Clinical trial NCT04613518
Conditions: Colitis, Ulcerative
Sponsor: Bristol-Myers Squibb
Start date: 2021-03-15; Completion date: 2023-11-29
Enrollment: 38 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to assess the safety and tolerability, efficacy, and biomarker response of BMS-986165 administered orally in participants with moderate to severe ulcerative colitis. The study was originally designed to test deucravacitinib at two doses for 12 weeks compared to placebo. After the initial 12-Week period, all subjects receive active therapy (open-label extension). With protocol amendment 2, one of the dose treatment arms is being removed from the 12-week double blind period with no change to the open-label extension.

Detailed description:

Arms: arm 1: None arm 2: None arm 3: None
Interventions: intervention 1: BMS-986165 intervention 2: Placebo Comparator
Intervention descriptions: intervention 1: Specified Dose on Specified Days intervention 2: Specified Dose on Specified Days

Protocol documents:
Prot_SAP_000.pdf: 
Official Title of Study: 
A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of the Safety, Efficacy, and Biomarker 
Response of BMS-986165 in Subjects with Moderate to Severe Ulcerative Colitis 
 
PROTOCOL(S) IM011-127 
 
NCT Number: NCT04613518 
  
Document Date (Date in which document was last revised): February 24, 2022 


Page:
1
Protocol Number:
IM011127
Date:
22-Apr-2020
Revised Date:
24-Feb-2022
REGULATORY AGENCY IDENTIFIER NUMBER(S)
IND:
141055
EudraCT:
2019-004878-26
NCT:
NCT04613518
WHO: 
U1111-1245-2970
CLINICAL PROTOCOL IM011127
A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of the Safety, Efficacy, and 
Biomarker Response of BMS-986165 in Subjects with Moderate to Severe Ulcerative Colitis
Short Title: Safety, Efficacy, and Biomarker Response of BMS-986165 in Subjects with Moderate 
to Severe Ulcerative Colitis
Protocol Amendment Number 02
Incorporates Administrative Letter 01
Medical Monitor
Bristol Myers Squibb Company
100 Binney Street
Cambridge, MA 02142
Bristol Myers Squibb Company
3033 Science Park Rd
San Diego, CA 92121
Telephone: 
Telephone: 
24-hr Emergency Telephone Number
USA: 
International: 
Bristol Myers Squibb Company
3401 Princeton Pike
Lawrenceville, NJ 08648
Avenue de Finlande 4
B-1420 Braine-l’Alleud, Belgium
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BMS-986165
TYK2 Inhibitor
Protocol Amendment No.: 02
Date: 24-Feb-2022
2
This document is the confidential and proprietary information of Bristol Myers Squibb Company 
and its global affiliates (BMS). By reviewing this document, you agree to keep it confidential and to 
use and disclose it solely for the purpose of assessing whether your organization will participate in 
and/or the performance of the proposed BMS sponsored study. Any permitted disclosures will be 
made only on a confidential "need to know" basis within your organization or to your independent 
ethics committee(s). Any other use, copying, disclosure, or dissemination of this information is strictly 
prohibited unless expressly authorized in writing by BMS. Any supplemental information (eg, 
amendments) that may be added to this document is also confidential and proprietary to BMS and 
must be kept in confidence in the same manner as the contents of this document. Any person who 
receives this document without due authorization from BMS is requested to return it to BMS or 
promptly destroy it. All other rights reserved. References to BMS in this protocol may apply to 
partners to which BMS has transferred obligations, eg, a Contract Research Organization.
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Protocol Amendment No.: 02
Date: 24-Feb-2022
3
DOCUMENT HISTORY
Document
Date of Issue
Approver(s)
Summary of Changes
Protocol Amendment 02
24-Feb-2022
 
Changes include the following:
1.
Removed the BMS-986165 6 mg 
BID treatment arm
2.
Clarified future treatment
regimen for subjects currently 
receiving treatment in the 
BMS-986165 6 mg BID arm
3.
Updated prior UC medication 
Inclusion Criterion to require
inadequate response, loss of 
response, or intolerance to a
treatment course of ≥1 of the 
standard of care UC medications;
added an Inclusion Criterion to 
require at least 1 prior treatment 
course of corticosteroids for UC; 
and added corticosteroids (must 
have had 2 exposures separated 
by a corticosteroid-free period)  
 
 to the list of these standard 
of care UC medications
4.
Added potential inclusion of 
subjects in the study who 
discontinue treatment with 
biologics due to inadequate 
funding (previously located in
Appendix 5)
5.
Added an enrollment target 
number of subjects 
 
 
 
 
 and included washout 
parameters for the medication 
class
 
 
 
 
 
 
 
 
 
 
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Protocol Amendment No.: 02
Date: 24-Feb-2022
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Document
Date of Issue
Approver(s)
Summary of Changes
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
12. Added study treatment 
interruption rule for skin AEs and 
clarified dose interruption criteria 
for medical procedures in OLE 
period in Section 8.1.1
13. Moved study treatment 
interruption information from 
Section 7.4 to Section 8.1.1
14. Added definitions/exploratory 
efficacy endpoints for durable 
clinical response and durable 
endoscopic response, and added 
definition for corticosteroid-free 
remission
15. Added Exclusion Criterion for 
subjects receiving CMV colitis 
treatment within 12 weeks of 
randomization
16. Added Exclusion Criterion for 
subjects with a positive 
diagnostic test for SARS-CoV-2 
during screening and added 
instruction that the screening 
SARS-CoV-2 diagnostic test 
must be performed and 
confirmed negative prior to 
randomization
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Protocol Amendment No.: 02
Date: 24-Feb-2022
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Document
Date of Issue
Approver(s)
Summary of Changes
17. Added to the guidance for 
rescreening of subjects with a 
positive SARS-CoV-2 test who 
had COVID-19 symptoms
18. Clarified reporting time 
requirements for AEs related to 
SARS-CoV-2
19. Removed Exclusion Criterion 
exception previously allowing
subjects with Gilbert’s syndrome 
to enroll in the study
20. Clarified potential acceptability 
of prophylactic use of 
antimicrobial agents during the 
study
21. Added calculation of modified 
Mayo score at Week 52 and 
symptomatic Mayo score for 
treatment response at Week 20
22. Clarified process for rescreening 
when qualifying endoscopy is 
completed, including 
determining stool frequency and 
rectal bleeding scores for 
eligibility. Additionally, for all 
rescreening, added a 45-day 
window after original screening 
during which select laboratory 
assessments do not need to be 
repeated if rescreening is 
required
23. Incorporated changes from 
Administrative Letter 01 and 
added guidance regarding the 
preference for usage of the 
central laboratory versus local 
laboratories for performing 
safety assessments
24. Added potential to extend 
14-day window for 
randomization after the initial 
screening endoscopy by an 
additional 3 days with BMS 
Medical Monitor/designee 
approval (rescreening only)
25. Removed details of potential 
exposure-response analyses and 
replaced with reference to 
separate analysis plan as needed
26. Removed reference to “legally 
acceptable” representatives in 
relation to signing the ICF only
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Protocol Amendment No.: 02
Date: 24-Feb-2022
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Document
Date of Issue
Approver(s)
Summary of Changes
27. Clarified in Section 10.4.4 that 
an interim analysis of data would 
potentially be conducted in 
addition to the primary efficacy 
analysis to be conducted, and 
added corresponding required 
steps related to SAP finalization 
and interim analysis plan 
approval if an interim analysis is 
to be conducted
28. Updated Appendix 4 according 
to the 25-Nov-2020 Protocol 
Model Document Appendix 
template
29. Updated Appendix 13 according 
to current enterprise COVID-19 
language
Protocol Administrative 
Letter 01
04-Jun-2021
 
Aligned the laboratory to be used for 
Clostridioides difficile testing in 
Table 11 with Section 9.4.3.
Protocol Amendment 01
06-May-2021
 
Changes include the following:
1. Added information, instructions,
and measures to be taken in 
relation to SARS-CoV-2 infection
2. Added clarification regarding 
additional research sample 
collection and use
3. Removed prohibition of medical 
marijuana
4. Added assessments of mean 
corpuscular volume and mean 
corpuscular hemoglobin to the list 
of hematology laboratory tests to 
be conducted.
5. Removed the endoscopic global 
severity score. This was included 
in error, and is not being collected 
in the study.
6. Clarified the definitions of 
steroid-dependent and 
steroid-resistant UC, to aid eCRF 
completion.
7. Clarified the definition of the 
Ulcerative Colitis Endoscopic 
Index of Severity (UCEIS).
8. Clarified male contraception 
requirements
Original Protocol
22-Apr-2020
 
Not applicable
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Date: 24-Feb-2022
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Document
Date of Issue
Approver(s)
Summary of Changes
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OVERALL RATIONALE FOR PROTOCOL AMENDMENT 02:
Rationale:
The primary purpose of this protocol amendment is to remove the BMS-986165 6  mg twice daily 
(BID) treatment arm from the induction phase (first 12 weeks) as a BMS-986165 Phase 2 study in 
subjects with ulcerative colitis (UC) (Study IM011024) did not meet prespecified efficacy 
endpoints during induction (the first 12 weeks of treatment) at the BMS-986165 6 mg BID dose.
Key additions and clarifications include:

Removed the BMS-986165 6 mg BID treatment arm, with subjects subsequently randomized 
in a 3:1 ratio to either 12 mg BID (~37 subjects) or placebo BID (~13 subjects) treatment.

Clarified that subjects currently receiving treatment in the BMS-986165 6 mg BID arm under 
the Original Protocol or Protocol Amendment 01 will continue to receive BMS-986165 6 mg
BID treatment throughout the double-blind period.

Updated prior UC medication Inclusion Criterion 4)a) to Criterion 4)b) to require inadequate 
response, loss of response, or intolerance to a treatment course of 1 or more of the standard of 
care UC medications; added Inclusion Criterion 4)c) to require at least 1 prior treatment course 
of corticosteroids for UC; and added corticosteroids (must have had 2 exposures separated by 
a corticosteroid-free period)
 to 
the list of these standard of care UC medications.

Added potential inclusion of subjects in the study who discontinue treatment with biologics 
due to inadequate funding (previously located in Appendix 5).

Added an enrollment target number of subjects 
 
 
 and included washout 
parameters for the medication class.
 
 
 
 
 
 
 
 

Added study treatment interruption rule for skin AEs and dose interruption criteria for medical 
procedures in the open-label extension (OLE) period in Section 8.1.1.
Protocol Amendment No.: 02
Date: 24-Feb-2022
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
Moved study treatment interruption information from Section 7.4 to Section 8.1.1.

Added definitions/exploratory efficacy endpoints for durable clinical response and durable 
endoscopic response at Week 52, and added a definition for corticosteroid-free remission
(clinical remission in subjects using oral corticosteroids at baseline who have discontinued 
corticosteroids for UC in the OLE period for ≥12 weeks prior to Week 52).

Added Exclusion Criterion 2)g) for subjects receiving cytomegalovirus colitis treatment within
12 weeks of randomization.

Added Exclusion Criterion 7)k) for subjects with a positive diagnostic test for Severe Acute 
Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) during screening and added instruction 
that the screening SARS-CoV-2 diagnostic test must be performed and confirmed negative 
prior to randomization.

Added to the guidance for rescreening of subjects with a positive SARS-CoV-2 test who had 
Coronavirus Disease 2019 (COVID-19) symptoms.

Clarified that AEs related to SARS-CoV-2 should be reported within 24 hours of site 
awareness.

Removed exception to Exclusion Criterion 7)g)ix previously allowing subjects with Gilbert’s 
syndrome to enroll in the study.

Clarified potential acceptability of prophylactic use of antimicrobial agents during the study.

Added calculation of modified Mayo score at Week 52 and symptomatic Mayo score for 
treatment response at Week 20.

Clarified process for rescreening when qualifying endoscopy is completed, including 
determining stool frequency and rectal bleeding scores for eligibility. Additionally, for all 
rescreening, added a 45-day window after the original screening of select laboratory 
assessments during which these laboratory assessments do not need to be repeated if 
rescreening is required.

Incorporated changes from Administrative Letter 01 (aligned the laboratory to be used for 
Clostridioides difficile testing in Table 11 with Section 9.4.3) and added guidance regarding 
the preference for usage of the central laboratory versus local laboratories for performing safety 
assessments.

Added the potential to extend the 14-day window for randomization after the initial screening 
endoscopy by an additional 3 days with BMS Medical Monitor/designee approval (rescreening 
only).

Removed details of potential exposure-response analyses and replaced them with reference to 
separate analysis plan as needed.

Removed reference to “legally acceptable” representatives in relation to signing the informed 
consent form only.

Clarified in Section 10.4.4 that an interim analysis of data would potentially be conducted in 
addition to the primary efficacy analysis to be conducted, and added corresponding required 
steps related to Statistical Analysis Plan finalization and interim analysis plan approval if an 
interim analysis is to be conducted.

Updated Appendix 4 according to the 25-Nov-2020 Protocol Model Document Appendix 
template.
Protocol Amendment No.: 02
Date: 24-Feb-2022
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
Updated Appendix 13 according to current enterprise COVID-19 language.
This protocol amendment will be implemented after the investigator receives all appropriate 
agency and Investigational Review Board/Independent Ethics Committee approvals.
All changes applied to the body were applied to the synopsis, as necessary, and synopsis changes 
are not included in the list below.
Only major additions and deletions are provided in this summary document, and all minor 
grammatical, formatting, rephrasing, stylistic changes, or clarifications, as well as reorganizational 
changes are not included.
The rationales for changes to this protocol amendment are provided in the summary of key changes 
table, as shown below:
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 02
Section Number & Title
Description of Change
Brief Rationale
Section 1.2: Schema
Section 2: Schedule of 
Activities, Table 2
Section 3.2: Benefit/Risk 
Assessment
Section 5.1: Overall Design, 
Figure 1
Section 5.1.2: Double-blind 
Treatment Period
Section 5.4: Scientific 
Rationale for Study Design
 
Section 7.1: Treatments 
Administered
Section 7.2: Method of 
Treatment Assignment
Section 10.1: Sample Size 
Determination
Section 10.1.1: Clinical 
Response Rate
Section 10.4.3.2: 
Exposure-response Modeling
Removed the BMS-986165 6 mg 
twice daily (BID) induction treatment 
arm from the study design, updated 
the randomization ratio to 3:1, and 
updated the subject numbers in each 
arm.
Removed the BMS-986165 6 mg BID 
treatment arm from the induction phase as
the Phase 2 study (Study IM011024) did not 
meet prespecified efficacy endpoints during 
induction (the first 12 weeks) at the 
BMS-986165 6 mg BID dose. The 
randomization ratio was updated to 
accommodate the change in randomization 
scheme; this ratio change will allow for a 
more robust assessment of treatment effect.
Section 1.2: Schema
Section 5.1: Overall Design, 
Figure 1
Section 5.1.2: Double-blind 
Treatment Period
 
Clarified that subjects randomized to 
the BMS-986165 6 mg BID dose arm 
under the Original Protocol or 
Protocol Amendment 01 will continue 
to receive this dose throughout the 
double-blind period.
Clarified that subjects who previously 
received the 6 mg BID dose will continue to 
receive the same dose during the double-
blind period.
Protocol Amendment No.: 02
Date: 24-Feb-2022
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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 02
Section Number & Title
Description of Change
Brief Rationale
Section 7: Treatment, Table 4
Section 7.1: Treatments 
Administered
Section 10.1: Sample Size 
Determination
Section 1.2: Schema
Section 5.1: Overall Design, 
Figure 1
Section 5.1.3: Open-label 
Extension Period
 
 
 
 
 
 
 
 
 
 
 
language added to allow more flexibility for 
the investigator.
Section 2: Schedule of 
Activities, Table 2
Section 9.6: Biomarkers, 
Table 13 and Table 14
 
 
 
 
 
 
 
Added
 sample 
collections to allow for a more complete
characterization of BMS-986165 
pharmacology over time.
Section 2: Schedule of 
Activities, Table 2
Section 5.1.3: Open-label 
Extension Period 
(symptomatic Mayo score 
only)
Added calculation of modified Mayo 
score at Week 52 and symptomatic 
Mayo score for treatment response at 
Week 20.
Clarified the need for sites to perform these 
calculations at these time points.
Section 2: Schedule of 
Activities, Table 1
Section 6.2: Exclusion 
Criteria, 7) Physical and 
Laboratory Test Findings
Added Exclusion Criterion 7)k) for 
subjects with a positive molecular 
(polymerase chain reaction) or antigen 
diagnostic test for Severe Acute 
Respiratory Syndrome Coronavirus 2 
(SARS-CoV-2) during screening
(Section 6.2 only), and added 
instruction (Section 2 only) that the 
screening SARS-CoV-2 diagnostic 
test must be performed and confirmed 
negative prior to randomization.
Added for clarification.
Section 4: Objectives and 
Endpoints
Section 5.1.3: Open-label 
Extension Period
 
 
 
 
 
 
Protocol Amendment No.: 02
Date: 24-Feb-2022
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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 02
Section Number & Title
Description of Change
Brief Rationale
Section 4: Objectives and 
Endpoints
 
 
Section 9.1.2: Disease 
Activity and Quality of Life 
Indices Used in this Study, 
Table 10
Added definitions/exploratory 
efficacy endpoints for durable clinical 
response and durable endoscopic 
response, and added definition of 
corticosteroid-free remission.
Added to assess the durability of efficacy 
with dose reduction in the open-label 
extension (OLE) period.
Section 5.1.1: Screening 
Period
Section 5.2: Number of 
Subjects
Section 5.4: Scientific 
Rationale for Study Design
Section 6.1: Inclusion 
Criteria, 4) Prior UC 
Medication Inclusion Criteria
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Revised to ensure that the study population 
reflects the range of patients with moderately 
to severely active UC.
Section 5.1.1: Screening 
Period
Section 6.5.2: Rescreening
Added the potential to extend the 
14-day window for randomization 
following the initial screening 
endoscopy by an additional 3 days 
with approval of the BMS Medical 
Monitor/designee (rescreening only).
Added to simplify study operations.
Section 5.1.5: Treatment 
Failure
 
 
Removed requirement 
 
Section 5.1.5: Treatment 
Failure
 
 
 
 
 
 
 
Expanded to include additional criteria that 
apply to the definition of treatment failure.
Protocol Amendment No.: 02
Date: 24-Feb-2022
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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 02
Section Number & Title
Description of Change
Brief Rationale
Section 5.2: Number of 
Subjects
Section 6: Study Population
Appendix 7: Examples of 
Washout Times Required 
Prior to Randomization
Added an enrollment target number of 
subjects previously exposed to 
biologics
 
 
 
 
 and included washout 
parameters for the medication class.
Added to ensure that the study population 
reflects the range of patients with moderately 
to severely active UC
 
.
Section 6.1: Inclusion 
Criteria, 4) Prior UC 
Medication Inclusion Criteria
Appendix 5: Criteria To 
Define Inadequate Response 
(Primary), Loss Of Response 
(Secondary), And Intolerance 
To Previous Standard Of Care 
Medication(s)
Moved potential study inclusion of 
subjects who stop treatment with 
biologics due to loss of funding
previously in Appendix 5 to Inclusion 
Criterion 4)b).
Moved for clarity/greater visibility.
Section 6.2: Exclusion 
Criteria, 2) UC Exclusion 
Criteria
Added Exclusion Criterion 2)g) for 
subjects receiving treatment for 
cytomegalovirus (CMV) colitis within 
12 week of randomization.
Added treatment for CMV colitis as 
exclusionary avoid confounding efficacy and 
safety assessments.
Section 6.2: Exclusion 
Criteria, 5) Immune and 
Infectious Disease Exclusion 
Criteria - updated 5)b) → 5)f)
Section 6.2: Exclusion 
Criteria, 6) Prior/Concomitant 
Therapy - updated 6)l) →6)n)
Section 7.7.1: Prohibited 
Treatments, Table 6
Added potential study eligibility of 
subjects being treated prophylactically 
with antimicrobial agents (including 
antibiotics) during the study.
Clarified inclusion/exclusion in the study by 
distinguishing antimicrobial therapy as either 
for direct treatment or strictly for 
prophylactic use.
Section 6.2: Exclusion 
Criteria, 7) Physical and 
Laboratory Test Findings -
updated 7)g)ix) → 7)g)xi)
Removed Exclusion Criterion 
exception which previously allowed 
subjects with Gilbert’s syndrome to 
participate in the study.
Removed Gilbert’s exception to simplify 
interpretation of liver abnormalities if they 
occur.
Section 6.5.2: Rescreening
Clarified process for rescreening 
when qualifying endoscopy is 
completed, including determining 
stool frequency and rectal bleeding 
scores for eligibility. Additionally, for 
all rescreening, added a 45-day 
window after the original screening of 
select laboratory assessments during 
which these laboratory assessments do 
not need to be repeated if rescreening 
is required.
Added to simplify study operations.
Protocol Amendment No.: 02
Date: 24-Feb-2022
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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 02
Section Number & Title
Description of Change
Brief Rationale
Section 7.4: Dosage 
Modification
Section 8.1.1: Temporary 
Interruption of Study 
Treatment
Moved study treatment interruption 
information from Section 7.4 to 
Section 8.1.1.
Moved for clarity/greater visibility.
Section 7.7.1: Prohibited 
Treatments, Table 6
Section 7.7.3: Dose 
Stabilization Rules for 
Permitted UC Treatments, 
Table 8
 
 
 
 
 
Expanded stabilization window for 
corticosteroids and 5-ASA to minimize 
impact on efficacy.
Section 8.1.1: Temporary 
Interruption of Study 
Treatment
Added a study treatment interruption 
rule for skin adverse events (AEs) and 
dose interruption criteria for medical 
procedures in the OLE period.
Aligned dose interruption criteria related to
skin AEs with Revised Protocol 00a 
CA-specific (dated 29-Oct-2020) and to 
clarify conditions under which dose 
interruption related to medical procedures is 
permitted.
Section 9.2.1: Time Period 
and Frequency for Collecting 
AE and SAE Information
Section 9.8: SARS-CoV-2 
Testing
Clarified reporting time requirements 
for AEs related to SARS-CoV-2 
(within 24 hours of site awareness).
Added to clarify safety reporting.
Section 9.4.3: Clinical 
Laboratory Assessments
Aligned the laboratory to be used for 
Clostridioides difficile testing in 
Table 11 with Section 9.4.3 (central or 
local laboratory acceptable) and added 
guidance regarding the preference for 
usage of the central laboratory versus 
local laboratories for performing 
safety assessments.
Added to incorporate changes from 
Administrative Letter 01 and to simplify 
study operations.
Section 9.8: SARS-CoV-2 
Testing
Added to the guidance for rescreening 
of subjects with a positive 
SARS-CoV-2 test who had 
Coronavirus Disease 2019 
(COVID-19) symptoms.
Clarified rescreening requirements related to 
resolution of COVID-19 symptoms.
Section 10.4.3.2: Exposure-
response Modeling
Removed details of potential 
exposure-response analyses and 
replaced with reference to separate 
analysis plan as needed.
Streamlined this section.
Section 10.4.4: Interim 
Analyses
Clarified that an interim analysis of 
data would potentially be conducted 
in addition to the primary efficacy 
analysis, and added that the Statistical 
Analysis Plan will be finalized and an 
interim analysis plan will be approved 
Clarified information related to an interim 
analysis.
Protocol Amendment No.: 02
Date: 24-Feb-2022
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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 02
Section Number & Title
Description of Change
Brief Rationale
prior to interim analysis database lock 
if an interim analysis is to be 
conducted.
Appendix 2: Study 
Governance Considerations
Removed reference to “legally 
acceptable” representatives in relation
to signing the ICF only.
Removed because all subjects must sign the 
ICF themselves.
Appendix 4: Women of Child 
Bearing Potential
Removed vaginal suppositories, gels, 
and creams from highly effective 
user-dependent contraceptive 
methods.
Harmonized with the 25Nov2020 Protocol 
Model Document Appendix template.
Appendix 5: Criteria To 
Define Inadequate Response 
(Primary), Loss Of Response 
(Secondary), And Intolerance 
To Previous Standard Of Care 
Medication(s)
 
 
 
 
Aligned criteria with updates to Inclusion 
and Exclusion criteria.
Appendix 13: Vaccine 
Guidance Including 
SARS-CoV-2 Vaccines
Updated appendix language related to 
SARS-CoV-2 vaccine guidance.
Harmonized with current enterprise 
COVID-19 language.
Please provide a copy to your Investigational Review Board/Independent Ethics 
Committee, unless agreed otherwise with BMS.
Protocol Amendment No.: 02
Date: 24-Feb-2022
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TABLE OF CONTENTS 
 
 
TITLE PAGE ................................................................................................................ 
 
DOCUMENT HISTORY .............................................................................................. 
 
OVERALL RATIONALE FOR PROTOCOL AMENDMENT 02: ............................ 
 
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 02 ................ 
 
TABLE OF CONTENTS .............................................................................................. 
 
1 PROTOCOL SUMMARY ......................................................................................... 
 
1.1 Synopsis ............................................................................................................ 
 
1.2 Schema .............................................................................................................. 
 
2 SCHEDULE OF ACTIVITIES.................................................................................. 
 
3 INTRODUCTION ..................................................................................................... 
 
3.1 Background ....................................................................................................... 
 
3.1.1 Nonclinical Toxicology ............................................................................ 
 
3.1.2 Early Clinical Experience ........................................................................ 
 
3.1.3 BMS-986165 12 mg QD or BID Dose Regimen Studies .......................... 
 
 
 
3.1.5 BMS-986165 and Inflammatory Bowel Disease Studies: Overview ........ 
 
 
 
3.2 Benefit/Risk Assessment .................................................................................. 
 
4 OBJECTIVES AND ENDPOINTS ........................................................................... 
 
5 STUDY DESIGN....................................................................................................... 
 
5.1 Overall Design .................................................................................................. 
 
5.1.1 Screening Period ...................................................................................... 
 
5.1.2 Double-blind Treatment Period ............................................................... 
 
5.1.3 Open-label Extension Period ................................................................... 
 
5.1.4 Follow-up Period ..................................................................................... 
 
5.1.5 Treatment Failure .................................................................................... 
 
5.1.6 Safety Monitoring and Data Monitoring Committee ............................... 
 
5.2 Number of Subjects ........................................................................................... 
 
5.3 End-of-Study Definition ................................................................................... 
 
5.4 Scientific Rationale for Study Design............................................................... 
 
 
 
6 STUDY POPULATION ............................................................................................ 
 
6.1 Inclusion Criteria .............................................................................................. 
 
6.2 Exclusion Criteria ............................................................................................. 
 
6.3 Randomization Criteria ..................................................................................... 
 
6.4 Lifestyle Restrictions ........................................................................................ 
 
6.5 Screen Failures .................................................................................................. 
 
6.5.1 Retesting During the Screening Period ................................................... 
 
6.5.2 Rescreening .............................................................................................. 
 
7 TREATMENT ........................................................................................................... 
 
7.1 Treatments Administered .................................................................................. 
 
7.2 Method of Treatment Assignment .................................................................... 
 
7.3 Blinding............................................................................................................. 
 
7.3.1 Maintaining the Blind .............................................................................. 
 
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7.3.2 Circumstances for Unblinding ................................................................. 
 
