A Phase 2b, Extension Study to Determine the Long-term Safety of Vedolizumab IV in Pediatric Subjects With Ulcerative Colitis or Crohn's Disease
Phase: PHASE2
Conditions: Ulcerative Colitis, Crohn's Disease
Sponsor: Takeda

For non-commercial use only

 
 
 
PROTOCOL 
A Phase 2b, Extension Study to Determine the Long-term Safety of Vedolizumab IV in 
Pediatric Subjects With Ulcerative Colitis or Crohn’s Disease 
Long-term Safety With Vedolizumab IV in Pediatric Subjects With Ulcerative Colitis or 
Crohn’s Disease 
Sponsor: 
Takeda Development Center Americas, Inc. 
95 Hayden Avenue, Lexington, MA 02421 
Study Number: 
Vedolizumab-2005 
IND Number: 
009125 
EU CT Number: 
2023-507766-35 
Compound: 
Vedolizumab IV 
Date: 
27 September 2024 
Amendment 
Number: 
8 
Amendment History: 
Date 
Amendment Number 
Region 
27 September 2024 
8 
Global 
08 March 2023 
7 
Global 
01 December 2021 
6 
Global 
24 August 2018 
05 
Global 
13 February 2018 
04 
Global 
13 October 2017 
03 
Local/United Kingdom 
25 May 2017 
02 
Global 
07 April 2017 
01 
Global 
17 October 2016 
Initial version 
Global 
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. 
For non-commercial use only

9HGROL]XPDE,9
6WXG\1R9HGROL]XPDE
3DJH RI
3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
 6HSWHPEHU 
&21),'(17,$/

$'0,1,675$7,9(,1)250$7,21

&RQWDFWV
$VHSDUDWHFRQWDFWLQIRUPDWLRQOLVWZLOOEHSURYLGHGWRHDFKVLWH
7DNHGD'HYHORSPHQW&HQWHU$PHULFDV,QF 7'& $PHULFDVVSRQVRUHGLQYHVWLJDWRUVSHU
LQGLYLGXDOFRXQWU\UHTXLUHPHQWVZLOOEHSURYLGHGZLWKDQHPHUJHQF\PHGLFDOFRQWDFW
LQIRUPDWLRQFDUGWREHFDUULHGE\HDFKVXEMHFW
*HQHUDODGYLFHRQSURWRFROSURFHGXUHVVKRXOGEHREWDLQHGWKURXJKWKHPRQLWRUDVVLJQHGWRWKH
VWXG\VLWH,QIRUPDWLRQRQVHUYLFHSURYLGHUVLVJLYHQLQ6HFWLRQ DQGUHOHYDQWJXLGHOLQHV
SURYLGHGWRWKHVLWH
&RQWDFW7\SH5ROH
$PHULFDVDQG(XURSH5HVWRI:RUOG
7'&&RQWDFW
6HULRXVDGYHUVHHYHQWDQGSUHJQDQF\
UHSRUWLQJ
$PHULFDV
)D[
(PDLO396DIHW\$PHULFDV#WDNHGDFRP
(XURSH5HVWRI:RUOG
3KDUPDFRYLJLODQFH0DLOER[#WDNHGDFRP
0HGLFDO0RQLWRU
PHGLFDODGYLFHRQSURWRFRODQG
FRPSRXQG
0'
± *,*OREDO&OLQLFDO6FLHQFH
7HOHSKRQH
5HVSRQVLEOH0HGLFDO2IILFHU
FDUULHVRYHUDOOUHVSRQVLELOLW\IRUWKH
FRQGXFWRIWKHVWXG\
0'
&OLQLFDO6FLHQFH
7HOHSKRQH
PPD
PPD
PPD
PPD
PPD
PPD
For non-c
7HOHSKR
7HOHSKR
on
omme
QH
0
mm
om
co
rcial use only
DV#WDNHG
WDNH
G
H0DLOER[
0DLOER
y
0'
0'
ia
r
merc
me
PPD

9HGROL]XPDE,9
6WXG\1R9HGROL]XPDE
3DJH RI
3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
 6HSWHPEHU 
&21),'(17,$/

$SSURYDO
5(35(6(17$7,9(62)7$.('$
7KLVVWXG\ZLOOEHFRQGXFWHGZLWKWKHKLJKHVWUHVSHFWIRUWKHLQGLYLGXDOSDUWLFLSDQWVLQ
DFFRUGDQFHZLWKWKHUHTXLUHPHQWVRIWKLVFOLQLFDOVWXG\SURWRFRODQGDOVRLQDFFRUGDQFHZLWKWKH
IROORZLQJ
x
7KHHWKLFDOSULQFLSOHVWKDWKDYHWKHLURULJLQLQWKH'HFODUDWLRQRI+HOVLQNL
x
,QWHUQDWLRQDO&RXQFLOIRU+DUPRQLVDWLRQRI7HFKQLFDO5HTXLUHPHQWVIRU3KDUPDFHXWLFDOVIRU
+XPDQ8VH,&+(*RRG&OLQLFDO3UDFWLFH *&3&RQVROLGDWHG*XLGHOLQH
x
5HJXODWLRQ(XURSHDQ8QLRQ >(8@1RRIWKH(XURSHDQ3DUOLDPHQWDQGRIWKH
&RXQFLO
x
(WKLFDOFRQVLGHUDWLRQVIRUFOLQLFDOWULDOVRQPHGLFLQDOSURGXFWVFRQGXFWHGZLWKPLQRUV
x
5HFRPPHQGDWLRQVRIWKHH[SHUWJURXSRQFOLQLFDOWULDOVIRUWKHLPSOHPHQWDWLRQRI5HJXODWLRQ
(81RRQFOLQLFDOWULDOVRQPHGLFLQDOSURGXFWVIRUKXPDQXVH
x
$OODSSOLFDEOHODZVDQGUHJXODWLRQVLQFOXGLQJZLWKRXWOLPLWDWLRQGDWDSULYDF\ODZVFOLQLFDO
WULDOGLVFORVXUHODZVDQGUHJXODWLRQV
6,*1$785(6
7KHVLJQDWXUHRIWKHUHVSRQVLEOH7DNHGDPHGLFDORIILFHUDQGRWKHUVLJQDWRULHVDVDSSOLFDEOHFDQ
EHIRXQGRQWKHVLJQDWXUHSDJH
(OHFWURQLFVLJQDWXUHVPD\EHIRXQGRQWKHODVWSDJHRIWKLVGRFXPHQW
0'
&OLQLFDO6FLHQFH
'DWH
*,6WDWLVWLFV
6WDWLVWLFDODQG4XDQWLWDWLYH6FLHQFHV
'DWD 6FLHQFHV,QVWLWXWH
'DWH
4XDQWLWDWLYH&OLQLFDO3KDUPDFRORJ\
'DWH

3KDUPDFRYLJLODQFH
'DWH
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
For non-commercial use only
WVFR
WVFR
IRUWKHLP
UWKH
GXFWVIR
GXFWVI
LWKRXWOLP
WKRXW
PHGLFDOR
GLFD
GRQWKH
RQWK
F

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 4 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
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. 
• ICH, E6 GCP: 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. 
• Responsibilities of the Investigator (Appendix B). 
I further authorize that my personal information may be processed and transferred in accordance 
with the uses contemplated in Appendix D of this protocol. 
 
Signature of Investigator 
Date 
Investigator Name (print or type) 
Investigator’s Title 
Location of Facility (City, State/Province) 
Location of Facility (Country) 
 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 5 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
1.3 
Protocol Amendment 8 Summary of Changes 
Protocol Amendment 8 Summary and Rationale: 
This section describes the changes in reference to the protocol incorporating Amendment 8. The 
primary reasons for this amendment are to: 
• Comply with European Union (EU) Clinical Trial Regulation (CTR) protocol requirements. 
• Update treatment-emergent adverse events (TEAEs) definition. 
• Harmonize serious infections adverse event of special interest (AESI) definition across the 
vedolizumab program. 
In this amendment, minor grammatical, editorial, formatting, and administrative changes not 
affecting the conduct of the study are included for clarification and administrative purposes only. 
Protocol Amendment 8 
Summary of Changes Since the Last Version of the Approved Protocol 
Change 
Number 
Sections Affected by Change 
Description of Each Change and Rationale 
Location 
Description 
Rationale 
1.  
Section 1.1 Contacts 
Contact information was updated and consolidated for ease of use. 
2.  
Section 1.2 Approval 
 
• 
A statement that the clinical trial 
will be conducted in compliance 
with Regulation [EU] No. 
536/2014 was added. 
• 
A statement that the clinical trial 
will be conducted in compliance 
with “Ethical considerations for 
clinical trials on medicinal products 
conducted with minors”, and 
“Recommendations of the expert 
group on clinical trials for the 
implementation of Regulation (EU) 
No. 536/2014 on clinical trials on 
medicinal products for human use. 
2017.” was added. 
To comply with EU 
CTR protocol 
requirements. 
3.  
Signatories 
The name of the responsible Takeda medical officer and other 
signatories were updated. 
4.  
Title Page 
Section 2.0 Study Summary 
Replaced EudraCT number with EU CT 
number to comply with EU CTR 
protocol requirements. 
To comply with EU 
CTR protocol 
requirements. 
5.  
Section 3.1 Study-Related 
Responsibilities 
Revised study related responsibilities. 
Revised for clarity. 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 6 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
Protocol Amendment 8 
Summary of Changes Since the Last Version of the Approved Protocol 
Change 
Number 
Sections Affected by Change 
Description of Each Change and Rationale 
Location 
Description 
Rationale 
6.  
Section 3.5 Study Definitions 
Definitions of ‘Study start’, ‘End of 
study’, and ‘Enrollment’ were added. 
To comply with EU 
CTR protocol 
requirements. 
7.  
Section 4.1.3 Vedolizumab IV 
• 
Subsection 4.1.3.2 
Clinical 
Revised ‘over 70 countries’ to ‘more 
than 70 countries’. 
Revised for clarity. 
8.  
Section 2.0 Study Summary 
Section 4.4 Risks Associated 
With Study Procedures 
The potential benefit/risk in the boxed 
protocol summary and benefit/risk 
section of the protocol with the 
potential risks for subjects exposed to 
the investigational medicinal product in 
the current trial were added.  
To comply with EU 
CTR protocol 
requirements. 
9.  
Section 7.3 Excluded 
Medications, Vaccinations, 
Procedures, and Treatments 
The following statement was added: 
“Subjects who do not respond to 
treatment or show worsening of their 
disease after entering the safety follow-
up period will no longer need to abstain 
from the medications that were 
prohibited during the screening and 
treatment periods. High dose 
glucocorticoids and other treatments 
will be allowed. Biologics or 
nonbiologic immunosuppressants 
should not be initiated during the safety 
follow-up period without prior 
discussion with the sponsor study 
physician or designee due to the long 
half-life of vedolizumab.” 
For clarity on whether 
starting other therapies 
during the safety follow-
up period would be 
permitted or not. 
10.  
Section 8.1.2 Storage 
Instruction was added to protect the 
study drug from light. 
Clarification regarding 
study drug storage. 
11.  
Section 9.1 Study Procedures 
• 
Subsection 9.1.2 
Demographics, Medical 
History, and Medication 
History Procedure 
Revised the demographic information 
that will be collected at screening. 
Revised for clarity and 
to comply with EU CTR 
protocol requirements.  
12.  
Section 9.1.6 Efficacy 
Measurements  
• 
Subsection 9.1.6.1.2 CD 
Activity 
Removed the specific visit window and 
referred to the Schedule of Study 
Procedures table to align with the 
changes made in the table.  
Revised for consistency 
between sections.  
For non-commercial use only

9HGROL]XPDE,9
6WXG\1R9HGROL]XPDE
3DJH RI
3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
 6HSWHPEHU 
&21),'(17,$/
3URWRFRO$PHQGPHQW
6XPPDU\RI&KDQJHV6LQFHWKH/DVW9HUVLRQRIWKH$SSURYHG3URWRFRO
&KDQJH
1XPEHU
6HFWLRQV$IIHFWHGE\&KDQJH
'HVFULSWLRQRI(DFK&KDQJHDQG5DWLRQDOH
/RFDWLRQ
'HVFULSWLRQ
5DWLRQDOH

6HFWLRQ  6WXG\3URFHGXUHV
x
6XEVHFWLRQ 7DQQHU
6WDJH(YDOXDWLRQ
$GGHGYLVLWZLQGRZ
$GGHGIRUFRQVLVWHQF\
EHWZHHQVHFWLRQV

6HFWLRQ 3UHJQDQF\
,QFRUSRUDWHGIROORZXSRIDOO
SUHJQDQFLHVDQGSUHJQDQF\RXWFRPHV
IRU\HDUDIWHUELUWK
,QFRUSRUDWHGSRVWSDUWXP
VDIHW\HYDOXDWLRQSHULRG
WRSURYLGHDGGLWLRQDO
LQIRUPDWLRQRQ
SUHJQDQF\RXWFRPHV

6HFWLRQ
$SSHQGL[ $ 6FKHGXOH RI
6WXG\3URFHGXUHV
$GGHGIRUFODULW\

6HFWLRQ )LQDO9LVLWRU(7
6HFWLRQ )LQDO6DIHW\
)ROORZXS9LVLW
x
&ODULILHGWKDWWKHILQDOYLVLWLVWREH
FRPSOHWHGZLWKLQZHHNV
IROORZLQJDSUHDJUHHGXSRQ
VXEMHFW¶VODVWGRVHGHWHUPLQHGE\
WKHLQYHVWLJDWRUDQGSULRUWRDQ\
SODQQHGGRVHLIWKHVXEMHFWLVWR
WUDQVLWLRQWRFRPPHUFLDOGUXJRU
RWKHU GUXJDFFHVV SURJUDP
6XEMHFWVDUHVWLOOH[SHFWHGWR
FRPSOHWHERWKWKHILQDOVDIHW\
IROORZXSYLVLW6HFWLRQ
ZKLFKLVSHUIRUPHGDWZHHNV
SRVWODVWGRVHDQGWKHORQJWHUP
IROORZXSVDIHW\VXUYH\SKRQH
FDOOZKLFKLVFRPSOHWHGPRQWKV
DIWHUWKHODVWGRVHRIVWXG\GUXJ
6HFWLRQ
x
$ VWDWHPHQW ³6XEMHFWVDUHH[SHFWHG
WRFRPSOHWHWKHILQDOVDIHW\IROORZ
XSYLVLW´ ZDVDGGHG
5HYLVHGIRUFODULW\

6HFWLRQ 3RVWVWXG\&DUH
5HYLVHGWKHVWDWHPHQWIURP µ3RVWWULDO
DFFHVVWRYHGROL]XPDE,9PD\EH
SURYLGHGE\WKHVSRQVRU¶ WRµ3RVWWULDO
DFFHVVWRFRPPHUFLDOO\DYDLODEOH
YHGROL]XPDE,9PD\EHSURYLGHGE\WKH
VSRQVRU¶
5HYLVHGIRUFODULW\
CCI
CCI
CC
For non-commercial use only
&ODULILHG
&ODULI
FRPS
FRP
IR
m
on
nly
on
se o
use
al u
cia
erc
me

9HGROL]XPDE,9
6WXG\1R9HGROL]XPDE
3DJH RI
3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
 6HSWHPEHU 
&21),'(17,$/
3URWRFRO$PHQGPHQW
6XPPDU\RI&KDQJHV6LQFHWKH/DVW9HUVLRQRIWKH$SSURYHG3URWRFRO
&KDQJH
1XPEHU
6HFWLRQV$IIHFWHGE\&KDQJH
'HVFULSWLRQRI(DFK&KDQJHDQG5DWLRQDOH
/RFDWLRQ
'HVFULSWLRQ
5DWLRQDOH

6HFWLRQ $OWHUQDWLYH
$SSURDFKHVWR6WXG\
3URFHGXUHVDQG'DWD
&ROOHFWLRQ'XHWRD3DQGHPLF
7KHIROORZLQJVWDWHPHQWKDVEHHQ
UHPRYHG ³$(VRI&29,'±UHODWHG
GLVHDVHDQG&29,'SQHXPRQLDDUH
QRZLQFOXGHGDVPHGLFDOO\VLJQLILFDQW
$(VVHH7DEOHE´7KHVHZLOO
FRQWLQXH WREHPRQLWRUHG DVURXWLQH
$(V
5HPRYHGWRHQVXUH
FRQVLVWHQF\DFURVVWKH
YHGROL]XPDE SURJUDP

6HFWLRQ 3UH7UHDWPHQW
(YHQWV DQG$GYHUVH(YHQWV
$WDEOHWLWOHGµ$(6XEW\SHV'HILQHGLQ
7KLV6HFWLRQ¶ZDVDGGHG
7RFRPSO\ZLWK(8
&75SURWRFRO
UHTXLUHPHQWV

6HFWLRQ  $(6,
5HSRUWLQJ
5HYLVHGIRUFRQVLVWHQF\
DFURVVWKHYHGROL]XPDE
SURJUDP

6HFWLRQ )ROORZXSRI
6$(V
x
6XEVHFWLRQ 6SHFLDO
6LWXDWLRQV5HSRUWLQJ
7KHVXEVHFWLRQRQUHSRUWLQJRIVSHFLDO
VLWXDWLRQVZDVDGGHG
7RFRPSO\ZLWK(8
&75SURWRFRO
UHTXLUHPHQWV

6HFWLRQ )ROORZXSRI
6$(V
x
6XEVHFWLRQ 6DIHW\
5HSRUWLQJWR
,QYHVWLJDWRUV,5%VRU
,(&VDQG5HJXODWRU\
$XWKRULWLHV
7KHUHTXLUHPHQWVIRUVXVSHFWHG
XQH[SHFWHGVHULRXVDGYHUVHUHDFWLRQV
UHSRUWLQJZHUHXSGDWHG
7RFRPSO\ZLWK(8
&75SURWRFRO
UHTXLUHPHQWV
CCI
For non-commerc
VHFWLRQRQ
WLRQ
RQVZDV
QVZDV
rc
6DIHW\
6DIHW
V R
V
7KH
7
XQ
-c
ial use onlyly
on
only
e on
se 
l us
ial u
rcia

9HGROL]XPDE,9
6WXG\1R9HGROL]XPDE
3DJH RI
3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
 6HSWHPEHU 
&21),'(17,$/
3URWRFRO$PHQGPHQW
6XPPDU\RI&KDQJHV6LQFHWKH/DVW9HUVLRQRIWKH$SSURYHG3URWRFRO
&KDQJH
1XPEHU
6HFWLRQV$IIHFWHGE\&KDQJH
'HVFULSWLRQRI(DFK&KDQJHDQG5DWLRQDOH
/RFDWLRQ
'HVFULSWLRQ
5DWLRQDOH

6HFWLRQ 6DPSOH
5HWHQWLRQDQG8VH
6HFWLRQ 6XEMHFW
,QIRUPDWLRQ,QIRUPHG
&RQVHQWDQG6XEMHFW
$XWKRUL]DWLRQ
x
6XEVHFWLRQ
,QIRUPHG&RQVHQWIRU8VH
RI5HPDLQLQJVDPSOHV
7KHGHWDLOVDERXWSURFHGXUHVIRU
FROOHFWLRQVWRUDJHDQGIXWXUH XVHRI
ELRORJLFDOVDPSOHVZHUHDGGHG
7RFRPSO\ZLWK(8
&75SURWRFRO
UHTXLUHPHQWV

6HFWLRQ 6WXG\6XPPDU\
6HFWLRQ 6WXG\'HILQLWLRQV
6HFWLRQ 6WDWLVWLFDODQG
$QDO\WLFDO3ODQV
x
6XEVHFWLRQ 6DIHW\
$QDO\VLV
5HYLVHG7($(V GHILQLWLRQ
5HYLVHGIRUFODULW\

6HFWLRQ 2WKHU $QDO\VHV
(QVXUHFRQVLVWHQF\
DFURVVWKHYHGROL]XPDE
SURJUDP

6HFWLRQ ,QWHULP$QDO\VLV
5HYLVHGLQWHULPDQDO\VLV
5HYLVHG WRRIIHUPRUH
IOH[LELOLW\IRULQWHULP
DQDO\VHV

6HFWLRQ 3URWRFRO
'HYLDWLRQV
6HFWLRQ 6XEMHFW
&RQILGHQWLDOLW\
7KHUHSRUWLQJDQGPHDVXUHVDGRSWHGE\
7DNHGDLQWKHHYHQWVRIVHULRXVGDWD
EUHDFKZHUHDGGHG
7RFRPSO\ZLWK(8
&75SURWRFRO
UHTXLUHPHQWV

$SSHQGL[ $ 6FKHGXOHRI
6WXG\ 3URFHGXUHV
7KHZHHNO\VFKHGXOHKDVEHHQH[WHQGHG
IURPZHHNWR
5HYLVHGWRDOLJQZLWK
6HFWLRQ

$SSHQGL[( 6SRQVRU
5HVSRQVLELOLWLHV
6SRQVRUUHVSRQVLELOLWLHVZHUHDGGHG
,WZDVPLVVLQJLQWKH
SUHYLRXVSURWRFRO
DPHQGPHQWVDQGDGGHG
WRSURYLGHFODULW\RQWKH
UHVSRQVLELOLWLHVRIWKH
VSRQVRU

*OREDO
8SGDWHG³OHJDOO\DFFHSWDEOH
UHSUHVHQWDWLYH´WR³OHJDOO\DXWKRUL]HG
UHSUHVHQWDWLYH´WKURXJKRXWWKHSURWRFRO
&RQVLVWHQF\DQG
FODULILFDWLRQWKURXJKRXW
SURWRFRO
CCI
For non-commercial use only
rc
5HYLV
5HY
c
on
RO
RO
or
mer
mme
omm
com

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 10 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
TABLE OF CONTENTS 
1.0 
ADMINISTRATIVE INFORMATION ..............................................................................2 
1.1 
Contacts..........................................................................................................................2 
1.2 
Approval ........................................................................................................................3 
1.3 
Protocol Amendment 8 Summary of Changes...............................................................5 
2.0 
STUDY SUMMARY.........................................................................................................16 
3.0 
STUDY REFERENCE INFORMATION .........................................................................20 
3.1 
Study-Related Responsibilities ....................................................................................20 
3.2 
Coordinating Investigator ............................................................................................20 
3.3 
List of Abbreviations ...................................................................................................21 
3.4 
Corporate Identification ...............................................................................................22 
3.5 
Study Definitions .........................................................................................................23 
4.0 
INTRODUCTION .............................................................................................................25 
4.1 
Background ..................................................................................................................25 
4.1.1 
Epidemiology of Ulcerative Colitis and Crohn’s Disease in the Pediatric 
Population ............................................................................................................25 
4.1.2 
Clinical Manifestations and Prognosis of UC and CD in Pediatric Patients .......26 
4.1.3 
Vedolizumab IV ..................................................................................................27 
4.1.3.1 
Nonclinical ..................................................................................................27 
4.1.3.2 
Clinical ........................................................................................................28 
4.2 
Rationale for the Proposed Study ................................................................................30 
4.3 
Benefit/Risk Assessment .............................................................................................30 
4.4 
Risks Associated With Study Procedures ....................................................................31 
5.0 
STUDY OBJECTIVES AND ENDPOINTS .....................................................................31 
5.1 
Objectives ....................................................................................................................31 
5.1.1 
Primary Objective ................................................................................................31 
5.1.2 
Secondary Objectives ..........................................................................................31 
5.1.3 
Additional Objectives ..........................................................................................32 
5.2 
Endpoints .....................................................................................................................32 
5.2.1 
Primary Endpoint .................................................................................................32 
5.2.2 
Secondary Endpoints ...........................................................................................32 
5.2.3 
Additional Endpoints ...........................................................................................33 
6.0 
STUDY DESIGN AND DESCRIPTION ..........................................................................33 
6.1 
Study Design ................................................................................................................33 
6.2 
Justification for Study Design, Dose, and Endpoints ..................................................38 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 11 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
6.2.1 
Justification for Study Design and Endpoints .....................................................38 
6.2.2 
Dose Justification ................................................................................................38 
6.3 
Premature Termination or Suspension of Study or Investigational Site ......................39 
6.3.1 
Criteria for Premature Termination or Suspension of the Study .........................39 
6.3.2 
Criteria for Premature Termination or Suspension of Investigational Sites ........40 
6.3.3 
Procedures for Premature Termination or Suspension of the Study or the 
Participation of Investigational Site(s) ................................................................40 
7.0 
SELECTION AND DISCONTINUATION/WITHDRAWAL OF SUBJECTS ...............40 
7.1 
Inclusion Criteria .........................................................................................................40 
7.2 
Exclusion Criteria ........................................................................................................41 
7.3 
Excluded Medications, Vaccinations, Procedures, and Treatments ............................42 
7.3.1 
Permitted Medications and Treatments for IBD .................................................43 
7.3.1.1 
Oral Corticosteroid Dosing .........................................................................43 
7.4 
Diet and Fluid Control .................................................................................................43 
7.5 
Criteria for Discontinuation or Withdrawal of a Subject .............................................43 
7.6 
Procedures for Discontinuation or Withdrawal of a Subject .......................................45 
8.0 
CLINICAL TRIAL MATERIAL MANAGEMENT .........................................................45 
8.1 
Study Medication and Materials ..................................................................................45 
8.1.1 
Dosage Form, Manufacturing, Packaging, and Labeling ....................................45 
8.1.1.1 
Vedolizumab IV ..........................................................................................45 
8.1.2 
Storage .................................................................................................................46 
8.1.3 
Dose and Regimen ...............................................................................................46 
8.1.4 
Overdose ..............................................................................................................47 
8.2 
Investigational Drug Assignment and Dispensing Procedures ....................................48 
8.3 
Randomization Code Creation and Storage .................................................................48 
8.4 
Investigational Drug Blind Maintenance .....................................................................48 
8.5 
Unblinding Procedure ..................................................................................................48 
8.6 
Accountability and Destruction of Sponsor-Supplied Drugs.......................................49 
9.0 
STUDY PLAN ...................................................................................................................50 
9.1 
Study Procedures .........................................................................................................50 
9.1.1 
Informed Consent Procedure ...............................................................................50 
9.1.2 
Demographics, Medical History, and Medication History Procedure ................50 
9.1.3 
Physical Examination Procedure .........................................................................51 
9.1.4 
Weight, Height ....................................................................................................51 
9.1.5 
Vital Signs Procedures ........................................................................................51 
9.1.6 
Efficacy Measurements .......................................................................................51 
For non-commercial use only

9HGROL]XPDE,9
6WXG\1R9HGROL]XPDE
3DJH RI
3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
 6HSWHPEHU 
&21),'(17,$/

&RPSOHWLRQDQG5HYLHZRI(QWULHVWR'LDULHV

,03$&7,,,4XHVWLRQQDLUH6XEMHFWVWR<HDUVRI$JH

7DQQHU6WDJH(YDOXDWLRQ

'RFXPHQWDWLRQRI&RQFRPLWDQW0HGLFDWLRQV DQG3URFHGXUHV 



8VHRI/RFDO$QHVWKHWLF 

3URFHGXUHVIRU&OLQLFDO/DERUDWRU\6DPSOHV

)HFDO&DOSURWHFWLQ6DPSOH&ROOHFWLRQ

6WRRO6DPSOHIRU &XOWXUH2YDDQG3DUDVLWH(YDOXDWLRQDQG&GLIILFLOH $VVD\

&RQWUDFHSWLRQDQG3UHJQDQF\$YRLGDQFH3URFHGXUH 

0DOH6XEMHFWVDQG7KHLU)HPDOH3DUWQHUV

)HPDOH6XEMHFWVDQG7KHLU0DOH3DUWQHUV

'HILQLWLRQVDQG3URFHGXUHVIRU&RQWUDFHSWLRQDQG3UHJQDQF\
$YRLGDQFH 

3UHJQDQF\ 



,PPXQRJHQLFLW\6DPSOH&ROOHFWLRQ

'RFXPHQWDWLRQRI6FUHHQ)DLOXUH

'RFXPHQWDWLRQRI6WXG\(QWUDQFH

(QGRVFRSLHV

0RQLWRULQJ6XEMHFW7UHDWPHQW&RPSOLDQFH

6FKHGXOHRI2EVHUYDWLRQVDQG3URFHGXUHV

5DQGRPL]DWLRQ

)LQDO9LVLWRU(7

)LQDO6DIHW\)ROORZXS9LVLW 

/RQJWHUP)ROORZXS6DIHW\6XUYH\

3RVWVWXG\&DUH

8QVFKHGXOHG9LVLWV'XHWR'LVHDVH([DFHUEDWLRQ

2WKHU 8QVFKHGXOHG9LVLWVLI$SSOLFDEOH 

$OWHUQDWLYH$SSURDFKHVWR6WXG\3URFHGXUHVDQG'DWD&ROOHFWLRQ'XHWRD
3DQGHPLF 

35(75($70(17(9(176$1'$'9(56((9(176

'HILQLWLRQV

$(V 

$GGLWLRQDO3RLQWVWR&RQVLGHUIRU$(V

6$(V
CCI
CCI
For non-commercial use only


DFHSWLRQ
SWLR






HFWLRQ
FWLRQ
)DLOXUH
DLOXUH
G\(QWUD
\(QWU


7UHDWPHQ
UHDWP
UYDWLRQV
UYDWLR
RQ
RQ
rci

9HGROL]XPDE,9
6WXG\1R9HGROL]XPDE
3DJH RI
3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
 6HSWHPEHU 
&21),'(17,$/

$(6,V

6HYHULW\RI$(V

&DXVDOLW\RI$(V

5HODWLRQVKLSWR6WXG\3URFHGXUHV

6WDUW'DWH

6WRS'DWH 
 )UHTXHQF\ 
 $FWLRQ&RQFHUQLQJ6WXG\'UXJ
 2XWFRPH 

3URFHGXUHV

&ROOHFWLRQDQG5HSRUWLQJRI$(V 

$(&ROOHFWLRQ3HULRG 

$(5HSRUWLQJ 

$(&ROOHFWLRQ,QYROYLQJ0HGLFDOO\$QWLFLSDWHG&OLQLFDO(YHQWV

$(6, 5HSRUWLQJ

&ROOHFWLRQDQG5HSRUWLQJRI6$(V 

5HSRUWLQJRI$EQRUPDO/)7V

3URGXFW&RPSODLQWV 

)ROORZXSRI6$(V 

6SHFLDO6LWXDWLRQV5HSRUWLQJ 

6DIHW\5HSRUWLQJWR,QYHVWLJDWRUV,5%VRU,(&VDQG5HJXODWRU\$XWKRULWLHV

678'<63(&,),&&200,77((

$GMXGLFDWLRQ&RPPLWWHH

'$7$+$1'/,1*$1'5(&25'.((3,1* 

H&5)V

5HFRUG5HWHQWLRQ 

6DPSOH5HWHQWLRQDQG8VH

67$7,67,&$/0(7+2'6

6WDWLVWLFDODQG$QDO\WLFDO3ODQV

$QDO\VLV6HWV 

$QDO\VLVRI'HPRJUDSKLFVDQG2WKHU%DVHOLQH&KDUDFWHULVWLFV 

6DIHW\$QDO\VLV

(IILFDF\$QDO\VLV



2WKHU$QDO\VHV 
CCI




\$QWLFL
$QWL

 
(V 







5HSRUWLQ
5HSRU
QJWR,QY
JWR,
&200
&200
PL

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 14 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
13.2 
Interim Analysis ...........................................................................................................81 
13.3 
Determination of Sample Size .....................................................................................81 
14.0 
QUALITY CONTROL AND QUALITY ASSURANCE .................................................81 
14.1 
Study-Site Monitoring Visits .......................................................................................81 
14.2 
Protocol Deviations ......................................................................................................82 
14.3 
Quality Assurance Audits and Regulatory Agency Inspections ..................................82 
15.0 
ETHICAL ASPECTS OF THE STUDY ...........................................................................82 
15.1 
IRB and/or IEC Approval ............................................................................................83 
15.2 
Subject Information, Informed Consent, and Subject Authorization ..........................83 
15.2.1 
Informed Consent for Use of Remaining Samples ..............................................85 
15.3 
Subject Confidentiality ................................................................................................85 
15.4 
Publication, Disclosure, and Clinical Trial Registration Policy ..................................85 
15.4.1 
Publication and Disclosure ..................................................................................85 
15.4.2 
Clinical Trial Registration ...................................................................................86 
15.4.3 
Clinical Trial Results Disclosure .........................................................................86 
15.5 
Insurance and Compensation for Injury .......................................................................86 
16.0 
REFERENCES ..................................................................................................................88 
 
LIST OF IN-TEXT TABLES 
Table 8.a 
Dose and Regimen .................................................................................................47 
Table 9.a 
Clinical Laboratory Tests .......................................................................................55 
Table 10.a 
AE Subtypes Defined in This Section ...................................................................65 
Table 10.b 
Takeda Medically Significant AE List ..................................................................69 
 
LIST OF IN-TEXT FIGURES 
Figure 6.a 
Schematic of Vedolizumab-2005 Study Design ....................................................36 
Figure 6.b 
Schematic of Dosing Algorithm for Subjects in High Dose Groups in Open-
label Period ............................................................................................................37 
Figure 6.c 
Schematic of Dosing Algorithm for Subjects in Low Dose Groups in Open-
label Period ............................................................................................................37 
 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 15 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
LIST OF APPENDICES 
Appendix A 
Schedule of Study Procedures ...............................................................................91 
Appendix B 
Responsibilities of the Investigator ........................................................................96 
Appendix C 
Elements of the Subject/Parental Informed Consent/Pediatric Assent ..................98 
Appendix D 
Investigator Consent to Use of Personal Information ..........................................101 
Appendix E 
Sponsor Responsibilities ......................................................................................102 
Appendix F 
PUCAI..................................................................................................................103 
Appendix G 
PCDAI..................................................................................................................104 
Appendix H 
Mayo Scoring System for the Assessment of UC Activity..................................106 
Appendix I 
SES-CD ................................................................................................................107 
Appendix J 
Tanner Scale.........................................................................................................108 
Appendix K 
CDAI Scoring System for the Assessment of CD Activity .................................110 
Appendix L 
Protocol History Appendix ..................................................................................111 
 
For non-commercial use only

9HGROL]XPDE,9
6WXG\1R9HGROL]XPDE
3DJH RI
3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
 6HSWHPEHU 
&21),'(17,$/

