................................................................3 
1.2 
Approval.................................................................................................................4 
2.0 
STUDY SUMMARY ..................................................................................................11 
3.0 
STUDY REFERENCE INFORMATION.....................................................................13 
3.1 
Study-Related Responsibilities...............................................................................13 
3.2 
Principal Investigator/Coordinating Investigator .....................................................13 
3.3 
List of Abbreviations .............................................................................................14 
4.0 
INTRODUCTION ......................................................................................................16 
4.1 
Background...........................................................................................................16 
4.1.1 The Inflammatory Bowel Diseases: Ulcerative Colitis and Crohn’s Disease.......16 
4.1.2 Vedolizumab ...................................................................................................16 
4.1.2.1 
Trial Data for UC...................................................................................17 
4.1.2.2 
Trial Data for Crohn’s Disease ...............................................................17 
4.1.2.3 
Safety Profile for UC and CD.................................................................17 
4.1.2.4 
Indian Experience ..................................................................................18 
4.2 
Rationale for the Proposed Study ...........................................................................18 
4.3 
Benefit/Risk Profile ...............................................................................................18 
5.0 
STUDY OBJECTIVES AND ENDPOINTS ................................................................20 
5.1 
Objectives .............................................................................................................20 
5.1.1 Primary objective.............................................................................................20 
5.1.2 Secondary objective .........................................................................................20 
5.2 
Endpoints..............................................................................................................20 
5.2.1 Primary endpoint .............................................................................................20 
5.2.2 Secondary endpoints ........................................................................................20 
6.0 
STUDY DESIGN AND DESCRIPTION .....................................................................21 
6.1 
Study Design.........................................................................................................21 
6.2 
Justification for Study Design, Dose, and Endpoints ...............................................22 
6.3 
Premature Termination or Suspension of Study or Study Site..................................22 
6.3.1 Criteria for Premature Termination or Suspension of the Study .........................22 
6.3.2 Criteria for Premature Termination or Suspension of Study Sites.......................22 
6.3.3 Procedures for Premature Termination or Suspension of the Study or the 
Participation of Study Site(s)............................................................................22 
7.0 
SELECTION AND DISCONTINUATION/WITHDRAWAL OF PATIENTS ..............23 
7.1 
Inclusion Criteria...................................................................................................23 
7.2 
Exclusion Criteria .................................................................................................23 
7.3 
Permitted Medications ...........................................................................................25 
7.3.1 Oral Corticosteroid Dosing and Tapering..........................................................25 
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7.4 
Criteria for Discontinuation or Withdrawal of a Patient...........................................25 
7.5 
Procedures for Discontinuation or Withdrawal of a Patient .....................................26 
8.0 
CLINICAL STUDY MATERIAL MANAGEMENT ...................................................27 
8.1 
Study Drug and Materials ......................................................................................27 
8.1.1 Dosage Form, Manufacturing, Packaging, and Labeling ....................................27 
8.1.1.1 
Vedolizumab IV ....................................................................................27 
8.1.2 Storage ............................................................................................................27 
8.1.3 Dose and Regimen ...........................................................................................27 
8.1.4 Overdose .........................................................................................................28 
8.2 
Study Drug Assignment and Dispensing Procedures ...............................................28 
8.3 
Accountability and Destruction of Sponsor-Supplied Drugs ....................................28 
9.0 
STUDY PLAN ...........................................................................................................30 
9.1 
Study Procedures...................................................................................................30 
9.1.1 Informed Consent Procedure ............................................................................30 
9.1.2 Demographics, Medical History, and Medication History..................................30 
9.1.3 Physical Examination Procedure ......................................................................30 
9.1.4 Weight and Height ...........................................................................................30 
9.1.5 Vital Sign Procedures ......................................................................................30 
9.1.6 Ulcerative colitis/Crohn’s Disease Presentation at Screening/Baseline ...............31 
9.1.6.1 
Full Mayo Score ....................................................................................31 
9.1.6.2 
Simple Clinical Colitis Activity Index ....................................................31 
9.1.6.3 
Harvey Bradshaw Index .........................................................................31 
9.1.6.4 
Simple Endoscopic Score for Crohn Disease Score .................................31 
9.1.7 Principal Investigator Reported Outcome Measures ..........................................31 
9.1.8 PML Checklist.................................................................................................32 
9.1.9 Efficacy measurements ....................................................................................32 
9.1.10 Patient Reported Outcome Measures ................................................................32 
9.1.10.1 Short Inflammatory Bowel Disease Questionnaire ..................................32 
9.1.11 Documentation of Concomitant Medications ....................................................33 
9.1.12 Procedures for Clinical Laboratory Samples .....................................................33 
9.1.13 Documentation of Concurrent Medical Conditions ............................................34 
9.1.14 Contraception and Pregnancy Avoidance Procedure..........................................34 
9.1.15 Pregnancy........................................................................................................35 
9.1.16 ECG Procedure................................................................................................35 
9.1.17 Tuberculosis Screening ....................................................................................35 
9.1.18 Harvey Bradshaw Index/Mayo Score................................................................35 
9.1.19 Documentation of Screen Failure .....................................................................36 
9.1.20 Documentation of Study Entrance ....................................................................36 
9.2 
Monitoring Patient Treatment Compliance .............................................................36 
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9.3 
Schedule of Observations and Procedures ..............................................................36 
9.3.1 Screening ........................................................................................................36 
9.3.2 Rescreening .....................................................................................................36 
9.3.3 Enrollment.......................................................................................................37 
9.3.4 Treatment Phase ..............................................................................................37 
9.3.5 End of Treatment Visit or Early Termination ....................................................37 
9.3.6 Postdose 16-Week Safety Follow-up ................................................................37 
9.3.7 Poststudy Long-term Follow-up .......................................................................37 
9.3.8 Unscheduled Visits Due to Disease Exacerbation ..............................................38 
9.3.9 Post Study Care ...............................................................................................38 
10.0 
PRETREATMENT EVENTS, ADVERSE EVENTS, ADVERSE DRUG REACTIONS, 
UNEXPECTED ADVERSE DRUG REACTIONS ......................................................39 
10.1 
Definitions ............................................................................................................39 
10.1.1 Pretreatment events..........................................................................................39 
10.1.2 Adverse events ................................................................................................39 
10.1.3 Additional Points to Consider for PTEs and AEs...............................................39 
10.1.4 Serious Adverse Events....................................................................................41 
10.1.5 Adverse events of special interest .....................................................................42 
10.1.6 Adverse drug reactions.....................................................................................42 
10.1.7 Unexpected Adverse drug reactions ..................................................................42 
10.1.8 Intensity of PTEs and AEs ...............................................................................42 
10.1.9 Causality of AEs ..............................................................................................42 
10.1.10 
Relationship to Study Procedures................................................................42 
10.1.11 
Start Date...................................................................................................43 
10.1.12 
Stop Date...................................................................................................43 
10.1.13 
Frequency ..................................................................................................43 
10.1.14 
Action Concerning Study Drug...................................................................43 
10.1.15 
Outcome ....................................................................................................43 
10.2 
Procedures ............................................................................................................44 
10.2.1 Collection and Reporting of AEs ......................................................................44 
10.2.1.1 PTE, AE, and ADR Collection Period ....................................................44 
10.2.1.2 PTE, AE, and ADR Reporting ................................................................44 
10.2.1.3 Adverse Event Collection Involving Medically Anticipated Clinical Events
 .............................................................................................................45 
10.2.2 Adverse event of special interest reporting ........................................................45 
10.2.3 Collection and Reporting of SAEs ....................................................................48 
10.2.4 Reporting of Abnormal Liver Tests ..................................................................49 
10.3 
Follow-up of SAEs................................................................................................49 
10.3.1 Safety Reporting to Investigators, IRBs/IECs, and Regulatory Authorities .........49 
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11.0 
STUDY-SPECIFIC COMMITTEES............................................................................50 
11.1 
Adjudication Committee........................................................................................50 
11.1.1 Risk Minimization Action Plan for PML (RAMP Program)...............................50 
12.0 
DATA HANDLING AND RECORDKEEPING ..........................................................51 
12.1 
CRFs (Electronic) .................................................................................................51 
12.2 
Record Retention...................................................................................................51 
13.0 
STATISTICAL METHODS ........................................................................................52 
13.1 
Statistical and Analytical Plans ..............................................................................52 
13.1.1 Analysis Sets ...................................................................................................52 
13.1.2 Analysis of Demographics and Other Baseline Characteristics ..........................52 
13.1.3 Primary (Safety) Analysis ................................................................................52 
13.1.3.1 Infections ..............................................................................................52 
13.1.3.2 Malignancies .........................................................................................53 
13.1.3.3 Infusion-Related Reaction and Hypersensitivity ......................................53 
13.1.3.4 Hepatic Injury........................................................................................53 
13.1.4 Analysis of Treatment Efficacy Endpoints ........................................................53 
13.1.5 Subgroup Analyses ..........................................................................................53 
13.2 
Determination of Sample Size................................................................................54 
14.0 
QUALITY CONTROL AND QUALITY ASSURANCE .............................................55 
14.1 
Study-Site Monitoring Visits .................................................................................55 
14.2 
Protocol Deviations ...............................................................................................55 
14.3 
Quality Assurance Audits and Regulatory Agency Inspections................................55 
15.0 
ETHICAL ASPECTS OF THE STUDY ......................................................................56 
15.1 
IRB/IEC Approval ................................................................................................56 
15.2 
Patient Information, Informed Consent, and Patient Authorization ..........................56 
15.3 
Patient Confidentiality ...........................................................................................57 
15.4 
Publication, Disclosure, and Clinical Trial Registration Policy ................................58 
15.4.1 Publication and Disclosure ...............................................................................58 
15.4.2 Clinical Trial Registration ................................................................................58 
15.4.3 Clinical Trial Results Disclosure ......................................................................58 
15.5 
Insurance and Compensation for Injury ..................................................................58 
REFERENCES ......................................................................................................................60 
LIST OF IN-TEXT TABLES 
Table 9. a 
Clinical Laboratory Tests .................................... Error! Bookmark not defined. 
Table 10. a 
Takeda Medically Significant AE List ................. Error! Bookmark not defined. 
LIST OF IN-TEXT FIGURE 
Figure 6. a Schematic of Study Design. ...................................................................................21 
LIST OF APPENDICES 
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Appendix A: Schedule of Study Procedures ............................................................................62 
Appendix B: Responsibilities of the Investigator ........................ Error! Bookmark not defined. 
Appendix C: Elements of the Patient Informed Consent...........................................................65 
Appendix D: Investigator Consent to Use of Personal Information ...........................................68 
Appendix E: Mayo Scoring System for the Assessment of Ulcerative Colitis Activity ..............69 
Appendix F: Harvey-Bradshaw Index for Crohn’s Disease ......................................................71 
Appendix G: Simple Clinical Colitis Activity Index (SCCAI) ..................................................73 
Appendix H: Simple Endoscopic Score for Crohn’s Disease (SES-CD)....................................75 
Appendix I: Short Inflammatory Bowel Disease Questionnaire (SIBDQ) .................................76 
Appendix J: Progresive Multifocal Leukoencephalopathy (PML) Symptom Checklist ..............80 
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2.0 
STUDY SUMMARY 
Name of Sponsor(s): 
Takeda Biopharmaceuticals India Pvt. Ltd 
Compound: 
Vedolizumab IV 
Title of Protocol: A Multicenter, Single-arm, Open-label, 
Phase 4 Study to Evaluate the Safety and Efficacy of 
Vedolizumab in Indian Patients With Ulcerative Colitis 
and Crohn’s Disease 
IND No.:  
Not Applicable 
EudraCT No.: 
Not Applicable 
Study Number: Vedolizumab-4020 
Phase: 4 
Study Design: 
This is an open-label, single-arm, prospective, Phase 4 study to be conducted at multiple sites in India to evaluate the 
safety and efficacy of vedolizumab 300 mg intravenous (IV) infusion in patients with moderately to severely active 
ulcerative colitis (UC) or Crohn’s Disease (CD). 
Approximately 150 patients with moderately to severely active UC or CD who have demonstrated inadequate 
response to, loss of response to, or intolerance to either conventional therapy or tumor necrosis factor-alpha (TNFα) 
antagonist will be enrolled in this study. At least 30% of the total recruited patients will be enrolled in each UC or 
CD group. 
The total duration of the study for each patient will be up to 74 weeks, consisting of a 4-week screening period 
(Days  -28 to -1), a 46-week treatment period, and 16-week (ie, 5 vedolizumab half-lives) safety follow-up period 
after the last dose of study drug. Additionally, patients will be required to participate in a long-term follow-up safety 
survey  through telephonic visit at 6 months after the last dose of study drug i.e. 8 weeks after 16-week follow-up 
visit. 
Patients who meet all the inclusion criteria and none of the exclusion criteria will be administered vedolizumab 
300 mg IV at the site. Patients will visit the site for dosing at Weeks 0 (Day 1), 2, 6, 10(CD  Patients who have not 
shown a response can receive a dose at 10 week),14, 22, 30, 38 and 46.  
Patients will be evaluated for safety and efficacy from initiation of vedolizumab treatment until 46 weeks (the 
treatment period), or until discontinuation of vedolizumab, whichever occurs earlier. All patients will be observed 
further for safety assessments for 16 weeks after the study treatment period or discontinuation of vedolizumab for 
post-treatment adverse event (AE) monitoring. In addition, patients will participate in the long-term follow-up safety 
survey through telephonic visit at 6 months after the last dose i.e. 8 weeks after the 16-week follow-up visit, during 
which information will be collected on events such as infections resulting in hospitalizations, cancer, UC or CD 
related surgeries, and development of progressive multifocal leukoencephalopathy. 
Primary Objective: 
• To assess the safety of vedolizumab IV in patients with UC or CD in India.
Secondary Objective: 
• To assess the efficacy of vedolizumab IV in patients with UC or CD in India.
Patient Population:  
Adult patients aged between 18 to 65 years both inclusive, with moderately to severely active UC or CD. 
Number of Patients: 
150 
Number of Sites:  
Approximately 20+ Sites in India 
Dose Level(s): 
Vedolizumab IV 300 mg 
Route of Administration: 
Intravenous 
Duration of Treatment: 
46-weeks 
Period of Evaluation: 
The study includes a 4-week screening period, a 
46-week treatment period, and a follow-up 
period of 6 months which includes first 
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follow-up visit at 16 weeks and second 
telephonic follow-up visit at 6 months after the 
last dose. The duration of the study for each 
patient will be approximately 74 weeks. 
Main Criteria for Inclusion: 
Adult patients aged 18 to 65 years both inclusive, diagnosed with moderately to severely active UC or CD for at 
least 3 months prior to screening with a Full Mayo Score of 6-12 for UC or a Harvey Bradshaw Index score of ≥8 
for CD at the time of enrollment, and have demonstrated an inadequate response to, loss of response to, or intolerance 
to either conventional therapy or tumor necrosis factor-alpha (TNFα) antagonist. 
Main Criteria for Exclusion: 
• 
Any evidence of an active infection during Screening 
• 
Patients who have received any biologics within 60 days (or 5-half-lives of the drug) of enrollment 
• 
Patients who have had prior exposure to vedolizumab, natalizumab, efalizumab, or rituximab 
Main Criteria for Evaluation and Analyses: 
Primary endpoint 
The primary endpoint includes: 
• 
Incidence of adverse events (AEs), serious AEs (SAEs), AEs of special interest (AESIs), adverse drug 
reactions (ADRs), and unexpected ADRs 
Secondary endpoints  
The secondary endpoints include: 
• 
Proportion of patients with clinical response at Weeks 14, 30, and 46 in UC and CD groups 
• 
Proportion of patients with clinical remission at Weeks 14, 30, and 46 in UC and CD groups 
• 
Proportion of patients with vedolizumab discontinuation in UC and CD groups 
• 
Proportion of patients with mucosal healing/endoscopic response at Week 46 in UC and CD groups 
• 
Change in the patient-reported Quality of Life (Short Inflammatory Bowel Disease Questionnaire) from 
baseline to Weeks 14, 30, and 46 
Statistical Considerations: 
Exposure-adjusted incidence rates and 95% confidence intervals (CIs) by Poisson method will be calculated for each 
safety endpoint based on total number of incident events and person-time at risk. 
The number and percentage of patients with treatment-emergent AEs (TEAEs; defined as any AEs, regardless of 
relationship to study drug), AEs leading to discontinuation, AESIs, and SAEs that occur on or after the first dose date 
and up to 6 months after the last dose date of the study drug, will be summarized by MedDRA system organ class, 
high level term, and preferred term overall, by severity, and by relationship to study drug.  
Treatment efficacy outcomes will be analyzed using descriptive statistics. 
Cox regression models may be used to explore predictors of time to treatment discontinuation . 
Sample Size Justification:  
The sample size of 150 patients was recommended by the Drugs Controller General of India (DCGI). At least 30% 
of the total recruited patients will be enrolled in each UC or CD group. This sample size will enable a serious 
infection rate of 6 per 100 person-years to be measured with a precision of ±3.8 with 95% CI based on a normal 
approximation of the annualized proportion of patients to be infected. This anticipated serious infection rate is based 
on observed rates in a post hoc pooled analysis of Indian sites participating in the vedolizumab global Phase 3 
Studies C13006 and C13007 and open label extension (Study C13008) of these studies. 
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3.0 
STUDY REFERENCE INFORMATION 
3.1 
Study-Related Responsibilities  
The sponsor will perform all study-related activities with the exception of those identified in the 
Study-Related Responsibilities template. The identified vendors for specific study-related 
activities will perform these activities in full or in partnership with the sponsor. 
3.2 
Principal Investigator/Coordinating Investigator  
Takeda will select a Signatory Coordinating Investigator from the investigators who participate in 
the study. Selection criteria for this investigator will include significant knowledge of the study 
protocol, the study drug, their expertise in the therapeutic area and the conduct of clinical research 
as well as study participation. The Signatory Coordinating Investigator will be required to review 
and sign the clinical study report and by doing so agrees that it accurately describes the results of 
the study. 
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3.3 
List of Abbreviations 
 