7.4 Dosage Modification ......................................................................................... 
 
7.5 Preparation/Handling/Storage/Accountability .................................................. 
 
7.5.1 Retained Samples for Bioavailability/Bioequivalence/Biocomparability 
 
7.6 Treatment Compliance ...................................................................................... 
 
7.7 Concomitant Therapy........................................................................................ 
 
7.7.1 Prohibited Treatments ............................................................................. 
 
7.7.2 Restricted Treatments .............................................................................. 
 
7.7.3 Dose Stabilization Rules for Permitted UC Treatments .......................... 
 
 
 
7.8 Treatment After the End of the Study ............................................................... 
 
8 DISCONTINUATION CRITERIA ........................................................................... 
 
8.1 Discontinuation from Study Treatment ............................................................ 
 
8.1.1 Temporary Interruption of Study Treatment ............................................ 
 
8.1.2 Poststudy Treatment Study Follow-Up .................................................... 
 
8.2 Discontinuation from the Study ........................................................................ 
 
8.3 Lost to Follow-Up ............................................................................................. 
 
8.4 Replacement of Subjects ................................................................................... 
 
8.5 Study Discontinuation ....................................................................................... 
 
9 STUDY ASSESSMENTS AND PROCEDURES ..................................................... 
 
9.1 Efficacy Assessments ........................................................................................ 
 
9.1.1 Capturing Data to Assess Disease Activity and Determine Efficacy ....... 
 
9.1.2 Disease Activity and Quality of Life Indices Used in this Study .............. 
 
9.2 Adverse Events ................................................................................................. 
 
9.2.1 Time Period and Frequency for Collecting AE and SAE Information .... 
 
9.2.2 Method of Detecting AEs and SAEs ......................................................... 
 
9.2.3 Follow-up of AEs and SAEs ..................................................................... 
 
9.2.4 Regulatory Reporting Requirements for SAEs ......................................... 
 
9.2.5 Pregnancy ................................................................................................ 
 
9.2.6 Laboratory Test Result Abnormalities ..................................................... 
 
9.2.7 Potential Drug-Induced Liver Injury (DILI) ............................................ 
 
9.2.8 Adverse Events of Interest (Clinical Safety Program) ............................. 
 
9.2.9 Other Safety Considerations .................................................................... 
 
9.3 Overdose ........................................................................................................... 
 
9.4 Safety ................................................................................................................ 
 
9.4.1 Physical Examinations ............................................................................. 
 
9.4.2 Tuberculosis Screening and Chest X-ray ................................................. 
 
9.4.3 Clinical Safety Laboratory Assessments .................................................. 
 
9.4.4 Imaging Safety Assessment ...................................................................... 
 
9.4.5 Vital Signs ................................................................................................ 
 
9.4.6 Electrocardiograms ................................................................................. 
 
 
 
 
 
 
 
9.6 Biomarkers ........................................................................................................ 
 
9.6.1 Additional Research Collection ............................................................... 
 
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9.7 Medical Resource Utilization and Health Economics ...................................... 
 
9.8 SARS-CoV-2 Testing ....................................................................................... 
 
10 STATISTICAL CONSIDERATIONS .................................................................... 
 
10.1 Sample Size Determination ............................................................................. 
 
10.1.1 Clinical Response Rate .......................................................................... 
 
10.1.2 Adverse Event Incidence ........................................................................ 
 
 
 
10.2 Populations for Analyses ................................................................................ 
 
10.3 Endpoints ........................................................................................................ 
 
10.4 Statistical Analyses ......................................................................................... 
 
10.4.1 Efficacy Analyses ................................................................................... 
 
10.4.1.1 Primary Endpoint.......................................................................... 
 
10.4.1.2 Exploratory Endpoints .................................................................. 
 
10.4.2 Safety Analyses....................................................................................... 
 
10.4.2.1 Adverse Events .............................................................................. 
 
10.4.2.2 Vital Signs and ECGs.................................................................... 
 
10.4.2.3 Clinical Laboratory Tests ............................................................. 
 
10.4.3 Other Analyses ....................................................................................... 
 
 
 
10.4.3.2 Exposure-response Modeling ........................................................ 
 
10.4.3.3 Quality of Life and Medical Resource Analyses ........................... 
 
10.4.4 Interim Analyses ..................................................................................... 
 
11 REFERENCES ........................................................................................................ 
 
12 APPENDICES ......................................................................................................... 
 
APPENDIX 1 ABBREVIATIONS AND TRADEMARKS ........................................ 
 
APPENDIX 2 STUDY GOVERNANCE CONSIDERATIONS ................................. 
 
APPENDIX 3 ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS: 
DEFINITIONS AND PROCEDURES FOR RECORDING, EVALUATING, 
FOLLOW-UP AND REPORTING ........................................................................ 
 
APPENDIX 4 WOMEN OF CHILDBEARING POTENTIAL DEFINITIONS AND 
METHODS OF CONTRACEPTION ..................................................................... 
 
APPENDIX 5 CRITERIA TO DEFINE INADEQUATE RESPONSE (PRIMARY), 
LOSS OF RESPONSE (SECONDARY), AND INTOLERANCE TO PREVIOUS 
STANDARD OF CARE MEDICATION(S) .......................................................... 
 
APPENDIX 6 COMMONLY USED CORTICOSTEROID EQUIVALENTS ........... 
 
APPENDIX 7 EXAMPLES OF WASHOUT TIMES REQUIRED PRIOR TO 
RANDOMIZATION............................................................................................... 
 
 
 
APPENDIX 9 MAYO SCORE: COMPONENT SUBSCORES AND ELECTRONIC 
SUBJECT DIARY ENTRY INSTRUCTIONS ...................................................... 
 
APPENDIX 10 ULCERATIVE COLITIS ENDOSCOPIC INDEX OF SEVERITY 
(UCEIS): SCORES AND DEFINITIONS.............................................................. 
 
APPENDIX 11 INFLAMMATORY BOWEL DISEASE QUESTIONNAIRE (IBDQ)
................................................................................................................................. 
 
APPENDIX 12 ULCERATIVE COLITIS-RELATED HEALTHCARE 
UTILIZATION ....................................................................................................... 
 
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APPENDIX 13 VACCINE GUIDANCE INCLUDING SARS-COV-2 VACCINES . 
 
APPENDIX 14 PROTOCOL AMENDMENT SUMMARY OF CHANGE HISTORY
................................................................................................................................. 
 
 
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IM011127
BMS-986165
TYK2 Inhibitor
1
PROTOCOL SUMMARY
1.1
Synopsis
Protocol Title: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of the Safety, 
Efficacy, and Biomarker Response of BMS-986165 in Subjects with Moderate to Severe 
Ulcerative Colitis
Short Title: Safety, Efficacy, and Biomarker Response of BMS-986165 in Subjects with 
Moderate to Severe Ulcerative Colitis
Study Phase: 2
Study Rationale: Study IM011127 is a Phase 2 randomized, double-blind, placebo-controlled, 
multicenter study designed to assess the safety and tolerability, efficacy, and biomarker response 
of BMS-986165 12 mg twice daily (BID) orally (PO) in subjects with moderate to severe 
ulcerative colitis (UC).
This study is being conducted in the context of a wider clinical development program of
BMS-986165
in inflammatory bowel disease (IBD; Section 3.1.5).
Study IM011023 
(NCT03599622) assesses safety and efficacy of BMS-986165 6 mg BID and 3 mg BID PO 
regimens compared with placebo in subjects with moderately to severely active Crohn’s disease 
(CD). Study IM011024 (NCT03934216) compares BMS-986165 6 mg BID PO with placebo in 
subjects with moderately to severely active UC.
BMS-986165 6 mg BID and placebo reference arms were originally included in this study to 
facilitate an integrated analysis of safety, efficacy, and biomarker data from the current study and
Study IM011024. The 6 mg BID treatment arm is being removed from the induction phase in 
Protocol Amendment 02 due to Study IM011024 not meeting prespecified efficacy endpoints 
during induction (the first 12 weeks of treatment) at the 6 mg BID dose. The placebo reference 
arm has also been included to manage bias in the reporting of safety data and the reporting of 
patient-reported outcomes (PROs), including the PRO components of the modified Mayo score
that contribute to the evaluation of disease activity-based Inclusion Criteria and the primary 
endpoint of this study.
BMS-986165 12 mg BID is being assessed in this study for the following reasons:
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BMS-986165
TYK2 Inhibitor
 
 
 
 
The safety and tolerability of BMS-986165 at single doses of up to 40 mg and at multiple doses of 
up to 12 mg BID was assessed in NHV studies. In addition, the safety, tolerability, and efficacy of 
BMS-986165 at doses of up to 6 mg BID and 12 mg QD have been explored in a Phase 2 clinical 
trial in psoriasis.
The safety and tolerability of BMS-986165 at 12 mg QD or 12 mg BID regimens in NHV studies 
is detailed in Section 3.1.3. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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IM011127
BMS-986165
TYK2 Inhibitor
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Clinical Protocol
IM011127
BMS-986165
TYK2 Inhibitor
 
 
 
 
 
 
 
 
 
 
 
 
 
The goals of this study are to:
1. Estimate the efficacy of BMS-986165 12 mg BID in subjects with UC
The efficacy of BMS-986165 12 mg BID PO will be estimated at Week 12, and over time, using 
both standard instruments (eg, modified Mayo score) and novel instruments specifically designed 
for use in exploratory studies (eg, UC-100; see Section 9.1.2).
2. Evaluate the safety and tolerability of BMS-986165 12 mg BID in subjects with UC
BMS-986165 12 mg QD and 12 mg BID have been explored in healthy volunteers for up to 
14 days (Section 3.1.3 and IB5). 
 
 BMS-986165 6 mg BID is currently 
being explored in subjects with UC and CD (Section 3.1.5). However, this study is the first 
experience of BMS-986165 12 mg BID PO in subjects with UC. Consequently, this study will 
carefully assess the safety and tolerability of this regimen in this patient population. Additional 
safety assessments will be incorporated into this study, based on experience at relevant dose levels 
in preceding studies. Multiple levels of study oversight will be provided by the Sponsor through 
medical monitoring as well as periodic review of collected safety data by an external, independent 
Data Monitoring Committee (DMC) (Section 5.1.6).
 
 
 
 
 
 
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IM011127
BMS-986165
TYK2 Inhibitor
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Population:
Key Inclusion Criteria (Section 6.1) include:

Males and females, ages 18 (or local age of majority) to 65 years, inclusive, at the time of 
screening

Documented diagnosis of UC ≥3 months’ duration prior to screening

UC disease distribution extending proximal to the rectum (ie, left-sided colitis or pancolitis)

Moderately to severely active UC, defined by a modified Mayo score of 5 to 9 points, inclusive 
(modified Mayo score range = 0 to 9 points), which includes all of the following:

A stool frequency (SF) subscore of ≥ 2, and

A rectal bleeding (RB) subscore ≥ 1, and
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IM011127
BMS-986165
TYK2 Inhibitor

An endoscopic (ES) subscore of ≥ 2 (screening endoscopy)

Inadequate response, loss of response, or intolerance to a treatment course of 1 or more of the 
following standard of care UC medications (APPENDIX 5):

Oral 5-aminosalicylic acids (5-ASAs) (eg, mesalamine, sulfasalazine, olsalazine, or 
balsalazide)

Corticosteroids (eg, prednisone or budesonide Multi-Matrix System [MMX]) (must have 
had 2 exposures separated by a corticosteroid-free period)

Immunomodulators (eg, azathioprine [AZA], 6-mercaptopurine [6-MP], or methotrexate 
[MTX])

Anti-TNF agents or integrin inhibitors (eg, vedolizumab) approved for the treatment of UC
 
 
 
 
 

Subjects who stop treatment with biologics due to loss of funding (eg, loss of insurance 
coverage) may also be eligible for inclusion into the study. Subject eligibility should be 
discussed with the BMS Medical Monitor/designee.
 
 
 
Key Exclusion Criteria (Section 6.2) include:

UC involving the rectum only (UC proctitis)

Current diagnosis of CD, indeterminate colitis, ischemic colitis or microscopic colitis, a 
monogenic cause of UC-like intestinal inflammation, or a diagnosis of pseudomembranous 
colitis other than that associated with Clostridioides difficile (formerly Clostridium difficile [C. 
difficile])

Current or recent (within 12 weeks prior to randomization) evidence of fulminant UC (also 
known as acute severe UC), toxic megacolon, evidence of bowel perforation, or intra-
abdominal abscess

Current colonic adenomas or mucosal dysplasia
 
 
 
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Clinical Protocol
IM011127
BMS-986165
TYK2 Inhibitor

Prior treatment failure (inadequate response or loss of response) 
 
Objectives and Endpoints:
The key efficacy, safety, 
 objectives and endpoints are summarized below:
Objective
Endpoints
Primary - Efficacy

To estimate the efficacy of
BMS-986165 at Week 12

Proportion of subjects in clinical response at 
Week 12
Safety

To assess the safety and tolerability
of BMS-986165

Number and proportion of subjects 
experiencing AEs, SAEs, AEs leading to 
discontinuation from the study, and AEIs 
throughout the study
Exploratory 
 
AE = adverse event; AEI = adverse event of interest; SAE = serious adverse event
A complete list of objectives and endpoints is provided in Section 4.
Overall Design:

Study design: Parallel, double-blind, placebo-controlled, multicenter clinical trial (12 weeks), 
with a 40-week open-label extension (OLE) period

Blinding: Double-blind, matching placebo oral tablets

Treatment assignment method/stratification:

Subjects who have completed screening procedures (up to 28 days duration) and met 
Inclusion/Exclusion criteria will be randomized on Day 1 of the treatment period.

Not Applicable to Subjects Enrolled Under Protocol Amendment 02. Subjects will be 
randomized in a 3:1:1 ratio using interactive response technology (IRT) to receive oral 
BMS-986165 12 mg BID, BMS-986165 6 mg BID, or placebo BID during the 12-week 
treatment period.

Subjects will be randomized in a 3:1 ratio using IRT to receive oral BMS-986165 
12 mg BID or placebo BID during the 12-week treatment period.

Subjects randomized to the BMS-986165 6 mg BID arm under the Original Protocol or
Protocol Amendment 01 will continue to receive BMS-986165 6 mg BID for the 12-week
double-blind treatment period.

Randomization will not be stratified.
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Clinical Protocol
IM011127
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TYK2 Inhibitor

Study periods:

Screening: up to 4 weeks (28 days)

Double-blind treatment: 12 weeks (84 days)

OLE: up to 40 weeks (280 days)

Follow-up: 4 weeks (28 days)
The total duration of study participation is approximately 60 weeks (420 days) in 4 periods.

Study assessments: Include assessments of medical and UC disease history, prior 
medications, concomitant medications and UC medications, tobacco use, baseline SF; physical 
examinations; chest x-ray (CXR); 12-lead electrocardiogram (ECG); blood, stool, and urine 
sample collections; endoscopies with biopsies; additional efficacy assessments and the 
Physician’s Global Assessment (PGA); and subject collection of PROs in daily electronic 
diaries as outlined in the Schedule of Activities (Section 2).
 
 
 

Discontinuation from the study: Subjects who discontinue study treatment will remain in the 
study and are required to continue to be followed for protocol-specified post-treatment 
follow-up procedures. The only exception to this is when a subject specifically withdraws 
consent for any further contact with him/her or persons previously authorized by the subject to 
provide this information.
Safety monitoring will occur at study sites, by the Sponsor, and also by an external, independent 
DMC (Section 5.1.6).
Number of Subjects: Approximately 50 subjects
Treatment Arms and Duration:
Double-blind Treatment Period: On Day 1, subjects will be randomized to receive 1 of the 
following study treatments:

BMS-986165 12 mg BID

Not Applicable to Subjects Enrolled Under Protocol Amendment 02. BMS-986165 6 mg 
BID

Placebo BID
OLE Period: Subjects who are likely to derive a clinical benefit from ongoing participation in the 
study following Week 12, as judged by the investigator, are eligible to enter the OLE period and 
receive the following study treatment:
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Clinical Protocol
IM011127
BMS-986165
TYK2 Inhibitor

BMS-986165 6 mg BID
Study Treatment:
Study Treatments for IM011127
Product Description/
Class and Dosage 
Form
Potency
IP/
Non-IP
Blinded or 
Open-label
Packaging/
Appearance
Storage Conditions
(per label)
BMS-986165
12 mg oral tablet
12 mg
IP
Blinded
Blister card 
containing 
72 tablets
Store 15° to 25°C; 
Protected from light
BMS-986165
6 mg oral tablet
Applicable only to 
subjects enrolled under 
the Original Protocol or 
Protocol Amendment 01
6 mg
IP
Blinded
Blister card 
containing 
72 tablets
Store 15° to 25°C; 
Protected from light
Placebo matching
BMS-986165
12 mg oral tablet
Not 
applicable
IP
Blinded
Blister card 
containing 
72 tablets
Store 15° to 25°C; 
Protected from light
Placebo matching
BMS-986165
6 mg oral tablet
Not 
applicable
IP
Blinded
Blister card 
containing 
72 tablets
Store 15° to 25°C; 
Protected from light
BMS-986165
6 mg oral tablet
6 mg
IP
Open-label
Bottle containing 
68 tablets
Store 15° to 25°C; 
Protected from light
IP = investigational product
Statistical Methods: Approximately 50 subjects will be randomized in a 3:1 ratio to BMS‑986165 
12 mg BID and placebo BID, respectively (ie, approximately 37 subjects receiving BMS‑986165 
12 mg BID and 13 subjects receiving placebo BID). Approximately 3 subjects (enrolled under the 
Original Protocol or Protocol Amendment 01) are expected to receive BMS-986165 6 mg BID and 
will also be included. The sample size for this study is not based on statistical power for 
comparisons among treatment groups. It has been selected to provide adequate precision for the 
estimation of efficacy (Section 10.1.1), safety (Section 10.1.2)
 
 in subjects treated with BMS‑986165 12 mg BID.
Categorical data will be summarized as frequency counts and percentages. Continuous data will 
be summarized using n, mean, standard deviation, median, minimum, and maximum, unless 
otherwise specified.
Efficacy data will be summarized using the full analysis set population, unless otherwise stated, 
and listed by treatment group.
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Clinical Protocol
IM011127
BMS-986165
TYK2 Inhibitor
The primary efficacy endpoint (proportion of subjects achieving clinical response at Week 12) and 
the associated 95% confidence interval (CI) for the BMS-986165 12 mg BID treatment arm will 
be estimated using the Clopper-Pearson exact method. Supportive analysis using logistic 
regression for the clinical response (binary endpoint) may be performed if the data are sufficient 
to do so.
Safety endpoint analyses will be descriptive in nature.
 
 
 
 
 
 
 
 
1.2
Schema
The study design schematic for this study is presented below:
BID = twice daily; OLE = open-label extension; PO = orally; R = randomization
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Clinical Protocol
IM011127
BMS-986165
TYK2 Inhibitor
Note: Subjects randomized to the BMS-986165 6 mg BID induction treatment arm under the Original Protocol or 
Protocol Amendment 01 will continue to receive this dose throughout the double-blind period and will receive 6 mg 
BID in the OLE period.
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Clinical Protocol
IM011127
BMS-986165
TYK2 Inhibitor
2
SCHEDULE OF ACTIVITIES
The schedules of procedures for the screening and on-treatment study periods are described in Table 1. The schedules of procedures for 
the OLE and post-treatment follow-up periods are described in Table 2.
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IM011127
BMS-986165
TYK2 Inhibitor
Table 1:
Screening and Double-Blind Treatment Period Procedural Outline (IM011127)
Study Procedure
Screening
Day -28 
to -1
Day 1
Week 1
(Day 8)
Week 2
(Day 15)
Week 4
(Day 29)
Week 8
(Day 57)
Week 12
(Day 85)
Notes
Visit window (± n days)
N/A
0
2
3
3
3
3
Eligibility and Disease Assessments
Informed Consent
X
Section 5.1.1
Obtain subject number (IRT)
X
Section 7.2
Medical history and UC disease history
X
Section 5.1
Prior medications
X
Section 5.1.1
Concomitant medications and UC 
medications
X
X
X
X
X
X
Section 7.7 and 
APPENDIX 7
Tobacco/e-cigarette use
X
X
X
X
X
X
Section 6.4
Baseline SF
X
APPENDIX 9
Review Inclusion/Exclusion criteria, 
eligibility
X
X
Section 6
Physical Examination
Section 9.4.1
Physical examination
X
X
X
Section 9.4.1
Weight
X
X
X
Section 9.4.1
Height
X
Section 9.4.1
Vital signs (HR, BP, Temp)
X
X
X
X
X
X
Section 9.4.5
Electronic Diary (eCOA Device)
Section 9.1.1
Dispense and train subject on electronic 
daily diary
X
APPENDIX 9
Subject completes electronic daily diary
X
X
APPENDIX 9
Review compliance with electronic daily 
diary
X
X
X
X
X
APPENDIX 9
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Clinical Protocol
IM011127
BMS-986165
TYK2 Inhibitor
Table 1:
Screening and Double-Blind Treatment Period Procedural Outline (IM011127)
Study Procedure
Screening
Day -28 
to -1
Day 1
Week 1
(Day 8)
Week 2
(Day 15)
Week 4
(Day 29)
Week 8
(Day 57)
Week 12
(Day 85)
Notes
Visit window (± n days)
N/A
0
2
3
3
3
3
CXR and ECG
CXR
Xg
Section 9.4.2
ECG
X
X
Section 9.4.6
Blood and Urine Tests
Hematology, chemistry, coagulation
X
X
Xh
X
X
X
X
Section 9.4.3 and Table 11
Fasting lipid panel and glucose
X
X
Section 9.4.3 and Table 11
TSH
X
Section 9.4.3 and Table 11
FSHb
X
Section 9.4.3 and 
APPENDIX 4
Serum hsCRP
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Table 1:
Screening and Double-Blind Treatment Period Procedural Outline (IM011127)
Study Procedure
Screening
Day -28 
to -1
Day 1
Week 1
(Day 8)
Week 2
(Day 15)
Week 4
(Day 29)
Week 8
(Day 57)
Week 12
(Day 85)
Notes
Visit window (± n days)
N/A
0
2
3
3
3
3
Urinalysis and urine chemistry
X
X
Section 9.4.3 and Table 11
Additional Blood Tests 
Whole blood for genotyping
Xl
Section 9.6 and Table 13
Whole blood for gene expression
X
X
X
X
X
Section 9.6 and Table 13
Whole blood for FACS
X
X
X
Section 9.6 and Table 13
Whole blood for PBMC
X
X
X
Section 9.6 and Table 13
Diagnostic test for SARS-CoV-2d
X
Section 9.8
Stool Collection
Aliquots from single 
sample
Stool culturee
X
Section 9.4.3
Stool for C. difficile testing
X
Section 9.4.3
Stool for fecal lactoferrin
X
Xm
X
X
X
X
Section 9.6 and Table 13
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Table 1:
Screening and Double-Blind Treatment Period Procedural Outline (IM011127)
Study Procedure
Screening
Day -28 
to -1
Day 1
Week 1
(Day 8)
Week 2
(Day 15)
Week 4
(Day 29)
Week 8
(Day 57)
Week 12
(Day 85)
Notes
Visit window (± n days)
N/A
0
2
3
3
3
3
Endoscopy and Endoscopic Biopsies
Endoscopy
X
X
Section 9.1.1
Biopsies for gene expression
X
X
Section 9.6 and Table 14
Biopsy from noninvolved area (if 
available) for gene expression
X
X
Section 9.6 and Table 14
Additional Efficacy Assessments
Site calculates the modified Mayo score
Xn
X
Section 9.1.2 and 
APPENDIX 9
PGA
X
X
X
X
X
X
Section 9.1.2 and 
APPENDIX 9
The partial Mayo score may be 
determined from data collected at these 
visitsf
X
X
X
X
X
X
Section 9.1.2 and 
APPENDIX 9
The modified Mayo score, total Mayo 
score, and UC-100 may be determined 
from data collected at these visitsf
X
X
X
Section 9.1.2 and 
APPENDIX 9
Health-related Quality of Life
Section 9.1.1
IBDQ
X
X
X
Section 9.1.2 and 
APPENDIX 11
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BMS-986165
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Table 1:
Screening and Double-Blind Treatment Period Procedural Outline (IM011127)
Study Procedure
Screening
Day -28 
to -1
Day 1
Week 1
(Day 8)
Week 2
(Day 15)
Week 4
(Day 29)
Week 8
(Day 57)
Week 12
(Day 85)
Notes
Visit window (± n days)
N/A
0
2
3
3
3
3
UC-related hospitalization and surgery
X
X
X
X
X
Section 9.1.2 and 
APPENDIX 12
Safety Assessment (in addition to the 
above)
APPENDIX 3
Monitor AEs
Xp
X
X
X
X
X
X
Section 0
Monitor SAEs
X
X
X
X
X
X
X
Section 0
IP Supply
Dispense IP
X
X
X
X
Xo
Section 5.1.2
Study treatment
X
X
Section 7.1
Review subject compliance with IP
X
X
X
X
Section 7.6
AE = adverse event; 
 BP = blood pressure; COVID-
19 = Coronavirus Disease 2019; CXR = chest x-ray; 
ECG = electrocardiogram; 
eCOA = electronic clinical outcome assessments; FACS = fluorescence-activated cell sorting; 
 HBsAg = hepatitis B surface 
antigen; 
 HR = heart rate; hsCRP = high-sensitivity C-reactive protein; 
IBDQ = Inflammatory Bowel Disease Questionnaire; ICF = informed consent form; 
 IP = investigational product; IRT = interactive response 
technology; N/A = not applicable; OLE = open-label extension; PBMC = peripheral blood mononuclear cells; PCR = polymerase chain reaction; 
PGA = Physician’s Global Assessment; 
 SAE = serious adverse event; SARS-CoV-2 = Severe Acute Respiratory Syndrome Coronavirus 
2; 
 SF = stool frequency; 
 Temp = temperature; TSH = thyroid-stimulating 
hormone; UC = ulcerative colitis; WOCBP = women of childbearing potential
b FSH may be performed in amenorrheic females < 55 years of age if indicated to confirm postmenopausal status (see APPENDIX 4). It will not be considered a 
protocol deviation if a site obtains an FSH level in error, ie, in male subjects.
 
 
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d Diagnostic testing for SARS-CoV-2 infection should be performed as close as possible to randomization and must be confirmed as “negative” prior to 
randomization.
e A multipathogen molecular panel for enteric pathogens (eg, multipathogen PCR) may be considered as an alternative to stool culture, if this is routinely performed 
at a site and its use is consistent with local standard of care. Use of this test within the study should be discussed with the BMS Medical Monitor/designee.
f Efficacy instruments listed in italics are for site reference only. These scores will not be calculated by the investigator.
g A CXR performed less than 6 months prior to signing of the ICF may be used in place of the screening CXR, provided the subject has no symptoms or signs 
suggestive of pulmonary disease in the interim.
h Chemistry only (liver function test panel).
 