678'<6800$5<
1DPHRI6SRQVRUV
7DNHGD'HYHORSPHQW&HQWHU$PHULFDV,QF
&RPSRXQG
9HGROL]XPDE,9
7LWOHRI3URWRFRO $3KDVHE([WHQVLRQ6WXG\WR
'HWHUPLQHWKH/RQJWHUP6DIHW\RI9HGROL]XPDE ,9 LQ
3HGLDWULF6XEMHFWV:LWK8OFHUDWLYH&ROLWLVRU&URKQ¶V
'LVHDVH
,1'1R
(8&71R

6WXG\1XPEHU 9HGROL]XPDE
3KDVH E
6WXG\'HVLJQ
7KLVLVDSKDVHEORQJWHUPH[WHQVLRQVWXG\HQUROOLQJPDOHDQGIHPDOHVXEMHFWVZLWKXOFHUDWLYHFROLWLV8&RU
&URKQ¶VGLVHDVH&'ZKRLQLWLDWHGYHGROL]XPDELQWUDYHQRXV,9WUHDWPHQWLQWKHSKDVH 6WXG\0/1
EHWZHHQWKHDJHVRIDQG\HDUV LQFOXVLYH7RHQWHUWKHH[WHQVLRQVWXG\VXEMHFWVZLOOKDYHFRPSOHWHG
6WXG\0/1DQGDW:HHNDFKLHYHGFOLQLFDOUHVSRQVHDVGHILQHGE\DUHGXFWLRQRISDUWLDO0D\R
VFRUHRISRLQWVDQGIURP%DVHOLQHRUDUHGXFWLRQRIWKH3HGLDWULF8OFHUDWLYH&ROLWLV$FWLYLW\,QGH[
38&$,RISRLQWVIURP%DVHOLQHIRUVXEMHFWVZLWK8&RUDUHGXFWLRQRIWKH&URKQ¶V'LVHDVH$FWLYLW\,QGH[
&'$,DVGHILQHGE\DSRLQWGHFUHDVHIURP%DVHOLQHRUDGHFUHDVHRI3HGLDWULF&URKQ¶V'LVHDVH$FWLYLW\
,QGH[3&'$,RI SRLQWVIRUVXEMHFWVZLWK&'7KHVWXG\ZLOOHYDOXDWHWKHORQJWHUPVDIHW\RIYHGROL]XPDE
DGPLQLVWHUHGE\,9LQIXVLRQ7KHVWXG\ZLOODOVRHYDOXDWHWKHHIIHFWRIORQJWHUPYHGROL]XPDE,9WUHDWPHQWRQ
WKHWLPHWRPDMRULQIODPPDWRU\ERZHOGLVHDVH ,%'UHODWHGHYHQWVKRVSLWDOL]DWLRQVVXUJHULHVRUSURFHGXUHV
KHDOWKUHODWHGTXDOLW\RIOLIHPHDVXUHPHQWVSDWWHUQVRIJURZWKDQGGHYHORSPHQW

$VVHVVPHQWRIHOLJLELOLW\IRU9HGROL]XPDEZLOOEHGHWHUPLQHGDQGLQIRUPHGFRQVHQWSHGLDWULFDVVHQWZLOOEH
REWDLQHGRQRUDIWHU:HHNWKURXJK:HHNRI6WXG\0/1EDVHGRQWKHFOLQLFDOUHVSRQVH
DVVHVVPHQWVGHVFULEHGDERYH7KHUHOHYDQWDVVHVVPHQWVIURPWKH:HHN 9LVLWVRI6WXG\0/1ZLOO
EHXVHGDVWKHEDVHOLQHDVVHVVPHQWVIRUWKLV H[WHQVLRQVWXG\6XEMHFWVHQWHULQJ9HGROL]XPDEZLOOUHPDLQ
EOLQGHGWRWKHLUGRVHDQGZLOOEHDGPLQLVWHUHGYHGROL]XPDE,9RQFHHYHU\ZHHNV4: DWWKHGRVH
DGPLQLVWHUHGDW:HHNLQ6WXG\0/1%OLQGLQJRIERWKVXEMHFWDQGLQYHVWLJDWRUZLOOFRQWLQXH
WKURXJKZHHNRIWKH9HGROL]XPDEVWXG\,IWKHVXEMHFWH[SHULHQFHVGLVHDVHZRUVHQLQJWKH\PD\EH
HOLJLEOHIRUGRVHHVFDODWLRQIRUVXEMHFWVRQWKHORZGRVHRIWKHDSSURSULDWHZHLJKWJURXS,IWKHVXEMHFWLV
UHFHLYLQJWKHKLJKGRVHIRUWKHDSSURSULDWHZHLJKWJURXSWKH\ZLOOQRWEHHOLJLEOHIRUGRVHHVFDODWLRQDQGZLOOEH
GLVFRQWLQXHGIURPWUHDWPHQW
6XEMHFWVZKRH[SHULHQFHGLVHDVHZRUVHQLQJDWDQ\WLPH
GXULQJ9HGROL]XPDEZKLOHUHFHLYLQJWKHORZGRVHPD\EHHVFDODWHGWRWKHKLJKGRVHE\VDWLVI\LQJFULWHULD
IRUGLVHDVHZRUVHQLQJGHILQHGE\HOHYDWLRQVLQWKHLUFOLQLFDODVVHVVPHQWV38&$,IRU8&SDWLHQWVDQG3&'$,IRU
&'SDWLHQWV6XEMHFWGRVLQJZLOOEHXQEOLQGHGDWWKH:HHNYLVLWVRWKDWDOO:HHNYLVLWSURFHGXUHVDUH
FRQGXFWHGLQDGRXEOHEOLQGIDVKLRQIRUDQDO\VLVSXUSRVHV$IWHUFRPSOHWLRQRIWKH0/1VWXG\
VXEMHFWVZKRKDYHWKHLUGRVHLQFUHDVHGEDVHGRQQRQUHVSRQVHVKRXOGEHGRVHGEDVHGRQZHLJKWDWWKHWLPHRI
QRQUHVSRQVHGXULQJWKH9HGROL]XPDEVWXG\
7KH
VWXG\ZLOOLQFOXGHDQZHHNIROORZXSSHULRGILQDOVDIHW\YLVLWDQGDORQJWHUPIROORZXSVDIHW\VXUYH\
PRQWKVDIWHUWKHVXEMHFW¶VODVWGRVHRIVWXG\GUXJIRUDOOVXEMHFWVLQFOXGLQJWKRVHZKRGLVFRQWLQXHWKHVWXG\
CCI
CCI
CCI
For non-commercial use only
OFHUH
QRIWKH&
RIWKH
HRI3HGLD
I3HG
YDOXDWHWK
DOXDWH
HFWRIORQJ
RIORQ
YHQWVKRV
HQWVK
ZWKDQGG
WKDQG
EHGHWHUP
HGHWH
6WXG\0
6WXG\0
VVPHQWVI
PHQW
H[WHQVLRQ
HQVLR
HUHGYHGR
HGY
1


DEV

XEMHFWVRQ
XEMHFWVR
SURSUL
SUR

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 17 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
Primary Objective: To determine the safety profile of long-term vedolizumab IV treatment in pediatric subjects 
with UC or CD. 
Secondary Objectives: 
• 
To evaluate the efficacy of long-term vedolizumab IV in pediatric subjects with UC or CD. 
• 
To determine the effect of long-term vedolizumab IV treatment on time to major IBD-related events 
(hospitalizations, surgeries, and procedures) in pediatric subjects with UC or CD. 
• 
To examine the effect of long-term vedolizumab IV treatment on health-related quality-of- life measurements 
in pediatric subjects with UC or CD. 
• 
To determine the effect of long-term vedolizumab IV treatment on patterns of growth and development in 
pediatric subjects with UC or CD. 
Subject Population: Male and female pediatric subjects with UC or CD who completed Study MLN0002-2003. 
Number of Subjects: Up to 80 rollover subjects from 
Study MLN0002-2003 
Number of Sites: Approximately 72 sites in North 
America, Europe, and the Middle East  
Dose Levels: 
Subjects who weigh ≥30 kg will receive vedolizumab IV 
300 mg (high dose) or 150 mg (low dose) Q8W. 
Subjects who weigh <30 kg will receive vedolizumab IV 
200 mg (high dose) or 100 mg (low dose) Q8W. 
Route of Administration: IV 
Duration of Treatment:  
It is anticipated that the duration of vedolizumab IV 
treatment will vary by subject on the basis of continued 
benefit but will be until vedolizumab IV is commercially 
available for pediatric indication(s) in the subject’s 
country or until other drug access programs become 
available (whichever comes first), the subject turns 18 
years of age and can be transitioned to commercial drug, 
the subject withdraws from the study, or the sponsor 
decides to close the study. 
Period of Evaluation: 
The first dose of vedolizumab IV in this extension 
study will be at the Week 22 Visit of Study 
MLN0002-2003 (or up to 1 week after). 
All subjects will have an 18-week follow-up period 
starting from their last dose of study drug and a 
long-term follow-up safety survey 6 months after 
their last dose of study drug. 
Potential Risks and Benefits  
The study will evaluate long-term safety of vedolizumab IV as maintenance therapy in pediatric subjects with 
moderately to severely active UC or CD who achieved clinical response following vedolizumab IV induction 
therapy. Vedolizumab IV may provide an alternative therapy and address the unmet medical need in pediatric 
patients who do not respond or who lose response to all existing therapies (including conventional therapy or 
TNF-α antagonists), or in whom side effects of these agents are intolerable or life threatening.  
Vedolizumab IV demonstrated clinically relevant efficacy in multiple completed clinical studies in adult subjects 
with moderately to severely active UC or CD. Similar clinical responses were observed in pediatric subjects with 
UC or CD in Study MLN0002-2003, as those seen in adults in previous phase 3 studies of vedolizumab IV 
induction therapy. 
In clinical studies, vedolizumab has shown an acceptable and consistent safety profile in adult subjects (≥18 years 
of age) with body weights ranging from 28.7 to 170 kg. In the pivotal phase 3 studies (C13006 and C13007), the 
most common (≥5% and at a higher incidence than placebo) adverse reactions in subjects administered 
vedolizumab IV were nausea, nasopharyngitis, upper respiratory tract infection, arthralgia, pyrexia, fatigue, 
headache, and cough. Most SAEs have been related to exacerbations or complications of the underlying UC or 
CD. For those infections that were reported more frequently in vedolizumab-treated subjects, the sites of these 
infections correlated with the known tissue distribution of mucosal addressin cell adhesion molecule-1 
(MAdCAM-1) binding sites. No additive risk of infection was identified among subjects who received a 
concomitant immunosuppressant.  
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 18 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
The safety of vedolizumab has been well characterized and the overall safety profile observed in pediatric Study 
MLN0002-2003 was consistent with the profile seen in adult subjects who received vedolizumab IV. Thus, on 
the basis of available clinical and postmarketing data, the benefit-risk profile in pediatric subjects with UC or CD 
is expected to be positive. Further information on vedolizumab is provided in the current edition of the 
Investigator’s Brochure. 
Main Criteria for Inclusion: 
• 
The subject is male or female with UC or CD and was between 2 to 17 years, inclusive, at the time of their 
randomization for Study MLN0002-2003. (Note: A subject remains eligible to participate in this study after 
they reach 18 years of age if they continue to meet the inclusion criteria and do not meet any exclusion 
criteria.) 
• 
The subject completed Study MLN0002-2003 and, at Week 22, achieved clinical response as defined by a 
reduction of partial Mayo score of ≥2 points and ≥25% from Baseline, or a reduction of the PUCAI of ≥20 
points from Baseline for subjects with UC; or a reduction of the CDAI as defined by a ≥70-point decrease 
from Baseline or a decrease of PCDAI of ≥15 points for subjects with CD. 
• 
The subject may be receiving a therapeutic dose of the following drugs: 
– 
Oral 5-aminosalicylic (5-ASA) compounds. 
– 
Oral corticosteroid therapy (prednisone or equivalent steroid at a dose ≤50 mg/day) provided the subject 
was receiving this medication during prior participation in MLN0002-2003. 
– 
Topical (rectal) treatment with 5-ASA or corticosteroids. 
– 
Probiotics (eg, Saccharomyces boulardii). 
– 
Antidiarrheals (eg, loperamide, diphenoxylate with atropine) for control of chronic diarrhea. 
– 
Antibiotics used for treatment of CD (eg, ciprofloxacin, metronidazole). 
– 
Azathioprine (AZA), 6-mercaptopurine (6-MP), or methotrexate (MTX) provided the subject was 
receiving this medication during prior participation in Study MLN0002-2003. 
Main Criteria for Exclusion: 
• 
The subject is female and is lactating or pregnant. 
• 
The subject has hypersensitivity or allergies to vedolizumab or any of its excipients. 
• 
The subject has withdrawn from Study MLN0002-2003. 
• 
The subject has developed any new unstable or uncontrolled cardiovascular, heart failure moderate to severe 
(New York Class Association III or IV), pulmonary, hepatic, renal, gastrointestinal, genitourinary, 
hematological, coagulation, immunological, endocrine/metabolic, neurological, or other medical disorder 
that, in the opinion of the investigator, would confound the study results or compromise subject safety. 
• 
The subject has a positive progressive multifocal leukoencephalopathy (PML) subjective symptom checklist 
prior to the administration of the first dose of study drug. 
• 
The subject currently requires major surgical intervention for UC or CD (eg, bowel resection), or is 
anticipated to require major surgical intervention for UC or CD during the study. 
• 
The subject has other serious comorbidities that will limit their ability to complete the study. 
For non-commercial use only

9HGROL]XPDE,9
6WXG\1R9HGROL]XPDE
3DJH RI
3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
 6HSWHPEHU 
&21),'(17,$/
0DLQ&ULWHULDIRU(YDOXDWLRQDQG$QDO\VHV
7KHSULPDU\HQGSRLQWIRUWKLVVWXG\LVSHUFHQWDJHRIVXEMHFWV ZLWKWUHDWPHQWHPHUJHQWDGYHUVHHYHQWV7($(V
7KHVHFRQGDU\HQGSRLQWVIRUWKLVVWXG\DUH
x
3HUFHQWDJHRI8&VXEMHFWVZKRDW:HHNDFKLHYHDQGPDLQWDLQFOLQLFDOUHVSRQVHEDVHGRQFRPSOHWH0D\R
VFRUHDVGHILQHGE\DFRQWLQXHGUHGXFWLRQLQFRPSOHWH0D\RVFRUHRISRLQWVIURPWKHEDVHOLQHDW
LQLWLDWLRQRI0/1DQGFRQWLQXHGGHFUHDVHLQUHFWDOEOHHGLQJVXEVFRUHRISRLQWIURPEDVHOLQH
RUDEVROXWHUHFWDOEOHHGLQJVXEVFRUHRISRLQWDW:HHN
x
3HUFHQWDJHRI&'VXEMHFWVZKRDW:HHNDFKLHYHDQGPDLQWDLQFOLQLFDOUHVSRQVHDVGHILQHGE\D
UHGXFWLRQLQ6(6&'VFRUHRQHQGRVFRS\FRPSDUHGWRWKHEDVHOLQHHQGRVFRS\DWLQLWLDWLRQRI0/1
DQGFRQWLQXHGUHGXFWLRQLQ&'$,WKDWLVD SRLQWGHFUHDVHIURPWKHEDVHOLQH&'$,VFRUHDWWKH
LQLWLDWLRQRI0/1
x
7LPHWRPDMRU,%'UHODWHGHYHQWVKRVSLWDOL]DWLRQVVXUJHULHVRUSURFHGXUHV
x
&KDQJHVIURP%DVHOLQHLQ,03$&7,,,ZKHUHWUDQVODWLRQVDUHDYDLODEOHWRWDODQGVXEVFDOHVFRUHVDW:HHN
DQGHYHU\ZHHNVWKHUHDIWHU
x
+HLJKWYHORFLW\DW:HHNDQGHYHU\ZHHNVWKHUHDIWHU
x
&KDQJHIURP%DVHOLQHLQKHLJKWZHLJKWDQGERG\PDVVLQGH[%0,DW:HHNDQGHYHU\ZHHNV
WKHUHDIWHU
x
3HUFHQWDJHRIVXEMHFWVDFKLHYLQJ7DQQHUVWDJH9DWRUEHIRUHDJH\HDUVIHPDOHVRU\HDUVPDOHV
6WDWLVWLFDO&RQVLGHUDWLRQV
7UHDWPHQWHPHUJHQW$(V7($(VDUHXQGHVLUDEOHHYHQWVQRWSUHVHQWSULRUWRPHGLFDOWUHDWPHQWRUDQDOUHDG\
SUHVHQWHYHQWWKDWZRUVHQVHLWKHULQLQWHQVLW\RUIUHTXHQF\IROORZLQJWKHWUHDWPHQWRFFXUULQJIURPWKHILUVWGRVH
RIVWXG\GUXJWRWKHGD\RIODVWGRVHRIVWXG\GUXJGD\VDFFRXQWLQJIRUWLPHVWKHKDOIOLIHRI
YHGROL]XPDE 7KHQXPEHUDQGSHUFHQWDJHRIVXEMHFWVZLWK7($(VGHILQHGDVDQ\7($(UHJDUGOHVVRI
UHODWLRQVKLSWRVWXG\GUXJ
$(VOHDGLQJWRGLVFRQWLQXDWLRQDQGVHULRXV$(VWKDWRFFXURQRUDIWHUWKHILUVW
GRVHGDWHDQGXSWRZHHNVDIWHUWKHODVWGRVHGDWHRIWKHVWXG\GUXJZLOOEHVXPPDUL]HGE\0HGLFDO'LFWLRQDU\
IRU5HJXODWRU\$FWLYLWLHVV\VWHPRUJDQFODVVKLJKOHYHOWHUPDQGSUHIHUUHGWHUP7($(VZLOODOVREH
VXPPDUL]HGE\VHYHULW\DQGE\UHODWLRQVKLSWRVWXG\GUXJ6HSDUDWHVXPPDULHVZLOOEHJHQHUDWHGIRUWUHDWPHQW
UHODWHG$(VRYHUDOODQGE\VHYHULW\([SRVXUHDGMXVWHGLQFLGHQFHUDWHVZLOODOVREHDQDO\]HG
7KHSHUFHQWDJHRIVXEMHFWVLQFOLQLFDOUHVSRQVHDW:HHNZLOOEHVXPPDUL]HG
7LPHWRPDMRU,%'UHODWHGHYHQWVKRVSLWDOL]DWLRQVVXUJHULHVDQGSURFHGXUHVZLOOEHDQDO\]HGDQG.DSODQ
0HLHUHVWLPDWHVSUHVHQWHGHYHU\ZHHNV
&KDQJHIURP%DVHOLQHLQ,03$&7,,,WRWDODQGVXEVFDOHVFRUHVKHLJKW
 ZHLJKWDQG%0,ZLOOEH
VXPPDUL]HGGHVFULSWLYHO\+HLJKWYHORFLW\ZLOOEHVXPPDUL]HGE\YLVLW7KHSHUFHQWDJHRIVXEMHFWVDFKLHYLQJ
7DQQHUVWDJH9DWRUEHIRUHDJH\HDUVIHPDOHVRU\HDUVPDOHVZLOOEHVXPPDUL]HG
6DPSOH6L]H-XVWLILFDWLRQ
'XHWRQRK\SRWKHVLVWHVWLQJWKHUHZHUHQRIRUPDOVDPSOHVL]HFDOFXODWLRQVGRQHIRUWKLVVWXG\,WLVHVWLPDWHG
WKDWXSWRVXEMHFWVZLWK8&DQGZLWK&'ZKRKDYHFRPSOHWHG6WXG\0/1ZLOOHQWHUWKLV
VWXG\
CCI
CCI
For non-co
WRGLVFRQ
RGLVF
VWGRVHGD
GRVH
QFODVVK
FODVV
DWLRQVKLS
LRQVKL
ommercial u
QRWSUHVH
QRWSUH
QF\IROORZ
\IROOR
GD\V
GD\
EMHFWVZLWK
HFWVZ
use only
0,DW:HH
DW:HH
DJH\
JH
LW\([SR
LW\([
DO
u
com

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 20 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
3.0 
STUDY REFERENCE INFORMATION 
3.1 
Study-Related Responsibilities 
The study is being funded by Takeda. Payments for the conduct of the study that will be made to 
study sites (and, if applicable, investigators and/or other study staff) will be specified in the 
Clinical Study Site Agreement(s). All investigators and subinvestigators must declare potential 
conflicts of interests to the sponsor. The sponsor will provide a financial disclosure form that 
must be signed by each investigator and subinvestigator before the study starts at their study site; 
in addition, any potential conflicts of interest that are not covered by this financial disclosure 
form should be disclosed separately to the sponsor before the start of the study at their site. All 
institutional affiliations of the investigators and subinvestigators should be declared on their 
curriculum vitae, which must be provided to the sponsor before participating in the study. 
Investigators and subinvestigators will provide the sponsor with sufficient accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests during the course of the study and for 
1 year after completion of the study. 
The sponsor will perform all study-related activities with the exception of those identified in the 
Clinical Study Supplier form. The vendors identified in the form for specific study-related 
activities will perform those activities in full or in partnership with the sponsor. 
3.2 
Coordinating Investigator 
The sponsor will select a Signatory Coordinating Investigator from the investigators who 
participate in the study. Selection criteria for this investigator will include significant knowledge 
of the study protocol, the study drug, their expertise in the therapeutic area and the conduct of 
clinical research as well as study participation. The Signatory Coordinating Investigator will be 
required to review and sign the clinical study report and by doing so agrees that it accurately 
describes the results of the study. 
For non-commercial use only

9HGROL]XPDE,9
6WXG\1R9HGROL]XPDE
3DJH RI
3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
 6HSWHPEHU 
&21),'(17,$/

/LVWRI$EEUHYLDWLRQV
7HUP
'HILQLWLRQ
$6$
DPLQRVDOLF\OLFDFLG
03
PHUFDSWRSXULQH
$(
DGYHUVHHYHQW
$(6,
DGYHUVHHYHQWRIVSHFLDOLQWHUHVW
$/7
DODQLQHDPLQRWUDQVIHUDVH
$67
DVSDUWDWHDPLQRWUDQVIHUDVH
$=$
D]DWKLRSULQH
%0,
ERG\PDVVLQGH[
ESP
EHDWVSHUPLQXWH
&'
&URKQ¶VGLVHDVH
&'$,
&URKQ¶V'LVHDVH$FWLYLW\,QGH[
&GLIILFLOH
&ORVWULGLXPGLIILFLOH
&)5
&RGHRI)HGHUDO5HJXODWLRQV
&//
OLQHDUWRWDOFOHDUDQFH
&09
F\WRPHJDORYLUXV
&29,'
FRURQDYLUXVGLVHDVH
&5)
FDVHUHSRUWIRUP
&75
&OLQLFDO7ULDO5HJXODWLRQ
&WURXJK
VHUXPFRQFHQWUDWLRQDWWKHHQGRIDGRVLQJLQWHUYDO
(&*
HOHFWURFDUGLRJUDP
H&5)
HOHFWURQLFFDVHUHSRUWIRUP
(65
HU\WKURF\WHVHGLPHQWDWLRQUDWH
(7
HDUO\WHUPLQDWLRQ
(8
(XURSHDQ8QLRQ
)$6
IXOODQDO\VLVVHW
)'$
)RRGDQG'UXJ$GPLQLVWUDWLRQ
)6+
IROOLFOHVWLPXODWLQJKRUPRQH
*&3
*RRG&OLQLFDO3UDFWLFH
**7
ȖJOXWDP\OWUDQVIHUDVH
*,
JDVWURLQWHVWLQDOO\
K&*
KXPDQFKRULRQLFJRQDGRWURSLQ
,$&
,QGHSHQGHQW$GMXGLFDWLRQ&RPPLWWHH
,%'
LQIODPPDWRU\ERZHOGLVHDVH
,&+
,QWHUQDWLRQDO&RXQFLOIRU+DUPRQLVDWLRQ RI7HFKQLFDO5HTXLUHPHQWVIRU
3KDUPDFHXWLFDOVIRU+XPDQ8VH
,'
LGHQWLILFDWLRQ
,(&
LQGHSHQGHQWHWKLFVFRPPLWWHH
CCI
CCI
JXODWLRQ
XODWLRQ
WUDWLRQ
WLRQ DW
GLRJUDP
RJUDP
QLFFDVHU
QLFFDVH
\WHW

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 22 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
Term 
Definition 
INR 
international normalized ratio 
IRB 
institutional review board 
IRT 
interactive web response technology 
IV 
intravenous(ly) 
LFT 
liver function test 
MAdCAM-1 
mucosal addressin cell adhesion molecule-1 
MedDRA 
Medical Dictionary for Regulatory Activities 
MLN0002 
Vedolizumab 
MTX 
methotrexate 
NOAEL 
no observed adverse effect level 
NSAID 
nonsteroidal anti-inflammatory drug 
OTC 
over-the-counter 
PCDAI 
Pediatric Crohn’s Disease Activity Index 
PK 
pharmacokinetic(s) 
PML 
progressive multifocal leukoencephalopathy 
PUCAI 
Pediatric Ulcerative Colitis Activity Index 
Q4W 
once every 4 weeks 
Q8W 
once every 8 weeks 
SAE 
serious adverse event 
SES-CD 
simple endoscopic score for Crohn’s disease 
SUSAR 
suspected unexpected serious adverse reaction 
TEAE 
treatment-emergent adverse event 
TNF-α 
tumor necrosis factor-alpha 
TYSABRI 
natalizumab 
UC 
ulcerative colitis 
ULN 
upper limit of normal 
Vedolizumab IV 
also known as ENTYVIO; KYNTELES 
WBC 
white blood cell 
 
3.4 
Corporate Identification 
TDC Americas 
Takeda Development Center Americas, Inc. 
 
 
For non-commercial use only

9HGROL]XPDE,9
6WXG\1R9HGROL]XPDE
3DJH RI
3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
 6HSWHPEHU 
&21),'(17,$/

6WXG\'HILQLWLRQV
7HUP
'HILQLWLRQ
8OFHUDWLYH&ROLWLV8&
6XEMHFWV
&OLQLFDOUHVSRQVHEDVHGRQ
FRPSOHWH0D\RVFRUHRUSDUWLDO
0D\RVFRUH
$UHGXFWLRQLQFRPSOHWH0D\RVFRUHRISRLQWVDQGIURP6WXG\
0/1%DVHOLQHRUDSDUWLDO0D\RVFRUHRISRLQWVDQGIURP
6WXG\0/1%DVHOLQHLIWKHFRPSOHWH0D\RVFRUHZDVQRWSHUIRUPHGDW
WKHYLVLWZLWKDQ DFFRPSDQ\LQJGHFUHDVHLQUHFWDOEOHHGLQJVXEVFRUHRISRLQWRU
DEVROXWHUHFWDOEOHHGLQJVXEVFRUHRISRLQW
&OLQLFDOUHVSRQVHEDVHGRQ
38&$,
$SRLQWGHFUHDVHIURP6WXG\0/1%DVHOLQHLQ3HGLDWULF8OFHUDWLYH
&ROLWLV$FWLYLW\,QGH[38&$, VFRUH
'LVHDVHZRUVHQLQJ
$QLQFUHDVHLQWKH38&$,RI!SRLQWVDWFRQVHFXWLYHYLVLWVDWOHDVWGD\V
DSDUWRUWKH38&$,ZDV! SRLQWVDWDQ\VFKHGXOHGRUXQVFKHGXOHGYLVLW
&URKQ¶V'LVHDVH&'
6XEMHFWV
&OLQLFDOUHVSRQVHEDVHGRQ
&'$,
$SRLQWGHFUHDVHIURP6WXG\0/1%DVHOLQHLQ&URKQ¶V'LVHDVH
$FWLYLW\,QGH[&'$, VFRUH
&OLQLFDOUHVSRQVHEDVHGRQ
3&'$,
$SRLQWGHFUHDVHIURP6WXG\0/1%DVHOLQHLQ3HGLDWULF&URKQ¶V
'LVHDVH$FWLYLW\,QGH[3&'$,VFRUHZLWKWRWDO3&'$,
&OLQLFDOUHVSRQVHEDVHGRQ6(6
&'
$UHGXFWLRQLQVLPSOHHQGRVFRSLFVFRUHIRU&URKQ¶VGLVHDVH6(6&'VFRUH
IURP 6WXG\0/1 %DVHOLQHHQGRVFRS\ RUPHHWVFULWHULDIRU FOLQLFDO
UHPLVVLRQEDVHGRQ6(6&'VFRUHWRZLWKDFFRPSDQ\LQJGHFUHDVHLQDYHUDJH
GDLO\DEGRPLQDOSDLQVFRUH&'$,FRPSRQHQWE\!
'LVHDVHZRUVHQLQJ
$QLQFUHDVHLQWKH3&'$,RI!SRLQWVDW FRQVHFXWLYHYLVLWVDWOHDVWGD\V
DSDUWRUWKH3&'$,ZDV! SRLQWVDWDQ\VFKHGXOHGRUXQVFKHGXOHGYLVLW
7UHDWPHQWHPHUJHQW$(V
7($(V
7($(VDUHXQGHVLUDEOHHYHQWVQRWSUHVHQWSULRUWRPHGLFDOWUHDWPHQWRUDQDOUHDG\
SUHVHQWHYHQWWKDWZRUVHQVHLWKHULQLQWHQVLW\RUIUHTXHQF\IROORZLQJWKHWUHDWPHQW
RFFXUULQJIURPWKHILUVWGRVHRIVWXG\GUXJWRWKHGD\RIODVWGRVHRIVWXG\GUXJ
GD\VDFFRXQWLQJIRUWLPHVWKHKDOIOLIHRIYHGROL]XPDE
$OO6XEMHFWV
&RQWLQXHGGLVHDVHZRUVHQLQJ
DIWHUDGRVHHVFDODWLRQ
1RUHGXFWLRQLQWKHHOHYDWHG3&'$,RU38&$,VFRUHVZKHQQH[WDVVHVVHGDIWHUWKH
LQFUHDVHGGRVHKDVEHHQDGPLQLVWHUHG
6WXG\VWDUW
'HILQHGDVWKHGDWHRIWKHILUVWVXEMHFWVFUHHQHGLQWKLVVWXG\
(QGRIVWXG\
7KHHQGRIVWXG\LVGHILQHGDV ODVWVXEMHFWODVWYLVLWLQFOXVLYHRIWKHZHHNV
SRVW±ODVWGRVHIROORZXSVDIHW\YLVLW
CCI
CCI
CCI
CCI
For non-commercial use only
WVDWFRQ
DWF
DWDQ\VF
DQ\V
P6WXG\0
6WXG\
VFRUH
FRUH
GHFUHDVH
FUHDV
FWLYLW\,Q
LYLW\,
UHGXFWL
UHGXF
P 6WXG\0
6WXG\
HPLVVLRQ
HPLVVLR
DLO\DE
DLO\

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 24 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
Term 
Definition 
Enrollment 
Subject is defined as enrolled when all of the following have occurred: 
• Subject/subject’s legally authorized representative or adult caregiver 
has provided informed consent (that is, in writing, documented via a 
signed and dated informed consent form). 
• Subject has provided assent to participate in the study, as required by 
local regulations. 
• Subject has completed screening, meeting all eligibility criteria. 
• Subject takes part in any study activity after screening. 
 