ADR 
Adverse Drug Reaction 
AE 
Adverse Event 
AESI 
Adverse Event of special interest 
ALT 
Alanine Aminotransferase 
AST 
Aspartate Aminotransferase 
β-hCG 
beta human chorionic gonadotropin 
CD 
Crohn’s Disease 
CI 
Confidence Interval  
CMV 
Cytomegalovirus 
CRO 
Contract Research Organization 
CRP 
C-reactive Protein 
DCGI 
Drugs Controller General of India 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Collection 
ET 
Early termination 
GCP 
Good Clinical Practice  
GI 
Gastrointestinal 
HBI 
Harvey-Bradshaw Index 
HBV 
Hepatitis B Virus 
HBsAg 
Hepatitis B surface antigen 
HCP 
Healthcare professional  
HCV 
Hepatitis C Virus 
HIV 
Human Immunodeficiency Virus 
HLT 
High-Level Term 
HRQoL 
Health-related quality of life 
IAC 
Independent Adjudication Committee 
IBD 
Inflammatory Bowel Disease 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
IEC 
Independent Ethics Committee  
INR 
International normalized ratio  
IRB 
Institutional Review Board 
IV 
Intravenous 
JC 
John Cunningham 
LAR 
Legally acceptable representative 
MAdCAM-1 
Mucosal Addressin Cell Adhesion Molecule-1 
MedDRA 
Medical Dictionary for Regulatory Activities 
PAC 
Patient alert card  
PV 
Pharamacovigilance 
PML 
Progressive multifocal leukoencephalopathy 
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PPAS 
Per-Protocol Analysis Set 
PT 
Preferred Term 
PTE 
Pretreatment Event 
QoL 
Quality of Life 
RAMP 
Risk Minimization Action Plan for PML 
SAE 
Serious Adverse Event 
SAS 
Safety analysis set 
SCCAI 
Simple Clinical Colitis Activity Index 
SES-CD 
Simple Endoscopic Score for Crohn’s Disease 
SIBDQ 
Short Inflammatory Bowel Disease Questionnaire 
SMQ 
Standardised MedDRA Queries 
SOC 
System Organ Class 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
TB 
Tuberculosis 
TDC 
Takeda Development Center 
TNF-α 
Tumor Necrosis Factor-alpha 
UC 
Ulcerative Colitis 
ULN 
Upper limit of normal 
WBC 
White blood cells 
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4.0 
INTRODUCTION 
4.1 
Background 
4.1.1 
The Inflammatory Bowel Diseases: Ulcerative Colitis and Crohn’s Disease 
Inflammatory bowel disease (IBD) encompasses ulcerative colitis (UC) and Crohn’s disease (CD), 
both of which are chronic, relapsing, and remitting inflammatory diseases. UC affects the colonic 
mucosa and submucosa, and CD may involve any portion of the gastrointestinal (GI) tract from 
mouth to anus, in a transmural fashion from mucosa to serosa. UC and CD are lifelong diseases that 
cause considerable morbidity in a relatively young patient population. The highest reported annual 
prevalence of UC and CD in North America was 249 per 100,000 persons and 319 per 100,000 
persons, respectively. In Europe, the highest annual reported prevalence of UC and CD was 505 per 
100,000 persons and 322 per 100,000 persons, respectively [1]. 
Incidence and prevalence in the Asia-Pacific region is comparatively lower, but reported to be rising 
rapidly [2]. Although, India is reported to have one of the highest incidence rates of UC in the 
Asia-Pacific region [2], there is still a paucity of recent prevalence and incidence data for IBD in 
India. A community-based study conducted in the year 1999 to 2000 [3] in Punjab, North India, 
reported an incidence and prevalence of UC of 6.02 per 100,000 patients (95% confidence interval 
[CI] 1.2 to 17.6) and 44.3 per 100,000 patients (95% CI 29.4 to 66.6) respectively [3]. 
Epidemiological data for CD in the Indian population is lacking. Higher rates of IBD have been 
observed among South Asian migrants (Indians, Bangladeshis and Pakistanis) compared with 
indigenous populations and other resident ethnic groups in studies in the United Kingdom, 
Singapore, and Malaysia, suggesting a genetic predisposition to IBD, particularly UC, among South 
Asians [2,4,5,6].  
While current conventional and biologic therapies have been effective for many patients with UC 
or CD, they have numerous limitations for patients with moderate to severe disease, posing a 
significant unmet medical need for safer and more effective therapies. Conventional therapies for 
UC and CD include 5-aminosalicylic acids, corticosteroids, and immunomodulators such as 
azathioprine, 6-mercaptopurine, and methotrexate. Biologic therapy is largely limited to tumor 
necrosis factor-alpha (TNF-α) antagonists which represent an important addition to the 
pharmacologic armamentarium. However, TNF-α antagonists are effective in only a subset of 
patients, with approximately two-thirds of patients in controlled trials failing treatment at the end 
of the first year of therapy [7,8,9].  
Therefore, it is clear that current treatments do not sufficiently address the unmet need in this 
population, with many patients still requiring frequent hospitalization, serial bowel resections, 
colectomies, and enteral nutrition, and regularly experiencing fistulae, GI abscesses, refractory 
diarrhea, and rectal bleeding. These patients are often unable to function normally in society. 
4.1.2 
Vedolizumab 
Vedolizumab is a humanized immunoglobulin G1 monoclonal antibody directed against the human 
lymphocyte integrin α4β7. The α4β7 integrin mediates lymphocyte trafficking to GI mucosa and gut-
associated lymphoid tissue through adhesive interactions with mucosal addressin cell adhesion 
molecule-1 (MAdCAM-1), which is expressed on the endothelium of mesenteric lymph nodes and 
GI mucosa. Vedolizumab exclusively targets the 47 integrin, antagonizing its adherence to 
MAdCAM-1 and thus impairing the migration of leukocytes into GI mucosa [10]. By virtue of its 
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gut-selective mechanism of action, vedolizumab is expected to have anti-inflammatory activity 
without the generalized immunosuppression found with current treatments for UC or CD. 
Detailed information regarding nonclinical and clinical pharmacology, toxicology, and clinical 
studies of vedolizumab is found in package insert. 
4.1.2.1 
Trial Data for UC 
The safety and efficacy of vedolizumab intravenous (IV) for the treatment of patients with 
moderately to severely active UC (Complete Mayo Score 6 to 12 with endoscopic subscore ≥2) 
was demonstrated in a randomized, double-blind, placebo-controlled study, comprising 2 phases 
and evaluating efficacy endpoints at Weeks 6 and 52 (C13006). Enrolled subjects had failed 
treatment with corticosteroids, immunomodulators, and/or TNF-α antagonists. 
Vedolizumab IV subjects with UC had a statistically significant improvement in clinical response, 
clinical remission, mucosal healing, durable clinical response, durable clinical remission, and 
corticosteroid-free remission compared with placebo. The beneficial effect of vedolizumab IV on 
clinical remission was observed both in UC subjects with no prior TNF-α antagonist exposure, as 
well as in those who had failed prior TNF-α antagonist therapy. 
4.1.2.2 
Trial Data for Crohn’s Disease 
The safety and efficacy of vedolizumab IV for the treatment of patients with moderately to severely 
active CD (Crohn’s Disease Activity Index score of 220 to 450) was evaluated in 2 studies (C13007 
and C13011). Study C13007 was a randomized, double-blind, placebo-controlled study comprising 
2 phases that evaluated efficacy endpoints at Weeks 6 and 52. Study C13011 was a randomized, 
double-blind, placebo-controlled study that evaluated efficacy at Weeks 6 and 10 in the subgroup 
of subjects defined as having failed TNF-α antagonist therapy, as well as in the overall population, 
which included subjects naïve to TNF-α antagonist therapy. 
In Study C13007, overall, a significantly higher proportion of vedolizumab IV subjects with CD, 
achieved clinical remission at Week 52, compared with placebo subjects. In Study C13011, the 
subset of vedolizumab IV subjects who had failed prior TNF-α antagonist therapy did not 
demonstrate significant benefit relative to placebo by Week 6. However, by Week 10, a higher 
proportion of vedolizumab IV subjects with CD who had failed prior TNF-α antagonist therapy 
achieved clinical remission. 
4.1.2.3 
Safety Profile for UC and CD 
In the pivotal Phase 3 study in UC (C13006), 12% of vedolizumab IV-treated subjects experienced 
a serious adverse event (SAE), compared with 11% of placebo-treated subjects. The most frequent 
SAE was UC, which occurred in 8% and 7% of vedolizumab- and placebo-treated subjects, 
respectively. Two percent of vedolizumab IV-treated subjects had at least 1 SAE in the infections 
and infestations system organ class (SOC), as compared with 3% of the placebo-treated subjects. 
The most common adverse drug reactions (ADRs) occurring in ≥3% of vedolizumab IV subjects, 
and in excess of 1% over placebo subjects included nasopharyngitis, headache, and cough. 
In the pivotal Phase 3 study of induction and maintenance in CD (C13007), 24% of vedolizumab 
IV-treated subjects experienced at least 1 SAE, compared with 16% of placebo-treated subjects. GI 
disorders were very common (16% of vedolizumab- and 12% of placebo-treated subjects), with CD 
being the most common SAE (12% and 9%, respectively). SAEs within the infections and 
infestations SOC were also common (6% and 3%, respectively), with anal abscess being the most 
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common SAE reported within this SOC (2% and <1%, respectively). The most common of the 
ADRs occurring in more than 3% of vedolizumab IV subjects and in excess of ≥1% over placebo 
subjects in Study C13007 were pyrexia, nasopharyngitis, nausea, and arthralgia. 
In a pivotal Phase 3, placebo-controlled study of vedolizumab IV induction treatment in CD 
(C13011), subjects received vedolizumab 300 mg IV or placebo at Weeks 0, 2, and 6. The majority 
of subjects had failed therapy with at least 1 TNF-α antagonist before enrollment. Safety data 
observed in the TNF-α antagonist failure safety subpopulation were generally similar to those 
observed in the overall safety population. 
An open-label study of vedolizumab 300 mg IV, every 4 weeks, is ongoing to evaluate long-term 
safety in subjects with CD or UC who had previously been enrolled in a vedolizumab IV study 
(rollover patients); de novo subjects (not previously enrolled in vedolizumab studies) were also 
enrolled. Results from an interim analysis of the safety data from rollover subjects appear to be 
consistent with the data from placebo-controlled clinical studies of vedolizumab IV. 
In pivotal Phase 3 studies, other reported SAEs, including extraintestinal infections (bronchitis, 
pneumonia, urinary tract infection, sepsis), were uncommon (<1%). Malignancy was diagnosed in 
15 subjects receiving vedolizumab IV across all clinical studies (9 subjects with UC and 6 subjects 
with CD). Patients with IBD have an increased risk for colon cancer [1], and colon cancer was 
reported in 4 vedolizumab IV-treated subjects; carcinoid tumor of the appendix was diagnosed in 1 
vedolizumab IV-treated subject. One case of B-cell lymphoma was reported in a subject who had 
received 21 infusions of vedolizumab IV. 
4.1.2.4 
Indian Experience 
A total of 92 subjects from India were enrolled in studies C13006 and C13007. Sixty-four Indian 
subjects (40 subjects with UC and 24 subjects with CD) received vedolizumab during these clinical 
studies. Post hoc descriptive subgroup analyses of efficacy in these trials showed similar favorable 
changes in disease status associated with vedolizumab treatment among subjects with UC and CD. 
This supports the use of vedolizumab in adult Indian patients as an efficacious therapeutic option for 
UC and CD.Post hoc analysis of safety data for the Indian subjects demonstrated no significant 
differences in the types of adverse events (AEs)/SAEs observed compared with the overall global 
population. Overall, 84% of the global subjects and 61% of the Indian subjects who received 
vedolizumab experienced at least 1 AE. Interim analysis (data cut off 08 May 2015) of an ongoing 
long-term open-label safety study (C13008) showed the safety profile in global and Indian subjects 
to be consistent with that seen in the pivotal studies. 
4.2 
Rationale for the Proposed Study 
The Drugs Controller General of India (DCGI) , has, as a requirement for the vedolizumab marketing 
authorization approval in India, requested a study to generate data on the safety of vedolizumab in 
India. Accordingly, the current study has been planned with the primary safety endpoint to provide 
such data. 
4.3 
Benefit/Risk Profile  
Data on the safety profile of vedolizumab is somewhat limited in India. This Phase 4 study is designed 
to gather important information on the safety and efficacy of vedolizumab in patients with UC and 
CD. The dosing and administration regimen and study population in this study are consistent with 
the approved vedolizumab IV label. Overall, vedolizumab has been well tolerated in clinical studies. 
The procedures performed during the study are part of usual clinical practice. Taking into account 
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the risks associated with procedures and the disease worsening in this population, the benefit-risk 
profile remains positive for vedolizumab in this study. 
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5.0 
STUDY OBJECTIVES AND ENDPOINTS 
5.1 
Objectives 
5.1.1 
Primary objective 
• To assess the safety of vedolizumab IV in patients with UC or CD in India 
5.1.2 
Secondary objective 
• To assess the efficacy of vedolizumab IV in patients with UC or CD in India 
5.2 
Endpoints 
5.2.1 
Primary endpoint 
The primary endpoint include: 
• 
Incidence of AEs, SAEs, AEs of special interest (AESIs), ADRs, and unexpected ADRs 
(Definitions are provided in Section 10.0). 
5.2.2 
Secondary endpoints  
The secondary endpoints include: 
• Proportion of patients with clinical response at Weeks 14, 30, and 46 in UC and CD groups 
• Proportion of patients with clinical remission at Weeks 14, 30, and 46 in UC and CD groups 
• Proportion of patients with vedolizumab discontinuation in UC and CD groups 
• Proportion of patients with mucosal healing/endoscopic response at Week 46 in UC and CD 
groups 
• Change in the patient-reported Quality of Life (Short Inflammatory Bowel Disease 
Questionnaire [SIBDQ]) from baseline to Weeks 14, 30, and 46 
(Definitions are provided in Section 9.1.9).
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6.0 
STUDY DESIGN AND DESCRIPTION 
6.1 
Study Design 
This is an open-label, single-arm, prospective, Phase 4 study to be conducted at multiple sites in India 
to evaluate the safety and efficacy of vedolizumab 300 mg IV infusion in patients with moderately 
to severely active UC or CD. 
Approximately 150 patients with moderately to severely active UC or CD who have demonstrated 
inadequate response to, loss of response to, or intolerance to either conventional therapy or tumor 
necrosis factor-alpha (TNFα) antagonist will be enrolled in this study. At least 30% of the total 
recruited patients will be enrolled in each UC or CD group. 
 The total duration of the study for each patients will be up to 74 weeks, consisting of a 4-week 
screening period (Days -28 to -1), a 46-week treatment period, and 16-week (ie, 5 vedolizumab 
half-lives) safety follow-up period after the last dose of study drug. Additionally, patients will be 
required to participate in a long-term follow-up safety survey through telephonic visit at 6 months 
after the last dose of study drug i.e. 8 weeks after the 16-week follow-up visit. 
Patients who meet all the inclusion criteria and none of the exclusion criteria will be administered 
vedolizumab 300 mg IV at the site. Patients will visit the site for dosing at Weeks 0 (Day 1), 2, 6, 10 
(CD- Patients who have not shown a response can receive a dose at 10 week),14, 22, 30, 38, and 46.  
Patients will be evaluated for safety and efficacy from initiation of vedolizumab until 46 weeks (the 
treatment period), or until discontinuation of vedolizumab, whichever occurs earlier. All patients 
will be observed further for safety assessments for 16 weeks after the study treatment period or 
discontinuation of vedolizumab for post-treatment AE monitoring. 
In addition, patients will participate in the long-term follow-up safety survey through telephonic 
visit at 6 months after the last dose i.e. 8 weeks after the 16-week follow-up visit, during which 
information will be collected on events such as infections resulting in hospitalizations, cancer, UC 
or CD related surgeries, and development of progressive multifocal leukoencephalopathy (PML). 
A schematic of the study design is included as Figure 6-a. A Schedule of Study Procedures is listed 
in Appendix A.  
Figure 6-a: Schematic of Study Design. 
 
 
 
 
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6.2 
Justification for Study Design, Dose, and Endpoints 
The study is being undertaken to collect data on the safety and efficacy of vedolizumab in Indian 
patients with moderately to severely active UC or CD for regulatory submission. DCGI has granted 
marketing authorization for vedolizumab in India based on efficacy studies of vedolizumab in UC 
and CD conducted across the globe; and so, safety data of vedolizumab in Indian patients needs to 
be submitted to DCGI. A Phase 4 study design is the most appropriate design to generate such data, 
as the focus of the study is primarily to collect information on safety and to additionally explore the 
clinical efficacy of the study drug.  
Vedolizumab 300 mg IV infusion is approved for the indications planned to be studied. The safety 
and treatment efficacy endpoints are similar to those used in other outcome studies in UC and CD. 
The study period of 74 weeks includes a 4 weeks screening period, 46 weeks treatment period and 
6 months safety monitoring period (16 weeks follow-up visit and 6 months telephonic visit). This 
study duration will help us in reporting safety endpoints of interest including AEs, SAEs, ADRs, and 
AESIs. 
6.3 
Premature Termination or Suspension of Study or Study Site 
6.3.1 
Criteria for Premature Termination or Suspension of the Study 
The study will be completed as planned unless 1 or more of the following criteria are satisfied that 
require temporary suspension or early termination of the study. 
• New information or other evaluation regarding the safety or efficacy of the study drug that 
indicates a change in the known risk/benefit profile for the vedolizumab, such that the risk/benefit 
is no longer acceptable for patients participating in the study. 
• Significant violation of Good Clinical Practice (GCP) that compromises the ability to achieve the 
primary study objectives or compromises patient safety. 
6.3.2 
Criteria for Premature Termination or Suspension of Study Sites 
A study site may be terminated prematurely or suspended if the site (including the investigator) is 
found in significant violation of GCP, protocol, or contractual agreement, is unable to ensure 
adequate performance of the study, or as otherwise permitted by the contractual agreement. 
6.3.3 
Procedures for Premature Termination or Suspension of the Study or the 
Participation of Study Site(s) 
In the event that the sponsor, an Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC) or regulatory authority elects to terminate or suspend the study or the participation of a study 
site, a study-specific procedure for early termination or suspension will be provided by the sponsor; 
the procedure will be followed by applicable study sites during the course of termination or study 
suspension.
 
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7.0 
 SELECTION AND DISCONTINUATION/WITHDRAWAL OF PATIENTS 
All entry criteria, including test results, need to be confirmed prior to the first dose.  
7.1 
Inclusion Criteria 
Patient eligibility is determined according to the following criteria before entry into the study: 
1. 
In the opinion of the investigator, the patient (or, when applicable, the patient’s legally 
acceptable representative) is capable of understanding and complying with the protocol 
requirements and able to provide a signed and dated written informed consent form (ICF) and 
any required privacy authorization prior to the initiation of any study procedures. 
2. 
The patient is aged between 18 to 65 years both inclusive at the screening visit. 
3. 
The patient has a diagnosis of moderately to severely active UC or CD at least 3 months prior 
to screening, with a Full Mayo Score of 6-12 for UC and a Harvey Bradshaw Index (HBI) 
score of ≥8 for CD at the time of enrollment. 
4. 
The patient has UC or CD with involvement of the ileum and/or colon that has been assessed 
by colonoscopy/ileo-colonoscopy as applicable within 30 days before or at the time of 
screening.  
5. 
Patients with extensive colitis or pancolitis of >8 years duration or left-sided colitis >12 years 
duration must have documented evidence that a surveillance colonoscopy was performed 
within 12 months of the initial Screening Visit (if not performed in previous 12 months, must 
be performed during Screening). 
6. 
The patient has demonstrated, an inadequate response to, loss of response to, or intolerance 
to at least 1 of the following agents: 
a. Conventional therapy 
b. TNF-α alpha antagonist 
7. 
A male patient who is nonsterilized* and sexually active with a female partner of childbearing 
potential* agrees to use adequate contraception* from signing of informed consent 
throughout the duration of the study and for 16 weeks after last dose. 
8. 
A female patient of childbearing potential* who is sexually active with a nonsterilized* male 
partner agrees to use routinely adequate contraception* from signing of informed consent 
throughout the duration of the study and for 16 weeks after last dose. Female patient not of 
childbearing potential are defined as those who have been surgically sterilized (hysterectomy, 
bilateral oophorectomy, or tubal ligation) or who are postmenopausal (eg, defined as at least 
1 year since last regular menses with an appropriate clinical profile [ie, age appropriate, 
history of vasomotor symptoms] , confirmed before any study drug is implemented). 
*Definitions and highly effective methods of contraception are defined in Section 9.1.14 and 
pregnancy reporting responsibilities are defined in Section 9.1.15. 
7.2 
Exclusion Criteria 
Any patient who meets any of the following criteria will not qualify for entry into the study:  
1. 
The patient has an evidence of abdominal abscess at the screening visit. 
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2. 
The patient has a history of extensive colon resections, subtotal or total colectomy.  
3. 
The patient has undergone an ileostomy, colostomy, or has known fixed symptomatic stenosis 
of the intestine. 
4. 
The patient has active or latent tuberculosis (TB). 
5. 
The patient has hepatitis B virus (HBV) or hepatitis C virus (HCV) infection; has any 
identified 
congenital 
or 
acquired 
immunodeficiency 
(eg, 
common 
variable 
immunodeficiency, human immunodeficiency virus [HIV] infection, organ transplantation). 
6. 
The patient has evidence of active Clostridium difficile infection or is having treatment for C. 
difficile infection or other intestinal pathogens during Screening or has evidence of an active 
infection during Screening. 
7. 
The patient currently requires or has a planned surgical intervention for the indication to be 
studied during the study. Patients who had a surgical procedure requiring general anesthesia 
within 30 days prior to screening or are planning to undergo major surgery during the study 
period will also be excluded from the study. 
8. 
The patient has received any investigational compound within 60 days of enrollment. 
9. 
The patient has received any live vaccinations within 30 days prior to enrollment. 
10. 
The patient has received any biologics within 60 days (or 5-half-lives of the drug) of 
enrollment. 
11. 
The patient has had a prior exposure to vedolizumab or a history of hypersensitivity or 
allergies to vedolizumab, natalizumab, efalizumab, or rituximab. 
12. 
The patient has any unstable or uncontrolled cardiovascular, pulmonary, hepatic, renal, GI, 
genitourinary, hematological, coagulation, immunological, endocrine/metabolic, an active 
psychiatric problem, or other medical disorder that, in the opinion of the investigator, would 
confound the study results or compromise patient safety. 
13. 
The patient has a history of malignancy. 
14. 
The patient has any of the following laboratory abnormalities during the Screening Period: 
a. Hemoglobin level <8 g/dL 
b. White blood cell (WBC) count <3 x 109/L 
c. Platelet count <100 x 109/L or >1200 x 109/L 
d. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 x the 
upper limit of normal (ULN) 
e. Serum creatinine >2 x ULN 
15. 
The patient has a history of any major neurological disorder, including stroke, multiple 
sclerosis, brain tumor, or neurodegenerative disease 
16. 
The patient has a positive PML subjective symptom checklist during screening or prior to the 
administration of study drug on Day 1 (Appendix J). 
17. 
The patient has a history of drug abuse (defined as any illicit drug use) or a history of alcohol 
abuse within 1 year prior to enrollment. 
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18. 
If female, the patient is pregnant or lactating or intending to become pregnant before, during, 
or within 16 weeks after completion of participation in the study; or intending to donate ova 
during such time period. 
19. 
If male, the patient intends to donate sperm during the course of this study or for 16 weeks 
thereafter. 
20. 
The patient is an immediate family member, study site employee, or is in a dependent 
relationship with a study site employee who is involved in conduct of this study (eg, spouse, 
parent, child, sibling) or may consent under duress. 
21. 
The patient has conditions which, in the opinion of the investigator, may interfere with the 
patient’s ability to comply with the study procedures. 
7.3 
Permitted Medications 
The medication that is permitted and can be co-administered with vedolizumab for the treatment of 
UC or CD should be consistent with prescribing information of vedolizumab. 
7.3.1 
Oral Corticosteroid Dosing and Tapering 
The maximum dose of oral corticosteroids for the treatment of UC or CD that may be co-administered 
with vedolizumab as a long-term regimen is prednisone 30 mg/day or budesonide 9 mg/day with 
6 mg/day for maintenance (or equivalent) as long as they have been stable for at least 4 weeks prior 
to enrollment or for 2 weeks prior to enrollment if being tapered. Short-term use (≤4 weeks) of higher 
doses is acceptable; however, patients who require consistent higher doses should be withdrawn from 
the study. 
7.4 
Criteria for Discontinuation or Withdrawal of a Patient 
The primary reason for discontinuation or withdrawal of the patient from the study or study drug 
should be recorded in the electronic case report form (eCRF) using the following categories. For 
screen failure patients, refer to Section 9.1.19. 
1. Pretreatment event (PTE) or AE. The patient has experienced a PTE or AE that requires early 
termination because continued participation imposes an unacceptable risk to the patient’s health 
or the patient is unwilling to continue because of the PTE or AE (Refer to Section 10.1 for 
definitions of AEs). 
2. Liver Test Abnormalities. 
Study drug should be discontinued immediately with appropriate clinical follow-up (including repeat 
laboratory tests, until a patient’s laboratory profile has returned to normal/baseline status, see Section 
9.1.12), if the following circumstances occur at any time during study drug treatment: 
– ALT or AST >8 × ULN, or 
– ALT or AST >5 × ULN and persists for more than 2 weeks, or 
– ALT or AST >3 × ULN in conjunction with elevated total bilirubin >2 × ULN or 
international normalized ratio (INR) >1.5, or 
– ALT or AST >3 × ULN with appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%). 
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3. Significant protocol deviation. If patient failed to meet protocol entry criteria or did not adhere 
to protocol requirements, and continued participation poses an unacceptable risk to the patient’s 
health. 
4. Lost to follow-up. The patient did not return to the clinic and attempts to contact the patient were 
unsuccessful. Attempts to contact the patient must be documented in the patient’s source 
documents.  
5. Voluntary withdrawal. The patient (or patient’s legally acceptable representative) wants to 
withdraw from the study. The reason for withdrawal, if provided, should be recorded in the eCRF. 
Note: All attempts should be made to determine the underlying reason for the withdrawal and, 
where possible, the primary underlying reason should be recorded (ie, withdrawal due to an 
AE or lack of efficacy). 
6. Study termination. The sponsor, IRB/IEC, or regulatory agency terminates the study. 
7. Pregnancy. The patient is found to be pregnant. 
Note: If the patient is found to be pregnant, the patient must be withdrawn immediately. The 
procedure is described in Section 9.1.15. 
8. Lack of efficacy. The investigator has determined that the patient is not benefiting from 
investigational treatment; and, continued participation would pose an unacceptable risk to the 
patient. Lack of efficacy is defined as evidence of active inflammation despite an adequate 
course of treatment (3 induction doses) eg, no change or even elevation of scores above baseline 
(Simple Clinical Colitis Activity Index [SCCAI] for UC and HBI for CD). 
Note:-  
• CD Patients not showing any evidence of benefit  at 14 weeks should discontinue 
Vedolizumab 
• UC  Patients not showing any evidence of benefit at 10 weeks should discontinue 
Vedolizumab 
 
9. Others.  
Note: The specific reasons should be recorded in the “specify” field of the eCRF. 
7.5 
Procedures for Discontinuation or Withdrawal of a Patient 
The investigator may discontinue a patient’s study participation at any time during the study when 
the patient meets the study termination criteria described in Section 7.4. In addition, a patient may 
discontinue his or her participation without giving a reason at any time during the study. Should a 
patient’s participation be discontinued, the primary criterion for termination must be recorded by the 
investigator. In addition, all procedures scheduled for the Early Termination Visit should be done. 
Discontinued or withdrawn patients will not be replaced.
 
