Clinical trial NCT03329209
Conditions: Colitis, Ulcerative Crohn Disease
Keywords: Drug therapy
Sponsor: Takeda
Start date: 2018-03-05; Completion date: 2018-09-05
Enrollment: 16 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this study is to assess the PK of vedolizumab following a single intravenous infusion in healthy adult Chinese participants.

Detailed description:
The drug being tested in this study is called vedolizumab. Vedolizumab is being tested to treat people who have ulcerative colitis (UC) or Crohn's disease (CD). This study will look at the PK, safety, and tolerability of vedolizumab following a single intravenous infusion of vedolizumab IV in healthy adult Chinese participants.

The study will enroll approximately 16 participants. All participants will be assigned to receive a single dose of vedolizumab IV 300 mg on Day 1.

This single center trial will be conducted in China. The overall time to participate in this study is approximately 7 months. Participants will make multiple visits to the clinic, and will be contacted by telephone, 6 months after single dose of study drug for a follow-up safety survey assessment.

Arms: arm 1: Vedolizumab 300 mg, infusion, intravenously over 30-minutes, once on Day 1.
Interventions: intervention 1: Vedolizumab
Intervention descriptions: intervention 1: Vedolizumab intravenous infusion.

Protocol documents:
Prot_000.pdf: 


•
Title: An Open-Label, Single-Center, Phase 1 Study to Determine the Pharmacokinetics of Single 
Intravenous Dose of Vedolizumab 300 mg in Healthy Adult Chinese Subjects
NCT Number: NCT03329209
Protocol Approve Date: 10 May 2018
Certain information within this protocol has been redacted (ie, specific content is masked irreversibly from 
view with a black/blue bar) to protect either personally identifiable information (PPD) or company 
confidential information (CCI). 
This may include, but is not limited to, redaction of the following: 
Named persons or organizations associated with the study.
Proprietary information, such as scales or coding systems, which are considered confidential 
information under prior agreements with license holder.
Other information as needed to protect confidentiality of Takeda or partners, personal information, or 
to otherwise protect the integrity of the clinical study.


PROTOCOL
An Open-Label, Single-Center, Phase 1 Study to Determine the Pharmacokinetics of Single 
Intravenous Dose of Vedolizumab 300 mg in Healthy Adult Chinese Subjects
Phase 1 Vedolizumab PK study in China
Sponsor:
Takeda Development Center Asia, Pte. Ltd.
21 Biopolis Road
Nucleos North Tower, Level 4
Singapore 138567
Study Number:
Vedolizumab-1014
IND Number:
Not Applicable 
EudraCT Number:
Not Applicable 
Compound:
Vedolizumab IV
Date:
10 May 2018
Amendment 
Number:
02
Amendment History:
Date
Amendment Number
Region
08 July 2015
Initial version
Asia
01 June 2017
01
Asia
10 May 2018
02
Asia
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 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.
TDC sponsored investigators per individual country requirements will be provided with 
emergency medical contact information cards to be carried by each subject.
General advice on protocol procedures should be obtained through the monitor assigned to the 
study site. Information on service providers is given in Section 3.1 and relevant guidelines should 
be provided to the site.
Contact Type / Role
China Contact
Serious adverse event and pregnancy 
reporting
Medical Monitor
(medical advice on protocol and 
compound)
Responsible Medical Officer (carries 
overall responsibility for the conduct of 
the study)
PPD


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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 clinical study protocol and also in accordance with the following:
!
The ethical principles that have their origin in the Declaration of Helsinki.
!
International Conference on Harmonisation E6 Good Clinical Practice Consolidated 
Guideline.
!
All applicable laws and regulations, including, without limitation, data privacy laws, 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.
Electronic Signatures may be found on the last page of this document.
PPD


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INVESTIGATOR AGREEMENT 
I confirm that I have read and that I understand this protocol, the Investigator’s Brochure, 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 subjects in accordance with the following:

The ethical principles that have their origin in the Declaration of Helsinki.

International Conference on Harmonisation, E6 Good Clinical Practice: Consolidated 
Guideline.

All applicable laws and regulations, including, without limitation, data privacy laws and 
regulations.

Regulatory requirements for reporting serious adverse events defined in Section 10.2 of this 
protocol.

Terms outlined in the Clinical Study Site Agreement.

Appendix B – Responsibilities of the Investigator.
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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1.3
Protocol Amendment 02 Summary of Changes
Rationale for Amendment 02
This document describes the changes in reference to the protocol incorporating Amendment 
No. 02.
The primary reason for this amendment is to provide clarification to some administrative terms of 
the protocol Vedolizumab-1014 amendment 01 (dated 01 Jun 2017).
For specific descriptions of text changes and where the changes are located, see Appendix F.
Changes in Amendment 02
1. Clarification for confirmation of entry criteria, including test results.
2. Clarification of the in-clinic diet.
3. Change in definition of timing for significant protocol deviation.
4. Revised Section 8.2 (Investigational Drug Assignment and Dispensing Procedures), to specify 
that the 3-digit Subject ID number will be used instead of 4-digit enrollment number.
5. Clarify list of serum chemistry laboratory tests.
6. Clarify timing of vital signs.
7. Clarification of dosing.
8. Deletion of collection and storage of specimens for genome/gene analysis.
9. Correction in approximate blood values to be drawn.
10. Clarification of timing for when subjects are assessed for signs and symptoms of PML.
11. Deletion of text regarding samples collected outside the window not being considered a 
protocol deviation.
12. Modifications to Appendix A (Schedule of Study Procedures) to add Day 8 timepoint for 
serum pregnancy test (hCG) and Final Visit/ET timepoint for dispensing PML Wallet Card.


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TABLE OF CONTENTS
1.0
ADMINISTRATIVE INFORMATION ...........................................................................2
1.1
Contacts.....................................................................................................................2
1.2
Approval....................................................................................................................3
1.3
Protocol Amendment 02 Summary of Changes ..........................................................5
2.0
STUDY SUMMARY ....................................................................................................11
Safety assessments ..............................................................................................................11
3.0
STUDY REFERENCE INFORMATION ......................................................................14
3.1
Study-Related Responsibilities.................................................................................14
3.2
Principal Investigator...............................................................................................14
3.3
List of Abbreviations ...............................................................................................15
3.4
Corporate Identification...........................................................................................16
4.0
INTRODUCTION.........................................................................................................17
4.1
Background .............................................................................................................17
4.2
Rationale for the Proposed Study.............................................................................18
5.0
STUDY OBJECTIVES AND ENDPOINTS..................................................................19
5.1
Objectives................................................................................................................19
5.1.1
Primary Objective ..............................................................................................19
5.1.2
Secondary Objective ..........................................................................................19
5.2
Endpoints.................................................................................................................19
5.2.1
Primary Endpoints .............................................................................................19
5.2.2
Secondary Endpoints..........................................................................................19
5.2.3
Safety Endpoints................................................................................................19
5.2.4
Additional Endpoints .........................................................................................19
6.0
STUDY DESIGN AND DESCRIPTION.......................................................................20
6.1
Study Design ...........................................................................................................20
6.2
Justification for Study Design, Dose, and Endpoints ................................................20
6.3
Premature Termination or Suspension of Study or Investigational Site.....................21
6.3.1
Criteria for Premature Termination or Suspension of the Study..........................21
6.3.2
Criteria for Premature Termination or Suspension of Investigational Sites .........21
6.3.3
Procedures for Premature Termination or Suspension of the Study or the 
Participation of Investigational Site(s)................................................................22
7.0
SELECTION AND DISCONTINUATION/WITHDRAWAL OF SUBJECTS..............23
7.1
Inclusion Criteria .....................................................................................................23
7.2
Exclusion Criteria ....................................................................................................23


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7.3
Excluded Medications, Dietary Products..................................................................25
7.4
Diet, Fluid, Activity Control ....................................................................................26
7.5
Criteria for Discontinuation or Withdrawal of a Subject...........................................26
7.6
Procedures for Discontinuation or Withdrawal of a Subject......................................27
8.0
CLINICAL TRIAL MATERIAL MANAGEMENT ......................................................28
8.1
Study Medication and Materials...............................................................................28
8.1.1
Dosage Form, Manufacturing, Packaging, and Labeling.....................................28
8.1.1.1 Vedolizumab For Injection, For Intravenous Use..........................................28
8.1.2
Storage...............................................................................................................28
8.1.3
Dose and Regimen .............................................................................................28
8.1.4
Overdose............................................................................................................28
8.2
Investigational Drug Assignment and Dispensing Procedures ..................................29
8.3
Accountability and Destruction of Sponsor-Supplied Drugs.....................................29
9.0
STUDY PLAN ..............................................................................................................31
9.1
Study Procedures.....................................................................................................31
9.1.1
Informed Consent Procedure..............................................................................31
9.1.2
Demographics, Medical History, and Medication History Procedure..................31
9.1.3
Physical Examination Procedure ........................................................................31
9.1.4
Weight, Height and BMI....................................................................................32
9.1.5
Vital Sign Procedure..........................................................................................32
9.1.6
Documentation of Concomitant Medications......................................................32
9.1.7
Documentation of Concurrent Medical Conditions.............................................32
9.1.8
Procedures for Clinical Laboratory Samples.......................................................33
9.1.9
Contraception and Pregnancy Avoidance Procedure...........................................34
9.1.10 Pregnancy ..........................................................................................................35
9.1.11 ECG Procedure..................................................................................................36
9.1.12 Immunogenicity Sample Collection ...................................................................36
9.1.13 Pharmacokinetic Sample Collection...................................................................36
9.1.13.1
Collection of Serum for Pharmacokinetic Sampling................................36
9.1.13.2
Bioanalytical Methods............................................................................37
9.1.14 Pharmacokinetic Parameters ..............................................................................37
9.1.15 Tuberculosis Screening ......................................................................................37
9.1.16 PML Checklist...................................................................................................38
9.1.17 Documentation of Screen Failure .......................................................................38
9.1.18 Documentation of Study Entrance......................................................................38


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9.2
Monitoring Subject Treatment Compliance..............................................................39
9.3
Schedule of Observations and Procedures................................................................39
9.3.1
Screening...........................................................................................................39
9.3.2
Study Entrance...................................................................................................39
9.3.3
Final Visit ..........................................................................................................39
9.3.4
Early Termination..............................................................................................39
9.3.5
Follow-up ..........................................................................................................39
9.4
Biological Sample Retention and Destruction ..........................................................40
9.5
Blood Volume .........................................................................................................40
10.0
PRETREATMENT EVENTS AND ADVERSE EVENTS ............................................41
10.1
Definitions...............................................................................................................41
10.1.1 PTEs..................................................................................................................41
10.1.2 AEs....................................................................................................................41
10.1.3 Additional Points to Consider for PTEs and AEs................................................41
10.1.4 SAEs..................................................................................................................43
10.1.5 Special Interest AEs...........................................................................................44
10.1.6 Severity of PTEs and AEs..................................................................................44
10.1.7 Causality of AEs ................................................................................................45
10.1.8 Relationship to Study Procedures.......................................................................45
10.1.9 Start Date...........................................................................................................45
10.1.10
Stop Date .....................................................................................................45
10.1.11
Frequency ....................................................................................................45
10.1.12
Action Concerning Study Medication...........................................................45
10.1.13
Outcome.......................................................................................................46
10.2
Procedures...............................................................................................................46
10.2.1 Collection and Reporting of AEs........................................................................46
10.2.1.1
PTE and AE Collection Period ...............................................................46
10.2.1.2
PTE and AE Reporting ...........................................................................46
10.2.1.3
Special Interest AE Reporting.................................................................47
10.2.2 Collection and Reporting of SAEs......................................................................48
10.2.3 Reporting of Abnormal Liver Function Tests .....................................................49
10.3
Follow-up of SAEs ..................................................................................................49
10.3.1 Safety Reporting to Investigators, IRBs or IECs, and Regulatory Authorities.....49
11.0
STUDY-SPECIFIC COMMITTEES .............................................................................50
11.1
Adjudication Committee..........................................................................................50


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11.1.1 Risk Minimization Action Program 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..........................................................................................53
13.1
Statistical and Analytical Plans ................................................................................53
13.1.1 Analysis Sets......................................................................................................53
13.1.2 Analysis of Demographics and Other Baseline Characteristics ...........................53
13.1.3 Pharmacokinetic Analysis ..................................................................................53
13.1.4 Immunogenicity Analysis...................................................................................53
13.1.5 Safety Analysis ..................................................................................................54
13.2
Interim Analysis and Criteria for Early Termination ................................................54
13.3
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 ................................56
15.0
ETHICAL ASPECTS OF THE STUDY........................................................................57
15.1
IRB and/or IEC Approval ........................................................................................57
15.2
Subject Information, Informed Consent, and Subject Authorization .........................57
15.3
Subject Confidentiality ............................................................................................59
15.4
Publication, Disclosure, and Clinical Trial Registration Policy.................................59
15.4.1 Publication and Disclosure.................................................................................59
15.4.2 Clinical Trial Registration..................................................................................59
15.4.3 Clinical Trial Results Disclosure ........................................................................60
15.5
Insurance and Compensation for Injury....................................................................60
16.0
REFERENCES..............................................................................................................61
LIST OF IN-TEXT TABLES
Table 7.a
Prohibited Medications ......................................................................................26
Table 8.a
Dose and Regimen .............................................................................................28
Table 9.a
Clinical Laboratory Tests...................................................................................33
Table 9.b
Collection of Blood Samples for Pharmacokinetic Analysis ...............................37
Table 9.c
Approximate Blood Volume ..............................................................................40
Table 10.a
Takeda Medically Significant AE List................................................................44


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Table 14.a
Windows for PK Blood Sample Collection ........................................................56
LIST OF IN-TEXT FIGURES
Figure 6.a
Schematic of Study Design ................................................................................20
LIST OF APPENDICES
Appendix A
Schedule of Study Procedures............................................................................62
Appendix B
Responsibilities of the Investigator.....................................................................65
Appendix C
Elements of the Subject Informed Consent.........................................................67
Appendix D
Investigator Consent to Use of Personal Information..........................................70
Appendix E
Collection, Storage, and Shipment of Bioanalytical Samples..............................71
Appendix F
Detailed Description of Amendments to Text.....................................................73


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2.0
STUDY SUMMARY
Name of Sponsor(s):
Takeda Development Center Asia, Pte. Ltd.
Compound:
Vedolizumab IV
Title of Protocol: An Open-Label, Single-Center, Phase 1 
Study to Determine the Pharmacokinetics of Single 
Intravenous Dose of Vedolizumab 300 mg in Healthy Adult 
Chinese Subjects
IND No.: 
Not Applicable
EudraCT No.:
Not Applicable
Study Number: Vedolizumab-1014
Phase: 1
Study Design:
This is an open-label, single-center, phase 1 study to determine the pharmacokinetics (PK) of single intravenous dose 
of vedolizumab 300 mg in healthy adult Chinese subjects. 
Subjects will be kept in the study unit for at least 3 days after the start of infusion on Day 1 for safety and PK 
assessments before discharge. The confinement period will be a minimum of 3 days to a maximum of 7 days.
Subjects will return to the study unit periodically according to the predetermined PK sampling scheduled until 
Day 127 or Early Termination (ET). Additionally, subjects will be required to participate in a long-term follow-up 
(LTFU) safety survey by telephone, 6 months after the dose of study drug. 
The total duration on study for each subject will be approximately 7.0 months, including Screening.
Screening
Treatment 
Follow-Up
Days
-28 to -2
Day -1
(Check-in)
Day 1
Day 2-3
Days 10, 15, 
29, 43, 64, 
85, 106 (a)
Final 
Visit/ET
Day 127 (b)
LTFU Safety 
Survey (c)
Day 168
Dosing and PK
PK and safety assessments
Safety assessments
Confinement 
(a) Days 10 and 15 have a ±1-day window. Days 29 and 43 a ±2-day window, and Days 64, 85, 106 and 127/ET all 
have a ±3 day window.
(b) In case abnormal, clinically significant findings are observed upon discharge, subjects may be brought back to the 
clinic for re-evaluation per investigator’s discretion.
(c) Subjects will be followed poststudy by telephone call at Day 168 (±3days) after the last dose of study drug to 
administer a LTFU safety survey.
Primary Objective:
To assess the PK of vedolizumab following a single intravenous infusion in healthy adult Chinese subjects. 
Secondary Objectives:
To evaluate the safety and tolerability of a single intravenous infusion of vedolizumab in healthy adult Chinese 
subjects.
Subject Population: Healthy male and female adult Chinese subjects aged 18 to 45 years, inclusive, at the time of 
informed consent.
Number of Subjects:
Estimated Total: 16 subjects dosed 
Number of Sites:
Estimated total: 1 site in China
Dose Level(s):
Single dose of vedolizumab IV 300 mg
Route of Administration:
IV infusion over approximately 30 minutes
Duration of Treatment:
Single dose on Day 1
Period of Evaluation:
196 days including Screening Period


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Main Criteria for Inclusion:
Healthy male or non-pregnant, non-lactating female Chinese subjects aged 18-45 years inclusive, who are willing and 
able to comply with the study schedule and assessments. The subject weighs at least 50 kg and has a body mass index 
(BMI) of between 19.0 and 26.0 kg/m2, inclusive at Screening.
Main Criteria for Exclusion:
The subject has received any investigational compound within 30 days prior to dosing of study medication or history 
of treatment with another monoclonal antibody within 6 months to dosing of study medication.
The subject has received vedolizumab in a previous clinical study or as a therapeutic agent.
The subject has uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, 
gastrointestinal, urologic, immunologic, endocrine disease, or psychiatric disease, or other abnormality, which may 
impact the ability of the subject to participate or potentially confound the study results. 
The subject has a known hypersensitivity to any component of the formulation of vedolizumab IV.
The subject is unable to attend all study days or comply with protocol requirements.
In addition, subject may not use any excluded medication or supplement to be outlined in the protocol.
Main Criteria for Evaluation and Analyses:
The primary endpoints for this study are:

Maximum observed serum concentration (Cmax).

Area under the serum concentration-time curve from time 0 to time of the last measureable concentration 
(AUClast).