 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 25 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
4.0 
INTRODUCTION 
4.1 
Background 
4.1.1 
Epidemiology of Ulcerative Colitis and Crohn’s Disease in the Pediatric 
Population 
The overall prevalence of ulcerative colitis (UC) in the adult and pediatric population is 
approximately 200 cases/100,000 persons in the United States and about 
150 cases/100,000 persons in Western Europe (Loftus 2004; Molodecky et al. 2012; Shivananda 
et al. 1996; Trallori et al. 1996). As of 2009, the prevalence rate of UC in the pediatric 
population was 34/100,000 persons, with the lowest prevalence rate being observed in children 
younger than 5 years (Kappelman et al. 2013). Although in recent years the UC incidence has 
increased in the age group of 11 to 15 years, this rate has remained stable in children younger 
than 10 years (da Silva et al. 2014). No significant differences in prevalence by sex have been 
reported for pediatric UC (Kappelman et al. 2013). However, a family history of UC does not 
seem to be a negative prognostic factor in UC patients (da Silva et al. 2014). 
In the United States, the overall prevalence of Crohn’s disease (CD) is approximately 
125 cases/100,000 of the population and 150 cases/100,000 in Western Europe (Loftus 2004; 
Shivananda et al. 1996; Trallori et al. 1996). As of 2009, the prevalence rate of CD in children 
was 58/100,000 persons, with the lowest prevalence rate being observed in children younger than 
5 years. Approximately 20% of all cases of CD occur in the pediatric population younger than 
15 years and a male preponderance is reported in pediatric CD (Kappelman et al. 2013), while a 
female preponderance is seen only among patients diagnosed during adolescence (13 to 19 years) 
(Nieuwenhuis and Escher 2008). 
A large study in the United States demonstrated that UC, CD, and indeterminate colitis 
(otherwise known as inflammatory bowel disease unclassified) were equally prevalent in the 
pediatric population up to 2 years of age and that definitive diagnoses were made in only 1% of 
patients before 1 year of age (Heyman et al. 2005). UC was the most prevalent disease type 
(47%) among those in the 3- to 5-year age group compared with CD (35%). The prevalence of 
indeterminate colitis decreased as children aged. A family history of inflammatory bowel disease 
(IBD) was noted in 3% of siblings, 9% of parents, and 22% of second-degree relatives, with the 
strongest family histories noted in the younger pediatric population and those with UC (44%). 
Although there are fewer studies of childhood IBD compared with adult-onset IBD, the pediatric 
population is unique in that there are fewer environmental confounders, such as smoking or 
contraceptive use, compared with adults. It is therefore possible that genetics and microbiology 
play a stronger role in the development of pediatric IBD. Compared with adult CD, pediatric CD 
appears to be associated with a higher frequency of mutation in the NOD2/CARD15 gene 
(Nieuwenhuis and Escher 2008). 
The incidence of pediatric IBD appears to be increasing. A large study in Finland showed a near 
doubling of the pediatric IBD incidence over a 15-year period (Benchimol et al. 2011; Turunen 
et al. 2006). In 1987, the incidence was 3.9 cases/100,000 of the population and increased to 7.0 
cases/100,000 of the population in 2003. The highest frequency of new-onset cases in the 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 26 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
pediatric population (33%) occurred in patients between ages 12 and 15 years; however, 5% of 
cases occurred in children younger than 3 years. According to the Crohn’s and Colitis 
Foundation of America, approximately 1 million Americans have either UC or CD, of which 
approximately 100,000 are younger than 21 years. 
4.1.2 
Clinical Manifestations and Prognosis of UC and CD in Pediatric Patients 
Although UC and CD are separate illnesses, they share many common signs and symptoms. In 
both the pediatric and adult populations, clinical manifestations include diarrhea, abdominal 
pain, fecal urgency, and incontinence. Fever, weight loss, malaise, and fatigue are indicators of 
more extensive disease. There are a number of extraintestinal manifestations of IBD, including 
arthropathy, primary sclerosing cholangitis, and uveitis. For approximately 25% of IBD patients, 
the onset of disease occurs during childhood or adolescence. The diagnosis of UC or CD is 
usually established histopathologically via endoscopic mucosal biopsies in both adult and 
pediatric populations. 
Disease localization appears to be affected by age. In CD, the most commonly affected sites in 
the pediatric population are the terminal ileum (71% of patients at diagnosis) and right colon 
(71%) (IBD Working Group of the European Society for Paediatric Gastroenterology and 
Nutrition 2005). Upper gastrointestinal (GI) involvement also is commonly seen in pediatric CD, 
although this may be a function of routine upper GI endoscopy with biopsies being routinely 
performed based upon consensus diagnostic recommendations (Kugathasan et al. 2003). In 
pediatric CD, simple inflammatory disease, which is predominant at diagnosis, appears to give 
way to complex stricturing and penetrating behavior over time. 
In UC, the extent of disease at diagnosis is more widespread in the pediatric population 
compared with adults; pancolitis occurs in up to 90% and proctitis in only a minority of patients 
(4% to 13%). Rectal sparing may occur in only 30% of pediatric patients with UC and, therefore, 
unlike adults, sigmoidoscopy alone may not be sufficient to establish the diagnosis in the 
pediatric population (Nieuwenhuis and Escher 2008). 
While the symptoms of UC are similar in both the pediatric and adult populations, pediatric 
patients usually present with more extensive disease. Less is known about the clinical course of 
long-term disease (Higuchi and Bousvaros 2004). Whether the course differs in children, 
adolescents, and adults is unknown at present (Nieuwenhuis and Escher 2008). Antineutrophil 
cytoplasmic antibody and anti-Saccharomyces cerevisiae antibody serologies have been 
associated with a greater risk of developing earlier and more frequent complications in pediatric 
CD (Amre et al. 2006) and may serve as a useful stratification variable in therapeutic trials of 
CD. 
Although growth failure is a common sequela of UC and CD in the pediatric population, 
pediatric patients with CD appear to be at twice the risk of growth failure compared with those 
with UC (Motil et al. 1993). Nutritional therapy and surgical resection have been shown to 
improve growth, but there remains a clear need for more effective and less morbid treatment 
options. As with adults, long-term complications of UC and CD in pediatric patients include 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 27 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
malignancy (eg, colorectal cancer), which may be attributable at least in part to the underlying 
inflammatory disease and also possibly to treatment with systemic immunosuppressants. 
Treatment options for adult and pediatric patients are similar. Pharmacological treatments for 
these diseases include the 5-aminosalicylic acids (5-ASA) and its derivatives, corticosteroids, 
and immunomodulators (thiopurines, such as azathioprine [AZA] and 6-mercaptopurine [6-MP]) 
for both UC and CD, along with methotrexate (MTX) for CD. AZA and 6-MP are often used in 
conjunction with corticosteroids or other therapy to induce remission. AZA and 6-MP show 
efficacy in maintaining remission in pediatric CD (Prefontaine et al. 2009) and also in moderate 
to severe pediatric UC (Kader et al. 1999). MTX has a rapid onset of action and has been shown 
to be effective in induction and maintenance of remission in pediatric patients with CD (Chande 
et al. 2007; El-Matary et al. 2009; Weiss et al. 2009). Over the past decade, tumor necrosis 
factor-alpha (TNF-α) antagonist therapies have been studied and approved for use in the 
pediatric population. Infliximab is approved for use in pediatric patients with moderately to 
severely active UC or CD in the United States and European Union (EU), and adalimumab is 
approved in the United States and EU for moderately to severely active CD (Abbvie 2017).  
4.1.3 
Vedolizumab IV 
Vedolizumab (also known as MLN0002) is a recombinant humanized monoclonal antibody 
composed of 2 light chains of the  subclass and 2 immunoglobulin G1 heavy chains. 
Vedolizumab binds specifically to the human lymphocyte integrin 4β7. The α4β7 integrin 
mediates lymphocyte trafficking to 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 (Briskin et al. 1997; 
Butcher et al. 1999; Erle et al. 1994; Salmi and Jalkanen 2005). As a result, vedolizumab impairs 
the migration of gut-homing leukocytes into GI mucosa (Soler et al. 2009) and acts as a gut-
selective immunomodulator. 
Vedolizumab IV (also known as ENTYVIO; KYNTELES; Vedolizumab for Injection, for 
Intravenous Use; Vedolizumab Powder for Concentrate for Solution for Infusion) has been 
granted marketing approval in more than 70 countries, including the United States and EU, for 
the treatment of adult patients with moderately to severely active UC or CD who have failed 
conventional treatment, including immunomodulators, corticosteroids, or TNF-α antagonists. 
The approved initial dose and administration regimen consists of 300 mg vedolizumab IV 
infused intravenously (IV), over approximately 30 minutes, at Day 1 and Weeks 2, 6, and then 
once every 8 weeks (Q8W) thereafter. 
4.1.3.1 
Nonclinical 
Extensive nonclinical evaluations of the cardiovascular, acute, local tolerance, subchronic, 
chronic, immunologic, and reproductive toxicity in pharmacologically responsive species (New 
Zealand white rabbits and cynomolgus monkeys) have been conducted with vedolizumab. In 
local tolerance studies in rabbits, no evidence of significant adverse local effects was seen 
following administration of vedolizumab IV or vedolizumab SC. No evidence of effects on 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 28 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
electrocardiogram (ECG), heart rate, or mean arterial pressure was seen in cynomolgus monkeys 
at vedolizumab doses up to 100 mg/kg. In addition, there was no evidence of embryo-fetal 
toxicity (gravid rabbits) or prenatal and postnatal toxicity (cynomolgus monkeys), or 
immunotoxicity (cynomolgus monkeys) at these doses. The no-observed-adverse-effect level 
(NOAEL) in both pharmacologically responsive species (monkeys and rabbits) was vedolizumab 
100 mg/kg. This dose was associated with an exposure 26 times (rabbits) and 18 times 
(cynomolgus monkeys) higher than the geometric mean clinical area under the serum 
concentration-time curve after a single dose of vedolizumab 300 mg IV by 30-minute infusion. 
A 13-week toxicity study (20063753) of vedolizumab IV in juvenile cynomolgus monkeys (11 to 
15 months old at study start) supports studies in the pediatric population (down to 2 years of 
age). Monkeys of this species typically are weaned at around 9 months old, making the specified 
ages of the monkeys equivalent to young children, although an exact age correspondence cannot 
be defined. Juvenile monkeys were dosed with the same dose regimen as previously studied in 
adult monkeys (approximately 3 to 7 years old): 0 (vehicle control), 10, 30, or 100 mg/kg 
administered by 30 minute IV infusion once every 2 weeks. There were no test article–related 
clinical observations, or effects on body weights, food consumption, ophthalmology, 
electrocardiology, clinical pathology parameters (hematology, coagulation, clinical chemistry, 
and urinalysis), T-cell–dependent antibody response, flow cytometry analyses (peripheral blood 
and cerebrospinal fluid), macroscopic and microscopic findings, and organ weights. Thus,  
100 mg/kg was considered to be the NOAEL in this study.  
4.1.3.2 
Clinical 
Single- and multiple-dose pharmacokinetics (PK) of vedolizumab IV have been studied in 
healthy adult subjects and in subjects with moderately to severely active UC or CD. Similar 
vedolizumab PK was observed in healthy subjects and subjects with UC or CD. Following IV 
infusion, vedolizumab serum concentrations generally fell in a biexponential fashion until 
approximately 1 to 10 µg/mL, with a 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 IV is approximately 5 L. 
Vedolizumab IV has demonstrated clinically relevant efficacy in multiple completed clinical 
studies in adult subjects with moderately to severely active UC or CD. 
In subjects with moderately to severely active UC (C13006; GEMINI I), vedolizumab IV 
300 mg administered as an IV infusion at Day 1 and Week 2 (induction) followed by either Q8W 
or once every 4 weeks (Q4W) administration from Week 6 through Week 52 (maintenance) 
induced a statistically significant increase in rates of clinical response at Week 6 and clinical 
remission at Week 52 (primary endpoint for the induction phase and maintenance phase, 
respectively) compared with placebo (Feagan et al. 2013). The study also met important 
secondary endpoints, including clinical remission at Week 6, durable clinical response, durable 
clinical remission, and mucosal healing at Weeks 6 and 52, and corticosteroid-free clinical 
remission at Week 52. Given the significant morbidity associated with chronic corticosteroid 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 29 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
treatment, the corticosteroid-sparing effects of vedolizumab provide an important benefit to 
patients with UC. 
In subjects with moderately to severely active CD (C13007; GEMINI II), vedolizumab IV 
300 mg administered as an IV infusion at Day 1 and Week 2 (induction) followed by either Q4W 
or Q8W administration from Week 6 through Week 52 (maintenance) demonstrated statistically 
significant differences in efficacy compared with placebo for both the induction phase and 
maintenance phase (Sandborn et al. 2013). The study met its first primary endpoint for the 
induction phase, clinical remission at Week 6 but did not meet the second primary endpoint of 
enhanced clinical response (CDAI-100) at Week 6 in the overall population, although the 
treatment difference favored vedolizumab. The study met its primary endpoint for the 
maintenance phase (clinical remission at Week 52), as well as important secondary endpoints, 
including enhanced clinical response at Week 52 and corticosteroid-free clinical remission at 
Week 52. 
In C13011 (GEMINI III), vedolizumab (300 mg IV at Day 1 and Weeks 2 and 6) was 
administered as induction therapy to subjects with moderately or severely active CD who had 
failed conventional therapies, including TNF-α antagonists. The primary endpoint of clinical 
remission at Week 6 in the TNF-α antagonist failure intention-to-treat population was not met; 
however, a treatment difference was observed at Week 10 in this population (Sands et al. 2014). 
Similar treatment differences favoring vedolizumab were also demonstrated for the overall 
population and in the subgroup of subjects who were TNF-α antagonist naïve. 
In the pivotal phase 3 studies (Studies C13006, C13007, and C13011), the most common (≥5% 
and at a higher incidence than placebo) adverse reactions in subjects administered vedolizumab 
IV were nausea, nasopharyngitis, upper respiratory tract infection, arthralgia, pyrexia, fatigue, 
headache, and cough. Most serious adverse events (SAEs) were related to exacerbations or 
complications of the underlying UC or CD. Overall, the safety data from long-term treatment 
with vedolizumab IV Q4W or Q8W in Study C13008 for up to approximately 8 years was 
consistent with the known safety profile of vedolizumab. For those infections that were reported 
more frequently in vedolizumab-treated subjects, the sites of these infections correlate with the 
known tissue distribution of MAdCAM-1 binding sites. Anal abscess, abdominal abscess, and 
gastroenteritis were the most frequently reported serious infections. Extraintestinal infections 
(bronchitis, pneumonia, urinary tract infection, sepsis) occurred at low frequency (<1%). 
Concomitant use of corticosteroids and/or conventional immunomodulators did not appear to be 
associated with any increased rate of infections based on the comparative rates of infections in 
the phase 3 clinical studies among subjects. Results from the clinical program to date do not 
suggest an increased risk of malignancy with vedolizumab IV treatment.  
Completed phase 2 pediatric vedolizumab IV Study MLN0002-2003 evaluated treatment with 
vedolizumab IV through Week 14. Treatment with 150 and 300 mg IV doses (≥30 kg weight 
group) and 100 and 200 mg IV doses (<30 kg cohort) in pediatric subjects with either UC or CD 
resulted in similar clinical responses in children compared with those seen in adults in previous 
phase 3 studies of vedolizumab induction therapy. The overall safety profile observed in 
pediatric Study MLN0002-2003 was consistent with the profile seen in adult subjects who 
For non-commercial use only

9HGROL]XPDE,9
6WXG\1R9HGROL]XPDE
3DJH RI
3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
 6HSWHPEHU 
&21),'(17,$/
UHFHLYHGYHGROL]XPDE,97KHPRVWFRPPRQ DGYHUVHHYHQWV$(VLQVXEMHFWVNJZHUH
KHDGDFKHDQGZRUVHQLQJ8&RU&'7KHPRVWFRPPRQ$(VLQVXEMHFWVNJZHUHDEGRPLQDO
SDLQDQDHPLDDQGZRUVHQLQJ&'6$(VLQERWKZHLJKWJURXSVZHUHSUHGRPLQDQWO\ZRUVHQLQJ
8&RU&'7KHUHZHUHQRQHZVDIHW\ VLJQDOVLGHQWLILHGIURPWKHVWXG\9HGROL]XPDEZDV
JHQHUDOO\VDIHZKHQDGPLQLVWHUHGHLWKHUDVDQGPJLQVXEMHFWVNJRUDVPJDQG
PJLQVXEMHFWVNJZLWKDFRPSDUDEOHVDIHW\SURILOHLQERWKZHLJKWJURXSV
9HGROL]XPDEKDVEHHQPDUNHWHGIRUPRUHWKDQ\HDUVDQGLVDSSURYHGLQPRUHWKDQ 
FRXQWULHV7KHVDIHW\RIYHGROL]XPDEKDVEHHQZHOOFKDUDFWHUL]HG
7KHPRVWFRPPRQO\UHSRUWHG$(VRWKHUWKDQRIIODEHOXVHDQGSURGXFWXVHLVVXHVZHUH
H[DFHUEDWLRQVFRPSOLFDWLRQVUHODWHGWRXQGHUO\LQJ&'DQG8&7KHVDIHW\SURILOHLQWKHSHGLDWULF
SRSXODWLRQZDVFRQVLVWHQWZLWKWKDWREVHUYHGLQWKHDGXOWSRSXODWLRQ
2YHUDOOYHGROL]XPDEKDVEHHQZHOOWROHUDWHGLQFOLQLFDOVWXGLHVDQGSRVWPDUNHWLQJH[SHULHQFH
7KHEHQHILWULVNSURILOHFRQWLQXHVWREHSRVLWLYH

5DWLRQDOHIRUWKH3URSRVHG6WXG\
7KLVH[WHQVLRQVWXG\LVLQWHQGHGWRFKDUDFWHUL]HWKHORQJWHUPVDIHW\SURILOHRIYHGROL]XPDE,9
WUHDWPHQWLQSHGLDWULFVXEMHFWVZLWK8&RU&'ZKRLQLWLDWHGWUHDWPHQWDJHGWR\HDUVDWWKH
WLPHRIUDQGRPL]DWLRQLQ6WXG\ 0/1
DQGWKH
FRUUHODWLRQRIWKHH[SRVXUHWRWKHGUXJZLWKWKHFOLQLFDOUHVSRQVH7RHQWHUWKHH[WHQVLRQVWXG\
VXEMHFWVZLOOKDYHFRPSOHWHG6WXG\0/1DQGDW:HHNDFKLHYHGFOLQLFDOUHVSRQVH
DVGHILQHGE\DUHGXFWLRQRISDUWLDO0D\RVFRUHRISRLQWVDQGIURP%DVHOLQHRUD
UHGXFWLRQRIWKH38&$,RISRLQWVIURP%DVHOLQHIRUVXEMHFWVZLWK8&RUDUHGXFWLRQRIWKH
&'$,DVGHILQHGE\DSRLQWGHFUHDVHIURP%DVHOLQHRUDGHFUHDVHRI3&'$,RISRLQWV
IRUVXEMHFWVZLWK&' (VWDEOLVKLQJWKHORQJWHUPVDIHW\DQGWROHUDELOLW\RIYHGROL]XPDE,9
WUHDWPHQWLQSHGLDWULFVXEMHFWVZLWK8&DQG&'LVHVVHQWLDOWRXQGHUVWDQGLQJWKHEHQHILWULVN
SURILOHLQWKLVSRSXODWLRQ'DWDUHJDUGLQJWKH PDLQWHQDQFHRIFOLQLFDOUHVSRQVHORQJWHUPDQGWKH
RFFXUUHQFHRILPSRUWDQWFOLQLFDOHYHQWVUHVXOWLQJIURPFKURQLFYHGROL]XPDE,9DGPLQLVWUDWLRQLQ
SHGLDWULF VXEMHFWVZLOOEHREWDLQHGIURPWKLVH[WHQVLRQVWXG\

%HQHILW5LVN$VVHVVPHQW
7KHUHUHPDLQVDQXQPHWPHGLFDOQHHGLQSHGLDWULFSDWLHQWVZKRIDLOWRUHVSRQGRUZKRORVH
UHVSRQVHWRDOOH[LVWLQJWKHUDSLHVLQFOXGLQJFRQYHQWLRQDOWKHUDS\RU71)ĮDQWDJRQLVWVRULQ
ZKRPVLGHHIIHFWVRIWKHVHDJHQWVDUHLQWROHUDEOHRUOLIHWKUHDWHQLQJ9HGROL]XPDE,9PD\
SURYLGHDQDOWHUQDWLYHWKHUDS\IRUWKLVSDWLHQWSRSXODWLRQ
9HGROL]XPDE,9GHPRQVWUDWHGFOLQLFDOO\UHOHYDQWHIILFDF\ LQPXOWLSOHFRPSOHWHGFOLQLFDOVWXGLHV
LQDGXOWVXEMHFWVZLWKPRGHUDWHO\WRVHYHUHO\DFWLYH8&RU&',Q6WXG\0/1VLPLODU
FOLQLFDOUHVSRQVHVZHUHREVHUYHGLQSHGLDWULFVXEMHFWVZLWK8& RU&'DVFRPSDUHGZLWKWKRVH
VHHQLQDGXOWVLQSUHYLRXVSKDVHVWXGLHVRIYHGROL]XPDE,9LQGXFWLRQWKHUDS\
CCI
For non-comm
KWKHFOL
WKHF
/1
1
0D\RVFR
D\RV
RLQWVIUR
LQWVIU
erc

cial use only
QJ
QJWHUP
WHUP
RLQLWLDWH
LQLWLDW
QWGHFUHD
WGHFU
LVKLQJW
LVKLQJ
ZL
erci
me
CCI

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 31 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
In clinical studies, vedolizumab has shown an acceptable and consistent safety profile in adult 
subjects (≥18 years of age) with body weights ranging from 28.7 to 170 kg. In the pivotal 
phase 3 studies (C13006 and C13007), the most common (≥5% and at a higher incidence than 
placebo) adverse reactions in subjects administered vedolizumab IV were nausea, 
nasopharyngitis, upper respiratory tract infection, arthralgia, pyrexia, fatigue, headache, and 
cough. Most SAEs have been related to exacerbations or complications of the underlying UC or 
CD. For those infections that were reported more frequently in vedolizumab-treated subjects, the 
sites of these infections correlated with the known tissue distribution of MAdCAM-1 binding 
sites. No additive risk of infection was identified among subjects who received a concomitant 
immunosuppressant.  
The safety of vedolizumab has been well characterized and the overall safety profile observed in 
pediatric Study MLN0002-2003 was consistent with the profile seen in adult subjects who 
received vedolizumab IV. Thus, on the basis of available clinical and postmarketing data, the 
benefit-risk profile in pediatric subjects with UC or CD is expected to be positive. Further 
information on vedolizumab is provided in the current edition of the Investigator’s Brochure. 
4.4 
Risks Associated With Study Procedures 
Subjects may experience discomfort and risks from some study procedures. These include: 
• Risks associated with infusion such as infusion site reactions. 
• Risks associated with endoscopy such as bleeding, abdominal pain or bloating, 
perforation. 
• Risks associated with general anesthetic during endoscopy such as nausea and vomiting, 
drowsiness, or confusion. 
Subjects will be monitored carefully for these risks. The principal investigator and medical team 
can implement mitigations to decrease the risk of these events and will also be prepared to treat 
any issues as needed. 
5.0 
STUDY OBJECTIVES AND ENDPOINTS 
5.1 
Objectives 
5.1.1 
Primary Objective 
• To determine the safety profile of long-term vedolizumab IV treatment in pediatric subjects 
with UC or CD. 
5.1.2 
Secondary Objectives 
• To evaluate the efficacy of long-term vedolizumab IV in pediatric subjects with UC or CD. 
• To determine the effect of long-term vedolizumab IV treatment on time to major IBD-related 
events (hospitalizations, surgeries, and procedures) in pediatric subjects with UC or CD. 
For non-commercial use only

9HGROL]XPDE,9
6WXG\1R9HGROL]XPDE
3DJH RI
3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
 6HSWHPEHU 
&21),'(17,$/
x
7RH[DPLQHWKHHIIHFWRIORQJWHUPYHGROL]XPDE,9WUHDWPHQWRQKHDOWKUHODWHGTXDOLW\RI
OLIHPHDVXUHPHQWV LQSHGLDWULFVXEMHFWV ZLWK8&RU&'
x
7RGHWHUPLQHWKHHIIHFWRIORQJWHUPYHGROL]XPDE ,9 WUHDWPHQWRQSDWWHUQVRIJURZWKDQG
GHYHORSPHQWLQSHGLDWULFVXEMHFWVZLWK8&RU&'

$GGLWLRQDO2EMHFWLYHV

(QGSRLQWV

3ULPDU\(QGSRLQW
x
3HUFHQWDJHRIVXEMHFWV ZLWKWUHDWPHQWHPHUJHQWDGYHUVHHYHQWV7($(V

6HFRQGDU\(QGSRLQWV
x
3HUFHQWDJHRI8&VXEMHFWVZKRDW:HHNDFKLHYHDQGPDLQWDLQFOLQLFDOUHVSRQVHEDVHGRQ
FRPSOHWH0D\RVFRUHDVGHILQHGE\DFRQWLQXHGUHGXFWLRQLQFRPSOHWH0D\RVFRUHRI
SRLQWVIURPWKHEDVHOLQHDWLQLWLDWLRQRI0/1DQGFRQWLQXHGGHFUHDVHLQUHFWDO
EOHHGLQJVXEVFRUHRISRLQWIURPEDVHOLQHRUDEVROXWHUHFWDOEOHHGLQJVXEVFRUHRISRLQW
DW:HHN
x
3HUFHQWDJHRI&'VXEMHFWVZKRDW:HHNDFKLHYHDQGPDLQWDLQFOLQLFDOUHVSRQVHDV
GHILQHGE\DUHGXFWLRQLQ6(6&'VFRUHRQHQGRVFRS\FRPSDUHGWRWKHEDVHOLQH
HQGRVFRS\DWLQLWLDWLRQRI0/1DQGFRQWLQXHGUHGXFWLRQLQ&'$,WKDWLVD
SRLQWGHFUHDVHIURPWKHEDVHOLQH&'$,VFRUHDWWKHLQLWLDWLRQRI0/1
x
7LPHWRPDMRU,%'UHODWHGHYHQWVKRVSLWDOL]DWLRQVVXUJHULHVRUSURFHGXUHV
x
&KDQJHVIURP%DVHOLQHLQ ,03$&7,,,ZKHUHWUDQVODWLRQVDUHDYDLODEOHWRWDODQGVXEVFDOH
VFRUHV DW:HHNDQGHYHU\ZHHNVWKHUHDIWHU
x
+HLJKWYHORFLW\DW:HHNDQGHYHU\ZHHNVWKHUHDIWHU
x
&KDQJHIURP%DVHOLQHLQKHLJKWZHLJKWDQGERG\PDVVLQGH[%0,DW:HHN DQGHYHU\
 ZHHNVWKHUHDIWHU
x
3HUFHQWDJHRIVXEMHFWVDFKLHYLQJ7DQQHUVWDJH9DWRUEHIRUHDJH\HDUVIHPDOHVRU
\HDUVPDOHV
CCI
CC
For non-commercial use only
DGYHUVH
DGYHUVH
HNDF
N
\DFRQWLQ
DFRQ
DWLRQRI0
LRQRI
IURPED
IURPE
WVZKR
WVZK

9HGROL]XPDE,9
6WXG\1R9HGROL]XPDE
3DJH RI
3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
 6HSWHPEHU 
&21),'(17,$/

$GGLWLRQDO (QGSRLQWV

678'<'(6,*1$1''(6&5,37,21

6WXG\'HVLJQ
6WXG\9HGROL]XPDELVDSKDVHEH[WHQVLRQVWXG\WRGHWHUPLQHWKHORQJWHUPVDIHW\RI
YHGROL]XPDE ,9 LQSHGLDWULFVXEMHFWVZLWK8&RU&'ZKRLQLWLDWHGYHGROL]XPDEWUHDWPHQWDWWR
\HDUVRIDJHLQFOXVLYHLQ6WXG\0/1DSKDVHGRVHUDQJLQJVWXG\8SWR
 SHGLDWULFVXEMHFWVZKRFRPSOHWHG6WXG\0/1DQGDW:HHNDFKLHYHGFOLQLFDO
UHVSRQVHDVGHILQHGE\DUHGXFWLRQRISDUWLDO0D\RVFRUHRISRLQWVDQGIURP%DVHOLQH
RUDUHGXFWLRQRIWKH38&$,RISRLQWVIURP%DVHOLQHIRUVXEMHFWVZLWK8&RUDUHGXFWLRQRI
CCI
CC
For non-commercial use onlyly
on
se 
al us
cial
merc
mme
n-co
non
For 
F

9HGROL]XPDE,9
6WXG\1R9HGROL]XPDE
3DJH RI
3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
 6HSWHPEHU 
&21),'(17,$/
WKH&'$,DVGHILQHGE\DSRLQWGHFUHDVHIURP%DVHOLQHRUDGHFUHDVHRI3&'$,RI
SRLQWVIRUVXEMHFWVZLWK&' ZLOOEHHQUROOHGLQWKHVWXG\7KHVWXG\ZLOODOVRHYDOXDWHWKHHIIHFW
RIORQJWHUPYHGROL]XPDE,9WUHDWPHQWRQWKHWLPHWRPDMRU,%'UHODWHGHYHQWV
KRVSLWDOL]DWLRQVVXUJHULHVRUSURFHGXUHVKHDOWKUHODWHGTXDOLW\RIOLIHPHDVXUHPHQWVSDWWHUQV
RIJURZWKDQGGHYHORSPHQW
6XEMHFWVDQGLQYHVWLJDWRUVZLOO
UHPDLQEOLQGHGWRWKHGRVHEHLQJDGPLQLVWHUHGWKURXJK:HHNRIWKHVWXG\,IWKHVXEMHFW
H[SHULHQFHVGLVHDVHZRUVHQLQJWKH\PD\EHHOLJLEOHIRUGRVHHVFDODWLRQIRUVXEMHFWVRQWKH
ORZGRVHRIWKHDSSURSULDWHZHLJKWJURXS,IWKHVXEMHFWLVUHFHLYLQJWKHKLJKGRVHIRUWKH
DSSURSULDWHZHLJKWJURXSWKH\ZLOOQRWEHHOLJLEOHIRUGRVHHVFDODWLRQDQGZLOOEHGLVFRQWLQXHG
IURPWUHDWPHQW
$W:HHN
WKHEOLQGZLOOEHOLIWHG$VFKHPDWLFRIWKHVWXG\GHVLJQLVVKRZQLQ)LJXUH D
$VVHVVPHQWRIHOLJLELOLW\IRU9HGROL]XPDEZLOOEHGHWHUPLQHGDQGLQIRUPHG
FRQVHQWSHGLDWULFDVVHQWIRUSDUWLFLSDWLRQLQ6WXG\9HGROL]XPDEZLOOEHREWDLQHGRQRUDIWHU
:HHNWKURXJK:HHNRI6WXG\0/1EDVHGRQWKHDVVHVVPHQWVRIFOLQLFDO
UHVSRQVHGHVFULEHGDERYH6XEMHFWVLQ0/1UDQGRPL]HGWRWKHORZGRVHJURXSZKR
KDYHQRW\HWVDWLVILHGWKHFULWHULDIRUFOLQLFDOUHVSRQVHDW:HHNZLOOXQGHUJRDEOLQGHGGRVH
HVFDODWLRQWRWKHKLJKGRVHJURXSDQGEHUHHYDOXDWHGIRUFOLQLFDOUHVSRQVHDW:HHNDQG
HOLJLELOLW\WRHQWHU9HGROL]XPDE7KHUHOHYDQWFOLQLFDODVVHVVPHQWVIURPWKH:HHN 9LVLWV
RI6WXG\0/1ZLOOEHXVHGDVWKH EDVHOLQHDVVHVVPHQWVIRU9HGROL]XPDE7KH
PDMRULW\RIDVVHVVPHQWVLQWKHH[WHQVLRQVWXG\ZLOOEHSHUIRUPHGDWZHHNLQWHUYDOVRUDW
XQVFKHGXOHGYLVLWVZKHQDSSURSULDWH
6DIHW\
DVVHVVPHQWV
ZLOOEHFRQGXFWHGDVOLVWHGLQWKH
6FKHGXOHRI6WXG\3URFHGXUHVLQ$SSHQGL[ $,WLVDQWLFLSDWHGWKDWWKHGXUDWLRQRIYHGROL]XPDE
,9WUHDWPHQWZLOOYDU\E\VXEMHFWRQWKHEDVLVRIFRQWLQXHGEHQHILWEXWZLOOEHXQWLOYHGROL]XPDE
,9LVFRPPHUFLDOO\DYDLODEOHIRUSHGLDWULFLQGLFDWLRQVLQWKHVXEMHFW¶VFRXQWU\RUXQWLORWKHU
GUXJDFFHVVSURJUDPVEHFRPHDYDLODEOHZKLFKHYHUFRPHVILUVWWKHVXEMHFWWXUQV\HDUVRI
DJHDQGFDQEHWUDQVLWLRQHGWRFRPPHUFLDOGUXJWKHVXEMHFWZLWKGUDZVIURPWKHVWXG\RUWKH
VSRQVRUGHFLGHVWRFORVHWKHVWXG\7KHVXEMHFWVZLOODWWHQGD)LQDO6DIHW\9LVLWZHHNVDIWHU
WKHODVWGRVHRIYHGROL]XPDELQ6WXG\9HGROL]XPDE7KHHQGRIVWXG\ZLOOEHZKHQWKHODVW
VXEMHFWFRPSOHWHVWKHLUILQDOVDIHW\YLVLWZHHNVDIWHUWKHLUODVWWUHDWPHQWLQ6WXG\
9HGROL]XPDE'XULQJWKHVDIHW\IROORZXSSHULRGLIVXEMHFWVWUDQVLWLRQWRYHGROL]XPDE
RWKHUWKDQVWXG\GUXJVDIHW\GDWDZLOOEHFROOHFWHGXQWLOWKHZHHNVDIHW\IROORZXSYLVLWHJ
ZHHNVDIWHUWKHODVWGRVHRIVWXG\GUXJ$GGLWLRQDOO\VXEMHFWVZLOOEHUHTXLUHGWRSDUWLFLSDWH
LQDORQJWHUPIROORZXSVDIHW\VXUYH\E\WHOHSKRQHPRQWKVDIWHUWKHLUODVWGRVHRI
YHGROL]XPDEVWXG\GUXJ
6XEMHFWVZLOOUHFHLYHWKHLUILUVWGRVHRIYHGROL]XPDE,9LQWKLVVWXG\RQ'D\ZLWKLQZHHNRI
WKH0/1:HHN DVVHVVPHQWV$WVWXG\HQWU\VXEMHFWVZLOOEHDGPLQLVWHUHGWKH
VDPHEOLQGHGGRVHRIYHGROL]XPDE,9WKDWZDVUHFHLYHGDW:HHNLQ6WXG\0/1
DQGZLOOWKHQFRQWLQXHWRUHFHLYHYHGROL]XPDE,9DWDIUHTXHQF\RI4:7KHGRVLQJDOJRULWKPV
IRUWKHKLJK GRVHDQGORZGRVHJURXSVDUHVXPPDUL]HGLQ )LJXUH E DQG)LJXUH FUHVSHFWLYHO\
CCI
CCI
CCI
CCI
For non-commercial use only

WKHDVV
KHDV
PL]HGWR
L]HG
:HHN
:HHN
IRUFOLQLF
IRUFOLQ
WFOLQLFDO
FOLQLF
HOLQHDV
OLQHD
\ZLOOEH
ZLOOE
$SSHQGL
SSHQG
HFWRQWKH
WRQW
IRUSHG
IRUSH
DYD
D
mm
com
n-c

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 35 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
Subjects receiving the low dose (150 or 100 mg) of vedolizumab IV may be escalated to the high 
dose (300 or 200 mg) at any time during Vedolizumab-2005 if the subject demonstrates disease 
worsening by PUCAI/PCDAI (Section 3.5) at 2 consecutive visits (scheduled or unscheduled) 
(Figure 6.c). For UC subjects, disease worsening is defined as an increase in the PUCAI of 
>20 points at 2 consecutive visits at least 7 days apart, or the PUCAI was >35 points at any 
scheduled or unscheduled visit. For CD subjects, disease worsening is defined as an increase in 
the PCDAI of >15 points at 2 consecutive visits at least 7 days apart, or the PCDAI was 
>30 points at any scheduled or unscheduled visit. 
No further dose escalation will be permitted beyond the high dose per weight category (300 or 
200 mg) Q8W. Subjects who experience continued disease worsening during the extension study 
despite being administered the high dose of vedolizumab Q8W (300 or 200 mg) will be 
discontinued from the study. Continued disease worsening after a dose escalation is defined as 
no reduction in the elevated PCDAI or PUCAI scores when next assessed after the increased 
dose has been administered. After completion of the MLN0002-2003 study, subjects who have 
entered the Vedolizumab-2005 study and who qualify for a dose increase because of disease 
worsening will have their dose increased to the maximum allowable dose in the cohort 
determined by their weight at the time of non-response during the Vedolozumab-2005 study. 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 36 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
Figure 6.a 
Schematic of Vedolizumab-2005 Study Design 
 
(a) Study Vedolizumab-2005 will begin after the Week 22 Visit for Study MLN0002-2003 (or up to 1 week after). 
Subjects who consent to participate in the extension study (Vedolizumab-2005) may continue blinded study dosing 
after MLN0002-2003 Week 22 End-of-Study Visit procedures have been completed. 
(b) Subjects will continue blinded study dosing through Week 32 of Study Vedolizumab-2005. If the subject 
experiences disease worsening, they may be eligible for dose escalation for subjects on the low-dose of the 
appropriate weight group. If the subject is receiving the high dose for the appropriate weight group they will not be 
eligible for dose escalation and will be discontinued from treatment. The dose will be unblinded at Week 40. 
(c) If a subject demonstrates disease worsening by PUCAI/PCDAI (Section 3.5) at 2 consecutive visits (scheduled or 
unscheduled) they may be eligible for dose escalation. This information will be entered into IRT. Subjects eligible 
for a dose escalation will be dosed based on their weight at the time of nonresponse in Study Vedolizumab-2005. 
Subjects who were on the high dose for their current weight group will not be eligible for a dose escalation and will 
be discontinued from treatment. Subjects who show continued disease worsening despite dose escalation will be 
discontinued from the study. Continued disease worsening after a dose escalation is defined as no reduction in the 
elevated PCDAI or PUCAI scores when next assessed after the increased dose has been administered. 
(d) Duration of vedolizumab IV treatment will vary by subject on the basis of continued benefit but will be until 
vedolizumab IV is commercially available for pediatric indication(s) in the subject’s country or until other drug 
access programs become available (whichever comes first), the subject turns 18 years of age and can be transitioned 
to commercial drug, the subject withdraws from the study, or the sponsor decides to close the study. 
(e) Subjects will complete a Final Safety Visit 18 weeks after their last dose of study drug and participate in a long-
term follow-up safety survey by telephone 6 months after the last dose of study drug. 
 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 37 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
Figure 6.b 
Schematic of Dosing Algorithm for Subjects in High Dose Groups in Open-
label Period 
 
(a) Definition of disease worsening: For UC, an increase in the PUCAI of >20 points at 2 consecutive visits at least 7 days apart, 
or the PUCAI was >35 points at any scheduled or unscheduled visit. For CD, an increase in the PCDAI of >15 points at 2 
consecutive visits at least 7 days apart, or the PCDAI was >30 points at any scheduled or unscheduled visit. 
(b) Subjects who have their dose increased based on nonresponse should be dosed based on weight at the time of nonresponse. If 
subjects' weight has remained <30 kg at time of nonresponse, discontinue treatment. If subjects' weight has increased to ≥30 kg at 
time of nonresponse, increase dose to 300 mg Q8W. 
 