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8.0 
CLINICAL STUDY MATERIAL MANAGEMENT 
This section contains information regarding all medications and materials provided directly by the 
sponsor, and/or sourced by other means, that are required by the study protocol, including important 
sections describing the management of study material. 
8.1 
Study Drug and Materials 
8.1.1 
Dosage Form, Manufacturing, Packaging, and Labeling 
8.1.1.1 
Vedolizumab IV 
The study sites will be supplied by the sponsor with the following drug in an open-label manner: 
vedolizumab (Kynteles) IV 300 mg/vial, for single use, in 20 mL vials. The study drug will be 
provided in a glass vial as a white to off-white lyophilized solid formulation for reconstitution using 
sterile water. Each vial will be packaged in an appropriately labeled single vial carton, as per the New 
Drugs and Clinical Trials Rule, 2019. 
Each carton will have a single-panel package insert that will contain, but will not be limited to the 
following: sponsor’s name and address, protocol number, packaging job/lot number, name and 
strength of the product, drug identification number, patient information, caution statement, directions 
for use, and storage conditions. 
Each carton will also contain patient alert card (PAC) along with package insert. This PAC will be 
distributed to the patients by the healthcare professional (HCP). The objective of providing PAC is 
to alert patients about the early signs and symptoms of PML and to remind patients that they may be 
at risk of infections and should consult HCP if they are unwell. 
Vedolizumab lyophilized powder must be reconstituted with sterile water for injection and diluted in 
250 mL of sterile 0.9% sodium chloride injection prior to administration. After the infusion is 
complete, 30 mL of sterile 0.9% sodium chloride injection will be flushed. Refer to vedolizumab 
package insert for detailed instructions on reconstitution and dilution. 
8.1.2 
Storage 
Investigational drug must be kept in an appropriate, limited-access, secure place until it is used or 
returned to the sponsor or designee for destruction. Investigational drug must be stored under the 
conditions specified on the label, and remain in the original container until dispensed. 
Vedolizumab IV must be stored at 2ºC to 8ºC (36ºF to 46ºF). A daily temperature log of the drug 
storage area must be maintained every working day. Refer to vedolizumab label for details on 
storage of reconstituted and diluted solutions. 
8.1.3 
Dose and Regimen 
The dose and dosing regimen for all patients is provided below. 
Treatment Group 
Dose 
Treatment Description 
All patients 
Vedolizumab IV 300mg 
Induction Phase: Weeks 0 (Day 1), 2, and 6 
Maintenance Phase: Weeks 14, 22, 30, 38, 46 
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Note:- 
CD Patients who have not shown a response can receive a dose (300 mg IV) at 10 week 
Patients who have shown a decrease in response can receive a 4 weekly Vedolizumab 300 mg IV 
No dose modifications will be allowed during the study.   
8.1.4 
Overdose 
An overdose is defined as a known deliberate or accidental administration of study drug, to or by a 
study patient, at a dose above that which is assigned to that individual patient according to the study 
protocol. All cases of overdose (with or without associated AEs) will be documented on an overdose 
page of the eCRF, in order to capture the important safety information consistently in the database. 
Cases of overdose without manifested signs or symptoms are not considered AEs. AEs associated 
with an overdose will be documented on AE page of eCRFs according to Section 10.0. 
SAEs associated with overdose should be reported according to the procedure outlined in Section 
10.2.3. 
In the event of drug overdose, the patient should be treated symptomatically. 
8.2 
Study Drug Assignment and Dispensing Procedures 
Since this is an open-label single-arm study, randomization procedures will not be applicable for this 
study. Patients will receive treatment sequentially as they enter the study and according to the study 
schedule. The patient identification number will be entered in to the eCRF. 
8.3 
Accountability and Destruction of Sponsor-Supplied Drugs 
Drug supplies will be counted and reconciled at the site before being returned to the sponsor or 
designee.The investigator or designee must ensure that the sponsor-supplied drug is used in 
accordance with the protocol and is dispensed only to patients enrolled in the study. To document 
appropriate use of sponsor-supplied drug (vedolizumab IV 300 mg), the investigator or designee must 
maintain records of all sponsor-supplied drug delivery to the site, site inventory, dispensation and 
use by each patient, and return to the sponsor or designee. Upon receipt of sponsor-supplied drug, 
the investigator or designee must verify the contents of the shipments against the packing list. The 
verifier should ensure that the quantity is correct, and the drug is in good condition. If quantity and 
conditions are acceptable, investigator or designee should acknowledge the receipt of the shipment. 
If there are any discrepancies between the packing list versus the actual product received, Takeda 
must be contacted to resolve the issue. The packing list should be filed in the investigator’s essential 
document file. The investigator or designee must maintain 100% accountability for all sponsor-
supplied drugs received and dispensed during his or her entire participation in the study. Proper drug 
accountability includes, but is not limited to:  
• Frequently verifying that actual inventory matches documented inventory. 
• Verifying that the log is completed with the drug identification used to prepare each 
dose. 
• Verifying that all containers used are documented accurately on the log. 
• Verifying that required fields are completed accurately and legibly. 
If any dispensing errors or discrepancies are discovered, the sponsor must be notified immediately. 
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The investigator or designee must record the current inventory of all sponsor-supplied drugs on a 
sponsor-approved drug accountability log. The following information will be recorded at a 
minimum: protocol number and title, name of investigator, site identifier and number, description 
of sponsor-supplied drugs, date and amount dispensed including initials, seal, or signature of the 
person dispensing the drug. 
Prior to site closure or at appropriate intervals, a representative from the sponsor or its designee will 
perform sponsor-supplied drug accountability and reconciliation before sponsor-supplied drugs are 
returned to the sponsor or its designee for destruction. The investigator or designee will retain a 
copy of the documentation regarding sponsor-supplied drug accountability, return, and/or 
destruction, and originals will be sent to the sponsor or designee. 
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9.0 
STUDY PLAN 
9.1 
Study Procedures 
The following sections describe the study procedures and data to be collected. For each procedure, 
patients are to be assessed by the same investigator or site personnel whenever possible. The Schedule 
of Study Procedures is located in Appendix A. 
9.1.1 
Informed Consent Procedure 
The requirements of the informed consent are described in Section 15.2. 
Informed consent must be obtained prior to the patient entering into the study, and before any 
protocol-directed procedures are performed. 
A unique patient identification number (patient number) will be assigned to each patient at the time 
of screening; this patient number will be used throughout the study. 
9.1.2 
Demographics, Medical History, and Medication History  
At screening, demographic information to be obtained will include date of birth and sex. Patient’s 
smoking and alcohol intake history will also be collected. 
Medical history to be obtained will include any significant conditions or diseases relevant to the 
disease under study that stopped at or prior to signing of informed consent. Ongoing conditions will 
be considered concurrent medical conditions (see Section 9.1.13).  
Medication history will include any medication relevant to eligibility criteria, concomitant 
medication, and medications stopped at or within 30 days prior to signing of informed consent. 
In addition, all prior biologic medication history for the treatment of UC or CD with the reason for 
discontinuation will be collected for patients where possible. 
9.1.3 
Physical Examination Procedure 
A baseline physical examination (defined as the assessment prior to first dose of study drug) will 
consist of the following body systems: (1) eyes; (2) ears, nose, throat; (3) cardiovascular system; 
(4) respiratory system; (5) gastrointestinal system; (6) dermatologic system; (7) extremities; (8) 
musculoskeletal system; (9) nervous system; (10) lymph nodes; and (12) others. All subsequent 
physical examinations will assess clinically significant changes from the assessment prior to first 
dose examination. 
9.1.4 
Weight and Height  
A patient should have weight and height measured while wearing indoor clothing and with shoes off. 
The Takeda standard for collecting height is centimeters without decimal places and for weight it is 
kilograms (kg) with 1 decimal place. 
9.1.5 
Vital Sign Procedures 
Vital signs will include body temperature, respiratory rate, blood pressure, and pulse (beats per 
minute). If the vital signs are scheduled at the same time as blood draws, the blood draw will take 
priority and vital signs will be obtained within 0.5 hours before or after the scheduled blood draw. 
On dosing days, vitals are taken predose. 
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9.1.6 
Ulcerative colitis/Crohn’s Disease Presentation at Screening/Baseline 
• UC/CD disease activity assessment at Screening: Full Mayo Score (UC patients) and 
HBI (CD patients). The components of the Full Mayo Score and HBI to determine 
eligibility must be completed within 14 days prior to enrollment. 
• UC/CD disease activity assessment at baseline: Simple Clinical Colitis Activity Index 
(SCCAI) (UC patients) and HBI (CD patients). 
• Endoscopic or imaging assessments: For UC, endoscopy is scored using the Mayo 
Score (Appendix E). For CD, endoscopy is scored using the Simple Endoscopic Score 
for Crohn’s Disease (SES-CD) (Appendix H). 
9.1.6.1 
Full Mayo Score 
The Full Mayo Score evaluates ulcerative colitis stage, based on four parameters: stool frequency, 
rectal bleeding, endoscopic evaluation, and Physician’s global assessment. Each parameter of the 
score ranges from zero (normal or inactive disease) to 3 (severe activity) [11]. The scores 0-2 are 
considered as clinical remission, 3-5 mild, 6-10 moderate, and 11-12 severe (Appendix E). 
9.1.6.2 
Simple Clinical Colitis Activity Index 
SCCAI is composed of six domains: bowel frequency (during the day) ranging from 0 to >9; bowel 
frequency (during the night) ranging from 0 to 6; urgency of defecation ranging from none to 
incontinence; blood in stool ranging from none to usually frank (>50% of defecation); general well-
being ranging from very well to terrible; and a number of defined extracolonic features of UC (ie. 
arthritis, erythema nodosum, pyoderma gangrenosum, and uveitis). The score of <5 is considered as 
inactive disease and score of ≥5 is active disease [12] (Appendix G). 
9.1.6.3 
Harvey Bradshaw Index 
The HBI was conceived in 1980 as a simplified version of the Crohn's Disease Activity Index to 
foster a systematic collection of clinical data related to CD. The index evaluates five clinical 
parameters: general well-being, abdominal pain, number of liquid stools per day, abdominal mass, 
and complications [13]. The score <5 is considered as clinical remission, 5-7 mild, 8-16 moderate, 
and >16 severe disease (Appendix F). 
9.1.6.4 
Simple Endoscopic Score for Crohn Disease Score 
The SES-CD assesses the size of mucosal ulcers, the ulcerated surface, the endoscopic extension, 
and the presence and type of narrowings in each bowel segment (ileum, [right/transverse/left] colon, 
and rectum). Each of the four SES-CD variables is scored from 0 to 3, with the sum of the scores for 
each variable ranging from 0 to 15 yielding a total SES-CD score of 0–60. More specifically, 
ileocolonoscopic findings can be scored according to SES-CD as following: presence and size of 
ulcers (none = 0; diameter 0.1–0.5 cm = 1; 0.5–2 cm = 2; >2 cm = 3); extent of ulcerated surface 
(none = 0; <10% = 1; 10%–30% = 2; >30% = 3); extent of affected surface (none = 0; <50% = 1; 
50%–75% = 2; >75% = 3); and presence and type of narrowings (none = 0; single, can be passed = 
1; multiple, can be passed = 2; cannot be passed = 3) [14]. The score 0-2 is considered as clinical 
remission, 3-6 mild, 7-15 moderate, and >15 severe (Appendix H). 
9.1.7 
Principal Investigator Reported Outcome Measures 
The investigator will complete the Full Mayo Score and HBI questionnaires at the time of screening 
to assess the UC/CD disease activity for enrollment. 
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The investigator will also complete the SCCAI and HBI questionnaires at the time points specified 
in the Schedule of Study Procedures post-screening to assess UC/CD disease activity for efficacy 
assessments. 
9.1.8 
PML Checklist 
Clinic staff will administer the subjective PML checklist during screening to exclude patients with 
positive responses from enrolling into the study. The subjective PML checklist will be administered 
(prior to dosing) at each visit, as shown in Appendix J, to evaluate symptoms suggestive of PML. 
Any patients reporting signs or symptoms of PML will undergo objective testing and may be referred 
to a neurologist for a full evaluation, as described in the Risk Assessment and Minimization for PML 
(RAMP) Algorithm referenced in Section 11.1.1. The symptoms from a positive PML checklist will 
be recorded as an AE. Additional information and tools for the RAMP can be found in the Study 
Manual. 
9.1.9 
Efficacy measurements 
Terms 
Definitions 
Vedolizumab discontinuation 
Vedolizumab discontinuation is defined as ceasing vedolizumab, or a 
treatment gap ≥90 days between consecutive doses. 
Clinical remission 
Clinical remission is defined as SCCAI [12] of ≤2 with no individual 
score >1 (UC patients) or a HBI ≤4 (CD patients) [13]. 
Clinical response 
Clinical response is defined as a decrease in SCCAI of ≥3 from baseline 
or by physician assessment of clinical response (UC patients) [12] or a 
decrease in HBI of ≥3 points from baseline* (CD patients) [13]. 
Mucosal healing** 
Mucosal healing is based on endoscopic evidence of no inflammation and 
healing of the mucosa as defined by a Mayo endoscopic subscore of ≤1 
point [15] or SES-CD 0-2 or SES-CD ≤4 and at least a 2 point reduction 
from baseline with no sub-score >1 [16]. 
Endoscopic response** 
Endoscopic response is defined as decrease in Mayo endoscopic subscore 
of ≥1 point in UC [15] and >50% decrease in SES-CD in CD [16]. 
Patient-reported QoL 
A score will be computed for the SIBDQ [17]. Linguistically validated 
translations of the SIBDQ are available in local languages. 
CD= Crohn’s disease, HBI= Harvey Bradshaw Index, SES-CD= Simple Endoscopic Score for Crohn Disease, SCCAI= Simple 
Clinical Colitis Activity Index, SIBDQ= Short Inflammatory Bowel Disease Questionnaire, QoL= Quality of life, 
UC= Ulcerative colitis 
* Baseline is defined as the assessment prior to first dose of study. 
** Colonoscopy/ Ileo-colonoscopy is not mandatory except screening visit, however if performed will be used to assess mucosal 
healing and endoscopic response. 
9.1.10 Patient Reported Outcome Measures 
Patients will complete the SIBDQ at the time points specified in the Schedule of Study Procedures.  
9.1.10.1 
Short Inflammatory Bowel Disease Questionnaire 
The SIBDQ is a valid and reliable [17] instrument used to assess quality of life in adult patients with 
IBD. It is a 10-item questionnaire that includes questions on 4 domains of health-related quality of 
life (HRQoL): Bowel systems, emotional function, social function, and systemic function and is 
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scored on a 7-point Likert scale from 1 (severe problem) to 7 (no problems at all). A total SIBDQ 
score is calculated by summing the scores from each domain; the total SIBDQ score ranges from 10 
(poor HRQoL) to 70 (optimum HRQoL).  
9.1.11 Documentation of Concomitant Medications 
Concomitant medication is any drug given in addition to the study drug. These may be prescribed by 
a physician or obtained by the patient over the counter. Concomitant medication is not provided by 
the sponsor. At each study visit, patients will be asked whether they have taken any medication other 
than the study drug (used from signing of informed consent through the end of the study), and all 
medication including vitamin supplements, over-the-counter medications, and oral herbal 
preparations, must be recorded in the eCRF. 
9.1.12 Procedures for Clinical Laboratory Samples 
All samples will be collected in accordance with acceptable laboratory procedures at the time points 
specified in the Schedule of Study Procedures. Details of these procedures and required safety 
monitoring will be given in the laboratory manual. 
Table 9. a lists the tests that will be obtained for each laboratory specimen. 
Table 9. a 
Clinical Laboratory Tests 
Hematology 
Serum Chemistry 
Urinalysis 
Red blood cells  
White blood cells  
Hemoglobin 
Hematocrit 
Platelets 
ALT 
Albumin 
Total bilirubin 
AST  
Total protein 
Creatinine 
Blood urea nitrogen 
Bilirubin 
Blood 
Glucose 
Ketones 
Leukocyte esterase 
Nitrite 
pH 
Protein 
Specific Gravity 
Serum 
Urine 
HIV test 
Hepatitis panel, including HBsAg and anti-HCV  
β-hCG (for pregnanacy) (female patients of childbearing 
potential) 
CRP 
Urine pregnancy test (female patients of childbearing 
potential) 
  
 
Mantoux test/Interferon gamma release assay and Chest X-ray for Tuberculosis 
Stool: 
Fecal calprotectin  
Clostridium difficile Test 
 
 
ALT=Alanine aminotransferase, anti-HCV= anti-hepatitis C virus, AST=Aspartate aminotransferase, CRP= C-reactive protein, 
HBsAg= Hepatitis B surface antigen, β-hCG= beta human chorionic gonadotropin, HIV= Human Immunodeficiency Virus 
The local laboratory will perform laboratory tests for hematology, serum chemistries, and urinalysis. 
The results of laboratory tests will be returned to the investigator, who is responsible for reviewing 
and filing these results. 
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If patients experience ALT or AST >3 ×ULN, follow-up laboratory tests (at a minimum, serum 
alkaline phosphatase, ALT, AST, total bilirubin, gamma glutamyl transferase, and INR) should be 
performed within a maximum of 7 days and preferably within 48-72 hours after the abnormality was 
noted (refer to Section 7.4 and Section 10.2.4 for the appropriate guidance on reporting abnormal 
liver tests).  
If ALT or AST remains elevated >3 ×ULN on these 2 consecutive occasions the investigator must 
contact the medical monitor for consideration of additional testing, close monitoring, possible 
discontinuation of study drug, discussion of the relevant patient details and possible alternative 
etiologies. The abnormality should be recorded as an AE (please refer to Section 10.2.4). 
9.1.13 Documentation of Concurrent Medical Conditions 
Concurrent medical conditions are those significant ongoing conditions or diseases that are present 
at signing of informed consent. This includes clinically significant (laboratory, electrocardiogram 
[ECG], or physical examination abnormalities) noted at (screening/baseline) examination, according 
to the judgment of the investigator. The condition (ie, diagnosis) should be described. 
9.1.14 Contraception and Pregnancy Avoidance Procedure 
From signing of informed consent, throughout the duration of the study, and for 16 weeks after last 
dose of study drug, nonsterilized** male patients who are sexually active with a female partner of 
childbearing potential* must use barrier contraception (eg, condom with spermicidal cream or jelly). 
In addition, they must be advised not to donate sperm during this period. From signing of informed 
consent, throughout the duration of the study, and for 16 weeks after last dose of study drug, female 
patients of childbearing potential* who are sexually active with a nonsterilized male partner** must 
use adequate contraception. In addition they must be advised not to donate ova during this period. 
*Females not of childbearing potential are defined as those who have been surgically sterilized 
(hysterectomy, bilateral oophorectomy or tubal ligation) or who are postmenopausal (eg, defined as 
at least 1 year since last regular menses with an appropriate clinical profile [ie, age appropriate, 
history of vasomotor symptoms], confirmed before any study drug is implemented). 
**Sterilized males should be at least 1 year postvasectomy and have confirmed that they have 
obtained documentation of the absence of sperm in the ejaculate. 
An acceptable method of contraception is defined as one that has no higher than a 1% failure rate. 
In this study, where medications and devices containing hormones are included the only acceptable 
methods of contraception are: 
Intrauterine devices: 
Hormonal contraceptives: 
Copper T PLUS condom or spermicide  
Implants 
Progesterone T PLUS condom or spermicide 
Hormone shot/injection 
 