Area under the serum concentration-time curve from time 0 to infinity (AUC∞).
The secondary endpoints for this study are:

Proportion of subjects with positive anti-vedolizumab antibody (AVA) during the study.

Proportion of subjects with positive neutralizing AVA during the study.

Safety assessment: Percentage of subjects with adverse events (AEs), percentage of subjects with adverse events 
of special interest (AESIs, including serious infections, including opportunistic infection such as progressive 
multifocal leukoencephalopathy (PML), liver injury, malignancies and infusion related reactions and 
hypersensitivity), percentage of subjects with serious adverse events (SAEs), number of subjects with markedly 
abnormal vital signs, number of subjects with markedly abnormal laboratory tests (clinical chemistry, 
hematology, coagulation, urinalysis), and number of subjects with markedly abnormal 12-lead 
electrocardiograms (ECGs).
Statistical Considerations:
Descriptive statistics will be used to summarize serum concentrations of vedolizumab over each scheduled sampling 
time. Individual serum concentration-time data will be presented as listings. 
Descriptive statistics will be used to summarize serum PK parameters of vedolizumab. Individual serum PK 
parameters will be presented in a data listing.
All AEs will be presented in listings: AEs and AESIs will be summarized. Individual results of laboratory tests 
(hematology, chemistry, and urinalysis), vital signs, and ECGs will be listed, and observed values will be summarized 
for every collection time point. Physical examination findings will be presented in the data listings.
The proportion of subjects with positive AVA will be summarized by the scheduled sampling time. The proportion of 
subjects with neutralizing AVA by the end of the study will be summarized. Titers of AVA and neutralizing AVA will 
be listed.
Additional analyses may be performed as needed.


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Sample Size Justification: A sample size of 16 subjects in this study is deemed sufficient to determine the PK and 
safety profile of a single dose of vedolizumab IV in healthy adult Chinese subjects. This sample size is not based on 
statistical considerations


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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 in the template for specific 
study-related activities will perform these activities in full or in partnership with the sponsor.
3.2
Principal Investigator
PPD


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3.3
List of Abbreviations
AE
adverse event
AESI
adverse event of special interest
ALT
alanine aminotransferase
AST
aspartate aminotransferase
AUC∞
area under the serum concentration-time curve from time 0 to infinity
AUClast
area under the serum concentration-time curve from time 0 to time of the last measureable 
concentration
AVA
anti-vedolizumab antibody
BMI
body mass index
bpm
beats per minute
CD
Crohn’s disease
Cmax
maximum observed serum concentration
CRO
contract research organization
CS
clinically significant
ECG
electrocardiogram
eCRF
electronic case report form
ELISA
enzyme-linked immunosorbent assay
ET
Early Termination
FDA
Food and Drug Administration
FSH
follicle-stimulating hormone 
GCP
Good Clinical Practice
GGT
-glutamyl transferase
GI
gastrointestinal
HBsAg
hepatitis B surface antigen
hCG
human chorionic gonadotropin
HCV
hepatitis C virus
HIV
human immunodeficiency virus
IAC
Independent Adjudication Committee
ICH
International Conference on Harmonisation
ID
identification
IEC
independent ethics committee
INR
international normalized ratio
IRB
institutional review board
IV
intravenous
JCV
John Cunningham virus
LFT
liver function test
LTFU
long-term follow up
MAdCAM-1
mucosal addressin cell adhesion molecule-1
MedDRA
Medical Dictionary for Regulatory Activities


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NCS
Not Clinically Significant
PGx
pharmacogenomics
PI
principal investigator
PK
pharmacokinetic
PML
progressive multifocal leukoencephalopathy
PTE
pretreatment event
Q8W
once every 8 weeks
QTcB
QT interval with Bazett correction method
QTcF
QT interval with Fridericia correction method
RAMP
Risk Assessment and Minimization Program for PML
SAE
serious adverse event
SAP
statistical analysis plan
SUSAR
suspected unexpected serious adverse reaction
t1/2z
terminal disposition phase half-life
TB
tuberculosis
TEAE
treatment-emergent adverse event
tmax
time of first occurrence of Cmax
TNF-α
tumor necrosis factor-alpha
UC
ulcerative colitis
ULN
upper limit of normal
VCAM-1
vascular cell adhesion molecule
WHODRUG
World Health Organization Drug Dictionary
3.4
Corporate Identification
TDC Asia
Takeda Development Center Asia, Pte Ltd
TDC Europe
Takeda Development Centre Europe Ltd.
TDC Americas
Takeda Development Center Americas, Inc.
TDC
TDC Japan, TDC Asia, TDC Europe and/or TDC Americas, as applicable
Takeda
TDC Japan, TDC Asia, TDC Europe and/or TDC Americas, as applicable


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4.0
INTRODUCTION
4.1
Background
Vedolizumab (also referred to as MLN0002 or Entyvio) is a humanized immunoglobulin G1 
monoclonal antibody directed against the human lymphocyte integrin α4β7. The α4β7integrin 
mediates lymphocyte trafficking to the gastrointestinal (GI) mucosa and gut-associated lymphoid 
tissue through adhesive interaction with mucosal addressin cell adhesion molecule-1 
(MAdCAM-1), which is expressed on the endothelium of mesenteric lymph nodes and GI mucosa
[1-4]. Vedolizumab binds the α4β7 integrin, antagonizing its adherence to MAdCAM-1 and as 
such, impairs the migration of gut homing leukocytes into GI mucosa. Due to its gut selective 
immunomodulatory properties [5], vedolizumab has been developed as a treatment for ulcerative 
colitis (UC) and Crohn’s disease (CD).
The effectiveness and safety of vedolizumab intended for intravenous (IV) use (vedolizumab IV, 
vedolizumab for injection, for intravenous use) for UC and CD have been established in pivotal 
clinical trials in subjects who had not responded adequately to corticosteroids, 
immunomodulators, or tumor necrosis factor-alpha (TNF-α) antagonists [6-8]. 
As of 19 November 2016 (the cut-off date of the most recent Periodic Benefit-Risk Evaluation 
Report), more than 4200 subjects have received at least 1 dose of vedolizumab across all studies in 
the clinical development program. As of 19 November 2016, vedolizumab exposure has extended 
for ≥12 months in 1832 subjects, ≥24 months in 1379 subjects, ≥36 months in 1169 subjects, 
≥48 months in 862 subjects, ≥60 months in 645 subjects, ≥72 months in 308 subjects, ≥84 months 
in 32 subjects, and ≥96 months in 22 subjects. Based on the most recent drug shipment data 
(19 November 2016), the cumulative patient exposure to vedolizumab IV since its marketing 
approval in May 2014 is estimated to be approximately 77,382 patient-years.
Single- and multiple-dose pharmacokinetics (PK) of vedolizumab have been studied in healthy 
subjects and in patients with moderately to severely active UC or CD. Similar PK was observed in 
healthy subjects, UC patients, and CD patients. Vedolizumab exhibits target-mediated drug 
disposition; hence, its elimination is characterized by linear and nonlinear processes. Following IV 
infusion, the serum concentrations of vedolizumab generally fell in a biexponential fashion until 
approximately 1 to 10 µg/mL, with a linear total body clearance of approximately 0.157 L/day and 
a serum half-life of around 25 days. Thereafter, the serum concentrations fell in a nonlinear 
fashion. The volume of distribution for vedolizumab is approximately 5 L. Vedolizumab was not 
detected in the cerebrospinal fluid at 5 weeks after a single IV administration in healthy subjects. 
Different intrinsic and extrinsic factors, including age, body weight, serum albumin, severity of 
disease state, prior treatment with TNF-α antagonist, coadministration with immunomodulators 
(including azathioprine, 6-mercaptopurine, methotrexate) or aminosalicylates, did not impact the 
PK of vedolizumab in subjects with UC or CD based on population PK analysis, as such, no dose 
adjustment is recommended for any of the above-mentioned covariates. PK of vedolizumab was 
similar between Japanese and Western subjects.
As of July 2014, vedolizumab IV has been granted marketing approval in the United States and 
additional countries for the treatment of adult patients with moderately to severely active UC or 


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CD, who have failed conventional treatment, including immunomodulators, corticosteroids, or 
TNF-α antagonists. The recommended dosage for UC and CD is 300 mg vedolizumab IV infused 
over approximately 30 minutes at Weeks 0, 2, and 6, then once every 8 weeks (Q8W) thereafter. 
4.2
Rationale for the Proposed Study
This phase 1 study is designed to meet the requirements of the China Food and Drug 
Administration (CFDA) for registration of vedolizumab IV in China. The effectiveness and safety 
of vedolizumab for UC and CD have been established in global clinical trials in support of 
marketing approval in the United States and additional countries. The main objective of this 
open-label, single-dose study is to assess the PK of vedolizumab in Chinese subjects and to allow 
comparison with the clinical data previously acquired in other regions, including North America, 
Europe, and Japan, etc. The results from this phase 1 study and the proposed phase 3 efficacy and 
safety studies in Chinese subjects with moderately to severely active UC or CD, along with 
available clinical data in other regions, will be used to support the registration of vedolizumab IV 
in China.


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5.0
STUDY OBJECTIVES AND ENDPOINTS
5.1
Objectives
5.1.1
Primary Objective

To assess the PK of vedolizumab following a single IV infusion in healthy adult Chinese 
subjects. 
5.1.2
Secondary Objective

To evaluate the safety and tolerability of a single IV infusion of vedolizumab in healthy adult 
Chinese subjects.
5.2
Endpoints
5.2.1
Primary Endpoints

Maximum observed serum concentration (Cmax).

Area under the serum concentration-time curve from time 0 to time of the last measureable 
concentration (AUClast).

Area under the serum concentration-time curve from time 0 to infinity (AUC∞).
5.2.2
Secondary Endpoints

Proportion of subjects with positive anti-vedolizumab antibody (AVA) during the study.

Proportion of subjects with positive neutralizing AVA during the study.
5.2.3
Safety Endpoints

Safety assessment: Percentage of subjects with adverse events (AEs), percentage of subjects 
with adverse events of special interest (AESIs, including serious infections, including 
opportunistic infection such as progressive multifocal leukoencephalopathy (PML), liver 
injury, malignancies and infusion related reactions and hypersensitivity), percentage of 
subjects with serious adverse events (SAEs), number of subjects with markedly abnormal vital 
signs, number of subjects with markedly abnormal laboratory tests (clinical chemistry, 
hematology, coagulation, urinalysis), and number of subjects with markedly abnormal 12-lead 
electrocardiograms (ECGs). 
5.2.4
Additional Endpoints

Time of first occurrence of Cmax (tmax).

Terminal disposition phase half-life (t1/2z).


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6.0
STUDY DESIGN AND DESCRIPTION
6.1
Study Design
This is an open-label, single-center, phase 1 study to determine the PK of single dose of 
vedolizumab IV 300 mg in healthy adult Chinese subjects. The number of subjects to be dosed in 
the study is 16. Since vedolizumab is intended to be used by both male and female subjects with 
UC or CD, effort will be made to enroll an equal number of male and female subjects in this study. 
Subjects will be kept in the study unit for at least 3 days after the start of infusion on Day 1 for 
safety and PK assessments before discharge. The confinement period will be a minimum of 3 days 
and a maximum of 7 days.
Subjects will return to the study units periodically according to the predetermined PK sampling 
scheduled until Day 127 or Early Termination (ET). Additionally, subjects will be required to 
participate in a long-term follow-up (LTFU) safety survey by telephone, 6 months after the dose of 
study drug. The total duration on study for each subject will be approximately 7.0 months, 
including screening. 
A schematic of the study design is included as Figure 6.a. A schedule of assessments is listed in 
Appendix A.
Figure 6.a
Schematic of Study Design
Screening
Treatment 
Follow-Up
Days
-28 to -2
Day -1
(Check-in)
Day 1
Day 2-3
Days 10, 15, 
29, 43, 64, 
85, 106 (a)
Final 
Visit/ET
Day 127 (b)
LTFU Safety 
Survey (c)
Day 168
Dosing and PK
PK and safety assessments
Safety 
assessments
Confinement 
(a) Days 10 and 15 have a ±1 day window. Days 29 and 43 a ±2 day window, and Days 64, 85, 106 and 127/ET all 
have a ±3 day window.
(b) In case abnormal, clinically significant findings are observed upon discharge, subjects may be brought back to the 
clinic for re-evaluation per investigator’s discretion.
(c) Subjects will be followed poststudy by telephone call at Day 168 (±3 days) after the last dose of study drug to 
administer a LTFU safety survey.
6.2
Justification for Study Design, Dose, and Endpoints
This is a single-center, open-label, single-dose study using vedolizumab IV 300 mg infused IV 
over 30 minutes. The objective of the study is to evaluate the PK of vedolizumab following a 
single IV infusion of 300 mg vedolizumab IV in healthy adult Chinese subjects. Vedolizumab IV 
300 mg dosing at Weeks 0, 2, and 6, and Q8W thereafter is the recommended regimen for subjects 
with moderately to severely active UC or CD in the United States, European Union, and Australia, 
as well as the dose regimen being used in the ongoing phase 3 studies in UC and CD subjects in 
Japan and the planned dose regimen in the phase 3 studies in China.


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Given the long half-life of vedolizumab (approximately 25 days), blood samples will be collected 
up to 18 weeks (>5 half-lives) to sufficiently assess vedolizumab PK after IV infusion. Since 
vedolizumab is intended to be administered Q8W during the maintenance phase in the phase 3 
studies in China, the accumulation after repeated dosing is expected to be minimal. This is 
supported by the fact that the trough serum concentration of vedolizumab was maintained at 
similar levels after reaching steady state in the completed phase 3 studies. Based on the population 
PK analyses conducted for the completed clinical studies, vedolizumab PK is similar in healthy 
subjects, as well as in subjects with UC or CD. Therefore, a single-dose PK study in healthy 
subjects is considered sufficient to provide the estimates of the steady-state exposure of 
vedolizumab following multiple Q8W maintenance doses in UC or CD patients, and a 
multiple-dose design is not necessary.
The impact of race (Westerns vs Japanese) was assessed through cross-study comparison using 
noncompartmental PK parameters. The dose- and weight-normalized PK parameters observed in 
Japanese subjects with UC (Study CPH-001) were similar to those observed in Western subjects 
with UC (Study C13002), suggesting that there is no effect of race on the PK of vedolizumab. The 
preliminary results from a recently completed single dose bioavailability study in healthy Japanese 
and non-Japanese subjects (MLN0002SC-101) further confirmed the lack of race effect on 
vedolizumab PK. 
The sample size of 16 subjects is considered sufficient to evaluate the PK profiles after single dose 
of vedolizumab IV in adult healthy Chinese subjects. This sample size is not based on statistical 
considerations.
6.3
Premature Termination or Suspension of Study or Investigational Site
6.3.1
Criteria for Premature Termination or Suspension of the Study
The study will be completed as planned unless one 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 medication 
that indicates a change in the known risk/benefit profile for the compound, such that the risk is 
no longer acceptable for subjects participating in the study.

Significant violation of Good Clinical Practice (GCP) that compromises the ability to achieve 
the primary study objectives or compromises subject safety.
6.3.2
Criteria for Premature Termination or Suspension of Investigational 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.


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6.3.3
Procedures for Premature Termination or Suspension of the Study or the 
Participation of Investigational 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 an 
investigational site, a study-specific procedure for early termination or suspension will be 
provided by the sponsor; the procedure will be followed by applicable investigational sites during 
the course of termination or study suspension.


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7.0
SELECTION AND DISCONTINUATION/WITHDRAWAL OF SUBJECTS
All entry criteria, including test results, need to be confirmed prior to dosing of study drug on 
Day 1. 
7.1
Inclusion Criteria
Subject eligibility is determined according to the following criteria prior to entry into the study:
1. In the opinion of the investigator, the subject is capable of understanding and complying with 
protocol requirements.
2. The subject or, when applicable, the subject’s legally acceptable representative signs and dates 
a written, informed consent form and any required privacy authorization prior to the initiation 
of any study procedures including requesting that a subject fast for any laboratory evaluations.
3. The subject is a healthy male or nonpregnant, nonlactating female adult Chinese subject aged 
18 to 45 years, inclusive, at the time of informed consent.
4. The subject weighs at least 50 kg and has a body mass index (BMI) from 19.0 to 26.0 kg/m2, 
inclusive at Screening. 
5. A male subject 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 18weeks after last dose.
6. A female subject of childbearing potential* who is sexually active with a nonsterilized* male 
partner agrees to use routinely adequate contraception* from signing of informed consent and 
throughout the duration of the study and for a minimum of 18 weeks after last dose. 
*Definitions and acceptable methods of contraception are defined in Section 9.1.9
Contraception and Pregnancy Avoidance Procedure and reporting responsibilities 
are defined in Section 9.1.10 Pregnancy.
7.2
Exclusion Criteria
Any subject who meets any of the following criteria will not qualify for entry into the study: 
1. The subject has received any investigational compound within 30 days prior to dosing of study 
medication or history of treatment with another monoclonal antibody within 6 months to 
dosing of study medication.
2. The subject has received vedolizumab in a previous clinical study or as a therapeutic agent.
3. The subject is an immediate family member, study site employee, or is in a dependent 
relationship with a study site employee who is involved in the conduct of this study 
(eg, spouse, parent, child, sibling) or may consent under duress. 
4. The subject has uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, 
hepatic, renal, metabolic, GI, urologic, immunologic, endocrine disease, or psychiatric disease, 


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or other abnormality, which may impact the ability of the subject to participate or potentially 
confound the study results. 
5. The subject has a known hypersensitivity to any component of the formulation of vedolizumab 
IV.
6. The subject has one or more positive response on the PML subjective symptoms checklist at 
Screening or before dosing on Day 1.
7. The subject has a positive result for drugs or alcohol abuse at Screening or Check-in (Day -1).
8. The subject has a history of drug abuse (defined as any illicit drug use) or a history of alcohol 
abuse within 1 year prior to the Screening visit or is unwilling to agree to abstain from alcohol 
for 48 hours prior to Check-in (Day -1) throughout the confinement and for 48 hours prior to 
each clinic visit and drugs throughout the study. 
9. The subject has taken any excluded medication listed in Section 7.3.
10. If female, the subject is pregnant or lactating or intending to become pregnant before, during, 
or within 18 weeks after the last dose in the study; or intending to donate ova during such time 
period. 
11. If male, the subject intends to donate sperm during the course of this study or for 18 weeks 
after the last dose of study medication.
12. The subject has evidence of current cardiovascular, central nervous system, hepatic, 
hematopoietic disease, renal dysfunction, metabolic or endocrine dysfunction, serious allergy, 
asthma, hypoxemia, hypertension, seizures, or allergic skin rash. There is any finding in the 
subject’s medical history, physical examination, or safety laboratory tests giving reasonable 
suspicion of a disease that would contraindicate taking vedolizumab, or a similar drug in the 
same class, or that might interfere with the conduct of the study. This includes, but is not 
limited to, peptic ulcer disease, seizure disorders, and cardiac arrhythmias.
13. The subject has had a surgical procedure requiring general anesthesia within 30 days before the 
initial Screening Visit or is planning to undergo a surgery that requires general anesthesia 
during the study period (through Final Visit/Day 127).
14. The subject has a history of cancer, except basal cell carcinoma which has been in remission 
for at least 5 years prior to Day 1.
15. The subject has a positive test result for chronic hepatitis B virus*, hepatitis C virus (HCV) 
antibody, human immunodeficiency virus (HIV) antibody at Screening.
* Subjects who are positive for hepatitis B surface antigen (HBsAg) will be excluded.
For subjects who are negative for HBsAg but are positive for either surface antibodies and/or 
core antibodies, hepatitis B virus DNA polymerase chain reaction will be performed and any 
result that meets or exceeds detection sensitivity will be excluded.