Figure 6.c 
Schematic of Dosing Algorithm for Subjects in Low Dose Groups in Open-
label Period 
 
(a) Definition of disease worsening: For UC, an increase in the PUCAI of >20 points at 2 consecutive visits at least 7 days apart, 
or the PUCAI was >35 points at any scheduled or unscheduled visit. For CD, an increase in the PCDAI of >15 points at 2 
consecutive visits at least 7 days apart, or the PCDAI was >30 points at any scheduled or unscheduled visit. 
(b) Continued disease worsening after a dose escalation is defined as no reduction in the elevated PCDAI or PUCAI scores 8 
weeks after the increased dose has been administered. 
(c) Subjects who have their dose increased based on nonresponse should be dosed based on weight at the time of nonresponse. If 
subjects' weight has remained <30 kg at time of nonresponse, dose will increase to 200 mg Q8W. If subjects' weight has 
increased to ≥30 kg at time of nonresponse, dose will increase to 300 mg Q8W. 
 
Weight 
Group
Current Dose
Dose Escalation Due to 
Disease Worsening (a)
≥30 kg
<30 kg
150 mg Q8W
100 mg Q8W
300 mg Q8W
200 mg Q8W
Continued Disease 
Worsening (a) (b)
Discontinue treatment
See footnote (c)
For non-commercial use only

9HGROL]XPDE,9
6WXG\1R9HGROL]XPDE
3DJH RI
3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
 6HSWHPEHU 
&21),'(17,$/

-XVWLILFDWLRQIRU6WXG\'HVLJQ'RVHDQG(QGSRLQWV

-XVWLILFDWLRQIRU6WXG\'HVLJQDQG(QGSRLQWV
7KLVVWXG\LVLQWHQGHGWRJDWKHUGDWDRQWKHORQJWHUPVDIHW\RIYHGROL]XPDE,9WUHDWPHQWLQ
HOLJLEOHSHGLDWULFVXEMHFWVZKRKDYHFRPSOHWHG6WXG\0/1,QWKLVH[WHQVLRQVWXG\RI
PDLQWHQDQFHWKHUDS\IRUVXEMHFWVZKRKDYHUHVSRQGHGWRLQGXFWLRQWKHUDS\VXEMHFWVZLOOUHFHLYH
WKHLUILUVWGRVHRIVWXG\GUXJZLWKLQZHHNRI WKH0/1:HHN DVVHVVPHQWV,WLV
DQWLFLSDWHGWKDWWKHGXUDWLRQRIYHGROL]XPDE,9WUHDWPHQWZLOOYDU\E\VXEMHFWRQWKHEDVLVRI
FRQWLQXHGEHQHILWEXWZLOOEHXQWLOYHGROL]XPDE,9LVFRPPHUFLDOO\DYDLODEOHIRUSHGLDWULF
LQGLFDWLRQVLQWKHVXEMHFW¶VFRXQWU\RUXQWLORWKHUGUXJDFFHVVSURJUDPVEHFRPHDYDLODEOH
ZKLFKHYHUFRPHVILUVWWKHVXEMHFWWXUQV\HDUVRIDJHDQGFDQEHWUDQVLWLRQHGWRFRPPHUFLDO
GUXJWKHVXEMHFWZLWKGUDZVIURPWKHVWXG\RUWKHVSRQVRUGHFLGHVWRFORVHWKHVWXG\
6DIHW\HYDOXDWLRQVZLOOEHEDVHGRQWKHLQFLGHQFHVHYHULW\DQGW\SHRI7($(VLQFOXGLQJ
FOLQLFDOO\VLJQLILFDQWFKDQJHVRUDEQRUPDOLWLHVLQWKHVXEMHFW¶VSK\VLFDOH[DPLQDWLRQV

7KHVWXG\ZLOODOVRHYDOXDWHWKHHIIHFWRIORQJWHUPYHGROL]XPDEWUHDWPHQWRQWKHWLPHWRPDMRU
,%'UHODWHGHYHQWVKRVSLWDOL]DWLRQVVXUJHULHVRUSURFHGXUHVKHDOWKUHODWHGTXDOLW\RIOLIH
PHDVXUHPHQWVDQGSDWWHUQVRIJURZWKDQGGHYHORSPHQWWRFKDUDFWHUL]HWKHEHQHILWULVNSURILOHLQ
SHGLDWULFVXEMHFWV

'RVH-XVWLILFDWLRQ
7KHDSSURYHGLQLWLDOGRVHDQGDGPLQLVWUDWLRQUHJLPHQRIYHGROL]XPDE,9LQDGXOWVXEMHFWVLV
 PJDGPLQLVWHUHGDW'D\DQG:HHNVDQG4:WKHUHDIWHU7KHGRVHUHJLPHQIRU
SHGLDWULFVXEMHFWVLQWKLVH[WHQVLRQVWXG\LVRUPJIRUVXEMHFWVZKRZHLJKNJRU
RUPJIRUVXEMHFWVZKRZHLJKNJYHGROL]XPDE,94:
CCI
CCI
For non-commercial use only
\SH
\SH
SK\VLFD
K\VLF
QJWHUP
WHUP
JHULHVR
HULHV
KDQGGHY
DQGG
or n
Fo
F
e on
use
al us
cial

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 39 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
Vedolizumab PK and exposure-response have not yet been established in pediatric subjects. 
Ctrough values at steady state for vedolizumab doses of 300, 200, 150, and 100 mg administered 
Q8W or Q4W were simulated using a population PK model developed from data from phase 3 
studies in adult subjects with UC or CD. Population-PK analyses suggest that while body weight 
is a predictor of linear total clearance (CLL) and volume of the central compartment, the 
magnitude of the effect is not considered to be clinically relevant. Population-PK analyses 
suggest that CLL of vedolizumab is not affected by subject age. Body weights in the adult pivotal 
phase 3 studies ranged from 28.7 to 170 kg; therefore, body weights ≥30 kg were represented in 
the adult population. No clinically meaningful differences in safety were observed in adult 
subjects across quartiles of body weights. 
The vedolizumab IV Q8W dosing regimen selected for the long-term extension study is intended 
to maintain clinical response at the lowest possible exposure. The doses and dosing regimen 
selected provide estimated Ctrough values in pediatric subjects that are between the 5th and 95th 
percentiles of Ctrough values observed in adults administered vedolizumab IV 300 mg at Weeks 0, 
2, 6 and Q8W or Q4W in phase 3 studies. 
Subjects receiving the low dose (150 or 100 mg) of vedolizumab IV may be escalated to the high 
dose (300 or 200 mg) if the subject demonstrates disease worsening by PUCAI/PCDAI 
(Section 3.5) at 2 consecutive visits (scheduled or unscheduled). No further dose escalation will 
be permitted over 300 or 200 mg Q8W. Subjects who experience continued disease worsening 
during the extension study despite being administered vedolizumab 300 or 200 mg Q8W will be 
discontinued from the study. Continued disease worsening after a dose escalation is defined as 
no reduction in the elevated PCDAI or PUCAI scores when next assessed after the increased 
dose has been administered. 
Results from a 13-week juvenile monkey toxicity study also showed that vedolizumab was safe 
and well tolerated at doses up to 100 mg/kg, which was the highest dose tested. Taken together, 
the nonclinical data in a 13-week toxicity study in juvenile cynomolgus monkeys and the long-
term safety data available in adult subjects administered vedolizumab IV support long-term 
treatment of pediatric subjects with UC or CD, who continue to benefit from the therapy. 
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 drug that 
indicates a change in the known risk/benefit profile for the product, such that the risk /benefit 
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. 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 40 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
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. 
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. 
In the event that this study is terminated and a subject who has benefited from treatment is not 
able to obtain vedolizumab commercially, the sponsor would seek to take steps to allow 
continued access to the drug via an extended access or similar program. 
7.0 
SELECTION AND DISCONTINUATION/WITHDRAWAL OF SUBJECTS 
All entry criteria, including test results, need to be confirmed prior to first dose. 
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, parent, or legal guardian is capable of 
understanding and complying with protocol requirements. 
2. The subject and/or the parent or legal guardian gives voluntary informed consent/assent and 
signs and dates a written, informed consent /assent form and any required privacy 
authorization prior to the initiation of any study procedures. 
3. The subject is male or female with UC or CD and was 2 to 17 years of age, inclusive, at the 
time of randomization for Study MLN0002-2003. (Note: A subject remains eligible to 
participate in this study after they reach 18 years of age if they continue to meet the inclusion 
criteria and do not meet any exclusion criteria.) 
4. The subject completed Study MLN0002-2003 and, at Week 22, achieved clinical response as 
defined by a reduction of partial Mayo score of ≥2 points and ≥25% from Baseline, or a 
reduction of the PUCAI of ≥20 points from baseline for subjects with UC; or a reduction of 
the CDAI as defined by a ≥70-point decrease from Baseline or a decrease of PCDAI of ≥15 
points for subjects with CD. 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 41 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
5. The subject may be receiving a therapeutic dose of the following drugs: 
a) Oral 5-ASA compounds. 
b) Oral corticosteroid therapy (prednisone or equivalent steroid at a dose ≤50 mg/day) 
provided the subject was receiving this medication during prior participation in 
MLN0002-2003. 
c) Topical (rectal) treatment with 5-ASA or corticosteroids. 
d) Probiotics (eg, Saccharomyces boulardii). 
e) Antidiarrheals (eg, loperamide, diphenoxylate with atropine) for control of chronic 
diarrhea. 
f) Antibiotics used for the treatment of CD (ie, ciprofloxacin, metronidazole). 
g) AZA or 6-MP or MTX, provided the subject was receiving this medication during prior 
participation in MLN0002-2003. 
6. A male subject who is sexually active with a female partner of childbearing potential* agrees 
to use adequate contraception* from signing of informed consent/assent throughout the 
duration of the study and for 18 weeks after last dose or agree to completely abstain from 
heterosexual intercourse. 
7. 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/assent throughout the duration of the study and for 18 weeks after last dose or agree 
to completely abstain from heterosexual intercourse. 
* Definitions and highly effective methods of contraception are defined in 
Section 9.1.15 and reporting responsibilities are defined in Section 9.1.16. 
8. The subject met inclusion criterion #10 in the MLN0002-2003 protocol (the subject’s 
vaccinations are up to date) prior to enrollment. 
7.2 
Exclusion Criteria 
Any subject who meets any of the following criteria will not qualify for entry into the study: 
1. The subject is female and is lactating or pregnant. 
2. The subject has hypersensitivity or allergies to vedolizumab or any of its excipients. 
3. The subject has withdrawn from Study MLN0002-2003. 
4. The subject has developed any new unstable or uncontrolled cardiovascular, heart failure 
moderate to severe (New York Class Association III or IV), pulmonary, hepatic, renal, GI, 
genitourinary, hematological, coagulation, immunological, endocrine/metabolic, 
neurological, or other medical disorder that, in the opinion of the investigator, would 
confound the study results or compromise subject safety. 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 42 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
5. The subject has a positive PML subjective symptom checklist prior to the administration of 
the first dose of study drug. 
6. The subject currently requires major surgical intervention for UC or CD (eg, bowel 
resection), or is anticipated to require major surgical intervention for UC or CD during the 
study. 
7. The subject has any history of malignancy, except for the following: (a) adequately treated 
nonmetastatic basal cell skin cancer; (b) squamous cell skin cancer that has been adequately 
treated and that has not recurred for at least 1 year prior to enrollment; and (c) history of 
cervical carcinoma in situ that has been adequately treated and that has not recurred for at 
least 3 years prior to first dose of study drug. Subjects with remote history of malignancy 
(eg, >10 years since completion of curative therapy without recurrence) will be considered 
based on the nature of the malignancy and the therapy received, and inclusion must be 
discussed with the sponsor on a case-by-case basis prior to first dose of study drug.  
8. The subject has other serious comorbidities that will limit his or her ability to complete the 
study. 
9. The subject has active psychiatric problems that, in the investigator’s opinion, may interfere 
with compliance with the study procedures. This includes affective disorders that may 
confound the interpretation of subject reporting of gastrointestinal symptoms (eg, abdominal 
pain) in the opinion of the investigator. 
10. The subject has history of lupus. 
11. The subject is unable to comply with all study assessments. 
12. 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 conduct of this study (eg, spouse, 
parent, child, sibling) or may consent under duress. 
7.3 
Excluded Medications, Vaccinations, Procedures, and Treatments 
The following medications are excluded from use during the study: 
• Any treatment for UC or CD other than those listed in Section 7.3.1 (either approved or 
investigational). 
• All live vaccines 30 days prior to first dose of study drug in Study MLN0002-2003 and for at 
least 6 months after the last dose of study drug in Study Vedolizumab-2005. 
• Either approved or investigational biological agents for the treatment of non-IBD conditions, 
other than localized injections (eg, intraocular injections for wet macular degeneration). 
• Chronic nonsteroidal anti-inflammatory drug (NSAID) use defined as daily use for >2 
consecutive weeks (note: occasional use of NSAIDs and acetaminophen for headache, 
arthritis, myalgias, menstrual cramps are permitted). 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 43 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
Subjects must be instructed not to take any medications including over-the-counter (OTC) 
products, without first consulting with the investigator. 
Subjects who do not respond to treatment or show worsening of their disease after entering the 
safety follow-up period will no longer need to abstain from the medications that were prohibited 
during the screening and treatment periods. High dose glucocorticoids and other treatments will 
be allowed. Biologics or nonbiologic immunosuppressants should not be initiated during the 
safety follow-up period without prior discussion with the sponsor study physician or designee 
due to the long half-life of vedolizumab. 
7.3.1 
Permitted Medications and Treatments for IBD 
The following medications and treatments are permitted during the study: 
• Immunomodulators (such as MTX, AZA, 6-MP as described in inclusion criterion 5.g). 
• Oral 5-ASAs, probiotics, enteral nutrition, or antibiotics. 
• Antidiarrheals for control of chronic diarrhea. 
• Topical (rectal) treatment with 5-ASAs or corticosteroids. 
• These treatments may be initiated at the discretion of the investigator during the long-term 
maintenance therapy with vedolizumab. 
7.3.1.1 
Oral Corticosteroid Dosing 
Newly initiated corticosteroids are prohibited. If a subject was receiving corticosteroids during 
their participation in MLN0002-2003, the maximum dose of oral corticosteroids for the 
treatment of UC or CD that may be coadministered with vedolizumab IV as a long-term regimen 
is ≤50 mg/day of prednisone (or equivalent steroid). Initiation of tapering of the corticosteroid 
dose during the Vedolizumab-2005 study is at the discretion of the investigator and should 
follow a schedule of a reduction of 5 mg each week down to a daily dose of 10 mg/day. 
Thereafter, the dose may be reduced by 2.5 mg each week until the subject has been weaned off 
corticosteroids (consult with the medical monitor for support, if needed). 
7.4 
Diet and Fluid Control  
There are no diet or fluid restrictions and subjects do not need to fast prior to study drug 
infusions or blood draws. 
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 drug 
should be recorded in the electronic case report form (eCRF) using the following categories. 
1. AE. The subject has experienced an AE that requires early termination (ET) because 
continued participation imposes an unacceptable risk to the subject’s health or the subject is 
unwilling to continue because of the AE. 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 44 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
• Liver function test (LFT) abnormalities. 
Study drug 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 9.1.12), if the following circumstances occur at any 
time during study drug treatment: 
– Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >8 times the 
upper limit of normal (ULN), or 
– ALT or AST >5×ULN and persists for more than 2 weeks, or 
– ALT or AST >3×ULN in conjunction with elevated total bilirubin >2×ULN or 
international normalized ratio (INR) >1.5, or 
– ALT or AST >3×ULN with appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash and/or eosinophilia (>5%). 
• Leukopenia or lymphopenia: White blood cell (WBC) and lymphocyte counts will be 
monitored for all subjects. AZA, 6-MP, or MTX, if applicable, should be discontinued 
and the dose of vedolizumab held for an absolute lymphocyte count <1.0×109/L at any 
point in the study. The absolute lymphocyte count must be repeated at appropriate 
intervals as determined by the investigator. The next dose of vedolizumab can be 
administered only if the absolute lymphocyte count is ≥1.0×109/L. If the absolute 
lymphocyte count remains <1.0×109/L, study drug should be discontinued and the subject 
withdrawn from the study. 
2. PML. Subjects with confirmed PML, as adjudicated by the PML Independent Adjudication 
Committee (IAC), will be withdrawn from the study. 
3. Any serious infection that meets the following criteria: 
a) Life threatening as defined in Section 10.1.3. 
b) Requires  intensive care unit admission. 
c) Systemic opportunistic infection including tuberculosis (including pulmonary), 
cytomegalovirus (CMV) (including CMV colitis), and listeriosis. 
4. Significant protocol deviation. The discovery after the first dose of study drug 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. 
5. 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 in the subject’s 
source documents. 
6. Voluntary withdrawal. The subject (or subject’s legally authorized representative) wishes to 
withdraw from the study. The reason for withdrawal, if provided, should be recorded in the 
eCRF. 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 45 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
Note: All attempts should be made to determine the underlying reason for the withdrawal 
and, where possible, the primary underlying reason should be recorded (eg, withdrawal due 
to an AE). 
7. Study termination. The sponsor, IRB, IEC, or regulatory agency terminates the study. 
8. 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 9.1.16. 
9. Death. 
10. 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 or if the 
investigator determines that discontinuation of the study drug is in the subject’s best interest. In 
addition, a subject or their parent/legal guardian 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 Final Visit/ET, the Final Safety Follow-up 
Visit and the 6-month long-term follow-up safety survey. Discontinued or withdrawn subjects 
will not be replaced. 
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 IV 
The sponsor will supply the study sites with the following study drug: vedolizumab IV 
300 mg/vial, for single use in a 20 mL vial. The study drug 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. The sponsor will only provide the study drug 
(vedolizumab). Sites will provide all other materials for infusion. 
Each carton will have a single-panel or multilingual booklet label that will contain, but will not 
be limited to the following: sponsor’s name and address, protocol number, packaging job/lot 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 46 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
number, name and strength of the product, medication identification number, subject 
information, caution statement, directions for use, and storage conditions. 
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 
(protected from light). 
Vedolizumab IV must be stored at 2ºC to 8ºC (36ºF to 46ºF) at the site. A daily temperature log 
of the drug storage area at the site must be maintained. For details regarding study drug storage, 
handling, and disposal please refer to the pharmacy manual. 
8.1.3 
Dose and Regimen 
Subjects will receive their first dose of study drug in this study on Day 1 (up to 1 week after the 
MLN0002-2003 Week 22 Visit). Subjects will continue to receive vedolizumab IV at the same 
dose administered at Week 14 in Study MLN0002-2003, which will be administered at a 
frequency of Q8W.  
Subjects receiving the low dose (150 or 100 mg) vedolizumab IV who demonstrate disease 
worsening by PUCAI/PCDAI (Section 3.5) at 2 consecutive visits (scheduled or unscheduled) 
may dose escalate to high dose (300 or 200 mg) vedolizumab IV Q8W (Section 6.2.2). No 
further dose escalation will be permitted beyond the high dose per weight category (300 or 200 
mg) Q8W. Subjects who experience continued disease worsening during the extension study 
despite being administered high dose vedolizumab Q8W will be discontinued from the study. 
Continued disease worsening after a dose escalation is defined as no reduction in the elevated 
PCDAI or PUCAI scores when next assessed after the increased dose has been administered. 
The predefined algorithm for determination of dose and dose frequency is summarized in 
Table 8.a. After completion of the MLN0002-2003 study, subjects who have their dose increased 
based on nonresponse should be dosed based on weight at the time of nonresponse. 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 47 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
Table 8.a 
Dose and Regimen 
Weight Category (a) 
Vedolizumab Dose at Week 14 
in Study MLN0002-2003 
Extension 
Study (Day 1) 
Disease Worsening (b)(c) 
≥30 kg 
300 mg (high dose) 
300 mg Q8W 
Discontinue from study 
150 mg (low dose) 
150 mg Q8W 
Escalate to 300 mg Q8W 
Discontinue from study for continued disease 
worsening 
<30 kg 
 
 
200 mg (high dose) 
200 mg Q8W 
See footnote (d) 
100 mg (low dose) 
100 mg Q8W 
See footnote (e) 
Discontinue from study for continued disease 
worsening 
(a) After completion of the MLN0002-2003 study, subjects who have their dose increased based on nonresponse 
should be dosed based on weight at the time of nonresponse.  
(b) For UC, disease worsening is defined as an increase in the PUCAI of >20 points at 2 consecutive visits at least 
7 days apart, or the PUCAI was >35 points at any scheduled or unscheduled visit. For CD, it is defined as an 
increase in the PCDAI of >15 points at 2 consecutive visits at least 7 days apart, or the PCDAI was >30 points at 
any scheduled or unscheduled visit. 
(c) Continued disease worsening after a dose escalation is defined as no reduction in the elevated PCDAI or 
PUCAI scores when next assessed after the increased dose has been administered. 
(d) If subjects' weight has remained <30 kg at time of nonresponse, discontinue treatment. If subjects' weight has 
increased to ≥30 kg at time of nonresponse, increase dose to 300 mg Q8W.  
(e) If subjects' weight has remained <30 kg at time of nonresponse, increase dose to 200 mg Q8W. If subjects' 
weight has increased to ≥30 kg at time of nonresponse, increase dose to 300 mg Q8W. 
 
The infusion will be administered intravenously over approximately 30 minutes for all subjects 
weighing ≥20 kg (longer infusion times up to 60 minutes may be used). For subjects weighing 
<20 kg, the infusion will be administered over approximately 2 hours. Instructions for 
reconstitution and administration will be provided in the pharmacy manual. Subjects should be 
observed for 1 hour after each infusion. 
Duration of vedolizumab IV treatment will vary by subject on the basis of continued benefit but 
will be until vedolizumab IV is commercially available for pediatric indication(s) in the subject’s 
country or until other drug access programs become available (whichever comes first), the 
subject turns 18 years of age and can be transitioned to commercial drug, the subject withdraws 
from the study, or the sponsor decides to close the study. 
8.1.4 
Overdose 
An overdose is defined as a known deliberate or accidental administration of investigational 
drug, to a study subject, at a dose above that which is assigned to that individual subject 
according to the study protocol. 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 48 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
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. 
Cases of overdose without manifested signs or symptoms are not considered AEs. AEs 
associated with an overdose will be documented 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 
Subjects will receive treatment according to the appropriate regimen as described in  
Section 8.1.3.  
The subject number assigned at Screening in Study MLN0002-2003 will be used in this study. 
The investigator or investigator’s designee will access the interactive web response technology 
(IRT) system and provide the necessary subject-identifying information. The medication 
identification (ID) number of the investigational drug to be dispensed will then be provided by 
the IRT. If sponsor-supplied drug is lost or damaged, the site can request a replacement from 
IRT. Refer to the IRT manual provided separately. At subsequent drug-dispensing visits, the 
investigator or designee will again contact the IRT to request additional investigational drug for a 
subject, and the medication ID number of the investigational drug to be dispensed will be 
provided by the IRT. 
8.3 
Randomization Code Creation and Storage 
Treatment assignment is not randomized in this study. However, subjects will retain the subject 
number assigned in Study MLN0002-2003.  
8.4 
Investigational Drug Blind Maintenance 
The study drug blind will be maintained using the IRT. 
The blind will be removed at the Week-40 study visit. 
8.5 
Unblinding Procedure 
The investigational drug blind may be broken by the investigator if information concerning the 
investigational drug is essential for the medical treatment of the subject. The medical monitor 
must be informed of the unblinding at the earliest possible opportunity. In nonurgent cases, the 
medical monitor must be contacted before the subject is unblinded. 
For unblinding a subject, the investigational drug blind can be obtained by the investigator, by 
accessing the IRT. 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 49 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
The sponsor must be notified as soon as possible if the investigational drug blind is broken. The 
date, time, and reason the blind is broken must be recorded in the source documents, and the 
same information (except the time) must be recorded on the eCRF. 
8.6 
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 or destroyed at the site. The site will maintain source documents in addition to entering 
data into the IRT. 
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, 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 in the IRT. 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 medication ID 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. 
The IRT will include all required information as a separate entry for each subject to whom 
sponsor-supplied drug is dispensed. 
The investigator or designee must record the current inventory of all sponsor-supplied drugs in 
the IRT. The following information will be recorded at a minimum: protocol number and title, 
name of investigator, site identifier and number, description of sponsor-supplied drugs, date and 
amount dispensed, and the initials, seal, or signature of the person dispensing the drug. 
Prior to site closure or at appropriate intervals, a representative from the sponsor or its designee 
will perform sponsor-supplied drug accountability and reconciliation before sponsor-supplied 
drugs are returned to the sponsor or its designee for destruction or destroyed at the site. 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 50 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
Accountability for clinical trial material being destroyed at the site must be documented using a 
Study Accountability Tracking Document or equivalent document. In addition, a Certificate of 
Destruction document must be provided by the sites that can identify or allow traceability to the 
batches, and/or medication ID numbers involved, and actual quantities destroyed. 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. 
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/pediatric assent are described in Section 15.2. 
Assessment of eligibility for Vedolizumab-2005 will be determined and informed 
consent/pediatric assent will be obtained on or after Week 14 through Week 22 of Study 
MLN0002-2003. 
Informed consent/pediatric assent must be obtained prior to the subject entering into this study, 
and before any protocol-directed procedures are performed. The unique subject identification 
number (subject number) assigned to each subject in Study MLN0002-2003 will be used 
throughout this extension study. 
Subjects reaching an age that is not covered by their pediatric assent must provide consent for 
their appropriate age group to remain in the study. Subjects who reach the age of consent must 
provide consent with a signed informed consent form to remain in the study. 
9.1.2 
Demographics, Medical History, and Medication History Procedure 
Subject demographic information will be obtained from Study MLN0002-2003 (depending on 
local regulations) and will include sex, Hispanic ethnicity, race as described by the subject or 
parent/guardian, and smoking status at Screening. Date of birth or age will be collected for 
Vedolizumab-2005. 
Race and ethnicity data will be collected in this study to understand how similar the 
enrolled population is to the population with UC or CD at large and to enable researchers 
understand if the efficacy and/or safety of vedolizumab IV could be different for people of 
different races or ethnicities. 
Medical history and medication history (including prior biologic medication history information) 
will be obtained from Study MLN0002-2003. 
For Vedolizumab-2005, medical history refers to any significant conditions or diseases relevant 
to the disease under study that stopped at or prior to signing of informed consent/assent for the 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 51 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
Vedolizumab-2005, and will include ongoing and resolved AEs from Study MLN0002-2003. 
Ongoing AEs from Study MLN0002-2003 which change in severity will be reported as new AEs 
in this study (Section 10.2.1). Where possible, all prior medications for the treatment of UC or 
CD, including date of diagnosis, with the reason for discontinuation, will be imported from the 
Study MLN0002-2003 data. Some medications for the treatment of UC or CD, other than the 
study drug vedolizumab, which started and stopped during Study MLN0002-2003 will need to be 
manually entered into the eCRF at the first visit. 
9.1.3 
Physical Examination Procedure 
The 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. 
Physical examinations should be conducted prior to dosing, if applicable. 
All physical examinations should assess clinically significant changes from the assessment prior 
to first dose examination in Study MLN0002-2003. A clinically significant finding will be 
recorded as an AE if it starts after the first dose of study drug in this study. 
9.1.4 
Weight, Height 
A subject should have weight and height measured while wearing indoor clothing and without 
shoes, socks, or hats. The Takeda standard for collecting weight is kilograms (kg) with 1 decimal 
place. Height should be recorded to the nearest tenth of a centimeter (if possible). Height may be 
measured using a wall-mounted stadiometer using replicated measurements (average of 
3 measurements). 
9.1.5 
Vital Signs Procedures 
Vital signs will include body temperature, respiratory rate, blood pressure, and pulse (beats per 
minute). On dosing days, vitals are taken predose. Vital signs should be measured prior to any 
venesection/cannulation procedures. 
9.1.6 
Efficacy Measurements 
9.1.6.1 
Completion and Review of Entries to Diaries 
After consenting/assenting, subjects and parents/legal guardians will be re-instructed on the 
completion of diary entries during the study. 
A minimum of 3 days (UC) or 5 days (CD) of completed daily diary data prior to the Day 1 visit 
is required for disease activity index calculation. During the rest of the study, 7 days (UC) or 10 
days (CD) of completed daily diary data prior to each scheduled visit per the Schedule of Study 
Procedures (Appendix A) is required for disease activity index calculation. For unscheduled 
visits due to flares, the subject should start filling out daily diary sheets when the flare begins (if 
possible) and then come in for the unscheduled visit for evaluation. A flare is confirmed by 
observing the subject during a one-week interval (to confirm that it is ongoing) and during that 
For non-commercial use only

9HGROL]XPDE,9
6WXG\1R9HGROL]XPDE
3DJH RI
3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
 6HSWHPEHU 
&21),'(17,$/
ZHHNWKHGLDULHVFDQFRQWLQXHWREHILOOHGRXWWRPDNHVXUHWKHVXEMHFWKDVGD\VRIV\PSWRP
GLDULHVLIWKH\KDYH8&DQGGD\VRIV\PSWRPGLDULHVLIWKH\KDYH&'
'LDU\HQWULHVZLOOEHUHYLHZHGE\VLWHSHUVRQQHODW'D\SULRUWRGRVLQJLIDSSOLFDEOHDQGDW
WKHYLVLWVVSHFLILHGLQWKH6FKHGXOHRI6WXG\3URFHGXUHV$SSHQGL[ $DQGDWDQ\XQVFKHGXOHG
YLVLWVGXHWRGLVHDVHH[DFHUEDWLRQ
(QWULHVVKRXOGEHUHYLHZHGDQGPRQLWRUHGE\WKHVWXG\VWDIIZKLOHWKHVXEMHFWSDUHQWRUOHJDO
JXDUGLDQLVLQWKHFOLQLFDQGDQ\FKDQJHVVKRXOGEHPDGHGLUHFWO\RQWRWKHGLDU\E\WKH
VXEMHFWSDUHQWRUOHJDOJXDUGLDQ'LDU\HQWULHVZLOOEHWUDQVFULEHGE\VLWHSHUVRQQHOLQWRWKH
H&5)

8&$FWLYLW\
$38&$,VFRUHVHH$SSHQGL[)ZLOOEHHYDOXDWHGXVLQJWKHVXEMHFW¶VSDUHQW¶VRUOHJDO
JXDUGLDQ¶VSDSHUGLDU\HQWULHVDQGODERUDWRU\UHVXOWVFROOHFWHGDWHYHU\VFKHGXOHGYLVLWGXULQJWKH
VWXG\DVSHUWKH6FKHGXOHRI6WXG\3URFHGXUHV $SSHQGL[ $
$SDUWLDO0D\RVFRUHZLOOEHGHULYHGDWDOOVFKHGXOHGYLVLWV SHUWKH6FKHGXOHRI6WXG\3URFHGXUHV
$SSHQGL[ $ DQGDWDQ\XQVFKHGXOHGYLVLWVGXHWRGLVHDVHH[DFHUEDWLRQVHH$SSHQGL[+
6XEMHFWVSDUHQWVRUOHJDOJXDUGLDQVZLOOPDNHGDLO\HQWULHVLQWRWKH
GLDU\IRUGD\VSULRUWRWKHVFKHGXOHGYLVLWZKLFKZLOOEHXVHGIRU0D\RVFRUHFDOFXODWLRQ7KH
V\PSWRPVRI8&PXVWEHUHFRUGHGWKURXJKRXWWKHVWXG\(QWULHVVKRXOGEHUHYLHZHGDQG
PRQLWRUHGE\WKHVWXG\VWDIIZKLOHWKHVXEMHFWSDUHQWRUOHJDOJXDUGLDQLVLQWKHFOLQLFDQGDQ\
FKDQJHVVKRXOGEHPDGHGLUHFWO\RQWRWKHGLDU\E\WKHVXEMHFWSDUHQWRUOHJDOJXDUGLDQ
'LDU\HQWULHVSUHFHGLQJHDFKVWXG\YLVLWZLOOEHXVHGWRFDOFXODWHWKH0D\RVFRUH%HFDXVHWKH
IOH[LEOHVLJPRLGRVFRS\SUHSDUDWLRQFDQLQWHUIHUHZLWKWKHDVVHVVPHQWRIRWKHUFOLQLFDO
SDUDPHWHUVGLDU\HQWULHVXVHGWRFDOFXODWHWKHFRPSOHWH0D\RVFRUHVKRXOGQRWEHIURPGD\V
GXULQJZKLFKWKHIOH[LEOHVLJPRLGRVFRS\SUHSDUDWLRQLVDGPLQLVWHUHG