Combined pill 
 
Minipill 
 
Patch 
 
Vaginal ring PLUS male condom and spermicide 
Barrier methods (eg, male condom PLUS spermicide, cap [plus spermicidal cream or jelly] PLUS male 
condom and spermicide, diaphragm [plus spermicidal cream or jelly] PLUS male condom and 
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spermicide) can be used each time the patient has intercourse in addition to methods listed in the 
table above to ensure acceptable protection level. 
Patients will be provided with information on acceptable methods of contraception as part of the 
patient informed consent process and will be asked to sign a consent form stating that they 
understand the requirements for avoidance of pregnancy, donation of ova, and sperm donation 
during the course of the study. 
During the course of the study, regular serum/urine hCG pregnancy tests will be performed only for 
women of childbearing potential and patients will receive continued guidance with respect to the 
avoidance of pregnancy and sperm donation as part of the study procedures (Appendix A). In 
addition to a negative serum β-hCG pregnancy test at Screening, patients also must have a negative 
urine pregnancy test at Week 0 Day 1, during the treatment phase, Week 46/ET and at the 16-week 
safety follow-up visit. 
9.1.15 Pregnancy 
If any patient is found to be pregnant during the study, the patient should be withdrawn and any 
sponsor-supplied drug should be immediately discontinued. In addition, any pregnancies in the 
partner of a male patient during the study or for 16 weeks after the last dose, should also be recorded 
following authorization from the patient’s partner. 
If the pregnancy occurs during administration of study drug or within 16 weeks of the last dose of 
study drug, the pregnancy should be reported immediately, using a pregnancy notification form, to 
the contact listed in Section 1.0. If the female patient and/or female partner of a male patient agrees 
to the primary care physician being informed, the investigator should notify the primary care 
physician that the patient/female partner of the patient was participating in a clinical study at the time 
she became pregnant and provide details of treatment the patient received. All pregnancies in patients 
on active study drug will be followed up to the final outcome, using the pregnancy form. The 
outcome, including any premature termination, must be reported to the sponsor. An evaluation after 
the birth of the child will also be conducted. 
9.1.16 ECG Procedure  
A standard 12-lead ECG will be recorded at the time points specified in the Schedule of Study 
Procedures (Appendix A). The investigator (or a qualified observer at the study site) will interpret 
the ECG using 1 of the following categories: within normal limits, abnormal but not clinically 
significant, or abnormal and clinically significant. 
9.1.17 Tuberculosis Screening 
All patients will complete TB screening to determine eligibility. All patients must complete a 
diagnostic tests of Mantoux test/Interferon gamma release assay and Chest X-ray during screening 
as per the decision of investigator and the feasibility of the site. Patients will be excluded from the 
study if they have active or latent TB, regardless of treatment history, as defined in Section 7.2. 
9.1.18 Harvey Bradshaw Index/Mayo Score  
A HBI/Mayo Score will be evaluated during screening to determine eligibility. A HBI/SCCAI score 
will also be derived at the time points specified in the Schedule of Study Procedures and at any 
unscheduled visit(s) due to disease exacerbation (See Appendix A). 
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9.1.19 Documentation of Screen Failure 
Investigators must account for all patients who sign informed consent. If the patient is found to be 
not eligible after screening, the investigator should complete the eCRF. 
The primary reason for screen failure is recorded in the eCRF using the following categories: 
• PTE/AE 
• Did not meet inclusion criteria or did meet exclusion criteria. 
• Significant protocol deviation 
• Lost to follow-up 
• Voluntary withdrawal (specify reason) 
• Others (specify reason) 
Patient numbers assigned to patients who fail screening should not be reused. 
9.1.20 Documentation of Study Entrance 
Only patients who meet all of the inclusion criteria and none of the exclusion criteria are eligible for 
enrolment into the treatment phase. 
If the patient is found to be not eligible for treatment phase, the investigator should record the primary 
reason for failure on the applicable eCRF. 
9.2 
Monitoring Patient Treatment Compliance 
If a patient is persistently noncompliant with the study drug administration visits, it may be 
appropriate to withdraw the patient from the study. All patients should be reinstructed about the 
dosing requirement during study contacts. The authorized study personnel conducting the re-
education must document the process in the patient source records. 
9.3 
Schedule of Observations and Procedures 
The schedule for all study-related procedures for all evaluations is shown in Appendix A. 
Assessments should be completed at the designated visit/time point(s). 
9.3.1 
Screening  
Patients will be screened within 28 days prior to 1st dose. Patients will be screened in accordance 
with predefined inclusion and exclusion criteria as described in Sections 7.1 and 7.2, respectively. 
See Section 9.1.19 for procedures for documenting screening failures. 
Procedures to be completed at Screening can be found in the Schedule of Study Procedures 
(Appendix A). 
9.3.2 
Rescreening 
Automatic rescreening of the patients is not allowed. If the investigator believes in the 
appropriateness of the patient for the study, and considers a rescreen, permission for the same must 
be obtained from the Medical Monitor. Rescreening at the investigator’s discretion without prior 
approval from the Medical Monitor is not allowed.  
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9.3.3 
Enrollment 
Enrollment will take place on Day 1. If the patient has satisfied all of the inclusion criteria and none 
of the exclusion criteria, the patient will be enrolled. Patients will be instructed on when the first 
dose of investigational drug will be given as described in Section 6.1.   
9.3.4 
Treatment Phase 
The treatment phase will be of 46 weeks. The study drug doses will be given at Week 0 (Day 1), 2, 
6, 10 (CD- Patients who have not shown a response can receive a dose at 10 week), 14, 22, 30, 38, 
and 46. 
9.3.5 
End of Treatment Visit or Early Termination 
The end of treatment visit will be performed on Week 46 or at early terimation.  
For all patients receiving study drug, the investigator must complete the end of treatment eCRF 
page. 
9.3.6 
Postdose 16-Week Safety Follow-up 
Upon receipt of the last dose of study drug (completers and ETs), all patients will complete a safety 
follow-up visit 16 weeks postdose. Assessments will be completed per the Schedule of Study 
Procedures for the postdose 16-week safety follow-up visit and end of study eCRF page must be 
completed. During this 16 week follow up period patients will be managed as per standard of care 
which includes Vedolizumab (an approved treatment in India for the current study patient 
population) or any other treatment per investigator discretion and it will be provided by the sponsor. 
Vedolizumab treatment during this follow period shall not be considered as study treatment as 
vedolizumab is an approved product and part of standard of care for this patient population. Any 
adverse event in patients receiving Vedolizumab as a part of standard of care during the follow up 
period will be compensated for medical management by the sponsor only if found to be related to 
the study treatment, as assessed by study investigator.  
9.3.7 
Poststudy Long-term Follow-up 
Upon completion of treatment phase or early termination from the study, all patients will participate 
in a long-term follow-up safety survey through telephonic visit. The survey will be administered at 
6 months after the last dose of study drug i.e. 8 weeks after the 16-week follow-up visit, and the 
information will be collected on events such as infections resulting in hospitalizations, cancer, UC 
or CD related surgeries, and development of PML. During this  follow up period patients will be 
managed as per standard of care which includes Vedolizumab (an approved treatment in India for 
the current study patient population) or any other treatment per investigator discretion and it will be 
provided by the sponsor. Vedolizumab treatment during this follow period shall not be considered 
as study treatment as vedolizumab is an approved product and part of standard of care for this patient 
population. Any adverse event in patients receiving Vedolizumab as a part of standard of care during 
the follow up period will be compensated for medical management by the sponsor only if found to 
be related to the study treatment, as assessed by study investigator.  
 