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16. The subject has active or latent tuberculosis (TB) as evidence by the following:
i.
A positive diagnostic TB test within 30 days of Day 1 defined as:
1. A positive QuantiFERON test, or 
2. Two successive indeterminate QuantiFERON tests, or
3. Chest X-ray within 3 months of Day 1 that is suspicious for pulmonary TB.
Note: subjects with documented previously treated TB, which was successful, 
with a negative QuantiFERON test, can be included in the study.
17. The subject has poor peripheral venous access.
18. The subject has donated or lost 450 mL or more of his or her blood volume (including 
serumpheresis), or had a transfusion of any blood product within 45 days prior to Day 1.
19. The subject has a Screening or Check-in (Day -1) abnormal clinically significant ECG. Entry 
of any subject with an abnormal (not clinically significant) ECG must be approved, and 
documented by signature by the principal investigator (PI).
20. The subject has a supine blood pressure outside the range of 90 to 140 mm Hg for systolic and 
50 to 90 mm Hg for diastolic, confirmed with 1 repeat testing within a maximum of 5 minutes, 
at the Screening Visit or Check-in (Day -1).
21. The subject has a resting heart rate outside of the range of 45 to 90 beats per minutes (bpm), 
confirmed with 1 repeat testing within a maximum of 5 minutes, at the Screening Visit or 
Check-in (Day-1).
22. The subject has a QT interval with Fridericia correction method (QTcF)>430 ms (males) or 
>450 ms (females) or PR outside the range 120 to 220 ms, confirmed with 1 repeat testing 
within a maximum of 5 minutes, at the Screening Visit or Check-in (Day -1).
23. The subject has abnormal Screening or Check-in (Day -1) laboratory values that suggest a 
clinically significant underlying disease or subject with the following lab abnormalities: 
alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >1.5 the upper limit 
of normal (ULN). 
24. The subject is unable to attend all study days or comply with protocol requirements.
7.3
Excluded Medications, Dietary Products 
Use of the agents in Table 7.a (prescription or nonprescription) is prohibited from the time points 
specified until completion of Final Visit (Day 127). 


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Table 7.a
Prohibited Medications
28 days prior to Check-in (Day -1)
Prescription medications
OTC medications and supplements (a)
All live vaccines
OTC=over-the-counter. 
(a) Occasional use of acetaminophen (1 g/day) or other medication as approved by Takeda on a case-by-case basis is 
allowed except on Day 1. Stable doses of multivitamins will be allowed.
During participation in the study, subjects must be instructed not to take any medications including 
over-the-counter products, without first consulting with the investigator.
7.4
Diet, Fluid, Activity Control
In the clinic, subjects will be provided 3 standard meals. and 2 snacks per day, each meal 
containing approximately 30% fat (relative to the total calories). The menu of the standardized 
meals from the clinical research site needs to be approved by Takeda before the implementation. 
The meals served on the day of dosing should be similar in nutritional content for each subject in 
the study. The study menu should be recorded and submitted to the study file with a copy provided 
with a copy provided to the sponsor. 
If a blood draw or any study procedure coincides with a meal, the blood draw will take precedence 
followed by the study procedure and then the meal.
Subjects will be advised to refrain from strenuous exercise from 72 hours before Check-in and 
throughout the confinement period of the study.
7.5
Criteria for Discontinuation or Withdrawal of a Subject
The primary reason for discontinuation or withdrawal of the subject from the study or study 
medication should be recorded in the electronic case report form (eCRF) using the following 
categories. For screen failure subjects, refer to Section 9.1.17.
1. Pretreatment event (PTE) or AE. The subject has experienced a PTE or AE that requires early 
termination because continued participation imposes an unacceptable risk to the subject’s 
health or the subject is unwilling to continue because of the PTE or AE.

Liver Function Test (LFT) Abnormalities
Study medication should be discontinued immediately with appropriate clinical follow-up 
(including repeat laboratory tests, until a subject’s laboratory profile has returned to 
normal/baseline status, see Section 9.1.8), if the following circumstances occur at any time 
during study medication treatment:
–
ALT or AST >8 × ULN, or
–
ALT or AST >5 × ULN and persists for more than 2 weeks, or


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–
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%).
2. Significant protocol deviation. The discovery after the dosing of study medication that the 
subject failed to meet protocol entry criteria or did not adhere to protocol requirements, and 
continued participation poses an unacceptable risk to the subject’s health.
3. Lost to follow-up. The subject did not return to the clinic and attempts to contact the subject 
were unsuccessful. Attempts to contact the subject must be documented.
4. Voluntary withdrawal. The subject (or subject’s legally acceptable representative) wishes 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).
5. Study termination. The sponsor, IRB, IEC, or regulatory agency terminates the study.
6. Pregnancy. The subject is found to be pregnant. 
Note: If the subject is found to be pregnant, the subject must be withdrawn immediately. The 
procedure is described in Section 9.1.10.
7. Other.
Note: The specific reasons should be recorded in the “specify” field of the eCRF.
7.6
Procedures for Discontinuation or Withdrawal of a Subject
The investigator may discontinue a subject’s study participation at any time during the study when 
the subject meets the study termination criteria described in Section 7.5. In addition, a subject may 
discontinue his or her participation without giving a reason at any time during the study. Should a 
subject’s participation be discontinued, the primary criterion for termination must be recorded by 
the investigator. In addition, efforts should be made to perform all procedures scheduled for the ET 
Visit. Discontinued or withdrawn subjects will not be replaced but additional subjects may be 
enrolled as needed.


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8.0
CLINICAL TRIAL MATERIAL MANAGEMENT
This section contains information regarding all medication 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 clinical trial material.
8.1
Study Medication and Materials
8.1.1
Dosage Form, Manufacturing, Packaging, and Labeling
8.1.1.1
Vedolizumab For Injection, For Intravenous Use
The study sites will be supplied by the sponsor with the following medication in an open-label 
manner: vedolizumab IV 300 mg/vial, for single use, in 20 mL vials. The study medication will be 
provided in a glass vial as a lyophilized solid formulation for reconstitution using sterile water. 
Each vial will be packaged in an appropriately labeled single vial carton.
Additional reference information and administration instructions can be found in the pharmacy 
manual.
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. 
8.1.3
Dose and Regimen
The investigator or investigator’s designee will instruct the subject on dosing procedures.
All dosing will occur while subjects are in the clinic under the supervision of the PI or designees as 
indicated in Table 8.a.
Table 8.a
Dose and Regimen
Treatment Group
No. of Subjects
Treatment 
1
16 subjects dosed
300 mg vedolizumab IV, infusion over 30 min.
8.1.4
Overdose
An overdose is defined as a known deliberate or accidental administration of investigational drug, 
to or by a study subject, at a dose above that which is assigned to that individual subject 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 this important safety information consistently in the database. 


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Cases of overdose without manifested signs or symptoms are not considered AEs. AEs associated 
with an overdose will be documented on AE eCRF(s) according to Section 10.0, Pretreatment 
Events and Adverse Events.
SAEs associated with overdose should be reported according to the procedure outlined in 
Section 10.2.2, Collection and Reporting of SAEs.
In the event of drug overdose, the subject should be treated symptomatically. 
8.2
Investigational Drug Assignment and Dispensing Procedures
The 3-digit subject number which is assigned at the time the informed consent is obtained, will be 
assigned by clinic site personnel in sequential order and which is used for all other procedures to 
identify the subjects throughout the study, as well as to facilitate the prelabeling of PK samples, 
contained on the PK transport vials shipped to the bioanalytical laboratory, and will be used by the 
laboratory to report the subject data results.
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 subjects 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 subject, 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 
medication 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 for the drug lot number 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
(vedolizumab IV 300 mg) 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, expiry and/or retest date, date and 
amount dispensed, including initials, seal, or signature of the person dispensing the drug. The log 
should include all required information as a separate entry for each subject to whom 
sponsor-supplied drug is dispensed.
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.
The investigator will be notified of any expiry date or retest date extension of sponsor-supplied 
drug during the study conduct. On expiry date notification from the sponsor or designee, the site 
must complete all instructions outlined in the notification, including segregation of expired 
sponsor-supplied drug for return to the sponsor or its designee for destruction.


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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, 
subjects 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 subject entering into the study, and before any 
protocol-directed procedures are performed, including requesting that a subject fast for laboratory 
evaluations.
A unique subject identification (ID) number (Subject ID = Site number + subject number) will be
assigned to each subject at the time that informed consent is obtained; this subject number will be 
used throughout the study.
9.1.2
Demographics, Medical History, and Medication History Procedure
Demographic information to be obtained will include date of birth, sex, race as described by the 
subject, alcohol use, and smoking status of the subject at Screening. 
Medical history to be obtained will include determining whether the subject has any significant 
conditions or diseases relevant to the disease under study that stopped at or prior to signing of 
informed consent. Ongoing conditions are considered concurrent medical conditions (see 
Section 9.1.7).
Medication history information to be obtained includes any medication relevant to eligibility 
criteria stopped at or within 28 days prior to signing of informed consent.
9.1.3
Physical Examination Procedure
A physical examination will consist of the following body systems: (1) eyes; (2) ears, nose, throat; 
(3) cardiovascular system; (4) respiratory system; (5) GI system; (6) dermatologic system; 
(7) extremities; (8) musculoskeletal system; (9) nervous system; (10) lymph nodes; (11) other.
Any abnormal finding on a pretreatment physical examination assessment must be assessed as Not 
Clinically Significant (NCS) or Clinically Significant (CS) by the investigator and recorded in the 
source document and eCRF. All CS findings/changes will be recorded as a PTE or concurrent 
medical condition in the source document and on the appropriate eCRF described in Section 10.0
or Section 9.1.7. 
On subsequent examinations, any abnormal change from the pretreatment physical examination 
assessment occurring immediately prior to the start of the investigational drug (Day 1) must be 
assessed as NCS or CS by the investigator and recorded in the source document and eCRF. Any 


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CS change or new diagnosis as a result of a CS change, as determined by the investigator, will be 
recorded as an AE in source documentation and on the PTE/AE eCRF described in Section 10.0.
9.1.4
Weight, Height and BMI
A subject should have weight and height measured while wearing indoor clothing and with shoes 
off. The BMI is calculated using metric units with the formula provided below. The Takeda 
standard for collecting height is centimeters without decimal places and for weight it is kg with 
1 decimal place. BMI should be derived as:
Metric:
BMI = weight (kg)/[height (m)]2
Note that although height is reported in centimeters, the formula uses meters for height; meters can 
be determined from centimeters by dividing by 100. Thus, for example, if height=176 cm 
(1.76 meters) and weight=79.2 kg, then BMI=79.2/1.762=25.5 kg/m2 
9.1.5
Vital Sign Procedure
Vital signs (temperature, respiration, pulse, and blood pressure) will be obtained at Screening, 
Check-in (Day -1), Day 1 (predose, and within ±5 minutes of 1 hour postdose and within 
±30 minutes of 8 hours postdose), Days 2, 8, 10(±1), 15 (±1), 29 (±2), 43(±2), 64 (±3), 85 (±3), 
106 (±3), and Final Visit Day 127(±3)/ET. For Days 1 and 2, heart rate and blood pressure will be 
measured after 5 minutes supine and again at 1 and 3 minutes after standing. For Days 8, 10(±1), 
15 (±1), 29 (±2), 43(±2), 64 (±3), 85 (±3), 106 (±3) and Final Visit Day 127(±3)/ET, heart rate and 
blood pressure will be measured after 5 minutes supine only. 
9.1.6
Documentation of Concomitant Medications
Concomitant medication is any drug given in addition to the study medication. These may be 
prescribed by a physician or obtained by the subject over the counter. Concomitant medication is 
not provided by Takeda. At each study visit, subjects will be asked whether they have taken any 
medication other than the study medication (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. Documentation will 
include generic medication name, dose, unit, frequency, route of administration, start and end 
dates, and reason for use. 
9.1.7
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, ECG, or physical 
examination abnormalities noted at screening examination. The condition (ie, diagnosis) should be 
described.


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9.1.8
Procedures for Clinical Laboratory Samples
All samples will be collected in accordance with acceptable laboratory procedures. Laboratory 
samples will be taken following a minimum 10-hour overnight fast on the days stipulated in the 
Schedule of Study Procedures (Appendix A).
Table 9.a lists the tests that will be obtained for each laboratory specimen.
Table 9.a
Clinical Laboratory Tests
Hematology
Serum Chemistry
Urinalysis
Special
RBCWBC with 
differential [% and 
absolute]
Hemoglobin
Hematocrit
Platelets
PT/INR (b)
ALT
Albumin
Alkaline phosphatase
AST
Total bilirubin
Direct bilirubin
Total protein
Creatinine
Blood urea
Creatine kinase
GGT
Potassium
Sodium
Glucose
Chloride
Bicarbonate or Carbon dioxide
Calcium
pH
Specific gravity
Protein
Glucose
Blood 
Nitrite
Microscopic Analysis
(only if positive dipstick 
results): 
RBC/high power field
WBC/high power field
Epithelial cells, casts etc
QuantiFERON test for 
TB (a)
Serum
Drug and Alcohol Screen
Serum hCG (c)
AVA
At Screening Only:
Hepatitis panel, including HBsAg, HBsAb, HBcAb, 
anti-HCV and HIV (d)
Drug screen, including amphetamines, barbiturates, 
benzodiazepines, cannabinoids, cocaine, opiates, 
alcohol, and cotinine (f)
Breathalyzer - Alcohol
FSH (e)
FSH=follicle-stimulating hormone, GGT=-glutamyl transferase, HBcAb=hepatitis B core antibody, hCG=human 
chorionic gonadotropin, PT=prothrombin time, RBC=red blood cells, WBC=white blood cells.
(a) Performed at Screening only. All subjects must have documented evidence of a negative QuantiFERON test at 
Screening.
(b) Prothrombin time/INR to be performed at Screening and last Study Visit (Day 127).
(c) Serum hCG pregnancy test will be done on all female subjects of childbearing potential at Screening, Check-in 
(Day -1), Day 8 and at Final Visit Day 127/ET.
(d) If subject is negative for HBsAg but is positive for either surface antibodies and/or core antibodies, hepatitis B 
virus DNA polymerase chain reaction will be performed.
(e) FSH level will be obtained for female subjects at Screening if they are postmenopausal by history (eg, defined as at 
least 1 year since last regular menses with an FSH >40 IU/L or at least 5 years since last regular menses, confirmed 
before any study medication is implemented) and not surgically sterile. The FSH result must be >40 IU/L for the 
subject to be permitted not to use adequate contraception.
(f) Subjects who do not meet the requirement for cotinine test can still be considered for recruitment at the discretion 
of the investigator.


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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.
If subjects experience ALT or AST >3 ×ULN, follow-up laboratory tests (at a minimum, serum 
alkaline phosphatase, ALT, AST, total bilirubin, GGT, and INR) should be performed within a 
maximum of 7 days and preferably within 48-72 hours after the abnormality was noted.
(Please refer to Section 7.5 for discontinuation criteria, and Section 10.2.3 for the appropriate 
guidance on Reporting of Abnormal Liver Function Tests in relation to ALT or AST >3 ×ULN in 
conjunction with total bilirubin >2 ×ULN.)
If the 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 medication, discussion of the relevant subject details and 
possible alternative etiologies. The abnormality should be recorded as an AE (please refer to 
Section 10.2.3 Reporting of Abnormal Liver Function Tests for reporting requirements).
9.1.9
Contraception and Pregnancy Avoidance Procedure
From signing of informed consent, throughout the duration of the study, and for 18 weeks after last 
dose of study medication, nonsterilized** male subjects 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 18 weeks after last 
dose of study medication, female subjects 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 (defined as at 
least 1 year since last regular menses with an FSH >40 IU/L or at least 5 years since last regular 
menses, confirmed before any study medication 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: 


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Barrier methods (each time the 
subject has intercourse):
Intrauterine devices 
(IUDs):
#Hormonal contraceptives:
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 spermicide.
Copper T PLUS condom 
or spermicide.
#Progesterone T PLUS 
condom or spermicide.
Implants.
Hormone shot/injection.
Combined pill.
Minipill.
Patch.
Vaginal ring PLUS male 
condom and spermicide.
Subjects will be provided with information on acceptable methods of contraception as part of the 
subject 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 hCG pregnancy tests 
will be performed only for women of childbearing potential and subjects will receive continued 
guidance with respect to the avoidance of pregnancy and sperm/ova donation as part of the study 
procedure (Appendix A). In addition to a negative serum hCG pregnancy test at Screening, 
subjects also must have a negative serum hCG pregnancy test at Check-in (Day -1).
In addition, male subjects must be advised not to donate sperm from signing of informed consent 
to 18 weeks after the last dose of study medication.
9.1.10 Pregnancy
If any subject is found to be pregnant during the study she should be withdrawn and any 
sponsor-supplied drug (vedolizumab IV) should be immediately discontinued. In addition, any
pregnancies in the partner of a male subject during the study or for 18 weeks after the last dose, 
should also be recorded following authorization from the subject’s partner. 
If the pregnancy occurs during administration of active study medication, eg, after Day 1or within 
18 weeks of the last dose of active study medication, the pregnancy should be reported 
immediately, using a pregnancy notification form, to the contact listed in Section 1.0.
If the female subject and/or female partner of a male subject agrees to the primary care physician 
being informed, the investigator should notify the primary care physician that the subject/female 
partner of the subject was participating in a clinical study at the time she became pregnant and 
provide details of treatment the subject received (blinded or unblinded, as applicable).
All reported pregnancies will be followed up to 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.