&'$FWLYLW\
$&'$,VFRUHVHH$SSHQGL[.ZLOOEHHYDOXDWHGXVLQJWKHVXEMHFW¶VSDUHQW¶VRUOHJDO
JXDUGLDQ¶VSDSHUGLDU\HQWULHVFROOHFWHGIRUGD\VSULRUWRWKHVFKHGXOHGYLVLWDQGODERUDWRU\
UHVXOWVFROOHFWHGDWHYHU\VFKHGXOHGYLVLWGXULQJWKHVWXG\DVSHUWKH6FKHGXOHRI6WXG\
3URFHGXUHV $SSHQGL[ $
$3&'$,VFRUHVHH$SSHQGL[* ZLOOEHHYDOXDWHGDFFRUGLQJWRWKH6FKHGXOHRI6WXG\
3URFHGXUHVVHH$SSHQGL[ $
(IILFDF\PHDVXUHPHQWVZLOOEHPDGH
DW:HHN

DQGDWH[LWEDVHGRQHQGRVFRS\XVLQJ6(6&'VFRUHVHH$SSHQGL[,DQG
WKH&'$,VHH$SSHQGL[.
CCI
CCI
CCI
CCI
JDOJXDUG
DOJXDU
ZKLFKZ
KLFKZ
KRXWWKH
RXWWK
VXEMHFWS
XEMHFW
RWKHGLD
WKHG
G\YLVLW
\YLVL
DUDWLRQFD
DUDWLRQ
GWRFD
GWR
al use only
WHYHU\
HYHU

LWV SHU
SHU WK
GLVHDVHH
LVHDVH
cial 

9HGROL]XPDE,9
6WXG\1R9HGROL]XPDE
3DJH RI
3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
 6HSWHPEHU 
&21),'(17,$/
7KH &'$,VKRXOGDOVREHFRPSOHWHGDWWKHWLPHRIDIODUHDQGDW
WLPHVRISRVVLEOHGRVHHVFDODWLRQ

,03$&7,,,4XHVWLRQQDLUH6XEMHFWVWR<HDUVRI$JH
7KH,03$&7,,,TXHVWLRQQDLUHLVDVHOIUHSRUWHGPHDVXUHZLWKFORVHGTXHVWLRQV
HQFRPSDVVLQJGRPDLQV%RZHO6\PSWRPVLWHPV6\VWHPLF6\PSWRPVLWHPV6RFLDO
)XQFWLRQLQJ LWHPV%RG\,PDJH LWHPV7UHDWPHQW,QWHUYHQWLRQVLWHPVDQG(PRWLRQDO
)XQFWLRQLQJLWHPV7KH,03$&7,,,XVHVDSRLQW/LNHUWVFDOHUDQJLQJIURPWRIRUDOO
DQVZHUV7KHRXWFRPHVFRUHUDQJHVIURPWRZLWKKLJKHUVFRUHVVXJJHVWLQJEHWWHUTXDOLW\
RIOLIH,03$&7,,,ZKHUHWUDQVODWLRQVDUHDYDLODEOHZLOOEHDGPLQLVWHUHGHYHU\ZHHNVWR
VXEMHFWVDJHGWR \HDUVDWWKHWLPHRIILUVWGRVHRIVWXG\GUXJIRU6WXG\9HGROL]XPDE
7KHFXUUHQWYHUVLRQZLOOEHSURYLGHGLQWKHVWXG\PDQXDO
4XHVWLRQQDLUHHQWULHVZLOOEHUHYLHZHGE\VLWHSHUVRQQHODWDSSURSULDWHVFKHGXOHGYLVLWVGXULQJ
WKHVWXG\ZKLOHWKHVXEMHFWLVSUHVHQW$Q\FKDQJHVVKRXOGEHPDGHGLUHFWO\WRWKHTXHVWLRQQDLUH
VRXUFHE\WKHVXEMHFWSDUHQWRUOHJDOJXDUGLDQ4XHVWLRQQDLUHHQWULHVZLOOEHWUDQVFULEHGE\VLWH
SHUVRQQHOLQWRWKHH&5)

7DQQHU6WDJH(YDOXDWLRQ
7DQQHU6WDJH(YDOXDWLRQVHH$SSHQGL[-LVDVFDOHXVHGWRHYDOXDWHJURZWKSDUDPHWHUV
VWDQGDUGL]HGIRUDJHVH[DQGSXEHUWDOGHYHORSPHQW 0DUVKDOODQG7DQQHU0DUVKDOODQG
7DQQHU DQGZLOOEHSHUIRUPHGHYHU\ZHHNVDVVSHFLILHGLQWKH6FKHGXOHRI6WXG\
3URFHGXUHV $SSHQGL[ $

'RFXPHQWDWLRQRI&RQFRPLWDQW0HGLFDWLRQV DQG3URFHGXUHV
&RQFRPLWDQWPHGLFDWLRQLVDQ\GUXJJLYHQLQDGGLWLRQWRWKHVWXG\PHGLFDWLRQ7KHVHPD\EH
SUHVFULEHGE\DSK\VLFLDQRUREWDLQHGE\WKHVXEMHFWRUSDUHQWOHJDOJXDUGLDQ27&&RQFRPLWDQW
PHGLFDWLRQLVQRWSURYLGHGE\7DNHGD$FRQFRPLWDQWSURFHGXUHLVDQ\QRQSKDUPDFRORJLFDO
PHGLFDOLQWHUYHQWLRQWRWUHDWDVXEMHFW¶V8&RU&'
$WHDFKVWXG\YLVLWIURPVLJQLQJRILQIRUPHGFRQVHQWDVVHQWWKURXJKWKHHQGRIWKHVWXG\
VXEMHFWVRUSDUHQWVOHJDOJXDUGLDQVZLOOEHDVNHGZKHWKHUWKHVXEMHFWKDV WDNHQDQ\PHGLFDWLRQ
RWKHUWKDQWKHVWXG\GUXJRUXQGHUJRQHDQ\SURFHGXUHVWRWUHDWWKHLU8&RU&'$OOPHGLFDWLRQ
LQFOXGLQJYLWDPLQVXSSOHPHQWV27&PHGLFDWLRQVDQGRUDOKHUEDOSUHSDUDWLRQVDQG
FRQFRPLWDQWSURFHGXUHVPXVWEHUHFRUGHGLQWKHH&5)

CCI
CCI
For non-commercial use only
SULD
SUL
PDGHGL
PDGHG
UHHQWULH
HHQWUL
VFDOHXV
FDOHX
ORSPHQW
RSPH
U\ZH
\Z
QFRPLW
FRP
Q\GUXJ
Q\GUX
REWDL
RE

9HGROL]XPDE,9
6WXG\1R9HGROL]XPDE
3DJH RI
3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
 6HSWHPEHU 
&21),'(17,$/

8VHRI/RFDO$QHVWKHWLF
,WLVUHFRPPHQGHGWRXVHORFDODQHVWKHWLFSDWFKHVHJ6\QHUDRUFUHDPVHJ(0/$IRUEORRG
GUDZVRU,9LQVHUWLRQVIRUWKHFRPIRUWRIWKHVXEMHFW7KLVZLOOQRWEHUHFRUGHGDVDFRQFRPLWDQW
PHGLFDWLRQ

3URFHGXUHVIRU&OLQLFDO/DERUDWRU\6DPSOHV
$OOVDPSOHVZLOOEHFROOHFWHGLQDFFRUGDQFH ZLWKDFFHSWDEOHODERUDWRU\SURFHGXUHV7KH
PD[LPXPYROXPHRIEORRGGUDZQDWDQ\VLQJOHYLVLWLVDSSUR[LPDWHO\P/IRUVXEMHFWVZKR
ZHLJK NJ DQGDSSUR[LPDWHO\P/IRUVXEMHFWVZKRZHLJK NJ7KHWRWDOYROXPHRI
EORRGGUDZQLVDSSUR[LPDWHO\P/IRUVXEMHFWVZKRZHLJKNJ DQGDSSUR[LPDWHO\ 
P/IRUVXEMHFWVZKRZHLJK NJRYHUHDFK PRQWKSHULRG
'HWDLOVRIWKHVHSURFHGXUHVDQGUHTXLUHGVDIHW\PRQLWRULQJZLOOEHJLYHQLQWKHODERUDWRU\
PDQXDO&OLQLFDOODERUDWRU\WHVWVWREHFRQGXFWHGDUHVXPPDUL]HGLQ7DEOHD7KHVHWHVWV
VKRXOGEHSHUIRUPHGDVVSHFLILHGLQWKH6FKHGXOHRI6WXG\3URFHGXUHV $SSHQGL[ $
7KHFHQWUDOODERUDWRU\ZLOOSHUIRUPODERUDWRU\WHVWVIRUKHPDWRORJ\DQGVHUXPFKHPLVWULHVZLWK
WKHH[FHSWLRQRIWKHXULQHSUHJQDQF\WHVWZKLFKZLOOEHSHUIRUPHGDWWKHVWXG\VLWHDQGWKH
HU\WKURF\WHVHGLPHQWDWLRQUDWH(65ZKLFKPD\EHSHUIRUPHGDWDORFDOODERUDWRU\7KHUHVXOWV
RIODERUDWRU\WHVWVZLOOEHUHWXUQHGWRWKHLQYHVWLJDWRUZKRLVUHVSRQVLEOHIRUUHYLHZLQJDQGILOLQJ
WKHVHUHVXOWV
,IVXEMHFWVH[SHULHQFH$/7RU$67!î8/1IROORZXSODERUDWRU\WHVWVDWDPLQLPXPVHUXP
DONDOLQHSKRVSKDWDVH$/7$67WRWDOELOLUXELQȖJOXWDP\OWUDQVIHUDVH>**7@DQG,15VKRXOG
EHSHUIRUPHGZLWKLQDPD[LPXPRIGD\VDQGSUHIHUDEO\ZLWKLQWRKRXUVDIWHUWKH
DEQRUPDOLW\ZDVQRWHG3OHDVHUHIHUWR6HFWLRQ IRUGLVFRQWLQXDWLRQFULWHULDDQG
6HFWLRQ IRUWKHDSSURSULDWHJXLGDQFHRQ5HSRUWLQJRI$EQRUPDO/LYHU)XQFWLRQ7HVWVLQ
UHODWLRQWR$/7RU$67!î8/1LQFRQMXQFWLRQZLWKWRWDOELOLUXELQ!î8/1
,IWKH$/7RU$67UHPDLQVHOHYDWHG!î8/1RQWKHVHFRQVHFXWLYHRFFDVLRQVWKHLQYHVWLJDWRU
PXVWFRQWDFWWKHPHGLFDOPRQLWRUIRUFRQVLGHUDWLRQRIDGGLWLRQDOWHVWLQJFORVHPRQLWRULQJ
SRVVLEOHGLVFRQWLQXDWLRQRIVWXG\GUXJGLVFXVVLRQRIWKHUHOHYDQWVXEMHFWGHWDLOVDQGSRVVLEOH
DOWHUQDWLYHHWLRORJLHV7KHDEQRUPDOLW\VKRXOGEHUHFRUGHGDVDQ$( 3OHDVHUHIHUWR
6HFWLRQ 5HSRUWLQJRI$EQRUPDO/)7V IRUUHSRUWLQJUHTXLUHPHQWV
CCI
For non-commercial use only
HGLQ
GLQ 7
URFHGXUH
RFHGXUH
KHPDWROR
PDWR
EHSHUIRU
HSHUIR
EHSHUIRU
HSHUI
JDWRUZ
JDWRUZ
7!î8
7!î8
67WRWDO
WRWD
PXPRI
PXPR
H UH
H
om
n-co

9HGROL]XPDE,9
6WXG\1R9HGROL]XPDE
3DJH RI
3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
 6HSWHPEHU 
&21),'(17,$/
7DEOHD
&OLQLFDO/DERUDWRU\7HVWV
+HPDWRORJ\
6HUXP&KHPLVWU\
5%&
:%&ZLWKGLIIHUHQWLDO
+HPRJORELQ
+HPDWRFULW
3ODWHOHWV
,15 LIUHTXLUHG
(65
$/7
$OEXPLQ
$ONDOLQHSKRVSKDWDVH
$67
7RWDOELOLUXELQ
'LUHFWELOLUXELQ
7RWDOSURWHLQ
&UHDWLQLQH
%ORRGXUHDQLWURJHQ
&UHDWLQHNLQDVH
**7
3RWDVVLXP
6RGLXP
*OXFRVH
&KORULGH
%LFDUERQDWH
&DOFLXP
$P\ODVH
2WKHU
6HUXP
8ULQH
)HPDOHVXEMHFWVRQO\K&*XULQHSUHJQDQF\WHVW
IHPDOHVXEMHFWVRIFKLOGEHDULQJSRWHQWLDORQO\ FROOHFWHGDW
HDFKVFKHGXOHGYLVLWSHU$SSHQGL[ $ IRUIHPDOHVZKRUHDFK
PHQDUFKHGXULQJWKHVWXG\
6WRRO
&GLIILFLOH WHVWLQJ DQGWR[LQ$DQG%
)HFDO FDOSURWHFWLQ
2YDDQGSDUDVLWHHYDOXDWLRQ
6WRROFXOWXUH
&GLIILFLOH&ORVWULGLXPGLIILFLOH (65HU\WKURF\WHVHGLPHQWDWLRQUDWH K&*KXPDQFKRULRQLFJRQDGRWURSLQ 5%&
UHGEORRGFHOO

)HFDO&DOSURWHFWLQ6DPSOH&ROOHFWLRQ
$VWRROVDPSOHZLOOEHFROOHFWHGIRUWKHDQDO\VLVRIIHFDOFDOSURWHFWLQDELRPDUNHURILQWHVWLQDO
LQIODPPDWRU\DFWLYLW\DVVSHFLILHGLQWKH6FKHGXOHRI6WXG\3URFHGXUHV $SSHQGL[ $DQGDWDQ\
SRLQWLQWKHVWXG\ZKHQDVXEMHFWEHFRPHVV\PSWRPDWLFLQFOXGLQJZRUVHQLQJRIGLVHDVHDFWLYLW\
7KHVWRROVDPSOHPXVWEHFROOHFWHGEHIRUHDQ\ERZHOSUHSDUDWLRQLVJLYHQIRUHQGRVFRS\

6WRRO6DPSOHIRU &XOWXUH2YDDQG3DUDVLWH(YDOXDWLRQDQG&GLIILFLOH $VVD\
$VWRROVDPSOHZLOOEHREWDLQHGIRUFXOWXUHRYDDQGSDUDVLWHHYDOXDWLRQDQG &GLIILFLOH DVVD\DW
DQ\SRLQWLQWKHVWXG\ZKHQDSDWLHQWEHFRPHVV\PSWRPDWLFLQFOXGLQJZRUVHQLQJRIGLVHDVH
DFWLYLW\7KHVWRROVDPSOHPXVWEHFROOHFWHGEHIRUHDQ\ERZHOSUHSDUDWLRQLVJLYHQIRU
HQGRVFRS\
CCI
CCI
For non-commercial use only
DVH
DVH
rc
8ULQ
8U
me
)
m
n
%
For
r

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 56 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
9.1.15 
Contraception and Pregnancy Avoidance Procedure 
9.1.15.1 
Male Subjects and Their Female Partners 
From signing of parental informed consent/assent form, throughout the duration of the study, and 
for 18 weeks after last dose of study drug, 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. 
9.1.15.2 
Female Subjects and Their Male Partners 
From signing of parental informed consent/assent form, throughout the duration of the study, and 
for 18 weeks after last dose of study drug, female subjects of childbearing potential* who are 
sexually active with a nonsterilized male partner** must use a highly effective/effective method 
of contraception (from the list below). In addition, they must be advised not to donate ova during 
this period. This will apply to female subjects of childbearing potential who have reached 
menarche prior to or during the study. 
9.1.15.3 
Definitions and Procedures for Contraception and Pregnancy Avoidance 
The following definitions apply for contraception and pregnancy avoidance procedures. 
* A female subject is considered a female subject of childbearing potential, ie, fertile, following 
menarche and until becoming postmenopausal unless permanently sterile. Permanent sterilization 
methods include hysterectomy, and bilateral oophorectomy. A postmenopausal state is defined as 
no menses for 12 months without an alternative medical cause. A high follicle-stimulating 
hormone (FSH) level in the postmenopausal range (FSH >40 IU/L) may be used to confirm a 
postmenopausal state in younger women (eg, those <45 years old) or women who are not using 
hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months 
of amenorrhea, a single FSH measurement is insufficient. 
** Sterilized males should be at least 1 year post–bilateral vasectomy and have confirmed that 
they have obtained documentation of the absence of sperm in the ejaculate or have had bilateral 
orchidectomy. 
The following procedures apply for contraception and pregnancy avoidance. 
1. Highly effective methods of contraception are defined as those, alone or in combination, that 
result in a low failure rate (ie, less than 1% failure rate per year when used consistently and 
correctly). In this study, where medications and devices containing hormones are included, 
the only acceptable methods of contraception are: 
• Nonhormonal Methods: 
– Intrauterine device.  
– Bilateral tubal occlusion. 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 57 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
– Vasectomized partner (provided that partner is the sole sexual partner of the study 
participant and that the vasectomized partner has received medical assessment of the 
surgical success 
– True sexual abstinence, only if this is in line with the preferred and usual lifestyle of 
the subject. True abstinence is defined as refraining from heterosexual intercourse 
during the entire period of the study, from 1 month prior to the first dose until 
18 weeks after last dose. 
• Hormonal Methods: 
– Combined (estrogen and progestogen) hormonal contraception associated with 
inhibition of ovulation initiated at least 3 months prior to the first dose of study drug 
OR combined with a barrier method (male condom, female condom or diaphragm) if 
for shorter duration until she has been on contraceptive for 3 months; 
• Oral. 
• Intravaginal (eg, ring). 
• Transdermal. 
– Progestogen-only hormonal contraception associated with inhibition of ovulation 
initiated at least 3 months prior to the first dose of study drug OR combined with a 
barrier method (male condom, female condom or diaphragm) if shorter till she has 
been on contraceptive for 3 months; 
• Oral. 
• Injectable. 
• Implantable. 
2. Standard-of-care medications and effective methods of contraception are: 
• Double-barrier method (contraceptive sponge, diaphragm or cervical cap with 
spermicidal jellies or creams PLUS male condom). 
• Progestogen only hormonal contraception, where inhibition of ovulation is not the 
primary mode of action PLUS condom with or without spermicide. 
3. Unacceptable methods of contraception are: 
• Periodic abstinence (eg, calendar, ovulation, symptothermal, postovulation methods). 
• Spermicides only. 
• Withdrawal. 
• No method at all. 
• Use of female and male condoms together. 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 58 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
• Cap/diaphragm/sponge without spermicide and without condom. 
4. Subjects will be provided with information on highly effective/effective methods of 
contraception as part of the subject informed consent/assent process and will be asked to sign 
a consent/assent form stating that they understand the requirements for avoidance of 
pregnancy, donation of ova, and sperm donation during the course of the study. 
5. During the course of the study, regular urine hCG pregnancy tests will be performed only for 
female subjects of childbearing potential and all subjects (male and female) will receive 
continued guidance with respect to the avoidance of pregnancy and sperm donation as part of 
the study procedures. Such guidance should include a reminder of the following: 
a) Contraceptive requirements of the study. 
b) Reasons for use of barrier methods (ie, condom) in male subjects with pregnant partners. 
c) Assessment of subject compliance through questions such as: 
i. 
Have you used the contraception consistently and correctly since the last visit? 
ii. 
Have you forgotten to use contraception since the last visit?  
iii. 
Are your menses late (even in female subjects with irregular or infrequent 
menstrual cycles a pregnancy test must be performed if the answer is “yes”)? 
iv. 
Is there a chance you could be pregnant? 
6. In addition to a negative serum hCG pregnancy test at the Study MLN0002-2003 Week 22 
Visit, female subjects of childbearing potential must also have confirmed menses in the 
month before first dosing (no delayed menses), a negative urine hCG pregnancy test prior to 
receiving any dose of study drug (as close as possible and prior to first dose of study drug, 
preferably on the same day). 
9.1.16 
Pregnancy 
If any subject is found to be pregnant during the study, she should be withdrawn and any 
sponsor-supplied drug should be immediately discontinued. In addition to the procedures 
summarized below, ET/follow-up procedures (ie, Final Safety Visit [18 weeks after the last dose 
of study drug] and the long-term follow-up safety survey by telephone [6 months after the last 
dose of study drug]) should be completed. Any pregnancies in the partner of a male subject 
during the study or for 18 weeks after the last dose of study drug should also be recorded, 
following authorization from the subject’s partner. 
If the pregnancy occurs during administration of active study drug or within 18 weeks of the last 
dose of active study drug, the pregnancy should be reported immediately, using a pregnancy 
notification form, to the contact listed in Section 1.1. 
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. 
For non-commercial use only

9HGROL]XPDE,9
6WXG\1R9HGROL]XPDE
3DJH RI
3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
 6HSWHPEHU 
&21),'(17,$/
$OOSUHJQDQFLHVLQFOXGLQJIHPDOHSDUWQHUVRIPDOHVXEMHFWVLQVXEMHFWVRQDFWLYHVWXG\GUXJZLOO
EHIROORZHGIRU\HDUDIWHUGHOLYHU\IRURXWFRPHVRIERWKWKHPRWKHUDQGFKLOGXVLQJWKH
SUHJQDQF\IRUP7KHRXWFRPHLQFOXGLQJDQ\SUHPDWXUHWHUPLQDWLRQPXVWEHUHSRUWHGWRWKH
VSRQVRU$QHYDOXDWLRQDIWHUWKHELUWKRIWKHFKLOGZLOODOVREHFRQGXFWHG


CCI
CCI
For non-commercial use only
only
se o
l use
cial 
erc
me
omm
com
on-c
non
or n
Fo
F

9HGROL]XPDE,9
6WXG\1R9HGROL]XPDE
3DJH RI
3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
 6HSWHPEHU 
&21),'(17,$/

'RFXPHQWDWLRQRI6FUHHQ)DLOXUH
,QYHVWLJDWRUVPXVWDFFRXQWIRUDOOVXEMHFWVZKRVLJQLQIRUPHGFRQVHQWDVVHQW
,IWKHVXEMHFWLVIRXQGWREHQRWHOLJLEOHDWWKLVYLVLWWKHLQYHVWLJDWRUVKRXOGFRPSOHWHWKHH&5)
7KH,57 VKRXOGEHFRQWDFWHGDVDQRWLILFDWLRQRIVFUHHQIDLOXUH
7KHSULPDU\UHDVRQIRUVFUHHQIDLOXUHLVUHFRUGHGLQWKHH&5)XVLQJWKHIROORZLQJFDWHJRULHV
x
$(
x
3RVLWLYH30/FKHFNOLVW
x
'LGQRWPHHWLQFOXVLRQFULWHULDRUGLGPHHWH[FOXVLRQFULWHULD
x
6LJQLILFDQWSURWRFROGHYLDWLRQ
x
/RVWWRIROORZXS
x
9ROXQWDU\ZLWKGUDZDO
x
6WXG\WHUPLQDWLRQ
x
2WKHU

'RFXPHQWDWLRQRI6WXG\(QWUDQFH
2QO\ VXEMHFWVZKRKDYHDVVHQWHGDQGWKHLUFDUHJLYHUVDVDSSOLFDEOHKDYHFRQVHQWHGDQGZKR
PHHWDOORIWKHLQFOXVLRQFULWHULDDQGQRQHRIWKHH[FOXVLRQFULWHULDDUHHOLJLEOHIRUHQWUDQFHLQWR
WKLVH[WHQVLRQVWXG\6RPHLQIRUPDWLRQWRFRQILUPHQWU\ZLOOEHREWDLQHGIURPWKH0/1
:HHNDVVHVVPHQWVZKLFKZLOOEHXVHGIRUWKHSUHHQUROOPHQW'D\9LVLWRIWKLVVWXG\
,IDVXEMHFWLVIRXQGWREHQRWHOLJLEOHIRUHQWU\WRWKLVVWXG\WKHLQYHVWLJDWRUVKRXOGUHFRUGWKH
SULPDU\UHDVRQIRUIDLOXUHRQWKHDSSOLFDEOHH&5)

(QGRVFRSLHV
$QHQGRVFRS\ZLOOEHSHUIRUPHGDW:HHNDVSDUWRIWKHFOLQLFDODVVHVVPHQW7KLVZLOOLQYROYH
DIOH[LEOHVLJPRLGRVFRS\VLJPRLGRVFRSHRUDFRORQRVFRS\SHUIRUPHGZLWKDQHQGRVFRSH
IROORZLQJDFOHDQVLQJSUHSDUDWLRQRUDORUUHFWDOFDWKDUWLF7KH:HHNHQGRVFRS\ZLOOEHUHDG
FHQWUDOO\IRUWKHHIILFDF\DQDO\VLVWKURXJKWKHXVHRIYLGHRUHFRUGLQJV2QWKHGD\VWKDW
HQGRVFRSLHVDUHSHUIRUPHGDOORWKHUVWXG\SURFHGXUHVIRUWKDWYLVLWVKRXOGEHSHUIRUPHGHLWKHU
SULRUWRWKHHQGRVFRS\RURQDQRWKHUGD\ZLWKLQWKHYLVLWZLQGRZ
CCI
CCI
For non-commercial use only

(QWUDQ
(QWUD
GDQGWKH
DQGWK
ULDDQGQ
ULDDQG
QIRUPD
QIRUP
KL

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 61 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
9.2 
Monitoring Subject Treatment Compliance 
Study drug will be administered in the clinic and treatment compliance will be monitored. If a 
subject is persistently noncompliant with the study drug (eg, fails to keep scheduled study visits), 
it may be appropriate to withdraw the subject from the study. 
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 
Randomization 
Treatment is not randomly assigned in this study. Subjects will be assigned to the same dose of 
study drug received at Week 14 of Study MLN0002-2003. 
9.3.2 
Final Visit or ET  
It is anticipated that the duration of vedolizumab treatment will vary by subject on the basis of 
continued benefit but will be until vedolizumab IV is commercially available for pediatric 
indication in the subject’s country or until other drug access programs become available 
(whichever comes first), the subject turns 18 years of age and can be transitioned to commercial 
drug, the subject withdraws from the study, or the sponsor decides to close the study. The final 
visit is to be completed within 8 weeks following a pre-agreed-upon subject’s last dose 
(determined by the investigator) and prior to any planned dose if the subject is to transition to 
commercial drug or other drug access program. Subjects are still expected to complete both the 
final safety follow-up visit (Section 9.3.3), which is performed at 18 weeks post-last dose, and 
the long-term follow-up safety survey (phone call), which is completed 6 months after the last 
dose of study drug (Section 9.3.4). The procedures listed in Schedule of Study Procedures 
(Appendix A) at the Final Visit/ET Visit will be performed and documented. 
For all subjects receiving study drug, the investigator must complete the End of Study eCRF 
page. 
9.3.3 
Final Safety Follow-up Visit  
The final safety follow-up visit will be performed 18 weeks after the last dose of study drug. 
Subjects are expected to complete the final safety follow-up visit. The procedures listed in 
Schedule of Study Procedures (Appendix A) will be performed and documented. 
9.3.4 
Long-term Follow-up Safety Survey 
Upon completion of treatment, or early termination from the study, all subjects will participate in 
the long-term follow-up safety survey, conducted by telephone 6 months after the last dose of 
study drug, unless the subject withdraws consent or is lost to follow-up. If the subject continues 
with treatment outside of the study, the 6-month follow-up by phone call will be based on the last 
dose of study drug in Study Vedolizumab-2005 (and not based on receipt of commercially 
available vedolizumab or vedolizumab provided in a drug access program). 
For non-commercial use only

9HGROL]XPDE,9
6WXG\1R9HGROL]XPDE
3DJH RI
3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
 6HSWHPEHU 
&21),'(17,$/

3RVWVWXG\ &DUH
6WXG\GUXJZLOOQRWEHDYDLODEOHXSRQFRPSOHWLRQRIWKHVXEMHFW¶VSDUWLFLSDWLRQLQWKHVWXG\7KH
VXEMHFWVKRXOGEHUHWXUQHGWRWKHFDUHRIDSK\VLFLDQDQGXVHVWDQGDUGWKHUDSLHVDVUHTXLUHG
3RVWWULDODFFHVVWRFRPPHUFLDOO\DYDLODEOHYHGROL]XPDE,9PD\EHSURYLGHGE\WKHVSRQVRU
&RQWLQXHGDFFHVVWRYHGROL]XPDE,9IRUSDUWLFLSDQWVZLOOEHWHUPLQDWHGIRUWKRVHLQGLYLGXDOVLQ
WKLVVWXG\ZKRQRORQJHUEHQHILWIURPWKHGUXJZKHQWKHEHQHILWULVNQRORQJHUIDYRUVWKH
LQGLYLGXDOLIYHGROL]XPDE,9EHFRPHVDYDLODEOHHLWKHUFRPPHUFLDOO\RUYLDDQRWKHUGUXJDFFHVV
PHFKDQLVPRUZKHQDQDOWHUQDWLYHDSSURSULDWHWKHUDS\EHFRPHVDYDLODEOH3RVWWULDODFFHVVPD\
EHWHUPLQDWHGLQDFRXQWU\RUJHRJUDSKLFDOUHJLRQZKHUHPDUNHWLQJDXWKRUL]DWLRQKDVEHHQ
UHMHFWHGRUWKHGHYHORSPHQWRIYHGROL]XPDE,9KDVEHHQVXVSHQGHGRUVWRSSHGE\WKHVSRQVRU

8QVFKHGXOHG9LVLWV'XHWR'LVHDVH([DFHUEDWLRQ
6XEMHFWVZKRDUHVHHQE\WKHLQYHVWLJDWRURUVLWHVWDIIDWDWLPHSRLQWQRWUHTXLUHGE\WKHSURWRFRO
LHXQVFKHGXOHG YLVLWGXHWRGLVHDVHH[DFHUEDWLRQZLOOXQGHUJRWKHIROORZLQJ
x
3K\VLFDOH[DPLQDWLRQ LQFOXGLQJZHLJKWDQGKHLJKW
x
)LVWXODDVVHVVPHQWVXEMHFWVZLWK&'RQO\
x
9LWDOVLJQVDVVHVVPHQW
x
'LDU\UHYLHZ
x
&ROOHFWLRQRIFRQFRPLWDQWPHGLFDWLRQVDQGSURFHGXUHV
x
&ROOHFWLRQRI$(VDQG6$(V
x
&OLQLFDOFKHPLVWU\DQGKHPDWRORJ\DVLQGLFDWHG
x
6WRROVDPSOHIRUFXOWXUH
x
6WRROVDPSOHIRUIHFDOFDOSURWHFWLQ
x
8ULQHK&* IRUIHPDOHVXEMHFWVRIFKLOGEHDULQJSRWHQWLDO
x
38&$,3&'$,
x
3DUWLDO0D\RVFRUH
7KHUHLVQRPLQLPXPWLPHIRUUHSHDWHYDOXDWLRQE\XQVFKHGXOHGYLVLWLQRUGHUWRGHWHUPLQHLID
VXEMHFWPHHWVWKHFULWHULDIRUGLVHDVHZRUVHQLQJ6HFWLRQ,QJHQHUDOKRZHYHUHQRXJKWLPH
VKRXOGEHSURYLGHGIRUFOLQLFDOO\PHDQLQJIXOFKDQJHWRRFFXUHJZHHN
CCI
CC
For non-commercial use only
SRLQWQ
RLQW
UJRWKHI
RWKHI
RQVDQG
QVDQ
PDWRORJ\
DWRORJ

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 63 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
9.3.7 
Other Unscheduled Visits (if Applicable) 
Subjects may return to the study center for unscheduled visit as needed. Unscheduled visits can 
be performed when the subject has a study related issue in between regular visits (ie, SAE 
follow-up, LFT elevations). The following procedures may be done during these visits: 
concomitant medications, clinical laboratory blood draws, urine sample and AE collection, as 
appropriate). Standard of care visits (routine check-ups) should not be captured as an 
unscheduled visit in eCRF. However, if the visit is due to disease exacerbation the procedures 
described in Section 9.3.6 should be performed.  
9.3.8 
Alternative Approaches to Study Procedures and Data Collection Due to a 
Pandemic 
In unavoidable circumstances, in particular a pandemic (eg, COVID-19 or other future similar 
unexpected public health concern), that impact the study site’s ability to conduct study 
procedures according to the Schedule of Study Procedures (Appendix A), contingency measures 
may be implemented. In acknowledgement of hospital, local, state, or national government 
restrictions or other site-related factors caused by unavoidable circumstances (ie, COVID-19 
pandemic) that may prevent investigators from conducting the study according to the Schedule 
of Study Procedures (Appendix A), investigators may seek approval from the medical monitor to 
continue subjects in the study despite departure from the Schedule of Study Procedures 
(Appendix A). Any procedures not conducted per the original study plan will be documented in 
the study records.  
Because a pandemic or other major health crisis (eg, COVID-19) may peak in different regions 
at different times and restrictions implemented by local laws and recommendations may vary, 
any decision on procedural changes should be made on a case-by-case basis by the principal 
investigator in consultation with the sponsor or designee, while maintaining subject safety and 
confidentiality as the priority.  
The principal investigator should also notify the IEC/IRB, as appropriate, about any deviation for 
temporary use of alternative methods for conducting subject visits (eg, video conferencing, 
telephone visits) in the event of restrictive measures due to a pandemic (eg, COVID-19), per 
local requirements. 
Procedural changes due to COVID-19 (or other similar pandemic) may include the following: 
• All attempts should be made to perform the assessments with the subject present at the site 
using the visit windows. Exceptions may be granted for alternative approaches to study 
procedures and data collection through approval by the sponsor or designee. Such instances 
must be documented in the study records and may include the following: 
– Sites impacted by a pandemic (eg, COVID-19) must contact the sponsor or designee to 
discuss individual subject and site circumstances to obtain approval for use of alternative 
approaches to study procedures and data collection.  
– Sites may seek approval from the medical monitor for subjects to continue in the study 
despite departure from the Schedule of Study Procedures (Appendix A). Principal 
For non-commercial use only