 
 
l
To be collected only from those subjects who sign the appropriate consent form.
m It will not be considered a protocol deviation if a subject is unable to produce a stool sample at Day 1, provided that 
 fecal lactoferrin have 
been successfully collected at the screening visit.
n The modified Mayo score calculated to determine eligibility will be used for randomization on Day 1 as the baseline score.
o IP will be dispensed only to those subjects who continue in the study and enter the OLE period (Table 2).
p AEs related to COVID-19 should be collected from time of signing informed consent.
General procedural note: The protocol does not mandate specific investigations at unscheduled visits. Unscheduled visit study procedures should be based on the 
clinical judgment of the investigator.
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TYK2 Inhibitor
Table 2:
Open-label Extension Period Procedural Outline (IM011127)
Study Procedure
Week 16 
(Day 
113)
Week 20 
(Day 
141)
Week 24 
(Day 
169)
Week 32 
(Day 
225)
Week 40 
(Day 
281)
Week 52
(Day 365) 
EOT/ETd
Week 
56
(Day 
393)
F/U
Notes
Visit window (± n days)
3
3
3
3
3
3
7
Disease Assessments
Concomitant medications and UC 
medications
X
X
X
X
X
X
X
Section 7.7 and APPENDIX 7
Tobacco/e-cigarette use
X
X
X
X
X
X
X
Section 6.4
Physical Examination
Section 9.4.1
Physical examination
X
X
X
X
X
X
X
Section 9.4.1
Weight
X
X
Section 9.4.1
Vital signs (HR, BP, Temp)
X
X
X
X
X
X
X
Section 9.4.5
Electronic Diary (eCOA Device)
Section 9.1.1
Subject completes electronic daily 
diary 
X
X
APPENDIX 9
Review compliance with electronic 
daily diary
X
X
X
X
X
X
APPENDIX 9
ECG
ECG
X
X
Xe
Section 9.4.6
Blood and Urine Tests
Hematology, chemistry, coagulation
X
X
X
X
X
X
X
Section 9.4.3 and Table 11
Fasting lipid panel and glucose
X
X
Section 9.4.3 and Table 11
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Table 2:
Open-label Extension Period Procedural Outline (IM011127)
Study Procedure
Week 16 
(Day 
113)
Week 20 
(Day 
141)
Week 24 
(Day 
169)
Week 32 
(Day 
225)
Week 40 
(Day 
281)
Week 52
(Day 365) 
EOT/ETd
Week 
56
(Day 
393)
F/U
Notes
Visit window (± n days)
3
3
3
3
3
3
7
Serum hsCRP
Urinalysis and urine chemistry
X
Section 9.4.3 and Table 11
Additional Blood Tests 
 
Whole blood for gene expression
X
X
X
Section 9.6 and Table 13
Stool Collection
Aliquots from single sample
Stool for fecal lactoferrin
X
X
X
X
X
X
X
Section 9.6 and Table 13
Endoscopy and Endoscopic 
Biopsies
Endoscopy
X
Section 9.1.1
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BMS-986165
TYK2 Inhibitor
Table 2:
Open-label Extension Period Procedural Outline (IM011127)
Study Procedure
Week 16 
(Day 
113)
Week 20 
(Day 
141)
Week 24 
(Day 
169)
Week 32 
(Day 
225)
Week 40 
(Day 
281)
Week 52
(Day 365) 
EOT/ETd
Week 
56
(Day 
393)
F/U
Notes
Visit window (± n days)
3
3
3
3
3
3
7
Biopsies for gene expression
X
Section 9.6 and Table 14
Biopsies from noninvolved area (if 
available) for gene expression
X
Section 9.6 and Table 14
Additional Efficacy Assessments
Site calculates the modified Mayo 
score
X
Site calculates the symptomatic 
Mayo score for treatment response
X
PGA
X
X
X
X
X
X
Section 9.1.2 and 
APPENDIX 9
The partial Mayo score may be 
determined from data collected at 
these visitsc
X
X
X
X
X
X
Section 9.1.2 and 
APPENDIX 9
The modified Mayo score, total 
Mayo score, and UC-100 may be 
determined from data collected at 
this visitc
X
Section 9.1.2 and 
APPENDIX 9
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BMS-986165
TYK2 Inhibitor
Table 2:
Open-label Extension Period Procedural Outline (IM011127)
Study Procedure
Week 16 
(Day 
113)
Week 20 
(Day 
141)
Week 24 
(Day 
169)
Week 32 
(Day 
225)
Week 40 
(Day 
281)
Week 52
(Day 365) 
EOT/ETd
Week 
56
(Day 
393)
F/U
Notes
Visit window (± n days)
3
3
3
3
3
3
7
Health-related Quality of Life 
Section 9.1.1
IBDQ
X
X
X
Section 9.1.2 and 
APPENDIX 11
UC-related hospitalization and 
surgery
X
X
X
X
X
X
Section 9.1.2 and 
APPENDIX 12
Safety Assessment (in addition to 
the above)
APPENDIX 3
Monitor AEs
X
X
X
X
X
X
X
Section 0
Monitor SAEs
X
X
X
X
X
X
X
Section 0
IP Supply
Dispense IP
X
X
X
X
X
Section 5.1.2
Study treatment
X
X
Section 7.1
Review subject compliance with IP
X
X
X
X
X
X
Section 7.6
AE = adverse event; 
 BP = blood pressure; 
 
 
ECG = electrocardiogram; eCOA = electronic clinical outcome assessments; EOT = end of treatment; ET = early termination; F/U = follow-up; 
 
 HR = heart rate; hsCRP = high-sensitivity C-reactive protein; IBDQ = Inflammatory Bowel Disease Questionnaire; 
 IP = investigational product; PGA = Physician’s Global Assessment; SAE = serious adverse event; 
 
 Temp = temperature; UC = ulcerative colitis; WOCBP = women of childbearing potential
 
 
c Efficacy instruments listed in italics are for site reference only. These scores will not be calculated by the investigator.
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d ET visit should be scheduled at least 4 weeks after the last per protocol-required endoscopy.
e Required only if Week 52 ECG is abnormal.
 
General procedural note: The protocol does not mandate specific investigations at unscheduled visits. Unscheduled visit study procedures should be based on the 
clinical judgment of the investigator.
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3
INTRODUCTION
3.1
Background
Ulcerative colitis (UC) is a chronic inflammatory disease of the gastrointestinal tract that causes 
significant morbidity, impact on quality of life, and healthcare expenditure. Outcomes for patients 
with UC have improved significantly over the last several years due to better treatment strategies 
and the emergence of highly targeted biological therapies. However, significant therapeutic 
challenges remain with this and other inflammatory bowel diseases (IBDs). Current treatment 
regimens often fail, induce only a partial response, or are poorly tolerated. For example, studies 
with tumor necrosis factor inhibitors (TNFi) report that 10% to 30% of subjects do not respond to 
their first treatment and 23% to 46% of subjects lose their response over time.6 Therefore, there is 
still an unmet need for novel, safe, well-tolerated, and orally administered therapies with a different 
mechanism of action that can effectively treat UC and modify the disease course.
Tyrosine kinase 2 (TYK2) is an intracellular kinase involved in interleukin (IL)-12, IL-23, and 
Type I interferon (IFN) signaling.7 TYK2 is a widely expressed, nonreceptor tyrosine kinase that 
catalyzes the phosphorylation of signal transducer and activator of transcription (STAT) proteins 
downstream of the receptors for the IL-12p40-containing cytokines IL-12 and IL-23 as well as the 
Type I IFN receptor. This results in the activation of STAT-dependent transcription and functional 
responses specific for these cytokines.8, 9, 10
 
 
 
 
 
 TYK2-dependent pathways and the cytokine networks they modulate have been 
implicated in the pathophysiology of multiple immune-mediated diseases including UC, Crohn’s 
disease (CD), psoriasis, psoriatic arthritis, systemic lupus erythematosus (SLE), and
spondyloarthropathies.
BMS-986165 is an orally administered, selective TYK2 inhibitor. A comprehensive in vitro and 
in vivo characterization of BMS-986165 has been established and supports the development of 
this compound in humans.11, 12
 
 
3.1.1
Nonclinical Toxicology
The projected systemic exposure multiples presented in this section are expressed relative to 
 
 
 
. These multiples were calculated as animal sex-combined mean AUC ÷ human sex-
combined mean AUC at the no-observed-adverse-effect level (NOAEL) or level associated with 
adverse findings in the pivotal toxicology studies.
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In vitro screening against a panel of receptors, ion channels, transporters, and enzymes 
demonstrated that BMS-986165 did not significantly alter ligand binding or functional activity at 
clinically relevant concentrations and is considered to have low potential to produce effects in vivo 
related to secondary pharmacology. Transient decreases in blood pressure (BP) and increases in 
heart rate (HR) were seen in anesthetized rabbits, and conscious telemetrized dogs and monkeys, 
with monkey being the most sensitive species. However, the HR or BP changes were not identified 
in repeat-dose monkey toxicity studies at higher doses or in healthy subjects in a Phase 1 single 
ascending dose study at plasma concentrations comparable to plasma levels at the lowest-
observed-effect-level in a Good Laboratory Practice study in telemetrized monkeys. In addition, 
 
 up to the highest evaluated dose of 12 mg BID or in the 
thorough QT (TQT) study in healthy subjects up to a single dose of 36 mg (Study IM011048). 
Overall, the totality of available data indicates that BMS-986165 has low potential for off-target 
effects at clinical doses and corresponding plasma concentrations.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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BMS-986165
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3.1.2
Early Clinical Experience
BMS-986165 has a favorable pharmacokinetic (PK) profile characterized by consistent oral 
absorption, 
 
 
 
 
 
 
 
 
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3.1.3
BMS-986165 12 mg QD or BID Dose Regimen Studies
Several studies of BMS-986165 have been conducted using single- or multiple-dose regimens of 
BMS-986165 12 mg BID PO or higher. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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BMS-986165
TYK2 Inhibitor
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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TYK2 Inhibitor
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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TYK2 Inhibitor
 
 
 
 
 
 
 
3.1.5
BMS-986165 and Inflammatory Bowel Disease Studies: Overview
Study IM011024 is a multicenter, randomized, double-blind, placebo-controlled, parallel group, 
Phase 2 clinical trial designed to evaluate the safety and efficacy of BMS-986165 6 mg BID PO, 
compared with placebo, in subjects with moderate to severe UC. The primary endpoint is at 
Week 12. Following a 12-week induction period, eligible subjects enter a 40-week maintenance 
period. An additional 52-week open-label extension (OLE) period (to Week 104) is available for 
subjects who continue to derive clinical benefit. Topline results from Study IM011024 indicate 
that BMS-986165 6 mg BID compared to placebo BID did not meet primary efficacy endpoint of 
clinical remission at Week 12 or the predefined secondary efficacy endpoints. The safety profile 
of BMS-986165 was consistent with previously reported studies in psoriasis and psoriatic arthritis, 
and no new safety signals were observed. The study remains ongoing, and results from the 
Week 52 and Week 104 endpoints are not yet available.
Study IM011023 is a multicenter, randomized, double-blind, placebo-controlled, parallel group, 
Phase 2 clinical trial designed to evaluate the safety and efficacy of BMS-986165 6 mg BID PO 
and 3 mg BID PO, compared with placebo, in subjects with moderate to severe CD, following a 
12-week induction period. After the induction period, eligible subjects enter a 40-week 
maintenance period. An additional 52-week OLE period (to Week 104) is available for subjects 
who continue to derive clinical benefit.
Study IM011077 is an open-label, long-term extension study to evaluate the long-term safety and 
efficacy of BMS-986165 6 mg BID in subjects who have previously been enrolled in a Phase 2 
BMS-986165 study for moderate to severe CD (Study IM011023) or moderate to severe UC 
(Studies IM011024 and IM011127).
Study IM011127 (the current study) is a multicenter, randomized, double-blind, placebo-
controlled, parallel group, Phase 2 clinical trial designed to assess the safety and tolerability, 
efficacy, and biomarker response of BMS-986165 12 mg BID PO following a 12-week treatment 
period. An additional 40-week OLE period (to Week 52) is available for eligible subjects.
Inclusion/Exclusion criteria, safety, and efficacy assessments for the current study are based on 
the design of Study IM011024. Data from this study will be analyzed alone and may be compared 
with the data collected in Study IM011024 (which is likely to recruit a similar patient population 
due to similarities in the eligibility criteria between studies).
 
 
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BMS-986165
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3.2
Benefit/Risk Assessment
Multiple lines of evidence suggest that inhibition of TYK2 signaling by BMS-986165 may be 
beneficial in patients with active UC.
In a cohort of healthy humans, carriage of a naturally occurring protein variant in TYK2 (P1104A, 
rs34536443) that results in reduction of TYK2 kinase function is associated with a reduced risk of 
inflammatory diseases, 
 
 
 
 
adoptive transfer model of murine colitis and 
the anti-CD40 agonist antibody murine model of colitis.11
 
 
 
 
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BMS-986165
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therapeutic effect in subjects with active UC.31 Taken together, these data support a hypothesis 
that BMS-986165 may be beneficial in the treatment of UC.
 BMS-986165 6 mg BID is currently 
being studied (compared to placebo in subjects with moderate to severe UC) in Study IM011024.
Briefly, BMS-986165 12 mg BID is being assessed in this study for the following reasons:
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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There is adequate safety information from the studies described above to understand expected 
TEAEs at BMS-986165 12 mg BID in the current study. The protocol includes design elements 
that may allow these events to be recognized and managed appropriately by investigators during 
the study, should they occur. Furthermore, assessment of the safety and tolerability of BMS-
986165 12 mg BID in this study population, and comparison with safety and tolerability data from 
Study IM011024, may inform Phase 3 dose selection of BMS-986165.
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BMS-986165 is a potential immunomodulator. The inclusion (Section 6.1) and exclusion 
(Section 6.2) criteria have been designed to minimize the risk for infections and malignancies, and 
additional data collection will be triggered if these AEIs are observed in this study.
Participants in UC clinical trials, particularly those receiving placebo, may experience an increase 
in disease activity (ie, a “flare”) during their participation. This protocol contains detailed criteria 
for treatment failure (Section 5.1.5) and detailed discontinuation criteria (Section 8) to assist 
investigators in the recognition and management of treatment failure within the study. Standard of 
care rescue therapy can be initiated at any time, at the investigator’s discretion (Section 5.1.5).
The risk for PK DDIs with BMS-986165 was assessed using Food and Drug Administration (FDA) 
and European Medicines Agency guidance documents for DDI assessments. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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The global coronavirus disease 2019 (COVID-19) pandemic has been identified as a potential risk 
to clinical trial subjects in general, and it may particularly affect individuals with underlying 
chronic diseases. The risk of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) 
infection in participants taking BMS-986165 is unknown. The individual benefit-risk 
considerations regarding COVID-19 infection remains the responsibility of the investigator.
BMS-986165 is an immunomodulatory IP. The inclusion (Section 6.1) and exclusion (Section 6.2) 
criteria have been designed to exclude people with active infections and people at higher risk of 
malignancies. In order to reduce the risk of asymptomatic SARS-CoV-2 at baseline, subjects will 
be tested for SARS-CoV-2 during the screening period, as close as possible prior to randomization 
and must be confirmed as “negative” prior to randomization (Section 9.8).
The study has been designed with study visits that allow for close monitoring of study subjects’ 
safety throughout the study, and additional data collection will be triggered if AEIs are observed 
in this study. Each study visit will include a clinical assessment for signs and/or symptoms of 
intercurrent illness, including COVID-19 and other infections. Subjects will also be encouraged to 
contact the investigator if they develop an intercurrent illness between study visits.
The Sponsor has developed guidance for investigators on how to manage a subject with a clinical 
suspicion of, or a diagnosis of, COVID-19. This includes criteria for temporary interruption of IP 
in the context of clinical suspicion of COVID-19, or a positive diagnostic test for SARS-CoV-2 
(Section 8.1.1). This also includes criteria for potentially recommencing IP upon complete 
resolution of a COVID-19 infection, confirmed by a negative diagnostic test (Section 9.8).
The study captures treatment-emergent AEs (occurring after randomization). In order to facilitate 
enhanced reporting of SARS-CoV-2 related AEs that occur during the study, these AEs (and 
SAEs) must be reported from the time of consent (Section 9.2.1). In addition, SARS-CoV-2 related 
AEs or SAEs will trigger additional data collection through specialized electronic case report form 
(eCRF) pages, which will enable additional evaluation of these events.
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4
OBJECTIVES AND ENDPOINTS
Study objectives and specific endpoints are listed in Table 3. Additional endpoints and analyses 
will be described in the statistical analysis plan (SAP), the Endoscopy Image Review Charter 
. Selected efficacy endpoints are further defined 
in Table 10.
Table 3:
Study Objectives and Endpoints
Objective
Endpoints
Primary - Efficacy

To estimate the efficacy of BMS-986165 at 
Week 12

Proportion of subjects in clinical response at Week 12 
Safety

To assess the safety and tolerability of 
BMS-986165

Number and proportion of subjects experiencing AEs, 
SAEs, AEs leading to discontinuation from the study, 
and AEIs throughout the study
Exploratory - Efficacy
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Table 3:
Study Objectives and Endpoints
Objective
Endpoints

To explore the efficacy of BMS-986165 at 
Week 52

Proportion of subjects in clinical remission at Week 52

Proportion of subjects in clinical response at Week 52

Proportion of subjects in endoscopic remission at 
Week 52

Proportion of subjects with endoscopic improvement at 
Week 52

Proportion of subjects with histologic improvement at 
Week 52

Proportion 
of 
subjects 
with 
corticosteroid-free 
remission at Week 52

Proportion of subjects in durable clinical response at 
Week 52

Proportion of subjects in durable endoscopic response at 
Week 52

Proportion of subjects in clinical response at Week 12 
Exploratory

To explore the effect of BMS-986165 on PB 
immune cells

Change from baseline in PB immune cells over time

To explore the effect of BMS-986165 on the 
transcriptome in blood and colon biopsies

Change from baseline in gene expression over time
Exploratory 
Exploratory - Health-related Quality of Life and Medical Resource Utilization

To explore the effect of BMS-986165 on PROs 
and quality of life

Change from baseline at various time points for the 
IBDQ
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Table 3:
Study Objectives and Endpoints
Objective
Endpoints

To explore the effect of BMS-986165 on 
UC-related hospitalization and surgery

Proportion 
of 
subjects 
with 
surgery 
and/or 
hospitalization due to UC at various time points
AE = adverse event; AEI = adverse event of interest; 
IBDQ = Inflammatory 
Bowel 
Disease 
Questionnaire; 
PB = peripheral 
blood; 
 
PRO = patient-reported 
outcomes; 
RB = rectal 
bleeding; 
 SAE = serious adverse event; 
 
 SF = stool frequency; UC = ulcerative colitis; 
5
STUDY DESIGN
5.1
Overall Design
Study IM011127 is a Phase 2 randomized, double-blind, placebo-controlled, multicenter clinical 
study designed to assess the safety and tolerability, efficacy, 
and biomarker response of
BMS-986165 12 mg BID in subjects with moderate to severe UC. The primary objective is to 
estimate the effect of BMS-986165 on clinical response at Week 12 (Table 10).
The duration of study participation is approximately 60 weeks (420 days) in 4 periods, as follows:

Screening period: up to 4 weeks (28 days; Section 5.1.1)

Double-blind treatment period: 12 weeks (84 days; Section 5.1.2)

OLE period: up to 40 weeks (280 days: Section 5.1.3)

Posttreatment follow-up period: 4 weeks (28 days; Section 5.1.4)
Assessments of medical and UC disease history; prior medications, concomitant medications, and 
UC medications; tobacco use; baseline SF; physical examinations; chest x-ray (CXR); 
12-lead ECG; and blood, stool, and urine sample collections; endoscopies with biopsies; additional 
efficacy assessments, PGA, PROs; and eligibility assessment will be performed as indicated in the 
Schedule of Activities (Section 2). Subjects will be closely monitored for AEs throughout the 
study.
The primary endpoint of this study is the proportion of subjects in clinical response at Week 12. 
This is assessed using the modified Mayo score. This instrument utilizes data from 2 sources: 
(1) PROs, ie, SF and RB captured by the subject in their electronic daily diary (modified Mayo 
score and total Mayo score); and (2) Centrally-read endoscopic assessments (modified Mayo score 
and total Mayo score). In addition, the physician-reported PGA, assessed by the investigator or 
designee at each study visit, will also be captured to facilitate the calculation of the total and partial 
Mayo scores. Efficacy will also be assessed using additional instruments, such as the UC-100 
instrument (which uses the modified Mayo score SF and ES subscores 
 
). Consequently, accurate and timely collection of each of these types of data 
(or samples that contribute to these data) is critical to the assessment of efficacy in this study. 
Additional detail on data capture for efficacy assessment and the efficacy instruments used in this 
study are given in Section 9.1.1.
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Subjects will receive and be trained on the electronic daily diary at the screening visit. Subjects 
are expected to complete this diary on a daily basis throughout their participation in the study. In 
order to confirm that subjects are successfully recording data in the electronic daily diary, sites 
should review subject compliance with completion of the electronic daily diary, as indicated in the 
Schedule of Activities (Section 2), or more frequently if required. For the purpose of eligibility 
assessment and efficacy analysis, the 3 most recent (not necessarily consecutive), valid, 
electronic subject diary entries recorded from the 7 days prior to the day of a study visit (or 
up to the day before a subject starts bowel preparation for an endoscopy, if that visit includes 
an endoscopy) will be used to calculate the SF and RB subscores (see APPENDIX 9). Electronic 
diary entries for SF and RB are considered valid when no medications for constipation, diarrhea, 
or bowel irregularity are reported (through E-diary) as taken that day. Review of electronic daily 
diary compliance during these previsit (or preendoscopy) periods is recommended. Subjects are 
not eligible to participate in this study if they are unable to complete study procedures, which 
includes daily completion of the electronic diary. The modified Mayo score calculated to 
determine eligibility will also be used as the baseline disease activity score.
Endoscopic evaluations and collection of colonic tissue biopsies will be performed during the 
screening period, at Weeks 12 and 52, at unscheduled visits (if clinically indicated), and at early 
termination (ET) visits that occur at least 4 weeks after the last per protocol-required endoscopy
in the double-blind period and any time after Week 20 in the OLE period. Endoscopy is encouraged 
in subjects terminating in the OLE period between Week 12 and Week 20. Endoscopic procedures 
will be video recorded and scored for disease activity by a blinded central reader. Histologic 
scoring of gastrointestinal tissue specimens will also be performed by a blinded central reader.
 
 
 
Subjects who meet the criteria for treatment failure will permanently discontinue IP and enter the 
posttreatment follow-up period (Section 5.1.3).
An independent Data Monitoring Committee (DMC) will be instituted to assess safety data 
(Section 5.1.6).
The study design schematic is presented in Figure 1.
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Figure 1:
Study Design Schematic
BID = twice daily; OLE = open-label extension; PO = orally; R = randomization
Note: Subjects randomized to the BMS-986165 6 mg BID induction treatment arm under the Original Protocol or 
Protocol Amendment 01 will continue to receive this dose throughout the double-blind period and will receive 6 mg 
BID in the OLE period.
5.1.1
Screening Period
Study procedures cannot be performed until subjects sign the informed consent form (ICF). Once 
subjects sign the ICF, they are considered “enrolled” in the study, and they enter the screening 
period. During the screening period, subjects will complete the study procedures and baseline 
assessments outlined in the Schedule of Activities (Section 2) to determine if they continue to meet 
eligibility criteria (Section 6). 
 
 
To be eligible for the study, a subject must meet minimum disease activity criteria outlined in 
Section 6.1, including a modified Mayo score of 5 to 9 points, inclusive.
 
 
 
 
 
 
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An endoscopy (colonoscopy or flexible sigmoidoscopy) will be performed to determine if a subject 
has active intestinal inflammation (assessed by central reading) and to obtain biopsies for 
biomarker 
 assessment. To avoid unnecessary endoscopies, best practice is to 
complete other screening investigations first and check the results of those investigations to 
confirm ongoing eligibility before a subject begins bowel preparation for endoscopy. Subjects 
must be randomized within 14 calendar days of the screening endoscopy.
NOTE: In the case of rescreening, the 14-day window to be randomized following endoscopy may 
be extended an additional 3 days with approval of the BMS Medical Monitor/designee.
A full colonoscopy will be required: (1) in subjects with a history of UC > 8 years, if endoscopy 
was not performed in the prior 12 months; or (2) in subjects who require a colonoscopy to screen 
or surveille for dysplasia, based on local guidelines; or (3) in subjects who require a colonoscopy 
to screen for colorectal carcinoma, based on local guidelines.
A full colonoscopy is encouraged if disease extent is unknown in order to define the proximal 
extent of colitis.
To be eligible for randomization, subjects must meet the Inclusion Criteria outlined in Section 6.1
and must not meet any of the Exclusion Criteria outlined in Section 6.2. Subjects must have had 
an inadequate response, loss of response, or intolerance to a treatment course of 1 or more of the 
standard medications for UC and completed at least 1 treatment course of corticosteroids 
(Section 6.1). Detailed criteria defining inadequate response, loss of response, or intolerance to 
biologic therapy are described in APPENDIX 5. The prior medication failure or intolerance used 
to qualify a subject for inclusion must be recorded in source documents and the appropriate eCRF.
Prohibited treatments are listed in Section 7.7.1 (Table 6).
Restricted treatments are listed in Section 7.7.2 (Table 7).
Dose stabilization rules are outlined in Section 0 (Table 8). Briefly, 5-aminosalicylic acids 
(5-ASAs) 
and 
oral 
corticosteroids 
(prednisone ≤20 mg QD PO or 
equivalent 
or 
budesonide ≤9 mg QD PO Multi-Matrix System [MMX®] colonic-delivery technology; 
eg, Uceris® or equivalent) are allowed, subject to dose stabilization rules. Equivalent doses of 
common corticosteroids are listed in APPENDIX 6.
Washout periods for immunomodulators and biologic medications are outlined in the eligibility 
criteria (Section 6) and Table 6, and detailed in APPENDIX 7. Subjects must comply with these 
washout periods in order to be eligible to be randomized. 
 
assays that test for drug levels of some biologic medications are commercially available in many 
countries for use in routine clinical practice. They are also available as an optional test during the 
screening period. The washout period for these biologics can be waived in subjects who have an 
undetectable drug level 
 that is performed either in routine clinical practice or 
during the screening period.
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 used to waive the washout period as described above, the result 
 
 must be available in source documents, and the subject cannot receive another dose of that 
biologic prior to randomization.
Investigators are also encouraged to confirm if screening for noncolorectal malignancy is up to 
date prior to randomization, according to local guidelines (eg, screening for breast cancer or 
cervical carcinoma in situ).
5.1.2
Double-blind Treatment Period
At the Day 1 study visit, subjects who have completed the screening procedures and meet the 
eligibility criteria will be randomized in a 3:1 ratio to receive BMS-986165 12 mg BID or placebo 
BID PO, respectively for the 12-week double-blind treatment period. Randomization criteria are 
outlined in Section 6.3. Subjects randomized to the 6 mg BID arm under the Original Protocol or
Protocol Amendment 01 will continue to receive 6 mg BID for the 12-week double-blind treatment 
period and will receive 6 mg BID in the OLE period.
Prior to each scheduled visit, the subject diary should be reviewed to ensure SF and RB data have 
been entered daily. Prior to each scheduled visit at which Mayo scores are to be calculated, study 
personnel should ascertain whether an adequate number of days of diary entries have been made 
(APPENDIX 9). If adequate entries have not been made, the site should contact the subject to 
reschedule the visit to allow time for a sufficient number of daily dairy entries for endpoint 
assessment, and the subject should be counseled about proper study procedures.
Endoscopy for the assessment of efficacy at Week 12 must occur in a window of 7 days prior 
to the Week 12 visit.
If a colonoscopy is performed during the screening visit, colonoscopy will be the preferred 
endoscopic procedure for subsequent endoscopies within the study. This approach will facilitate 
comparison between the individual colonic segments assessed at the screening visit and subsequent 
assessments.
Treatment discontinuation criteria are detailed in Section 8.1. Subjects who temporarily 
interrupt study treatment will remain in the study and continue to participate in study procedures 
(Section 8.1.1).
Subjects who permanently discontinue study treatment will complete an ET visit. For subjects 
who permanently discontinue study treatment between Weeks 4 and 12, the ET visit will include 
an endoscopy. For subjects who permanently discontinue study treatment prior to Week 4, 
endoscopy at the ET visit is optional but encouraged. Subjects who permanently discontinue study 
treatment will be followed for protocol-specified posttreatment follow-up procedures. The only 
exception to this is when a subject specifically withdraws consent for any further contact with 
him/her or with persons previously authorized by the subject to provide this information (see 
Section 8.2).
5.1.3
Open-label Extension Period
Subjects who are likely to derive a clinical benefit from ongoing participation in the study 
following Week 12, as judged by the investigator, are eligible to enter the OLE period. The OLE 
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period will last up to 40 weeks, to Week 52. Subjects will receive BMS-986165 6 mg BID PO 
during the OLE. There is no provision for dose escalation of IP during the OLE.
 
 
 
 
The symptomatic Mayo score at the Week 20 visit will be calculated using the 3 most recent (not 
necessarily consecutive) valid electronic subject diary entries recorded from the 7 days prior 
to the day of the study visit.
 