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9.1.11 ECG Procedure
A standard 12-lead ECG will be recorded at Screening Visit, Check-in (Day -1), Day 1 (predose 
[within 0.5 hours prior to dosing] and at 8 hours after the start of infusion, Day 8 and Final Visit 
Day 127 (±3)/ET. When ECG recording is scheduled for the same visit day as blood draws (eg, PK 
or AVA sampling), the ECG recording should be collected before the blood sample. Single ECGs 
will be taken for all applicable visits. Additional unscheduled ECGs may be recorded where 
clinically necessary for subject safety.
ECGs will be read automatically and also, the investigator or sub-investigator will manually 
interpret the ECG using 1 of the following categories: within normal limits, abnormal but not 
clinically significant, or abnormal and clinically significant. All 12-lead ECGs will be stored for 
manual measurement of intervals, if necessary. Twelve-lead ECGs will be recorded using an ECG 
machine that automatically calculates the heart rate and measures PR interval, RR interval, QRS 
interval, QT interval, QTcF and QT interval with Bazett correction method (QTcB) intervals. 
Paper ECG traces will be recorded for 10 seconds at a standard paper speed of 25 mm/sec and gain 
of 10 m/mV or digital recordings will be used.
One copy of the 12-lead ECG with the physician’s signature and date of assessment will be filed 
with the source documents and captured in the appropriate eCRF. If the original ECG is printed on 
thermal paper, the ECG report must be photocopied and certified. The photocopy will be filed with 
the original ECG in source.
9.1.12 Immunogenicity Sample Collection
Blood specimens for determination of AVA will be collected at day 1 predose (within 0.5 hours 
prior to dosing), Days 10 (±1), 29 (±2), 43 (±2), 64 (±3), 85 (±3), 106 (±3) and 127(±3)/ET 
postdose. A sample will be assessed for neutralizing AVA if AVA is detected.
Serum titers of AVA will be determined using a validated assay. Neutralizing AVA will be 
determined using a validated assay.
Please refer to the Study Manual for information on sample collection and preparation.
A blood sample for AVA assessment will also be obtained at the unscheduled visit for subjects 
experience an SAE.
9.1.13 Pharmacokinetic Sample Collection
9.1.13.1 Collection of Serum for Pharmacokinetic Sampling
Blood samples (one 5-mL sample per scheduled time) for PK analysis of vedolizumab will be 
collected into red-top Vacutainers for serum according to the schedule in Appendix A. Instructions 
for sample processing and shipment are provided in Appendix E.
Note: On Day 1, PK samples should not be collected from the arm where the vedolizumab IV 
infusion is performed. All PK samples should be collected as specified in Table 9.b even if the 
vedolizumab IV infusion is discontinued before the complete dose is administered to the subject.


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Serial blood samples for determination of vedolizumab will be collected according to Table 9.b.
Table 9.b
Collection of Blood Samples for Pharmacokinetic Analysis
Sample Type
Dosing Day
Time of Blood Sample Collection
Serum
1
Within 0.5 hour prior to the start of the IV infusion, 0.25 hour (15 minutes), 
0.58 hour (35 minutes; 5 min after the end of infusion) and, 2, 8, 24, 72, 120, 
and 168 hours after the start of the infusion, and on Days 10 (±1), 15 (±1), 29 
(±2), 43 (±2), 64 (±3), 85 (±3), 106 (±3), and Final Visit Day 127(±3)/ET.
The actual time of dosing administration and sample collection will be recorded on the source 
document and eCRF.
9.1.13.2 Bioanalytical Methods
Serum concentrations of vedolizumab will be measured using a validated assay.
9.1.14 Pharmacokinetic Parameters
The PK parameters of vedolizumab will be determined from the concentration-time profiles for all 
evaluable subjects using a non-compartmental analysis method. The PK parameters, including 
tmax, Cmax, AUClast, AUC, and t1/2z, will be determined from serum concentration-time data for all 
evaluable subjects. Actual sampling times, rather than scheduled sampling times, will be used in 
all computations involving sampling times. 
Symbol/Term
Definition
AUClast
Area under the serum concentration-time curve from time 0 to time of the last quantifiable 
concentration.
AUC∞
Area under the serum concentration-time curve from time 0 to infinity, calculated as 
AUC∞=AUClast+Clast/λz
Cmax
Maximum observed serum concentration.
t1/2z
Terminal disposition phase half-life, calculated as ln(2)/λz.
tmax
Time of first occurrence of Cmax.
Additional PK parameters may be calculated as appropriate.
9.1.15 Tuberculosis Screening
All subjects will complete TB screening to determine eligibility. All subjects must complete a 
diagnostic during Screening. Subjects will be excluded from the study if they have active or latent 
TB, regardless of treatment history, as defined in Section 7.2.


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9.1.16 PML Checklist
Staff will administer the subject PML checklist during Screening to exclude subjects with positive 
responses from enrolling into the study. The PML subjective checklist will be administered at 
Screening Visit, on Day 1 prior to dose, Day 127(±3)/ET Visit, and at any unscheduled visits.
Any subjects 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 Program for PML (RAMP). 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.
9.1.17 Documentation of Screen Failure
Investigators must account for all subjects who sign informed consent. If the subject is found to be 
not eligible at this visit, the investigator should complete the eCRF screen failure form.
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 

Study termination.

Other 
Subject numbers assigned to subjects who fail Screening should not be reused. 
If a subject fails screening, but is later successfully rescreened, the data for the subject will be 
entered as if these were 2 separate subjects. Therefore the data should be entered as follows:
1. The screen failure data should be entered as a screen failure subject.
2. Rescreened subjects should be assigned a new subject number and treated as a stand-alone 
subject.
9.1.18 Documentation of Study Entrance
Only subjects who meet all of the inclusion criteria and none of the exclusion criteria are eligible 
for entrance into the treatment phase.
If the subject is found to be not eligible for entrance, the investigator should record the primary 
reason for failure on the applicable eCRF.


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9.2
Monitoring Subject Treatment Compliance
Study medication will be administered while subjects are under observation in the clinical research 
unit. The date and time of each dose will be recorded in the source documents and on the eCRFs. 
An inventory of the study medication supplies dispensed will be performed by the site pharmacist 
or authorized study designee and recorded onto the Drug Accountability Log in the subject’s 
source document records or equivalent. The exact dose time of consecutive subjects may be 
staggered to facilitate logistics at the site.
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 
Subjects will be screened within 28 days prior to the dosing of study medication. Subjects will be 
screened in accordance with predefined inclusion and exclusion criteria as described in 
Section 7.0. See Section 9.1.15 for procedures for documenting screening failures.
9.3.2
Study Entrance
Study entrance into the treatment phase will take place on Day 1.
If the subject has satisfied all of the inclusion criteria and none of the exclusion criteria for study 
entrance, the subject should be assigned to treatment as described in Section 8.2. Subjects will be 
administered a dose of study medication in the unit under the supervision of the investigator or 
designee, as described in Section 8.2. The procedure for documenting Screening failures is 
provided in Section 9.1.15.
9.3.3
Final Visit
The Final Visit will be performed on Day 127 (±3 days). 
For all subjects receiving study medication, the investigator must complete the End of Study eCRF 
page.
9.3.4
Early Termination
The reason for discontinuation must be documented in the source document and eCRF. 
For all subjects receiving study medication, the investigator must complete the End of Study eCRF 
page.
9.3.5
Follow-up
Additionally, upon completion of or early termination from the study, all subjects will participate 
in a LTFU safety questionnaire on Day 168 (±3 days). The questionnaire will be administered by 
telephone at 6 months from the last dose of study drug. 


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9.4
Biological Sample Retention and Destruction
The sponsor has put into place a system to protect the subjects’ personal information to ensure 
optimal confidentiality and defined standard processes for sample and data collection, storage, 
analysis, and destruction.
The samples will be sent to a central laboratory that processes the blood sample and serves as a 
secure storage facility. The sponsor and researchers working with the sponsor will have access to 
the samples collected and any test results. All samples collected during the study will be stored 
securely with limited access and the sponsor will require anyone who works with the samples to 
agree to hold the research information and any results in confidence.
The sample will be labeled with a unique sample identifier similar to labeling in the main study but 
using a code that is different from the code attached to the health information and other clinical test 
results collected in the study. The sample and data are linked to personal health information with 
code numbers. This link means that the subject may be identified but only indirectly. The code 
numbers will be kept secure by or on behalf of the sponsor.
9.5
Blood Volume
Total blood sampling volume for an individual subject is shown in Table 9.c.
Table 9.c
Approximate Blood Volume
Approximate Blood Volume
Sample Type
Sample 
Volume 
(mL)
Number of Samples
Total Volume
(mL)
Screening
Day -1
Days 1 -127
Safety Laboratory 
Samples
20
1
1
4
120
QuantiFERON
3
1
--
--
3
PK Samples
5
--
--
17
85
Immunogenicity 
Samples
8.5
--
--
8
68
Total Blood Sampling Volume
276
Subject may be asked to provide additional safety laboratory blood samples at the follow-up visit, as appropriate. If a 
catheter will be used for PK blood collection, 1 mL of extra blood may be discarded for each PK sample.
The maximum volume of blood at any single day is approximately 38.5 mL, and the approximate 
total volume of blood for the study is 276 mL.


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10.0
PRETREATMENT EVENTS AND ADVERSE EVENTS
10.1
Definitions
10.1.1 PTEs
A PTE is defined as any untoward medical occurrence in a clinical investigation subject who has 
signed informed consent to participate in a study but prior to administration of any study 
medication; it does not necessarily have to have a causal relationship with study participation.
10.1.2 AEs
An AE is defined as any untoward medical occurrence in a clinical investigation subject 
administered a drug; it does not necessarily have to have a causal relationship with this treatment.
An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal 
laboratory finding), 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 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 medication 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 parameters 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 re-test and/or continued monitoring of an abnormal value are not considered an 


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intervention. In addition, repeated or additional noninvasive testing for verification, evaluation 
or monitoring of an abnormality is not considered an intervention.

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 subject experiences a worsening or complication 
of such a concurrent condition, the worsening or complication should be recorded 
appropriately as a PTE (worsening or complication occurs before start of study medication) or 
an AE (worsening or complication occurs after start of study medication). Investigators should 
ensure that the event term recorded captures the change in the condition (eg, “worsening 
of…”).

If a subject has a pre-existing episodic condition (eg, asthma, epilepsy) any occurrence of an 
episode should only be captured as a PTE/AE if the episodes become more frequent, serious or 
severe in nature, that is, investigators should ensure that the AE term recorded captures the 
change in the condition from Baseline (eg “worsening of…”).

If a subject has a degenerative concurrent condition (eg, cataracts, rheumatoid arthritis), 
worsening of the condition should only be captured as a PTE/AE if occurring to a greater 
extent to that which would be expected. Again, investigators should ensure that the AE term 
recorded captures the change in the condition (eg, “worsening of…”).
Worsening of PTEs or AEs:

If the subject experiences a worsening or complication of a PTE after starting administration of 
the study medication, the worsening or complication should be recorded appropriately as an 
AE. Investigators should ensure that the AE term recorded captures the change in the condition 
(eg, “worsening of…”).

If the subject experiences a worsening or complication of an AE after any change in study 
medication, 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 severity of AEs /Serious PTEs:

If the subject experiences changes in severity of an AE/serious PTE, the event should be 
captured once with the maximum severity recorded.


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Preplanned surgeries or procedures:

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 captured appropriately 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 subject’s medical condition 
should not be recorded as PTEs or AEs, but should be documented in the subject’s source 
documents. Complications resulting from an elective surgery should be reported as AEs.
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 SAEs
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 subject 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 subject 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).


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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
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 Special Interest AEs
A Special Interest Adverse Event (serious or non-serious) 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. Refer to 
Section 10.2.1.3 for information for special interest AE reporting.
10.1.6 Severity of PTEs and AEs
The different categories of intensity (severity) are characterized as follows:
Mild:
The event is transient and easily tolerated by the subject.
Moderate:
The event causes the subject discomfort and interrupts the subject’s usual activities.
Severe:
The event causes considerable interference with the subject’s usual activities.


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10.1.7 Causality of AEs
The relationship of each AE to study medication(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 drugs 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 drugs and concurrent treatments.
10.1.8 Relationship to Study Procedures
Relationship (causality) to study procedures should be determined for all PTEs and AEs.
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.
10.1.9 Start Date
The start date of the AE/PTE is the date that the first signs/symptoms were noted by the subject 
and/or physician.
10.1.10
Stop Date 
The stop date of the AE/PTE is the date at which the subject recovered, the event resolved but with 
sequelae or the subject died.
10.1.11
Frequency 
Episodic AEs/PTE (eg, vomiting) or those which occur repeatedly over a period of consecutive 
days are intermittent. All other events are continuous.
10.1.12
Action Concerning Study Medication 

Drug withdrawn – a study medication is stopped due to the particular AE.

Dose not changed – the particular AE did not require stopping a study medication.

Unknown – only to be used if it has not been possible to determine what action has been taken.

Not Applicable – a study medication was stopped for a reason other than the particular AE 
eg, the study has been terminated, the subject died, dosing with study medication was already 
stopped before the onset of the AE.


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10.1.13
Outcome

Recovered/Resolved – Subject returned to first assessment status with respect to the AE/PTE.

Recovering/Resolving – the intensity is lowered by one 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 subject 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 
subject died from another cause with the particular AE/PTE state remaining “Not 
recovered/not resolved”.

Resolved with sequelae – the subject recovered from an acute AE/PTE but was left with 
permanent/significant impairment (eg, recovered from a cardiovascular accident but with 
some persisting paresis.

Fatal – the AEs/PTEs which are considered as the cause of death.

Unknown – the course of the AE/PTE cannot be followed up due to hospital change or 
residence change at the end of the subject’s participation in the study.
10.2
Procedures
10.2.1 Collection and Reporting of AEs
10.2.1.1 PTE and AE Collection Period
Collection of PTEs will commence from the time the subject signs the informed consent to 
participate in the study and continue until the subject is first administered study medication
(Day 1) or until screen failure. For subjects who discontinue prior to study medication 
administration, PTEs are collected until the subject discontinues study participation.
Collection of AEs will commence from the time that the subject is first administered study 
medication (Day 1). Routine collection of AEs will continue until the Final Visit (Day 127±3).
10.2.1.2 PTE and AE 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. 
Subjects may report AEs occurring at any other time during the study. Subjects 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.


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All subjects experiencing AEs, whether considered associated with the use of the study medication 
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 and time.
3. Frequency.
4. Severity.
5. Investigator’s opinion of the causal relationship between the event and administration of study 
medication(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 medication (not applicable for PTEs).
8. Outcome of event.
9. Seriousness.
10.2.1.3 Special Interest AE Reporting
If this special interest AE, 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 an 
special interest AE eCRF or an SAE Form. The Form should be completed and reported to the 
SAE reporting contact in Section 1.0 within 24 hours.
Hypersensitivity Reactions (Including Infusion-Related Reactions). 
Currently, there is no evidence to support the routine prophylactic administration of premedication 
(eg, antihistamines, corticosteroids) to subjects receiving vedolizumab; hence such 
premedications are unlikely to be necessary or beneficial. At the discretion of the investigator, 
however, subjects may be administered premedication prior to any study drug administration. 
Corticosteroids, if given as a premedication, should be limited to the day of administration. 
Vedolizumab IV should be administered by a health care professional prepared to manage 
hypersensitivity reactions including anaphylaxis, if they occur. Appropriate monitoring and 
medical support measure should be available for immediate use.
Subjects should be observed for 2 hours following the infusion at a minimum.
If signs or symptoms of an infusion-related reaction are observed during the administration of 
study medication, it should be immediately discontinued and the subject treated as medically 
appropriate. In the case of a mild reaction, study drug administration may be reinitiated (with 
appropriate premedication) at the discretion of the investigator. Subjects with a severe or serious 


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administration-related reaction (eg, shortness of breath, wheezing, stridor, angioedema, life 
change in vital signs) must be withdrawn from the study (see Study Manual).
In all cases of infusion-related reaction, the medical monitor must be informed as soon as practical. 
The disposition of subjects with less severe infusion-related reactions should be discussed with the 
medical monitor.
Serious Infection 
Subjects will be monitored for signs and symptoms of infection and for lymphopenia during the 
study. Subjects with signs and symptoms suggestive of infections, including GI infections, will be 
treated as clinically indicated. Interventions may include antibiotic treatment, if appropriate and/or 
discontinuation of concomitant immunomodulators. Blood, sputum, urine, and/or stool cultures 
should be obtained as appropriate for the detection and diagnosis of infection. Withholding or 
terminating study drug administration may be considered as described in Section 7.5.
Malignancy
All cases of malignancies that are detected during the study will be reported as AEs. Local medical 
practices for the management of malignances will apply. Subjects with history of malignancy 
(except for specific cancers) or at high risk for malignancy will be excluded from the study per the 
exclusion criteria. 
Other 
Other special interest AEs include liver injury and PML, which are discussed in Sections 10.2.3
and 11.1.1, respectively.
The special interest AEs have to be recorded as AEs in the eCRF. An evaluation form along with 
all other required documentation must be submitted to the sponsor.
10.2.2 Collection and Reporting of SAEs
When an SAE occurs through the AE collection period it should be reported according to the 
following procedure:
A Takeda SAE form must be completed, in, 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.