9HGROL]XPDE,9
6WXG\1R9HGROL]XPDE
3DJH RI
3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
 6HSWHPEHU 
&21),'(17,$/
LQYHVWLJDWRUVDUHH[SHFWHGWRHYDOXDWHWKHLPSDFWRQWKHVDIHW\RIWKHVWXG\SDUWLFLSDQWV
DQGVLWHSHUVRQQHOIRUVXEMHFWVWRFRQWLQXH,QHYDOXDWLQJVXFKUHTXHVWVWKHVSRQVRURU
GHVLJQHHZLOOJLYHWKHKLJKHVWSULRULW\WRWKHVDIHW\DQGZHOIDUHRIWKHVXEMHFWV6XEMHFWV
PXVWEHZLOOLQJDQGDEOHWRFRQWLQXHWDNLQJVWXG\PHGLFDWLRQDQGUHPDLQFRPSOLDQWZLWK
WKHSURWRFRO
x
,QIRUPHGFRQVHQWSURFHGXUH,IQHFHVVDU\DQGUHTXLUHGORFDOO\LQIRUPHGFRQVHQWIURPD
VWXG\SDUWLFLSDQWPD\EHREWDLQHGYLDYHUEDOFRQVHQWZKHQWKHVHLQGLYLGXDOVDUHXQDEOHWR
WUDYHOWRWKH VLWH,QIRUPHGFRQVHQWIRUPVZLOOEHVLJQHGRQFHWKHVXEMHFWFDQUHWXUQLQSHUVRQ
WRWKHVWXG\VLWH
x
&OLQLFYLVLWV)RUFOLQLFYLVLWVRWKHUWKDQWKHILQDOYLVLW(7YLVLWDQGWKHVDIHW\IROORZXS
YLVLWDOWHUQDWLYHPHWKRGVIRUFRQGXFWLQJVXEMHFWYLVLWVHJWHOHPHGLFLQHYLVLWVVXFKDVYLGHR
FRQIHUHQFLQJRUWHOHSKRQHYLVLWVPD\EHXVHGZLWKSULRUDSSURYDOE\WKHVSRQVRURU
GHVLJQHH
±
:KHQDSSURYDOLVJLYHQIRUDFOLQLFYLVLWWREHFRQGXFWHGXVLQJDQDOWHUQDWLYHDSSURDFKD
VWXG\VLWHSK\VLFLDQZLOOVSHDNGLUHFWO\ZLWKWKHVXEMHFWE\WHOHSKRQHRURWKHUPHGLXP
HJDFRPSXWHUEDVHGYLGHRFRPPXQLFDWLRQGXULQJHDFKYLVLWZLQGRZWRDVVHVVVXEMHFW
VDIHW\DQGRYHUDOOFOLQLFDOVWDWXV
±
$VVHVVPHQWV'XULQJYLVLWVXVLQJDQDOWHUQDWLYHPHWKRGWKHVWXG\VLWHSK\VLFLDQRURWKHU
TXDOLILHGVLWHSHUVRQQHOVKRXOGFRQWDFWWKHVXEMHFWDQGFRQGXFWWKHIROORZLQJDVVHVVPHQWV
ZLWKLQVSHFLILHGYLVLWZLQGRZWLPHIUDPHV$(6$(FROOHFWLRQGRFXPHQWDWLRQRI
FRQFRPLWDQWPHGLFDWLRQDQGSURFHGXUHVGLDU\UHYLHZVXEMHFWDVVHVVPHQWRI GLVHDVH
DFWLYLW\EDVHGRQVXEMHFWUHSRUWHGV\PSWRPVDQGSDWLHQWUHSRUWHGRXWFRPHDVVHVVPHQW
,03$&7,,,6LWHVPD\UHFRUGWKHVFRUHVRIWKH,03$&7,,,DVVHVVPHQWVRQEHKDOIRI
WKHVXEMHFWZLWKWKHVXEMHFW¶VDJUHHPHQWLQWKHHYHQWRIDWHOHPHGLFLQHYLVLW)RUVXEMHFWV
ZLWK8&VXEMHFWUHSRUWHGFRPSRQHQWVRIWKHSDUWLDO0D\RVFRUHVKRXOGEHUHFRUGHGLQ
WKHGDLO\GLDU\SHUSURWRFRO)RUDOOVXEMHFWVWKHLQYHVWLJDWRU¶VDVVHVVPHQWRIGLVHDVH
DFWLYLW\VKRXOGVWLOOEHSHUIRUPHGEDVHGRQVXEMHFWUHSRUWHGV\PSWRPVDQGUHFRUGHGLQ
WKHVRXUFHGRFXPHQWVHYHQLIDSK\VLFDOH[DPLQDWLRQFDQQRWEHSHUIRUPHG
±
&ROOHFWLRQRIFOLQLFDOODERUDWRU\VDPSOHV6DIHW\ODERUDWRU\DVVHVVPHQWVLHFOLQLFDO
FKHPLVWU\DQGKHPDWRORJ\VKRXOGEHFRQGXFWHGDWOHDVWHYHU\ZHHNV,ID VXEMHFWLV
XQDEOHWRYLVLWWKHVWXG\VLWHEHFDXVHRIDSDQGHPLFHJ&29,'VLWHVPD\HOHFWWR
XVHORFDOODERUDWRULHVLILWLVIHDVLEOHIRUWKHVXEMHFWWRYLVLWDORFDOODERUDWRU\VRRQHUWKDQ
WKHVWXG\VLWHIRUVDPSOHFROOHFWLRQ/RFDOODERUDWRU\DVVHVVPHQWVVKRXOGLQFOXGHFOLQLFDO
FKHPLVWU\DQGKHPDWRORJ\DVVSHFLILHGLQ7DEOHDDQGUHVXOWVVKRXOGEHFRPPXQLFDWHG
WRWKHPHGLFDOPRQLWRUDQGXVHG WRHQVXUHVXEMHFWVDIHW\6WRROVDPSOHVDQGFROOHFWLRQRI
VDPSOHVIRU)6+IHFDOFDOSURWHFWLQ
DUHQRWUHTXLUHGZKHQORFDO
ODERUDWRULHVDUHXVHGKRZHYHUVDPSOLQJIRUWKHVHDVVHVVPHQWVZLOOEHUHVXPHGRQWKH
VXEMHFW¶VVXEVHTXHQWYLVLWWRWKHVLWH
CCI
For non-commercial use only
XFWHGXVLQ
HGXV
XEMHFWE
EMHF
GXULQJHD
GXULQJ
HUQDWLYH
QDWLY
FWWKHVX
WWKHV
HIUDPHV
IUDPH
RFHGXUH
HGXU
SRUWHGV\
RUWHG
UHFRUGW
HFRUG
XEMHFW¶V
XEMHFW¶V
RUWHGF
RUWHG

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 65 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
– Protocol deviations: Any deviations from the protocol-specified procedures due to a 
pandemic (eg, COVID-19 or other similar pandemic) will be recorded as related to a 
pandemic (eg, COVID-19). 
• Final visit/ET visit and safety follow-up visit: The final visit/ET visit and the safety follow-
up visit should be performed with the subject present at the study site. If the visit cannot be 
conducted onsite within the visit window, sites may conduct final visit procedures remotely 
as is feasible, including using local laboratories for assessment of clinical chemistry and 
hematology (as specified in Table 9.a). Assessments that cannot be completed during the 
protocol-specified window will be recorded as a protocol deviation, and such deviations will 
be recorded in the study records as related to a pandemic (eg, COVID-19 or other similar 
pandemic). 
• Discontinuation or withdrawal from the study or study medication: If a subject chooses to 
withdraw from the study or study medication because of personal concerns related to a 
pandemic (eg, COVID-19), this must be specified as the reason for subject withdrawal in the 
eCRF.  
For subjects who are impacted, any alternative approaches to study procedures (ie, procedures 
not conducted per the Schedule of Study Procedures [Appendix A]) due to a pandemic (eg, 
COVID-19 or other similar pandemic) must be documented in the study records as related to a 
pandemic (eg, COVID-19). Data collected using alternative methods may be handled differently 
in the final data analyses. This will be documented in the statistical analysis plan. 
10.0 
PRE-TREATMENT EVENTS AND ADVERSE EVENTS 
Table 10.a 
AE Subtypes Defined in This Section  
Safety Event 
How to Reports Event to Safety 
Reporting Timelines to Sponsor 
SAEs/AESIs 
• 
Complete AE eCRF (If EDC is 
down, submit paper SAE form) 
Within 24 hours of awareness 
Pregnancy 
• 
Complete and submit paper 
pregnancy form 
24 hours 
SSRs 
• 
Complete and submit paper 
SSR form 
7 days 
AE: adverse event; AESI: adverse event of special interest; eCRF: electronic case report form; EDC: electronic 
data capture; SAE: serious adverse event; SSR: special situation reporting. 
 
 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 66 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
10.1 
Definitions 
10.1.1 
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.  
10.1.2 
Additional Points to Consider for 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 AEs.) 
• Necessitate therapeutic intervention. 
• Require an invasive diagnostic procedure. 
• Require discontinuation or a change in dose of study drug or a concomitant medication. 
• Be considered unfavorable by the investigator for any reason. 
• AEs caused by a study procedure (eg, a bruise after blood draw) should be recorded as an 
AE. 
Diagnoses vs signs and symptoms: 
• Each event should be recorded to represent a single diagnosis. Accompanying signs 
(including abnormal laboratory values) or symptoms should NOT be recorded as additional 
AEs. If a diagnosis is unknown, sign(s) or symptom(s) should be recorded appropriately as 
an AE(s). 
Laboratory values: 
• Changes in laboratory values are only considered to be 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 retest and/or 
continued monitoring of an abnormal value are not considered an intervention. In addition, 
repeated or additional noninvasive testing for verification, evaluation or monitoring of an 
abnormality is not considered an intervention. 
• If abnormal laboratory values 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 an AE. 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 67 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
Pre-existing conditions: 
• Pre-existing conditions (present at the time of signing of informed consent) are considered 
ongoing medical history and should NOT be recorded as AEs. Baseline evaluations (eg, 
laboratory tests) should NOT be recorded as AEs unless related to study procedures. 
However, if the subject experiences a worsening or complication of such an ongoing medical 
history, the worsening or complication should be recorded appropriately as an AE (worsening 
or complication occurs after start of study drug). Investigators should ensure that the event 
term recorded captures the change in the condition (eg, “worsening of…”). 
• If a subject has a pre-existing episodic condition (eg, asthma, epilepsy) any occurrence of an 
episode should only be captured as an 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 ongoing medical history (eg, cataracts, rheumatoid arthritis), 
worsening of the condition should only be captured as an 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 AEs: 
• If the subject experiences a worsening or complication of an AE (from MLN0002-2003) after 
first administration of the study drug in Vedolizumab-2005, 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 
drug, the worsening or complication should be recorded as a new AE. Investigators should 
ensure that the AE term recorded captures the change in the condition (eg, “worsening 
of…”). 
Changes in severity of AEs: 
• If the subject experiences changes in severity of an AE, the event should be captured once 
with the maximum severity recorded. 
Preplanned surgeries or procedures: 
• Preplanned procedures (surgeries or therapies) that were scheduled prior to signing of 
informed consent are not considered 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 an AE. Complications resulting from any 
planned surgery should be reported as AEs. 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 68 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
Elective surgeries or procedures: 
• Elective procedures performed where there is no change in the subject’s medical condition 
should not be recorded as AEs, but should be documented in the subject’s source documents. 
Complications resulting from an elective surgery should be reported as AEs. 
Insufficient clinical response (lack of efficacy): 
• Insufficient clinical response, efficacy, or pharmacologic action, should NOT be recorded as 
an AE. The investigator must make the distinction between exacerbation of pre-existing 
illness and lack of therapeutic efficacy. 
Overdose: 
• Cases of overdose with any medication without manifested side effects are NOT considered 
AEs, but instead will be documented on an Overdose page of the eCRF. Any manifested side 
effects will be considered AEs and will be recorded on the AE page of the eCRF. 
10.1.3 
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.b). 
For non-commercial use only

9HGROL]XPDE,9
6WXG\1R9HGROL]XPDE
3DJH RI
3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
 6HSWHPEHU 
&21),'(17,$/
7DEOH E
7DNHGD0HGLFDOO\6LJQLILFDQW$(/LVW
7HUP
$FXWHOLYHUIDLOXUH
*URZWKIDLOXUH
$FXWHUHQDOIDLOXUH
*URZWKUHWDUGDWLRQ
$FXWHUHVSLUDWRU\IDLOXUHDFXWHUHVSLUDWRU\GLVWUHVV
V\QGURPH
+HSDWLFQHFURVLV
$JUDQXORF\WRVLV
0DOLJQDQWK\SHUWHQVLRQ
$QDSK\ODFWLFVKRFN
1HXUROHSWLFPDOLJQDQWV\QGURPHPDOLJQDQWK\SHUWKHUPLD
$SODVWLFDQHPLD
3XOPRQDU\ILEURVLV
&RQILUPHGRUVXVSHFWHGHQGRWR[LQVKRFN
3XOPRQDU\K\SHUWHQVLRQ
&RQILUPHGRUVXVSHFWHGWUDQVPLVVLRQRILQIHFWLRXV
DJHQWE\DPHGLFLQDOSURGXFW
6SRQWDQHRXVDERUWLRQVWLOOELUWKDQGIHWDOGHDWK
&RQYXOVLYHVHL]XUH
7RUVDGHGHSRLQWHVYHQWULFXODUILEULOODWLRQYHQWULFXODU
WDFK\FDUGLD
)DLOXUHWRWKULYH
7R[LFHSLGHUPDOQHFURO\VLV6WHYHQV-RKQVRQV\QGURPH

$(6,V
$Q$(6,VHULRXVRUQRQVHULRXVLVDQHYHQWRIVFLHQWLILFDQGPHGLFDOFRQFHUQVSHFLILFWRWKH
FRPSRXQGRUSURJUDPIRUZKLFKRQJRLQJPRQLWRULQJDQGUDSLGFRPPXQLFDWLRQE\WKH
LQYHVWLJDWRUWR7DNHGDPD\EHDSSURSULDWH6XFKHYHQWVPD\UHTXLUHIXUWKHULQYHVWLJDWLRQLQ
RUGHUWRFKDUDFWHUL]HDQGXQGHUVWDQGWKHP

6HYHULW\RI$(V
7KHGLIIHUHQWFDWHJRULHVRILQWHQVLW\VHYHULW\DUHFKDUDFWHUL]HGDVIROORZV
0LOG
7KHHYHQWLVWUDQVLHQWDQGHDVLO\WROHUDWHGE\WKHVXEMHFW
0RGHUDWH
7KHHYHQWFDXVHVWKHVXEMHFWGLVFRPIRUWDQGLQWHUUXSWVWKHVXEMHFW¶VXVXDO
DFWLYLWLHV
6HYHUH
7KHHYHQWFDXVHVFRQVLGHUDEOHLQWHUIHUHQFHZLWKWKHVXEMHFW¶VXVXDODFWLYLWLHV
CCI
For non-commercial use only
VYHQWULF
YHQWU
UPDOQHFU
PDOQHF
se
RIVFLHQW
IVFLHQ
PRQLWRU
PRQLWR
DWH6XFK
WH6XF
WKHP
KHP
c
non
or n

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 70 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
10.1.6 
Causality of AEs 
The relationship of each AE to study drug(s) will be assessed using the following categories: 
Related: 
An AE that follows a reasonable temporal sequence from administration of 
a drug (including the course after withdrawal of the drug), or for which 
possible involvement of the drug can be argued, 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. 
10.1.7 
Relationship to Study Procedures 
Relationship (causality) to study procedures should be determined for all 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. 
10.1.8 
Start Date 
The start date of the AE is the date that the first signs/symptoms were noted by the subject and/or 
physician. 
10.1.9 
Stop Date 
The stop date of the AE is the date at which the subject recovered, the event resolved but with 
sequelae or the subject died. 
10.1.10 Frequency 
Episodic AEs (eg, vomiting) or those which occur repeatedly over a period of consecutive days 
are intermittent. All other events are continuous. 
10.1.11 Action Concerning Study Drug 
• Drug withdrawn – a study drug is stopped due to the particular AE. 
• Dose not changed – the particular AE did not require stopping a study drug. 
• Unknown – only to be used if it has not been possible to determine what action has been 
taken. 
• Not applicable – a study drug was stopped for a reason other than the particular AE eg, the 
study has been terminated, the subject died, dosing with study drug was already stopped 
before the onset of the AE. 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 71 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
• Dose reduced – the dose was reduced due to the particular AE. 
• Dose increased – the dose was increased due to the particular AE. 
• Dose interrupted – the dose was interrupted due to the particular AE. 
10.1.12 Outcome 
• Recovered/Resolved – Subject returned to first assessment status with respect to the AE. 
• 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 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 state remaining “Not 
recovered/not resolved”. 
• Resolved with sequelae – the subject recovered from an acute AE but was left with 
permanent/significant impairment (eg, recovered from a cardiovascular accident but with 
some persisting paresis. 
• Fatal – the AEs which are considered as the cause of death. 
• Unknown – the course of the AE 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 
AE Collection Period 
Collection of AEs will commence from the time the subject is administered study drug in this 
study. Pretreatment events and AEs in the prior study (MLN0002-2003) will be considered 
Medical History in this study (Section 9.1.2). 
Routine collection of AEs will continue until the safety follow-up visit which is 18 weeks after 
the last dose of study drug. 
10.2.1.2 
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.  
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 72 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
All subjects experiencing AEs, whether considered associated with the use of the study drug or 
not, must be monitored until the symptoms subside and any clinically relevant changes in 
laboratory values have returned to baseline or until there is a satisfactory explanation for the 
changes observed. All AEs will be documented in the AE page of the eCRF, whether or not the 
investigator concludes that the event is related to the drug treatment. The following information 
will be documented for each event: 
1. Event term. 
2. Start and stop date. 
3. Severity. 
4. Investigator’s opinion of the causal relationship between the event and administration of 
study drug(s) (related or not related). 
5. Investigator’s opinion of the causal relationship to study procedure(s), including the details 
of the suspected procedure. 
6. Action concerning study drug. 
7. Outcome of event. 
8. Seriousness. 
10.2.1.3 
AE Collection Involving Medically Anticipated Clinical Events 
UC and CD are associated with certain characteristic signs and symptoms including diarrhea, 
rectal bleeding, and abdominal pain that may be present at baseline and persist or fluctuate based 
on the individual subject’s disease history during the course of the study. These signs and 
symptoms will not be collected as AEs. These characteristics of disease activity will be regularly 
captured in the disease severity scores used for UC and CD. 
Exacerbations of disease activity (eg, increase in the daily amount of rectal bleeding or 
abdominal pain beyond the subject’s normal fluctuation, new signs and symptoms of UC and 
CD) will be collected as AEs and reported according to regulatory reporting requirements. 
Extra-intestinal manifestations of the subject’s disease (eg, arthralgia, arthritis, uveitis) that 
develop or worsen during the study are considered AEs. 
10.2.1.4 
AESI Reporting 
If an AESI occurs during the treatment period or the follow-up period and is considered to be 
clinically significant based on the criteria below, it should be recorded in the AESI eCRF or an 
SAE Form. The eCRF or SAE Form should be completed and reported to the SAE reporting 
contact in Section 1.1 within 24 hours. 
For non-commercial use only

9HGROL]XPDE,9
6WXG\1R9HGROL]XPDE
3DJH RI
3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
 6HSWHPEHU 
&21),'(17,$/
CCI
For non-commercial use onlyly
only
e o
use
al u
mer
mm
r no
For 
F

9HGROL]XPDE,9
6WXG\1R9HGROL]XPDE
3DJH RI
3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
 6HSWHPEHU 
&21),'(17,$/
CCI
For non-commercial use only
nly
only
se
l us
cial 
erci
me
omm
com
on
r no
For 
Fo

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 75 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
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 eCRF or SAE Form must be completed, in English, and signed by the 
investigator immediately or within 24 hours of first onset or notification of the event. The 
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 identification number. 
• Investigator’s name. 
• Name of the study drug(s). 
• Causality assessment. 
The SAE eCRF should be transmitted within 24 hours of first onset or notification of the event. 
However, as a back-up, if required, the SAE Form should be completed and reported to the 
attention of the contact listed in Section 1.1. 
Any SAE spontaneously reported to the investigator following the AE collection period should 
be reported to the sponsor if considered related to study participation. 
10.2.3 
Reporting of Abnormal LFTs 
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, follow-up of additional 
information on relevant recent history, risk factors, clinical signs and symptoms and results of 
any additional diagnostic tests performed should be reported appropriately. 
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. Follow-up laboratory tests as described in 
Section 9.1.12 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). 
10.2.4 
Product Complaints 
A product complaint is a verbal, written, or electronic expression that implies dissatisfaction 
regarding the identity, strength, purity, quality, or stability of a drug product. An investigator 
who is made aware of or identifies a potential product complaint should immediately report the 
event to Takeda in accordance with the contact list provided to the site. Whenever possible, the 
associated product should be maintained in accordance with the instructions pending further 
guidance from a Takeda representative. 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 76 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
10.3 
Follow-up of SAEs 
If information not available at the time of the first report becomes available at a later date, the 
investigator should 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 
Special Situations Reporting 
For vedolizumab, pregnancies, and uses not foreseen in the protocol (abuse, misuse, medication 
error, overdose, or other) are subject to the same reporting obligations as adverse drug reactions. 
Any special situation event should be reported to the Pharmacovigilance database using a 
separate paper-based form. Pregnancies are to be reported within 24 hours, with all other special 
situations to be reported within 7 calendar days. 
10.3.2 
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, including the European 
Medicines Agency, 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 and Eudravigilance database, according to EU Regulation No. 
536/2014, 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 study. The investigational site also will forward a copy of all expedited reports to 
his or her IRB or IEC in accordance with national regulations. 
11.0 
STUDY-SPECIFIC COMMITTEE 
11.1 
Adjudication Committee 
A PML IAC will be instituted for this study. The PML IAC will consist of a panel of leading 
PML experts, including a neurologist, neuroradiologist, and a virologist. 
12.0 
DATA HANDLING AND RECORD KEEPING 
The full details of procedures for data handling will be documented in the Data Management 
Plan. AEs, medical history, and concomitant procedures will be coded using the Medical 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 77 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
Dictionary for Regulatory Activities (MedDRA). Drugs will be coded using the World Health 
Organization Drug Dictionary (WHODrug). 
12.1 
eCRFs 
Completed eCRFs are required for each subject who signs an informed consent/assent. 
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 during the conduct of this study to the sponsor and 
regulatory authorities. All eCRFs must be completed in English. Data are transcribed directly 
onto eCRFs. 
After completion of the entry process, computer logic checks will be run to identify items, such 
as inconsistent dates, missing data, and questionable values. Queries may be issued by Takeda 
personnel (or designees) and will be answered by the site. 
The principal investigator must review the eCRFs for completeness and accuracy and must sign 
and date the appropriate eCRFs as indicated. Furthermore, the investigator must retain full 
responsibility for the accuracy and authenticity of all data entered on the eCRFs. 
The eCRFs will be reviewed for completeness and acceptability at the study site during periodic 
visits by study the sponsor or its designee. 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/assent 
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 Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use (ICH) E6 Section 4.9.5 requires the investigator to retain 
essential documents until at least 2 years after the last approval of a marketing application for a 
specified drug indication being investigated or, if an application is not approved, until at least 
2 years after the investigation is discontinued and regulatory authorities are notified. In addition, 
ICH E6 Section 4.9.5 states that the study records should be retained until an amount of time 
specified by applicable regulatory requirements or for a time specified in the Clinical Study Site 
Agreement between the investigator and sponsor. 
For non-commercial use only

9HGROL]XPDE,9
6WXG\1R9HGROL]XPDE
3DJH RI
3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
 6HSWHPEHU 
&21),'(17,$/
5HIHUWRWKH&OLQLFDO6WXG\6LWH$JUHHPHQWIRUWKHVSRQVRU¶VUHTXLUHPHQWVRQUHFRUGUHWHQWLRQ
7KHLQYHVWLJDWRUVKRXOGFRQWDFWDQGUHFHLYHZULWWHQDSSURYDOIURPWKHVSRQVRUEHIRUHGLVSRVLQJ
RIDQ\VXFKGRFXPHQWV

6DPSOH5HWHQWLRQDQG8VH
6HUXPVDPSOHVFROOHFWHGDVSDUWRIWKHVWXG\ZLOOEHVWRUHGDQGPD\EHXVHGIRUIXWXUHUHVHDUFK
SXUSRVHVXSWR\HDUVDIWHUWKHGDWHRIVWXG\FRPSOHWLRQ6DPSOHVZLOOEHGHVWUR\HGE\DWKLUG
SDUW\YHQGRUSHUFRPSDQ\VWDQGDUGRSHUDWLQJSURFHGXUHV6DPSOHVZLOOEHVWRUHGDFFRUGLQJWR
WKHODERUDWRU\PDQXDO,IDSDUWLFLSDQWZLWKGUDZVFRQVHQWIRUIXWXUHXVHRIVDPSOHVWKH
LQYHVWLJDWRUPXVWLQIRUPWKHVSRQVRULPPHGLDWHO\DQGWKHVDPSOHVZLOOEHGLVFDUGHGIROORZLQJ
WKHORFDOSURFHGXUHLHZKHUHWKHVDPSOHUHVLGHVDWWKHWLPHRIZLWKGUDZDO7KHWHVWVSHUIRUPHG
ZLWKWKHVHVDPSOHVDUHQRWLQWHQGHGWRPDNH GHWHUPLQDWLRQVDERXWDSDUWLFLSDQW¶VKHDOWKRUWKH
OLNHOLKRRGWKDWDSDUWLFLSDQWZLOOGHYHORSDQ\GLVHDVHVRQRWHVWUHVXOWVZLOOEHSURYLGHGWRWKH
LQYHVWLJDWRURUSXWLQWRDSDUWLFLSDQW¶VPHGLFDOUHFRUG7HVWUHVXOWVVKRXOGQRWEHGLVFXVVHGZLWKD
SDUWLFLSDQWXQOHVVUHTXLUHGE\ORFDOODZ

67$7,67,&$/0(7+2'6

6WDWLVWLFDODQG$QDO\WLFDO3ODQV
7KHVWDWLVWLFDODQDO\VLVSODQZLOOEHILQDOL]HGSULRUWRWKHILUVWLQWHULPDQDO\VLV7KLVGRFXPHQW
ZLOOSURYLGHIXUWKHUGHWDLOVUHJDUGLQJWKHGHILQLWLRQRIDQDO\VLVYDULDEOHVDQGDQDO\VLV
PHWKRGRORJ\WRDGGUHVVDOOVWXG\REMHFWLYHV'DWDZLOOEHDQDO\]HGE\LQGLFDWLRQ

$QDO\VLV6HWV
7KHIXOODQDO\VLVVHW)$6ZLOOLQFOXGHDOOHQUROOHGVXEMHFWVZKRUHFHLYHDWOHDVWGRVHRIVWXG\
GUXJDQGZLOOEHXVHGLQERWKHIILFDF\DQGVDIHW\DQDO\VHV

$QDO\VLVRI'HPRJUDSKLFVDQG2WKHU%DVHOLQH&KDUDFWHULVWLFV
'HPRJUDSKLFDQGEDVHOLQHFKDUDFWHULVWLFVZLOOEHVXPPDUL]HGGHVFULSWLYHO\E\GRVHUHJLPHQDQG
RYHUDOOEDVHGRQDOOHQUROOHGVXEMHFWV)RUFRQWLQXRXVYDULDEOHVVXPPDU\VWDWLVWLFVQRQPLVVLQJ
YDOXHVPHDQPHGLDQ6'PLQLPXPDQGPD[LPXPZLOOEHJHQHUDWHG)RUFDWHJRULFDOYDULDEOHV
WKHFRXQWVDQGSHUFHQWDJHVRIHDFKSRVVLEOHYDOXHZLOOEHJHQHUDWHG
0HGLFDOKLVWRU\ZLOOEHVXPPDUL]HGE\V\VWHPRUJDQFODVVDQGSUHIHUUHGWHUP0HGLFDWLRQ
KLVWRU\DQGFRQFRPLWDQWPHGLFDWLRQVZLOOEHVXPPDUL]HGE\WKHUDSHXWLFFODVVDQG SUHIHUUHG
QDPH
CCI
For non-commercial use only
XOWVVKR
WVVK
SULRUWRW
ULRUWR
HILQLWLRQ
ILQLWLR
WLYHV'D
YHV'
OOLQFOXG
OOLQFOX
K HIILFD
HIILF

9HGROL]XPDE,9
6WXG\1R9HGROL]XPDE
3DJH RI
3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
 6HSWHPEHU 
&21),'(17,$/

6DIHW\$QDO\VLV
7KHSULPDU\REMHFWLYHRIWKHVWXG\LVWRGHWHUPLQHWKHVDIHW\SURILOHRIORQJWHUPYHGROL]XPDE
,9WUHDWPHQWLQSHGLDWULFVXEMHFWVZLWK8&RU&'6DIHW\DQDO\VHVZLOOEHSHUIRUPHGXVLQJWKH
)$66DIHW\GDWDZLOOEHVXPPDUL]HGE\GRVHUHJLPHQDQGYDULRXVVXEJURXSVLQFOXGLQJE\
LQGLFDWLRQ8&RU&'1RVWDWLVWLFDOLQIHUHQFHZLOOEHPDGHIRUVDIHW\DQDO\VHV
7UHDWPHQWHPHUJHQW$(V7($(VDUHXQGHVLUDEOHHYHQWVQRWSUHVHQWSULRUWRPHGLFDOWUHDWPHQW
RUDQDOUHDG\SUHVHQWHYHQWWKDWZRUVHQVHLWKHULQLQWHQVLW\RUIUHTXHQF\IROORZLQJWKHWUHDWPHQW
RFFXUULQJIURPWKHILUVWGRVHRIVWXG\GUXJWRWKHGD\RIODVWGRVHRIVWXG\GUXJGD\V
DFFRXQWLQJIRUWLPHVWKHKDOIOLIHRIYHGROL]XPDE 7KHQXPEHUDQGSHUFHQWDJHRIVXEMHFWV
ZLWK7($(VGHILQHGDVDQ\$(UHJDUGOHVVRIUHODWLRQVKLSWRVWXG\GUXJ

$(VOHDGLQJWR
GLVFRQWLQXDWLRQDQG6$(VWKDWRFFXURQRUDIWHUWKHILUVWGRVHGDWHDQGXSWR ZHHNVDIWHUWKH
ODVWGRVHGDWHRIWKHVWXG\GUXJZLOOEHVXPPDUL]HGE\0HG'5$V\VWHPRUJDQFODVVKLJKOHYHO
WHUPDQGSUHIHUUHGWHUP7($(VZLOODOVREHVXPPDUL]HGE\VHYHULW\DQGE\UHODWLRQVKLSWR
VWXG\GUXJ6HSDUDWHVXPPDULHVZLOOEHJHQHUDWHGIRUWUHDWPHQWUHODWHG$(VRYHUDOODQGE\
VHYHULW\([SRVXUHDGMXVWHGLQFLGHQFHUDWHVZLOODOVREHDQDO\]HG
3K\VLFDOH[DPLQDWLRQILQGLQJV
ZLOOEHSUHVHQWHGLQGDWDOLVWLQJV

(IILFDF\$QDO\VLV
CCI
CCI
CCI
CCI
CCI
For non-commercial use only
$V\V
$V\
VHYHULW\
HYHULW
PHQW
PHQWUHO
UH
DQDO\]H
QDO\]
ial u
ercia
omm
r no
F

9HGROL]XPDE,9
6WXG\1R9HGROL]XPDE
3DJH RI
3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
 6HSWHPEHU 
&21),'(17,$/


2WKHU$QDO\VHV
6HFRQGDU\REMHFWLYHVRIWKHVWXG\LQFOXGHGHWHUPLQLQJWKHHIIHFWRQSDWWHUQVRIJURZWKDQG
GHYHORSPHQWKHDOWKUHODWHGTXDOLW\RIOLIH PHDVXUHPHQWVDQGWLPHWRPDMRU,%'UHODWHGHYHQWV
7LPHWRPDMRU,%'UHODWHGHYHQWVKRVSLWDOL]DWLRQVVXUJHULHVDQGSURFHGXUHVZLOOEHDQDO\]HG
DQG.DSODQ0HLHUHVWLPDWHVSUHVHQWHGHYHU\ZHHNV
&KDQJHIURP%DVHOLQHLQ,03$&7,,,WRWDODQGVXEVFDOHVFRUHVKHLJKW
ZHLJKW
DQG%0,ZLOOEHVXPPDUL]HGGHVFULSWLYHO\E\GRVHUHJLPHQ+HLJKWYHORFLW\ZLOOEHVXPPDUL]HG
E\YLVLW7KHSHUFHQWDJHRIVXEMHFWVDFKLHYLQJ7DQQHUVWDJH9DWRUEHIRUHDJH\HDUVIHPDOHV
RU\HDUVPDOHVZLOOEHVXPPDUL]HGE\GRVHUHJLPHQ
CCI
CCI
CCI
For non-commercial use only
GS
FRUHV
RUHV K
LPHQ+
PHQ+
HUVWDJH9
VWDJH
HJLPHQ
JLPHQ
om
-co
or n
For

9HGROL]XPDE,9
6WXG\1R9HGROL]XPDE
3DJH RI
3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
 6HSWHPEHU 
&21),'(17,$/