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9.3.8 Unscheduled Visits Due to Disease Exacerbation 
Patients who are seen by the investigator or site staff at a time point not required by the protocol (ie, 
unscheduled visit) due to disease exacerbation will undergo the following procedures: 
• Physical examination 
• Vital signs assessment 
• Collection of concomitant medications and procedures 
• Collection of AEs and SAEs 
• Serum chemistry and hematology, as indicated 
• Other (per investigator discretion and approval by Sponsor) 
There is no minimum time for repeat evaluation by unscheduled visits in order to determine if a 
patient meets the criteria for disease exacerbation. In general, however, enough time should be 
provided for clinically meaningful change to occur (eg, 1 week). 
9.3.9 
Post Study Care 
The patient should be returned to the care of a physician and standard therapies as required. If the 
Investigator decides to continue Vedolizumab or any other treatment during the follow up period i.e. 
following the end of treatment phase (46 weeks) or Early Termination, the same will be provided by 
the sponsor. . Vedolizumab treatment during this follow period shall not be considered as study 
treatment as vedolizumab is an approved product and part of standard of care for this patient 
population. Any adverse event in patients receiving Vedolizumab will be compensated for medical 
management by the sponsor only if found to be related to the study treatment, as assessed by study 
investigator.
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10.0 
PRETREATMENT EVENTS, ADVERSE EVENTS, ADVERSE DRUG 
REACTIONS, UNEXPECTED ADVERSE DRUG REACTIONS  
10.1 
Definitions 
10.1.1 Pretreatment events 
A PTE is defined as any untoward medical occurrence in a clinical investigation patient who has 
signed informed consent to participate in a study but prior to administration of any study drug; it does 
not necessarily have to have a causal relationship with study procedure. 
10.1.2 Adverse events 
An AE is defined as any untoward medical occurrence in a clinical investigation patient administered 
a drug; it does not necessarily have to have a causal relationship with the treatment. 
An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal 
laboratory value), symptom, or disease temporally associated with the use of a drug whether or not 
it is considered related to the drug. 
10.1.3 Additional Points to Consider for PTEs and AEs 
An untoward finding generally may: 
• Indicate a new diagnosis or unexpected worsening of a pre-existing condition. Intermittent 
events for pre-existing conditions or underlying disease should not be considered PTEs or AEs. 
• Necessitate therapeutic intervention 
• Require an invasive diagnostic procedure 
• Require discontinuation or a change in dose of study drug or a concomitant medication 
• Be considered unfavorable by the investigator for any reason. 
• PTEs/AEs caused by a study procedure (eg, a bruise after blood draw) should be recorded as a 
PTE/AE. 
Diagnoses vs signs and symptoms: 
• Each event should be recorded to represent a single diagnosis. Accompanying signs (including 
abnormal laboratory values or ECG findings) or symptoms should not be recorded as additional 
AEs. If a diagnosis is unknown, sign(s) or symptom(s) should be recorded appropriately as a 
PTE(s) or as an AE(s). 
Laboratory values and ECG findings: 
• Changes in laboratory values or ECG findings are only considered to be PTEs or AEs if they are 
judged to be clinically significant (ie, if some action or intervention is required or if the 
investigator judges the change to be beyond the range of normal physiologic fluctuation). A 
laboratory or ECG re-test and/or continued monitoring of an abnormal value or finding are not 
considered an intervention. In addition, repeated or additional noninvasive testing for 
verification, evaluation, or monitoring of an abnormality is not considered an intervention. 
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• If abnormal laboratory values or ECG findings are the result of pathology for which there is an 
overall diagnosis (eg, increased creatinine in renal failure), the diagnosis only should be reported 
appropriately as a PTE or as an AE. 
Pre-existing conditions: 
• Pre-existing conditions (present at the time of signing of informed consent) are considered 
concurrent medical conditions and should not be recorded as PTEs or AEs. Baseline evaluations 
(eg, laboratory tests, ECG, X-rays, etc) should not be recorded as PTEs unless related to study 
procedures. However, if the patient experiences a worsening or complication of such a concurrent 
medical condition, the worsening or complication should be recorded appropriately as a PTE 
(worsening or complication occurs before start of study drug) or an AE (worsening or 
complication occurs after start of study drug). Investigators should ensure that the event term 
recorded captures the change in the condition (eg, “worsening of…”). 
• If a patient has a pre-existing episodic concurrent medical condition (eg, asthma, epilepsy), any 
occurrence of an episode should be captured as a PTE/AE only if the condition becomes more 
frequent, serious, or severe in nature. Investigators should ensure that the AE term recorded 
captures the change in the condition from Baseline (eg “worsening of…”). 
• If a patient has a degenerative concurrent medical condition (eg, cataracts, rheumatoid arthritis), 
worsening of the condition should only be recorded as a PTE/AE if occurring to a greater extent 
to that which would be expected. Investigators should ensure that the AE term recorded captures 
the change in the condition (eg, “worsening of…”). 
Worsening of PTEs or AEs: 
• If the patient experiences a worsening or complication of a PTE after the start of study drug, the 
worsening or complication should be recorded as an AE. Investigators should ensure that the AE 
term recorded captures the change in the PTE (eg, “worsening of…”). 
• If the patient experiences a worsening or complication of an AE after any change in study drug, 
the worsening or complication should be recorded as a new AE. Investigators should ensure that 
the AE term recorded captures the change in the condition (eg, “worsening of…”). 
Changes in intensity of AEs /PTEs: 
• If the patient experiences changes in intensity of an AE/serious PTE, the event should be captured 
once with the maximum intensity recorded. 
Preplanned procedures (surgeries or interventions): 
• Preplanned procedures (surgeries or therapies) that were scheduled prior to signing of informed 
consent are not considered PTEs or AEs. However, if a preplanned procedure is performed early 
(eg, as an emergency) due to a worsening of the pre-existing condition, the worsening of the 
condition should be recorded as a PTE or an AE. Complications resulting from any planned 
surgery should be reported as AEs. 
Elective surgeries or procedures: 
• Elective procedures performed where there is no change in the patient’s medical condition should 
not be recorded as PTEs or AEs, but should be documented in the patient’s source documents. 
Complications resulting from an elective surgery should be reported as AEs. 
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Insufficient clinical response (lack of efficacy): 
• Insufficient clinical response, efficacy, or pharmacologic action should not be recorded as an AE. 
The investigator must make the distinction between exacerbation of pre-existing illness and lack 
of therapeutic efficacy. 
Overdose: 
• Cases of overdose with any medication without manifested side effects are not considered PTEs 
or AEs, but instead will be documented on an Overdose page of the eCRF. Any manifested side 
effects will be considered PTEs or AEs and will be recorded on the AE page of the eCRF. 
10.1.4 Serious Adverse Events 
An SAE is defined as any untoward medical occurrence that at any dose: 
1. Results in DEATH. 
2. Is LIFE THREATENING. 
• The term “life threatening” refers to an event in which the patient was at risk of death at the 
time of the event; it does not refer to an event that hypothetically might have caused death if 
it were more severe. 
3. Requires inpatient HOSPITALIZATION or prolongation of existing hospitalization. 
4. Results in persistent or significant DISABILITY/INCAPACITY. 
5. Leads to a CONGENITAL ANOMALY/BIRTH DEFECT. 
6. Is an IMPORTANT MEDICAL EVENT that satisfies any of the following: 
• May require intervention to prevent items 1 through 5 above. 
• May expose the patient to danger, even though the event is not immediately life threatening 
or fatal or does not result in hospitalization. 
• Includes any event or synonym described in the Takeda medically significant AE List 
(Table 10. a). 
Table 10. a 
Takeda Medically Significant AE List  
Term 
Acute respiratory failure/acute respiratory distress 
syndrome 
Hepatic necrosis 
Torsade de pointes / ventricular fibrillation / ventricular 
tachycardia 
Acute liver failure 
Anaphylactic shock 
Malignant hypertension 
Acute renal failure 
Convulsive seizure  
Pulmonary hypertension 
Agranulocytosis 
Pulmonary fibrosis  
Aplastic anemia 
Confirmed or suspected endotoxin shock 
Toxic epidermal necrolysis/Stevens-Johnson syndrome Confirmed or suspected transmission of infectious agent by a 
medicinal product 
Neuroleptic malignant syndrome / malignant hyperthermia 
Spontaneous abortion / stillbirth and fetal death 
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Note: Terms identified on the Medically Significant AE List represent the broad medical concepts to be considered as “Important 
Medical Events” satisfying SAE reporting requirements.  
PTEs that fulfill 1 or more of the serious criteria above are also to be considered SAEs and should 
be reported and followed up in the same manner (see Sections 10.2.2 and 10.3). 
10.1.5 Adverse events of special interest 
A special interest adverse event (serious or nonserious) is one of scientific and medical concern 
specific to the compound or program, for which ongoing monitoring and rapid communication by 
the investigator to Takeda may be appropriate. Such events may require further investigation in order 
to characterize and understand them and would be described in protocols and instructions provided 
for investigators as to how and when they should be reported to Takeda. 
AESIs in this study are listed in Section 10.2.2. 
10.1.6 Adverse drug reactions 
An ADR is an AE for which there is at least a reasonable suspicion of a causal relationship between 
an AE and a suspected medicinal product. 
10.1.7 Unexpected Adverse drug reactions 
An unexpected ADR is an ADR with the nature, severity, or outcome which is not consistent with 
the Product Insert. 
10.1.8 Intensity of PTEs and AEs 
The different categories of intensity (severity) are characterized as follows: 
Mild: 
The event is transient and easily tolerated by the patient. 
Moderate: 
The event causes the patient discomfort and interrupts the patient’s usual activities. 
Severe: 
The event causes considerable interference with the patient’s usual activities. 
10.1.9 Causality of AEs 
The relationship of each AE to study drug(s) will be assessed using the following categories: 
Related: 
An AE that follows a reasonable temporal sequence from administration of a drug 
(including the course after withdrawal of the drug), or for which possible 
involvement of the drug cannot be ruled out, although factors other than the drug, 
such as underlying diseases, complications, concomitant medications and 
concurrent treatments, may also be responsible. 
Not Related: 
An AE that does not follow a reasonable temporal sequence from administration 
of a drug and/or that can reasonably be explained by other factors, such as 
underlying diseases, complications, concomitant medications and concurrent 
treatments. 
10.1.10 Relationship to Study Procedures 
Relationship (causality) to study procedures should be determined for all PTEs and AEs. 
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The relationship should be assessed as Related if the investigator considers that there is reasonable 
possibility that an event is due to a study procedure. Otherwise, the relationship should be assessed 
as Not Related.  
10.1.11 Start Date 
The start date of the AE/PTE is the date at which the first signs/symptoms were noted by the patient 
and/or investigator. 
10.1.12 Stop Date  
The stop date of the AE/PTE is the date at which the event resolved/recovered with or without 
sequelae or the patient died. 
10.1.13 Frequency  
Episodic AEs/PTE (eg, vomiting) or those which occur repeatedly over a period of consecutive days 
are intermittent. All other events are continuous. 
10.1.14 Action Concerning Study Drug  
• Drug withdrawn – a study drug is stopped due to the particular AE. 
• Dose not changed – the particular AE did not require stopping a study drug. 
• Unknown – only to be used if it has not been possible to determine what action has been taken. 
• Not Applicable – a study drug was stopped for a reason other than the particular AE eg, the study 
has been terminated, the patient died, dosing with study drug was already stopped before the 
onset of the AE. 
• Dose reduced – the dose was reduced due to the particular AE. 
• Dose interrupted – the dose was interrupted due to the particular AE. 
10.1.15 Outcome 
• Recovered/Resolved – Patient returned to first assessment status with respect to the AE/PTE. 
• Recovering/Resolving – the intensity is lowered by 1 or more stages: the diagnosis or 
signs/symptoms has almost disappeared; the abnormal laboratory value improved, but has not 
returned to the normal range or to baseline; the patient died from a cause other than the particular 
AE/PTE with the condition remaining “recovering/resolving”. 
• Not recovered/not resolved – there is no change in the diagnosis, signs or symptoms; the intensity 
of the diagnosis, signs/ symptoms or laboratory value on the last day of the observed study period 
has got worse than when it started; is an irreversible congenital anomaly; the patient died from 
another cause with the particular AE/PTE state remaining “Not recovered/not resolved”. 
• Resolved with sequelae – the patient recovered from an acute AE/PTE but was left with 
permanent/significant impairment (eg, recovered from a cerebrovascular accident but with some 
persisting paresis. 
• Fatal – the AEs/PTEs which are considered as the cause of death.  
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• Unknown – the course of the AE/PTE cannot be followed up due to hospital change or residence 
change at the end of the patient’s participation in the study. 
10.2 
Procedures 
10.2.1 Collection and Reporting of AEs 
10.2.1.1 
PTE, AE, and ADR Collection Period 
Collection of PTEs will commence from the time the patient signs the informed consent to participate 
in the study and continue until the patient is first administered study drug or until screen failure. For 
patients who discontinue prior to study drug administration, PTEs are collected until the patient 
discontinues study participation. 
Collection of AEs will commence from the time that the patient is first administered study drug. 
Routine collection of AEs will continue until 16 weeks (safety follow-up period) followed by a 
telephonic survey 6 months (long-term follow-up period) after the last dose of study drug . 
10.2.1.2 
PTE, AE, and ADR Reporting 
At each study visit, the investigator will assess whether any subjective AEs have occurred. A neutral 
question, such as “How have you been feeling since your last visit?” may be asked. Patients may 
report AEs occurring at any other time during the study. Patients experiencing a serious PTE must 
be monitored until the symptoms subside and any clinically relevant changes in laboratory values 
have returned to baseline or there is a satisfactory explanation for the change. Non-serious PTEs, 
related or unrelated to the study procedure, need not to be followed-up for the purposes of the 
protocol. 
All patients experiencing AEs, whether considered associated with the use of the study drug or not, 
must be monitored until the symptoms subside and any clinically relevant changes in laboratory 
values have returned to baseline or until there is a satisfactory explanation for the changes observed. 
All PTEs and AEs will be documented in the PTE/AE page of the eCRF, whether or not the 
investigator concludes that the event is related to the drug treatment. The following information will 
be documented for each event: 
1. Event term. 
2. Start and stop date. 
3. Frequency. 
4. Intensity. 
5. Investigator’s opinion of the causal relationship between the event and administration of study 
drug(s) (related or not related) (not completed for PTEs). 
6. Investigator’s opinion of the causal relationship to study procedure(s), including the details of the 
suspected procedure. 
7. Action concerning study drug (not applicable for PTEs). 
8. Outcome of event. 
9. Seriousness. 
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SIBDQ will be used in this study. It will not be used as a primary means to collect AEs. However, 
should the investigator become aware of a potential AE through the information collected with this 
instrument, proper follow-up with the patient for medical evaluation should be undertaken. Through 
this follow-up if it is determined that an AE not previously reported has been identified, normal 
reporting requirements should be applied. 
10.2.1.3 
Adverse Event Collection Involving Medically Anticipated Clinical Events 
UC or CD is associated with certain characteristic signs and symptoms including diarrhea, rectal 
bleeding, and abdominal pain that may be present at baseline and persist or fluctuate based on the 
individual patient’s disease history during the course of the study. These signs and symptoms will 
not be collected as AEs. These characteristics of disease activity will be regularly captured in the 
SCCAI score/HBI. 
Exacerbations of disease activity (eg, increase in the daily amount of rectal bleeding or abdominal 
pain beyond the patient’s normal fluctuation, new signs and symptoms) will be collected as AEs and 
reported according to regulatory reporting requirements. 
Extra-intestinal manifestations of the patient’s disease (eg, arthralgia, arthritis, uveitis) that develop 
or worsen during the study are considered AEs. 
10.2.2 Adverse event of special interest reporting 
If an AESI, which occurs during the treatment period or the follow-up period, is considered to be 
clinically significant based on the criteria below, it should be recorded in the Special Interest AE 
eCRF or SAE Form. The applicable form should be completed and reported to the SAE reporting 
contact in Section 1.1 within 24 hours. The list of AESIs are as follows:  
Serious infections 
Serious infection is defined as any event coded to a Medical Dictionary for Regulatory Activities 
(MedDRA) preferred terms (PT) within the MedDRA SOC of infections and infestations that meet 
the ‘serious’ definition (see Section 10.1.4). 
Opportunistic infections 
This is defined as infections included in the United States Center for Disease Control’s list of 
opportunistic infections. This includes TB and PML. 
Opportunistic infections include: 
• Candidiasis of bronchi, trachea, esophagus, or lungs: This is defined as any event coded 
to a MedDRA term for candidiasis of the bronchi, trachea, esophagus, or lung. 
• Coccidioidomycosis: This is defined as any event coded to a MedDRA term for 
coccidioidomycosis, pulmonary coccidioidomycosis, cutaneous coccidioidomycosis, or 
extrapulmonary coccidioidomycosis. 
• Cryptococcosis: This is defined as any event coded to a MedDRA term for cryptococcosis, 
pulmonary cryptococcosis, extrapulmonary cryptococcosis, disseminated cryptococcosis, 
and recurrent cryptococcosis. 
• Cryptosporidiosis: This is defined as any event coded to a MedDRA term for 
cryptosporidiosis or recurrent cryptosporidiosis. 
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• Cytomegalovirus (CMV) disease: This is defined as events coded to a MedDRA term for 
CMV disease, including CMV chorioretinitis, colitis, duodenitis, enteritis, gastritis, 
hepatitis, mononucleosis, mucocutaneous ulcer, myelomeningoradiculitis, myocarditis, 
esophagitis, pancreatitis, pericarditis, proctocolitis, urinary tract infection, encephalitis, 
CMV pneumonia, and CMV syndrome. 
• Encephalopathy-related infections: This is defined as encephalitis or encephalopathy due 
to infections, excluding those transmitted by arthropod (such as Japanese B encephalitis) 
or rodents, or due to influenza, measles, mumps, polio, or rabies. Includes PML (see 
below). 
• Herpes simplex: This is defined as events coded to MedDRA terms for herpes simplex 
esophagitis, bronchitis, or pneumonitis, or to herpes esophagitis, bronchitis, or pneumonia. 
• Histoplasmosis: This is defined as events coded to any MedDRA term for histoplasmosis 
and includes both acute and chronic infections of any site. 
• Isosporiasis, chronic intestinal: This is defined as events coded to MedDRA terms 
forisosporiasis of the MedDRA high-level term (HLT) isospora infection. 
• Kaposi’s sarcoma: This is defined as events coded to the MedDRA HLT Kaposi sarcoma. 
• Mycobacterium avium complex: This is defined as events coded to the MedDRA term 
Mycobacterium avium complex infection. 
• TB: This is defined as all events coded to the MedDRA HLT TB infections, including new 
infections and reactivation of latent infections, of pulmonary and extra pulmonary sites. 
• Pneumocystis jiroveci pneumonia (formerly Pneumocystis carinii pneumonia): This is 
defined as events coded to the MedDRA term Pneumocystis jiroveci pneumonia 
Pneumonia, recurrent. This is defined as events coded to the MedDRA term pneumonia 
recurrent. 
• PML: All reports of suspected PML (Appendix J) (reports coded to the following 
MedDRA PTs: human polyomavirus infection, John Cunningham (JC) virus infection, JC 
virus test positive, leukoencephalopathy, polyomavirus test positive, progressive 
multifocal leukoencephalopathy) will be reviewed by PML Independent Adjudication 
Committee (IAC) and assessed against the PML diagnostic criteria of the American 
Academy of Neurology [18]. Where incomplete information is provided, the physician 
shall seek to obtain all relevant information).  
Investigators will be provided with the vedolizumab HCP educational brochure and 
instructed to monitor patients for any new onset or worsening of neurological signs and 
symptoms, consistent with standard of care clinical practice and the information contained 
in the approved prescribing information, which describes the typical signs and symptoms 
of PML and recommended action if PML is suspected. The patient will be given 
vedolizumab Patient Alert Card. 
• Salmonella septicemia, recurrent: This is defined as events coded to the MedDRA terms 
Salmonella sepsis or Salmonella septicemia. 
• Toxoplasmosis of brain: This is defined as events coded to MedDRA term cerebral 
toxoplasmosis. 
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Other rare infections that are not normally seen in immunocompetent persons may also be 
considered as opportunistic infections. 
GI infections 
This is defined as events within the infections and infestation SOC that are coded to the MedDRA 
HLT GI infections. The treating physician should record and report all GI infections, including those 
occurring as a result of UC or CD. 
Respiratory infections 
This is defined as events within the respiratory, thoracic and mediastinal disorders SOC that are 
coded to the MedDRA HLT respiratory tract infection. As respiratory infections are common and 
often mild in nature, the treating physician should ask study participants at each clinic visit if they 
have had any respiratory infections since last visit, and collect all relevant information. 
Other clinically significant infections 
This is defined as events within the infections and infestation SOC that are not included in any of 
the above categories, are classified as moderate or severe (Section 10.1.8), and require anti-infective 
treatment. 
Malignancies 
All malignant and benign neoplasms should be recorded on the eCRF. The analyses will focus on 
malignancies and include all events within the MedDRA Malignant tumors Standardised MedDRA 
Queries (SMQ). This SMQ includes all malignancies and carcinomas in situ. 
The treating physician should seek all available clinical and histopathology information on the 
malignancy, including site, cell type, size, stage, and grade (including nodal status and metastases), 
clinical history, prior history of malignancy or premalignant disorders, family history, history of 
screening and diagnostic tests, and history of risk factors and medication history. 
Infusion-related reactions and hypersensitivity 
All suspected cases of infusion reactions, hypersensitivity, and anaphylaxis should be reported on 
the eCRF, regardless of time since last drug exposure. 
Events that are coded to PTs in the following will be considered as suspected reports of 
hypersensitivity: 
• Anaphylactic reaction (narrow SMQ) 
• Anaphylactic/anaphylactoid shock conditions (narrow SMQ) 
• Hypersensitivity (narrow SMQ) 
• Angioedema (narrow SMQ) 
All suspected reports will be adjudicated by a Takeda or contract research organization (CRO) 
pharmacovigilance (PV) physician using the hypersensitivity criteria of the National Institute of 
Allergy & Infectious Diseases [19]. 
The physician shall seek all information on clinical history, presenting signs and symptoms, time 
interval between biologic exposure and onset of symptoms, and treatments received. 
Hepatic injury 
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Events coded to PTs in the following MedDRA SMQs (narrow) will be considered as suspected 
reports of liver injury: 
• Cholestasis and jaundice of hepatic origin (narrow SMQ) 
• Hepatic failure, fibrosis and cirrhosis, and other liver damage-related conditions 
(narrow SMQ) 
• Hepatitis non-infectious (narrow SMQ) 
• Liver related investigations, signs, and symptoms (narrow SMQ) 
The treating physician shall seek all relevant information on the hepatic injury, including signs and 
symptoms, initial and follow-up laboratory results (including serology results), time course of the 
hepatic injury, diagnosis, concurrent medications and doses, pre-existing liver disease, infections, 
suspected etiology (and treating physician to rule out alternative etiologies), and outcome. 
10.2.3 Collection and Reporting of SAEs 
When an SAE occurs through the AE collection period it should be reported according to the 
following procedure: 
The SAE page of the eCRF must be completed, in English, and signed by the investigator 
immediately or within 24 hours of first onset or notification of the event. The information should be 
completed as fully as possible but contain, at a minimum: 
A short description of the event and the reason why the event is categorized as serious. 
• Patient identification number 
• Investigator’s name 
• Name of the study drug(s) 
• Causality assessment 
In the event that electronic data collection (EDC) is unavailable, a paper SAE form must be 
completed, in English, and signed by the investigator immediately or within 24 hours of first onset 
or notification of the event. 
The SAE form should be transmitted within 24 hours to the attention of the contact listed in Section 
1.1.  
If reporting by fax, the site personnel need to confirm successful transmission of all pages and include 
an email address on the fax cover sheet so that an acknowledgment of receipt can be returned via 
email within 1 business day. 
If reporting by email, site personnel need to confirm successful transmission by awaiting an 
acknowledgment of the receipt via email within 1 business day.  
Once EDC is available, the SAE should immediately be entered into the SAE form within EDC. 
Any SAE spontaneously reported to the investigator following the AE collection period should be 
reported to the sponsor if considered related to study participation. 
Reporting of serious PTEs will follow the procedure described for SAEs. 
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10.2.4 Reporting of Abnormal Liver Tests  
If a patient is noted to have ALT or AST >3 ×ULN and total bilirubin >2 ×ULN for which an 
alternative etiology has not been identified, the event should be recorded as an SAE and reported as 
per Section 10.2.2. The investigator must contact the Medical Monitor for discussion of the relevant 
patient details and possible alternative etiologies, such as acute viral hepatitis A or B or other acute 
liver disease or medical history/concurrent medical conditions. Follow-up laboratory tests as 
described in Section 9.1.12 must also be performed. 
10.3 
 Follow-up of SAEs 
If information not available at the time of the first report becomes available at a later date, the 
investigator should enter this information into the SAE form page of the eCRF or provide other 
written documentation and fax it immediately within 24 hours of receipt. Copies of any relevant data 
from the hospital notes (eg, ECGs, laboratory tests, discharge summary, postmortem results) should 
be sent to the addressee, if requested. 
All SAEs should be followed up until resolution or permanent outcome of the event. The timelines 
and procedure for follow-up reports are the same as those for the initial report. 
10.3.1 Safety Reporting to Investigators, IRBs/IECs, and Regulatory Authorities 
The sponsor will be responsible for reporting all suspected unexpected serious adverse reactions 
(SUSARs) and any other applicable SAEs to regulatory authorities, including investigators and 
IRBs/IECs, as applicable. Relative to the first awareness of the event by/or further provision to the 
sponsor or sponsor’s designee, SUSARs will be submitted to the regulatory authorities as expedited 
report within 7 days for fatal and life-threatening events and 15 days for other serious events, unless 
otherwise required by national regulations. The sponsor will also prepare an expedited report for 
other safety issues where these might materially alter the current benefit-risk assessment of a study 
drug/sponsor supplied drug or that would be sufficient to consider changes in the study drug/sponsor 
supplied drug administration or in the overall conduct of the trial. The study site also will forward a 
copy of all expedited reports to his or her IRB/IEC in accordance with local regulations. 
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11.0 
STUDY-SPECIFIC COMMITTEES 
No data safety monitoring committee, or clinical endpoint committee will be used in this study. 
11.1 
Adjudication Committee 
Considering PML is an AESI, a PML IAC will be implemented for this study. The PML IAC will 
consist of a panel of leading PML experts, including a neurologist, neuroradiologist, and a virologist.  
11.1.1 Risk Minimization Action Plan for PML (RAMP Program) 
Natalizumab (TYSABRI), another integrin receptor antagonist, has been associated with PML, a 
rare and often fatal opportunistic infection of the central nervous system. PML is caused by the JCV 
and typically only occurs in patients who are immunocompromised [20,21]. Natalizumab is a pan-α4 
integrin antagonist that binds to both the α4β1 and α4β7 integrins and inhibits cellular adhesion to 
VCAM-1 and MAdCAM-1 [22,23]. In contrast, vedolizumab binds to the α4β7 integrin only [24] 
and inhibits adhesion to MAdCAM-1, but not VCAM-1. However, a risk of PML cannot be ruled 
out. 
To address the theoretical risk of the development of PML in patients treated with vedolizumab, the 
sponsor, with input from renowned PML experts, has developed a Risk Minimization Action Plan 
for PML, the RAMP. The complete description of the RAMP program, including materials and 
instructions for its implementation and monitoring, is included in the Study Manual. 
The RAMP is focused on early clinical detection and management of that specific safety risk, 
including the discontinuation of study drug, if applicable. Patients are assessed for signs and 
symptoms of PML prior to the administration of each dose of study drug using a PML subjective 
symptom checklist. Patients with a positive PML subjective symptom checklist at any time after 
enrollment in a vedolizumab clinical study will be evaluated according to a prespecified algorithm 
(the PML Case Evaluation Algorithm). The next dose of study drug will be held until the evaluation 
is complete and results are available. Subsequent doses of study will be administered only if the 
possibility of PML is definitively excluded, as described in the RAMP algorithm. An IAC has been 
stabled as part of the RAMP program to review new neurological signs and symptoms potentially 
consistent with PML, and will provide input regarding patient evaluation and management as defined 
in the IAC charter. 
To ensure success of the RAMP program, site personnel will be trained to recognize the features of 
PML, and patients will be trained to report specific neurological signs and symptoms without delay. 
Educational materials for teaching site personnel and patients about PML and the RAMP procedures 
will be distributed to all sites and are included in the study manual. Formal teaching and training will 
be performed for site personnel prior to the start of the study. Patients will receive training and 
educational materials prior to receiving treatment. The ICF will contain specific information on the 
hypothetical risk of PML.  
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12.0 
DATA HANDLING AND RECORDKEEPING 
The full details of procedures for data handling will be documented in the Data Management Plan. 
AEs, PTEs, ADRs, medical history, and concurrent conditions will be coded using MedDRA. 
Drugs will be coded using the World Health Organization drug dictionary. 
12.1 
CRFs (Electronic) 
Completed eCRFs are required for each patient who signs an informed consent. 
The sponsor or its designee will supply investigative sites with access to eCRFs. The sponsor will 
make arrangements to train appropriate site staff in the use of the eCRFs. These forms are used to 
transmit the information collected in the performance of this study to the sponsor and regulatory 
authorities. eCRFs must be completed in English. Data are transcribed directly onto eCRFs. 
After completion of the entry process, computer logic checks will be run to identify items, such as 
inconsistent dates, missing data, and questionable values. Queries may be issued by Takeda 
personnel (or designees) and will be answered by the site. 
The investigator must review the eCRFs for completeness and accuracy and must sign and date the 
appropriate eCRFs as indicated. Furthermore, the investigator must retain full responsibility for the 
accuracy and authenticity of all data entered on the eCRFs. 
eCRFs will be reviewed for completeness and acceptability at the study site during periodic visits 
by study monitors. The sponsor or its designee will be permitted to review the patient’s medical 
and hospital records pertinent to the study to ensure accuracy of the eCRFs. The completed eCRFs 
are the sole property of the sponsor and should not be made available in any form to third parties, 
except for authorized representatives of appropriate governmental health or regulatory authorities, 
without written permission of the sponsor. 
12.2 
Record Retention 
The investigator agrees to keep the records stipulated in Section 12.1 and those documents that 
include (but are not limited to) the study-specific documents, the identification log of all 
participating patients, medical records, temporary media such as thermal sensitive paper, source 
worksheets, all original signed and dated ICFs, patient authorization forms regarding the use of 
personal health information (if separate from the ICFs), and detailed records of drug disposition to 
enable evaluations or audits from regulatory authorities, the sponsor or its designees. Any source 
documentation printed on degradable thermal sensitive paper should be photocopied by the site and 
filed with the original in the patient’s chart to ensure long term legibility. Furthermore, 
International Conference on Harmonisation of Technical Requirements for Pharmaceuticals for 
Human Use (ICH) E6 Section 4.9.5 requires the investigator to retain essential documents specified 
in ICH E6 (Section 8) until at least 2 years after the last approval of a marketing application for a 
specified drug indication being investigated or, if an application is not approved, until at least 
2 years after the investigation is discontinued and regulatory authorities are notified. In addition, 
ICH E6 Section 4.9.5 states that the study records should be retained until an amount of time 
specified by applicable regulatory requirements or for a time specified in the study site agreement 
between the investigator and sponsor. 
Refer to the study site agreement for the sponsor’s requirements on record retention. The 
investigator should contact and receive written approval from the sponsor before disposing of any 
such documents.
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13.0 
STATISTICAL METHODS 
13.1 
Statistical and Analytical Plans 
This section provides information on the statistical analysis approach. All analyses will be 
performed using standard software such as SAS (Version 9.3 or later). 
All analyses will be performed separately by IBD disease type (CD and UC). Missing data will not 
be imputed for analyses.  
13.1.1 Analysis Sets 
• The safety analysis set (SAS) will include all enrolled patients who receive at least 1 
dose of study drug. 
• The per-protocol analysis set (PPAS) is a subset of the SAS and consists of all patients 
who do not violate the terms of the protocol in a way that would impact the study outcome 
significantly. 
Significant protocol violations and significant protocol deviations will be identified prior to 
database lock. 
The sponsor will verify the validity of the definitions of the analysis sets as well as the rules for 
handling data, with consulting a medical expert as needed. If necessary, the handling rules for 
analysis data will be supplemented with new handling rules that were not discussed at the planning 
stage. The Handling Rules for Analysis Data must be finalized prior to database lock. 
13.1.2 Analysis of Demographics and Other Baseline Characteristics 
Descriptive statistics, including numbers of observations (n), means (SD), and medians (10th to 90th 
percentiles) for continuous variables, and frequency (n) and percentages for categorical variables will 
be used to examine patient baseline characteristics. 
13.1.3 Primary (Safety) Analysis 
Analyses will present 1) all AEs and SAEs, regardless of association with vedolizumab, and 2) all 
ADRs and Unexpected ADRs, which is the subset of AEs where the physician believes there is 
reasonable suspicion of a causal relationship between vedolizumab and the AE (Section 10.1). 
Exposure-adjusted incidence rates and 95% CIs by Poisson method will be calculated for each safety 
endpoint using the total numbers of incident events and person-time at risk. Two separate incidence 
calculations will be used: incidence rates for events that occur while on vedolizumab therapy, and 
incidence rate for events that occur after discontinuation of vedolizumab. 
The number and percentage of patients with treatment-emergent adverse events (TEAEs; defined as 
any AEs, regardless of relationship to study drug), AEs leading to discontinuation, and SAEs that 
occur on or after the first dose date and up to 6 months after the last dose date of the study drug, will 
be summarized by MedDRA SOC, HLT, and PT overall, by severity, and by relationship to study 
drug.  
13.1.3.1 
Infections 
The analysis of new infections will be based on the first occurrence of an infection event after 
initiation of vedolizumab. Patients with a history of a chronic infection of interest before study entry 
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will be excluded from the analysis for that AE to enable the analyses to focus on incident events only. 
For acute infections, all patients will be included except those with the infection of interest at study 
entry. 
Analysis of reactivation of latent infections will include patients with a history of that inf ection. 
Cases of PML as confirmed by the IAC will be included in the analyses. Unconfirmed cases of PML 
will be listed in the study report but not in the main analyses. 
13.1.3.2 
Malignancies 
Analyses will focus on incident malignant neoplasms and carcinomas in situ. Benign neoplasms 
will be listed in the study report but not in the main analyses. Analyses will examine all malignancies 
pooled, then separately for each of the most common malignancies. 
13.1.3.3 
 Infusion-Related Reaction and Hypersensitivity 
Currently, vedolizumab is available for infusion only. Infusion-related reaction, as determined by 
the treating physician, will be included in the analyses. Suspected cases not confirmed by the 
treating physician will be listed in the study report but not in the main analyses. A risk window 
covering the infusion day and the day after the infusion will be used for infusion-related reactions 
and hypersensitivity. 
13.1.3.4 
 Hepatic Injury 
Cases of drug-induced liver injury adjudicated as “Related” will be included in the analyses, as these 
are the events most likely to be due to drug-related hepatotoxicity. Cases adjudicated as “Unrelated” 
will be listed in the study report but not in the main analyses. 
13.1.4 
Analysis of Treatment Efficacy Endpoints 
Descriptive statistics, including means, standard deviations, quartiles, frequencies (n) and 
percentages will be presented for the efficacy and QoL endpoints. The results at Week 14, Week 30 
and Week 46 for treatment efficacy endpoints and QoL assessments will be summarized. More 
specifically, for binary endpoints, proportions and associated 95% CIs by exact method will be 
provided. For changes from baseline in continuous endpoints, paired t-test will be used if normality 
assumption holds based on the Shapiro–Wilk test, or the Wilcoxon signed rank test will be used if 
otherwise. 
Cox regression models may be used to explore predictors (including UC/CD presentation at baseline) 
of time to treatment discontinuation. 
13.1.5 
Subgroup Analyses 
Subgroups to be explored include 
• Biologic-naïve patients  
• Biologic-experienced patients  
The details of the subgroup analysis will be detailed in the statistical analysis plan. 
The interim analysis will be performed after all subjects completes week 14 weeks assessment. All 
statistical testing at Week 14 will be two-sided and will be performed using a significance (alpha) 
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level of 0.05. A separate Interim analysis plan will be prepared for elaborative discussion about the 
analysis plan and mocks for interim assessment 
 