Subject ID number.

Investigator’s name.

Name of the study medication(s)

Causality assessment.
The SAE form should be transmitted within 24 hours to the attention of the contact listed in 
Section 1.0. 


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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.
10.2.3 Reporting of Abnormal Liver Function Tests 
If a subject is noted to have ALT or AST elevated >3 ×ULN on 2 consecutive occasions, the 
abnormality should be recorded as an AE. In addition, an <LFT Increases eCRF> must be 
completed providing additional information on relevant recent history, risk factors, clinical signs 
and symptoms and results of any additional diagnostic tests performed.
If a subject 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 subject 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 9.1.8 must also be performed. In addition, an <LFT Increases eCRF> 
must be completed and transmitted with the Takeda SAE form (as per Section 10.2.2).
10.3
Follow-up of SAEs
If information is not available at the time of the first report becomes available at a later date, the 
investigator should complete a follow-up SAE form 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 or 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, investigators and IRBs or 
IECs, as applicable, in accordance with national regulations in the countries where the study is 
conducted. 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 an 
investigational medicinal product or that would be sufficient to consider changes in the 
investigational medicinal products administration or in the overall conduct of the trial. The 
investigational site also will forward a copy of all expedited reports to his or her IRB or IEC in 
accordance with national regulations.


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11.0
STUDY-SPECIFIC COMMITTEES
No steering committee, data safety monitoring committee, or clinical endpoint committee will be 
used in this study. 
11.1
Adjudication Committee
A PML Independent Adjudication Committee (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 Program 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 
John Cunningham virus (JCV) and typically only occurs in patients who are immunocompromised 
[9,10]. Natalizumab is a pan-α4 integrin antagonist that binds to both the α4β1 and α4β7 integrins 
and inhibits cellular adhesion to vascular cell adhesion molecule-1 (VCAM-1) and MAdCAM-1 
[11,12]. In contrast, vedolizumab binds to the α4β7 integrin only [5] and inhibits adhesion to 
MAdCAM-1, but not VCAM-1. Although no cases of PML have been reported in clinical trials 
with vedolizumab to date, a risk of PML cannot be ruled out.
To address the theoretical risk of the development of PML in subjects treated with vedolizumab, 
the sponsor, with input from renowned PML experts, has developed a Risk Minimization Action 
Program 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. Subjects are assessed for signs and 
symptoms of PML prior to the administration of study drug using a PML subjective symptom 
checklist. Subjects 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 subject 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 subjects will be trained to report specific neurological signs and symptoms without 
delay. Educational materials for teaching site personnel and subjects 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. Subjects will 
receive training and educational materials prior to receiving treatment. The informed consent form 
will contain specific information on the hypothetical risk of PML. Any documented case of PML 
will be reported as an SAE, regardless of whether hospitalization occurs. 


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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, medical history, and concurrent conditions will be coded using the Medical Dictionary 
for Regulatory Activities (MedDRA). Drugs will be coded using the World Health Organization 
Drug Dictionary (WHODRUG).
12.1
CRFs (Electronic)
Completed eCRFs are required for each subject 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 eCRF. 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. 
Corrections to eCRFs are recorded in an audit trail that captures the old information, the new 
information, identification of the person making the correction, the date the correction was made, 
and the reason for change. Reasons for significant corrections should additionally be included. 
The PI 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 subject’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 subjects, medical records, temporary media such as thermal sensitive paper, source 
worksheets, all original signed and dated informed consent forms, subject authorization forms 
regarding the use of personal health information (if separate from the informed consent forms), 
electronic copy of eCRFs, including the audit trail, 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 subject’s chart to ensure long-term legibility. Furthermore, 
International Conference on Harmonisation (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 


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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 Clinical Study Site Agreement between the investigator and sponsor.
Refer to the Phase 1 Site Specifications document 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
A statistical analysis plan (SAP) will be prepared and finalized prior to database lock. This 
document will provide further details regarding the definition of analysis variables and analysis 
methodology to address all study objectives.
A targeted data review will be conducted prior to database lock. This review will assess the 
accuracy and completeness of the study database, subject evaluability, and appropriateness of the 
planned statistical methods.
13.1.1 Analysis Sets
Safety Set:
The safety analysis set will consist of all subjects who are enrolled and received 1 dose of study 
drug. Subjects in this analysis set will be used for demographic, baseline characteristics and safety 
summaries.
Pharmacokinetic Set:
The PK set will consist of all subjects who receive study drug and have at least 1 measurable serum 
concentration.
13.1.2 Analysis of Demographics and Other Baseline Characteristics
Demographic and baseline characteristics will be summarized. Summary statistics (number of 
subjects, mean, SD, median, minimum and maximum) will be generated for continuous variables 
(eg, age and weight) and the number and percentage of subjects within each category will be 
presented for categorical variables (eg, gender, ethnicity, and race).
Demographic variables of screen failure subjects and reasons for screen failures will be 
summarized for subjects who are screened, but not enrolled in the study. Individual demographic 
characteristics, date of informed consent, and reason for screen failure will be listed.
13.1.3 Pharmacokinetic Analysis
Descriptive statistics will be used to summarize serum concentrations of vedolizumab over each 
scheduled sampling time. Individual serum concentration-time data will be presented as listings. 
Descriptive statistics will be used to summarize serum PK parameters of vedolizumab. Individual 
serum PK parameters will be presented in a data listing.
More detailed description will be provided in the SAP.
13.1.4 Immunogenicity Analysis
The proportion of subjects with positive AVA will be summarized by the scheduled sampling 
time. The proportion of subjects with neutralizing AVAs by the end of the study will be 


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summarized. Titers of AVA and neutralizing AVA will be listed. The impact of AVA on PK and 
safety may be explored.
More detailed description will be provided in the SAP.
Additional analyses may be performed as needed.
13.1.5 Safety Analysis
The number and percentage of subjects with treatment-emergent adverse events (TEAEs) defined 
as any AEs, regardless of relationship to study drug), AESIs for vedolizumab (ie, serious 
infections including opportunistic infection such as PML, liver injury, malignancies, 
infusion-related or systemic reactions and hypersensitivity and SAEs, which occur on or after 
dosing in patients, will be summarized by MedDRA system organ class, and preferred term 
overall, by severity, and by relationship to study drug. Separate summaries will also be generated 
for treatment-related AEs overall and by severity. Data listings will be provided for all AEs 
(including PTEs for enrolled subjects), AEs leading to study drug discontinuation, AEs leading to 
study visit discontinuation, SAEs, and AEs resulting in death.
Baseline, postbaseline and change from baseline in clinical laboratory tests, vital signs and ECG 
results will be summarized. Subjects with markedly abnormal values for laboratory tests, vital 
signs and ECG results will be tabulated. The mapping of the subjects who meet the markedly 
abnormal value criteria will be listed as a table. Individual results for clinical laboratory tests, vital 
signs and ECG measures will be listed.
13.2
Interim Analysis and Criteria for Early Termination
No interim analysis is planned.
13.3
Determination of Sample Size
A sample size of 16 subjects in this study is deemed sufficient to determine the PK and safety 
profile of a single dose of vedolizumab IV in healthy adult Chinese subjects. This sample size is 
not based on statistical considerations.


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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 or 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 medication, subject medical records, 
informed consent documentation, documentation of subject authorization to use personal health 
information (if separate from the informed consent forms), 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 subjects. Should other unexpected circumstances arise that will require 
deviation from protocol-specified procedures, the investigator should consult with the sponsor or 
designee (and IRB or 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 subject’s source documents. In the event of 
a significant deviation, the site should notify the sponsor or its designee (and IRB or EC, as 
required). Significant deviations include, but are not limited to, those that involve fraud or 
misconduct, increase the health risk to the subject, 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.
Every attempt will be made to collect each PK blood sample at the designated time point, and the 
actual time of each blood sample will be recorded on the source document and eCRF. Table 14.a
defines the windows allowed for sample collections. 
The Significant Protocol Deviation eCRF is to be completed for deviations that are identified the 
sponsor prior to the study. Protocol Deviation Forms are to be completed for PK samples collected 
outside of the following intervals:


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Table 14.a
Windows for PK Blood Sample Collection
Minutes
Nominal Sampling Time
no more than 30 minutes predose
0 hour
±5
immediately postdose to ≤6 hours
±10
>6 hours to 12 hours postdose
±15
>12 hours to 24 hours
±30
>24 hours
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 medication is stored and prepared, and any other facility used during the study. In 
addition, there is the possibility that this study may be inspected by regulatory agencies, including 
those of foreign governments (eg, the Food and Drug Administration [FDA], the United Kingdom 
Medicines and Healthcare products Regulatory Agency, the Pharmaceuticals and Medical Devices 
Agency of Japan). 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
The principles of Helsinki are addressed through the protocol and through appendices containing 
requirements for informed consent and investigator responsibilities.
15.1
IRB and/or IEC Approval
IRBs and IECs must be constituted according to the applicable state and federal/local 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 or IEC. If any member of the IRB or IEC 
has direct participation in this study, written notification regarding his or her abstinence from 
voting must also be obtained. Those Americas sites unwilling to provide names and titles of all 
members due to privacy and conflict of interest concerns should instead provide a Federal Wide 
Assurance Number or comparable number assigned by the Department of Health and Human 
Services.
The sponsor or designee will supply relevant documents for submission to the respective IRB or 
IEC for the protocol’s review and approval. This protocol, the Investigator’s Brochure, a copy of 
the informed consent form, and, if applicable, subject recruitment materials and/or advertisements 
and other documents required by all applicable laws and regulations, must be submitted to a 
central or local IRB or IEC for approval. The IRB’s or IEC’s written approval of the protocol and 
subject 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 or IEC approval must refer to the study by exact protocol title, 
number, and version date; identify versions of other documents (eg, informed consent form) 
reviewed; and state the approval date. The sponsor will {ship drug/notify site 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 trial. Until the site receives 
notification no protocol activities, including Screening may occur.
Sites must adhere to all requirements stipulated by their respective IRB or IEC. This may include 
notification to the IRB or IEC regarding protocol amendments, updates to the informed consent 
form, recruitment materials intended for viewing by subjects, local safety reporting requirements, 
reports and updates regarding the ongoing review of the study at intervals specified by the 
respective IRB or IEC, and submission of the investigator’s final status report to IRB or IEC. All 
IRB and IEC approvals and relevant documentation for these items must be provided to the 
sponsor or its designee.
Subject incentives should not exert undue influence for participation. Payments to subjects must 
be approved by the IRB or IEC and sponsor.
15.2
Subject Information, Informed Consent, and Subject 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 informed consent form, subject authorization form (if 
applicable), and subject information sheet (if applicable) describe the planned and permitted uses, 


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transfers, and disclosures of the subject’s personal and personal health information for purposes of 
conducting the study. The informed consent form and the subject 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 informed consent form 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.
The investigator is responsible for the preparation, content, and IRB or IEC approval of the 
informed consent form and if applicable, the subject authorization form. The informed consent 
form, subject authorization form (if applicable), and subject information sheet (if applicable) must 
be approved by both the IRB or IEC and the sponsor prior to use.
The informed consent form, subject authorization form (if applicable), and subject information 
sheet (if applicable) must be written in a language fully comprehensible to the prospective subject. 
It is the responsibility of the investigator to explain the detailed elements of the informed consent 
form, subject authorization form (if applicable), and subject information sheet (if applicable) to the 
subject. Information should be given in both oral and written form whenever possible and in the 
manner deemed appropriate by the IRB or IEC. In the event the subject is not capable of rendering 
adequate written informed consent, then the subject’s legally acceptable representative may 
provide such consent for the subject in accordance with applicable laws and regulations.
The subject, or the subject’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 
subject, or the subject’s legally acceptable representative, determines he or she will participate in 
the study, then the informed consent form and subject authorization form (if applicable) must be 
signed and dated by the subject, or the subject’s legally acceptable representative, at the time of 
consent and prior to the subject entering into the study. The subject or the subject’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 informed consent 
form and subject authorization (if applicable) at the time of consent and prior to subject entering 
into the study; however, the sponsor may allow a designee of the investigator to sign to the extent 
permitted by applicable law.
Once signed, the original informed consent form, subject authorization form (if applicable), and 
subject information sheet (if applicable) will be stored in the investigator’s site file. The 
investigator must document the date the subject signs the informed consent in the subject’s 
medical record. Copies of the signed informed consent form, the signed subject authorization form 
(if applicable), and subject information sheet (if applicable) shall be given to the subject.
All revised informed consent forms must be reviewed and signed by relevant subjects or the 
relevant subject’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 subject’s medical 
record, and the subject should receive a copy of the revised informed consent form.


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15.3
Subject Confidentiality
The sponsor and designees affirm and uphold the principle of the subject’s right to protection 
against invasion of privacy. Throughout this study, a subject’s source data will only be linked to 
the sponsor’s clinical study database or documentation via a unique ID number. As permitted by 
all applicable laws and regulations, limited subject attributes, such as sex, age, or date of birth, and 
subject initials may be used to verify the subject and accuracy of the subject’s unique ID number.
To comply with ICH Guidelines for GCP and to verify compliance with this protocol, the sponsor 
requires the investigator to permit its monitor or designee’s monitor, 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 and IECs to review the subject’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 subject’s study participation, 
and autopsy reports. Access to a subject’s original medical records requires the specific 
authorization of the subject as part of the informed consent process (see Section 15.2).
Copies of any subject source documents that are provided to the sponsor must have certain 
personally identifiable information removed (ie, subject name, address, and other identifier fields 
not collected on the subject’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. 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 Americas investigators), country, and 


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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 subjects 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 subject 
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 or other publicly accessible 
websites, as required by Takeda Policy/Standard, applicable laws and/or regulations.
15.5
Insurance and Compensation for Injury
Each subject in the study must be insured in accordance with the regulations applicable to the site 
where the subject is participating. If a local underwriter is required, then the sponsor or sponsor’s 
designee will obtain clinical study insurance against the risk of injury to clinical study subjects. 
Refer to the Clinical Study Site Agreement regarding the sponsor’s policy on subject 
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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16.0
REFERENCES
1. Butcher EC, Williams M, Youngman K, Rott L, Briskin M. Lymphocyte trafficking and 
regional immunity. Adv Immunol 1999;72:209-53.
2. Salmi M, Jalkanen S. Lymphocyte homing to the gut: attraction, adhesion, and commitment. 
Immunol Rev 2005;206:100-13.
3. Briskin M, Winsor-Hines D, Shyjan A, Cochran N, Bloom S, Wilson J, et al. Human mucosal 
addressin cell adhesion molecule-1 is preferentially expressed in intestinal tract and associated 
lymphoid tissue. Am J Pathol 1997;151(1):97-110.
4. Erle DJ, Briskin MJ, Butcher EC, Garcia-Pardo A, Lazarovits AI, Tidswell M. Expression and 
function of the MAdCAM-1 receptor, integrin alpha 4 beta 7, on human leukocytes. Immuno 
1994;153(2):517-28.
5. 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.
6. Feagan BG, Rutgeerts P, Sands BE, Hanauer S, Colombel JF, Sandborn WJ, et al. 
Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med 
2013;369(8):699-710.
7. Sandborn WJ, Feagan BG, Rutgeerts P, Hanauer S, Colombel JF, Sands BE, et al. 
Vedolizumab as induction and maintenance therapy for Crohn's disease. N Engl J Med 
2013;369(8):711-21.
8. Sands B, Feagan B, Rutgeerts P, Colombel J-F, Sandborn W, Sy R, et al. Vedolizumab 
induction therapy for patients with Crohn's disease and prior anti-tumour necrosis factor 
antagonist failure: a randomised, placebo-controlled, double-blind, multicentre trial. Journal of 
Crohn's and Colitis 2013;7(Suppl. 1):Pages S5–S6. 8th Congress of the European Crohn's and 
Colitis Organisation.
9. Major EO. Progressive multifocal leukoencephalopathy in patients on immunomodulatory 
therapies. Annu Rev Med 2010;61:35-47.
10. Steiner I, Berger JR. Update on progressive multifocal leukoencephalopathy. Curr Neurol 
Neurosci Rep 2012;12(6):680-6.
11. 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.
12. TYSABRI (natalizumab) injection. Full Prescribing Information. Cambridge, MA: Biogen 
Idec Inc., Revised June 2013.


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Appendix A
Schedule of Study Procedures
Procedures or 
Observations
Screening
Treatment
Follow up (a)
Days
-28 to 
-2
Check-in 
Day -1
Day 1
Day 2
Day 4
Day 6
Day 8
Day 10 
(±1)
Day 15 
(±1)
Day 29
(±2)
Day 43 
(±2)
Day 64 
(±3)
Day 85 
(±3)
Day 
106 
(±3) 
Final 
Visit 
Day 
127 
/ET/ 
(±3) (b)
LTFU 
Safety 
Survey
Day 168/ 
(±3)
Informed consent (c)
X
Dispense PML wallet 
card
X
X
Inclusion/exclusion 
criteria
X
X
Demographics and 
medical history 
X
Medication history
X
Chest X-ray
X
QuantiFERON test (d)
X
PML checklist (e)
X
X
X
Follow-up safety 
questionnaire
X
Physical exam (f)
X
X
X
X
X
X
Vital signs (g)
X
X
X
X
X
X
X
X
X
X
X
X
X
Height, weight and 
BMI (h)
X
X
X
Concomitant 
medications (i)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
12-lead ECG (j)
X
X
X
X
X
Laboratory 
evaluations (k)
X
X
X
X
X
X
Footnotes are on last table page.