,QWHULP$QDO\VLV
6HYHUDOLQWHULPDQDO\VHVPD\EHFRQGXFWHGWRVXSSRUWIXWXUHSHGLDWULFVWXGLHV7KHVHPD\RFFXU
 ZKHQDOO VXEMHFWVLQWKHNJZHLJKWJURXSKDYHFRPSOHWHG:HHNRUZLWKGUDZQIURPWKH
VWXG\RUZKHQDOOVXEMHFWVLQWKHNJZHLJKWJURXSKDYHFRPSOHWHG:HHNRUZLWKGUDZQ
IURPWKHVWXG\7KHSXUSRVHRIFRQGXFWLQJLQWHULPDQDO\VHVZRXOGEHWRJDLQLQWHUPHGLDWH
LQIRUPDWLRQRQ
HIILFDF\DQGVDIHW\DQGUHVXOWVPD\EHXVHGWRLQIRUPGHVLJQDQGGRVH
VHOHFWLRQIRURWKHUSHGLDWULFVWXGLHV7KHUHLVQRLQWHQWLRQIRUHDUO\WULDOWHUPLQDWLRQEDVHGRQWKH
UHVXOWVRIWKHLQWHULPDQDO\VLV RWKHUWKDQVDIHW\FRQFHUQV

'HWHUPLQDWLRQRI6DPSOH6L]H
'XHWRQRK\SRWKHVLVWHVWLQJWKHUHZHUHQRIRUPDOVDPSOHVL]HFDOFXODWLRQVGRQHIRUWKLVVWXG\,W
LVHVWLPDWHGWKDWXSWRVXEMHFWVZLWK8&DQGZLWK&'ZKRFRPSOHWHG
6WXG\ 0/1 ZLOOHQWHUWKLVVWXG\

48$/,7<&21752/$1'48$/,7<$6685$1&(

6WXG\6LWH0RQLWRULQJ9LVLWV
0RQLWRULQJYLVLWVWRWKHVWXG\VLWHZLOOEHPDGHSHULRGLFDOO\GXULQJWKHVWXG\WRHQVXUHWKDWDOO
DVSHFWVRIWKHSURWRFRODUHIROORZHG6RXUFHGRFXPHQWVZLOOEHUHYLHZHGIRUYHULILFDWLRQRIGDWD
UHFRUGHGRQWKHH&5)V6RXUFHGRFXPHQWVDUHGHILQHGDVRULJLQDOGRFXPHQWVGDWDDQGUHFRUGV
7KHLQYHVWLJDWRUDQGLQVWLWXWLRQJXDUDQWHHDFFHVVWRVRXUFHGRFXPHQWVE\WKHVSRQVRURULWV
GHVLJQHHFRQWUDFWUHVHDUFKRUJDQL]DWLRQDQGE\WKH,5%RU,(&
$OODVSHFWVRIWKHVWXG\DQGLWVGRFXPHQWDWLRQZLOOEHVXEMHFWWRUHYLHZE\WKHVSRQVRURU
GHVLJQHHLQFOXGLQJEXWQRWOLPLWHGWRWKH,QYHVWLJDWRU¶V%LQGHUVWXG\GUXJVXEMHFWPHGLFDO
UHFRUGVLQIRUPHGFRQVHQWDVVHQWGRFXPHQWDWLRQGRFXPHQWDWLRQRIVXEMHFWDXWKRUL]DWLRQWRXVH
SHUVRQDOKHDOWKLQIRUPDWLRQLIVHSDUDWHIURPWKHLQIRUPHGFRQVHQWDVVHQWIRUPVDQGUHYLHZRI
H&5)VDQGDVVRFLDWHGVRXUFHGRFXPHQWV,WLVLPSRUWDQWWKDWWKHLQYHVWLJDWRUDQGRWKHUVWXG\
SHUVRQQHODUHDYDLODEOHGXULQJWKHPRQLWRULQJYLVLWVDQGWKDWVXIILFLHQWWLPHLVGHYRWHGWRWKH
SURFHVV
,QWKHHYHQWDPRQLWRUFDQQRWYLVLWWKHVLWHLQDWLPHO\PDQQHUGXHWRWKH&29,'SDQGHPLF
DOWHUQDWLYHPRQLWRULQJDSSURDFKHVVXFKDVUHPRWHVRXUFHGDWDYHULILFDWLRQRUWHOHSKRQHFRQWDFW
PD\EHXVHG$OWHUQDWLYHPRQLWRULQJDSSURDFKHVVKRXOGEHXVHGRQO\ZKHUHDOORZHGE\WKHORFDO
KHDOWKDXWKRULW\DQGSHUPLWWHGE\WKH,5%,(&LIUHTXLUHG
CCI
CCI
CCI
CCI
For non-commercial use only
S
XOGEH
OGE
VHG
HGWRLQ
WRLQ
IRUHDUO\
UHDU
QV
V
RUPDOVD
UPDOV
K8&DQG
8&DQ
XG\
G\
$1'48
1'4
ULQJ9LV
ULQJ9
VLWL

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 82 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
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. 
The sponsor will assess any protocol deviation; if it is likely to affect to a significant degree the 
safety and rights of a subject or the reliability and robustness of the data generated, it will be 
reported to regulatory authorities as a serious breach of GCP and the protocol. 
Takeda will notify the concerned EU Member States of a serious breach of EU Clinical Trial 
Regulation (CTR) or the applicable protocol version through the EU portal not later than 7 days 
after becoming aware of the breach. In this instance a “serious breach” is one likely to affect to a 
significant degree the safety and rights of a participant or the reliability and robustness of trial 
data. All parties involved in the conduct of the clinical trial must immediately report any events 
they encounter that might meet the definition of a serious breach to the contact point designated 
in the applicable study document. 
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. 
15.0 
ETHICAL ASPECTS OF THE STUDY 
This study will be conducted with the highest respect for the individual participants (ie, subjects) 
according to the protocol, the ethical principles that have their origin in the Declaration of 
Helsinki, and the ICH Harmonised Tripartite Guideline for GCP. Each investigator will conduct 
the study according to applicable local or regional regulatory requirements and align his or her 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 83 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
conduct in accordance with the “Responsibilities of the Investigator” that are listed in 
Appendix B. The principles of Helsinki are addressed through the protocol and through 
appendices containing requirements for informed consent and investigator responsibilities. 
15.1 
IRB and/or IEC Approval 
IRBs and IECs must be constituted according to the applicable requirements of each 
participating region. The sponsor or designee will require documentation noting all names and 
titles of members who make up the respective IRB 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 notify the 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 study. Until the site 
receives notification from the sponsor or its designee, 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/pediatric assent 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/assent form, subject 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 84 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
authorization form (if applicable), and subject information sheet (if applicable) describe the 
planned and permitted uses, transfers, and disclosures of the subject’s personal and personal 
health information for purposes of conducting the study. The informed consent/assent 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/assent is given. The 
informed consent/assent 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/assent form and if applicable, the subject authorization form. The informed 
consent/assent 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/assent 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/assent 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/assent, then the 
subject’s legally authorized representative may provide such consent/assent for the subject in 
accordance with applicable laws and regulations. 
The subject, or the subject’s legally authorized 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 authorized representative, determines he or she will 
participate in the study, then the informed consent/assent form and subject authorization form (if 
applicable) must be signed and dated by the subject, or the subject’s legally authorized 
representative, at the time of consent/assent and prior to the subject entering into the study. The 
subject or the subject’s legally authorized 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/assent form and subject authorization (if applicable) at the time of 
consent/assent 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/assent 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/assent in the 
subject’s medical record. Copies of the signed informed consent/assent form, the signed subject 
authorization form (if applicable), and subject information sheet (if applicable) shall be given to 
the subject. 
All revised informed consent/assent forms must be reviewed and signed by relevant subjects or 
the relevant subject’s legally authorized representative in the same manner as the original 
informed consent/assent. The date the revised consent/assent was obtained should be recorded in 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 85 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
the subject’s medical record, and the subject should receive a copy of the revised informed 
consent/assent form. 
15.2.1 
Informed Consent for Use of Remaining Samples 
Consent will be obtained separately for the future use of samples. Those not consenting to the 
future use of samples, or withdrawing consent for this at any time, will be able to participate in 
all other portions of the trial unimpeded and without bias to their care. 
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 identification 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 identification number. 
In the event that a serious data breach is detected, the sponsor or its designee and the investigator 
(as applicable) will take appropriate corrective and preventative actions in response. These 
actions will be documented, and the relevant regulatory agency(ies) will be notified as 
appropriate. Where appropriate, the relevant individuals materially affected by the breach would 
also be notified; in the case of study subjects, this would be done through the investigator. 
Takeda applies certain measures to protect participants’ personal data and prevent data breaches, 
detailed in a separate document (Compliance with National Requirements on Data Protection). 
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/pediatric assent 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 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 86 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
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 US investigators), country, and 
recruiting status will be registered and available for public viewing. 
For some registries, Takeda will assist callers in locating trial sites closest to their homes by 
providing the investigator name, address, and phone number to the callers requesting trial 
information. Once 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. 
EU has a specific demographic breakdown that is required for all studies by age and enrollment 
by country. For this study, children (aged 2 to 11 years) and adolescents (aged 12 to 17 years) 
will be summarized. 
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 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 87 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
compensation and treatment for injury. If the investigator has questions regarding this policy, he 
or she should contact the sponsor or sponsor’s designee. 
 
For non-commercial use only

  
Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 88 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
16.0 
REFERENCES 
Abbvie 2017. Humira (adalimumab) injection for  subcutaneous use. Prescribing Information. 
Amre, D. K., Lu, S. E., Costea, F. and Seidman, E. G. 2006. Utility of serological markers in 
predicting the early occurrence of complications and surgery in pediatric Crohn's disease 
patients. Am J Gastroenterol, 101(3), 645-52. 
Benchimol, E. I., Fortinsky, K. J., Gozdyra, P., Van den Heuvel, M., Van Limbergen, J. and 
Griffiths, A. M. 2011. Epidemiology of pediatric inflammatory bowel disease: a 
systematic review of international trends. Inflamm Bowel Dis, 17(1), 423-39. 
Briskin, M., Winsor-Hines, D., Shyjan, A., Cochran, N., Bloom, S., Wilson, J., et al. 1997. 
Human mucosal addressin cell adhesion molecule-1 is preferentially expressed in 
intestinal tract and associated lymphoid tissue. Am J Pathol, 151(1), 97-110. 
Butcher, E. C., Williams, M., Youngman, K., Rott, L. and Briskin, M. 1999. Lymphocyte 
trafficking and regional immunity. Adv Immunol, 72, 209-53. 
Chande, N., MacDonald, J. K. and McDonald, J. W. 2007. Methotrexate for induction of 
remission in ulcerative colitis. Cochrane Database Syst Rev, (4), CD006618. 
da Silva, B. C., Lyra, A. C., Rocha, R. and Santana, G. O. 2014. Epidemiology, demographic 
characteristics and prognostic predictors of ulcerative colitis. World J Gastroenterol, 
20(28), 9458-67. 
El-Matary, W., Vandermeer, B. and Griffiths, A. M. 2009. Methotrexate for maintenance of 
remission in ulcerative colitis. Cochrane Database Syst Rev, (3), CD007560. 
Erle, D. J., Briskin, M. J., Butcher, E. C., Garcia-Pardo, A., Lazarovits, A. I. and Tidswell, M. 
1994. Expression and function of the MAdCAM-1 receptor, integrin alpha 4 beta 7, on 
human leukocytes. J Immuno, 153(2), 517-28. 
Feagan, B. G., Rutgeerts, P., Sands, B. E., Hanauer, S., Colombel, J. F., Sandborn, W. J., et al. 
2013. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J 
Med, 369(8), 699-710. 
Heyman, M. B., Kirschner, B. S., Gold, B. D., Ferry, G., Baldassano, R., Cohen, S. A., et al. 
2005. Children with early-onset inflammatory bowel disease (IBD): analysis of a 
pediatric IBD consortium registry. J Pediatr, 146(1), 35-40. 
Higuchi, L. and Bousvaros, A. 2004. Ulcerative Colitis. In: Guandalini, S. (ed.) Textbook of 
Pediatric Gastroenterology and Nutrition. London: Taylor & Francis, p. 385-409. 
IBD Working Group of the European Society for Paediatric Gastroenterology, H. and Nutrition 
2005. Inflammatory bowel disease in children and adolescents: recommendations for 
diagnosis--the Porto criteria. J Pediatr Gastroenterol Nutr, 41(1), 1-7. 
Kader, H. A., Mascarenhas, M. R., Piccoli, D. A., Stouffer, N. O. and Baldassano, R. N. 1999. 
Experiences with 6-mercaptopurine and azathioprine therapy in pediatric patients with 
severe ulcerative colitis. J Pediatr Gastroenterol Nutr, 28(1), 54-8. 
Kappelman, M. D., Moore, K. R., Allen, J. K. and Cook, S. F. 2013. Recent trends in the 
prevalence of Crohn's disease and ulcerative colitis in a commercially insured US 
population. Dig Dis Sci, 58(2), 519-25. 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 89 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
Kugathasan, S., Judd, R. H., Hoffmann, R. G., Heikenen, J., Telega, G., Khan, F., et al. 2003. 
Epidemiologic and clinical characteristics of children with newly diagnosed 
inflammatory bowel disease in Wisconsin: a statewide population-based study. J Pediatr, 
143(4), 525-31. 
Loftus, E. V., Jr. 2004. Clinical epidemiology of inflammatory bowel disease: Incidence, 
prevalence, and environmental influences. Gastroenterology, 126(6), 1504-17. 
Marshall, W. A. and Tanner, J. M. 1969. Variations in pattern of pubertal changes in girls. Arch 
Dis Child, 44(235), 291-303. 
Marshall, W. A. and Tanner, J. M. 1970. Variations in the pattern of pubertal changes in boys. 
Arch Dis Child, 45(239), 13-23. 
Molodecky, N. A., Soon, I. S., Rabi, D. M., Ghali, W. A., Ferris, M., Chernoff, G., et al. 2012. 
Increasing incidence and prevalence of the inflammatory bowel diseases with time, based 
on systematic review. Gastroenterology, 142(1), 46-54.e42; quiz e30. 
Motil, K. J., Grand, R. J., Davis-Kraft, L., Ferlic, L. L. and Smith, E. O. 1993. Growth failure in 
children with inflammatory bowel disease: a prospective study. Gastroenterology, 
105(3), 681-91. 
Nieuwenhuis, E. E. and Escher, J. C. 2008. Early onset IBD: what's the difference? Dig Liver 
Dis, 40(1), 12-5. 
Prefontaine, E., Sutherland, L. R., Macdonald, J. K. and Cepoiu, M. 2009. Azathioprine or 6-
mercaptopurine for maintenance of remission in Crohn's disease. Cochrane Database 
Syst Rev, (1), CD000067. 
Salmi, M. and Jalkanen, S. 2005. Lymphocyte homing to the gut: attraction, adhesion, and 
commitment. Immunol Rev, 206, 100-13. 
Sandborn, W. J., Feagan, B. G., Rutgeerts, P., Hanauer, S., Colombel, J. F., Sands, B. E., et al. 
2013. Vedolizumab as induction and maintenance therapy for Crohn's disease. N Engl J 
Med, 369(8), 711-21. 
Sands, B. E., Feagan, B. G., Rutgeerts, P., Colombel, J. F., Sandborn, W. J., Sy, R., et al. 2014. 
Effects of Vedolizumab Induction Therapy for Patients With Crohn's Disease in Whom 
Tumor Necrosis Factor Antagonist Treatment Had Failed. Gastroenterology. 
Shivananda, S., Lennard-Jones, J., Logan, R., Fear, N., Price, A., Carpenter, L. and van 
Blankenstein, M. 1996. Incidence of inflammatory bowel disease across Europe: is there 
a difference between north and south? Results of the European Collaborative Study on 
Inflammatory Bowel Disease (EC-IBD). Gut, 39(5), 690-7. 
Soler, D., Chapman, T., Yang, L. L., Wyant, T., Egan, R. and Fedyk, E. R. 2009. The binding 
specificity and selective antagonism of vedolizumab, an anti-alpha4beta7 integrin 
therapeutic antibody in development for inflammatory bowel diseases. J Pharmacol Exp 
Ther, 330(3), 864-75. 
Trallori, G., Palli, D., Saieva, C., Bardazzi, G., Bonanomi, A. G., d'Albasio, G., et al. 1996. A 
population-based study of inflammatory bowel disease in Florence over 15 years (1978-
92). Scand J Gastroenterol, 31(9), 892-9. 
Turunen, P., Kolho, K. L., Auvinen, A., Iltanen, S., Huhtala, H. and Ashorn, M. 2006. Incidence 
of inflammatory bowel disease in Finnish children, 1987-2003. Inflamm Bowel Dis, 
12(8), 677-83. 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 90 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
Weiss, B., Lerner, A., Shapiro, R., Broide, E., Levine, A., Fradkin, A. and Bujanover, Y. 2009. 
Methotrexate treatment in pediatric Crohn disease patients intolerant or resistant to purine 
analogues. J Pediatr Gastroenterol Nutr, 48(5), 526-30. 
 
 
 
 
 
 
 
 
For non-commercial use only

9HGROL]XPDE,9
6WXG\1R9HGROL]XPDE
3DJH RI
3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
 6HSWHPEHU 
&21),'(17,$/
$SSHQGL[ $
6FKHGXOHRI6WXG\3URFHGXUHV
6WXG\3URFHGXUHV
3UHHQUROOPHQWD
<HDUWKURXJKF
8QVFKHGXOHG9LVLWH
)LQDO9LVLW
(79LVLW I
)ROORZ8S6DIHW\9LVLW
I
'D\
ZN
E
:HHNVGD\VG











































































F

GD\V

ZN
,QIRUPHGFRQVHQWSHGLDWULF
DVVHQWJ
;
,QFOXVLRQH[FOXVLRQ
;
30/ZDOOHWFDUG
;
$OOHUJ\UHDFWLRQFDUG
;
'HPRJUDSKLFV
3
0HGLFDOKLVWRU\K
3
;
0HGLFDWLRQKLVWRU\
3
;
8&&'SULRUELRORJLFVKLVWRU\
3
,57GUXJGLVSHQVLQJ
;
;
;
;
;
;
;
;
;
;
;
;
;
;
'RVLQJL
;
;
;
;
;
;
;
;
;
;
;
;
;
;
3K\VLFDOH[DPLQDWLRQMN
3
;
;
;
;
;
;
;
;
;
;
;
;
;
;
;
;
;
:HLJKWNO
3
;
;
;
;
;
;
;
;
;
;
;
;
;
;
;
;
;
+HLJKWN
3
;
;
;
;
;
;
;
;
;
;
;
;
;
;
;
;
;
9LWDOVLJQVN
3
;
;
;
;
;
;
;
;
;
;
;
;
;
;
;
;
;
&RQFRPLWDQWPHGLFDWLRQVQ
3
;
;
;
;
;
;
;
;
;
;
;
;
;
;
;
;
;
&RQFRPLWDQWSURFHGXUHVQ
3
;
;
;
;
;
;
;
;
;
;
;
;
;
;
;
;
;
$(DVVHVVPHQWK
3
;
;
;
;
;
;
;
;
;
;
;
;
;
;
;
;
;
6$(DVVHVVPHQWK
3
;
;
;
;
;
;
;
;
;
;
;
;
;
;
;
;
;
)RRWQRWHVDUHRQODVWWDEOHSDJH
CCI
For non-commercial use only


l



ly
onl


on
on
on
on


e o
us
o
l u
cia u
cicicici
er
m
m
co
co
co
co
co
n-c
on
no
;
n
;
For
F

9HGROL]XPDE,9
6WXG\1R9HGROL]XPDE
3DJH RI
3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
 6HSWHPEHU 
&21),'(17,$/
$SSHQGL[$
6FKHGXOHRI6WXG\3URFHGXUHVFRQWLQXHG
6WXG\3URFHGXUHV
3UHHQUROOPHQWD
<HDUWKURXJKF
8QVFKHGXOHG9LVLWH
)LQDO9LVLW
(79LVLW I
)ROORZ8S
6DIHW\9LVLW
I
'D\
ZN
E
:HHNVGD\VG








































GD\V
ZN




































F
7DQQHUVWDJHHYDOXDWLRQ
;
7REHFRPSOHWHGTZHHNV:N

DQG
;
8ULQHSUHJQDQF\WHVWR
;
;
;
;
;
;
;
;
;
;
;
;
;
;
;
;
;
&OLQLFDOFKHPLVWU\
3
7REHFRPSOHWHGTZHHNV:N

DQG
;
;
;
+HPDWRORJ\S
3
7REHFRPSOHWHGTZHHNV:N

DQG 
;
;
;
)HFDOFDOSURWHFWLQV
;
7REHFRPSOHWHGTZHHNV:NVDQG

;
;
6WRROVDPSOHIRUFXOWXUHW
;
6XEMHFWGLDU\GLVSHQVHGX
;
;
;
;
;
;
;
;
;
;
;
;
;
;
;
38&$,Y
;
;
;
;
;
;
;
;
;
;
;
;
;
;
;
;
3&'$,Y
;
7REHFRPSOHWHGTZHHNV:N

DQG 
;
;
CCI
CCI
non-co
ZHHNV:
ZHHNV:


commercial use only



y



nly
o



o
u
o






 
us
;
erc
rc
rc
m rc
:N
N




me
co
For n

9HGROL]XPDE,9
6WXG\1R9HGROL]XPDE
3DJH RI
3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
 6HSWHPEHU 
&21),'(17,$/
6WXG\3URFHGXUHV
3UHHQUROOPHQWD
<HDUWKURXJKF
8QVFKHGXOHG9LVLWH
)LQDO9LVLW
(79LVLW I
)ROORZ8S
6DIHW\9LVLW
I
'D\
ZN
E
:HHNVGD\VG








































GD\V
ZN




































F
3DUWLDO0D\R 8&VXEMHFWV
;
;
;
;
;
;
;
;
;
;
;
;
;
;
;
;
&RPSOHWH0D\R[ 8&
VXEMHFWV6(6&'&'
VXEMHFWV
7REHFRPSOHWHGDW:HHN
;
&'$,\
7REHFRPSOHWHGDW:HHN
,03$&7,,,]
;
7REHFRPSOHWHGTZHHNV:NV 
DQG 
G GD\ZN ZHHN
D3 SUHYLRXVGDWDREWDLQHGIURP6WXG\0/1
E 'D\ZLOOEHDIWHUFRPSOHWLRQRI0/1:HHNDVVHVVPHQWVRUXSWRZHHNDIWHU,IWKH0/1:HHNDQG9HGROL]XPDE'D\YLVLWV
FRLQFLGHWKH'D\SURFHGXUHVGRQRWQHHGWREHUHSHDWHG
F 'XUDWLRQRIYHGROL]XPDE,9WUHDWPHQWZLOOYDU\E\VXEMHFWRQWKHEDVLVRIFRQWLQXHGEHQHILWEXWZLOOEHXQWLOYHGROL]XPDE,9LVDYDLODEOHIRUSHGLDWULFLQGLFDWLRQVLQ
WKHVXEMHFW¶VFRXQWU\RUXQWLORWKHUGUXJDFFHVVSURJUDPVEHFRPHDYDLODEOHZKLFKHYHUFRPHVILUVWWKHVXEMHFWWXUQV\HDUVRIDJHDQGFDQEHWUDQVLWLRQHGWR
FRPPHUFLDOGUXJWKHVXEMHFWZLWKGUDZVIURPWKHVWXG\RUWKHVSRQVRUGHFLGHVWRFORVHWKHVWXG\
G,IDFOLQLFYLVLWPXVWEHFRQGXFWHGYLDDOWHUQDWLYHPHWKRGVEHFDXVHRIDSDQGHPLFHJFRURQDYLUXVSDQGHPLF VDIHW\ODERUDWRU\DVVHVVPHQWVPD\EHGRQHXVLQJ
ORFDOODERUDWRULHVLILWLVIHDVLEOHIRUWKHVXEMHFWWRYLVLWDORFDOODERUDWRU\VRRQHUWKDQWKHVWXG\VLWHIRUVDPSOHFROOHFWLRQ6HH6HFWLRQ IRUJXLGDQFHRQDOWHUQDWLYH
PHWKRGVIRUFRQGXFWLQJVWXG\SURFHGXUHVGXHWRDSDQGHPLF
H6XEMHFWVVHHQDWDQXQVFKHGXOHGYLVLWIRUGLVHDVHH[DFHUEDWLRQZLOOFRPSOHWHDOORIWKHXQVFKHGXOHGYLVLWDVVHVVPHQWV2WKHUXQVFKHGXOHGYLVLWVPD\LQFOXGH
FRQFRPLWDQWPHGLFDWLRQVYLWDOVLJQVFOLQLFDOODERUDWRU\EORRGGUDZVXULQHVDPSOHDQG$(FROOHFWLRQDVDSSURSULDWH
I6XEMHFWVZKRGLVFRQWLQXHGIURPWKHVWXG\IRUDQ\UHDVRQZLOOFRPSOHWHWKH(79LVLW$OOVXEMHFWVZLOOFRPSOHWHD)LQDO6DIHW\9LVLWZHHNVZHHNDIWHUWKHLUODVW
GRVHRIVWXG\GUXJDVZHOODVWKHORQJWHUPIROORZXSVDIHW\VXUYH\E\WHOHSKRQHPRQWKVDIWHUWKHLUODVWGRVHRIVWXG\GUXJ
CCI
CCI
CCI
For non-com

ommercial use only

y


ly
o y
;
e o
om
ZHHNV
ZHHN
 

n
r n
ercial use
me
mm
co
n-c
CCI

9HGROL]XPDE,9
6WXG\1R9HGROL]XPDE
3DJH RI
3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
 6HSWHPEHU 
&21),'(17,$/
J,QIRUPHGFRQVHQWDVVHQWPD\EHREWDLQHGVWDUWLQJDW:HHNRI0/1'HSHQGLQJRQUHOHYDQWUHJXODWRU\JXLGHOLQHVWKHVXEMHFWPD\QHHGWRUHSURYLGH
LQIRUPHGFRQVHQWDVDQDGXOWGXULQJWKLVVWXG\
K&ROOHFWLRQRI$(VDQG6$(VZLOOFRPPHQFHIURPWKHWLPHWKHVXEMHFWLVDGPLQLVWHUHGVWXG\GUXJLQWKLVVWXG\DQGZLOOFRQWLQXHWKURXJK)LQDO6DIHW\9LVLW$(6$(
DVVHVVPHQWPXVWEHFRQGXFWHGRQ'D\LIWKHSUHYLRXVGDWDREWDLQHGIURP6WXG\0/1ZDVFROOHFWHGEHIRUH'D\ (YHQWVWKDWZHUHUHSRUWHGDV$(VRU
6$(VLQ6WXG\0/1QHHGWREHUHFRUGHGRQWKH0HGLFDO+LVWRU\IRU6WXG\9HGROL]XPDE(YHQWVWKDWZHUHUHSRUWHGDV$(VRU6$(VLQ6WXG\
0/1WKDWZHUHRQJRLQJDWWKHHQGRIWKDWVWXG\QHHGWREHUHUHFRUGHGDV$(VIRU6WXG\9HGROL]XPDELIWKH\FKDQJHLQVHYHULW\
L6XEMHFWVZLOOLQLWLDOO\UHFHLYHYHGROL]XPDE,9DWWKHVDPHGRVHDGPLQLVWHUHGDW:HHNLQ6WXG\0/1$WWKHGLVFUHWLRQRIWKHLQYHVWLJDWRUVXEMHFWV
UHFHLYLQJWKHORZGRVHPJIRUVXEMHFWVNJPJIRUVXEMHFWVNJYHGROL]XPDE,9ZKRGHPRQVWUDWHGLVHDVHZRUVHQLQJE\38&$,3&'$,DW
FRQVHFXWLYHYLVLWVVFKHGXOHGRUXQVFKHGXOHGPD\GRVHHVFDODWHWRKLJKGRVHIRUVXEMHFWVNJ PJIRUVXEMHFWVNJYHGROL]XPDE,94:EDVHGRQ
ZHLJKWDWWKHWLPHRIQRQUHVSRQVH
M3K\VLFDOH[DPLQDWLRQFOLQLFDOO\VLJQLILFDQWILQGLQJVZLOOEHUHFRUGHGDVPHGLFDOKLVWRU\LIVWDUWLVSULRUWRVLJQLQJWKHLQIRUPHGFRQVHQWSHGLDWULFDVVHQWRUDV$(VLI
VWDUWLVDIWHUWKHILUVWGRVHRIVWXG\GUXJ
N7REHSHUIRUPHGSULRUWRGRVLQJ
O$IWHUFRPSOHWLRQRI6WXG\0/1VXEMHFWVZKRKDYHGRVHLQFUHDVHGEDVHGRQQRQUHVSRQVHVKRXOGEHGRVHGEDVHGRQZHLJKWDWWKHWLPHRIQRQUHVSRQVH
7DEOH D
Q0RQLWRULQJRIFRQFRPLWDQWPHGLFDWLRQVDQGFRQFRPLWDQWSURFHGXUHVZLOOEHJLQDWVLJQLQJRIWKHLQIRUPHGFRQVHQWSHGLDWULFDVVHQW
R$XULQHSUHJQDQF\WHVWZLOOEHFRPSOHWHGIRUDOOIHPDOHVRIFKLOGEHDULQJSRWHQWLDOSULRUWRHDFKGRVHRIVWXG\GUXJDQGDWWKH(7)LQDO6DIHW\9LVLW
S7KH(65PD\EHSHUIRUPHGDWDORFDOODERUDWRU\
V$VWRROVDPSOHZLOOEHFROOHFWHGIRUWKHDQDO\VLVRIIHFDOFDOSURWHFWLQDELRPDUNHURILQWHVWLQDOLQIODPPDWRU\DFWLYLW\HYHU\ZHHNVZKHQDVXEMHFWEHFRPHV
V\PSWRPDWLFHJZRUVHQLQJRIGLVHDVHDFWLYLW\DQGDW(7)LQDO6DIHW\9LVLW7KHVWRROVDPSOHIRUWKHDQDO\VLVRIIHFDOFDOSURWHFWLQPXVWEHFROOHFWHGEHIRUHDQ\ERZHO
SUHSDUDWLRQLVJLYHQIRUHQGRVFRS\DQGEHIRUHGRVLQJ
W$VWRROVDPSOHZLOOEHREWDLQHGIRUFXOWXUHRYDDQGSDUDVLWHHYDOXDWLRQDQG&GLIILFLOH DVVD\$VDPSOHZLOOEHFROOHFWHGDQGFXOWXUHGDWDQ\SRLQWLQWKHVWXG\ZKHQD
VXEMHFWEHFRPHVV\PSWRPDWLFLQFOXGLQJZRUVHQLQJRI8&RU&'
X)RUVFKHGXOHGYLVLWVWKHGDLO\GLDULHVIRUWKHQH[WVFKHGXOHGYLVLWIRU8&DQGIRU&'FDQEHGLVSHQVHGZKHQWKHSDWLHQWOHDYHVWKHRIILFHIURPWKHODVWYLVLW7KH
VXEMHFWZLOOWKHQVWDUWILOOLQJWKHPRXWGD\VSULRUWRWKHQH[WVFKHGXOHGYLVLWIRU8&RUGD\VSULRUWRWKHQH[WVFKHGXOHGYLVLWIRU&'DQGWKHQUHWXUQWKHFRPSOHWHG
GLDULHVZKHQWKH\FRPHIRUWKHYLVLW)RUXQVFKHGXOHGYLVLWVGXHWRIODUHVWKHVXEMHFWVKRXOGVWDUWILOOLQJRXWGDLO\GLDU\VKHHWVZKHQWKHIODUHEHJLQVLISRVVLEOHDQGWKHQ
FRPHLQIRUWKHXQVFKHGXOHGYLVLWIRUHYDOXDWLRQ$IODUHLVFRQILUPHGE\REVHUYLQJWKHVXEMHFWGXULQJDRQHZHHNLQWHUYDOWRFRQILUPWKDWLWLVRQJRLQJDQGGXULQJWKDW
ZHHNWKHGLDULHVFDQFRQWLQXHWREHILOOHGRXWWRPDNHVXUHWKHVXEMHFWKDVGD\VRIV\PSWRPGLDULHVLIWKH\KDYH8&DQG GD\VRIV\PSWRPGLDULHVLIWKH\KDYH&'
$OVR%HFDXVHWKHIOH[LEOHVLJPRLGRVFRS\FRORQRVFRS\SUHSDUDWLRQFDQLQWHUIHUHZLWKWKHDVVHVVPHQWRIRWKHUFOLQLFDOSDUDPHWHUVGLDU\HQWULHVXVHGWRFDOFXODWHWKH
FRPSOHWH0D\RRU&'$,VFRUHVKRXOGQRWEHIURPGD\VGXULQJZKLFKWKHIOH[LEOHVLJPRLGRVFRS\FRORQRVFRS\SUHSDUDWLRQLVDGPLQLVWHUHG
Y7KHFRPSRQHQWVRIWKH38&$,3&'$,VFRUHVFDQEHFRPSOHWHGZLWKLQGD\VSULRUWRUHFHLYLQJVWXG\GUXJ
CCI
CCI
Fo
URWHFWL
URW
mme
DWVLJQLQJ
WVLJQLQ
WHQWLDOSULR
QWLDOSU
or non-com
on-
non
r n
For
ercial use only
IRUU
WRVLJQLQJ
VLJQL
HVSRQVHVK
VSRQVH
erci
mer

9HGROL]XPDE,9
6WXG\1R9HGROL]XPDE
3DJH RI
3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
 6HSWHPEHU 
&21),'(17,$/
[7KHFRPSOHWH0D\RDVVHVVPHQWLQFOXGHVWKH0D\RHQGRVFRSLFVXEVFRUH
\7KH&'$,ZLOOEHFRPSOHWHGZKHQDQHQGRVFRS\LVSHUIRUPHG
]7KH,03$&7,,,TXHVWLRQQDLUHZKHUHWUDQVODWLRQVDUHDYDLODEOHZLOOEHDGPLQLVWHUHGWRVXEMHFWVDJHGWR\HDUVDWWKHWLPHRIILUVWGRVHRIVWXG\GUXJLQ6WXG\
9HGROL]XPDEHYHU\ZHHNVIURP:HHN
CCI
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 96 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
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 responsibilities imposed on investigators by the FDA are 
summarized in the “Statement of Investigator” (Form FDA 1572), which must be completed and 
signed before the investigator may participate in this study. 
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 21 Code of Federal Regulations (CFR) Part 56, 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 21 CFR Part 50, 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 authorized 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 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 97 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
contact and receive written approval from the sponsor before disposing of any such 
documents. 
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. 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 98 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
Appendix C Elements of the Subject/Parental Informed Consent/Pediatric Assent 
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 authorized 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 or the subject’s legally authorized representative 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 99 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
otherwise is entitled, and that the subject may discontinue 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 authorized 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 efficacy of the study drug(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. 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 100 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
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 throughout the duration of the study and for 18 weeks after the last dose of 
study drug. 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 
drug will be discontinued. 
26. Male subjects must use adequate contraception (as defined in the informed consent) from 
Screening throughout the duration of the study and for 18 weeks after the last dose of study 
drug. 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 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. 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 101 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
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 drug. 
• Inspections and investigations by regulatory authorities relating to the study. 
• Self-inspection and internal audit within Takeda, its affiliates, and licensing partners. 
• Archiving and audit of study records. 
• Posting investigator site contact information, study details and results on publicly accessible 
clinical trial registries, databases, and websites. 
Investigator’s personal information may be transferred to other countries that do not have data 
protection laws that offer the same level of protection as data protection laws in investigator’s 
own country. 
Investigator acknowledges and consents to the use of his or her personal information by Takeda 
and other parties for the purposes described above. 
 