13.2 
Determination of Sample Size 
The study will recruit 150 patients. This sample size was recommended by the DCGI on approval of 
vedolizumab as a new drug. At least 30% of the total recruited patients will be enrolled in each UC 
or CD group.  
This sample size will enable a serious infection rate of 6 per 100 person-years to be measured with a 
precision of ±3.8 with 95% CI based on a normal approximation of the annualized proportion of 
patients to be infected. This anticipated serious infection rate is based on observed rates in a post hoc 
pooled analysis of data from Indian sites participating in the vedolizumab global Phase 3 C13006 
and C13007 clinical studies and open label extension (Study C13008) of these studies. 
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14.0 
QUALITY CONTROL AND QUALITY ASSURANCE 
14.1 
Study-Site Monitoring Visits 
Monitoring visits to the study site will be made periodically during the study to ensure that all 
aspects of the protocol are followed. Source documents will be reviewed for verification of data 
recorded on the eCRFs. Source documents are defined as original documents, data, and records. 
The investigator and institution guarantee access to source documents by the sponsor or its 
designee (CRO) and by the IRB/IEC. 
All aspects of the study and its documentation will be subject to review by the sponsor or designee, 
including but not limited to the Investigator’s Binder, study drug, patient medical records, informed 
consent documentation, documentation of patient authorization to use personal health information 
(if separate from the ICFs), and review of eCRFs and associated source documents. It is important 
that the investigator and other study personnel are available during the monitoring visits and that 
sufficient time is devoted to the process. 
14.2 
Protocol Deviations 
The investigator should not deviate from the protocol, except where necessary to eliminate an 
immediate hazard to study patients. Should other unexpected circumstances arise that will require 
deviation from protocol-specified procedures, the investigator should consult with the sponsor or 
designee (and IRB/IEC, as required) to determine the appropriate course of action. There will be no 
exemptions (a prospectively approved deviation) from the inclusion or exclusion criteria. 
The site should document all protocol deviations in the patient’s source documents. In the event of 
a significant deviation, the site should notify the sponsor or its designee (and IRB/IEC, as required). 
Significant deviations include, but are not limited to, those that involve fraud or misconduct, 
increase the health risk to the patient, or confound interpretation of primary study assessment. 
Significant protocol deviations will be entered into the eCRF, which is reviewed by the study 
sponsor or designee. 
14.3 
Quality Assurance Audits and Regulatory Agency Inspections 
The study site also may be subject to quality assurance audits by the sponsor or designees. In this 
circumstance, the sponsor-designated auditor will contact the site in advance to arrange an auditing 
visit. The auditor may ask to visit the facilities where laboratory samples are collected, where the 
drug is stored and prepared, and any other facility used during the study. If the study site is contacted 
for an inspection by a regulatory body, the sponsor should be notified immediately. The investigator 
and institution guarantee access for quality assurance auditors to all study documents as described 
in Section 14.1.
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15.0 
ETHICAL ASPECTS OF THE STUDY 
This study will be conducted with the highest respect for the individual participants (ie, patients) 
according to the protocol, the ethical principles that have their origin in the Declaration of Helsinki 
(DOH), and the ICH Harmonised Tripartite Guideline for GCP. Each investigator will conduct the 
study according to applicable local or regional regulatory requirements and align his or her conduct 
in accordance with the “Responsibilities of the Investigator” that are listed in Appendix B. The 
principles of Helsinki are addressed through the protocol and through appendices containing 
requirements for informed consent and investigator responsibilities. 
15.1 
IRB/IEC Approval 
IRBs/IECs must be constituted according to the applicable requirements of each participating region. 
The sponsor or designee will require documentation noting all names and titles of members who 
make up the respective IRB/IEC. If any member of the IRB/IEC has direct participation in this study, 
written notification regarding his or her abstinence from voting must also be obtained.  
The sponsor or designee will supply relevant documents for submission to the respective IRB/IEC 
for the protocol’s review and approval. This protocol, the Package Insert, a copy of the ICF, and, if 
applicable, patient recruitment materials and/or advertisements and other documents required by all 
applicable laws and regulations, must be submitted to a central or local IRB/IEC for approval. The 
IRB’s or IEC’s written approval of the protocol and patient informed consent must be obtained and 
submitted to the sponsor or designee before commencement of the study (ie, before shipment of the 
sponsor-supplied drug or study specific screening activity). The IRB/IEC approval must refer to the 
study by exact protocol title, number, and version date; identify versions of other documents 
(eg, ICF) reviewed; and state the approval date. The sponsor will ship drug once the sponsor has 
confirmed the adequacy of site regulatory documentation and, when applicable, the sponsor has 
received permission from competent authority to begin the study. Until the site receives notification, 
no protocol activities including screening may occur. 
Study sites must adhere to all requirements stipulated by their respective IRB/IEC. This may include 
notification to the IRB/IEC regarding protocol amendments, updates to the ICF, recruitment 
materials intended for viewing by patients, local safety reporting requirements, reports and updates 
regarding the ongoing review of the study at intervals specified by the respective IRB/IEC, and 
submission of the investigator’s final status report to IRB/IEC. All IRB/IEC approvals and relevant 
documentation for these items must be provided to the sponsor or its designee. 
Patient incentives should not exert undue influence for participation. Payments to patients must be 
approved by the IRB/IEC and sponsor. 
15.2 
Patient Information, Informed Consent, and Patient Authorization 
Written consent documents will embody the elements of informed consent as described in the 
Declaration of Helsinki and the ICH Guidelines for GCP and will be in accordance with all applicable 
laws and regulations. The ICF, patient authorization form (if applicable), and patient information 
sheet (if applicable) describe the planned and permitted uses, transfers, and disclosures of the 
patient’s personal and personal health information for purposes of conducting the study. The ICF and 
the patient information sheet (if applicable) further explain the nature of the study, its objectives, and 
potential risks and benefits, as well as the date informed consent is given. The ICF will detail the 
requirements of the participant and the fact that he or she is free to withdraw at any time without 
giving a reason and without prejudice to his or her further medical care. 
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The investigator is responsible for the preparation, content, and IRB/IEC approval of the ICF and if 
applicable, the patient authorization form. The ICF, patient authorization form (if applicable), and 
patient information sheet (if applicable) must be approved by both the IRB/IEC and the sponsor prior 
to use. 
The ICF, patient authorization form (if applicable), and patient information sheet (if applicable) must 
be written in a language fully comprehensible to the prospective patient. It is the responsibility of the 
investigator to explain the detailed elements of the ICF, patient authorization form (if applicable), 
and patient information sheet (if applicable) to the patient. Information should be given in both oral 
and written form whenever possible and in the manner deemed appropriate by the IRB/IEC. In the 
event the patient is not capable of rendering adequate written informed consent, then the patient’s 
legally acceptable representative may provide such consent for the patient in accordance with 
applicable laws and regulations. 
The patient, or the patient’s legally acceptable representative, must be given ample opportunity to: 
(1) inquire about details of the study and (2) decide whether or not to participate in the study. If the 
patient, or the patient’s legally acceptable representative, determines he or she will participate in the 
study, then the ICF and patient authorization form (if applicable) must be signed and dated by the 
patient, or the patient’s legally acceptable representative, at the time of consent and prior to the patient 
entering into the study. The patient or the patient’s legally acceptable representative should be 
instructed to sign using their legal names, not nicknames, using blue or black ballpoint ink. The 
investigator must also sign and date the ICF and patient authorization (if applicable) at the time of 
consent and prior to patient entering into the study. 
Once signed, the original ICF, patient authorization form (if applicable), and patient information 
sheet (if applicable) will be stored in the investigator’s site file. The investigator must document the 
date the patient signs the informed consent in the patient’s medical record. Copies of the signed ICF, 
the signed patient authorization form (if applicable), and patient information sheet (if applicable) 
shall be given to the patient. 
All revised ICFs must be reviewed and signed by relevant patients or the relevant patient’s legally 
acceptable representative in the same manner as the original informed consent. The date the revised 
consent was obtained should be recorded in the patient’s medical record, and the patient should 
receive a copy of the revised ICF. 
15.3 
Patient Confidentiality 
The sponsor and designees affirm and uphold the principle of the patient’s right to protection against 
invasion of privacy. Throughout this study, a patient’s source data will only be linked to the sponsor’s 
clinical trial database or documentation via a patient identification number. As permitted by all 
applicable laws and regulations, limited patient attributes, such as sex, age, or date of birth, and 
patient initials may be used to verify the patient and accuracy of the patient’s unique identification 
number. 
To comply with ICH Guidelines for GCP and to verify compliance with this protocol, the sponsor 
requires the investigator to permit the monitor or the sponsor’s designee, representatives from any 
regulatory authority (eg, FDA, Medicines and Healthcare products Regulatory Agency, 
Pharmaceuticals and Medical Devices Agency), the sponsor’s designated auditors, and the 
appropriate IRBs/IECs to review the patient’s original medical records (source data or documents), 
including, but not limited to, laboratory test result reports, ECG reports, admission and discharge 
summaries for hospital admissions occurring during a patient’s study participation, and autopsy 
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reports. Access to a patient’s original medical records requires the specific authorization of the patient 
as part of the informed consent process (see Section 15.2). 
Copies of any patient source documents that are provided to the sponsor must have certain personally 
identifiable information removed (ie, patient name, address, and other identifier fields not collected 
on the patient’s eCRF). 
15.4 
Publication, Disclosure, and Clinical Trial Registration Policy 
15.4.1 Publication and Disclosure 
The investigator is obliged to provide the sponsor with complete test results and all data derived by 
the investigator from the study. During and after the study, only the sponsor may make study 
information available to other study investigators or to regulatory agencies, except as required by law 
or regulation. Except as otherwise allowable in the clinical study site agreement, any public 
disclosure (including publicly accessible websites) related to the protocol or study results, other than 
study recruitment materials and/or advertisements, is the sole responsibility of the sponsor. 
The sponsor may publish any data and information from the study (including data and information 
generated by the investigator) without the consent of the investigator. Manuscript authorship for any 
peer-reviewed publication will appropriately reflect contributions to the production and review of the 
document as per ICMJE. All publications and presentations must be prepared in accordance with this 
section and the clinical study site agreement. In the event of any discrepancy between the protocol 
and the clinical study site agreement, the clinical study site agreement will prevail.  
15.4.2 Clinical Trial Registration 
In order to ensure that information on clinical trials reaches the public in a timely manner and to 
comply with applicable laws, regulations and guidance, Takeda will, at a minimum register 
interventional clinical trials it sponsors anywhere in the world on ClinicalTrials.gov or other 
publicly accessible websites before start of study, as defined in Takeda Policy/Standard. Takeda 
contact information, along with investigator’s city, state (for American investigators), country, and 
recruiting status will be registered and available for public viewing. 
For some registries, Takeda will assist callers in locating trial sites closest to their homes by 
providing the investigator name, address, and phone number to the callers requesting trial 
information. Once patients receive investigator contact information, they may call the site 
requesting enrollment into the trial. The investigative sites are encouraged to handle the trial 
inquiries according to their established patient screening process. If the caller asks additional 
questions beyond the topic of trial enrollment, they should be referred to the sponsor. 
Any investigator who objects to Takeda providing this information to callers must provide Takeda 
with a written notice requesting that their information not be listed on the registry site. 
15.4.3 Clinical Trial Results Disclosure 
Takeda will post the results of clinical trials on ClinicalTrials.gov and/or other publicly accessible 
websites, as required by Takeda Policy/Standard, applicable laws and/or regulations. 
15.5 
Insurance and Compensation for Injury 
Each patient in the study must be insured in accordance with the regulations applicable to the site 
where the patient is participating. If a local underwriter is required, then the sponsor or sponsor’s 
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designee will obtain clinical study insurance against the risk of injury to study patients. Refer to the 
study site agreement regarding the sponsor’s policy on patient compensation and treatment for injury. 
If the investigator has questions regarding this policy, he or she should contact the sponsor or 
sponsor’s designee.
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REFERENCES 
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and prevalence of the inflammatory bowel diseases with time, based on systematic review. 
Gastroenterology 2012;142(1):46-54 e42; quiz e30. 
2. Ahuja V, Tandon RK. Inflammatory bowel disease in the Asia-Pacific area: a comparison with 
developed countries and regional differences. J Dig Dis 2010;11(3):134-47. 
3. Sood A, Midha V, Sood N, Bhatia AS, Avasthi G. Incidence and prevalence of ulcerative colitis 
in Punjab, North India. Gut 2003;52(11):1587-90. 
4. Lee YM, Fock K, See SJ, Ng TM, Khor C, Teo EK. Racial differences in the prevalence of 
ulcerative colitis and Crohn's disease in Singapore. J Gastroenterol Hepatol 2000;15(6):622-5. 
5. Probert CS, Jayanthi V, Hughes AO, Thompson JR, Wicks AC, Mayberry JF. Prevalence and 
family risk of ulcerative colitis and Crohn's disease: an epidemiological study among Europeans 
and south Asians in Leicestershire. Gut 1993;34(11):1547-51. 
6. Tan YM, Goh KL. Ulcerative colitis in a multiracial Asian country: racial differences and clinical 
presentation among Malaysian patients. World J Gastroenterol 2005;11(37):5859-62. 
7. Hanauer SB, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, Colombel JF, et al. 
Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet 
2002;359(9317):1541-9. 
8. Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, et al. Infliximab for 
induction and maintenance therapy for ulcerative colitis. N Engl J Med 2005;353(23):2462-76. 
9. Colombel JF, Sandborn WJ, Rutgeerts P, Enns R, Hanauer SB, Panaccione R, et al. Adalimumab 
for maintenance of clinical response and remission in patients with Crohn's disease: the CHARM 
trial. Gastroenterology 2007;132(1):52-65. 
10. Soler D, Chapman T, Yang L, Wyant T, Egan R, Fedyk ER. The binding specificity and selective 
antagonism of vedolizumab, an anti-alpha4beta7 integrin therapeutic antibody in development 
for inflammatory bowel diseases. J Pharmacol Exp Ther. 2009; 330(3): 864-875.  
11. Elizabeth R. Paine, Colonoscopic evaluation in ulcerative colitis, Gastroenterology Report 2014; 
29(3):161-168. 
12. Evertsz FB, Nieuwkerk PT, Stokkers PCF, Ponsioen CY, Bockting CLH, Sanderman R, 
Sprangers MAG. The Patient Simple Clinical Colitis Activity Index (P-SCCAI) can detect 
ulcerative colitis (UC) disease activity in remission: A comparison of the P-SCCAI with 
clinician-based SCCAI and biological markers, Journal of Crohn's and Colitis 2013; 7(11):890-
900. 
13. Gajendran M, Loganathan P, Catinella AP, Hashash JG. A comrehensive review and update on 
Crohn’s disease. Dis Mon 2018;64(2):20-57.  
14. Ferrante M, Colobel J, Sandborn W, et al. Validation of endoscopic activity scores in patients 
with Crohn’s disease based on a post hoc analysis of data from SONIC. Gastroenterology. 
2013;145:978-986.  
15. Vuitton L, Peyrin-Biroulet L, Colombel JF, Pariente B, Pineton de Chambrun G, Walsh AJ, et al. 
Defining endoscopic response and remission in ulcerative colitis clinical trials: an international 
consensus. Aliment Pharmacol Ther 2017;45:801-13. 
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16. .Vuitton L, Marteau P, Sandborn WJ, Levesque BG, Feagan B, Vermeire S, et al. IOIBD technical 
review on endoscopic indices for Crohn's disease clinical trials. Gut 2016; 20:1447-55 
17. Irvine EJ, Zhou Q, Thompson AK. The Short Inflammatory Bowel Disease Questionnaire: a 
quality of life instrument for community physicians managing inflammatory bowel disease. 
CCRPT Investigators. Canadian Crohn’s Relapse Prevention Trial. Am J Gastroenterol 
1996;91:1571-8. 
18.  Berger JR, Aksamit AJ, Clifford DB, Davis L, Koralnik IJ, Sejvar JJ, et al. PML diagnostic 
criteria: consensus statement from the AAN Neuroinfectious Disease Section. Neurology 
2013;80(15):1430-8. 
19. Sampson HA, Munoz-Furlong A, Campbell RL, Adkinson NF, Jr., Bock SA, Branum A, et al. 
Second symposium on the definition and management of anaphylaxis: summary report--Second 
National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network 
symposium. J Allergy Clin Immunol 2006;117(2):391-7. 
20. Major EO. Progressive multifocal leukoencephalopathy in patients on immunomodulatory 
therapies. Annu Rev Med 2010;61:35-47. 
21. Steiner I, Berger JR. Update on progressive multifocal leukoencephalopathy. Curr Neurol 
Neurosci Rep 2012;12(6):680-6. 
22. Sandborn WJ, Colombel JF, Enns R, Feagan BG, Hanauer SB, Lawrance IC, et al. Natalizumab 
induction and maintenance therapy for Crohn’s disease. N Engl J Med 2005;353(18):1912-25. 
23. TYSABRI (natalizumab) injection. Full Prescribing Information. Cambridge, MA: Biogen Idec 
Inc., Revised June 2013. 
24. Soler D, Chapman T, Yang LL, Wyant T, Egan R, Fedyk ER. The binding specificity and 
selective antagonism of vedolizumab, an anti-alpha4beta7 integrin therapeutic antibody in 
development for inflammatory bowel diseases. J Pharmacol Exp Ther 2009;330(3):864-75. 
25. Lewis JD, Chuai S, Nessel L, Lichtenstein GR, Aberra FN, Ellenberg JH. Use of the noninvasive 
components of the Mayo score to assess clinical response in ulcerative colitis. Inflamm Bowel 
Dis 2008;14(12):1660-6. 
26. Harvey RF, Bradshaw JM. A simple index of Crohn's-disease activity. Lancet 
1980;315(8167):514. 
27. Vitali R, Stronati L, Negroni A, Di Nardo G, Pierdomenico M, del Giudice E, et al. Fecal 
HMGB1 is a novel marker of intestinal mucosal inflammation in pediatric inflammatory bowel 
disease. Am J Gastroenterol 2011;106(11):2029-40. 
 
 
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Appendix A: Schedule of Study Procedures 
AE= Adverse event, AESI= Adverse event of special interest, anti-HCV= anti-hepatitis C virus, CD= Crohn’s disease, 
CRP= C-reactive protein, ECG= Electrocardiogram, ET= Early Termination, HBI= Harvey Bradshaw Index, HBsAg= Hepatitis B 
surface antigen, HIV= Human Immunodeficiency Virus, IBD= Inflammatory bowel disease, PML= Progressive multifocal 
Study Day/Week 
Screening 
 
Treatment 
Follow-up 
 
Days  
-28 to -1 
(a) 
(Day 
1) (a) 
Week 
0 
Week 
2 
Week 
6 
Week 
10 
Week 
14 
Week 
22 
Week 
30 
Week 
38 
Week 46 
End of 
treatment 
Visit or 
ET (b) 
Safety 
Follow-
up 
(16weeks 
postdose) 
Long-
term 
Follow-up 
(l) 
(6 
months 
postdose) 
Unscheduled 
visit 
Visit Windows 
(Days): 
 
 
±3 
±3 
±3 
±3 
±7 
±7 
±7 
±7 
±7 
 
 
Visit Number: 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion 
criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
/medical and 
medication 
history/concurrent 
medical conditions 
X 
 
 
 
 
 
 
 
 
 
 
 
 
CD or UC prior 
biologics history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
Height and weight (c) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
IBD and other 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Dosing 
 
X 
X 
X 
Xm 
X 
X 
X 
X 
X 
 
 
 
Full Mayo Score/SES-
CD/SCCAI/HBI 
assessments  
X (d) 
X (e) 
 
 
 
X (e) 
 
X (e) 
 
X (e) 
 
 
 
PML Checklist 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
QoL (SIBDQ) 
X 
X 
 
 
 
X 
 
X 
 
X 
X 
 
 
Inflammatory 
biomarkers (CRP if 
measured) 
X 
 
X 
X 
X 
Inflammatory 
biomarkers (Fecal 
calprotectin if 
measured) 
X 
 
 
 
 
X 
 
X 
 
X 
 
 
 
Colonoscopy/ Ileo-
colonoscopy 
X (f) 
 
 
 
 
X (g) 
 
 
 
X (g) 
 
 
 
ECG 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
Sample Collection: 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clostridium difficile 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Tuberculosis screening 
(h) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Hepatitis test (i) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
HIV test (i) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Serum chemistry and 
hematology 
X 
 
 
 
 
X 
 
X 
 
X 
 
 
X (j) 
Urinalysis 
X 
 
 
 
 
X 
 
X 
 
X 
 
 
  
Pregnancy test (k) 
X 
X 
X 
X 
X  
X 
X 
X 
X 
X 
X 
 
X 
PTE/AE/SAE/AESIs 
collection 
X 
X 
X 
X 
X  
X 
X 
X 
X 
X 
X 
X 
X 
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Study no. Vedolizumab-4020 
Page 63 of 83 
Protocol Amendment 4 
09 November 2022 
 
 
 
leukoencephalopathy, PTE= Pretreatment event, QoL= Quality of life, SAE= Serious adverse event, SCCAI= Simple Clinical Colitis 
Activity Index, SIBDQ= Short Inflammatory Bowel Disease Questionnaire, UC= Ulcerative colitis  
a) 
The day of first study drug administration for treatment period is Day 1. The day before first study drug administration for Treatment 
period is Day -1. 
b) 
The end of treatment visit or ET is defined as the date of the last visit (Week 46) of the patient or until discontinuation of vedolizumab. 
c) 
Height data collected only at the Screening Visit. 
d) 
Full Mayo Score for UC and HBI score for CD will be calculated at the time of screening. The components of the Full Mayo score 
and HBI to determine eligibility must be completed within 14 days prior to enrollment. The investigator will complete the Full Mayo 
Score and HBI questionnaires at the time of screening. SES-CD score will be calculated at the time of screening in CD patients. 
e) 
SCCAI/HBI will be calculated at the baseline (Day 1 prior to dosing/Week 0) and at Weeks 14, 30, and 46 for efficacy assessments. 
The investigator will complete the SCCAI and HBI questionnaires at the time of visit.  
f) 
Colonoscopy/Ileo-colonoscopy should have been performed within 30 days before the patient enrollment or at the time of screening. 
g) 
Colonoscopy/ Ileo-colonoscopy is not mandatory, however if performed will be used to assess mucosal healing and endoscopic 
response using Mayo endoscopic subscore in UC patients and SES-CD score in CD patients.  
h) 
Mantoux test/Chest X-ray/Interferon gamma release assay as per the feasibility of the site and investigator’s decision. 
i) 
Hepatitis panel, including HBsAg and anti-HCV and HIV testing done only at the Screening Visit. 
j) 
Serum chemistry and hematology will be done at investigator’s decision. 
k) 
Serum pregnanacy (β-hCG) test will be done at Screening, and only urine pregnancy test will be done at other visits. 
l) 
Patients will participate in the long-term follow-up safety survey by telephonic visit 
m)  Patients who have not shown a response can receive a dose at 10 week 
. 
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Study no. Vedolizumab-4020 
Page 64 of 83 
Protocol Amendment 4 
09 November 2022 
 
 
 
Appendix B: Responsibilities of the Investigator 
Clinical research studies sponsored by the sponsor are subject to International Conference on 
Harmonisation E6 Good Clinical Practice (ICH GCP) and all the applicable local laws and 
regulations.  
The investigator agrees to assume the following responsibilities: 
1. Conduct the study in accordance with the protocol. 
2. Personally conduct or supervise the staff who will assist in the protocol. 
3. Ensure that study related procedures, including study specific (non routine/non standard panel) 
screening assessments are NOT performed on potential patients, prior to the receipt of written 
approval from relevant governing bodies/authorities. 
4. Ensure that all colleagues and employees assisting in the conduct of the study are informed of 
these obligations. 
5. Secure prior approval of the study and any changes by an appropriate Institutional Review Board 
(IRB)/Independent Ethics Committee (IEC) that conform to ICH, and local regulatory 
requirements. 
6. Ensure that the IRB/IEC will be responsible for initial review, continuing review, and approval 
of the protocol. Promptly report to the IRB/IEC all changes in research activity and all anticipated 
risks to patients. Make at least yearly reports on the progress of the study to the IRB/IEC, and 
issue a final report within 3 months of study completion. 
7. Ensure that requirements for informed consent, as outlined in ICH and local regulations, are met. 
8. Obtain valid informed consent from each patient who participates in the study, and document the 
date of consent in the patient’s medical chart. Valid informed consent is the most current version 
approved by the IRB/IEC. Each informed consent form should contain a patient authorization 
section that describes the uses and disclosures of a patient’s personal information (including 
personal health information) that will take place in connection with the study. If an informed 
consent form does not include such a patient authorization, then the investigator must obtain a 
separate patient authorization form from each patient or the patient’s legally acceptable 
representative. 
9. Prepare and maintain adequate case histories of all persons entered into the study, including 
eCRFs, hospital records, laboratory results, etc, and maintain these data for a minimum of 2 years 
following notification by the sponsor that all investigations have been discontinued or that the 
regulatory authority has approved the marketing application. The investigator should contact and 
receive written approval from the sponsor before disposing of any such documents. 
10. Allow possible inspection and copying by the regulatory authority of GCP-specified essential 
documents. 
11. Maintain current records of the receipt, administration, and disposition of sponsor-supplied drugs, 
and return all unused sponsor-supplied drugs to the sponsor.  
12. Report adverse reactions to the sponsor promptly. In the event of an serious adverse event (SAE), 
notify the sponsor within 24 hours. 
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Study no. Vedolizumab-4020 
Page 65 of 83 
Protocol Amendment 4 
09 November 2022 
 
 
 