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Appendix A
Schedule of Study Procedures (continued)
Procedures or 
Observations
Screening
Treatment
Follow up (a)
Days
-28 to 
-2
Check-in 
Day -1
Day
1
Day 2
Day 4
Day 6
Day 8
Day 10 
(±1)
Day 15 
(±1)
Day 29 
(±2)
Day 43 
(±2)
Day 64 
(±3)
Day 85 
(±3)
Day 
106 
(±3) 
Final 
Visit 
Day 
127 
/ET/ 
(±3) (b)
LTFU 
Safety 
Survey
Day 168/ 
(±3)
Urine drug screen 
X
X
Alcohol screen 
(breathalyzer)
X
X
PT/INR (l)
X
X
Serum pregnancy test 
(hCG) (m)
X
X
X
X
FSH (n)
X
HBsAg, HBsAb, 
HBcAb, anti-HCV and 
HIV(1 & 2)
X
Confinement (o)
X
X
X
X
X
Study drug dosing
X
AVA assessment (p)
X
X
X
X
X
X
X
X
PK blood collection 
(q)
X
X
X
X
X
X
X
X
X
X
X
X
X
PTE/AE assessment 
(r)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Footnotes are on the following page.


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HBcAb=hepatitis B core antibody.
(a) Days 10 and 15 have a ±1 day window. Days 29 and 43 have a, ±2 day window. Days 64, 85, 106, 127/ET and 168 telephone call all have a ±3 day window.
(b) Procedures for subjects discontinued early. A PK sample should be collected at the ET Visit, if possible.
(c) Informed Consent must be signed before any study-specific procedures are performed.
(d) All subjects must have a negative QuantiFERON test at Screening. Initial indeterminate results should be repeated. A subject with 2 indeterminate results will be excluded. 
(e) The PML checklist will be administered at Screening Visit, on Day 1 prior to dose, Day 127(±3)/ET Visit, and at any unscheduled visits. 
(f) Physical examination performed at the Screening Visit, Check-in Day -1, Day 1, Day 8, Day 29 (±2) and at the Final Visit Day 127 (±3) or /ET. All physical examinations are to
be performed by the PI or subinvestigator. CS findings on the physical examination that occur postdose of study drug will be recorded as AEs.
(g) Vital signs (temperature, respiration, pulse, and blood pressure) will be obtained at Screening, Check-in (Day -1), Day 1 (predose, and within ±5 minutes at 1 hour postdose, and 
within ±30 minutes at 8 hours postdose), Days 2, 8, 15 (±1), 29 (±2), 43(±2), 64(±3), 85 (±3), Day 106 (±3), and Final Visit Day 127(±3)/ET. For Days 1 and 2, heart rate and blood 
pressure will be measured after 5 minutes supine and again at 1 and 3 minutes after standing. For Days 8, 15 (±1), 29 (±2), 43(±2), 64(±3), 85 (±3), Day 106 (±3) and Final Visit Day 
127(±3)/ET, heart rate, and blood pressure will be measured after 5 minutes supine only. 
(h) Height, weight and BMI will only be collected at Screening. Only weight will be collected at Check-in Day -1 and Day 106 (±3).
(i) Record all ongoing medications from Screening through Final Visit Day 127/ET.
(j) Standard 12-lead ECGs will be recorded at Screening Visit, Check-in (Day -1), Day 1 (predose [within 0.5 hours prior to dosing] and at 8 hours after the start of infusion, Day 8, 
and Final Visit Day 127 (±3)/ET. When ECG recording is scheduled for the same visit day as blood draws (eg, PK or AVA sampling), the ECG recording should be collected before 
the blood sample. 
(k) Clinical laboratory tests (hematology, serum chemistry, and urinalysis) will require a minimum 10-hour overnight fast night prior to clinical laboratory tests with the exception of 
the Screening Visit. 
(l) PT/ INR will be performed at the Screening Visit and Final Visit (Day 127/ET).
(m) For women of childbearing potential only. Includes pregnancy avoidance counseling. 
(n) A FSH level will be obtained on postmenopausal women (eg, defined as at least 1 year since last regular menses with an FSH >40 IU/L or at least 5 years since last regular menses, 
confirmed before any study medication is implemented) and not surgically sterile. The FSH result must be 40>IU/L for the subject to be permitted not to use adequate contraception).
(o) The total confinement period will be a minimum of 3 days and a maximum of 7 days. Subjects should be considered clinically stable by the investigator or designee prior to 
discharge.
(p) Blood samples (one 8.5 mL sample per scheduled time) for determination of AVA will be collected at predose (within 0.5 hours prior to dosing), Days 10, 29 (±2), 43 (±2), 64 
(±3), 85 (±3), 106 (±3) and 127(±3)/ET postdose. AVA positive samples will be further analyzed for neutralizing AVA. A blood sample for AVA assessment will also be obtained at 
the unscheduled visit for subjects experience an SAE.
(q) Blood samples (5 mL sample per scheduled time) for PK analyses of vedolizumab will be collected at predose (within 0.5 hour prior to the start of the IV infusion), 0.25 hour (15 
minutes), 0.58 hour (35 minutes; 5 min after the end of infusion) and, 2, 8, 24, 72, 120, and 168 hours after the start of the infusion, and on Days 10 (±1), 15 (±1), 29 (±2), 43 (±2), 64 
(±3), 85 (±3), 106 (±3), and Final Visit Day 127(±3)/ET. 
(r) PTEs will be captured immediately following the signing of the informed consent at Screening until the start of the infusion. The routine collection of AEs will be captured from 
the start of infusion and will continue until the Final Visit (Day 127/ET). Any new AEs/SAEs (reported at Final Visit Day 127/ET) will be recorded in the eCRFs and site source 
document. Any SAE spontaneously reported to the investigator following the AE collection period should be reported to the sponsor if considered related to study participation.


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Appendix B
Responsibilities of the Investigator
Clinical research studies sponsored by the sponsor are subject to 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. If the investigator/institution retains the services of any individual or party to perform study 
related duties and functions, the investigator/institution should ensure that this individual or 
party is qualified to perform those study related duties and functions and should implement 
procedures to ensure the integrity of the study related duties and functions performed and any 
data generated.
4. Ensure that study related procedures, including study specific (nonroutine/nonstandard panel) 
screening assessments are NOT performed on potential subjects, prior to the receipt of written 
approval from relevant governing bodies/authorities.
5. Ensure that all colleagues and employees assisting in the conduct of the study are informed of 
these obligations.
6. Secure prior approval of the study and any changes by an appropriate IRB/IEC that conform to 
ICH, and local regulatory requirements.
7. 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 subjects. 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.
8. Ensure that requirements for informed consent, as outlined in ICH and local regulations, are 
met.
9. Obtain valid informed consent from each subject who participates in the study, and document 
the date of consent in the subject’s medical chart. Valid informed consent is the most current 
version approved by the IRB/IEC. Each informed consent form should contain a subject 
authorization section that describes the uses and disclosures of a subject’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 subject authorization, then the 
investigator must obtain a separate subject authorization form from each subject or the 
subject’s legally acceptable representative.
10. 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.


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11. Allow possible inspection and copying by the regulatory authority of GCP-specified essential 
documents.
12. Maintain current records of the receipt, administration, and disposition of sponsor-supplied 
drugs, and return all unused sponsor-supplied drugs to the sponsor. 
13. Report adverse reactions to the sponsor promptly. In the event of an SAE, notify the sponsor 
within 24 hours.


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Appendix C
Elements of the Subject Informed Consent 
In seeking informed consent, the following information shall be provided to each subject:
1. A statement that the study involves research.
2. An explanation of the purposes of the research.
3. The expected duration of the subject’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 subjects involved in the study.
7. A description of the subject’s responsibilities.
8. A description of the conduct of the study.
9. A statement describing the treatment(s) and the probability for random assignment to each 
treatment.
10. A description of the possible side effects of the treatment that the subject may receive.
11. A description of any reasonably foreseeable risks or discomforts to the subject and, when 
applicable, to an embryo, fetus, or nursing infant.
12. A description of any benefits to the subject or to others that reasonably may be expected from 
the research. When there is no intended clinical benefit to the subject, the subject should be 
made aware of this.
13. Disclosures of appropriate alternative procedures or courses of treatment, if any, that might be 
advantageous to the subject and their important potential risks and benefits.
14. A statement describing the extent to which confidentiality of records identifying the subject 
will be maintained, and a note of the possibility that regulatory agencies, auditor(s), IRB/IEC, 
and the monitor may inspect the records. By signing a written informed consent form, the 
subject or the subject’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 subject for participating in the study.
17. The anticipated expenses, if any, to the subject for participating in the study.
18. An explanation of whom to contact for answers to pertinent questions about the research 
(investigator), subject’s rights, and IRB/IEC and whom to contact in the event of a 
research-related injury to the subject.
19. A statement that participation is voluntary, that refusal to participate will involve no penalty or 
loss of benefits to which the subject otherwise is entitled, and that the subject may discontinue 


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participation at any time without penalty or loss of benefits to which the subject is otherwise 
entitled.
20. The consequences of a subject’s decision to withdraw from the research and procedures for 
orderly termination of participation by the subject.
21. A statement that the subject or the subject’s legally acceptable representative will be informed 
in a timely manner if information becomes available that may be relevant to the subject’s 
willingness to continue participation in the study.
22. A statement that results of pharmacogenomic analysis will not be disclosed to an individual, 
unless prevailing laws require the sponsor to do so.
23. The foreseeable circumstances or reasons under which the subject’s participation in the study 
may be terminated.
24. A written subject authorization (either contained within the informed consent form or provided 
as a separate document) describing to the subject the contemplated and permissible uses and 
disclosures of the subject’s personal information (including personal health information) for 
purposes of conducting the study. The subject authorization must contain the following 
statements regarding the uses and disclosures of the subject’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 
subjects 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 effectiveness of the study medication(s), studying other therapies for patients, 
developing a better understanding of disease, and improving the efficiency of future 
clinical studies;
d) that subjects 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 subject’s identity will remain confidential in the event that study results are 
published.


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25. Female subjects of childbearing potential (eg, nonsterilized, premenopausal female subjects) 
who are sexually active must use adequate contraception (as defined in the informed consent) 
from Screening and throughout the duration of the study, and for <X> weeks after last dose of 
study medication. Regular pregnancy tests will be performed throughout the study for all 
female subjects of childbearing potential. If a subject is found to be pregnant during study, 
study medication will be discontinued and the investigator will offer the subject the choice to 
receive unblinded treatment information. 
26. Male subjects must use adequate contraception (as defined in the informed consent) from 
Screening and throughout the duration of the study. If the partner or wife of the subject is found 
to be pregnant during the study, the investigator will offer the subject the choice to receive 
unblinded treatment information. 
27. 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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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.

IRBs and IECs.
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 medication.

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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Appendix E
Collection, Storage, and Shipment of Bioanalytical Samples 
Instructions for Processing of Serum Samples for PK Vedolizumab Analysis 
1. Collect 5 mL of venous blood into a Becton-Dickinson Vacutainer or equivalent manufacturer. 
For all Vedolizumab samples, blood samples should be collected into red-stopper Vacutainers 
which contain no anticoagulant. Direct venipuncture is the preferred method of blood 
collection.
2. Allow the red top Vacutainer to sit at room temperature for approximately 30 to 60 minutes 
(refer to product information for correct time) to ensure proper clot formation.
3. To separate the serum samples, centrifuge the Vacutainers for 10 minutes at approximately 
1100 to 1300 relative centrifugal force (RCF) in a room temperature centrifuge. Note: if using 
a collection device other than Becton-Dickinson, refer to manufacturer’s instruction for proper 
centrifugation force and time.
4. To ensure a more homogeneous sample, all serum should first be transferred into 1 aliquot. 
From there, split the serum evenly between the 2 aliquots into polypropylene tubes. A 
minimum of 1.0 mL needs to be obtained for each sample. Labeling may include protocol 
number (Vedolizumab-1014), matrix (ie, serum), PK assay, analyte (Vedolizumab), 
randomization number, nominal day and time, and either “SET 1” (for original sample) or 
“SET 2” (for duplicate sample).
5. Cap the labeled storage tubes and freeze the serum samples immediately at approximately -
70°C or lower. No more than 1 hour and 45 minutes must be allowed to elapse between 
collecting blood and freezing the serum sample.
6. Keep samples frozen at approximately -70°C or lower until shipment to the selected laboratory 
in China. “SET 1” samples will be shipped first on dry ice, followed by shipment of duplicate 
“SET 2” samples after “SET 1” samples have been received by the analytical laboratory.
Instructions for Processing of Serum Vedolizumab Samples Immunogenicity Testing
1. Collect 8.5 mL of venous blood into a Becton-Dickinson Vacutainer (Serum Separator Tube, 
red/gray top SST, catalog# 367988 or equivalent). Direct venipuncture is the preferred method 
of blood collection.
2. Invert sample 5 times immediately after the blood collection and allow the Vacutainer to sit at 
room temperature for approximately 30 minutes to ensure proper clot formation.
3. Centrifuge the sample at 1000 to 1300 x g for 10 to 15 minutes at room temperature to isolate 
serum.
a) For swing bucket rotors centrifuge samples for 10 minutes. 
b) For fixed-angle rotors centrifuge samples for 15 minutes. 
c) Refer to the centrifuge manual for proper operation of the centrifuge. 


Vedolizumab IV
Study No. Vedolizumab-1014
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Protocol Incorporating Amendment No. 02
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CONFIDENTIAL
d) If using blood collection tubes other than BD Vacutainer Serum Separator Tube, follow the 
manufacturer’s recommended procedures
4. Remove serum using a transfer pipette and transfer:
a) 1.0 mL into the first 2 mL polypropylene cryovial. (Vial# 1)
b) 1.0 mL into the second 2 mL polypropylene cryovial. (Vial# 2)
c) 1.0 mL into the third 2 mL polypropylene cryovial. (Vial# 3)
d) Transfer any remaining serum into the fourth 2 mL polypropylene cryovial. (Vial# 4) 
5. Vial# 1 and vial #2 are the primary samples. Vial #3 and vial #4 are back up samples.
6. Cap the labeled cryovials and freeze the serum samples immediately at approximately -70°C or 
lower. No more than 1 hour and 45 minutes must be allowed to elapse between collecting 
blood and freezing the serum sample. 
7. If a -70°C freezer is not available, the samples may be stored at approximately -20°C in a 
commercial grade freezer with no auto-defrost until shipment to selected laboratory in China.
Shipping off Serum Samples for PK Analysis and Immunogenicity Testing for Vedolizumab
To be determined.
Detailed instructions for the handling and shipping of samples are provided in the Study Manual.


Vedolizumab IV
Study No. Vedolizumab-1014
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Protocol Incorporating Amendment No. 02
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CONFIDENTIAL
Appendix F
Detailed Description of Amendments to Text
The primary sections of the protocol affected by the changes in Amendment No. 02 are indicated. 
The corresponding text has been revised throughout the protocol. 
Change 1: Clarification for confirmation of entry criteria, including test results.
The primary change occurs in Section 7.0 SELECTION AND 
DISCONTINUATION/WITHDRAWAL OF SUBJECTS
Initial 
wording:
All entry criteria, including test results, need to be confirmed prior to first dose of 
study drug on Day 1.
Amended 
or new 
wording:
All entry criteria, including test results, need to be confirmed prior to first dose dosing
of study drug on Day 1.
Rationale for Change:
There is no change to the meaning of the sentence, just to avoid confusion since we only have one 
dose in the study.
Change 2: Clarification of the in-clinic diet.
The primary change occurs in Section 7.4 Diet, Fluid, Activity Control
Initial 
wording:
In the clinic, subjects will be provided 3 standard meals and 2 snacks per day, each 
meal containing approximately 30% fat (relative to the total calories).
Amended 
or new
wording:
In the clinic, subjects will be provided 3 standard meals and 2 snacks per day each 
meal containing approximately 30% fat (relative to the total calories). The menu of 
the standardized meals from the clinical research site needs to be approved by
Takeda before the implementation.
Rationale for Change:
This was revised based on the Site’s request per their standard practice for all studies in China
Change 3: Change in definition of timing for significant protocol deviation.
The primary change occurs in 7.5 Section Criteria for Discontinuation or Withdrawal of a Subject
Initial 
wording:
2. Significant protocol deviation. The discovery after the first dose of study 
medication that the subject failed to meet protocol entry criteria or did not adhere to 
protocol requirements, and continued participation poses an unacceptable risk to the 
subject’s health. 


Vedolizumab IV
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CONFIDENTIAL
Amended 
or new 
wording:
2. Significant protocol deviation. The discovery after the first dose dosing of study 
medication that the subject failed to meet protocol entry criteria or did not adhere to 
protocol requirements, and continued participation poses an unacceptable risk to the 
subject’s health. 
Rationale for Change:
There is no change to the meaning of the sentence, just to avoid confusion since we only have one 
dose in the study.
Change 4: Revised Section 8.2 (Investigational Drug Assignment and Dispensing Procedures), to 
specify that the 3-digit Subject ID number will be used instead of 4-digit enrollment number.
The primary change occurs in Section 8.2 Investigational Drug Assignment and Dispensing 
Procedures
Initial 
wording:
Subjects will be assigned to receive a 4-digit enrollment number. The number will be 
assigned by the clinic site personnel in sequential order beginning with 1001. This 
4-digit number will be used by the clinical site to facilitate the prelabeling of PK 
samples, and will be the only subject identifier used on all PK sample collections. It 
should also be contained on the PK transport vials shipped to the bioanalytical 
laboratory, and will be used by the laboratory to report the subject data results. This 
4-digit number should only be used for the purposes described in this section. It does 
not replace the 3-digit subject number which is assigned at the time the informed 
consent is obtained and which is used for all other procedures to identify the subjects 
throughout the study.
Amended 
or new 
wording:
The 3-digit subject number which is assigned at the time the informed consent is 
obtained, will be assigned by clinic site personnel in sequential order and which 
is used for all other procedures to identify the subjects throughout the study, as 
well as to facilitate the prelabeling of PK samples, contained on the PK transport 
vials shipped to the bioanalytical laboratory, and will be used by the laboratory 
to report the subject data results.
Rationale for Change:
To specify that the 3-digit Subject ID number will be used to identify subjects, PK samples, and 
bioanalytical samples throughout study.