 
 
 
 Subjects who require any rescue therapy during the OLE period 
(Section 5.1.5) must permanently discontinue from study treatment (Section 8.1).
Endoscopy for the assessment of efficacy at Week 52 must occur in a window of 7 days prior 
to the Week 52 visit.
Endoscopy is required at the ET visit for subjects who permanently discontinue study treatment 
between Week 20 and prior to Week 52. Endoscopy is optional, but encouraged, for subjects who 
have an ET visit between Weeks 12 and 20.
5.1.4
Follow-up Period
Subjects who complete the Week 12 visit and decline to enter the OLE period, those who complete 
the Week 52 visit and do not roll-over into a long-term extension study, or those who permanently 
discontinue study drug at any time during the study (Section 8) will enter a 4-week posttreatment 
follow-up period.
5.1.5
Treatment Failure
For the purpose of this study, treatment failure will be defined as:
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5.1.6
Safety Monitoring and Data Monitoring Committee
Study IM011127 is the first experience of subjects with moderate to severe UC to BMS-986165 
at doses above 6 mg BID PO. Consequently, this study has been designed to closely monitor 
subjects’ safety throughout the duration of the study. Safety monitoring will occur at study sites, 
by the Sponsor, and by an external, independent DMC.
Subject Safety Assessments at the Study Site
Subject safety will be closely assessed at study sites by the investigator and appropriately delegated 
members of the study team. The assessments outlined in the Schedule of Activities (see Section 2) 
have been designed to facilitate assessment of safety in addition to efficacy. Based on the timing 
of hepatic AEs observed 
, liver function 
testing during the treatment phase will commence at Week 1 (~Day 8) (Table 1). In addition, the 
Sponsor has implemented additional data collection for AEIs, including skin SOC TEAEs (see 
Section 9.2.8), in order to more completely characterize these TEAEs (were they to occur) and 
understand the tolerability of BMS-986165 in this study.
Additional clinical assessments or investigations can be performed during the study as indicated, 
based on the judgment of the investigator.
Medical Monitoring by the Sponsor
Subject safety will be monitored in a blinded manner by the Sponsor on a regular basis. The 
Sponsor will review blinded subject-level data entered in the clinical database as well as 
aggregated safety data across studies. This approach facilitates close monitoring of individual 
safety events as well as surveillance for potential safety signals.
Data Monitoring Committee
An external, independent DMC will provide oversight on the safety of trial subjects within this 
study, The DMC will regularly review accumulating data from this study and advise the Sponsor 
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regarding the continuing safety of trial subjects and those yet to be recruited to the trial, as well as 
the continuing validity and scientific merit of the trial.
Data summaries and listings will be provided to the DMC to facilitate their safety assessment at 
regularly scheduled meetings and on an ad hoc basis if needed. Efficacy data will be made 
available on request by the DMC to assess ongoing acceptability of the benefit-risk profile. The 
DMC will also be provided with suspected, unexpected serious adverse reaction (SUSAR) reports 
relating to BMS-986165 and recommendations from other DMCs supporting the BMS-986165 
clinical development program.
Regular DMC safety reviews will include all AEs, SAEs, and AEs of special interest. Based on 
their review of safety data, the DMC will make recommendations regarding the appropriateness 
of continuing the study, with or without study modifications, or stopping the study.
In addition to regularly scheduled DMC meetings, ad hoc DMC meetings will occur in the 
following circumstances:

Two or more subjects experience an SAE of the same PT and that is considered related to the 
study treatment by the investigator (for example, not explained by intercurrent medical 
condition or concomitant medication)

Two or more subjects are discontinued due to the same laboratory abnormality as defined by 
criteria in Section 8.1
Additional details on the DMC’s processes and procedures will be outlined in the DMC Charter.
5.2
Number of Subjects
Approximately 50 subjects will be randomized in the main study protocol. The sample size 
justification is included in Section 10.1.
 
 
 
 
 
 
 
5.3
End-of-Study Definition
The duration of study participation for individual subjects may be up to approximately 60 weeks 
(420 days).
The start of the study is defined as the first visit for the first subject screened. The end of the study 
is defined as the last scheduled procedure shown in the Schedule of Activities (Section 2) for the 
last subject. Study completion is defined as the final date on which data were or are expected to be 
collected. The end of study for analysis of 
 samples is outlined in Section 9.6.
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5.4
Scientific Rationale for Study Design
This is a Phase 2 randomized, double-blind, placebo-controlled, multicenter study to assess the 
safety and tolerability, efficacy, 
and biomarker response of BMS-986165 12 mg BID in 
subjects with moderate to severe UC.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
This study will estimate the effect of BMS-986165 on clinical response at Week 12 using standard 
UC efficacy instruments to determine eligibility and assess efficacy (Section 9.1).38, 39
 
 
 
 
 
 
 
 
 
 
 
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Study IM011127 also includes a placebo control arm. 
 
 
 
 
 
 
 
 
 
 
 
 
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6
STUDY POPULATION
Eligibility criteria for this study have been carefully considered to ensure both the safety of the 
study subjects and the validity of the study results. It is imperative that subjects fully meet all 
eligibility criteria.
 
 
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All screening and randomization evaluations must be completed and reviewed by the responsible 
investigator to confirm that potential subjects meet all eligibility criteria. The investigator will 
maintain a screening log to record details of all subjects screened and to either confirm eligibility 
or to record the reason(s) for screening failure. Procedures conducted as part of the subject’s 
routine clinical management (eg, blood count) and obtained before the ICF was signed may be 
used for prescreening purposes, unless otherwise specified in the protocol.
The duration of the screening period is up to 4 weeks. If eligibility parameters cannot be obtained 
within this time period, the screening period may be extended by up to 5 days, if approved by the 
BMS Medical Monitor/designee. Rules for retesting and rescreening are provided in Section 6.5.1.
To be eligible for the study, subjects must meet all Inclusion Criteria (Section 6.1) and must not 
meet any of the Exclusion criteria (Section 6.2). To be randomized into the study on Day 1, 
subjects must meet the criteria in Section 6.3.
In this section, Inclusion and Exclusion criteria are listed in standard text. Additional instructions 
to investigators, designed to further clarify selected eligibility criteria, are presented in italics.
6.1
Inclusion Criteria
In order to be eligible to participate in this study, an individual must meet all of the following 
criteria:
1) Signed Written Informed Consent
a) Willing to participate in the study and sign the ICF
b) Willing and able to complete all study specific procedures and visits
2) Type of Participant and Target Disease Characteristics
a) A diagnosis of UC ≥3 months’ duration prior to screening
Subject must have a clinical diagnosis of UC ≥3 months’ duration prior to screening, and 
source documents must include (i) an endoscopy report, which shows features consistent 
with UC, and (ii) a histopathology report showing features consistent with UC.
If an endoscopy report is not available prior to screening, the screening endoscopy can be 
used to confirm the diagnosis. If a histopathology report is not available prior to screening, 
endoscopic biopsies can be obtained at the screening endoscopy (with appropriate 
consent) and sent to a local histopathology laboratory for reporting, to meet the criteria 
described above prior to randomization.
b) UC disease distribution extending proximal to the rectum (ie, left-sided colitis or 
pancolitis)
c) Moderately to severely active UC, defined by a modified Mayo score of 5 to 9 points 
inclusive (see Section 9.1 and APPENDIX 9), which includes all of the following:
i)
A stool frequency (SF) subscore of ≥2, and
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ii) A rectal bleeding (RB) subscore ≥1, and
iii) An endoscopic (ES) subscore of ≥2
d) Must be up to date with surveillance for dysplasia and screening for colorectal neoplasia, 
according to local standard of care
3) Age and Reproductive Status
Investigators shall counsel women of childbearing potential (WOCBP), and male subjects who are 
sexually active with WOCBP, on the importance of pregnancy prevention and the implications of 
an unexpected pregnancy.

The investigator shall evaluate the effectiveness of the contraceptive method in relationship to 
the first dose of study intervention.

Local laws and regulations may require the use of alternative and/or additional contraception 
methods.
a) Female Subjects
i)
Females, ages 18 (or local age of majority) to 65 years, inclusive, at the time of 
screening.
ii) Women who are not of childbearing potential are exempt from contraceptive 
requirements.
iii) Female subjects must have documented proof that they are not of childbearing 
potential.
iv) Not applicable per Protocol Amendment 02 - WOCBP must have a negative highly 
sensitive 
 test (minimum sensitivity 25 IU/L or equivalent 
units of human chorionic gonadotropin) within 24 hours prior to the start of study 
treatment.
If a urine test cannot be confirmed as negative (eg, an ambiguous result), a 
 
 test is required. In such cases, the participant must be excluded from 
participation if the 
 result is positive.
v) WOCBP must have a negative highly sensitive 
 test 
(minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) 
within 24 hours prior to the start of study treatment (applicable to Canada only, a 
negative highly sensitive 
 test with the same minimum sensitivity as 
indicated above is also required at the screening visit).
If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum 
pregnancy test is required. In such cases, the participant must be excluded from 
participation if the serum pregnancy result is positive.
vi) Additional requirements for pregnancy testing during and after study intervention are 
located in the Schedule of Activities (Section 2).
vii)The investigator is responsible for review of medical history, menstrual history, and 
recent sexual activity to decrease the risk for inclusion of a woman with an early 
undetected pregnancy.
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viii) Not applicable per Protocol Amendment 02 - WOCBP must agree to follow 
instructions for method(s) of contraception defined in APPENDIX 4 and as described 
below and included in the ICF.
ix) WOCBP must agree to use 1 of the highly effective or 1 of the less than highly effective 
methods of contraception defined in APPENDIX 4 (applicable to Germany only, 
1 highly effective method of contraception is required; applicable to Canada only, 
1 highly effective contraception method or 2 less than highly effective contraception 
methods are required).
x) WOCBP are permitted to use hormonal contraception methods as described in 
APPENDIX 4.
xi) A female subject is eligible to participate if she is not pregnant or breastfeeding and at 
least one of the following conditions applies:
(1) Is not a WOCBP
OR
(2) Is a WOCBP and using a contraceptive method(s) as described in 
APPENDIX 4 during the intervention period (at a minimum until after the last dose 
of study intervention)
b) Male Subjects
i)
Males, ages 18 (or local age of majority) to 65 years, inclusive, at the time of screening.
ii) Not applicable per Protocol Amendment 01 - Males who are sexually active with 
WOCBP must agree to follow instructions for method(s) of contraception defined in 
APPENDIX 4 and as described below.
iii) Not applicable per Protocol Amendment 01 - Azoospermic males are exempt from 
contraceptive requirements.
iv) Not applicable per Protocol Amendment 01 - No additional contraceptive measures 
are required to be used.
v) Male participants should maintain their usual practice with regards to contraception (if 
any); however no specific contraceptive measures are required.
4) Prior UC Medication Inclusion Criteria
a) Not applicable per Protocol Amendment 02 - Documentation of an inadequate response, 
loss of response, or intolerance to a treatment course of 1 or more of the following standard 
of care medications:
i)
Oral 5-aminosalicylic acids (5-ASAs) (eg, mesalamine, sulfasalazine, olsalazine, or 
balsalazide).
ii) Corticosteroids (eg, prednisone or budesonide MMX).
iii) Immunomodulators (eg, azathioprine [AZA], 6-mercaptopurine [6-MP], or 
methotrexate [MTX]).
iv) Anti-TNF agents (eg, infliximab, adalimumab, or golimumab).
v) Integrin inhibitors (eg, vedolizumab).
 
 
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b) Inadequate response, loss of response, or intolerance to a treatment course of 1 or more of 
the following standard of care UC medications:
i)
Oral 5-aminosalicylic acids (5-ASAs) (eg, mesalamine, sulfasalazine, olsalazine, or 
balsalazide).
ii) Corticosteroids (eg, prednisone or budesonide MMX) (must have had 2 exposures 
separated by a corticosteroid-free period).
iii) Immunomodulators (eg, azathioprine [AZA], 6-mercaptopurine [6-MP], or 
methotrexate [MTX]).
iv) Anti-TNF agents (eg, infliximab, adalimumab, or golimumab).
v) Integrin inhibitors (eg, vedolizumab).
 
 
 
 
 
viii) Subjects who stop treatment with biologics due to loss of funding (eg, loss of insurance 
coverage) may be eligible for inclusion in the study. Subject eligibility should be 
discussed with the BMS Medical Monitor/designee.
Specific prior medication failure/intolerance criteria are listed in APPENDIX 5.
 
 
5) Washout and Dose Stabilization Inclusion Criteria
a) Must comply with washout periods for prohibited concomitant medications summarized in 
Table 6 (Section 7.7.1) and listed in APPENDIX 7
b) Must comply with dose stabilization rules for 5-ASAs, corticosteroids and probiotics (if 
applicable) prior to randomization, listed in Table 8 (Section 0)
6.2
Exclusion Criteria
An individual who meets any of the following criteria will be excluded from participation in this 
study:
1) Medical Conditions
a) Women who are pregnant or breastfeeding
2) UC Exclusion Criteria
a) UC involving the rectum only (UC proctitis)
b) Current diagnosis of CD, indeterminate colitis, ischemic colitis or microscopic colitis, a 
monogenic cause of UC-like intestinal inflammation, or a diagnosis of pseudomembranous 
colitis other than that associated with Clostridioides difficile (formerly Clostridium difficile 
[C. difficile])
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c) Current or recent (within 12 weeks prior to randomization) evidence of fulminant UC (also 
known as acute severe UC) or toxic megacolon
d) Current or recent (within 12 weeks prior to randomization) evidence of bowel perforation 
or intra-abdominal abscess
e) Current or recent colonic diverticulitis. Subject must be adequately treated and off 
antibiotics for diverticulitis for 60 days prior to randomization.
f)
Current colonic adenomas or mucosal dysplasia
A subject with adenomatous polyps may be eligible if the polyps have been completely 
removed or eradicated (documented), and the subject is free of polyps at randomization.
A subject with mucosal dysplasia may be eligible if the dysplasia has been completely 
removed/resected/eradicated (as applicable, documented), and the subject is free of 
dysplasia at randomization. This should be discussed with the BMS Medical 
Monitor/designee prior to screening.
Subjects with a history of UC > 8 years’ duration (who have not had a colonoscopy in the 
prior 12 months), subjects who require a colonoscopy to screen or surveille for dysplasia 
(based on local guidelines), and subjects who require a colonoscopy to screen for 
colorectal cancer (based on local guidelines) must have a full colonoscopy at screening.
g) Treatment for CMV colitis within 12 weeks of randomization
3) Gastrointestinal Surgery Exclusion Criteria
a) History or evidence of extensive colonic resection, subtotal or total colectomy, with or 
without a stoma or pouch
b) Current need for, or anticipated need for, surgical intervention for UC during the study
c) Gastrointestinal surgery within 3 months prior to randomization
Subject must have adequate wound healing prior to randomization.
4) Additional Gastrointestinal Exclusion Criteria
a) Current or recent (within 12 weeks prior to randomization) gastrointestinal disease that 
may confound efficacy assessment or be associated with poor absorption of IP, eg, 
untreated celiac sprue, bile salt-mediated diarrhea, or short bowel syndrome
b) Receiving enteral feeding, defined formula diets, or total parenteral alimentation
5) Immune and Infectious Disease Exclusion Criteria
a) History of congenital or acquired immunodeficiency
b) Not applicable per Protocol Amendment 02 - Known serious infection, defined as any 
infection requiring hospitalization or treatment with parenteral (intramuscular [IM] or IV) 
antimicrobial agents (eg, antibiotics, antiviral, antifungal, or antiparasitic agents) within 
30 days of the first dose of study treatment, or completion of oral antimicrobial agents 
within 2 weeks of the first dose of study treatment. Antibiotics used to cover a procedure 
such as endoscopy would not exclude the subject.
c) Not applicable per Protocol Amendment 01 - Current or recent (within 12 weeks prior 
to randomization) herpes zoster, herpes simplex, or influenza infection
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d) History of disseminated or complicated herpes zoster infection (including, but not limited 
to, multi-dermatomal involvement, ophthalmic zoster, central nervous system 
involvement, or post-herpetic neuralgia)
e) Current or recent (within 12 weeks prior to randomization) herpes zoster, herpes simplex, 
or influenza infection. In the case of prior SARS-CoV-2 infection, symptoms must have 
completely resolved 4 weeks prior to screening and based on investigator assessment in 
consultation with the Medical Monitor, there are no sequelae that would place the 
participant at a higher risk when receiving BMS-986165. See Section 9.8 for additional 
information regarding retesting subjects who have prior SARS-CoV-2 infection.
f)
Known serious infection, defined as any infection requiring hospitalization or treatment 
with parenteral (intramuscular [IM] or IV) antimicrobial agents (eg, antibiotics, antiviral, 
antifungal, or antiparasitic agents) within 30 days of the first dose of study treatment, or 
treatment with oral antimicrobial agent(s) within 2 weeks of the first dose of study 
treatment. Antibiotics used to cover a procedure such as endoscopy would not exclude the 
subject.
Study inclusion eligibility of subjects being treated with chronic prophylactic antimicrobial 
agents should be discussed with the BMS Medical Monitor/designee.
6) Prior/Concomitant Therapy
Prohibited concomitant medications and washout periods are further detailed in Table 6
(Section 7.7.1) and APPENDIX 7). Subjects must also comply with the protocol 
requirements for restricted concomitant medications (Table 7 [Section 7.7.2]) and dose 
stabilization rules (Table 8 [Section 0]).
 
 
 
Subjects who have been exposed to the medications listed above, but who have not had a 
treatment failure, may be eligible for inclusion. Similarly, subjects who have experienced 
intolerance to the medications listed above (eg, an infusion reaction) without a treatment 
failure may be eligible for inclusion.
c) Prior treatment failure (inadequate response or loss of response) 
 
 
e) Not applicable per Protocol Amendment 02 - Use of topical rectal treatment with 5-ASA 
or corticosteroid within 2 weeks prior to randomization
f)
Use of intravenous (IV) corticosteroids within 2 weeks prior to the screening period 
(signing the ICF)
g) Use of immunomodulators (AZA, 6-MP, or MTX) within 4 weeks prior to randomization
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h) Use of other investigational agents within 4 weeks or 5 half-lives (whichever is longer) 
prior to randomization
Fecal transplant is considered an investigational agent for the purpose of this protocol and 
is subject to a 4-week washout period prior to randomization.
 
k) Administration of a live vaccine within 90 days prior to randomization
Live vaccines should not be used during the study or within the 2 months following last 
dose.
Heat-killed, or otherwise inactivated vaccines, or protein or subunit vaccines (eg, influenza 
and pneumococcal vaccines) may be received at any time on study. The efficacy of 
vaccination in subjects who are receiving BMS-986165 is unknown.
l)
Not applicable per Protocol Amendment 02 - Currently on any therapy for chronic 
infection (eg, pneumocystis, cytomegalovirus, herpes simplex, herpes zoster, invasive 
bacterial or fungal infections, or atypical mycobacteria).
m) Use of topical rectal treatment with 5-ASA or corticosteroid within 2 weeks prior to 
screening (signing of ICF).
n) Currently on any therapy for chronic infection (eg, pneumocystis, CMV, herpes simplex, 
herpes zoster, invasive bacterial or fungal infections, or atypical mycobacteria).
Study inclusion eligibility of subjects being treated with antimicrobial agents strictly for 
prophylaxis should be discussed with the BMS Medical Monitor/designee.
7) Physical and Laboratory Test Findings
a) Evidence of organ dysfunction or any clinically significant deviation from normal in 
physical examination, vital signs, ECG, CXR, or clinical laboratory determinations beyond 
what is consistent with the target population
b) Clinically significant abnormalities on CXR or ECG
c) Evidence of active or latent tuberculosis (TB), as follows:
i)
History of active TB prior to the screening visit, regardless of completion of adequate 
treatment
OR
ii) Has signs or symptoms of active TB as judged by the investigator
OR
iii) CXR obtained during the screening period or anytime within 6 months before 
screening, with documentation, with evidence of current active or old active pulmonary
TB
OR
iv) Not applicable per Protocol Amendment 02 - Latent TB infection (LTBI) defined as 
positive 
 
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at screening, or other diagnostic test in the 
absence of clinical manifestations
v) LTBI 
defined 
as 
positive 
 
 
 
 
 
at screening
OR
vi) An indeterminate 
 result at screening with no signs or symptoms of active TB
Subjects diagnosed with LTBI during screening may be eligible if (1) there are no current 
signs or symptoms of active TB and (2) the subject has received adequate documented 
treatment for LTBI within 5 years of screening OR has initiated prophylactic treatment for 
LTBI per local guidelines and is now rescreened after 1 month of treatment. The subject 
must agree to complete a locally recommended course of treatment for LTBI to continue 
in the study.
A subject with an indeterminate 
 test result may be retested within the same screening 
period. If the second result is also indeterminate, the subject will be excluded from the 
study. If the second result is positive, the subject should be treated as having LTBI. If the 
second result is negative, the subject may be eligible provided no other Exclusion Criterion 
for TB is met.
 
 
g) Clinically significant abnormalities in laboratory testing including (but not limited to):
Hematology:
i)
Hemoglobin level < 8.5 g/dL
ii) White blood cell count < 3.0 × 109/L (< 3000/mm3)
iii) Lymphocyte count < 0.75 × 109/L (< 750/mm3)
iv) Neutrophil count < 1.0 × 109/L (< 1000/mm3)
v) Platelet count < 100 × 109/L (< 100,000/mm3)
Renal function:
vi) Serum creatinine > 2 × ULN or renal impairment based on an estimated glomerular 
filtration rate (eGFR) < 45 mL/min/1.73 m2 (calculated using the Modification of Diet 
in Renal Disease [MDRD] equation)
Liver-related blood tests and liver function:
vii)Serum ALT > 2 × ULN
viii) Serum AST > 2 × ULN
ix) Not applicable per Protocol Amendment 02 - Serum total bilirubin > 1.5 × ULN 
(Subjects with total bilirubin > 1.5 × ULN who have a confirmed diagnosis of Gilbert’s 
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syndrome are not excluded from this study but must be discussed with the BMS 
Medical Monitor/designee.)
x) Alkaline phosphatase (ALP) > 1.5 × ULN
xi) Serum total bilirubin > 1.5 × ULN
h) Positive stool culture for enteric pathogens (not including flora that are considered 
commensal within a study region)
Subject may rescreen 30 days after completion of a standard treatment course with 
antimicrobial agents, with a subsequent “negative” stool culture.
A multipathogen molecular panel for enteric pathogens (eg, multipathogen PCR) may be 
considered as an alternative to stool culture, if this is routinely performed at a site and its 
use is consistent with local standard of care. Use of this test within the study should be 
discussed with the BMS Medical Monitor/designee.
i)
A diagnosis of C. difficile infection
C. difficile toxin A and B, and C. difficile glutamate dehydrogenase (GDH) antigen, with 
reflex to a confirmatory C. difficile nucleic acid amplification test (NAAT) are provided 
within the study. Subjects should not be randomized if there is a clinical suspicion of 
C. difficile infection.
Subjects may be rescreened 30 days after completion of an adequate course of treatment 
for C. difficile (ie, standard of care antibiotics, fecal transplantation, etc.) and subsequent 
negative testing for C. difficile stool toxin and a C. difficile NAAT. Test results should be 
discussed with the BMS Medical Monitor/designee prior to rescreening.
j)
Any other findings on physical examination, vital signs, or clinical laboratory testing that, 
in the opinion of the investigator, may place the subject at an unacceptable risk for 
participation in this study
k) A positive 
 test for SARS-CoV-2 during screening
See Section 9.8 for additional information regarding retesting subjects who have a positive 
diagnostic test for SARS-CoV-2 infection during the screening period.
8) Allergies and Adverse Drug Reaction
a) History of any significant drug allergy (eg, anaphylaxis) or significant adverse drug 
reaction (eg, hepatotoxicity)
9) Other Exclusion Criteria
a) Any major illness or evidence of an unstable clinical condition (eg, renal, hepatic, 
hematologic, gastrointestinal, endocrine, pulmonary, cardiac, immunologic, psychiatric), 
or local active infection/infectious illness that, in the investigator’s judgment, will 
substantially increase the risk to the subject if he or she participates in the study
b) Any major surgery (requiring general anesthesia) within the last 30 days prior to 
randomization, or any other major surgery planned during the course of the study
Such subjects should be discussed with the BMS Medical Monitor/designee. Subject must 
have adequate wound healing prior to randomization. This criterion does not include 
endoscopy performed using sedation or general anesthesia (eg, propofol).
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c) History of bleeding disorders or recent use of anti-platelet or anti-thrombotic agents that in 
the investigator’s judgment preclude safely performing endoscopic procedures and biopsy 
within the timeframe outlined in the study protocol
d) Cancer or history of cancer or lymphoproliferative disease within the previous 5 years 
(other than adequately treated cutaneous basal cell or squamous cell carcinoma or resected
cervix carcinoma in situ with no evidence of recurrence)
e) Subjects with cancer screening or surveillance that is suspicious for malignancy, or where 
the possibility of malignancy cannot be reasonably excluded after additional clinical, 
laboratory, or other diagnostic evaluations
f)
Class III or IV congestive heart failure, as classified by the New York Heart Association 
(NYHA) Functional Classification or any recent onset of heart failure resulting in NYHA 
Class III/IV symptoms
g) Acute coronary syndrome (eg, myocardial infarction, unstable angina pectoris) and/or any 
history of significant cerebrovascular disease (eg, stroke, cerebral hemorrhage, transient 
ischemic attack) within 24 weeks before screening
h) Known history of hereditary galactose intolerance, total lactase deficiency, or glucose-
galactose malabsorption
i)
Significant blood loss (> 500 mL) or blood transfusion within 4 weeks prior to the 
randomization visit
j)
Not applicable per Protocol Amendment 01 - Drug or alcohol abuse, as determined by 
the investigator, within 6 months prior to Day 1 (Note: medical marijuana is not allowed.)
k) Any other sound medical, psychiatric, and/or social reason as determined by the 
investigator
l)
Prisoners or subjects who are involuntarily incarcerated
m) Unable to comply with study procedures and visits
n) Unable to tolerate oral medication
o) Unable to undergo venipuncture and/or tolerate venous access
p) Drug or alcohol abuse, as determined by the investigator, within 6 months prior to Day 1
6.3
Randomization Criteria
Subjects must meet the following criteria at the randomization visit on Day 1 in order to be eligible 
to be randomized and to receive the first dose of study treatment:
1. The subject continues to meet the Inclusion Criteria, listed in Section 6.1.
2. The subject continues to not meet any of the Exclusion Criteria, listed in Section 6.2.
3. The subject has discontinued any prohibited treatments (Table 6, Section 7.7.1).
4. The subject meets the dose stabilization rules for permitted UC medications, outlined in 
Section 7.7.3 (Table 8).
5. The subject meets the washout periods for prior concomitant medications, outlined in 
APPENDIX 7.
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6.4
Lifestyle Restrictions
Subjects are required to fast for a minimum of 10 hours before the randomization visit (Day 1) and 
the Week 12 (Day 85) visit, as fasting lipid and glucose samples will be obtained at those times.
WOCBP must agree to follow instructions for methods of contraception for the duration of 
treatment with IP (APPENDIX 4).
Otherwise, no lifestyle restrictions are required.
Smoking can have an influence on the severity of UC disease symptoms. Consequently, use of 
tobacco products will be assessed at each study visit. Use of a nicotine patch should be recorded 
as a concomitant medication.
Study treatment may be taken without regard to meals.
6.5
Screen Failures
Screen failures are defined as subjects who consent to participate in the clinical study but who are 
not subsequently randomized in the study/included in the analysis population. A minimal set of 
screen failure information is required to ensure transparent reporting of screen failure subjects, to 
meet the Consolidated Standards of Reporting Trials (CONSORT) publishing requirements, as 
applicable, and to respond to queries from regulatory authorities. Minimal information includes 
date of consent, demography, screen failure details, eligibility criteria, and any SAEs. Additional 
screening data, such as SF, RB, and ES subscores; PGAs; fecal calprotectin; and other clinically 
relevant data may also be required.
6.5.1
Retesting During the Screening Period
For laboratory parameters and/or assessments (Section 2) that initially do not meet eligibility 
requirements, a single retest within the screening period may be permitted after consultation with 
the BMS Medical Monitor/designee. The investigator should have a reasonable expectation that 
the retested laboratory parameter and/or assessment is likely to meet eligibility requirements.
Confirmatory testing of parameters that require confirmation per protocol (eg, indeterminate or 
borderline 
 result) and repeat testing of laboratory parameters that are unable to be reported 
(eg, due to an inadequate sample) can be performed without consultation with the BMS Medical 
Monitor/designee.
6.5.2
Rescreening
This study permits the rescreening of a subject who has been deemed as ineligible (a screen failure) 
during the screening period (ie, the subject has not been randomized/has not been treated). Subjects 
who wish to be rescreened should be discussed with the BMS Medical Monitor/designee prior to 
rescreening. The subject must be re-consented and will be assigned a new identification number, 
and a full screening visit must be performed again (unless individual screening investigations can 
be waived, as discussed below). The most current result prior to randomization is the value by 
which study eligibility will be assessed.
A subject can only be rescreened 1 time. If the subject fails 1 rescreening attempt, no additional 
rescreening is allowed.
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For subjects requiring rescreening, the initial screening endoscopy result may be used, 
provided that randomization occurs within 14 days of the initial screening endoscopy. In that 
circumstance, the screening endoscopy does not have to be repeated. Subjects who are likely to 
benefit from this approach should be discussed with the BMS Medical Monitor/designee prior to 
rescreening.

In the case of rescreening after an initial eligible screening endoscopy, the SF and RB scores 
for eligibility will be based on the Day 1 visit date rather than the bowel preparation date.