Appendix C: Elements of the Patient Informed Consent  
In seeking informed consent, the following information shall be provided to each patient: 
1. A statement that the study involves research. 
2. An explanation of the purposes of the research. 
3. The expected duration of the patient’s participation. 
4. A description of the procedures to be followed, including invasive procedures. 
5. The identification of any procedures that are experimental. 
6. The estimated number of patients involved in the study. 
7. A description of the patient’s responsibilities. 
8. A description of the conduct of the study. 
9. A statement describing the treatment. 
10. A description of the possible side effects of the treatment that the patient may receive. 
11. A description of any reasonably foreseeable risks or discomforts to the patient and, when 
applicable, to an embryo, fetus, or nursing infant. 
12. A description of any benefits to the patient or to others that reasonably may be expected from the 
research. When there is no intended clinical benefit to the patient, the patient should be made 
aware of this. 
13. Disclosures of appropriate alternative procedures or courses of treatment, if any, that might be 
advantageous to the patient and their important potential risks and benefits. 
14. A statement describing the extent to which confidentiality of records identifying the patient will 
be maintained, and a note of the possibility that regulatory agencies, auditor(s), Institutional 
Review Board (IRB)/Independent Ethics Committee (IEC), and the monitor may inspect the 
records. By signing a written informed consent form, the patient or the patient’s legally 
acceptable representative is authorizing such access. 
15. For research involving more than minimal risk, an explanation as to whether any compensation 
and an explanation as to whether any medical treatments are available if injury occurs and, if so, 
what they consist of or where further information may be obtained. 
16. The anticipated prorated payment(s), if any, to the patient for participating in the study. 
17. The anticipated expenses, if any, to the patient for participating in the study. 
18. An explanation of whom to contact for answers to pertinent questions about the research 
(investigator), patient’s rights, and IRB/IEC and whom to contact in the event of a research-
related injury to the patient. 
19. A statement that participation is voluntary, that refusal to participate will involve no penalty or 
loss of benefits to which the patient otherwise is entitled, and that the patient (or the patient’s 
legally acceptable representative) may discontinue participation at any time without penalty or 
loss of benefits to which the patient is otherwise entitled. 
20. The consequences of a patient’s decision to withdraw from the research and procedures for 
orderly termination of participation by the patient. 
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Study no. Vedolizumab-4020 
Page 66 of 83 
Protocol Amendment 4 
09 November 2022 
 
 
 
21. A statement that there is a possibility of failure of investigational product to provide intended 
therapeutic effect. 
22. A statement that the patient (or the patient’s legally acceptable representative) will be informed 
in a timely manner if information becomes available that may be relevant to the patient’s 
willingness to continue participation in the study. 
23. A statement that results of pharmacogenomic analysis will not be disclosed to an individual, 
unless prevailing laws require the sponsor to do so. 
24. The foreseeable circumstances or reasons under which the patient’s participation in the study may 
be terminated. 
25. A written patient authorization (either contained within the informed consent form or provided 
as a separate document) describing to the patient the contemplated and permissible uses and 
disclosures of the patient’s personal information (including personal health information) for 
purposes of conducting the study. The patient authorization must contain the following statements 
regarding the uses and disclosures of the patient’s personal information: 
a) that personal information (including personal health information) may be processed by or 
transferred to other parties in other countries for clinical research and safety reporting 
purposes, including, without limitation, to the following: (1) Takeda, its affiliates, and 
licensing partners; (2) business partners assisting Takeda, its affiliates, and licensing partners; 
(3) regulatory agencies and other health authorities; and (4) IRBs/IECs; 
b) it is possible that personal information (including personal health information) may be 
processed and transferred to countries that do not have data protection laws that offer patients 
the same level of protection as the data protection laws within this country; however, Takeda 
will make every effort to keep your personal information confidential, and your name will 
not be disclosed outside the clinic unless required by law; 
c) that personal information (including personal health information) may be added to Takeda’s 
research databases for purposes of developing a better understanding of the safety and 
efficacy of the study drug, studying other therapies for patients, developing a better 
understanding of disease, and improving the efficiency of future clinical studies; 
d) that patients agree not to restrict the use and disclosure of their personal information 
(including personal health information) upon withdrawal from the study to the extent that the 
restricted use or disclosure of such information may impact the scientific integrity of the 
research; and 
e) that the patient’s identity will remain confidential in the event that study results are published. 
26. Female patients of childbearing potential (eg, nonsterilized, premenopausal female patients) who 
are sexually active must use highly effective contraception (as defined in the informed consent) 
from Screening throughout the duration of the study, and for 16 weeks after last dose. Regular 
pregnancy tests will be performed throughout the study for all female patients of childbearing 
potential. If a patient is found to be pregnant during study, study drug will be discontinued and 
the investigator will offer the patient the choice to receive unblinded treatment information. 
27. Male patients must use highly effective contraception (as defined in the informed consent) from 
signing the informed consent throughout the duration of the study, and for 16 weeks after last 
dose. If the partner or wife of the patient is found to be pregnant during the study, the investigator 
will offer the patient the choice to receive unblinded treatment information. 
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Study no. Vedolizumab-4020 
Page 67 of 83 
Protocol Amendment 4 
09 November 2022 
 
 
 
28. A statement that clinical trial information from this trial will be publicly disclosed in a publicly 
accessible website, such as ClinicalTrials.gov. 
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Vedolizumab IV 
Study no. Vedolizumab-4020 
Page 68 of 83 
Protocol Amendment 4 
09 November 2022 
 
 
 
Appendix D: Investigator Consent to Use of Personal Information  
Takeda will collect and retain personal information of investigator, including his or her name, 
address, and other personally identifiable information. In addition, investigator’s personal 
information may be transferred to other parties located in countries throughout the world (eg, the 
United Kingdom, United States, and Japan), including the following: 
• Takeda, its affiliates, and licensing partners 
• Business partners assisting Takeda, its affiliates, and licensing partners 
• Regulatory agencies and other health authorities 
• Institutional Review Board 
Investigator’s personal information may be retained, processed, and transferred by Takeda and 
these other parties for research purposes including the following: 
• Assessment of the suitability of investigator for the study and/or other clinical studies 
• Management, monitoring, inspection, and audit of the study 
• Analysis, review, and verification of the study results 
• Safety reporting and pharmacovigilance relating to the study 
• Preparation and submission of regulatory filings, correspondence, and communications to 
regulatory agencies relating to the study. 
• Preparation and submission of regulatory filings, correspondence, and communications to 
regulatory agencies relating to other medications used in other clinical studies that may contain 
the same chemical compound present in the study drug. 
• Inspections and investigations by regulatory authorities relating to the study 
• Self-inspection and internal audit within Takeda, its affiliates, and licensing partners 
• Archiving and audit of study records 
• Posting investigator site contact information, study details and results on publicly accessible 
clinical trial registries, databases, and websites. 
Investigator’s personal information may be transferred to other countries that do not have data 
protection laws that offer the same level of protection as data protection laws in investigator’s own 
country. 
Investigator acknowledges and consents to the use of his or her personal information by Takeda 
and other parties for the purposes described above. 
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Vedolizumab IV 
Study no. Vedolizumab-4020 
Page 69 of 83 
Protocol Amendment 4 
09 November 2022 
 
 
 
Appendix E: Mayo Scoring System for the Assessment of Ulcerative Colitis Activity 
 
Component 
Score 
Stool Frequency 
Normal 
0 
1–2 stools/day more than normal 
1 
3–4 stools/day more than normal 
2 
>4 stools/day more than normal 
3 
Rectal Bleeding 
None 
0 
Visible blood with stool less than half the time 
1 
Visible blood with stool half of the time or more 
2 
Passing blood alone 
3 
Physician Rating of Disease Activity 
Normal 
0 
Mild 
1 
Moderate 
2 
Severe 
 
3 
Endoscopic Findings 
Score 
 
Normal or inactive disease 
0 
 
Mild disease (erythema, decreased vascular pattern, mild friability) 
1 
 
 
Moderate disease (marked erythema, absent vascular pattern, friability, erosions) 
2 
 
Severe disease (spontaneous bleeding, ulceration) 
3 
Full Mayo Score 
 
(sum) 
 
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Study no. Vedolizumab-4020 
Page 70 of 83 
Protocol Amendment 4 
09 November 2022 
 
 
 
Assessments 
Mucosal healing 
Mayo endoscopic subscore of ≤1 point 
Endoscopic response 
Decrease in Mayo endoscopic subscore of ≥1 point 
Clinical remission 
0-2 
Mild 
3-5 
Moderate 
6-10 
Severe 
11-12 
Source: [25]
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Study no. Vedolizumab-4020 
Page 71 of 83 
Protocol Amendment 4 
09 November 2022 
 
 
 
Appendix F: Harvey-Bradshaw Index for Crohn’s Disease 
Component 
Score 
General Well-Being 
Very well 
0 
Slightly below average 
1 
Poor 
2 
Very poor 
3 
Terrible 
4 
Abdominal Pain 
None 
0 
Mild 
1 
Moderate 
2 
Severe 
3 
Number of Liquid Stools per Day 
(#) 
Abdominal Mass 
None 
0 
Dubious 
1 
Definite 
2 
Tender 
3 
Complications 
Arthralgia 
1 
Uveitis 
1 
Erythema nodosum 
1 
Aphthous ulcers 
1 
Pyoderma gangrenosum 
1 
Anal fissures 
1 
New fistula 
1 
Abscess 
1 
Total 
(sum) 
Assessments 
Clinical remission 
≤4 
Clinical response  
Decrease in HBI of ≥3 points from baseline  
Mild disease 
5-7 
Moderate disease 
8-16 
Severe disease  
>16 
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Study no. Vedolizumab-4020 
Page 72 of 83 
Protocol Amendment 4 
09 November 2022 
 
 
 
Source: [26]. 
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Study no. Vedolizumab-4020 
Page 73 of 83 
Protocol Amendment 4 
09 November 2022 
 
 
 
Appendix G: Simple Clinical Colitis Activity Index (SCCAI) 
Symptoms refer to the previous week: 
Component 
Score 
Bowel frequency (day), n (1 per occurrence) 
0-3 
0 
4-6 
1 
7-9 
2 
>9 
3 
Bowel frequency (night) 
0 
0 
1-3 
1 
4-6 
2 
Urgency of defecation 
 
None 
0 
Hurry 
1 
Immediately (toilet nearby) 
2 
Incontinence 
3 
Blood in stool 
None 
0 
Trace 
1 
 Occasionally frank (<50% of defecation) 
2 
 Usually frank (>50% of defecation) 
3 
General well-being (0-10) 
 
 
 
≥7 (very well) 
0 
6 (slightly below par) 
1 
5 (poor) 
2 
4 (very poor) 
3 
<4 (terrible) 
4 
Extracolonic features (1 per manifestation) 
 
 
 
Arthritis 
 
Yes 
1 
No 
0 
Uveitis 
 
Yes 
1 
No 
0 
Erythema nodosum 
 
Yes 
1 
No 
0 
Pyoderma gangrenosum 
 
Yes 
1 
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Study no. Vedolizumab-4020 
Page 74 of 83 
Protocol Amendment 4 
09 November 2022 
 
 
 
Component 
Score 
No 
0 
Total 
(sum) 
Assessments 
Inactive UC 
SCCAI score of <5  
Active UC  
SCCAI score of ≥5 
Clinical response  
Decrease in SCCAI ≥3 from baseline 
Clinical remission  
SCCAI score of ≤2 with no individual subscore >1 
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Study no. Vedolizumab-4020 
Page 75 of 83 
Protocol Amendment 4 
09 November 2022 
 
 
 
Appendix H: Simple Endoscopic Score for Crohn’s Disease (SES-CD) 
Definition - scoring of elementary lesions considered: 
SES-CD values (evaluated for each of the 5 ileo-colonic segments 
Variable 
0 
1 
2 
3 
Size of ulcers 
None 
Aphthous ulcers 
Large ulcers 
Very large ulcers 
(Ø 0.1 to 0.5 cm) 
(Ø 0.5 to 2 cm) 
(Ø >2 cm) 
Ulcerated surface 
None 
<10% 
10-30% 
>30% 
Affected surface Unaffected segment 
<50% 
50-75% 
>75% 
Stenosis 
None 
Single, can be passed 
Multip le, can be passed 
Cannot be passed 
 
Transverse 
Ileum 
Right Colon 
Colon 
Left 
Colon 
Rectum 
Total 
Presence and size of ulcers (0-3) 
0-3 
0-3 
0-3 
0-3 
0-3 
0-15 
Extent of ulcerated surface (0-3) 
0-3 
0-3 
0-3 
0-3 
0-3 
0-15 
Extent of affected surface (0-3) 
0-3 
0-3 
0-3 
0-3 
0-3 
0-15 
Presence and type of narrowings 
0-3 
0-3 
0-3 
0-3 
0-3 
0-15 
SES -CD = 
0-60 
 
 
Assessments 
Mucosal healing 
SES-CD 0-2 or SES-CD ≤4 and at least a 2 point reduction from baseline with no 
sub-score >1 
Endoscopic 
response 
>50% decrease in SES-CD 
 
Source: [27].
For non-commercial use only


  
Vedolizumab 
 
Study No. Vedolizumab-4020 
Page 76 of 83 
Protocol Amendment no. 2 
09 October 2020 
 
 
 
Appendix I: Short Inflammatory Bowel Disease Questionnaire (SIBDQ) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Vedolizumab 
 
Study No. Vedolizumab-4020 
Page 77 of 83 
Protocol Amendment no. 2 
09 October 2020 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Vedolizumab 
 
Study No. Vedolizumab-4020 
Page 78 of 83 
Protocol Amendment no. 2 
09 October 2020 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Vedolizumab 
 
Study No. Vedolizumab-4020 
Page 79 of 83 
Protocol Amendment no. 2 
09 October 2020 
 
 
 
 
 
 
 
 
 
 
For non-commercial use only


Vedolizumab 
 
Study No. Vedolizumab-4020 
Page 80 of 83 
Protocol Amendment no. 2 
09 October 2020 
 
 
Appendix J: Progresive Multifocal Leukoencephalopathy (PML) Symptom Checklist 
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Vedolizumab 
 
Study No. Vedolizumab-4020 
Page 81 of 83 
Protocol Amendment no. 2 
09 October 2020 
 
 
 
 
 
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Vedolizumab 
 
Study No. Vedolizumab-4020 
Page 82 of 83 
Protocol Amendment no. 2 
09 October 2020 
 
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Vedolizumab 
 
Study No. Vedolizumab-4020 
Page 83 of 83 
Protocol Amendment no. 2 
09 October 2020 
 
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SAP_001.pdf: 
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STATISTICAL ANALYSIS PLAN 
Study Number: Vedolizumab-4020 
Study Title: A Multicenter, Single arm, Open- label, Phase 4 study to Evaluate Safety and 
Efficacy of Vedolizumab in Indian Patients with Ulcerative Colitis and Crohn’s Disease. 
Phase: Phase 4 
Version: 1.0 
Date: 23-Sept-2022 
Prepared by: 
 
Based on: Protocol 
Protocol Version: 3.0 
Protocol Date: 30-March-2021 
CONFIDENTIAL PROPERTY OF TAKEDA 
This document is a confidential communication of Takeda. Acceptance of this document constitutes the agreement 
by the recipient that no information contained herein will be published or disclosed without written authorization 
from Takeda. 
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Vedolizumab-4020
Page 2 of 25
Statistical Analysis Plan -01
                                                                   23-09-2022
CONFIDENTIAL
Signatures:
Study Statistician
SIRO Clinpharm Pvt. Ltd
 
SIRO Clinpharm Pvt. Ltd.
Medical Writer
SIRO Clinpharm Pvt. Ltd.
Date
Dr 
Medical and Safety Monitor 
SIRO Clinpharm Pvt. Ltd.
Date
SIRO Clinpharm Pvt. Ltd.
Date
Dr 
 
Takeda Pharmaceutical company
Date
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Vedolizumab-4020 
Page 3 of 25
Statistical Analysis Plan -01 
                                                                   23-09-2022 
 
CONFIDENTIAL 
 
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Vedolizumab-4020 
Page 4 of 25
Statistical Analysis Plan -01 
                                                                   23-09-2022 
 
CONFIDENTIAL 
REVISION HISTORY 
 
Version  
Approval Date 
 
Primary Rationale for Revision 
 
1.0 
23-Sept-2022 
Baseline Version 
  
 
[To make SAP consistent with Amendment 1 of the protocol] 
 
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Vedolizumab-4020 
Page 5 of 25
Statistical Analysis Plan -01 
                                                                   23-09-2022 
 
CONFIDENTIAL 
TABLE OF CONTENTS 
1.0 
OBJECTIVES, ENDPOINTS AND ESTIMANDS ............................................................8 
1.1 
Objectives ......................................................................................................................8 
1.1.1   Primary Objective .....................................................................................................8 
1.1.2   Secondary Objective(s) .............................................................................................8 
1.1.3 
Additional Objective(s) .........................................................................................8 
1.2 
Endpoints .......................................................................................................................8 
1.2.1 
Primary Endpoint(s) ..............................................................................................8 
1.2.2 
Secondary Endpoint(s) ..........................................................................................8 
1.2.2.1 
Key Secondary Endpoints(s) .........................................................................8 
1.2.2.2 
Other Secondary Endpoint(s) ........................................................................9 
1.2.3 
Exploratory Endpoint(s) ........................................................................................9 
1.2.4 
Safety Endpoints ....................................................................................................9 
1.2.5 
Other Endpoints .....................................................................................................9 
1.3 
Estimand(s) ....................................................................................................................9 
2.0 STUDY DESIGN.....................................................................................................................10 
3.0 
SAMPLE-SIZE DETERMINATION ................................................................................11 
4.0 
ANALYSIS SETS .............................................................................................................11 
4.1 
Safety Analysis Set ......................................................................................................11 
4.2 
Per-Protocol Analysis Set ............................................................................................11 
4.3 
Pharmacokinetic Analysis Set......................................................................................11 
5.0 
STATISTICAL ANALYSIS .............................................................................................12 
5.1 
General Considerations ................................................................................................12 
5.1.1 
Analysis Approach for Continuous Variables .....................................................12 
5.1.2 
Analysis Approach for Binary Variables ............................................................13 
5.1.3 
Analysis Approach for Time-to-Event Variables ................................................13 
5.2 
Disposition of Subjects ................................................................................................13 
5.3 
Demographic and Other Baseline Characteristics .......................................................14 
5.3.1 
Demographics ......................................................................................................14 
5.3.2 
Medical History and Concurrent Medical Conditions .........................................15 
5.3.3 
Baseline Characteristics .......................................................................................15 
5.4 
Medication History and Concomitant Medications .....................................................15 
5.4.1 
Prior Medications ................................................................................................15 
5.4.2 
Concomitant Medications ....................................................................................16 
5.5 
Efficacy Analysis .........................................................................................................16 
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Statistical Analysis Plan -01 
                                                                   23-09-2022 
 
CONFIDENTIAL 
5.5.1 
Primary Endpoint(s) Analysis .............................................................................16 
5.5.2 
Secondary Endpoint(s) Analysis .........................................................................18 
5.5.3 
Subgroup Analyses ..............................................................................................20 
5.6 
Safety Analysis ............................................................................................................21 
5.6.1 
Adverse Events ....................................................................................................22 
5.6.2 
Adverse Events of Special Interest ......................................................................23 
5.6.3 
Extent of Exposure and Compliance ...................................................................23 
5.7 
Interim Analyses ..........................................................................................................24 
5.8 
Data Monitoring Committee/Internal Review Committee/ [Other Data Review 
Committees] .................................................................................................................24 
6.0 
REFERENCES ..................................................................................................................24 
7.0 
CHANGES TO PROTOCOL PLANNED ANALYSES ...................................................24 
8.0 
APPENDIX ........................................................................................................................24 
8.1 
Changes from the Previous Version of the SAP ..........................................................24 
8.2 
Data Handling Conventions .........................................................................................24 
8.2.1 
General Data Reporting Conventions ..................................................................24 
8.2.2 
Definition of Baseline ..........................................................................................25 
8.2.3 
Definition of Visit Windows ...............................................................................25 
8.3 
Analysis Software ........................................................................................................25 
 
 
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Page 7 of 25
Statistical Analysis Plan -01 
                                                                   23-09-2022 
 
CONFIDENTIAL 
ABBREVIATIONS 
 
% 
Percentage 
ADR 
Adverse Drug Reaction 
AE 
Adverse Event 
AESI 
Adverse Event of Special Interest 
ATC 
Anatomical Therapeutic Chemical 
BMI 
Body Mass Index 
CD 
Crohn’s disease 
CI 
Confidence Interval 
CM 
Centimeter 
DCGI 
Drug Controller General of India 
EAIR 
Exposure-Adjusted Incidence Rates 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report form 
HBI 
Harvey-Bradshaw Index 
IBD 
Inflammatory Bowel Disease 
IV 
Intravenous 
Kg 
Kilogram 
MedDRA 
Medical Dictionary for Regulatory Activities 
N 
Number/count 
PK 
Pharmacokinetic 
PPAS 
Per-Protocol Analysis Set 
PRO 
Patient-Reported Outcomes 
PT 
Preferred Term  
Q1 
First Quartile 
Q3 
Third Quartile 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SAS 
Safety Analysis Set 
SCCAI 
Simple Clinical Colitis Activity Index 
SD 
Standard Deviation 
SIBDQ 
Short Inflammatory Bowel Disease Questionnaire 
SOC 
System Organ Class 
TEAE  
Treatment-Emergent Adverse Event 
UC 
Ulcerative Colitis 
WHODD 
World Health Organization Drug Dictionary 
 
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1.0 
OBJECTIVES, ENDPOINTS AND ESTIMANDS 
1.1 
Objectives 
 
1.1.1   Primary Objective 
 
x To assess the safety of vedolizumab IV in patients with UC or CD in India  
 
1.1.2   Secondary Objective(s) 
x To assess the efficacy of vedolizumab IV in patients with UC or CD in India  
 
1.1.3 
Additional Objective(s) 
Not Applicable 
1.2 
Endpoints 
 
1.2.1 
Primary Endpoint(s) 
The primary endpoint includes: 
 
x Incidence of AEs, SAEs, AEs of special interest (AESIs), ADRs, and unexpected ADRs  
 
1.2.2 
Secondary Endpoint(s)  
1.2.2.1 
Key Secondary Endpoints(s) 
• Proportion of patients with clinical response at Weeks 14, 30, and 46 in UC and CD groups  
• Proportion of patients with clinical remission at Weeks 14, 30, and 46 in UC and CD groups  
• Proportion of patients with vedolizumab discontinuation in UC and CD groups  
• Proportion of patients with mucosal healing/endoscopic response at Week 46 in UC and CD 
groups  
• Change in the patient-reported Quality of Life (Short Inflammatory Bowel Disease Questionnaire 
[SIBDQ]) from baseline to Weeks 14, 30, and 46  
 
 
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1.2.2.2 
Other Secondary Endpoint(s) 
 Not applicable 
1.2.3 
Exploratory Endpoint(s) 
Not Applicable. 
1.2.4 
Safety Endpoints 
Since safety endpoints are used in the analysis of primary endpoints, the analysis of these 
variable are described in section 1.2.1. 
1.2.5 
Other Endpoints 
Not Applicable. 
1.3 
Estimand(s) 
Not applicable 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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2.0 STUDY DESIGN 
This is an open-label, single-arm, prospective, Phase 4 study to be conducted at multiple sites in 
India to evaluate the safety and efficacy of vedolizumab 300 mg IV infusion in patients with 
moderately to severely active UC or CD.  
Approximately 150 patients with moderately to severely active UC or CD who have demonstrated 
inadequate response to, loss of response to, or intolerance to either conventional therapy or tumor 
necrosis factor-alpha (TNFα) antagonist will be enrolled in this study. At least 30% of the total 
recruited patients will be enrolled in each UC or CD group.  
      The total duration of the study for each patients will be up to 74 weeks, consisting of a 4-week 
screening period (Days -28 to -1), a 46-week treatment period, and 16-week (ie, 5 vedolizumab 
half-lives) safety follow-up period after the last dose of study drug. Additionally, patients will be 
required to participate in a long-term follow-up safety survey through telephonic visit at 6 months 
after the last dose of study drug i.e. 8 weeks after the 16-week follow-up visit.  
Patients who meet all the inclusion criteria and none of the exclusion criteria will be administered 
vedolizumab 300 mg IV at the site. Patients will visit the site for dosing at Weeks 0 (Day 1), 2, 6, 
10 (CD- Patients who have not shown a response can receive a dose at 10 week), 14, 22, 30, 38, 
and 46.  
Patients will be evaluated for safety and efficacy from initiation of vedolizumab until 46 weeks 
(the treatment period), or until discontinuation of vedolizumab, whichever occurs earlier. All 
patients will be observed further for safety assessments for 16 weeks after the study treatment 
period or discontinuation of vedolizumab for post-treatment AE monitoring.  
In addition, patients will participate in the long-term follow-up safety survey through telephonic 
visit at 6 months after the last dose i.e. 8 weeks after the 16-week follow-up visit, during which 
information will be collected on events such as infections resulting in hospitalizations, cancer, UC 
or CD related surgeries, and development of progressive multifocal leukoencephalopathy (PML).  
 