Vedolizumab IV
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Protocol Incorporating Amendment No. 02
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CONFIDENTIAL
Change 5: Clarify list of serum chemistry laboratory tests.
The primary change occurs in Table 9.a
Clinical Laboratory Tests
Initial 
wording:


Vedolizumab IV
Study No. Vedolizumab-1014
Page 76 of 81
Protocol Incorporating Amendment No. 02
10 May 2018
CONFIDENTIAL
Amended 
or new 
wording:
Rationale for Change:
Under serum chemistry of clinical laboratory tests to be performed, blood urea can be tested in lieu 
of blood urea nitrogen and carbon dioxide can be tested as an alternative to bicarbonate.
Change 6: Clarify timing of vital signs.
The primary change occurs in Section 9.1.5 Vital Sign Procedure
Initial 
wording:
Vital signs (temperature, respiration, pulse, and blood pressure) will be obtained at 
Screening, Check-in (Day -1), Day 1 (predose, and at 1 and 8 hours postdose), Days 2, 
8, 10(±1), 15 (±1), 29 (±2), 43(±2), 64 (±3), 85 (±3), 106 (±3), and Final Visit Day 
127(±3)/ET. For Days 1 and 2, heart rate and blood pressure will be measured after 5 
minutes supine and again at 1 and 3 minutes after standing. For Days 8, 10(±1), 15 
(±1), 29 (±2), 43(±2), 64 (±3), 85 (±3), 106 (±3) and Final Visit Day 127(±3)/ET, heart 
rate and blood pressure will be measured after 5 minutes supine only.
Amended 
or new 
wording:
Vital signs (temperature, respiration, pulse, and blood pressure) will be obtained at 
Screening, Check-in (Day -1), Day 1 (predose, and within ±5 minutes of 1 hour 
postdose and within ±30 minutes of 8 hours postdose), Days 2, 8, 10(±1), 15 (±1), 29 
(±2), 43(±2), 64 (±3), 85 (±3), 106 (±3), and Final Visit Day 127(±3)/ET. For Days 1 
and 2, heart rate and blood pressure will be measured after 5 minutes supine and again 
at 1 and 3 minutes after standing. For Days 8, 10(±1), 15 (±1), 29 (±2), 43(±2), 64
(±3), 85 (±3), 106 (±3) and Final Visit Day 127(±3)/ET, heart rate and blood pressure 


Vedolizumab IV
Study No. Vedolizumab-1014
Page 77 of 81
Protocol Incorporating Amendment No. 02
10 May 2018
CONFIDENTIAL
will be measured after 5 minutes supine only.
Rationale for Change:
Several procedures need to be done at specific time points, like vital signs, PK blood sample 
collection, and ECG at 8h postdose. PK blood sample collection should be the first priority as this 
is a PK study, so we added a time window for vital signs procedures.
Change 7: Clarification of dosing.
The primary change occurs in Section 9.3.2 Study Entrance
Initial 
wording:
If the subject has satisfied all of the inclusion criteria and none of the exclusion criteria 
for study entrance, the subject should be assigned to treatment as described in 
Section 8.2. Subjects will be administered the first dose of study medication in the unit 
under the supervision of the investigator or designee, as described in Section 8.2.
Amended 
or new 
wording:
If the subject has satisfied all of the inclusion criteria and none of the exclusion criteria 
for study entrance, the subject should be assigned to treatment as described in 
Section 8.2. Subjects will be administered the first a dose of study medication in the 
unit under the supervision of the investigator or designee, as described in Section 8.2.
Rationale for Change:
There is no change to the meaning of the sentence, just to avoid confusion since we only have one 
dose in the study.
Change 8: Deletion of collection and storage of specimens for genome/gene analysis.
The primary change occurs in 9.4 Biological Sample Retention and Destruction
Initial 
wording:
In this study, specimens for genome/gene analysis will be collected as described. The 
genetic material will be preserved and retained for up to but not longer than 15 years 
or as required by applicable law. The sponsor has put into place a system to protect the 
subjects’ personal information to ensure optimal confidentiality and defined standard 
processes for sample and data collection, storage, analysis, and destruction.
Amended 
or new 
wording:
In this study, specimens for genome/gene analysis will be collected as described. The 
genetic material will be preserved and retained for up to but not longer than 15 years 
or as required by applicable law. The sponsor has put into place a system to protect the 
subjects’ personal information to ensure optimal confidentiality and defined standard 
processes for sample and data collection, storage, analysis, and destruction.
Rationale for Change:
This study will not collect specimens for genome/gene analysis nor collect and store such 
specimens.


Vedolizumab IV
Study No. Vedolizumab-1014
Page 78 of 81
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10 May 2018
CONFIDENTIAL
Change 9: Correction in approximate blood values to be drawn.
The primary change occurs in Table 9.c Approximate Blood Volume
Initial 
wording:
The maximum volume of blood at any single day is approximately 59.5 mL, and the 
approximate total volume of blood for the study is 278.5 mL.
Amended 
or new 
wording:
The maximum volume of blood at any single day is approximately 59.5 38.5 mL, and 
the approximate total volume of blood for the study is 278.5 276 mL.
Rationale for Change:
The maximum volume of blood at any single day and total volume for the study should be more 
accurately described as approximately 38.5 mL and approximately 276 mL, respectively.
Change 10: Clarification of timing for when subjects are assessed for signs and symptoms of 
PML.
The primary change occurs in Section 11.1.1 Risk Minimization Action Program for PML (RAMP 
Program)
Initial 
wording:
The RAMP is focused on early clinical detection and management of that specific 
safety risk, including the discontinuation of study drug, if applicable. Subjects are 
assessed for signs and symptoms of PML prior to the administration of each dose of 
study drug using a PML subjective symptom checklist.
Amended 
or new 
wording:
The RAMP is focused on early clinical detection and management of that specific 
safety risk, including the discontinuation of study drug, if applicable. Subjects are 
assessed for signs and symptoms of PML prior to the administration of each dose of
study drug using a PML subjective symptom checklist.
Rationale for Change:
There is no change to the meaning of the sentence, just to avoid confusion since we only have one 
dose in the study.
Change 11: Deletion of text regarding samples collected outside the window not being considered 
a protocol deviation
The primary change occurs in Section 14.2 Protocol Deviations
Initial 
wording:
Samples collected outside the window will not be considered a protocol deviation.
Amended 
or new 
wording:
Samples collected outside the window will not be considered a protocol deviation.


Vedolizumab IV
Study No. Vedolizumab-1014
Page 79 of 81
Protocol Incorporating Amendment No. 02
10 May 2018
CONFIDENTIAL
Rationale for Change:
Original wording was deleted, because collection of samples outside the window is definitely 
considered a protocol deviation.


Vedolizumab IV
Study No. Vedolizumab-1014
Page 80 of 81
Protocol Incorporating Amendment No. 02
10 May 2018
CONFIDENTIAL
Change 12: Modifications to Appendix A (Schedule of Study Procedures) to add Day 8 timepoint for serum pregnancy test (hCG) and 
Final Visit/ET timepoint for dispensing PML Wallet Card.
The primary change occurs in Appendix A Schedule of Study Procedures
Initial wording:
Procedures or 
Observations
Screening
Treatme
nt
Follow up (a)
Days
-28 
to -2
Check-
in Day 
-1
Day 1
Day 2 Day 4 Day 6 Day 8
Day 1
0 (±1)
Day 1
5 (±1)
Day 2
9 (±2)
Day 4
3 (±2)
Day 
64 
(±3)
Day 8
5 (±3)
Day 
106 
(±3) 
Final 
Visit 
Day 
127 
/ET/ 
(±3) 
(b)
LTFU 
Safety 
Survey
Day 
168/ 
(±3)
Informed consent 
(c)
X
Dispense PML 
wallet card
X
Serum pregnancy 
test (hCG) (m)
X
X
X


Vedolizumab IV
Study No. Vedolizumab-1014
Page 81 of 81
Protocol Incorporating Amendment No. 02
10 May 2018
CONFIDENTIAL
Amended or 
new wording:
Procedures or 
Observations
Screening
Treatme
nt
Follow up (a)
Days
-28 
to -2
Check-
in Day 
-1
Day 1
Day 2 Day 4 Day 6 Day 8
Day 1
0 (±1)
Day 1
5 (±1)
Day 2
9 (±2)
Day 4
3 (±2)
Day 
64 
(±3)
Day 8
5 (±3)
Day 
106 
(±3) 
Final 
Visit 
Day 
127 
/ET/ 
(±3) 
(b)
LTFU 
Safety 
Survey
Day 
168/ 
(±3)
Informed consent 
(c)
X
Dispense PML 
wallet card
X
X
Serum pregnancy 
test (hCG) (m)
X
X
X
X
Rationale for Change:
PML is the major AESI we are monitoring. After receiving the final dose of vedolizumab, all subjects should continue to check for 
symptoms of PML and inform the doctor if they have any symptoms of PML. The study doctor or nurse will call subjects 6 months after 
the dose of vedolizumab to ask a few questions about their health. The LTFU PML Wallet Card will not only help the subjects recognize 
the symptoms of PML but also help regular doctors become familiar with PML reporting process which is part of RAMP.
“X” should also be marked for Day 8 in order to be consistent with the footnote (c) specified under Table 9.2 of the protocol, which states 
“(c) Serum hCG pregnancy test will be done on all female subjects of childbearing potential at Screening, Check-in (Day -1), Day 8 and 
at Final Visit Day 127/ET.”


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PPD

SAP_001.pdf: 


• Other information as needed to protect confidentiality of Takeda or partners, personal
information, or to otherwise protect the integrity of the clinical study.
Title: An Open-Label, Single-Center, Phase 1 Study to Determine the Pharmacokinetics of 
Single Intravenous Dose of Vedolizumab 300 mg in Healthy Adult Chinese Subjects
NCT Number: NCT03329209
SAP Approve Date: 07 December 2018
Certain information within this Statistical Analysis Plan has been redacted (ie, specific content is masked 
irreversibly from view with a black/blue bar) to protect either personally identifiable (PPD) information 
or company confidential information (CCI). 
This may include, but is not limited to, redaction of the following: 
Named persons or organizations associated with the study.
Proprietary information, such as scales or coding systems, which are considered confidential 
information under prior agreements with license holder.


1.0
TITLE PAGE
STATISTICAL ANALYSIS PLAN
STUDY NUMBER: Vedolizumab-1014
An Open-Label, Single-Center, Phase 1 Study to Determine the Pharmacokinetics of Single
Intravenous Dose of Vedolizumab 300 mg in Healthy Adult Chinese Subjects
PHASE 1
Version: Final 
Date:07 December 2018
Prepared by:
Based on:
Protocol Version: 1
Protocol Date: 01 June 2017
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.
PPD


Vedolizumab-1014
Page 2of 20
Statistical Analysis Plan
07December2018
CONFIDENTIAL
1.1
Approval Signatures
Electronic signatures can be found on the last page ofthis document.
PPD
Approvals:


Vedolizumab-1014
Page 3of 20
Statistical Analysis Plan
07December2018
CONFIDENTIAL
2.0
TABLE OF CONTENTS
1.0
TITLE PAGE..................................................................................................................1
1.1
Approval Signatures..................................................................................................2
2.0
TABLE OF CONTENTS.................................................................................................3
3.0
LIST OF ABBREVIATIONS..........................................................................................5
4.0
OBJECTIVES.................................................................................................................6
4.1
Primary Objective......................................................................................................6
4.2
Secondary Objective..................................................................................................6
4.3
Study Design.............................................................................................................6
5.0
ANALYSIS ENDPOINTS...............................................................................................7
5.1
Primary Endpoints.....................................................................................................7
5.2
Secondary Endpoints.................................................................................................7
5.3
Safety Endpoints........................................................................................................7
5.4
Additional Endpoints.................................................................................................7
6.0
DETERMINATION OF SAMPLE SIZE.........................................................................8
7.0
METHODS OF ANALYSIS AND PRESENTATION.....................................................9
7.1
General Principles......................................................................................................9
7.1.1 Study Definitions.................................................................................................9
7.1.2 Definition of Study Days......................................................................................9
7.1.3 Definition of Study Visit Windows......................................................................9
7.1.4 Conventions for Missing Adverse Event Dates...................................................10
7.1.5 Conventions for Missing Concomitant Medication Dates...................................11
7.2
Analysis Sets...........................................................................................................12
7.3
Disposition of Subjects............................................................................................12
Disposition of screen failure subjects will be summarized descriptively, as described in 
Section7.4...............................................................................................................12
7.4
Demographic and Other Baseline Characteristics.....................................................12
7.5
Medical History and Concurrent Medical Conditions...............................................12
7.6
Medication History and Concomitant Medications...................................................13
7.7
Study Drug Exposure and Compliance.....................................................................13
7.8
Efficacy Analysis.....................................................................................................13
7.9
Pharmacokinetic/Pharmacodynamic Analysis..........................................................13
7.9.1 Pharmacokinetic Analysis..................................................................................13
7.9.2 Pharmacodynamic Analysis...............................................................................14
7.10 Immunogenicity Analysis........................................................................................14


Vedolizumab-1014
Page 4of 20
Statistical Analysis Plan
07December2018
CONFIDENTIAL
7.10.1AVA Definitions................................................................................................14
7.11 Safety Analysis........................................................................................................15
7.11.1Adverse Events..................................................................................................15
7.11.2Clinical Laboratory Evaluations.........................................................................15
7.11.3Vital Signs 
................................ 
................................ 
.........................................16
7.11.412-Lead ECGs...................................................................................................16
7.11.5Other Observations Related to Safety.................................................................16
7.12 Interim Analysis......................................................................................................16
7.13 Changes in the Statistical Analysis Plan...................................................................16
8.0
REFERENCES..............................................................................................................17
LIST OF IN-TEXT FIGURES
Figure 4.a
Schematic of Study Design..................................................................................6
Figure 7.a
Study visits........................................................................................................10
LIST OF APPENDICES
Appendix A Criteria for Identification of Markedly Abnormal Laboratory Values.................18
Appendix B
Criteria for Vital Signs 
................................ 
.......................................................19
Appendix C
Criteria for Out-of-Range Values for the 12-Lead ECG Parameters....................20


Vedolizumab-1014
Page 5of 20
Statistical Analysis Plan
07December2018
CONFIDENTIAL
3.0
LIST OF ABBREVIATIONS
AE
adverse event
AESI
adverse event of special interest
ALT
alanine aminotransferase
AST
aspartate aminotransferase
AUC∞
areaunder the serum concentration-time curvefrom time 0 to infinity
AUClast
area under the serum concentration-time curvefrom time 0 to time of the last 
measurable concentration
AVA
anti-vedolizumab antibody
Cmax
maximum observed serum concentration
CPK
creatine phosphokinase
ECG
electrocardiogram
eCRF
electronic case report form
ET
early termination
GGT
-glutamyl transferase
IV
intravenous
LLN
lower limit of normal
LTFU
long-tern follow-up
MedDRA
Medical Dictionary for Regulatory Activities
PK
pharmacokinetics
PML 
progressive multifocal leukoencephalopathy
PTE
pretreatment event
SAE
serious adverse event
SD
standard deviation
t
1/2z
terminal disposition phase half-life
t
max
time of first occurrence of C
max
ULN
upper limit of normal
WHODrug
World Health Organization Drug Dictionary


Vedolizumab-1014
Page 6of 20
Statistical Analysis Plan
07December2018
CONFIDENTIAL
4.0
OBJECTIVES
4.1
Primary Objective
To assess the PK of vedolizumab following a single intravenous (IV)infusion in healthy 
adult Chinese subjects.
4.2
Secondary Objective
To evaluate the safety and tolerability of a single IV infusion of vedolizumab in healthy adult 
Chinese subjects.
4.3
Study Design
This is an open-label, single-center, phase 1 study to determinethe pharmacokinetics (PK) of 
single dose of vedolizumab IV 300 mg in healthy adult Chinese subjects. The number of subjects 
to be dosed in the study is 16. Since vedolizumab is intended to be used by both male and female 
subjects with ulcerative colitisor Crohn’s disease, effort will be made to enroll an equal number 
of male and female subjects in this study. 
Subjects will be kept in the study unit for at least 3 days after the start of infusion on Day 1 for 
safety and PK assessments before discharge. The confinement period will be a minimum of 
3days and a maximum of 7 days.
Subjects will return to the study units periodically according to the predetermined PK sampling 
scheduled until Day 127 or Early Termination (ET). Additionally, subjects will be required to 
participate in a long-term follow-up (LTFU) safety survey by telephone, 6 months after the dose 
of study drug. The total duration on study for each subject will be approximately 7.0 months, 
including screening.
A schematic of the study design is included asFigure 4.a.
Figure 4.a
Schematic of Study Design
Screening
Treatment 
Follow-Up
Days
-28 to -2
Day -1
(Check-in)
Day 1
Day 2-3
Days 10, 15, 
29, 43, 64, 
85, 106 (a)
Final 
Visit/ET
Day 127 (b)
LTFU Safety 
Survey (c)
Day 168
Dosing and PK
PK and safety assessments
Safety 
assessments
Confinement 
(a) Days 10 and 15 have a ±1 day window. Days 29and 43 a ±2 day window, and Days 64, 85, 106 and 127/ET all 
have a ±3 day window.
(b)In case abnormal, clinically significant findings are observed upon discharge, subjects may be brought back to 
the clinic for re-evaluation per investigator’s discretion.
(c) Subjects will be followed poststudy by telephone call at Day 168 (±3 days) after the last dose of study drug to 
administer a LTFU safety survey.


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5.0
ANALYSIS ENDPOINTS
5.1
Primary Endpoints
Maximum observed serum concentration(C
max).
Area under the serum concentration-time curvefrom time 0 to time of the last measurable 
concentration (AUC
last).
Areaunder the serum concentration-time curvefrom time 0 to infinity (AUC∞).
5.2
Secondary Endpoints
Proportion of subjects with positive anti-vedolizumab antibody (AVA) during the study.
Proportion of subjects with positive neutralizing AVA during the study.
5.3
Safety Endpoints
Safety assessment: Percentage of subjects with adverse events (AEs), percentage of subjects 
with adverse events of special interest (AESIs, including serious infections, including 
opportunistic infection such as progressive multifocal leukoencephalopathy (PML), liver 
injury,malignancies and infusion related reactions and hypersensitivity), percentage of 
subjects with serious adverse events (SAEs),number of subjects with markedly abnormal 
vital signs, number of subjects with markedly abnormal laboratory tests (clinical chemistry, 
hematology, coagulation, urinalysis), and number of subjects with markedly abnormal 12-
lead electrocardiograms (ECGs). 
5.4
Additional Endpoints
Time of first occurrence of C
max(t
max).
Terminal disposition phase half-life (t
1/2z).