The window between the initial screening endoscopy and randomization may be extended up 
to an additional 3 days with approval of the BMS Medical Monitor/designee.
Duration of existing treatments and required discontinuation periods shall be considered relative 
to the successful screening visit and/or randomization.
Subjects who are diagnosed with C. difficile infection during screening may be rescreened 30 days 
after completion of an adequate course of treatment for C. difficile (ie, standard of care antibiotics, 
fecal transplantation, etc.) and subsequent negative testing for C. difficile stool toxin and a 
C. difficile NAAT. Test results should be discussed with the BMS Medical Monitor/designee prior 
to rescreening.
Subjects who are diagnosed with LTBI during screening may be eligible to be rescreened for this 
study provided they have completed at least 4 weeks of treatment for LTBI and they comply with 
treatment for LTBI (both according to local standard of care) during study participation. For these 
subjects, a repeat CXR is required during rescreening, but 
 should not be repeated. LTBI 
screening is further discussed in Section 9.4.2.
The following laboratory assessments are not required to be repeated during rescreening if the 
subject is randomized within 45 days of the original screening results: 
 
 thyroid-stimulating 
hormone (TSH).
7
TREATMENT
Study treatment is defined as any investigational treatment(s), marketed product(s), placebo or 
medical device intended to be administered to a study subject according to the study randomization 
or treatment allocation.
An IP, also known as an investigational medicinal product (IMP) in some regions, is defined as a 
pharmaceutical form of an active substance or placebo being tested or used as a reference in a 
clinical study, including products already with a marketing authorization but used or assembled 
(formulated or packaged) differently than the authorized form, or used for an unauthorized 
indication, or when used to gain further information about the authorized form.
IM011127 consists of IP study treatments BMS-986165 and placebo (see Table 4). Information 
about the pharmacology and previous experience with BMS-986165 is provided in Section 3.1.1
and Section 3.1.2.
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Other medications used as support or escape medication for preventative, diagnostic, or therapeutic 
reasons, as components of the standard of care for a given diagnosis, may be considered as non-IPs.
Table 4:
Study Treatments for IM011127
Product Description/
Class and Dosage 
Form
Potency
IP/
Non-IP
Blinded or 
Open-label
Packaging/
Appearance
Storage Conditions
(per label)
BMS-986165
12 mg oral tablet
12 mg
IP
Blinded
Blister card 
containing 
72 tablets
Store 15° to 25°C; 
Protected from light
BMS-986165
6 mg oral tablet
Applicable only to 
subjects enrolled under 
the Original Protocol or 
Protocol Amendment 01
6 mg
IP
Blinded
Blister card 
containing 
72 tablets
Store 15° to 25°C; 
Protected from light
Placebo matching
BMS-986165
12 mg oral tablet
Not 
applicable
IP
Blinded
Blister card 
containing 
72 tablets
Store 15° to 25°C; 
Protected from light
Placebo matching
BMS-986165
6 mg oral tablet
Not 
applicable
IP
Blinded
Blister card 
containing 
72 tablets
Store 15° to 25°C; 
Protected from light
BMS-986165
6 mg oral tablet
6 mg
IP
Open-label
Bottle containing 
68 tablets
Store 15° to 25°C; 
Protected from light
IP = investigational product
7.1
Treatments Administered
During the double-blind treatment period (induction), subjects will receive BMS-986165 12 mg
BID or placebo BID PO over 12 weeks (Section 5.1.2), once in the morning and once in the 
evening. Subjects randomized to the 6 mg BID dose arm under the Original Protocol or Protocol 
Amendment 01 will continue to receive 6 mg BID during the double-blind treatment period. Dose 
information for each treatment group is provided in 
 The morning dose should be taken 
 Study treatment 
will be supplied in blister cards, each containing 72 active or placebo tablets. Blister cards are to 
be stored at 15°C to 25°C and protected from light.
During the OLE period, subjects will take BMS-986165 6 mg BID PO over 40 weeks 
(Section 5.1.3), once in the morning and once in the evening. Dose information is provided in 
 Study treatment will be supplied in bottles containing 68 (6 mg) active tablets. Bottles are 
to be stored at 15°C to 25°C and protected from light.
If a subject forgets a dose, but remembers within 4 hours of the expected dose, the dose should be 
taken. If it is past 4 hours (or if the dose is vomited), that dose should be missed, and the next 
expected dose should be taken at the usual time.
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7.2
Method of Treatment Assignment
At the time of the screening visit, immediately after informed consent is obtained and before any 
study-related procedures are performed, the investigative site will access the interactive response 
technology (IRT) system for assignment of the subject number. This number will be unique across 
all sites. All subjects who sign the ICF will be assigned sequential subject numbers. The subject 
number may not be used for any other subject. If a potential subject is rescreened, they will be 
given a new subject number.
Eligible subjects will be centrally randomized using IRT at a 3:1 randomization ratio to receive 
oral treatment during the treatment period with either BMS-986165 12 mg BID or placebo BID, 
according to a computer-generated block randomization scheme. Randomization numbers will be 
assigned prior to dosing.
Before the study is initiated, each user (at investigative sites) will receive log-in information and 
directions on how to access the IRT. Study treatment will be dispensed at study visits as shown in
the Schedule of Activities (Section 2).
7.3
Blinding
7.3.1
Maintaining the Blind
Blinded treatment assignments will be managed using IRT.
Each BMS-986165 tablet (12 mg and 6 mg) has an identical matching placebo tablet in order to 
maintain the blind. Tablets will be supplied in blister cards (see Section 7.1). Investigative site 
staff, Sponsor and designee personnel, and subjects and their families will remain blinded to 
treatment assignments.
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The Sponsor may perform an unblinded interim analysis of study data prior to final data analysis. 
A SAP, which will include a section on interim analysis, will be created to fully detail the activities 
around the interim analysis.
The DMC may review unblinded data summaries and listings, at their request (see Section 5.1.6). 
DMC processes and procedures will be outlined in the DMC Charter.
Designated staff of BMS may be unblinded (obtain the randomization codes) prior to database 
lock to facilitate the bioanalytical analysis of 
 samples and immunogenicity. A 
bioanalytical scientist in the Bioanalytical Sciences department of BMS (or a designee in the 
external central bioanalytical laboratory) may be unblinded to the randomized treatment 
assignments in order to minimize unnecessary bioanalytical analysis of samples.
7.3.2
Circumstances for Unblinding
Blinding of treatment assignment is critical to the integrity of this clinical study. However, in the 
event of a medical emergency or pregnancy in an individual subject in which knowledge of the IP 
is critical to the subject’s management, the blind for that subject may be broken by the investigator. 
The subject’s safety takes priority over any other considerations in determining if a treatment 
assignment should be unblinded.
Before breaking the blind of an individual subject’s treatment, the investigator should determine 
that the unblinded information is necessary, ie, that it will alter the subject’s immediate 
management. In many cases, particularly when the emergency is clearly not related to the IP, the 
problem may be properly managed by assuming that the subject is receiving active product. It is 
highly desirable that the decision to unblind treatment assignment be discussed with the BMS 
Medical Monitor/designee, but the investigator always has ultimate authority for the decision to 
unblind. The actual TASK of unblinding can be delegated by the investigator to a designee 
assigned the task on the Delegation of Authority. The principal investigator or appointed designee 
should only call in for emergency unblinding AFTER the decision to unblind the subject has been 
documented.
In case of an emergency, the investigator has unrestricted access to randomization information via 
IRT and is capable of breaking the blind through the IRT system without prior approval from the 
Sponsor. After the unblinding via IRT, the investigator shall notify the BMS Medical 
Monitor/designee and/or study director. The method of unblinding for emergency purposes is 
described in the IRT manual. Subject and unblinded treatment information and the reason for the 
blind being broken, must be recorded on the appropriate study status page of the eCRF.
In cases of accidental unblinding, contact the BMS Medical Monitor/designee and ensure every
attempt is made to preserve the blind. Any request to unblind a subject for nonemergency purposes 
must be discussed with the BMS Medical Monitor/designee.
7.4
Dosage Modification
There is no provision for dose modification of study treatment.
Dose stabilization criteria for permitted UC treatments are detailed in Section 0 (Table 8).
Modification of permitted UC treatments or dose regimens is allowed for safety reasons, or if a 
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subject experiences an AE attributable to that treatment. Subjects should continue to take their 
assigned treatment even if their clinical condition worsens (ie, they experience a “flare”), unless 
any of the criteria in Section 8.1 are met. If a subject’s clinical condition worsens before Week 12 
of the treatment period to the extent that rescue therapy is required, based on the investigator’s 
judgment, the subject must discontinue study treatment (IP or placebo) in favor of appropriate 
alternative available treatment.
See Section 8.1.1 for information regarding temporary interruption of study treatment.
7.5
Preparation/Handling/Storage/Accountability
The IP should be stored in a secure area according to local regulations. It is the responsibility of 
the investigator to ensure that IP is only dispensed to study subjects. The IP must be dispensed 
only from official study sites by authorized personnel according to local regulations.
The product storage manager should ensure that the study treatment is stored in accordance with 
the environmental conditions (temperature, light, and humidity) as determined by BMS. If 
concerns regarding the quality or appearance of the study treatment arise, the study treatment 
should not be dispensed and BMS should be contacted immediately.
Study treatment not supplied by BMS will be stored in accordance with the package insert.
IP documentation (whether supplied by BMS or not) must be maintained that includes all processes 
required to ensure drug is accurately administered. This includes documentation of drug storage, 
administration and, as applicable, storage temperatures, reconstitution, and use of required 
processes (eg, required diluents, administration sets).
Further guidance and information for final disposition of unused study treatment are provided in 
APPENDIX 2 and the Study Reference Manual.
7.5.1
Retained Samples for Bioavailability/Bioequivalence/Biocomparability
Not applicable.
7.6
Treatment Compliance
Study treatment compliance will be monitored as indicated in the Schedule of Activities 
(Section 2) using standard drug accountability procedures (comparing the number of tablets 
returned to number dispensed, considering the expected regimen and any reported missed doses). 
Drug accountability will be reviewed by the investigative site staff at each visit to confirm 
treatment compliance. Site staff will discuss any discrepancies with the subject and remind the 
subject of the importance of compliance with the assigned regimen.
7.7
Concomitant Therapy
All medications taken from within 4 weeks before the first dose of study treatment until 30 days 
after the last dose of IP or last visit (whichever comes later) must be recorded on the appropriate 
eCRF.
Other than existing treatment for UC (with restrictions as described in the eligibility criteria 
[Section 6]), concomitant medications (prescription, over-the-counter [OTC], or herbal) should be 
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administered during the study only if they are prescribed for treatment of specific medical reasons 
separate from UC.
7.7.1
Prohibited Treatments
Prohibited prior and current concomitant medications are summarized in Table 6. Additional 
details on washout periods are listed in APPENDIX 7.
Table 6:
Summary of Prohibited Concomitant Medications
Prohibited Treatments 
Medication/Formulation 
Notes 
BMS-986165 or other TYK2 inhibitors
Prior exposure is prohibited
Immunomodulatory drugs
Prohibited within required washout periods (APPENDIX 7) and 
during the study
Biologic drugs
Prohibited within required washout periods (APPENDIX 7) and 
during the study
Live vaccines
Prohibited 90 days prior to the randomization visit, during the 
treatment period, or within the 2 months after the last dosea. 
Vaccine guidance for the study is outlined in APPENDIX 13
Apheresis
Receipt of either lymphocyte apheresis or selective monocyte, 
granulocyte apheresis (eg, Cellsorba™) is prohibited within 
12 months prior to the randomization visit and during the study
Investigational agents
Prohibited within 4 weeks or 5 half-lives (whichever is longer)
before the randomization visit and during the study
Traditional Chinese medicines, 
herbal medicines, or herbal supplements
Prohibited within 1 week prior to the randomization visit; any 
exceptions to this must be cleared by the BMS Medical 
Monitor/designee
Fluvoxamine
Prohibited within 1 week of the randomization visit and during 
study
Therapy for chronic infections
Subjects who require treatment for chronic infections are excluded
NOTE: Eligibility of subjects receiving prophylactic antibiotic 
therapy for study inclusion should be discussed with the BMS
Medical Monitor/designee.
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TYK2 = tyrosine kinase 2; 
a Heat-killed (or otherwise inactivated) or protein or subunit vaccines such as influenza and pneumococcal vaccines, 
nucleic acid vaccines that do not encode potentially infectious virus, and replication-incompetent recombinant 
vector vaccines may be received at any time during the study. The efficacy of vaccination in subjects who are 
receiving BMS-986165 is unknown (see APPENDIX 13 for vaccine guidance).
7.7.2
Restricted Treatments
Restricted concomitant medications are summarized in Table 7.
Table 7:
Summary of Restricted Concomitant Medications
Restricted Treatments 
Medication/Formulation 
Notes 
NSAIDs
May be used on an as needed basis during the study, but 
use is not recommended, as NSAIDs may be associated 
with gastrointestinal toxicity, including mucosal injury
NSAID = nonsteroidal anti-inflammatory drug; 
7.7.3
Dose Stabilization Rules for Permitted UC Treatments
Use of concomitant oral 5-ASAs or oral corticosteroids 
 
 is permitted, subject to the dose stabilization rules 
outlined in Table 8. Probiotics are allowed with no restrictions on use. Subjects will continue their 
existing UC treatment(s) during the study, provided the treatment complies with the eligibility 
criteria (see Section 6.1, Section 6.2, and Table 6).
Dose reduction or discontinuation of 5-ASAs or corticosteroids is allowed during the study if this 
is required for subject safety reasons, such as if a subject experiences an AE attributable to those 
medications. The rationale for dose reduction or discontinuation must be documented in source 
documents. The AE or SAE eCRF must be completed, if applicable.
Table 8:
Dose Stabilization Rules for Allowed Concomitant Medications
Medication/Formulation 
Notes 
5-ASAs (oral):

The oral 5-ASA regimen must be at a stable dose for at least 2 weeks prior 
to the initial screening visit (signing of ICF). Dose reduction (or 
discontinuation) is only allowed within this period for safety reasons, or if 
a subject experiences an AE attributable to the 5-ASA regimen.
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Table 8:
Dose Stabilization Rules for Allowed Concomitant Medications
Medication/Formulation 
Notes 

Stable doses are encouraged after randomization for the duration of the 
12-week double-blind treatment period.

 
 must be at a stable dose for 
at least 2 weeks prior to the initial screening visit (signing of ICF). Dose 
reduction (or discontinuation) is only allowed within this period for safety 
reasons or if the subject experiences an AE attributable to the 
. This must be discussed with the BMS Medical 
Monitor/designee.

After randomization, a stable dose is required for the duration of the 
12-week treatment period. Dose reduction (or discontinuation) is only 
allowed within the treatment period for safety reasons, or if the subject 
experiences an AE attributable to the 
. This must be 
discussed with the BMS Medical Monitor/designee.

Throughout the study, an increase in 
dose above the baseline 
dose is not permitted.
Probiotics:

Probiotics are allowed. Dose stabilization is not required. 
5-ASA = 5-aminosalicyclic acid; AE = adverse event; ICF = informed consent form; 
 
 
 
 
 
 
 
 
 
 
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7.8
Treatment After the End of the Study
At the end of the study (Section 5.3), the investigator should ensure that subjects continue to 
receive appropriate standard of care to treat the condition under study.
In addition, for subjects who continue to demonstrate clinical benefit, BMS may continue to 
provide study treatment via an extension of the current study (ie, Study IM011077) or through 
another mechanism at the discretion of BMS.
BMS reserves the right to terminate access to BMS supplied study treatment if any of the following 
occur: a) the study is terminated due to safety concerns; b) the development of BMS-986165 is 
terminated for any reason, including but not limited to lack of efficacy and/or not meeting the 
study objectives; c) the subject can obtain medication from a government sponsored or private 
health program. In all cases BMS will follow local regulations.
8
DISCONTINUATION CRITERIA
8.1
Discontinuation from Study Treatment
Subjects MUST discontinue IP (and non-IP at the discretion of the investigator) for any of the 
following reasons:

Subject’s request to stop study treatment. Subjects who request to discontinue study treatment 
will remain in the study and must continue to be followed for protocol-specified posttreatment 
follow-up procedures (Section 5.1.4). The only exception to this is when a subject specifically 
withdraws consent for any further contact with him/her or persons previously authorized by 
subject to provide this information.

Any clinical AE, laboratory abnormality, or intercurrent illness which, in the opinion of the 
investigator, indicates that continued participation in the study is not in the best interest of the 
subject
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
Termination of the study by BMS

Loss of ability to freely provide consent through imprisonment or involuntarily incarceration 
for treatment of either a psychiatric or physical (eg, infectious disease) illness. (Note: Under 
specific circumstances and only in countries where local regulations permit, a participant who 
has been imprisoned may be permitted to continue as a participant. Strict conditions apply and 
BMS approval is required).

Subject meets 1 of the following criteria for laboratory abnormalities in 2 sequential laboratory 
measurements taken 3 to 5 days apart:
 
 
 
 
 
 

Subject meets any of the following criteria for liver-related laboratory abnormalities. If these 
abnormalities are identified, repeat testing should occur within 48-72 hours and these results 
should be discussed with the BMS Medical Monitor/designee. Additional recommendations 
on the recognition and investigation of potential DILI are given in Section 9.2.7.

ALT or AST > 8 × ULN on a single occasion

ALT or AST > 5 × ULN for more than 2 weeks

ALT or AST > 3 × ULN and total bilirubin > 2 × ULN or international normalized ratio 
(INR) > 1.5

ALT or AST > 3 × ULN with the appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash, and/or eosinophilia (> 5%)
 
 
 
 

Unblinding of a subject’s treatment assignment for any reason (emergency or nonemergency)

Inability or failure to comply with protocol requirements

Pregnancy, positive pregnancy test, or subject no longer wishes to comply with study 
requirements relating to prevention of pregnancy (Refer to Section 9.2.5)
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All subjects who discontinue study treatment should comply with protocol-specified ET and 
follow-up procedures as outlined in the Schedule of Activities (Section 2). The only exception to 
this requirement is when a subject withdraws consent for all study procedures including 
posttreatment study follow-up or loses the ability to consent freely (ie, is imprisoned or 
involuntarily incarcerated for the treatment of either a psychiatric or physical illness).
If study treatment is discontinued prior to the subject’s completion of the study, the reason for the 
discontinuation must be documented in the subject’s medical records and entered on the 
appropriate eCRF page.
8.1.1
Temporary Interruption of Study Treatment
The following criteria for temporary interruption of study treatment apply at any time during the
52-week treatment period:

For those subjects who present with signs and/or symptoms of COVID-19 during the study, 
the study treatment should be temporarily interrupted while the subject undergoes diagnostic 
testing for SARS-CoV-2 (see Section 9.8 [SARS-CoV-2 Testing]).

Study treatment must be temporarily interrupted for subjects who test positive for 
SARS-CoV-2 until complete recovery (if symptomatic) and a negative molecular test result is 
obtained. Study treatment may be restarted at investigator discretion following consultation 
with the BMS Medical Monitor/designee provided that the subject meets the criteria outlined 
in Section 9.8 (SARS-CoV-2 Testing).

Study treatment should be temporarily withheld if a subject develops a skin-related AE that is 
either severe in intensity, or meets the criteria for an SAE (see APPENDIX 3 for definitions), 
or is sufficient to require temporary discontinuation in the judgment of the investigator. Study 
treatment should be temporarily withheld until the intensity of the AE decreases or the AE 
resolves, and may be restarted only after discussion of the case with the BMS Medical 
Monitor/designee.
Additional criteria for temporary interruption applicable to the OLE period only are as follows:

Study treatment may be interrupted by the investigator for medical procedures not related to 
UC or for AEs that do not meet criteria for study discontinuation and are assessed by the 
investigator as not related to the study drug under the following conditions:
o
Documented prior approval from the BMS Medical Monitor/designee
o
Agreement between the investigator and the BMS Medical Monitor/designee that the 
subject has benefited from study treatment and that temporary interruption (rather than 
discontinuation) of study drug will result in the greatest benefit to the subject
o
Dose interruption is expected to be 4 weeks or less
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Study treatment may be restarted at investigator discretion following consultation with the 
BMS Medical Monitor/designee provided that there has been adequate resolution of AE or 
post-procedure condition.
8.1.2
Poststudy Treatment Study Follow-Up
Subjects who discontinue study treatment will continue to be followed for 28 days post last dose 
of study drug, or longer, as required, and in line with Section 9.2.3 (Follow-up of AEs and SAEs). 
The posttreatment follow-up visit (Week 56) is not required for subjects who transition to a 
BMS-sponsored roll-over/follow-on study (eg, Study IM011077).
8.2
Discontinuation from the Study
Subjects who request to discontinue study treatment (Section 8.1) will remain in the study and 
continue to be followed for protocol-specified posttreatment follow-up procedures. The only 
exception to this is when a subject specifically withdraws consent for any further contact with 
him/her or persons previously authorized by subject to provide this information.

Subjects should notify the investigator of the decision to withdraw consent from future 
follow-up in writing, whenever possible.

The withdrawal of consent should be explained in detail in the medical records by the 
investigator and entered on the appropriate eCRF page.

In the event that vital status (whether the subject is alive or dead) is being measured, publicly 
available information should be used to determine vital status only as appropriately directed in 
accordance with local law.

If the subject withdraws consent for disclosure of future information, the Sponsor may retain 
and continue to use any data collected before such a withdrawal of consent.
8.3
Lost to Follow-Up

All reasonable efforts must be made to locate subjects to determine and report their ongoing 
status. This includes follow-up with persons authorized by the subject.

Lost to follow-up is defined by the inability to reach the subject after a minimum of 
3 documented phone calls, faxes, or emails as well as lack of response by subject to 1 registered 
mail letter. All attempts should be documented in the subject’s medical records.

If it is determined that the subject has died, the site will use permissible local methods to obtain 
date and cause of death.

If investigator’s use of third-party representative to assist in the follow-up portion of the study 
has been included in the subject’s ICF, then the investigator may use a Sponsor retained third-
party representative to assist site staff with obtaining subject’s contact information or other 
public vital status data necessary to complete the follow-up portion of the study.

The site staff and representative will consult publicly available sources, such as public health 
registries and databases, to obtain updated contact information.

If after all attempts, the subject remains lost to follow-up, then the last known alive date as 
determined by the investigator should be reported and documented in the subject’s medical 
records.
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8.4
Replacement of Subjects
Subject replacement is not permitted.
8.5
Study Discontinuation
A DMC will provide oversight of the safety of trial subjects as outlined in Section 5.1.6 of the 
protocol and in the DMC Charter.
The DMC will periodically review safety data and make recommendations regarding the 
appropriateness of continuing the study, with or without study modifications, or stopping the study.
BMS reserves the right to terminate access to BMS supplied study treatment if any of the following 
occur: a) the study is terminated due to safety concerns; b) the development of BMS-986165 is 
terminated for other reasons, including but not limited to lack of efficacy and/or not meeting the 
study objectives; c) the participant can obtain medication from a government sponsored or private 
health program. In all cases BMS will follow local regulations.
9
STUDY ASSESSMENTS AND PROCEDURES
Study procedures and timing are summarized in the Schedule of Activities (Section 2). Waivers or 
exemptions from protocol-required evaluations are not allowed.
All immediate safety concerns must be discussed with the BMS Medical Monitor/designee 
immediately upon occurrence or awareness to determine if the subject should continue or 
discontinue treatment.
Adherence to the study design requirements, including those specified in the Schedule of Activities 
(Section 2), is essential and required for study conduct.
All screening evaluations must be completed and reviewed to confirm that potential subjects meet 
all eligibility criteria before randomization. The investigator will maintain a screening log to record 
details of all subjects screened and to confirm eligibility or record reasons for screening failure, as 
applicable.
Procedures conducted as part of the subject’s routine clinical management (eg, complete blood 
count) and obtained before signing of the ICF may be utilized for screening purposes provided the 
procedure meets the protocol-defined criteria and this approach has been discussed and agreed 
with the BMS Medical Monitor/designee (Section 2). A CXR performed less than 6 months prior 
to signing of the ICF may be used in place of the screening CXR, provided the subject has no 
symptoms or signs suggestive of pulmonary disease in the interim.
Assessments at the randomization visit (Day 1) must be performed per protocol. Standard of care 
assessments may not be used to establish pretreatment baseline parameters (ie, at the 
randomization visit). Procedures not specified in the protocol that are part of standard care may be 
performed if they do not interfere with study procedures. Any data arising from such procedures 
are not to be reported in the eCRF.
The study data includes all the information that is collected as a result of the study, including 
participant demographics, disease characteristics, clinical information, blood tests, biomarker 
tests, endoscopic videos, intestinal biopsies obtained during endoscopy, and other tests listed in 
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Table 1. Study data collected during this study will be used to help us understand how
BMS-986165 works in people with UC, and related health conditions. The study data may also be 
used to help us understand the biology of UC and related health conditions, how study tests 
perform in people with UC, and for other relevant health research relating to BMS-986165 or these 
health conditions.
9.1
Efficacy Assessments
Every effort must be made to ensure that the same evaluator(s) complete the assessment for each 
subject. If the evaluator(s) is unable to complete the evaluation, then a qualified individual with 
overlapping experience may perform the evaluation. Documentation of who performed the 
evaluation is to be recorded in source documents. Assessments are to be performed at 
approximately the same time of day throughout the duration of the study.
9.1.1
Capturing Data to Assess Disease Activity and Determine Efficacy

Subject’s Electronic Daily Diary: An electronic diary will be provided to each subject for 
daily recording of SF and RB data. Baseline SF (either reference remission SF or pre-UC SF; 
see Mayo score, below) and health-related quality of life (Inflammatory Bowel Disease 
Questionnaire [IBDQ]) will also be captured in the electronic diary at the timepoints indicated 
in the Schedule of Activities (Section 2).
Data derived from the electronic daily diary are used for assessment of Inclusion Criteria and 
outcome measures. Subjects will be trained on the use of the electronic diary at the screening 
visit. Sites should periodically assess subject compliance with the electronic daily diary. 
Should the subject miss daily entries prior to a study visit, the investigator should assess if the 
visit should be rescheduled to ensure that an adequate number of daily entries for efficacy 
assessment are recorded.

Medidata Rave Electronic Data Capture (EDC): The PGA (see Mayo score, below) and 
UC-related medical resource utilization (see Section 9.7) will be evaluated by the 
investigator or designee and recorded in the Medidata Rave EDC system at the timepoints 
indicated in the Schedule of Activities (Section 2).

Endoscopy: Endoscopy (colonoscopy or flexible sigmoidoscopy) will be performed at the 
timepoints indicated in the Schedule of Activities 
 
 
 
 
 
 
 
 
 
 
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
Endoscopic biopsies: 
 
 
 
 
 
 
 
 

Serum high-sensitivity C-reactive protein (hsCRP): 
 
 
 

 fecal lactoferrin: 
 
 
 
 
 
9.1.2
Disease Activity and Quality of Life Indices Used in this Study
The following instruments will be used to assess UC disease activity and health-related quality of 
life during the study as indicated in the Schedule of Activities (Section 2). Selected endpoints that 
use these indices are defined in Table 10:

Total Mayo score: The total Mayo score is a composite disease activity index that is 
comprised of 4 subscores: SF, RB, and ES subscores, and a PGA subscore.47 Consistent with 
regulatory draft guidance, the ES subscore scale has been modified so that friability is no longer 
included in the definition of an ES subscore = 1.38, 48 Each subscore is scored on a 4-point scale, 
ranging from 0-3, leading to a maximum total score of 12. Higher scores indicate more severe 
disease. The total Mayo score may be determined at screening and/or Day 1 and at Weeks 12 
and 52, and ET visit (if applicable). It will be used in endpoint assessment.

Modified Mayo score: The modified Mayo score is a composite of the following total Mayo 
score subscores: SF, RB, and ES.38 Friability is not included in the definition of an 
ES subscore = 1, and the PGA is not included in the calculation of the modified Mayo score.
38, 39, 48 The maximum total score of the modified Mayo score is 9. The modified Mayo score 
calculated to determine eligibility will be used as the baseline score for randomization on 
Day 1. The modified Mayo score will also be determined at Weeks 12 and 52, and ET visit (if 
applicable). It will be used in endpoint assessment.