 
 
 
 
 
 
 
 
 
 
 
 
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3.0 
SAMPLE-SIZE DETERMINATION 
 
The study will recruit 150 patients. This sample size was recommended by the DCGI on approval 
of vedolizumab as a new drug. At least 30% of the total recruited patients will be enrolled in each 
UC or CD group.  
This sample size will enable a serious infection rate of 6 per 100 person-years to be measured with 
a precision of ±3.8 with 95% CI based on a normal approximation of the annualized proportion of 
patients to be infected. This anticipated serious infection rate is based on observed rates in a post 
hoc pooled analysis of data from Indian sites participating in the vedolizumab global Phase 3 
C13006 and C13007 clinical studies and open label extension (Study C13008) of these studies. 
 
4.0 
ANALYSIS SETS 
4.1 
Safety Analysis Set 
The Safety Analysis Set (SAS) will include all enrolled who receive at least 1 dose of study drug. 
 
4.2 
Per-Protocol Analysis Set  
The per-protocol analysis set (PPAS) is a subset of the SAS (safety analysis set) and consists of 
all patients who do not violate the terms of the protocol in a way that would impact the study 
outcome significantly. All significant protocol deviations will be reviewed manually to decide 
which subjects will be excluded prior to database lock.  The hierarchy of reasons for exclusion is 
as follows: inclusion and exclusion criteria violations, study medication dosing errors, receiving 
forbidden concomitant medications. 
 
4.3 
Pharmacokinetic Analysis Set  
 
Not Applicable. 
 
 
 
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5.0 
STATISTICAL ANALYSIS  
5.1 
General Considerations 
 Baseline values are defined as the last observed value before the first dose of study medication.  
Where applicable, variables will be summarized descriptively by study visit. For the categorical 
variables, the counts and proportions of each possible value will be tabulated by treatment group. 
The denominator for the proportion will be based on the number of subjects who provided 
non-missing responses to the categorical variable. For continuous variables, the number of 
subjects with non-missing values, mean, median, SD, minimum, and maximum values will be 
tabulated.  
A windowing convention will be used to determine the analysis value for a given study visit for 
observed data analyses. 
Mean, Median, Q1 and Q3 will have one more decimal place than the raw data and SD will have 
2 decimal places more than the raw data. The decimal place for minimum and maximum values 
will be same as the raw data. 
If relevant, the normality of distribution of continuous variables will be examined using the 
Shapiro-Wilk test/ Kolmogorov–Smirnov test in order to determine whether or not to use 
parametric methods for the analysis of the sample data. All statistical tests will be two-sided and 
will be performed at a 0.05 significance level. The interpretation of all results will be performed 
in a descriptive and explorative manner and no adjustment for multiple testing will be applied. All 
P-values will be rounded to four decimal places; P-values less than 0.0001 will be presented as '< 
0.0001'. 
95% confidence intervals will be provided when appropriate 
Analysis of the data will be performed by the Biostatistics and Statistical Programming team at 
SIRO Clinpharm Pvt Ltd. All statistical analyses will be performed using SAS® Enterprise 
Guide® 7.1. 
 
5.1.1 
Analysis Approach for Continuous Variables 
 All continuous variables in this trial will use the analysis method below unless stated otherwise 
in the section specific to an endpoint. 
 
All continuous variables will be summarized using descriptive statistics such as 
x Number of subjects (n), number of subjects with missing values (Missing), 
x Mean, 
x Standard Deviation (SD), 
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x Median, 
x First Quartile (Q1), Third Quartile (Q3), 
x Minimum, Maximum, 
x 95% confidence interval for the mean 
 
The number of observations (n) will be presented with no decimal place, arithmetic mean and 
median will be presented up to two decimal places from the original value, SD up to three decimal 
places from the original value, minimum and maximum value as an original value. For changes 
from baseline in continuous endpoints, paired t-test will be used if normality   assumption holds 
based on the Shapiro–Wilk test, or the Wilcoxon signed rank test will be used otherwise.  
 
5.1.2 
Analysis Approach for Binary Variables 
 All binary variables in this trial will use the analysis method below unless stated otherwise in 
the section specific to an endpoint. 
The categorical variables will be summarized using the frequency count (n) and percentage 
(%) for each possible value. The frequencies will be presented up to no decimal places and 
percentage up to 1 decimal place.  
 
5.1.3 
Analysis Approach for Time-to-Event Variables 
Not applicable 
5.2 
Disposition of Subjects 
The following data on subject disposition will be summarized across treatment groups:  
 Number of subjects screened (i.e. who provided informed consent) 
 Number of screen failures 
 Number of subjects in Safety Population 
 Number of subjects in UC Safety Population 
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 Number of subjects in CD Safety Population 
 Number of subjects in PPAS Population 
 Number of subjects in UC PPAS Population 
 Number of subjects in CD PPAS Population 
 Number of subjects who completed the study 
 Number of subjects who completed the study in CD group. 
 Number of subjects who completed the study in UC group 
 Number of subjects discontinued/withdrawn 
 Primary Reasons for discontinuation/withdrawal 
 
5.3 
Demographic and Other Baseline Characteristics 
5.3.1 
Demographics 
The following patient demographics will be summarized for safety population: 
 Age (years) 
 Age (years) = ((Date of informed consent – Date of Birth) + 1)/365.25 
 Gender 
 Height (cm) 
 Weight (kg) 
 BMI 
 BMI= weight/ℎ݁݅݃ℎݐଶ 
Subjects’ data listings will be provided. 
 
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5.3.2 
Medical History and Concurrent Medical Conditions 
Medical history and Concurrent Medical Conditions will be coded using Medical Dictionary 
for Regulatory Activities (MedDRA) version 24.0. The frequency count (n) and percentage (%) 
of patients will be tabulated according to the coded terms of system organ class (SOC) and 
preferred term (PT) for the safety population. 
 
5.3.3 
Baseline Characteristics 
The following patient baseline characteristics will be summarized for safety population 
Smoking and Alcohol Consumption History: 
 Smoking status 
 Alcohol consumption status 
Tuberculosis History 
 Outcome 
5.4 
Medication History and Concomitant Medications  
 
5.4.1 
Prior Medications 
Medications, started up to 30 days prior to screening, per protocol (except biologics for which all past 
data will be recorded) other than study drug, started and stopped prior to the administration of first 
study drug administration are defined as prior medications. 
Prior medications will be coded using World Health Organization Drug Dictionary (WHODD) 
Mar 2021 or higher version which employs the Anatomical Therapeutic Chemical (ATC) 
Classification system.  
For all prior  medications, counts (n) & percentages (%) of patients will be presented by ATC main 
group and preferred drug name/verbatim terms and will be sorted in descending order of frequency 
in total for safety population. Patients with more than one medication of the same verbatim term 
will be counted only once. 
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Patient data listings will be provided for safety population. 
5.4.2 
Concomitant Medications 
Medications other than study medications, 
x 
Started prior but ongoing at the time of first study drug administration 
OR 
x Started on or after the day of first study drug administration will be defined as concomitant 
medications. 
Concomitant medications will be coded using World Health Organization Drug Dictionary 
(WHODD) Mar 2021 or higher version which employs the Anatomical Therapeutic Chemical 
(ATC) Classification system.  
For all  concomitant medications, counts (n) & percentages (%) of patients will be presented by 
ATC main group and preferred drug name/verbatim terms and will be sorted in descending 
order of frequency in total for safety population. Patients with more than one medication of the 
same verbatim term will be counted only once. 
Patient data listings will be provided for safety population. 
5.5 
Efficacy Analysis 
All the data and analysis would be provided for UC and CD groups and for overall study population. 
5.5.1 
Primary Endpoint(s) Analysis 
 
Incidence of AEs, SAEs, AEs of special interest (AESIs), ADRs, and unexpected ADRs 
 
If a patient has more than one AE, patients will be counted only once in system organ class and 
once for each PT. If a patient has more than one episode of an AE, the patient will be counted only 
once within a specific preferred term. If the same TEAE (Treatment Emergent Adverse Event) 
occurs on multiple occasions, the highest severity and relationship will be assumed. 
 
Number (n) and percentage (%) of patients with adverse events will be provided by system organ 
class and preferred term: 
x Incidence of AEs 
x Serious AEs  
x AEs of special interest (AESIs) 
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x AEs leading to discontinuation 
x ADRs, and unexpected ADRs 
 
No statistical inference between the treatment groups will be performed on AEs. Patient data 
listings will be provided for all AEs and TEAEs with information on causality, severity, frequency, 
seriousness, relationship to investigational product, outcome and action taken with the patient and 
study treatment.  
 
Exposure-adjusted incidence rates 
 
EAIR of AEs is defined as the number of subjects exposed to the drug and experiencing a certain 
event divided by the total exposure time of all subjects who are at risk for the event. Specifically, 
for subjects with no event, the exposure time is the time from the first drug intake to the last follow-
up assessment; for subjects with at least one event, the exposure time is the time from the first drug 
exposure to first event.  
 
x Incidence rates for events that occur while on vedolizumab therapy,  
x Incidence rate for events that occur after discontinuation of vedolizumab.  
 It will be summarized by number of events (n), Incidence rate and its 95% CI using Poisson rate 
confidence Interval by using safety analysis set for all safety endpoints. The person time at risk of 
event (T) will be derived  by adding the number of patients in the group and multiplying that 
number times the years that patients currently in the vedolizumab therapy/ after discontinuation of 
vedolizumab.  
 
The Poisson (e.g. incidence) rate estimate ߣመ=Number of events (n)/person time at risk of event (T).  
 
The 95-percent Poisson confidence interval is calculated as: ߣመ± 1.96 ∗ߣመ/√݊. 
 
Adverse Drug Reactions (ADRs) & unexpected ADRs / Events 
 
Expected Adverse events – An expected AE is any adverse reaction whose nature and intensity 
have been previously observed and documented for the study product (e.g. in the investigator 
brochure, product information). 
 
Unexpected Adverse Event – An AE or suspected adverse reaction is considered "unexpected" if 
it is not listed in the investigator brochure or is not listed at the specificity or severity that has been 
observed; or, if an investigator brochure is not required or available, is not consistent with the risk 
information described in the general investigational plan or elsewhere in the current application, 
as amended. 
 
AEs/ ADR will be summarized per subject using number and percentage by SOC and PT from 
Safety Analysis Set. If an AE/ ADR is reported for a subject more than once during treatment, the 
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worst severity and the worst relationship to trial treatment will be tabulated. Listings will also be 
provided for all the AEs/ ADRs. AEs/ ADRs will be coded using MedDRA version 24.0. 
 
Pre Treatment Event –  
A PTE is defined as any untoward medical occurrence in a clinical investigation patient who has 
signed informed consent to participate in a study but prior to administration of any study drug; it 
does not necessarily have to have a causal relationship with study procedure. It will be summarized 
per subject using number and percentage by SOC and PT from SAS 
 
5.5.2 
Secondary Endpoint(s) Analysis 
1) Proportion of patients with clinical response (defined as SCCAI ≥3 points decrease from 
baseline of clinical response (UC patients) and HBI≥3 point decrease from baseline of clinical 
response (CD patients) [Time frame: Week 14, 30 and 46]. 
Note: Baseline is defined as the assessment prior to first dose of study. 
The patients with clinical response (defined as SCCAI ≥3 points decrease from baseline of clinical 
response (UC patients) and HBI≥3 point decrease from baseline of clinical response (CD patients)) 
will be summarized by using Number(n) and percentage (%) of responders and will be reported 
up to the time frame of Week 14, 30 and 46 by UC and CD groups from SAS. 
Further, patients with clinical response will be summarized by using Number(n) and percentage 
(%) by visit, by UC and CD groups and by subgroups (Biologic-naïve patients and Biologic-
experienced patients) as defined in section 5.5.3 
95% CI by exact method will be used for proportion of patients with clinical response. 
Patient data listings will be provided for SAS population. 
 
2) Proportion of patients with clinical remission (as SCCAI of ≤2 with no individual score >1 (UC 
patients) or a HBI ≤4 (CD patients) [Time frame: Week 14, 30, 46]. 
Note: Baseline is defined as the assessment prior to first dose of study. 
 
The patients with clinical remission (defined as SCCAI ≤2 points increase from baseline of clinical 
response (UC patients) and HBI≤4 point increase from baseline of clinical response (CD patients)) 
will be summarized by using Number (n) and percentage (%) of responders and will be reported 
up to the time frame of Week 14, 30 and 46 by UC and CD groups from SAS. 
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Further, patients with clinical remission will be summarized by using Number(n) and percentage 
(%) by visit, by UC and CD groups and by subgroups (Biologic-naïve patients and Biologic-
experienced patients) as defined in section 5.5.3 
95% CI by exact method will be used for proportion of patients with clinical remission. 
 
 
Patient data listings will be provided for SAS population. 
 
 3) Proportion of patient with vedolizumab discontinuation in UC and CD groups 
Vedolizumab discontinuation is defined as ceasing vedolizumab, or a treatment gap ≥90 days 
between consecutive doses.  
The patients with vedolizumab discontinuation will be summarized by using number (n) and 
percentage (%) by UC and CD groups from SAS. 
Further, patients with vedolizumab discontinuation will be summarized by using number(n) and 
percentage (%) by visit, by UC and CD groups and by subgroups (Biologic-naïve patients and 
Biologic-experienced patients) as defined in section 5.5.3 
95% CI by exact method will be used for proportion of patients with vedolizumab discontinuation. 
 
Patient data listings will be provided for SAS population. 
 
4) Proportion of patients with mucosal healing/endoscopic response at Week 46 in UC and CD 
groups 
Mucosal healing: Mucosal healing is defined as a Mayo endoscopic sub score of ≤1 point for UC 
or SES-CD 0-2 or SES-CD ≤4 and at least a 2 point reduction from baseline with no sub-score >1 
for CD will be summarized by using number (n) and percentage (%) by visit, by UC and CD group 
and by subgroup (Biologic-naïve patients and Biologic-experienced patients). 
Endoscopic response: Endoscopic response is defined as decrease in Mayo endoscopic sub score 
of ≥1 point in UC and >50% decrease in SES-CD in CD will be summarized by using number (n) 
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and percentage (%) by visit, by UC and CD group and by subgroup (Biologic-naïve patients and 
Biologic-experienced patients). 
95% CI by exact method will be used for proportion of patients with mucosal healing/endoscopic 
response. 
 
Patient data listings will be provided for SAS population. 
 
5) Change in the patient-reported Quality of Life (Short Inflammatory Bowel Disease 
Questionnaire [SIBDQ]) from baseline to Weeks 14, 30, and 46  
The patients-reported Quality of Life score of Actual, change from Baseline and Percentage 
change from Baseline will be summarized descriptively by using number of observations (n),  
mean, standard deviations (SD), median, first quartile (Q1), third quartile (Q3), minimum and 
maximum value by visit and by UC and CD groups. The change from baseline to Weeks 14, 30, 
and 46 respectively, paired t-test will be used if normality  assumption holds based on the Shapiro–
Wilk test, or the Wilcoxon signed rank test will be used otherwise. 
 
Patient data listings will be provided for SAS population. 
 
We will provide additional analysis by Biologic-naïve patients and Biologic-experienced patients 
group for primary and secondary endpoints. BNP and BEP group will be summarized by using 
number of observations (n),  mean, standard deviations (SD), median, first quartile (Q1), third 
quartile (Q3), minimum and maximum value  for SAS Population. 
The change from baseline to Weeks 14, 30, and 46 respectively, paired t-test will be used if 
normality  assumption holds based on the Shapiro–Wilk test, or the Wilcoxon signed rank test will 
be used otherwise. 
 
5.5.3 
Subgroup Analyses  
 
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Depending on number of subjects, subgroup analysis will be performed for primary and secondary 
endpoints on subjects as follows: 
Subgroups to be explored include  
x Biologic-naïve patients  
x Biologic-experienced patients  
 
Subjects who have received biologics for IBD treatment in past will be considered “Biologic-
experienced”. Subjects who have never received biologics for IBD treatment in past will be 
considered “Biologic-naïve” based on prior medication history from CRF. 
 
5.6 
Safety Analysis 
All safety analyses will be performed for the safety population. 
Safety will be analyzed based on: 
x Adverse Events 
x Vital signs 
x ECG 
x Laboratory variables 
x Physical examination 
x Urine analysis 
 
Vital signs: 
Vital signs (Body temperature, Diastolic Blood Pressure, Pulse rate, Systolic Blood Pressure and 
Respiratory rate) will be assessed daily till discharge. 
Actual and change from baseline to each visit will be summarized using descriptive statistics (n, 
mean, SD, median, minimum, maximum) from safety population 
Vital signs assessments will also be summarized categorically by response across treatment 
groups at each time point for safety population. 
Patient data listings will be provided. 
 
ECG: 
ECG will be performed at screening and end of treatment visits. 
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Overall ECG will be summarized categorically by response across treatment at each time point 
for safety population. 
Patient data listings will be provided 
 
Laboratory Variables: 
All laboratory parameters will be summarized descriptively and categorically by response from 
safety population. 
Actual and change from baseline to each visit will be summarized using descriptive statistics (n, 
mean, SD, median, minimum, maximum) by treatment group for safety population 
Patient data listings will be provided. 
 
Physical Examination: 
Physical examination and other examination assessments will be summarized descriptively and 
categorically by response at each time point for safety population. 
Patient data listings will be provided. 
 
5.6.1 
Adverse Events 
If a patient has more than one AE, patients will be counted only once in system organ class 
(SOC) and once for each PT. If a patient has more than one episode of an AE, the patient will be 
counted only once within a specific preferred term. If the same TEAE (Treatment Emergent 
Adverse Event) occurs on multiple occasions, the highest severity and relationship will be 
assumed. 
Number (n) and percentage (%) of patients with adverse events will be provided across 
treatment groups by system organ class and preferred term: 
 All AEs 
 All TEAEs 
 All Serious TEAEs 
 All TEAEs by severity 
 All TEAEs by outcome 
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 All TEAEs by Relationship 
No statistical inference between the treatment groups will be performed on AEs. Patient 
data listings will be provided for all AEs and TEAEs with information on causality, 
severity, frequency, seriousness, relationship to investigational product, outcome and 
action taken with the patient and study treatment. 
 
5.6.2 
Adverse Events of Special Interest  
If an AESI, which occurs during the treatment period or the follow-up period, is considered to be 
clinically significant based on the criteria below, it should be recorded in the Special Interest AE 
eCRF or SAE Form. 
Adverse Events of Special Interest will be summarized per subject using number and percentage 
by SOC and PT from Safety Analysis Set in 
1) Serious Infections 
2) Malignancies 
3) Infusion Related Reaction 
4) Hypersensitivity 
5) Hepatic Injury 
 
5.6.3 
Extent of Exposure and Compliance 
 
Descriptive statistical summaries will be provided for the following variables: 
x Overall treatment duration 
Overall treatment duration is defined as the time from first study drug intake (dayfirst) until last 
study drug intake (day last), calculated as: 
Overall treatment duration = day last – day first +1 
x Number of doses received. 
 
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5.7 
Interim Analyses 
 
The interim analysis will be performed after all subjects completes week 14 weeks 
assessment.  All statistical testing at Week 14 will be two-sided and will be performed 
using a significance (alpha) level of 0.05. All endpoint assessment including safety and 
efficacy analysis will be done till week 14 visit data.  A separate Interim analysis plan 
will be prepared for elaborative discussion about the analysis plan and mocks for interim 
assessment. 
5.8 
Data Monitoring Committee/Internal Review Committee/ [Other Data Review 
Committees] 
Not applicable 
 
6.0 
REFERENCES 
1) Vedolizumab-4020_Protocol Amendment_V3.0_30MAR2021 
2) Vedolizumab-4020_eCRF_V1_02-Sep-2021 
3) ICH E9: Statistical Principles for Clinical Trial. 
7.0 
CHANGES TO PROTOCOL PLANNED ANALYSES 
This SAP contains no changes to the planned analyses described in the Protocol 
8.0 
APPENDIX  
8.1 
Changes from the Previous Version of the SAP 
Not applicable 
8.2 
Data Handling Conventions  
 
Missing data will not be imputed. Only data recorded in the CRF will be analyzed. 
All missing data or partial dates will be presented in the subject data listing, as they are     
recorded on the Case Report Form (CRF).  Except as noted, missing data will not be  
Estimated or carried forward in any statistical analysis. 
 
8.2.1 
General Data Reporting Conventions  
        Not applicable 
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For non-commercial use only


 
Vedolizumab-4020 
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Statistical Analysis Plan -01 
                                                                   23-09-2022 
 
CONFIDENTIAL 
8.2.2 
Definition of Baseline  
Non-missing values collected at immediately prior to the first dose of study drug 
administration will be considered as baseline values.  
8.2.3 
Definition of Visit Windows  
          The range of days in which a subject can occur according to the study protocol, typically        
around a date determined by the number of days since the initial visit. A study with every four-
week visit schedule may have a visit window +/- 3 days. A study with every eight week visit 
schedule may have a visit window +/- 7 days. A safety follow up 16 weeks post dose visit schedule 
may have a visit window +/- 7 days. 
8.3 
Analysis Software  
 
All statistical analyses will be performed using SAS® Enterprise Guide® 7.1. 
   	
		
For non-commercial use only