 
 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 102 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
Appendix E Sponsor Responsibilities 
The study sponsor and any third party to whom aspects of the study management or monitoring 
have been delegated will undertake their assigned roles for this study in compliance with all 
applicable industry regulations, current ICH GCP Guidelines, as well as all applicable national 
and local laws and regulations. 
Visits to sites are conducted by representatives of the study sponsor and/or the company 
organizing/managing the research on behalf of the sponsor to inspect study data, participants’ 
source documents, and CRFs in accordance with current GCP and the respective local and 
(inter)national government regulations and guidelines. Records and data may additionally be 
reviewed by auditors or by regulatory authorities. 
The sponsor ensures that local regulatory authority requirements are met before the start of the 
study. The sponsor (or designee) is responsible for the preparation, submission, and confirmation 
of receipt of any regulatory authority approvals required before release of study intervention for 
shipment to the site. 
 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 103 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
Appendix F PUCAI 
The PUCAI is composed of 6 clinical items. Weights of the included items were assigned 
according to a multivariate regression analysis of 157 children with UC, in which rectal bleeding 
assumed the highest weight. 
The historical parameters should reflect a daily average of the patient’s last 48 hours. However, 
if the patient’s condition is changing rapidly, the last 24 hours may be used. The PUCAI score 
ranges from 0 to 85; a score of <10 denotes remission, 10 to 34 mild disease, 35 to 64 moderate 
disease, and 65 to 85 severe disease. A clinically significant response is defined as a PUCAI 
change of ≥20. 
Item 
Points 
1 
Abdominal pain 
No pain 
0 
Pain can be ignored 
5 
Pain cannot be ignored 
10 
2 
Rectal bleeding 
None 
0 
Small amount only, in <50% of stools 
10 
Small amount with most stools 
20 
Large amount 
30 
3 
Stool consistency of most stools 
 
Formed 
0 
Partially formed 
5 
Completely unformed 
10 
4 
Number of stools per 24 hours 
0-2 
0 
3-5 
5 
6-8 
10 
>8 
15 
5 
Nocturnal stools (any episode causing wakening) 
 
No 
0 
Yes 
10 
6 
Activity level 
No limitation of activity 
0 
Occasional limitation of activity 
5 
Severe restricted activity 
10 
SCORE 
Total Max 85 
 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 104 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
Appendix G PCDAI 
The PCDAI was specifically designed for use in children. The PCDAI includes a child-specific 
item: the height velocity variable as well as 3 laboratory parameters: hematocrit (adjusted for age 
and sex), ESR, and albumin level. 
The limitation of activity should be based on the most significant limitation during the past week, 
even if it is only for 1 day. However, if the activity limitation is due to another illness (eg, upper 
respiratory infection), the illness period should be excluded from the subject’s PCDAI score. 
The PCDAI score can range from 0-100, with higher scores signifying more active disease. A 
score of <10 is consistent with inactive disease, 11 to 30 indicates mild disease, and >30 is 
moderate-to-severe disease. A decrease of 12.5 points is taken as evidence of improvement. 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 105 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
PCDAI Scoring 
 
History (recall 1 week) 
Abdominal pain 
None 
0 
Mild (brief episodes, not interfering with activities) 
5 
Moderate/severe (frequent or persistent, affecting activities) 
10 
Stools 
0-1 liquid stools, no blood 
0 
2-5 liquid or up to 2 semi-formed with small blood 
5 
Gross bleeding, >6 liquid stools or nocturnal diarrhoea 
10 
Patient functioning, general well-being (Recall, 1 week) 
No limitation of activities, well 
0 
Occasional difficulties in maintaining age-appropriate activities, below par 
5 
Frequent limitation of activities, very poor 
10 
EXAMINATION 
Weight 
Weight gain or voluntary weight loss 
0 
Involuntary weight loss 1-9% 
5 
Weight loss >10% 
10 
Height 
<1 channel decrease (or height velocity >-SD) 
0 
>1<2 channel decrease (or height velocity <-1SD>-2SD) 
5 
>2 channel decrease (or height velocity <-2SD) 
10 
Abdomen 
No tenderness, no mass 
0 
Tenderness, or mass without tenderness 
5 
Tenderness, involuntary guarding, definite mass 
10 
Peri-rectal disease 
None, asymptomatic tags 
0 
1-2 indolent fistula, scant drainage, tenderness of abscess 
5 
Active fistula, drainage, tenderness or abscess 
10 
Extra-intestinal manifestations 
(Fever >38.5 x 3 days in week, arthritis, uveitis, erythema nodosum, or pyoderma gangrenosum) 
none 
0 
one 
5 
two 
10 
LABORATORY 
Hematocrit (%) 
<10 years 
11-14 (male) 
11-19 (female) 
15-19 (male) 
>33 
>35 
>34 
>37 
0 
28-33 
30-34 
29-33 
32-36 
2.5 
<28 
<30 
<29 
<32 
5 
ESR (mm/hr) 
<20 
0 
20-50 
2.5 
>50 
5 
Albumin (g/L) 
>35 
0 
31-34 
5 
<30 
10 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 106 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
Appendix H Mayo Scoring System for the Assessment of UC Activity 
Category(a) 
Stool frequency (b) 
0=Normal no. of stools for this patient 
1=1 to 2 stools more than normal 
2=3 to 4 stools more than normal 
3=5 or more stools more than normal 
Subscore, 0 to 3 
Rectal bleeding (c) 
0=No blood seen 
1=Streaks of blood with stool less than half the time 
2=Obvious blood with stool most of the time 
3=Blood alone passes 
Subscore, 0 to 3 
Findings on endoscopy 
0=Normal or inactive disease 
1=Mild disease (erythema, decreased vascular pattern, mild friability) 
2=Moderate disease (marked erythema, lack of vascular pattern, friability, erosions) 
3=Severe disease (spontaneous bleeding, ulceration) 
Subscore, 0 to 3; 0=Normal or inactive disease 
Physician’s global assessment (d) 
0=Normal 
1=Mild disease 
2=Moderate disease 
3=Severe disease 
Subscore, 0 to 3 
Source: Adapted from: Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for 
mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med 1987;317(26):1625-9.  
(a) The Mayo score ranges from 0−12, with higher scores indicating more severe disease. Partial Mayo score 
excludes endoscopy and ranges from 0−9. 
(b) Each patient serves as his or her own control to establish the degree of abnormality of the stool frequency. 
(c) The daily bleeding score represents the most severe bleeding of the day. 
(d) The physician’s global assessment acknowledges the 3 other criteria, the patient’s daily recollection of 
abdominal discomfort and general sense of well-being, and other observations, such as physical findings and the 
patient’s performance status. 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 107 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
Appendix I 
SES-CD 
Variable 
SES Score 
0 
1 
2 
3 
Size of ulcers (cm) 
None 
Aphthous ulcers 
(diameter 0.1-0.5) 
Large ulcers 
(diameter 0.5-2) 
Very large ulcers 
(diameter >2) 
Ulcerated surface 
None 
<10% 
10-30% 
>30% 
Affected surface 
Unaffected 
segment 
<50% 
50-75% 
>75% 
Presence of narrowings 
None 
Single, can be 
passed 
Multiple, can be 
passed 
Cannot be passed 
SES-CD=sum of all variables for the 5 bowel segments. 
Values are given to each variable for every examined bowel segment. 
Source: Adapted from Daperno M, D’Haens G, Van Assche G, Baert F, Bulois P, Maunoury V, et al. Development 
and validation of a new, simplified endoscopic activity score for Crohn’s disease: the SES-CD. Gastrointest Endosc 
2004;60(4):505-12. 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 108 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
Appendix J 
Tanner Scale 
Puberty and the Tanner Stages - developed by Professor James M Tanner  
Introduction 
Adolescents experience several types of maturation, including cognitive (the development of 
formal operational thought), psychosocial (the stages of adolescence), and biologic. The complex 
series of biologic transitions are known as puberty, and these changes may impact psychosocial 
factors.  
The most visible changes during puberty are growth in stature and development of secondary 
sexual characteristics. Equally profound are changes in body composition; the achievement of 
fertility; and changes in most body systems, such as the neuroendocrine axis, bone size, and 
mineralization; and the cardiovascular system. As an example, normal cardiovascular changes, 
including greater aerobic power reserve, electrocardiographic changes, and blood pressure 
changes, occur during puberty.  
The normal sequence of pubertal events and perils of puberty are reviewed here. This is within 
the normal ranges and does not take into account Precocious Puberty or Delayed Puberty.  
Tanner Stages 
Conceptually, pubertal maturation can be described in terms of sequence, timing, and tempo 
(Puberty consists of a series of predictable events, and the sequence of changes in secondary 
sexual characteristics has been categorized by several groups. The staging system utilized most 
frequently is that published by Marshall and Tanner and the sequence of changes, commonly 
referred to as “Tanner stages”, is described below.  
Boys - development of external genitalia 
Stage 1:  
Prepubertal  
Stage 2:  
Enlargement of scrotum and testes; scrotum skin reddens and changes in texture  
Stage 3:  
Enlargement of penis (length at first); further growth of testes  
Stage 4:  
Increased size of penis with growth in breadth and development of glans; testes 
and scrotum larger, scrotum skin darker  
Stage 5:  
Adult genitalia  
 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 109 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
Girls - breast development 
Stage 1:  
Prepubertal  
Stage 2:  
Breast bud stage with elevation of breast and papilla; enlargement of areola  
Stage 3:  
Further enlargement of breast and areola; no separation of their contour  
Stage 4:  
Areola and papilla form a secondary mound above level of breast  
Stage 5:  
Mature stage: projection of papilla only, related to recession of areola  
 
Boys and girls - pubic hair 
Stage 1:  
Prepubertal (can see vellus hair similar to abdominal wall)  
Stage 2:  
Sparse growth of long, slightly pigmented hair, straight or curled, at base of 
penis or along labia  
Stage 3:  
Darker, coarser and more curled hair, spreading sparsely over junction of pubes  
Stage 4:  
Hair adult in type, but covering smaller area than in adult; no spread to medial 
surface of thighs  
Stage 5:  
Adult in type and quantity, with horizontal distribution (“feminine”)  
 
Boys Growth 
• Stage 1:  5-6 cm/year. 
• Stage 2:  5-6 cm/year. 
• Stage 3:  7-8 cm/year. 
• Stage 4:  10 cm/year. 
• Stage 5:  No further height increase after 17 years. 
 
Girls Growth 
• Stage 1:  5-6 cm/year. 
• Stage 2:  7-8 cm/year. 
• Stage 3:  8 cm/year. 
• Stage 4:  7 cm/year. 
• Stage 5:  No further height after 16 years. 
 
Source: Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child. 1969 Jun; 
44(235): 291–303. Marshall WA, Tanner JM. Variations in pattern of pubertal changes in boys. Arch Dis Child. 
1970 Feb; 45(239): 13–23. 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 110 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
Appendix K CDAI Scoring System for the Assessment of CD Activity 
Category 
Count 
Initial 
Total 
Multiplication 
Factor 
Total 
Number of liquid or 
very soft stools 
7-day total number of liquid or very soft stools (reported 
on the 7 days immediately prior to the study visit) 
 
×2 
 
Abdominal pain 
7-day total of daily abdominal pain scores on a 3-point 
scale: 0=none, 1=mild, 2=moderate, 3=severe (reported 
on the 7 days immediately prior to the study visit) 
 
×5 
 
General well-being 
7-day total of daily general well-being scores on a 4-point 
scale: 0=generally well, 1=slightly under par, 2=poor, 
3=very poor, 4=terrible (reported on the 7 days 
immediately prior to the study visit) 
 
×7 
 
Extra-intestinal 
manifestations of CD 
Total number of checked boxes (check all that apply): 
□ Arthritis/arthralgia 
□ Iritis/uveitis 
□ Erythema nodosum/pyoderma 
gangrenosum/aphthous stomatitis 
□ Anal fissure, fistula, or abscess 
□ Other fistula 
□ Fever over 37.8°C during past week 
 
×20 
 
Lomotil/Imodium/ 
opiates for diarrhea 
Yes=1 
No=0 
 
×30 
 
Abdominal mass 
None=0 
Questionable=2 
Definite=5 
 
×10 
 
Hematocrit (%)(a) 
Males: subtract value from 47 
Females: subtract value from 42 
 
×6 
 
Body weight (b) 
[1 – (body weight/ideal weight for height)]×100 
 
×1 
 
Final score 
 
 
Add totals: 
 
Source: Adapted from: Best WR, Beckel JM, Singleton JW, Kern F, Jr. Development of a Crohn’s disease activity 
index. National Cooperative Crohn’s Disease Study. Gastroenterology 1976; 70 (3):439-44.  
(a) If hematocrit subtotal <0, enter 0. 
(b) To calculate body weight: 
1. Identify the weight in kilogram (kg) for this visit. 
2. Find the child’s measured height to determine the percentile for that height by gender and age, using Centers 
for Disease Control and Prevention Stature-for-Age growth chart 
(cdc.gov/growthcharts/html_charts/statage.htm). 
3. The child’s Ideal Weight for Height is the weight on the same percentile for the child’s gender and age, using 
Centers for Disease Control and Prevention Weight-for-Age growth chart. For example, for a boy’s height at the 
25th percentile for his age, his ideal weight will be considered to also be the 25th percentile weight for his age 
(cdc.gov/growthcharts/html_charts/wtage.htm) 
4. Calculate the total score using the formula above, rounding to the nearest integer. If the body weight total 
score is <-10, the body weight total score is set to -10. 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 111 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
Appendix L Protocol History Appendix 
Date 
Amendment Number 
Region 
27 September 2024 
8 
Global 
08 March 2023 
7 
Global 
01 December 2021 
6 
Global 
24 August 2018 
05 
Global 
13 February 2018 
04 
Global 
13 October 2017 
03 
Local/United Kingdom 
25 May 2017 
02 
Global 
07 April 2017 
01 
Global 
17 October 2016 
Initial version 
Global 
 
Protocol Amendment 7 Summary and Rationale: 
This section describes the changes in reference to the protocol incorporating Amendment 7. The 
primary reasons for this amendment are to: 
• Describe the management of study procedures to maintain subject safety, confidentiality, and 
study integrity in the context of healthcare delivery challenges due to a pandemic (eg, 
coronavirus disease 2019 [COVID-19]). 
• Remove the data and safety monitoring board. 
• Remove the Risk Assessment and Minimization Program for Progressive Multifocal 
Leukoencephalopathy. 
• Describe posttrial access to vedolizumab. 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 112 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
In this amendment, minor grammatical, editorial, formatting, and administrative changes not 
affecting the conduct of the study are included for clarification and administrative purposes only. 
Protocol Amendment 7 
Summary of Changes Since the Last Version of the Approved Protocol 
Change 
Number 
Sections Affected by Change 
Description of Each Change and Rationale 
Location 
Description 
Rationale 
1. 
Section 2.0 STUDY 
SUMMARY 
Section 6.1 Study Design 
Figure 6.a Schematic of 
Vedolizumab-2005 Study 
Design 
Section 6.2.1 Justification for 
Study Design and Endpoints 
Section 8.1.3 Dose and Regimen 
Section 9.3.2 Final Visit or ET 
Section 9.3.5 Poststudy Care 
Appendix A Schedule of Study 
Procedures 
Updated the duration of 
vedolizumab intravenous (IV) 
treatment to allow treatment to 
continue until vedolizumab IV 
is commercially available for 
pediatric indication(s) in the 
subject’s country or until other 
drug access programs become 
available (whichever comes 
first), the subject turns 18 years 
of age and can be transitioned 
to commercial drug, the subject 
withdraws from the study, or 
the sponsor decides to close the 
study. 
Change made to ensure 
uninterrupted study 
medication availability for 
subjects who continue to 
receive clinical benefit from 
vedolizumab IV treatment. 
2. 
Section 2.0 STUDY 
SUMMARY 
Section 7.1 Inclusion Criteria 
Section 7.3.1.1 Oral 
Corticosteroid Dosing 
Clarified acceptable use of 
corticosteroids. 
Change made to ensure that 
corticosteroids are not 
introduced during 
Vedolizumab-2005. 
3. 
Section 6.2.1 Justification for 
Study Design and Endpoints 
Section 6.3.1 Criteria for 
Premature Termination or 
Suspension of the Study 
Section 11.1 Independent Data 
Safety Monitoring Board 
(deleted) 
Removed the data and safety 
monitoring board (DSMB). 
This committee was no longer 
required for this open-label 
study once the last subject 
reached the Week 40 visit of 
Vedolizumab-2005 (the 
DSMB members endorsed 
decommissioning of the 
DSMB after subject dosing 
was unblinded). 
4. 
Section 4.1.3.2 Clinical 
Section 4.3 Benefit/Risk 
Assessment 
Updated content to include 
information on conduct of 
completed pediatric study 
MLN0002-2003 and 
availability of data from 
completed pediatric study and 
the vedolizumab development 
program. Included reference to 
current edition of Investigator’s 
Brochure as the most up-to-date 
source for clinical experience 
data. 
Revised to provide the most 
current information for 
vedolizumab. 
For non-commercial use only

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 113 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
Protocol Amendment 7 
Summary of Changes Since the Last Version of the Approved Protocol 
Change 
Number 
Sections Affected by Change 
Description of Each Change and Rationale 
Location 
Description 
Rationale 
5. 
Section 6.1 Study Design 
Section 9.3.4 Long-term Follow-
up Safety Survey 
Section 9.3.5 Poststudy Care 
Added posttrial access 
information for vedolizumab 
and clarified safety follow-up 
procedures. 
Revised to ensure that subjects 
completing the study will have 
an option to continue 
vedolizumab treatment. 
6. 
Section 6.2.1 Justification for 
Study Design and Endpoints 
Section 7.5 Criteria for 
Discontinuation or Withdrawal 
of a Subject 
Section 9.1.19 PML Checklist 
(deleted) 
Section 9.3.6 Unscheduled 
Visits Due to Disease 
Exacerbation 
Section 11.2.1 RAMP Program 
(deleted) 
Section 13.1.3 Safety Analysis 
Appendix A Schedule of Study 
Procedures 
Removed the Risk Assessment 
and Minimization Program for 
Progressive Multifocal 
Leukoencephalopathy (RAMP). 
Change made because the 
RAMP is no longer required, 
per Food and Drug 
Administration (FDA) 
communication. 
7. 
Section 9.1.6.1 Completion and 
Review of Entries to Diaries 
Added reference to Pediatric 
Crohn’s Disease Activity Index 
(PCDAI) completion with links 
to the correct appendices. 
Corrected an omission. 
8. 
Section 9.3.2 Final Visit or ET 
Appendix A Schedule of Study 
Procedures 
Clarified that treatment will 
vary by subject on the basis of 
continued benefit but will be 
until vedolizumab IV is 
commercially available for 
pediatric indication in the 
subject’s country or until other 
drug access programs become 
available (whichever comes 
first), the subject turns 18 years 
of age and can be transitioned 
to commercial drug, the subject 
withdraws from the study, or 
the sponsor decides to close the 
study. Also added a column for 
the safety follow-up visit. 
Revised to clarify that dosing 
continues throughout a 
subject’s participation, as 
defined in the description. The 
column for the safety follow-
up visit detailing the 
assessments to be performed 
had been unintentionally 
omitted and has now been 
added. 
For non-commercial use only

9HGROL]XPDE,9
6WXG\1R9HGROL]XPDE
3DJH RI
3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
 6HSWHPEHU 
&21),'(17,$/
3URWRFRO$PHQGPHQW
6XPPDU\RI&KDQJHV6LQFHWKH/DVW9HUVLRQRIWKH$SSURYHG3URWRFRO
&KDQJH
1XPEHU
6HFWLRQV$IIHFWHGE\&KDQJH
'HVFULSWLRQRI(DFK&KDQJHDQG5DWLRQDOH
/RFDWLRQ
'HVFULSWLRQ
5DWLRQDOH

6HFWLRQ $OWHUQDWLYH
$SSURDFKHVWR6WXG\3URFHGXUHV
DQG'DWD&ROOHFWLRQ'XHWRD
3DQGHPLF
6HFWLRQ 6WXG\6LWH
0RQLWRULQJ9LVLWV
$SSHQGL[ $ 6FKHGXOHRI6WXG\
3URFHGXUHV
$GGHGJXLGDQFHRQDOWHUQDWLYH
DSSURDFKHVWRH[HFXWLQJVWXG\
SURFHGXUHVDQGFROOHFWLQJVWXG\
GDWDGXHWRDSDQGHPLFHJWKH
FRURQDYLUXVGLVHDVH
>&29,'@SDQGHPLFRURWKHU
IXWXUHVLPLODUXQH[SHFWHG
SXEOLFKHDOWKFRQFHUQUHTXLULQJ
SK\VLFDOGLVWDQFLQJLQFOXGLQJ
XVHRIORFDOODERUDWRULHV
UHPRWHYLVLWVDQGUHPRWH
PRQLWRULQJYLVLWV
$GGLWLRQPDGHWRSURYLGH
IOH[LELOLW\LQDGPLQLVWUDWLRQRI
VWXG\SURFHGXUHVGXULQJD
SDQGHPLFHJWKH&29,'
SDQGHPLFRURWKHUIXWXUH
VLPLODUXQH[SHFWHGSXEOLF
KHDOWKFRQFHUQUHTXLULQJ
SK\VLFDOGLVWDQFLQJZKLOH
HQVXULQJWKHVDIHW\RIVWXG\
SDUWLFLSDQWVPDLQWDLQLQJ
FRPSOLDQFHZLWK*RRG
&OLQLFDO3UDFWLFHDQG
PLQLPL]LQJULVNVWRVWXG\
LQWHJULW\

6HFWLRQ $(6, 5HSRUWLQJ

6HFWLRQ &OLQLFDO7ULDO
5HVXOWV'LVFORVXUH
$GGHGLQIRUPDWLRQDERXW
UHVXOWVUHTXLUHGIRUGLVFORVXUH
SHUWKH(XURSHDQ8QLRQ
$GGLWLRQPDGHWRHQVXUHWKDW
WKHUHTXLUHGGDWDVXPPDULHV
E\DJHDUHFOHDU

$SSHQGL[ $ 6FKHGXOHRI6WXG\
3URFHGXUHV
&ODULILHGWKDW3&'$,VFRULQJLV
FRPSOHWHGHYHU\ZHHNV
UDWKHUWKDQHYHU\ZHHNVLQ
DOLJQPHQWZLWKFROOHFWLRQRI
ODERUDWRU\UHVXOWV
/DERUDWRU\UHVXOWVFROOHFWHG
KHPDWRFULWDOEXPLQDQG
HU\WKURF\WHVHGLPHQWDWLRQ
UDWHDUHNH\HOHPHQWVRIWKH
3&'$,&URKQ¶VGLVHDVH
DFWLYLW\VFRULQJ/DERUDWRU\
UHVXOWVDUHFROOHFWHGHYHU\
ZHHNVWKHUHIRUHWKH3&'$,
VFRULQJVKRXOGIROORZWKLV
VDPHVFKHGXOH7KLVDOLJQV
ZLWKSURWRFRO6HFWLRQ
&RPSOHWLRQDQG5HYLHZRI
(QWULHVWR'LDULHV
CCI
CCI
on-comm
n-
n-comm
GHGL
com
UHVXO
co
SH
m
n-
erc
rc
rciaiaial u
l u
l use
se only
nly
se
se
se
For non
non
G\
or non
use
al u
cia
erc
me

9HGROL]XPDE,9
6WXG\1R9HGROL]XPDE
3DJH RI
3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
 6HSWHPEHU 
&21),'(17,$/
3URWRFRO$PHQGPHQW6XPPDU\DQG5DWLRQDOH
7KLVVHFWLRQGHVFULEHVWKHFKDQJHVLQUHIHUHQFHWRWKHSURWRFROLQFRUSRUDWLQJ$PHQGPHQW7KH
SULPDU\UHDVRQIRUWKLVDPHQGPHQWLVWR
x
$OLJQWKHOHJDOHQWLW\VSRQVRUQDPHDFURVV7DNHGDVWXGLHV
,QWKLVDPHQGPHQWPLQRUJUDPPDWLFDOHGLWRULDOIRUPDWWLQJDQGDGPLQLVWUDWLYHFKDQJHVQRW
DIIHFWLQJWKHFRQGXFWRIWKHVWXG\DUHLQFOXGHGIRUFODULILFDWLRQDQGDGPLQLVWUDWLYHSXUSRVHVRQO\
3URWRFRO$PHQGPHQW
6XPPDU\RI&KDQJHV6LQFHWKH/DVW9HUVLRQRIWKH$SSURYHG3URWRFRO
&KDQJH
1XPEHU
6HFWLRQV$IIHFWHGE\&KDQJH
'HVFULSWLRQRI(DFK&KDQJHDQG5DWLRQDOH
/RFDWLRQ
'HVFULSWLRQ
5DWLRQDOH

&RYHUSDJH
5HPRYHG7DNHGD'HYHORSPHQW
&HQWUH7'&(XURSHDVD
VSRQVRUDQGXSGDWHGWKH
DGGUHVVIRU7'&$PHULFDV
5HYLVHGWRDOLJQWKHVSRQVRU
QDPHDFURVV7DNHGDVWXGLHV
DQGFRUUHFWWKHDGGUHVVIRU
7'&$PHULFDV

&RQWDFWV
5HYLVHGWKHLGHQWLILHGFRQWDFWV
&KDQJHVPDGHWRUHIOHFW
FXUUHQWO\DYDLODEOH
UHSUHVHQWDWLYHVWRFRQWDFW

6HFWLRQ$SSURYDO
5HYLVHGWKHLGHQWLILHG
DSSURYHUV
&KDQJHVPDGHEDVHGRQ
FXUUHQWIXQFWLRQDODUHD
UHSUHVHQWDWLYHVDSSURYLQJWKLV
GRFXPHQW
5DWLRQDOHIRU$PHQGPHQW
7KLVGRFXPHQWGHVFULEHVWKHFKDQJHVLQUHIHUHQFHWRWKH3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
7KHSULPDU\SXUSRVHRIWKLVDPHQGPHQWLVWRDGGSDWLHQWGLDULHVIRUV\PSWRPDVVHVVPHQWDQG
FODULI\WKHUHTXLUHGHYDOXDWLRQWRROVWREHXVHGZKHQDQHQGRVFRS\LVSHUIRUPHG
0LQRUJUDPPDWLFDOHGLWRULDODQGIRUPDWWLQJFKDQJHVDUHLQFOXGHGIRUFODULILFDWLRQSXUSRVHV
RQO\
&KDQJHV LQ$PHQGPHQW
 5HYLVHGWH[WWRDOLJQZLWK&RUH'DWD6KHHW
 6SHFLILHGWKDWWKHHQGRVFRSLF VXEVFRUHLVLQFOXGHGLQWKHFRPSOHWH0D\RDVVHVVPHQWIRU
SDWLHQWVZLWKXOFHUDWLYHFROLWLVDQGFODULILHGWKDWWKHFRPSOHWH0D\RVFRUHIRUSDWLHQWVZLWK
XOFHUDWLYHFROLWLVRUWKHVLPSOHHQGRVFRSLFVFRUHIRU&URKQ¶VGLVHDVHDQG&URKQ¶V'LVHDVH
$FWLYLW\,QGH[IRUSDWLHQWVZLWK&URKQ¶VGLVHDVHDUHJHQHUDWHGDW:HHN

 $GGHGFRPSOHWLRQDQGUHYLHZRISDWLHQWGLDULHV
 $GGHG&URKQ¶V'LVHDVH$FWLYLW\,QGH[TXHVWLRQQDLUHDVDQHZDSSHQGL[
CCI
For non-commercial use only
ULFDV
DV
y
ILHGFRQWD
HGFR
e
WKHLGHQWL
KHLGHQ
YHUV
HUV
cia
o
KDQJHVLQ
DQJHV
KLVDPH
KLVDP
WRR
W

9HGROL]XPDE,9
6WXG\1R9HGROL]XPDE
3DJH RI
3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
 6HSWHPEHU 
&21),'(17,$/
5DWLRQDOHIRU$PHQGPHQW
7KLVGRFXPHQWGHVFULEHVWKHFKDQJHVLQUHIHUHQFHWRWKH3URWRFRO,QFRUSRUDWLQJ$PHQGPHQW1R
7KHSULPDU\SXUSRVHVRIWKLVDPHQGPHQWDUHWRLQFRUSRUDWHLQLWLDOEOLQGLQJRIGRVLQJWRDGG
DQDGGLWLRQDOUHTXLUHGHQGRVFRS\DQGWRFODULI\,QFOXVLRQ&ULWHULDDQG([FOXVLRQ&ULWHULDWKH
GHILQLWLRQRIGLVHDVHZRUVHQLQJDQGFRQFRPLWDQWPHGLFDWLRQXVDJH
0LQRUJUDPPDWLFDOHGLWRULDODQGIRUPDWWLQJFKDQJHVDUHLQFOXGHGIRUFODULILFDWLRQSXUSRVHV
RQO\
&KDQJHV LQ$PHQGPHQW
 &ODULILHG WKHGHILQLWLRQRIGLVHDVHZRUVHQLQJDIWHUGRVHHVFDODWLRQ
 $GGHGSUHYLRXVO\RPLWWHGDGGLWLRQDOHQGSRLQWV
 'HOHWHG+DUYH\%UDGVKDZ,QGH[
 ,QFRUSRUDWHGLQLWLDOEOLQGLQJWRGRVH
 &ODULILHGHOLJLELOLW\DQGHQUROOPHQWSURFHGXUHV
 &ODULILHG,QFOXVLRQ&ULWHULRQ
 'HOHWHG,QFOXVLRQ&ULWHULRQ
 $PHQGHG([FOXVLRQ&ULWHULRQ
 &ODULILHGSHUPLWWHGPHGLFDWLRQVGXULQJWKHVWXG\
 $PHQGHGWKHFRQFRPLWDQWRUDOFRUWLFRVWHURLGGRVLQJLQIRUPDWLRQ
 'HILQHGFKURQLFQRQVWHURLGDODQWLLQIODPPDWRU\GUXJXVH
 6SHFLILHGWKDWWKHHU\WKURF\WHVHGLPHQWDWLRQUDWHPD\EHSHUIRUPHGDWDORFDOODERUDWRU\
 5HPRYHGXULQDO\VLV
 'HOHWHG6HFWLRQ
 &ODULILHGWKH(QGRI6WXG\GHILQLWLRQ
 $PHQGHGLQWHULPDQDO\VLVODQJXDJH
 8SGDWHGWKHSURWRFROGHYLDWLRQLQIRUPDWLRQ
 5HPRYHGHOHFWURFDUGLRJUDPDVVHVVPHQWV
CCI
CCI
For non-commercial use only
QJWKHVW
JWKH
RUWLFRVWH
UWLFRV
ODQWL
QWLLQL
RF\WHVH
RF\WHV

Vedolizumab IV 
 
Study No. Vedolizumab-2005 
Page 117 of 117 
Protocol Incorporating Amendment No. 8 
27 September 2024 
 
CONFIDENTIAL 
Rationale for Amendment 03 
This document describes the changes in reference to the Protocol Incorporating Amendment No. 
03. The primary purposes of this amendment are to clarify Inclusion Criterion 4 and the 
definition of disease worsening.  
Minor grammatical, editorial, and formatting changes are included for clarification purposes 
only. 
Changes in Amendment 03 
1. Clarified Inclusion Criterion 4. 
2. Clarified the definition of disease worsening. 
3. Clarified the End of Study definition. 
 
Rationale for Amendment 02 
This document describes the changes in reference to the Protocol Incorporating Amendment No. 
02. The primary purpose of this amendment is to update the EudraCT number.  
Changes in Amendment 02 
1. Update to the EudraCT number. 
 
Rationale for Amendment 01 
This document describes the changes in reference to the Protocol Incorporating Amendment No. 
01. The primary purpose of this amendment is to update the protocol to allow enrollment of 
pediatric subjects aged 2 to 17 years, inclusive, who weigh <30 kg. The vedolizumab IV dose 
and dosing regimen for subjects in this weight category was added. Other minor changes in 
procedures are proposed. Minor grammatical and editorial changes are included for clarification 
purposes only. 
Changes in Amendment 01 
1. Update to allow enrollment of pediatric subjects who weigh <30 kg. 
2. Corrected typographical errors, punctuation, grammar, and formatting. 
 
For non-commercial use only

6LJQDWXUH3DJHIRU9HGROL]XPDE3URWRFRO$PHQGPHQW6HS
7LWOH9HGROL]XPDE3URWRFRO$PHQGPHQW6HS
'RFXPHQW1XPEHU7'1Y
$SSURYDO
&OLQLFDO
6HS*07
$SSURYDO
3KDUPDFRYLJLODQFH
6HS*07
$SSURYDO
6WDWLVWLFV
6HS*07
$SSURYDO
&OLQLFDO
6HS*07
PPD
PPD
PPD
PPD
For non-commer
1XPEHU
XPEH
me
merc
mercial use only


us
&OLQLFD
&OLQL
6

nly
rcial u