Details regarding the recording of the individual Mayo score components and the calculation 
of the total Mayo score and modified Mayo score are provided in APPENDIX 9, while timing 
of assessments are detailed in the Schedule of Activities (Section 2). Briefly, the investigator 
records the baseline SF at the screening visit, and the PGA at each study visit, while the subject 
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records daily SF and RB scores in the study diary. The ES subscore will be determined by a 
central reader who is blinded to subject details, including visit number and treatment 
assignment. The investigator will also record an ES subscore (local read) which will be used 
for post hoc analyses.

Partial Mayo score: The partial Mayo score is a composite of the following Mayo score 
subscores: SF, RB, and PGA.49 The partial Mayo score may be determined at the timepoints 
indicated in the Schedule of Activities (Section 2).

Symptomatic Mayo score: The symptomatic Mayo score is a composite and defined as the
sum of the Mayo SF and RB subscores. It may be calculated at various timepoints and will be 
used in endpoint assessment.

UCEIS:50, 51 The UCEIS is a composite index that evaluates the endoscopic appearance of the 
mucosa. Three descriptors are scored as follows: vascular pattern (0 to 2), bleeding (0 to 3), 
and erosions and ulcers (0 to 3), to give a score ranging from 0-8, where higher scores indicate 
more severe disease (APPENDIX 10). 
 
Additional details on endoscopy image acquisition, image quality control and central reading 
for the assessment of Mayo ES subscore and UCEIS will be provided in the Endoscopy Image 
Review Charter.

 
 
 
 
 
 
 
 

UC-10040: The UC-100 is a composite index that uses the weighted Mayo SF subscore, Mayo 
ES subscore, 
 to derive a score that ranges from 1 to 100, where higher scores indicate 
a greater degree of disease activity. 40
Additional details regarding calculation of UC-100 scores will be provided in the SAP.

Patient-reported Outcomes (PROs): The following instruments will be used for the 
assessment of additional PROs, health-related quality of life, and healthcare utilization. All 
instruments are to be completed by subjects:

IBDQ54: The IBDQ is a well-established assessment to measure disease-specific health-
related quality of life. It is composed of 32 items and 4 domains including gastrointestinal 
symptoms, systemic symptoms, emotional dysfunction, and social dysfunction. 
Questionnaire items have a 2-week recall period and are scored on a 7-point Likert scale 
from worst health (1) to best health (7) (APPENDIX 11).
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
UC-related Hospitalization and Surgeries: This instrument provides questions/prompts 
representative of the data to be collected through eCRF regarding subjects’ UC-related 
hospitalizations and surgical procedures (APPENDIX 12).
Table 10:
Selected Endpoint Definitions
Endpoint
Definition
Clinical response
Achieving the following changes in the modified Mayo score:

A decrease from baseline in the modified Mayo score of 
≥2 points, and

A decrease from baseline in the modified Mayo score 
≥30%, and

A decrease in RB subscore of ≥1 point or absolute 
RB subscore ≤1
Clinical remission
(modified Mayo score)
A modified Mayo scorea with the following:

SF subscore ≤1, with ≥1 point decrease from baseline, 
and

RB subscore = 0, and

Modified ESb subscore ≤1
Clinical remission
(total Mayo score)
A total Mayo scorea ≤2, with no individual subscore > 1
Symptomatic remission
A symptomatic Mayo scorea with the following:

SF subscore ≤1, with ≥1 point decrease from baseline, 
and

RB subscore = 0
Corticosteroid-free remission
Clinical remission in subjects using oral corticosteroids at 
baseline who have discontinued corticosteroids for UC in the 
OLE period for ≥12 weeks prior to Week 52
Durable clinical response
Clinical response at Week 12, which is maintained at 
Week 52
Endoscopic remission
Mayo ES subscore = 0
Endoscopic improvement
Mayo ES subscore ≤1b
Endoscopic response
A decrease from baseline of ≥1 point in Mayo ES subscore
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Table 10:
Selected Endpoint Definitions
Endpoint
Definition
Durable endoscopic response
Endoscopic response at Week 12 which is maintained at 
Week 52
ES = endoscopic; OLE = open-label extension; RB = rectal bleed; SF = stool frequency; UC = ulcerative colitis
a See Section 9.1.2 and APPENDIX 9 for a description of the total, modified, and symptomatic Mayo scores.
b Obtained from centrally-read endoscopy (Section 9.1.1). Friability is not included in the modified definition of 
ES = 1.
9.2
Adverse Events
The definitions of an AE or SAE can be found in APPENDIX 3.
AEs will be reported by the subject (or, when appropriate, by a caregiver, surrogate, or the subject’s 
legally authorized representative).
The investigator and any designees are responsible for detecting, documenting, and reporting 
events that meet the definition of an AE or SAE and remain responsible for following up AEs that 
are serious, considered related to the study treatment or the study, or that caused the subject to 
interrupt or discontinue study treatment before completing the study.
Contacts for SAE reporting are specified in APPENDIX 3.
9.2.1
Time Period and Frequency for Collecting AE and SAE Information
The collection of nonserious AE information should begin at initiation of study treatment and 
continue until the follow-up visit at Week 56 or the last visit, at the time points specified in the 
Schedule of Activities (Section 2). Nonserious AE information should also be collected from the 
start of the treatment period at Day1. The Reference Safety Information 
 
 should be used to determine the expectedness of SAEs for expedited reporting.
All AEs related to SARS-CoV-2 infection, and all SAEs, must be collected from the time of 
signing the consent to the end of the safety follow-up period (within 30 days of treatment 
discontinuation) or roll-over into a follow-on study.
The investigator must report any SAE that occurs after these time periods and that is believed to 
be related to study drug or protocol-specified procedure (eg, a follow-up skin biopsy).

Medical occurrences that begin before the start of study treatment but after obtaining informed 
consent will be recorded on the appropriate section of the eCRF module.
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
All SAEs and AEs related to SARS-CoV-2 infection (including a positive diagnostic 
SARS-CoV-2 test) will be recorded and reported immediately to the Sponsor or designee but 
no later than 24 hours after awareness of the event, as indicated in APPENDIX 3.

The investigator will submit any updated SAE data to the Sponsor or designee immediately 
but no later than 24 hours of updated information being available.
Investigators are not obligated to actively seek AEs or SAEs in former study subjects. However, 
if the investigator learns of any SAE, including a death, at any time after a subject has been 
discharged from the study, and he/she considers the event reasonably related to the study treatment 
or study participation, the investigator must promptly notify the Sponsor or designee.
The method of evaluating and assessing causality of AEs and SAEs and the procedures for 
completing and reporting/transmitting SAE reports are provided in APPENDIX 3.
9.2.2
Method of Detecting AEs and SAEs
AEs can be spontaneously reported or elicited during open-ended questioning, examination, or 
evaluation of a subject. To prevent reporting bias, subjects should not be questioned regarding the 
specific occurrence of one or more AEs.
9.2.3
Follow-up of AEs and SAEs

Nonserious AEs should be followed to resolution or stabilization or reported as SAEs if they 
become serious (see APPENDIX 3).

Follow-up is also required for nonserious AEs that cause interruption or discontinuation of 
study treatment and for those present at the end-of-study treatment as appropriate.

All identified nonserious AEs must be recorded and described on the nonserious AE page of 
the case report form (CRF). Completion of supplemental CRFs may be requested for AEs 
and/or laboratory abnormalities that are reported/identified during the course of the study.
After the initial AE/SAE report, the investigator is required to proactively follow each subject at 
subsequent visits/contacts. All SAEs and nonserious AEs of special interest (as defined in 
Section 9.2.8) will be followed until resolution, until the condition stabilizes, until the event is 
otherwise explained, or until the subject is lost to follow-up (as defined in Section 8.3).
Further information on follow-up procedures is given in APPENDIX 3.
9.2.4
Regulatory Reporting Requirements for SAEs

Prompt notification by the investigator to the Sponsor or designee of SAEs is essential so that 
legal obligations and ethical responsibilities toward the safety of subjects and the safety of a 
product under clinical investigation are met.

An investigator who receives an investigator safety report describing SAEs or other specific 
safety information (eg, summary or listing of SAEs) from the Sponsor or designee will file it 
along with the IB and will notify the Institutional Review Board (IRB)/Independent Ethics 
Committee (IEC), if appropriate according to local requirements.
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Sponsor or designee will be reporting AEs to regulatory authorities and ethics committees 
according to local applicable laws including European Directive 2001/20/EC and FDA Code of 
Federal Regulations 21 CFR Parts 312 and 320. A SUSAR is a subset of SAEs and will be reported 
to the appropriate regulatory authorities and investigators following local and global guidelines 
and requirements.
9.2.5
Pregnancy
If, following initiation of the study treatment, it is subsequently discovered that a participant is 
pregnant or may have been pregnant at the time of study exposure, including during and at least 
for 30 days after study product administration, the investigator must immediately notify the BMS 
Medical Monitor/designee of this event and complete and forward a Pregnancy Surveillance Form 
to BMS Designee within 24 hours of awareness of the event and in accordance with SAE reporting 
procedures described in APPENDIX 3.
Follow-up information regarding the course of the pregnancy, including perinatal and neonatal 
outcome and, where applicable, offspring information must be reported on the Pregnancy 
Surveillance Form. Protocol-required procedures for study discontinuation and follow-up must be 
performed on the participant.
Any pregnancy that occurs in a female partner of a male study subject should be reported to 
Sponsor or designee. In order for the Sponsor or designee to collect any pregnancy surveillance 
information from the female partner, the female partner must sign an ICF for disclosure of this 
information. Information on this pregnancy will be collected on the Pregnancy Surveillance Form.
9.2.6
Laboratory Test Result Abnormalities
The following laboratory test result abnormalities should be captured on the nonserious AE CRF 
page or SAE Report Form electronic, as appropriate. Paper forms are only intended as a back-up 
option when the electronic system is not functioning.

Any laboratory test result that is clinically significant or meets the definition of an SAE

Any laboratory test result abnormality that required the participant to have study treatment 
discontinued or interrupted

Any laboratory test result abnormality that required the participant to receive specific 
corrective therapy
It is expected that wherever possible, the clinical rather than laboratory term would be used by the 
reporting investigator (eg, anemia versus low hemoglobin value).
9.2.7
Potential Drug-Induced Liver Injury (DILI)
Clinical chemistry and coagulation tests will be assessed as indicated in the Schedule of Activities 
(Section 2). Subjects with abnormal liver blood tests should be further assessed to determine if 
these meet the criteria for discontinuation of the study drug (see Section 8.1) or the criteria for 
potential DILI.
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Potential DILI is defined as:
1) ALT or AST elevation > 3 × ULN,
AND
2) Total bilirubin > 2 × ULN, without initial findings of cholestasis (elevated serum alkaline 
phosphatase),
AND
3) No other immediately apparent possible causes of ALT or AST elevation and 
hyperbilirubinemia, including, but not limited to, viral hepatitis, preexisting chronic or acute 
liver disease, or the administration of other drug(s) known to be hepatotoxic.
Identification of a clinically significant elevation(s) in liver-related chemistry or coagulation tests 
(including those defined in Section 8.1, or meeting the definition for potential DILI) should be 
followed by repeat testing of ALT, AST, total bilirubin, ALP, and INR within 48-72 hours to: 
(1) confirm the abnormalities, and (2) determine if they are increasing or decreasing.
Investigators should consult with the BMS Medical Monitor/designee immediately if a subject 
meets the laboratory criteria for potential DILI.
Investigators should consider gathering additional clinical information and laboratory and imaging 
tests to seek other possible causes of the observed liver blood test abnormalities, including (but 
not limited to) acute viral hepatitis, alcoholic and autoimmune hepatitis, biliary obstruction (small 
and large duct), cardiovascular causes (eg, ischemic hepatitis), nonalcoholic steatohepatitis 
(NASH), and the effect of concomitant treatments.
A review of all concomitant medications should include herbal medicines, dietary supplements, 
nonprescription OTC medications, including acetaminophen/paracetamol, and occupational 
exposure to chemical agents.
Wherever possible, timely confirmation of initial liver-related laboratory abnormalities should 
occur prior to the reporting of a potential DILI event. All occurrences of potential DILIs, meeting 
the defined criteria, must be reported as SAEs (see Section 9.2 and APPENDIX 3 for reporting 
details). All subjects with clinically significant abnormalities in liver-related blood tests, or 
potential DILI, must be followed until all abnormalities return to normal or to the baseline state.
9.2.8
Adverse Events of Interest (Clinical Safety Program)
All AEs and SAEs that arise in the study will be reported and investigated. However, because of 
the characteristics of the disease under study, and BMS-986165 in particular, some AEs are 
considered adverse events of interest (AEIs). AEIs may be serious or nonserious. Such events may 
require further investigation to better characterize and understand them.
 
 
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In addition, given that immunosuppression is consistent with the mechanism of action of
BMS-986165, malignancies are considered to be an important potential risk of therapy with
BMS-986165 and will be monitored as AEIs. Malignancies were not identified as adverse findings 
in nonclinical studies and no serious adverse reactions of malignancy have been reported to date 
in clinical studies of BMS-986165.
Additional information on AEIs will be collected in this study. Reporting of an AE or SAE that 
includes a PT that is linked to an AEI will trigger specialized eCRF pages to collect additional 
information related to characterization, social/family history, risk factors, signs/symptoms, 
diagnostics, and treatments. Additional information may also be requested to aid in the evaluation 
of these AEs.
9.2.9
Other Safety Considerations
Any significant worsening noted during interim or final physical examinations, ECG, x-ray 
filming, any other potential safety assessment required or not required by protocol should also be 
recorded as a nonserious AE or SAE, as appropriate, and reported accordingly.
9.3
Overdose
 
In the event of an overdose the investigator should do the following:
1) Contact the BMS Medical Monitor/designee immediately
2) Closely monitor the subject for AEs/SAEs and laboratory abnormalities until BMS-986165 
can no longer be detected systemically (at least 3 days)
3) Document the quantity of the excess dose as well as the duration of the overdosing in the eCRF.
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the BMS Medical Monitor/designee based on the clinical evaluation of the 
subject.
9.4
Safety
Planned time points for all safety assessments are listed in the Schedule of Activities (Section 2). 
All urgent safety concerns must be discussed with the Sponsor immediately upon occurrence or 
awareness to determine if the subject should continue or discontinue treatment.
Safety evaluations that will be performed in addition to AE monitoring are physical examination 
(Section 9.4.1), TB screening (Section 9.4.2), vital signs (Section 9.4.5), ECGs (Section 9.4.6), 
concomitant medication use (Section 7.7), and laboratory tests (Section 9.4.3).
9.4.1
Physical Examinations
Schedules for physical examinations are provided in the Schedule of Activities (Section 2). 
Complete physical examinations must be performed by someone who is authorized to perform the 
examinations by training and has been delegated this task by the principal investigator. Key aspects 
of the examination should evaluate important body systems, including skin, as clinically indicated. 
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Every effort should be made to ensure the same evaluator will complete the examination for each 
subject at all visits throughout the study. Documentation of who performed the examination is to 
be recorded in source notes.
9.4.2
Tuberculosis Screening and Chest X-ray
Screening for active TB and LTBI includes medical history, physical examination, 
 and 
CXR. A tuberculin skin test (eg, Mantoux test) may also be performed, at the investigator’s 
discretion, but this does not replace the requirement for 
. A CXR at the screening visit is 
required if not already performed and documented within 6 months of obtaining written informed 
consent.
In order to be eligible for the study, a subject must not have symptoms or signs of active TB, as 
judged by the investigator.
 
 is provided as part of the screening investigation kit. 
This will be collected and sent to a central laboratory. An 
 test sent to a local laboratory may 
be an acceptable alternative, provided that this approach is agreed with the BMS Medical 
Monitor/designee.
A subject with a “negative” 
 test may be eligible to participate in the 
study, provided they do not have any clinical or radiologic (CXR) evidence supporting a diagnosis 
of active TB or LTBI.
A subject with an “indeterminate” QuantiFERON test or a “borderline” T-Spot test must have a 
retest before they are eligible to participate in the study. If the second result is again 
“indeterminate” or “borderline,” the subject will be excluded from the study. If the second result 
is negative, the subject may be eligible provided there is no clinical or radiologic suspicion of 
active TB or LTBI.
A subject with a positive 
 result should be further assessed in order to determine if active TB 
or LTBI is present.
Subjects who are diagnosed with LTBI during screening may be eligible to be rescreened for this 
study provided they have completed at least 4 weeks of treatment for LTBI and they comply with 
treatment for LTBI (both according to local standard of care) during study participation. For these 
subjects, a medical history, physical examination, and a repeat CXR are required during 
rescreening, but 
 should not be repeated.
9.4.3
Clinical Safety Laboratory Assessments

A central or local laboratory will perform safety laboratory assessments (as indicated in 
operational documents; except 
 tests and diagnostic SARS-CoV-2 tests [where 
applicable], which may be performed in clinic [if that is local standard of care]) and provide 
reference ranges and laboratory reports. The central laboratory is preferred (over the local 
laboratory) for safety assessments.

Investigators must document their review of each laboratory safety report.
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
Any laboratory test result that the investigator considers clinically relevant for safety is to be 
recorded on the appropriate AE page of the eCRF (Section 9.2.6).

Results of clinical laboratory tests performed during the screening period must be available 
prior to randomization.

The timing of laboratory assessments is indicated in the Schedule of Activities (Section 2).
The laboratory parameters to be assessed for clinical safety throughout the study are listed in 
Table 11.
Table 11:
Summary of Laboratory Parameters used to Assess Clinical Safety
Hematology

Hemoglobin

MCV

MCH

Hematocrit

WBC (Total leukocyte count)

Platelet count

RBC count
CBC Differential (including absolute neutrophil count 
and absolute lymphocyte count)
Chemistry
AST
ALT
GGT
Total bilirubin
Direct bilirubin
ALP
LDH
Creatinine
BUN
Uric acid
Total protein
Albumin
Sodium
Potassium
Chloride
Calcium
Phosphorus
Magnesium
Creatine kinase
Creatinine clearance (screening only) with eGFR 
calculated using the MDRD equation (screening only)
TSH (with reflex T3/T4 testing for abnormal TSH 
results) (screening only)
Performed after ≥10 hour fast at Day 1 and 
Week 12 (Day 85):
Lipid panel (total cholesterol, high-density lipoprotein 
cholesterol, low-density lipoprotein cholesterol, and 
triglycerides)
Glucose
Coagulation
PT
INR
Either partial thromboplastin time or aPTT
Urinalysis
Protein
Glucose
Blood
Leukocyte esterase
Specific gravity
pH
Microscopic examination of the sediment if blood, 
protein, or leukocyte esterase are positive on the dipstick
Spot urine for protein and creatinine
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Table 11:
Summary of Laboratory Parameters used to Assess Clinical Safety
Additional Analyses
 
 
 
Stool Tests

Stool culture: culture for potentially pathogenic enteric bacteria, including (but not limited to) Salmonella, 
Shigella, Campylobacter, and EHEC (tested at screening visit and when deemed medically appropriate by the 
investigator) Testing for additional enteric pathogens including bacteria, protozoa, ova, and parasites may be 
performed based on the investigator’s clinical judgment.

Stool for Clostridioides (formerly Clostridium) difficile testing: stool for C. difficile Toxin A and B test (EIA) 
and GDH antigen test (EIA), with reflex to NAAT (C. difficile PCR) if either positive (screening only, 
performed at central laboratory, or local laboratory). A direct NAAT test approach may be used if discussed 
with, and approved by, the BMS Medical Monitor/designee.
ALP = Alkaline phosphatase; ALT = alanine aminotransferase; 
 
 aPTT = activated partial thromboplastin time; AST = aspartate 
aminotransferase; 
BUN = blood 
urea 
nitrogen; 
CBC = complete 
blood 
count; 
 eGFR = estimated glomerular filtration rate; EHEC = enterohemorrhagic 
Escherichia 
coli; 
EIA = enzyme-linked 
immunosorbent 
assay; 
 
 
GDH = glutamate dehydrogenase; GGT = gamma glutamyltransferase; 
 
 
 INR = international normalized ratio; LDH = lactate dehydrogenase; MCH = mean 
corpuscular hemoglobin; MCV = mean corpuscular volume; MDRD = modification of diet in renal disease; 
NAAT = nucleic acid amplification test; PCR = polymerase chain reaction; PT = prothrombin time; RBC = red blood 
cell; 
 
 TSH = thyroid-stimulating hormone; 
WBC = white blood cell; 
9.4.4
Imaging Safety Assessment
Not applicable.
9.4.5
Vital Signs
Vital signs will be obtained as indicated in the Schedule of Activities (Section 2) and recorded in 
the relevant eCRF.
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9.4.6
Electrocardiograms
ECGs will be performed as indicated in the Schedule of Activities (Section 2). ECGs will be read 
locally. Clinically significant ECG findings will be recorded in the relevant eCRF and should be 
discussed with the BMS Medical Monitor/designee.
 
 
 
 
 
 
 
 
 
 
 
 
 
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9.6
Biomarkers
The 
 effects of BMS-986165 will be explored based on biomarker analyses of 
 
 
 biopsy 
sample collection are in Table 13 and Table 14, respectively.
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Further details of blood, biopsy, and stool collection and processing will be provided to the site in 
the laboratory manual.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 13:
Blood and Stool Sample Collection
Study Day of 
Sample Collection
Screening
X
X
X
X
X
X
Double-blind On-treatment
Day 1
X
X
X
X
X
X
Week 2 (Day 15)
X
X
X
Week 4 (Day 29)
X
X
X
X
X
X
X
X
Week 8 (Day 57)
X
X
Week 12 (Day 85)
X
X
X
X
X
X
X
X
Open-label Extension
Week 16 (Day 113)
X
X
X
Week 20 (Day 141)
X
X
Week 24 (Day 169)
X
X
X
Week 32 (Day 225)
X
X
Week 40 (Day 281)
X
X
Week 52 (Day 365) 
EOT/ET
X
X
X
X
X
X
Follow-up
Week 56 (Day 393)
F/U
X
X
 EOT = end of treatment; ET = early termination; 
 F/U = follow-up; 
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Table 14:
Colon Biopsy Sample Collection 
Study Day of 
Sample Collection
Biopsies/
Gene 
Expression
Biopsy
Noninvolved
Areab
Screening
X
X
Double-blind On-treatment
Week 12 (Day 85)
X
X
Open-label Extension
Week 52 (Day 365) 
EOT/ET
X
X
 EOT = end of treatment; ET = early termination; 
 
b Biopsy samples will be collected from noninvolved areas, if available, for gene expression.
 
9.6.1
Additional Research Collection
This protocol will include residual sample storage for additional research (see Table 15).
For All sites:
Additional research is required for all study participants, except where prohibited by IRBs/ethics 
committees, prohibited by local laws or regulations, or academic/institutional requirements. Where 
one or more of these exceptions occurs, participation in the additional research will not be a 
condition of overall study participation.

If the IRB/ethics committees and site agree to the mandatory additional research retention 
and/or collection, then the study participant must agree to the mandatory additional research 
as a requirement for inclusion in the study.

If optional participation is permitted and approved, then the study participants may opt out of 
the additional research retention and/or collection.
Additional research is intended to expand the research and development capability at 
Bristol Myers Squibb, and will support as yet undefined research aims that will advance our 
understanding of disease and options for treatment. This may also include genetic/genomic 
exploration aimed at exploring disease pathways, progression, and response to treatment etc.
Sample Collection and Storage
All requests for access to samples or data for additional research will be vetted through a diverse 
committee of the study Sponsor’s senior leaders in Research and Development (or designee) to 
ensure the research supports appropriate and well-defined scientific research activities.
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
Residual blood, stool, biopsies, DNA, and RNA samples from 
 collections (see Table 
1 and Table 2) will be retained for additional research purposes where local laws/regulations 
allow.

Residual blood samples from 
 will also be retained for additional 
research purposes where local laws/regulations allow.
Samples kept for future research will be stored at the BMS Biorepository in 
 USA or 
an independent, BMS-approved storage vendor.
The manager of these samples will ensure they are properly used throughout their usable life and 
will destroy the samples at the end of the scheduled storage period, no longer than 15 years after 
the end of the study or the maximum allowed by applicable law.
Transfers of samples by research Sponsor to third parties will be subject to the recipient’s 
agreement to establish similar storage procedures.
Samples will be stored in a coded fashion, and no researcher will have access to the key. The key 
is securely held by the investigator at the clinical site, so there is no direct ability for a researcher 
to connect a sample to a specific individual.
Further details of sample collection and processing will be provided to the site in the laboratory 
manual.
Table 15:
Residual Sample Retention for Additional Research Schedule
Sample Type
Time points for which residual samples will be retained
DNA and RNA
All
Blood samples (blood, serum, plasma)
All
Stool samples
All
DNA = deoxyribonucleic acid; 
 RNA = ribonucleic acid
9.7
Medical Resource Utilization and Health Economics
Medical resource utilization and health economics data associated with medical encounters will 
be collected in the relevant eCRF by the investigator and study site personnel for all subjects during 
the treatment period of the study. Protocol-mandated procedures, tests, and encounters are 
excluded.
The data collected may be used to conduct exploratory economic analyses and may include the 
number and duration of the following:

UC-related emergency room visits and hospitalizations

All-cause emergency room visits and hospitalizations
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An example of the data collection form to be used is in APPENDIX 12.
9.8
SARS-CoV-2 Testing
Diagnostic testing for SARS-CoV-2 infection refers to 
 test for 
SARS-CoV-2 infection, performed according to local standard of care. 
 testing is preferred. 
 testing is not acceptable as a diagnostic test for SARS-CoV-2 infection.
Diagnostic testing for SARS-CoV-2 infection should be performed as close as possible to 
randomization and must be confirmed as “negative” prior to randomization.
Subjects will be screened for AEs (including signs and symptoms of COVID-19) at each study 
visit. Subjects will be instructed to contact the investigator at any time if they develop an 
intercurrent illness, including a diagnosis, or signs and symptoms of COVID-19, which will enable 
close monitoring and additional screening for the infection between study visits.
The investigator should obtain a diagnostic test for SARS-CoV-2 infection if COVID-19 is 
clinically suspected. If a subject reports having recent direct contact with someone known to have 
COVID-19, the subject should undergo diagnostic testing for SARS-CoV-2.
IP should be temporarily interrupted in subjects who present with signs and/or symptoms 
suggestive of COVID-19 while the subject undergoes diagnostic testing for SARS-CoV-2 
infection. This testing should be performed as soon as feasible.
Study subjects with a positive diagnostic test for SARS-CoV-2 must be reported to BMS within 
24 hours by entering the AE into the EDC.
IP must be temporarily interrupted in subjects who test positive for SARS-CoV-2 infection. Such 
subjects should continue to be followed by the investigator. Such subjects must meet all the criteria 
outlined below prior to restarting IP. The final decision to restart IP must be made in consultation 
with the BMS Medical Monitor/designee.
Subjects with a positive diagnostic test for SARS-CoV-2 infection during the screening period 
may be considered eligible for the study once they meet all eligibility criteria related to active 
infection, and after meeting the criteria outlined below.
Criteria to rescreen or recommence IP after a positive SARS-CoV-2 test:

At least 10 days (20 days for severe/critical illness) have passed since symptoms first appeared 
or positive test result, and

At least 24 hours have passed since last fever without the use of fever-reducing medications, 
and

Acute symptoms (eg, cough, shortness of breath) have resolved, and

In the opinion of the investigator, there are no COVID-19 sequelae that may place the subject 
at a higher risk from receiving investigational treatment, and

There are no COVID-19 sequelae that may confound the assessment of safety or efficacy 
within the study, and

Negative follow-up molecular or antigen test for SARS-CoV-2 based on institutional, local, or 
regional guidelines, and
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For rescreening only, symptoms must have completely resolved 4 weeks prior to rescreening, 
and based on investigator assessment in consultation with the BMS Medical Monitor/designee, 
there are no sequelae that would place the subject at a higher risk when receiving BMS-986165

The above must be discussed with the BMS Medical Monitor prior to rescreening or 
recommencing IP (as applicable).
10
STATISTICAL CONSIDERATIONS
10.1
Sample Size Determination
Approximately 50 subjects will be randomized in a 3:1 ratio to BMS‑986165 12 mg BID or
placebo BID, respectively (ie, approximately 37 subjects receiving BMS‑986165 12 mg BID and 
approximately 13 subjects receiving placebo BID). Subjects randomized to BMS-986165 6  mg 
BID under the Original Protocol or Protocol Amendment 01 will continue receiving BMS-986165 
6  mg  BID in the double-blind treatment period. Approximately 3 subjects are expected to be 
randomized to the BMS-986165 6 mg BID dose arm.
 