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6.0
DETERMINATION OF SAMPLE SIZE
The sample size of 16 subjects is considered sufficient to evaluate the PK profiles after single 
dose of vedolizumabIV in adult healthy Chinese subjects.This sample size is not based on 
statistical considerations.


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7.0
METHODS OF ANALYSIS AND PRESENTATION
7.1
General Principles 
Baseline values are defined as thelast observed value before dosing of study medication. 
All statistical analyses will be conducted using SAS
® Version 9.4, or higher.
All confidence intervals, statistical tests, and resulting P-values will be reported as 2-sided and 
will be assessed at α=0.05 significance level unless otherwise stated. P-values will be rounded to 
3 decimal places prior to assessment of statistical significance.
Means and medians will be presented to 1 more decimal place than the recorded data. The 
standard deviations (SDs) will be presented to 2 more decimal places than the recorded data. 
Confidence intervals about a parameter estimate will be presented using the same number of 
decimal places as the parameter estimate.
Where appropriate, variables will be summarized descriptively by study visit. For the categorical 
variables, the count 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. 
Screen failure subjects will be grouped and listed at the end.
7.1.1 Study Definitions
7.1.2 Definition of Study Days
Study Day 1 is defined as the date on which asubject is administered their first dose of the 
medication. Other study days are defined relative to the Study Day 1 with Day 1 being Study 
Day 1 and Day -1 being the day prior to Study Day 1.
7.1.3 Definition of Study Visit Windows
A windowing convention will be used to determine the analysis value for a given study visit that 
applies to observed data. For each visit, a window will be defined such that the lower and upper 
bounds of each window is generally the midpoint between 2 consecutive study visits. 
More than 1 result for a parameter may be obtained in a visit window. In such an event, the result 
with the date closest to the scheduled visit day will be used. In the event of 2 observations 
equidistant to the scheduled visit day, the later of the observations will be used.


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Figure 7.a
Study visits
Visit
Scheduled 
Visit Day
Visit Window (Days)
Vital Signs
ECG
Labs
AVA
PK
Safety 
Survey
10
9-11
9-11
9-11
15
14-16
14-16
29
27-31
27-31
27-31
27-31
43
41-45
41-45
41-45
64
61-67
61-67
61-67
85
82-87
82-87
82-87
82-87
106
103-109
103-109
103-109
Final Visit
127
124-130
124-130
124-130
124-130
124-130
LTFU 
Safety 
Survey
168
165-171
7.1.4 Conventions for Missing Adverse Event Dates
Adverse event (AE)dates that are completely or partially missing willbe imputed. The imputed 
dates will only be used to evaluate the treatment-emergent status as specified in Section 7.11.1. 
The imputation will be performed on start date first, and then on end dates for each record of AE.
7.1.4.1 Impute Incomplete or Missing Start Dates
1. If the start date has non-missingmonth and year but day is missing.
a) Impute the AE start date as 15thday of the month. 
b) If the combination of year and month is the same as the year and month of first dose date, 
impute the AE start date as the later of (first dose date, 15
thday of the month).
2. If the start date has non-missingyear, but day and months are missing.
a) Impute the AE start date as June 15thof the year.
b) If the year is the same as the year of first dose date, impute the AE start date as the late of 
(first dose date, June 15
thof the year).
3. If the start date is completely missing, the impute AE start date as.
a) First dose date or date of Informed Consent if patient is not dosed.
4. If the imputed AE start date is later than the un-imputed AE end date after steps 1-3, then 
impute the AE start date the same as the AE end date.
5. If theimputed AE start date is later than the database cutoff date after steps 1-4, then impute 
the AE start date the same as the database cutoff date.


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7.1.4.2 Impute Incomplete or Missing End Dates
1. If the AE end date has month and year,but day is missing, impute the date the last day of the 
month (for example, February 2018 will be imputed as 28 February 2018).
2. If the AE end date has year,but month and day is missing, impute the date as the last day of 
the year (i.e. December 31
stof the year).
3. If the AE end date is completely missing, impute the date as the last assessment date of the 
subject.
4. If the imputed AE end date is earlier than the AE start date (imputed version) after steps 1-3, 
then impute the AE end date the same as the AE start date (imputed version).
5. If the imputed AE end date is later than the database cutoff date after steps 1-4, then impute 
the AE end date the same as the database cutoff date.
7.1.5 Conventions for Missing Concomitant Medication Dates
Start and stop dates for all prior and concomitant medications, and start date for concomitant 
procedures are collected on the eCRF. Dates for prior concomitant medication and procedures 
that are completely or partially missing will be imputed. The imputation will be performed on 
start date first, and then on end dates for each record of medication as follows
7.1.5.1 Impute for Incomplete or Missing Start Dates of Medication or Procedure
1. If the day is missing, the start date will be the first day of the month.
2. If the month is missing, the start month will be the month corresponding to 90 days prior to 
the date of first dose of study drug.
3. If the year is missing, the start year will be the minimum of (the year of the first clinic visit, 
the year of the informed consent date).
4. If the entire date is unknown, the start datewill be the date of first dose of study drug.
7.1.5.2 Impute for Incomplete or Missing End Dates of Medication
1. If the day is missing, the stop day will be the last day of the month reported.
2. If the month is missing, the stop month will be to the month during which the last assessment 
occurred.
3. If the year is missing or the entire date is unknown or if the medication is “ongoing”, the stop 
year will be the year in which the last assessment occurred.
No dates will be imputed for previous medications.


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7.2
Analysis Sets
Safety Set:
The safety analysis set will consist of all subjects who are enrolled and received 1 dose of study 
drug. Subjects in this analysis set will be used for demographic, baseline characteristics and 
safety summaries.
Pharmacokinetic Set:
The PK set will consist of all subjects who receive study drug and have at least 1 measurable 
serum concentration.
7.3
Disposition of Subjects
Disposition of all subjectsin the Safety Setwill be tabulated: 
All subjects received study drug (denominator).
Subjects who completed the study.
Subjects who prematurely discontinued study treatment.
Subjects who prematurely discontinued study.
Primaryreasons for discontinuation of study treatment or study will be entered on the electronic 
case report form (eCRF), will be tabulated. Reasons for premature discontinuation of study an 
and/or study treatment include death, adverse event, protocol deviation, lost to follow-up, 
withdrawal by subject, study termination by sponsor, pregnancy, and other. The date of dosing
and the reason for premature discontinuation of study drug/study visit will be presented for each 
subject in listings. 
Disposition of screenfailure subjects will be summarized descriptively, as described in 
Section7.4.
7.4
Demographic and Other Baseline Characteristics
Demographic and baseline characteristics will be summarized. Summary statistics (number of 
subjects, mean, SD, median, minimum and maximum) will be generated for continuous variables 
(eg, age and weight) and the number and percentage of subjects within each category will be 
presented for categorical variables (eg, gender, ethnicity, and race).
Demographic variables of screen failure subjects and reasons for screen failures will be 
summarized for subjects who are screened, but not enrolled in the study. Individual demographic 
characteristics,date of informed consent, and reason for screen failure will be listed.
7.5
Medical History and Concurrent Medical Conditions
Medical history to be obtained will include determining whether the subject has any significant 
conditions or diseases relevant to the disease under study that stopped at or prior to signing of 
informed consent.Concurrent medical conditions are those significant ongoing conditions or 


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diseases that are present at signing of informed consent. This includes clinically significant 
laboratory, ECG, or physical examination abnormalitiesnoted at screening examination.
Medical history and concurrent medical conditions will be coded using MedDRA and will be 
separately summarized by system organ class and preferred term. They will also be presented in 
data listings.
7.6
Medication History and Concomitant Medications
Concomitant medication is any drug given in addition to the study medication. These may be 
prescribed by a physician or obtained by the subject over the counter. Concomitant medication is
not provided by Takeda. At each study visit, subjects will be asked whether they have taken any 
medication other than the study medication (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. Documentation will 
include generic medication name, dose, unit, frequency, route of administration, start and end 
dates, and reason for use.
Medication history information to be obtained includes any medication relevant to eligibility 
criteria stopped at or within 28 days prior to signing of informed consent.
Prior and concomitant medications will be summarized by drug class (ATC Pharmacological 
subgroup), WHODrugpreferred term. All prior and concomitant medications will be listed.
Concomitant procedures will not be coded, but will be presented in listings as appropriate.
7.7
Study Drug Exposure and Compliance
The single dose of study medication will be administered while subjects are under observation in 
the clinical research unit.The date and time of the single dose will be recorded, as well as any 
dose adjustment (drug withdrawn, drug infusion interrupted) and the reason for it These results 
will be listed and summarized.
7.8
Efficacy Analysis
Not applicable 
7.9
Pharmacokinetic/Pharmacodynamic Analysis
7.9.1 Pharmacokinetic Analysis
Descriptive statistics will be used to summarize serum concentrations of vedolizumab over each 
scheduled sampling time. Individual serum concentration-time data will be presented as listings. 
Additionally, graphical plots of individual and mean plasma concentration vs time profiles will 
be presented (untransformed and semi-log scales).
The PK parameters of vedolizumab will be determined from the concentration-time profiles for 
all evaluable subjects using a non-compartmental analysis method. The PK parameters, including


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t
max, C
max, AUC
last, AUC
∞, Vz, CLandt
1/2z, will be determined from serum concentration-time 
data for all evaluable subjects. Actual sampling times, rather than scheduled sampling times, will 
be used in all computations involving sampling times.
Descriptive statistics will be used to summarize serum PK parameters of vedolizumab. 
Individual serum PK parameters will be presented in a datalisting.
Serum concentrations that are below the limit of quantification (BLQ) will be treated as zero in 
the summarizing concentration values and deriving of PK parameters. These values will be 
flagged in the data listings, and deviations from this convention may be considered on a 
case-by-case basis as deemed appropriate.
7.9.2 Pharmacodynamic Analysis
Not applicable 
7.10 Immunogenicity Analysis
Titers of AVA and neutralizing AVA will be listed. The following tables for immunogenicity 
analysis will be produced:
Summary of AVA status.
Summary of AVA status by study visit.
Summary of AVA status by titer.
In addition, the impact of AVA on PK and safety may be explored.
7.10.1AVA Definitions
1. Definition of AVA positive and negative
Negative AVA: defined as a sample that wasevaluated as negative in the AVA screening 
assay.Samples that were determined to be positive in the AVA screening assay but the 
result was not confirmed in the AVA confirmatory assay were considered negative.
Positive AVA:defined as a sample that was evaluated as positive in both the AVA 
screening and confirmatory assays.
Positive neutralizing AVA:defined as a sample that wasevaluated as positive in the 
neutralizing AVA assay.
SubjectAVA status will be grouped into 3categories as follows:
Negative:defined as subjectswho didnot have confirmed AVA results.
Positive:defined as subjectswho had at least 1 positive AVA result.
– Transiently positive:defined as subjectswith confirmed positive AVA in 1sample.
– Persistently positive:defined as subjectswith confirmed positive AVA in 2or more 
consecutive positive AVA samples.


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Subject AVA positive at baseline is defined as a positive AVA sample at Week0 
(predose).
7.11 Safety Analysis
7.11.1Adverse Events
7.11.1.1Definitions
A pretreatment event (PTE)is defined as any untoward medical occurrence in a clinical 
investigation subject who has signed informed consent to participate in a study but prior to 
administration of any study medication; it does not necessarily have to have a causal relationship 
with study participation. An AE is defined as any untoward medical occurrence in a clinical 
investigation subject administered a drug; it does not necessarily have to have a causal 
relationship with this treatment.A treatment-emergent adverse event (TEAE) is defined as AE 
whichoccurs upon or after dosing with study drug, up to day 130.
Adverse events of special interest (AESIs) for vedolizumab include serious infections (including 
opportunistic infection such as PML), liver injury, malignancies, infusion-related or systemic 
reactions and hypersensitivity.
7.11.1.2Analysis and Reporting
The number and percentage of subjects with TEAEs,AESIs for vedolizumab, and serious 
adverse, which occur on or after dosing in patients, will be summarized by MedDRA system 
organ class, and preferred term overall, by severity, and by relationship to study drug. Separate 
summaries will also be generated for treatment-related AEs overall and by severity. Data listings 
will be provided for all AEs (including PTEs for enrolled subjects), AEs leading to study drug 
discontinuation, AEs leading to study visit discontinuation, SAEs, AESIs, and AEs resulting in 
death.The Medical Dictionary for Regulatory Activities (MedDRAv20.1 or higher)will be used 
for coding AEs.
7.11.2Clinical Laboratory Evaluations
Baseline, postbaseline and change from baseline in clinical laboratory tests will be summarized. 
Subjects with markedly abnormal valuesfor laboratory testswill be tabulated. The mapping of 
the subjects who meet the markedly abnormal value criteria will be listed as a table. Individual 
results for clinical laboratory testswill be listed.
For the purposes of summarization in both the tables and listings, all laboratory values will be 
converted to System International (SI) units.If a lab value is reported using a non-numeric 
qualifier (e.g., less than (<, ≤) a certain value, or greater than (>, ≥) a certain value), the given 
numeric value will be used in the summary statistics, ignoring the non-numeric qualifier.
Laboratory abnormalities will be evaluated based on themarkedly abnormal value (MAV) 
criteria in Appendix A. 


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7.11.3Vital Signs
Baseline, postbaseline and change from baseline in vital signswill be summarized. Subjects with 
markedly abnormal values for vital signswill be tabulated. The mapping of the subjects who 
meet the markedly abnormal value criteria will be listed as a table. Individual results for vital 
signs will be listed.
See Appendix Bfor MAVcriteriafor vital signs.
7.11.412-Lead ECGs
Baseline, postbaseline and change from baseline in ECG results will be summarized. Subjects 
with markedly abnormal values for ECG results will be tabulated. The mapping of the subjects 
who meet the markedly abnormal value criteria will be listed as atable. Individual results for 
ECG measures will be listed.
See Appendix Cfor MAVcriteria for ECGs.
7.11.5Other Observations Related to Safety
Physical examination findings and PML checklist data will be presented in data listings.
7.12 Interim Analysis
Not applicable 
7.13 Changes in the Statistical Analysis Plan 
Not applicable


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8.0
REFERENCES
Not applicable


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Appendix A Criteria for Identification of Markedly Abnormal Laboratory Values 
Hematology—Criteria for Markedly Abnormal Values
Parameter
Unit
Low Abnormal
High Abnormal
Hemoglobin
Both 
<0.8 × LLN
>1.2 × ULN
Hematocrit
Both
<0.8 × LLN
>1.2 × ULN
RBC count 
Both
<0.8 × LLN 
>1.2 × ULN
WBC count 
Both 
<0.5x LLN
>1.5 x ULN
Platelet count
Conventional
<75x 103/L
>600 x 103/L
SI
<75 x 109/L
>600 x 109/L
LLN=lower limit of normal, RBC=red blood cell, ULN=upper limit of normal, WBC=white blood cell. 
Serum Chemistry—Criteria for Markedly Abnormal Values
Parameter
Unit 
Low Abnormal
High Abnormal
ALT
Both
--
>3x ULN
AST
Both
--
>3x ULN
GGT
Both
--
>3x ULN
Alkaline phosphatase
Both
--
>3x ULN
Total bilirubin
Conventional
--
>2.0 mg/dL
SI
--
>34.2 mol/L
Albumin
Conventional 
<2.5 g/dL
--
SI 
<25 g/L
--
Total protein
Both
<0.8x LLN
>1.2x ULN
Creatinine
Conventional 
--
>2.0 mg/dL
SI
>177 mol/L
Blood urea nitrogen
Conventional 
>30 mg/dL
SI
>10.7 mmol/L
Sodium
Conventional
<130 mEq/L
>150 mEq/L
SI
<130 mmol/L
>150 mmol/L
Potassium
Conventional
<3.0 mEq/L
>6.0 mEq/L
SI
<3.0 mmol/L
>6.0 mmol/L
CPK
Both
--
>5x ULN
Glucose
Conventional
<50 mg/dL
>350 mg/dL
SI
<2.8 mmol/L
>19.4 mmol/L
Calcium
Conventional
<7.0 mg/dL
>11.5 mg/dL
SI
<1.75 mmol/L
>2.88 mmol/L
ALT=alanine aminotransferase, AST=aspartate aminotransferase, CPK=creatine phosphokinase, GGT=-glutamyl 
transferase, LLN=lower limit of normal, ULN=upper limit of normal.


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Appendix B Criteria for Vital Signs
Parameter
Unit
Lower Criteria
Upper Criteria
Pulse
bpm
<50 
>120
Systolic blood pressure
mm Hg
<85
>180 
Diastolic blood pressure
mm Hg
<50
>110
Body temperature
oC
<35.6
>37.7


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Appendix C Criteria for Out-of-Range Values for the 12-Lead ECG Parameters
Parameter
Lower Criteria
Upper Criteria
Heart rate
<50 beatsper minute
>120 beatsper minute
PR
≤80 milliseconds
≥200 milliseconds
QT Interval
≤300milliseconds
≥460milliseconds
QTcB Interval
≤300milliseconds
≥500milliseconds OR 
≥30milliseconds change from baseline and
≥450 milliseconds
QTcF Interval
≤300milliseconds
≥500milliseconds OR 
≥30milliseconds change from baseline and
≥450 milliseconds
QRS
≤80 milliseconds
≥180milliseconds


 
  
ELECTRONIC SIGNATURES 
Signed by 
Meaning of Signature 
Server Date 
(dd-MMM-yyyy HH:mm ‘UTC’) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
090101d6809e5215
Copy of An Open-Label, Single-Center, Phase 1 Study to Determine the Pharmacokinetics of Single Intravenous
Dose of Vedolizumab 300 mg in Healthy Adult Chinese Subjects
PPD
Biostatistics Approval
09-Dec-2018 15:08 UTC
Clinical Pharmacology Approval
09-Dec-2018 23:27 UTC
Clinical Science Approval
10-Dec-2018 01:22 UTC
Biostatistics Approval
10-Dec-2018 14:01 UTC