 
 
10.1.1
Clinical Response Rate
The assumed rate of clinical response at Week 12 is based on the observed rates of clinical 
response in recent clinical trials of mirikizumab (an anti–IL-23p19 antibody; Week 12 endpoint, 
NCT02589665)31
and 
ustekinumab 
(an 
anti–IL-12p40 
antibody; 
Week 8 
endpoint, 
NCT02407236).1
Assuming BMS‑986165 12 mg BID will provide a similar clinical response rate as was observed 
in these UC trials, the expected clinical response rate is assumed to be approximately 60%. If the 
observed clinical response rate in this study is the same as the assumed rate reported above, the 
estimated 95% CI of clinical response rate is expected to be (42%, 75%) for the BMS‑986165 
12 mg BID arm at Week 12 using the Clopper-Pearson exact method.
With the sample size selected for this study, the expected 95% CI of clinical response rate for the 
BMS‑986165 12 mg BID arm will exclude a placebo rate of 33% (95% CI: 29%, 37%) reported 
in a recent meta-analysis of clinical trials in UC.56
10.1.2
Adverse Event Incidence
Administration of BMS‑986165 12 mg BID to 37 subjects provides a 98% probability of observing 
at least 1 occurrence of any AE that occurs with 10% incidence in the population from which the 
sample is drawn. However, if the incidence rate is 6%, the probability of observing at least 
1 occurrence of that AE with a sample size of 37 subjects is 90%.
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10.2
Populations for Analyses
For purposes of analysis, the following populations are defined in Table 16.
Table 16:
Analysis Populations
Population
Description
Enrolled Set
All subjects who sign the ICF.
Full Analysis Set (FAS)
All subjects who are randomized to study treatment; subjects will be grouped 
according to the treatment to which they are randomized within the IRT. The 
FAS population is the primary efficacy analysis population.
Safety Analysis Set
All randomized subjects who receive at least 1 dose of double-blind study 
treatment. Subjects will be analyzed according to treatment received.
ICF = informed consent form; IRT = interactive response technology; 
10.3
Endpoints
Study endpoints are defined in Section 4.
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10.4
Statistical Analyses
The SAP will be developed and finalized before the database lock for the primary analysis or 
interim analysis (if applicable) and will describe the selection of subjects to be included in the 
analyses, and procedures for accounting for missing, unused, and spurious data.
Categorical data will be summarized as frequency counts and percentages. Continuous data will 
be summarized using n, mean, SD, median, minimum, and maximum unless otherwise specified.
During the treatment period, data will be presented for the following treatments:

BMS-986165 12 mg BID

BMS-986165 6 mg BID

Placebo
10.4.1
Efficacy Analyses
Efficacy data will be summarized using the FAS population unless otherwise stated. Variables will 
be summarized for all visits in which the variable is assessed. Efficacy data will be listed by 
treatment group. Baseline values are defined as the last nonmissing value prior to the first dose of 
study drug unless otherwise indicated.
10.4.1.1
Primary Endpoint
Analysis Method:
The proportion of subjects achieving clinical response at Week 12 and the associated 95% CI for 
the BMS-986165 12 mg BID treatment arm will be estimated using the Clopper-Pearson exact 
method. Supportive analysis using logistic regression for the clinical response (binary endpoint) 
may be performed, and the odds ratio between treatment groups and the corresponding 95% CI 
may be provided if the data are sufficient to do so.
Imputation Method:
Occurrence of intercurrent events may have an impact on the estimand of interest for the following 
types of subjects: (1) subjects who discontinue treatment or study early (ie, prior to Week 12); 
(2) subjects who start a protocol prohibited medication/therapy; or (3) subjects who are lost to 
follow-up or have otherwise missing endpoint data at or prior to the Week 12 assessment. In these 
cases, the primary endpoint will be determined using the “Composite Strategy” as defined in the 
International Council for Harmonisation (ICH) E9 (R1) addendum and will be considered a 
measure of nonresponse to treatment.58 Subjects with the identified intercurrent event(s) will have 
their clinical response endpoint imputed as being a “nonresponder.” This is commonly known as 
nonresponder imputation.
Sensitivity analyses using different imputation methods may be performed and will be defined in 
the SAP.
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10.4.1.2
Exploratory Endpoints
Statistical analyses of exploratory endpoints will be described in the SAP and finalized before 
database lock.
10.4.2
Safety Analyses
Safety endpoint analyses will be descriptive in nature. Safety data for each period will be 
summarized separately and combined. All safety data will be listed by treatment group.
10.4.2.1
Adverse Events
Treatment-emergent AEs (TEAEs) are defined as AEs that occur after the subject received first 
dose of study treatment or if a preexisting condition worsens in severity or becomes serious after 
receiving the first dose of study treatment up to 30 days after the last dose of study treatment. All 
reported TEAEs, SAEs, deaths, AEs leading to study treatment discontinuation, and target AEIs 
will be summarized by the Medical Dictionary for Regulatory Activities (MedDRA) SOC and PT.
10.4.2.2
Vital Signs and ECGs
Vital signs and ECGs will be summarized as raw, change from baseline, including the maximum 
postbaseline value. Baseline values are defined as the last nonmissing value prior to the first dose 
of study drug. The number and proportion of subjects with vital signs and ECG abnormalities will 
be summarized at each scheduled visit.
10.4.2.3
Clinical Laboratory Tests
Laboratory analytes will be summarized as raw, change from baseline, including the maximum 
postbaseline value. Incidence of abnormal, high, or low values will be summarized. Shift tables 
will also be provided. Baseline values are defined as the last nonmissing value prior to the first 
dose of study drug. The number and proportion of subjects with clinical laboratory abnormalities 
will be summarized at each scheduled visit.
10.4.3
Other Analyses
Statistical analyses of exploratory endpoints will be described in the SAP and finalized before 
database lock.
 
 
 
 
 
 
 
 
 
 
 
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10.4.3.2
Exposure-response Modeling
A detailed 
 efficacy exploratory analyses plan will be described in the SAP, which 
will be finalized before database lock. Exposure-response analysis may be performed for key 
efficacy and safety endpoints. The detailed plan for this analysis will be described in a separate 
document as needed.
Data from this study may be combined with data from other BMS-986165 studies to conduct 
 analyses. 
 
10.4.3.3
Quality of Life and Medical Resource Analyses
Quality of life data analyses will be described in the SAP, which will be finalized before database 
lock and included in the CSR.
Medical resource utilization exploratory analyses will be described in the SAP, which will be 
finalized before database lock. These results will be presented separately from the main CSR.
10.4.4
Interim Analyses
In addition to the primary efficacy analysis conducted when subjects have either completed 
Week 12 efficacy assessments or have discontinued prior to Week 12 (as outlined above), the 
Sponsor may perform an unblinded interim analysis of study data prior to final data analysis to 
make a timely decision. In such circumstances, the SAP will be finalized and an interim analysis 
plan will be approved prior to the database lock for the interim analysis. The interim analysis report 
will be prepared by a separate unblinded statistical team who will provide the report to the Sponsor, 
who will be unblinded at the treatment group level. A select group of Sponsor personnel, who will 
have no contact with the study site, will be unblinded to data at the participant level. Summary 
level unblinded data may be communicated externally. A SAP, which will include a section on 
interim analysis, will be created prior to any unblinding to fully detail the activities around the 
interim analysis.
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11
REFERENCES
 
 
 
 
 
 
 
 
 
 
 
 
6.
Roda G, Jharap B, Neeraj N, et al. Loss of response to anti-TNFs: definition, epidemiology, 
and management. Clin Transl Gastroenterol 2016;7:e135.
7.
Min X, Ungureanu D, Maxwell S, et al. Structural and functional characterization of the 
JH2 pseudokinase domain of JAK family tyrosine kinase 2 (TYK2). J Biol Chem 
2015;290(45):27261-70.
8.
Shaw MH, Boyartchuk V, Wong S, et al. A natural mutation in the Tyk2 pseudokinase 
domain underlies altered susceptibility of B10.Q/J mice to infection and autoimmunity. 
Proc Natl Acad Sci U S A 2003;100(20):11594-9.
9.
Tokarski JS, Zupa-Fernandez A, Tredup JA, et al. Tyrosine kinase 2-mediated signal 
transduction in T lymphocytes is blocked by pharmacological stabilization of its 
pseudokinase domain. J Biol Chem 2015;290(17):11061-74.
10.
Watford WT, Hissong BD, Bream JH, et al. Signaling by IL-12 and IL-23 and the 
immunoregulatory roles of STAT4. Immunol Rev 2004;202:139-56.
11.
Burke JR, Cheng L, Gillooly KM, et al. Autoimmune pathways in mice and humans are 
blocked by pharmacological stabilization of the TYK2 pseudokinase domain. Sci Transl 
Med 2019;11(502).
12.
Wrobleski ST, Moslin R, Lin S, et al. Highly selective inhibition of tyrosine kinase 2 
(TYK2) for the treatment of autoimmune diseases: Discovery of the allosteric inhibitor 
BMS-986165. Presented at American Chemical Society. Journal of Medicinal Chemistry 
2019;62(20):8973-95.
 
 
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31.
Sandborn WJ, Ferrante M, Bhandari BR, et al. Efficacy and safety of mirikizumab in a 
randomized Phase 2 study of patients with ulcerative colitis. Gastroenterology 
2020;158(3):537-49.
 
 
 
 
 
 
 
38.
Draft Guidance for Industry, Ulcerative Colitis: Clinical Trial Endpoints U.S. Department 
of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation 
and Research. Draft August 2016. Publication UCM515143.
39.
Guideline on the development of new medicinal products for the treatment of ulcerative 
colitis. European Medicines Agency Committee for Medicinal Products for Human Use 
(CHMP). Adopted 28 June 2018. Publication CHMP/EWP/18463/2006 Rev. 1.
40.
Jairath V, Jeyarajah J, Zou G, et al. A composite disease activity index for early drug 
development in ulcerative colitis: development and validation of the UC-100 score. Lancet 
Gastroenterol Hepatol 2019;4(1):63-70.
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47.
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.
48.
Scherl EJ, Pruitt R, Gordon GL, et al. Safety and efficacy of a new 3.3 g b.i.d. tablet 
formulation in patients with mild-to-moderately-active ulcerative colitis: a multicenter, 
randomized, 
double-blind, 
placebo-controlled 
study. 
Am 
J 
Gastroenterol 
2009;104(6):1452-9.
49.
Lewis JD, Chuai S, Nessel L, et al. Use of the noninvasive components of the Mayo score 
to assess clinical response in ulcerative colitis. Inflamm Bowel Dis 2008;14(12):1660-6.
50.
Travis SP, Schnell D, Krzeski P, et al. Reliability and initial validation of the ulcerative 
colitis endoscopic index of severity. Gastroenterology 2013;145(5):987-95.
51.
Ikeya K, Hanai H, Sugimoto K, et al. The Ulcerative Colitis Endoscopic Index of Severity 
More Accurately Reflects Clinical Outcomes and Long-term Prognosis than the Mayo 
Endoscopic Score. J Crohns Colitis 2016;10(3):286-95.
 
 
54.
Guyatt G, Mitchell A, Irvine EJ, et al. A new measure of health status for clinical trials in 
inflammatory bowel disease. Gastroenterology 1989;96(3):804-10.
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55.
Montreal Heart Institute Pharmacogenomics Center - PharmaADME.org. ADME Gene 
List. 2019. Accessed 30 September 2019.
56.
Jairath V, Zou G, Parker CE, et al. Systematic review and meta-analysis: Placebo rates in 
induction and maintenance trials of ulcerative colitis. J Crohns Colitis 2016;10(5):607-18.
 
58.
ICH E9 (R1) addendum on estimands and sensitivity analysis in clinical trials to the 
guideline on statistical principles for clinical trials Step 2b. European Medicines Agency 
Committee 
for 
Medicinal 
Products 
Adopted 
20 
July 
2017. 
Publication 
EMA/CHMP/ICH/436221/2017.
 
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APPENDICES
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APPENDIX 1
ABBREVIATIONS AND TRADEMARKS
Term
Definition
5-ASA
5-aminosalicylic acid
6-MP
6-mercaptopurine
ADME
absorption, distribution, metabolism, and excretion
AE
adverse event
AEI
adverse event of interest
ALP
alkaline phosphatase
ALT
alanine aminotransferase
AST
aspartate aminotransferase
AUC
area under the concentration-time curve
AZA
azathioprine
BID
twice daily
BMS
Bristol Myers Squibb
BP
blood pressure
C. difficile 
Clostridioides (formerly Clostridium) difficile 
CD
Crohn’s disease
CFR
Code of Federal Regulations
CI
confidence interval
CMV
cytomegalovirus
CONSORT
Consolidated Standards of Reporting Trials 
COVID-19
Coronavirus Disease 2019
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Term
Definition
CRF
case report form
CSR
clinical study report
CXR
chest x-ray
DDI
drug-drug interaction
DILI
drug-induced liver injury
DMC
Data Monitoring Committee
DNA
deoxyribonucleic acid
ECG
electrocardiogram
eCRF
electronic case report form
eCOA
electronic clinical outcome assessment(s)
eGFR
estimated glomerular filtration rate
EOT/ET
end of treatment/early termination
ES
endoscopic (Mayo score component)
FACS
fluorescence-activated cell sorting
FAS
full analysis set
FDA
Food and Drug Administration
FSH
follicle-stimulating hormone
GDH
glutamate dehydrogenase 
HR
heart rate
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Term
Definition
hsCRP
high-sensitivity C-reactive protein
IB
Investigator’s Brochure
IBD
inflammatory bowel disease
IBDQ
Inflammatory Bowel Disease Questionnaire
ICF
informed consent form
ICH
International Council for Harmonisation
IEC
Independent Ethics Committee
IFN
interferon
IL
interleukin
IM
intramuscular
IMP
investigational medicinal product
INR
international normalized ratio
IP
investigational product 
IRB
Institutional Review Board
IRT
interactive response technology
IV
intravenous
LTBI
latent tuberculosis infection
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Term
Definition
MAR
missing at random
MDRD
Modification of Diet in Renal Disease
Min
minute(s)
MMRM
mixed model repeated measure
MMX
Multi-Matrix System
MTX
methotrexate
N/A
not applicable
NAAT
nucleic acid amplification test
NHV
normal healthy volunteer 
NOAEL
no-observed-adverse-effect level
NSAID
nonsteroidal anti-inflammatory drug
NYHA
New York Heart Association
OLE
open-label extension
OTC
over-the-counter
PB
peripheral blood 
PCR
polymerase chain reaction
PBMC
peripheral blood mononuclear cells
PGA
Physician’s Global Assessment
PK
pharmacokinetic(s)
PO
oral(ly)
PRO
patient-reported outcome
PT
preferred term
QD
every day
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Term
Definition
RB
rectal bleeding (Mayo score component)
RBC
red blood cell
RNA
ribonucleic acid
RNA-seq
RNA sequencing technology
SAE
serious adverse event
SAP
statistical analysis plan
SARS-CoV-2
Severe Acute Respiratory Syndrome Coronavirus 2
SD
standard deviation 
SF
stool frequency (Mayo score component)
SLE
systemic lupus erythematosus
SOC
system organ class
STAT
signal transducer and activator of transcription
SUSAR
suspected, unexpected serious adverse reaction
TB
tuberculosis
TDAR 
T cell-dependent antibody response
TEAE
treatment-emergent AE
TNF
tumor necrosis factor
TNFi
tumor necrosis factor inhibitor(s)
TSH
thyroid-stimulating hormone
TQT
thorough QT
TYK2
tyrosine kinase 2
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Term
Definition
UC
ulcerative colitis
UCEIS
Ulcerative Colitis Endoscopic Index of Severity
ULN
upper limit of normal
WOCBP
women of childbearing potential
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APPENDIX 2
STUDY GOVERNANCE CONSIDERATIONS
The term ‘Subject’ is used in the protocol and eCRF to refer to a person who has consented to 
participate in the clinical research study.
REGULATORY AND ETHICAL CONSIDERATIONS
GOOD CLINICAL PRACTICE
This study will be conducted in accordance with:

Good Clinical Practice (GCP)

As defined by the International Council for Harmonisation (ICH)

In accordance with the ethical principles underlying European Union Directive 2001/20/EC

United States Code of Federal Regulations, Title 21, Part 50 (21CFR50)

Applicable local requirements.
The study will be conducted in compliance with the protocol. The protocol and any amendments 
and the subject informed consent will receive approval/favorable opinion by Institutional Review 
Board/Independent Ethics Committee (IRB/IEC), and regulatory authorities according to 
applicable local regulations prior to initiation of the study.
All potential serious breaches must be reported to Sponsor or designee immediately. A potential 
serious breach is defined as a Quality Issue (eg, protocol deviation, etc) that is likely to affect, to 
a significant degree, one or more of the following: (1) the physical, safety or mental integrity of 
one or more subjects/participants; (2) the scientific value of the trial (eg, reliability and robustness 
of generated data). Items (1) or (2) can be associated with either GCP Regulation(s) or Trial 
protocol(s).
Personnel involved in conducting this study will be qualified by education, training, and 
experience to perform their respective tasks.
This study will not use the services of study personnel where sanctions have been invoked or where 
there has been scientific misconduct or fraud (eg, loss of medical licensure, debarment).
INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS COMMITTEE
Before study initiation, the investigator must have written and dated approval/favorable opinion 
from the IRB/IEC for the protocol, consent form, subject recruitment materials 
(eg, advertisements), and any other written information to be provided to subjects. The investigator 
or BMS should also provide the IRB/IEC with a copy of the Investigator’s Brochure (IB) or 
product labeling information to be provided to subjects and any updates.
The investigator, Sponsor or designee should provide the IRB/IEC with reports, updates and other 
information (eg, expedited safety reports, amendments, and administrative letters) according to 
regulatory requirements or institution procedures.
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COMPLIANCE WITH THE PROTOCOL AND PROTOCOL REVISIONS
The investigator should not implement any deviation or change to the protocol without prior 
review and documented approval/favorable opinion of an amendment from the IRB/IEC (and if 
applicable, also by local Health Authority) except where necessary to eliminate an immediate 
hazard(s) to study subjects.
If a deviation or change to a protocol is implemented to eliminate an immediate hazard(s) prior to 
obtaining relevant approval/favorable opinion(s) the deviation or change will be submitted, as soon 
as possible to:

IRB/IEC for

Regulatory Authority(ies), if applicable by local regulations (per national requirements)
Documentation of approval/favorable opinion signed by the chairperson or designee of the 
IRB(s)/IEC(s) and if applicable, also by local Health Authority must be sent to BMS.
If an amendment substantially alters the study design or increases the potential risk to the subject: 
(1) the consent form must be revised and submitted to the IRB(s)/IEC(s) for review and 
approval/favorable opinion; (2) the revised form must be used to obtain consent from subjects 
currently enrolled in the study if they are affected by the amendment; and (3) the new form must 
be used to obtain consent from new subjects prior to enrollment.
If the revision is done via an administrative letter, investigators must inform their IRB(s)/IEC(s).
FINANCIAL DISCLOSURE
Investigators and subinvestigators will provide the Sponsor with sufficient, accurate financial 
information in accordance with local regulations to allow the Sponsor to submit complete and 
accurate financial certification or disclosure statements to the appropriate health 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.
INFORMED CONSENT PROCESS
Investigators must ensure that subjects are clearly and fully informed about the purpose, potential 
risks, and other critical issues regarding clinical studies in which they volunteer to participate.
Sponsor or designee will provide the investigator with an appropriate (ie, Global or Local) sample 
informed consent form (ICF) which will include all elements required by ICH, GCP, and 
applicable regulatory requirements. The sample ICF will adhere to the ethical principles that have 
their origin in the Declaration of Helsinki.
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Investigators must:

Provide a copy of the consent form and written information about the study in the language in 
which the subject is most proficient prior to clinical study participation. The language must be 
nontechnical and easily understood.

Allow time necessary for subject or subject’s legally acceptable representative to inquire about 
the details of the study.

Obtain an ICF signed and personally dated by the subject and by the person who conducted 
the informed consent discussion.

Obtain the IRB/IEC’s written approval/favorable opinion of the written ICF and any other 
information to be provided to the subjects, prior to the beginning of the study, and after any 
revisions are completed for new information.
Revise the ICF whenever important new information becomes available that is relevant to the 
subject’s consent. The investigator, or a person designated by the investigator, should fully inform 
the subject of all pertinent aspects of the study and of any new information relevant to the subject’s 
willingness to continue participation in the study. This communication should be documented.
The confidentiality of records that could identify subjects must be protected, respecting the privacy 
and confidentiality rules applicable to regulatory requirements, the subjects’ signed ICF and, in 
the US, the subjects’ signed Health Insurance Portability and Accountability Act Authorization.
The consent form must also include a statement that BMS and regulatory authorities have direct 
access to subject records.
The rights, safety, and well-being of the study subjects are the most important considerations and 
should prevail over interests of science and society.
SOURCE DOCUMENTS
The investigator is responsible for ensuring that the source data are accurate, legible, 
contemporaneous, original, and attributable, whether the data are hand-written on paper or entered 
electronically. If source data are created (first entered), modified, maintained, archived, retrieved, 
or transmitted electronically via computerized systems (and/or any other kind of electronic 
devices) as part of regulated clinical trial activities, such systems must be compliant with all 
applicable laws and regulations governing use of electronic records and/or electronic signatures. 
Such systems may include, but are not limited to, electronic medical/health records (EMRs/EHRs), 
adverse event (AE) tracking/reporting, protocol-required assessments, and/or drug accountability 
records).
When paper records from such systems are used in place of electronic format to perform regulated 
activities, such paper records should be certified copies. A certified copy consists of a copy of 
original information that has been verified, as indicated by a dated signature, as an exact copy 
having all of the same attributes and information as the original.
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STUDY TREATMENT RECORDS
Records for study treatments (whether supplied by BMS, its vendors, or the site) must substantiate 
study treatment integrity and traceability from receipt, preparation, administration, and through 
destruction or return. Records must be made available for review at the request of BMS/designee 
or a Health Authority.
If
Then
Supplied by BMS (or its vendors):
Records or logs must comply with applicable 
regulations and guidelines and should include:

amount received and placed in storage 
area

amount currently in storage area

label identification number or batch 
number

amount dispensed to and returned by each 
subject, including unique subject 
identifiers

amount transferred to another area/site for 
dispensing or storage

nonstudy disposition (eg, lost, wasted)

amount destroyed at study site, if 
applicable

amount returned to BMS

retain samples for 
bioavailability/bioequivalence, if 
applicable

dates and initials of person responsible for 
Investigational Product (IP)
dispensing/accountability, as per the 
Delegation of Authority Form.
Sourced by site, and not supplied by BMS or 
its vendors (examples include IP sourced from 
the sites stock or commercial supply, or a 
specialty pharmacy)
The 
investigator 
or 
designee 
accepts 
responsibility for documenting traceability and 
study treatment integrity in accordance with 
requirements applicable under law and the 
standard 
operating 
procedures 
(SOPs)/
standards of the sourcing pharmacy.
These records should include:

label identification number or batch 
number
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If
Then

amount dispensed to and returned by each 
subject, including unique subject 
identifiers

dates and initials of person responsible for 
IP dispensing/accountability, as per the 
Delegation of Authority Form.
BMS or designee will provide forms to facilitate inventory control if the investigational site does 
not have an established system that meets these requirements.
CASE REPORT FORMS
An investigator is required to prepare and maintain adequate and accurate case histories designed 
to record all observations and other data pertinent to the investigation on each individual treated 
or entered as a control in the investigation. Data that are derived from source documents and 
reported on the CRF must be consistent with the source documents or the discrepancies must be 
explained. Additional clinical information may be collected and analyzed in an effort to enhance 
understanding of product safety. CRFs may be requested for AEs and/or laboratory abnormalities 
that are reported or identified during the course of the study.
For sites using the Sponsor or designee electronic data capture (EDC) tool, electronic CRFs will 
be prepared for all data collection fields except for fields specific to SAEs and pregnancy, which 
will be reported on the electronic SAE form and paper Pregnancy Surveillance Form, respectively. 
If electronic SAE form is not available, a paper SAE form can be used.
The confidentiality of records that could identify subjects must be protected, respecting the privacy 
and confidentiality rules in accordance with the applicable regulatory requirement(s).
The investigator will maintain a signature sheet to document signatures and initials of all persons 
authorized to make entries and/or corrections on CRFs.
The completed CRF, SAE/pregnancy CRFs, must be promptly reviewed, signed, and dated by the 
investigator or qualified physician who is a subinvestigator and who is delegated this task on the 
Delegation of Authority Form. Subinvestigators in Japan may not be delegated the CRF approval 
task. For electronic CRFs, review and approval/signature is completed electronically through the 
EDC tool. The investigator must retain a copy of the CRFs including records of the changes and 
corrections.
Each individual electronically signing electronic CRFs must meet Sponsor or designee training 
requirements and must only access the EDC tool using the unique user account provided by 
Sponsor or designee. User accounts are not to be shared or reassigned to other individuals
MONITORING
Monitoring details describing strategy, including definition of study critical data items and 
processes (eg, risk-based initiatives in operations and quality, such as risk management and 
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mitigation strategies and analytical risk-based monitoring), methods, responsibilities, and 
requirements, including handling of noncompliance issues and monitoring techniques (central, 
remote, or on-site monitoring) are provided in the monitoring plan.
Representatives of BMS must be allowed to visit all study site locations periodically to assess the 
data quality and study integrity. On site, they will review study records and directly compare them 
with source documents, discuss the conduct of the study with the investigator, and verify that the 
facilities remain acceptable. Certain CRF pages and/or electronic files may serve as the source 
documents:
In addition, the study may be evaluated by Sponsor or designee internal auditors and government 
inspectors who must be allowed access to CRFs, source documents, other study files, and study 
facilities. BMS audit reports will be kept confidential.
The investigator must notify BMS promptly of any inspections scheduled by regulatory authorities, 
and promptly forward copies of inspection reports to Sponsor or designee.
RECORDS RETENTION
The investigator (or head of the study site in Japan) must retain all study records and source 
documents for the maximum period required by applicable regulations and guidelines, or 
institution procedures, or for the period specified by BMS or designee, whichever is longer. The 
investigator (or head of the study site in Japan) must contact BMS prior to destroying any records 
associated with the study.
BMS or designee will notify the investigator (or head of the study site in Japan) when the study 
records are no longer needed.
If the investigator withdraws from the study (eg, relocation, retirement), the records shall be 
transferred to a mutually agreed upon designee (eg, another investigator, study site, IRB). Notice 
of such transfer will be given in writing to BMS or designee.
RETURN OF STUDY TREATMENT
For this study, study treatments (those supplied by BMS, a vendor or sourced by the investigator) 
such as partially used study treatment containers, vials, and syringes may be destroyed on site.
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If...
Then
Study treatments supplied by BMS (including 
its vendors)
Any unused study treatments supplied by BMS
can only be destroyed after being inspected and 
reconciled by the responsible Study Monitor 
unless study treatments containers must be 
immediately destroyed as required for safety, 
or to meet local regulations (eg, cytotoxics or 
biologics).
If study treatments will be returned, the return 
will be arranged by the responsible Study 
Monitor.
Study treatments sourced by site, not supplied 
by BMS (or its vendors) (examples include 
study treatments sourced from the sites stock 
or 
commercial 
supply, 
or 
a 
specialty 
pharmacy)
It 
is 
the 
investigator’s 
or 
designee’s 
responsibility to dispose of all containers 
according to the institutional guidelines and 
procedures.
It is the investigator’s or designee’s responsibility to arrange for disposal, provided that procedures 
for proper disposal have been established according to applicable federal, state, local, and 
institutional guidelines and procedures, and provided that appropriate records of disposal are kept. 
The following minimal standards must be met:

On-site disposal practices must not expose humans to risks from the drug.

On-site disposal practices and procedures are in agreement with applicable laws and 
regulations, including any special requirements for controlled or hazardous substances.

Written procedures for on-site disposal are available and followed. The procedures must be 
filed with the site’s SOPs and a copy provided to BMS upon request.

Records are maintained that allow for traceability of each container, including the date 
disposed of, quantity disposed, and identification of the person disposing the containers. The 
method of disposal, ie, incinerator, licensed sanitary landfill, or licensed waste disposal vendor 
must be documented.

Accountability and disposal records are complete, up to date, and available for the Monitor to 
review throughout the clinical trial period.
It is the investigator’s or designee’s responsibility to arrange for disposal of all empty containers.
If conditions for destruction cannot be met, the responsible Study Monitor will make arrangements 
for return of study treatments provided by BMS (or its vendors). Destruction of non- study 
treatments sourced by the site, not supplied by BMS, is solely the responsibility of the investigator 
or designee.
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DISSEMINATION OF CLINICAL STUDY DATA
In order to benefit potential study participants, patients, healthcare providers, and researchers, and 
to help BMS honor its commitments to study participants, BMS will make information about 
clinical research studies and a summary of their results available to the public as per regulatory 
and BMS requirements. BMS will post study information on local, national, or regional databases 
in compliance with national and international standards for disclosure. BMS may also voluntarily 
disclose information to applicable databases.
CLINICAL STUDY REPORT
A Signatory Investigator must be selected to sign the clinical study report.
For this protocol, the Signatory Investigator will be selected as appropriate based on the following 
criteria:

External Principal Investigator designated at protocol development

National Coordinating Investigator

Study Steering Committee chair or their designee

Subject recruitment (eg, among the top quartile of enrollers)

Involvement in trial design

Regional representation (eg, among top quartile of enrollers from a specified region or country)

Other criteria (as determined by the study team)
SCIENTIFIC PUBLICATIONS
The data collected during this study are confidential and proprietary to Sponsor or designee. Any 
publications or abstracts arising from this study must adhere to the publication requirements set 
forth in the clinical trial agreement (CTA) governing [Study site or investigator] participation in 
the study. These requirements include, but are not limited to, submitting proposed publications to 
Sponsor or designee at the earliest practicable time prior to submission or presentation and 
otherwise within the time period set forth in the CTA.
Scientific Publications (such as abstracts, congress podium presentations and posters, and 
manuscripts) of the study results will be a collaborative effort between the study Sponsor and the 
external authors. No public presentation or publication of any interim results may be made by any 
principal investigator, subinvestigator, or any other member of the study staff without the prior 
written consent of the Sponsor.
Authorship of publications at BMS is aligned with the criteria of the International Committee of 
Medical Journal Editors (ICMJE, www.icmje.org). Authorship selection is based upon significant 
contributions to the study (ie, ICMJE criterion #1). Authors must meet all 4 ICMJE criteria for 
authorship:
1) Substantial intellectual contribution to the conception or design of the work; or the acquisition 
of data (ie, evaluable subjects with quality data), analysis, or interpretation of data for the work 
(eg, problem solving, advice, evaluation, insights, and conclusion); AND
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2) Drafting the work or revising it critically for important intellectual content; AND
3) Final approval of the version to be published; AND
4) Agreement to be accountable for all aspects of the work in ensuring that questions related to 
the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Those who make the most significant contributions, as defined above, will be considered by BMS 
for authorship of the primary publication. Subinvestigators will generally not be considered for 
authorship in the primary publication. Geographic representation will also be considered.
Authors will be listed by order of significant contributions (highest to lowest), with the exception 
of the last author. Authors in first and last position have provided the most significant contributions 
to the work.
For secondary analyses and related publications, author list and author order may vary from 
primary to reflect additional contributions.
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APPENDIX 3
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS: 
DEFINITIONS AND PROCEDURES FOR RECORDING, 
EVALUATING, FOLLOW-UP AND REPORTING
ADVERSE EVENTS
Adverse Event Definition:
An AE is defined as any new untoward medical occurrence or worsening of a preexisting 
medical condition in a clinical investigation participant administered study drug and that does 
not necessarily have a causal relationship with this treatment. 
An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of study drug, whether or not 
considered related to the study drug.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
results from other safety assessments (eg, ECG, radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically significant 
in the medical and scientific judgment of the investigator. Note that abnormal lab tests or 
other safety assessments should only be reported as AEs if the final diagnosis is not 
available. Once the final diagnosis is known, the reported term should be updated to be the 
diagnosis.

Exacerbation of a chronic or intermittent preexisting condition including either an increase 
in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study intervention administration even though it 
may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study intervention 
or a concomitant medication. Overdose, as a verbatim term (as reported by the investigator), 
should not be reported as an AE/SAE unless it is an intentional overdose taken with possible 
suicidal/self-harming intent. Such overdoses should be reported regardless of sequelae and 
should specify “intentional overdose” as the verbatim term. 
Events NOT Meeting the AE Definition

Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to 
the procedure is the AE.

Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).
Definition of SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met.
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SERIOUS ADVERSE EVENTS
Serious Adverse Event Definition: Any untoward medical occurrence that, at any dose:
Results in death
Is life-threatening (defined as an event in which the participant was at risk of death at the time 
of the event; it does not refer to an event which hypothetically might have caused death if it were 
more severe)
Requires inpatient hospitalization or causes prolongation of existing hospitalization (see note 
below)
Note: The following hospitalizations are not considered SAEs in BMS clinical studies:

a visit to the emergency room or other hospital department < 24 hours, that does not result 
in admission (unless considered an important medical or life-threatening event).

elective surgery, planned prior to signing consent.

admissions as per protocol for a planned medical/surgical procedure.

routine health assessment requiring admission for baseline/trending of health status (eg, 
routine colonoscopy).

medical/surgical admission other than to remedy ill health and planned prior to entry into 
the study. Appropriate documentation is required in these cases.

admission encountered for another life circumstance that carries no bearing on health status 
and requires no medical/surgical intervention (eg, lack of housing, economic inadequacy, 
caregiver respite, family circumstances, administrative reason).

admission for administration of anticancer therapy in the absence of any other SAEs (applies 
to oncology protocols).
Results in persistent or significant disability or permanent damage
Is a congenital anomaly/birth defect
Is an important medical event (defined as a medical event(s) that may not be immediately life-
threatening or result in death or hospitalization but, based upon appropriate medical and 
scientific judgment, may jeopardize the participant, or may require intervention [eg, medical, 
surgical] to prevent one of the other serious outcomes listed in the definition above). Examples 
of such events include, but are not limited to, intensive treatment in an emergency room or at 
home for allergic bronchospasm; blood dyscrasias or convulsions that do not result in 
hospitalization. Potential drug-induced liver injury (DILI) is also considered an important 
medical event (see Section 9.2.7 for the definition of potential DILI).
Pregnancy and potential DILI must follow the same transmission timing and processes to BMS as 
used for SAEs (see Section 9.2.5 for reporting pregnancies).
Any component of a study endpoint that is considered related to study therapy should be reported 
as SAE (eg, death is an endpoint, if death occurred due to anaphylaxis, anaphylaxis must be 
reported).
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EVALUATING AES AND SAES
Assessment of Intensity
The intensity of AEs is determined by a physician and will use the following levels:

Mild: An event that is easily tolerated by the subject, causing minimal discomfort, and not 
interfering with everyday activities.

Moderate: An event that causes sufficient discomfort and interferes with normal everyday 
activities.

Severe: An event that prevents normal everyday activities. An AE that is assessed as severe 
should not be confused with an SAE. Severe is a category utilized for rating the intensity of 
an event; and both AEs and SAEs can be assessed as severe.
Assessment of Causality

The investigator is obligated to assess the relationship between study intervention and each 
occurrence of each AE/SAE. A “reasonable possibility of a relationship” conveys that there 
are facts, evidences, and/or arguments to suggest a causal relationship rather than a 
relationship cannot be ruled out.

The investigator will use clinical judgment to determine the relationship.

Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention administration 
will be considered and investigated.

The investigator will also consult the IB and/or Product Information, for marketed products, 
in his/her assessment.

For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality.

There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report to Sponsor. However, it is very important that the 
investigator always make an assessment of causality for every event before the initial 
transmission of the SAE data to Sponsor.

The investigator may change his/her opinion of causality in light of follow-up information 
and send a SAE follow-up report with the updated causality assessment.

The causality assessment is one of the criteria used when determining regulatory reporting 
requirements.
Follow-up of AEs and SAEs
If only limited information is initially available, follow-up reports are required. Note: Follow-
up SAE reports must include the same investigator term(s) initially reported.
If an ongoing SAE changes in its intensity or relationship to study drug or if new information 
becomes available, the SAE report must be updated and submitted within 24 hours to BMS (or 
designee) using the same procedure used for transmitting the initial SAE report.
All SAEs and nonserious AEs that cause interruption or discontinuation of study treatment must 
be followed to resolution or stabilization. 
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REPORTING OF SAES TO SPONSOR OR DESIGNEE

SAEs, whether related or not related to study treatment, and pregnancies must be reported 
to BMS (or designee) immediately but no later than 24 hours after awareness of the event.

SAEs must be recorded on the SAE Report Form.
o
The required method for SAE data reporting is through the eCRF.
o
The paper SAE Report Form is only intended as a back-up option when the EDC system 
is unavailable/not functioning for transmission of the eCRF to BMS (or designee).
o
In this case, the paper form is transmitted via email or confirmed facsimile (fax) 
transmission
o
When paper forms are used, the original paper forms are to remain on site

Pregnancies must be recorded on a paper Pregnancy Surveillance Form and transmitted via 
email or confirmed facsimile (fax) transmission
SAE Email Address: Refer to Contact Information list.
SAE Facsimile Number: Refer to Contact Information list.
SAE Telephone Contact (required for SAE and pregnancy reporting): Refer to Contact 
Information list
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APPENDIX 4
WOMEN OF CHILDBEARING POTENTIAL DEFINITIONS AND 
METHODS OF CONTRACEPTION
Appendix 4 provides general information and definitions related to Woman of Childbearing 
Potential (WOCBP) and methods of contraception that can be applied to most clinical trials. For 
information specific to this study regarding acceptable contraception requirements for female and 
male participants, refer to Section 6.1 of the protocol. Only the contraception methods as described 
in Section 6.1 are acceptable for this study.
DEFINITIONS
WOCBP
A woman is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile. Permanent sterilization methods include hysterectomy, bilateral 
salpingectomy, and bilateral oophorectomy.
Women in the following categories are not considered WOCBP

Premenarchal

Premenopausal female with 1 of the following:
o
Documented hysterectomy
o
Documented bilateral salpingectomy
o
Documented bilateral oophorectomy
Note: Documentation can come from the site personnel’s review of the subject’s medical records, 
medical examination, or medical history interview.
 
 
 
Note: Females treated with hormone replacement therapy (HRT) are likely to have artificially 
suppressed 
 levels and may require a washout period to obtain a physiologic 
 level. The 
duration of the washout period is a function of the type of HRT used. The duration of the washout 
period below are suggested guidelines and the investigators should use their judgment in checking 
serum 
 levels.

1-week minimum for vaginal hormonal products (rings, creams, gels)

4-week minimum for transdermal products

8-week minimum for oral products
Other parenteral products may require washout periods as long as 6 months. If the serum 
 
level is > 40 mIU/mL at any time during the washout period, the woman can be considered 
.
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End of Relevant Systemic Exposure
End of relevant systemic exposure is the time point where the investigational medicinal product 
(IMP) or any active major metabolites has decreased to a concentration that is no longer considered 
to be relevant for human teratogenicity or fetotoxicity. This should be evaluated in context of 
safety margins from the no-observed-adverse-effect level (NOAEL) or the time required for 
5 half-lives of the IMP to pass.
METHODS OF CONTRACEPTION
Local laws and regulations may require use of alternative and/or additional contraception methods.
Highly Effective Contraceptive Methods That Are User-Dependent
Failure rate of < 1% per year when used consistently and correctly.a

Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulation and/or implantation (This method of contraception can only be used 
by WOCBP participants in studies where hormonal contraception is permitted by the study 
protocol)b
o
Oral (birth control pills)
o
Intravaginal (rings)
o
Transdermal

Combined (estrogen-and progestogen-containing) hormonal contraception must begin at 
least 30 days prior to initiation of study therapy

Progestogen-only hormonal contraception associated with inhibition of ovulation (This 
method of contraception can only be used by WOCBP participants in studies where 
hormonal contraception is permitted by the study protocol)b
o
Oral
o
Injectable

Progestogen-only hormonal contraception must begin at least 30 days prior to initiation of 
study therapy
Highly Effective Methods That Are User-Independent

Implantable progestogen-only hormonal contraception associated with inhibition of 
ovulation and/or implantation (This method of contraception can only be used by WOCBP 
participants in studies where hormonal contraception is permitted by the study protocol)b

Intrauterine device (IUD)c

Intrauterine hormone-releasing system (IUS). (This method of contraception can only be 
used by WOCBP participants in studies where hormonal contraception is permitted by the 
study protocol)b,c

Bilateral tubal occlusion
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
Vasectomized partner
Having a vasectomized partner is a highly effective contraception method provided that the 
partner is the sole male sexual partner of the WOCBP and the absence of sperm has been 
confirmed. If not, an additional highly effective method of contraception should be used.

Sexual abstinence
Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study treatment. 
The reliability of sexual abstinence needs to be evaluated in relation to the duration of the 
study and the preferred and usual lifestyle of the subject.

Continuous abstinence must begin at least 30 days prior to initiation of study therapy.

It is not necessary to use any other method of contraception when complete abstinence is 
elected.

WOCBP subjects who choose complete abstinence must continue to have pregnancy tests, 
as specified in Section 2.

Acceptable alternate methods of highly effective contraception must be discussed in the 
event that the WOCBP subjects chooses to forego complete abstinence.

Periodic abstinence (including but not limited to calendar, symptothermal, postovulation
methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea 
method (LAM) are not acceptable methods of contraception for this study.
NOTES:
a Typical use failure rates may differ from those when used consistently and correctly. Use should be consistent 
with local regulations regarding the use of contraceptive methods for subjects participating in clinical studies.
b Hormonal contraception may be susceptible to interaction with the study treatment, which may reduce the 
efficacy of the contraceptive method. Hormonal contraception is permissible only when there is sufficient 
evidence that the IMP and other study medications will not alter hormonal exposures such that contraception 
would be ineffective or result in increased exposures that could be potentially hazardous. In this case, alternative 
methods of contraception should be utilized. For information specific to this study regarding permissibility of 
hormonal contraception, refer to Section 6.1 INCLUSION CRITERIA and Section 7.7.1 PROHIBITED 
AND/OR RESTRICTED TREATMENTS of the protocol.
c IUSs are acceptable methods of contraception in the absence of definitive drug interaction studies when hormone 
exposures from intrauterine devices do not alter contraception effectiveness. For information specific to this 
study regarding permissibility of hormonal contraception, refer to Section 6.1 INCLUSION CRITERIA and 
Section 7.7.1 PROHIBITED AND/OR RESTRICTED TREATMENTS of the protocol.
Less Than Highly Effective Contraceptive Methods That Are User-Dependent
Failure rate of > 1% per year when used consistently and correctly.

Male or female condom with or without spermicide. Male and female condoms cannot be 
used simultaneously

Diaphragm with spermicide

Cervical cap with spermicide
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
Vaginal sponge with spermicide

Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the 
primary mechanism of action (This method of contraception cannot be used by WOCBP 
participants in studies where hormonal contraception is prohibited.)
Unacceptable Methods of Contraception

Periodic abstinence (calendar, symptothermal, postovulation methods)

Withdrawal (coitus interruptus)

Spermicide only

LAM
COLLECTION OF PREGNANCY INFORMATION
Guidance for collection of Pregnancy Information and outcome of pregnancy on the Pregnancy 
Surveillance Form is provided in Section 9.2.5 and APPENDIX 3.
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APPENDIX 5
CRITERIA TO DEFINE INADEQUATE RESPONSE (PRIMARY), 
LOSS OF RESPONSE (SECONDARY), AND INTOLERANCE TO 
PREVIOUS STANDARD OF CARE MEDICATION(S)
Inadequate response, loss of response, and/or intolerance to each standard of care UC treatment is 
defined as follows:

Oral 5-aminosalicylic acids (5-ASAs) (eg, mesalamine, sulfasalazine, olsalazine, or 
balsalazide):

Signs and symptoms of persistently active disease despite a history of at least one 4-week 
regimen at highest dose (institutional practice)

Documented history of intolerance

Corticosteroids (eg, prednisone [or equivalent] or budesonide [or equivalent]):
o
Signs and symptoms of persistently active disease despite a history of at least one 4-week 
induction regimen that included a dose equivalent to 
 
 
 OR
o
At least 2 failed attempts to 
 corticosteroids below a dose that is equivalent to oral 
prednisone 10 mg/day (or equivalent) or budesonide 3 mg/day (or equivalent) on 2 separate 
occasions (ie, steroid-dependent disease); OR
o
Documented history of intolerance of corticosteroids where subject developed adverse 
reactions including, but not limited to, Cushing's syndrome, osteopenia/osteoporosis, 
hyperglycemia, insomnia, cataracts, refractory steroid acne, or infection.

Immunomodulators (eg, azathioprine [AZA], 6-mercaptopurine [6-MP], or methotrexate 
[MTX]):

Signs and symptoms of persistently active disease despite a history of at least one 8-week 
regimen of oral AZA, oral 6-MP, or oral or injectable MTX (per country's approved label); 
OR

History of intolerance of at least 1 immunomodulator (eg, nausea/vomiting, abdominal 
pain, pancreatitis, liver function test abnormalities, lymphopenia).

Anti-tumor necrosis factor (TNF) agents (eg, infliximab, adalimumab, or golimumab):

Signs and symptoms of persistently active disease despite an adequate trial of induction 
treatment with an anti-TNF agent (per country's approved label); OR

Recurrence of symptoms during maintenance dosing following prior clinical benefit; OR

History of intolerance (including, but not limited to, infusion-related reaction, 
demyelination, congestive heart failure, development of TNF inhibitor (TNFi) antibodies, 
or infection).

Integrin inhibitors (eg, vedolizumab):

Signs and symptoms of persistently active disease despite an adequate trial of induction 
treatment with an integrin inhibitor (per country's approved label); OR

Recurrence of symptoms during maintenance dosing following prior clinical benefit; OR

History of intolerance (including, but not limited to, infusion-related reaction, arthralgia, 
liver test abnormalities, or infection).
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APPENDIX 6
COMMONLY USED CORTICOSTEROID EQUIVALENTS
Medication
Dose Equivalence
Cortisone
100 mg
Hydrocortisone
80 mg
Prednisolone
20 mg
Methylprednisolone
16 mg
Triamcinolone
16 mg
Dexamethasone
3 mg
Betamethasone
2 to 4 mg
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APPENDIX 7
EXAMPLES OF WASHOUT TIMES REQUIRED PRIOR TO 
RANDOMIZATION
Medication/treatments
Discontinuation Prior 
to Randomization
Notes
5-azathioprine (AZA)
≥ 4 weeks
6-mercaptopurine (6-MP)
≥ 4 weeks
Abatacept (CTLA4Ig)
≥ 12 weeks
Adalimumaba
≥ 8 weeks
Washout period waived if undetectable levels 
.
Alefacept
≥ 8 weeks
Alemtuzumab
≥ 12 months
AMG 623
≥ 12 weeks
Apheresis
≥ 12 months
Lymphocyte apheresis or selective monocyte 
or granulocyte apheresis (eg, Cellsorba™).
Atacicept (TACI-Ig)
≥ 48 weeks
Belimumab
≥ 14 weeks
Certolizumab pegol
≥ 8 weeks
Cyclophosphamide
≥ 4 weeks
Cyclosporine
≥ 4 weeks
Danazol
≥ 4 weeks
Dapsone
≥ 4 weeks
Darvadstrocel
≥ 24 weeks
Eculizumab
≥ 12 weeks
Efalizumab
≥ 8 weeks
Epratuzumabb
≥ 18 weeks
Fecal transplant
≥4 weeks
This treatment is considered an investigational 
agent for the purposes of this study.
Golimumaba
≥ 8 weeks
Washout period waived if undetectable levels 
.
Infliximaba
≥ 8 weeks
Washout period waived if undetectable levels 
.
Interferon
≥ 12 weeks (or more 
than 5 half-lives, 
whichever is longer)
Intravenous globulin
≥ 4 weeks
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Medication/treatments
Discontinuation Prior 
to Randomization
Notes
Investigational therapies
≥ 4 weeks (or 5 half-
lives, whichever is 
longer)
Subjects treated with investigational agents 4-
12 weeks prior to first dose of study treatment 
must be discussed with the BMS Medical 
Monitor/designee.
IPP-201101
≥ 12 weeks
 
≥ 8 weeks
Subjects treated 
 
8-12 weeks prior to first dose of study 
treatment must be discussed with the BMS 
Medical Monitor/designee.
Leflunomide
≥ 12 weeks (or more 
than 5 half-lives, 
whichever is longer)
Lenalidomide with cholestyramine
≥ 24 weeks
Memantine
≥ 4 weeks
Methotrexate
≥ 4 weeks
Mycophenolate mofetil
≥4 weeks
Washout period may be waived after 
discussion with the BMS Medical 
Monitor/designee if undetectable 
mycophenolic acid (MMA) level on a relevant 
assay; test not provided within the study.
Natalizumab
≥ 8 weeks
Ocrelizumabb
≥ 24 weeks
Pimecrolimus
≥ 4 weeks
Plasmapheresis
24 weeks
Retinoids
≥ 4 weeks
Rituximab
≥ 12 months
Sphingosine 1-phosphate receptor 
modulators (eg, ozanimod)
≥ 8 weeks
Sirolimus (rapamycin)
≥ 4 weeks
Washout period may be waived after 
discussion with the BMS Medical 
Monitor/designee if undetectable sirolimus 
level on a relevant assay; test not provided 
within the study.
Tabalumab
≥ 14 weeks
Tacrolimus
≥ 4 weeks
Washout period may be waived after 
discussion with the BMS Medical 
Monitor/designee if undetectable tacrolimus 
level on a relevant assay; test not provided 
within the study.
Thalidomide
≥ 4 weeks
Other TNF inhibitors
≥ 8 weeks
Washout period waived if undetectable levels 
.
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Medication/treatments
Discontinuation Prior 
to Randomization
Notes
Tocilizumab
≥ 12 weeks
Ustekinumaba, d
≥ 8 weeks
For subjects who have received > 12 weeks of 
ustekinumab treatment, the washout period 
may be waived if undetectable levels 
 
.
Vedolizumaba
≥4 weeks
Subjects who have received > 14 weeks 
vedolizumab treatment; or washout period 
waived if undetectable levels 
 
.
≥ 8 weeks
Subjects who have received ≤14 weeks of 
vedolizumab treatment.
 TNF = tumor necrosis factor
a The washout period for this biologic can be waived for subjects who have an undetectable drug level 
 
, performed either in routine clinical practice or during the screening period. 
 used to waive 
the washout period for this biologic, the result 
 must be available in source documents, and the 
subject cannot receive another dose of that biologic 
 is obtained (Section 5.1.1).
b For epratuzumab, ocrelizumab, and any other B-cell-depleting agent, follow the required washout or document 
recovery of B cells (CD19+) after discontinuation of these therapies before a subject can be randomized.
d Failure or loss of response to previous treatment with ustekinumab (as well as other 
 antibodies 
or 
 antibodies) is exclusionary.
Note: Investigators should consult with the BMS Medical Monitor/designee for information about compounds not 
included in this list.
Some subjects will require adequate washout of biologics to be eligible for randomization. 
 assays that test for drug levels of these biologic medications 
can be commercially available in routine clinical practice and also available as an optional test 
during the screening period. The washout period for the following biologics can be waived in 
subjects who have an undetectable drug level 
, performed either in routine clinical 
practice or during the screening period: (1) infliximab, (2) adalimumab, (3) golimumab, (4) other 
TNF inhibitors, (5) vedolizumab (> 14 weeks of vedolizumab therapy), or (6) ustekinumab 
(> 12 weeks of ustekinumab therapy).
 used to waive the washout period for any of the biologics listed in the table 
above, the result 
 must be available in source documents, and the subject cannot 
receive another dose of that biologic prior to randomization.
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APPENDIX 9
MAYO SCORE: COMPONENT SUBSCORES AND ELECTRONIC 
SUBJECT DIARY ENTRY INSTRUCTIONS
The Mayo score is a composite instrument designed to assess ulcerative colitis (UC) disease 
activity. It includes patient-reported outcomes (PROs), an objective assessment of disease activity 
by endoscopy, and a Physician’s Global Assessment (PGA). The Mayo score was first proposed 
by Schroeder et al.47 Scherl et al48 proposed that the Mayo score should be modified by removing 
“mild friability” from the definition of an endoscopic (ES) subscore = 1. This was supported by 
draft guidance from the US Food and Drug Administration (FDA) that states the presence of 
friability is not consistent with the concept of “clinical remission” (Lines 249-251).38 As the PGA 
is neither a PRO nor an objective assessment of disease activity, and the concept that it purports 
to measure is not distinct from the other components of the modified Mayo score, use of the PGA 
as a component of the modified Mayo score is no longer recommended by US38 or European 
regulatory authorities.39
Consequently, disease activity assessments for inclusion and efficacy assessment will use the 
9-point modified Mayo score (ie, excluding PGA). The PGA will continue to be captured as part 
of this study to facilitate the calculation of the total Mayo score, which will allow these data to be 
compared with previous clinical trials.
Table 1 outlines the components and scoring used to calculate the modified and total Mayo scores.
Table 1:
Components of the Modified and Total Mayo Scores 
Stool Frequency (SF)a
0 
Normal number of stools for this patient
1
1 to 2 stools/day more than normal
2
3 to 4 stools/day more than normal
3
> 4 stools/day more than normal
Rectal Bleeding (RB)b
0
No blood seen
1
Streaks of blood with stool less than half the time
2
Obvious blood (more than just streaks) or streaks of blood with stool most of the 
time
3
Blood alone passed
Findings of flexible proctosigmoidoscopy (endoscopy used to determine ES subscore)
0
Normal or inactive disease
1
Mild disease (erythema, decreased vascular pattern)c
2
Moderate disease (marked erythema, absent vascular pattern, friability, erosions)
3
Severe disease (spontaneous bleeding ulceration)
PGA (not included in the 9-point modified Mayo score)d
0
Normal
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Table 1:
Components of the Modified and Total Mayo Scores 
1
Mild disease
2
Moderate disease
3
Severe disease
Sources: after 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;317:1625–29; Draft Guidance for 
Industry, Ulcerative Colitis: Clinical Trial Endpoints US Department of Health and Human Services, Food and Drug 
Administration, Center for Drug Evaluation and Research. Draft August 2016. Publication UCM515143.
PGA = Physician’s Global Assessment
a Each subject serves as his or her own control to establish the degree of abnormality of the SF.
b The daily bleeding score represents the most severe bleeding of the day.
c The original description of the Mayo score included “mild friability” in an ES subscore = 1. The modified Mayo 
score removed friability from an ES subscore = 0.
d The PGA acknowledges the patient’s SF, RB, and endoscopy reports; the patient’s daily record of abdominal 
discomfort and general sense of well-being; and other observations, such as physical findings and the patient’s 
performance status.
MAYO SCORES: DEFINITIONS
Two different versions of the Mayo score will be used as efficacy endpoints:
Modified Mayo Score: The modified Mayo score is a 9-point scale; a score of 5 to 9 points 
(inclusive), which is required for randomization, denotes moderate to severe disease (by protocol 
definition). The modified Mayo score is an adaptation of the total Mayo score (defined below) that 
excludes the PGA subscore.
The modified Mayo score incorporates the following 3 components:

Stool frequency (SF) subscore (0 to 3)

Rectal bleeding (RB) subscore (0 to 3)

ES subscore (0 to 3)
Total Mayo Score: The original total Mayo score incorporates all 4 components of UC severity 
listed in Table 1; each component subscore ranges from 0 to 3. The total Mayo score is a 12-point 
scale in which a higher score equals more severe disease.
The modified and total Mayo scores will be calculated using component subscores entered into the 
electronic case report form (eCRF).
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MAYO SCORES: SF AND RB COMPONENT SUBSCORES
SF and RB data will be recorded and calculated using an electronic subject diary.
Stool Frequency and Rectal Bleeding Subscores
Subjects will enter SF and RB data into the electronic subject diaries on a daily basis throughout 
their participation in the study. Instructions for recording the number of stools and worst rectal 
bleeding and definitions of SF and RB are provided in Table 2.
NOTE: The subject daily diary information should be reviewed prior to each scheduled visit at 
which Mayo scores are to be calculated and during each study visit to ensure that subjects are 
successfully entering and uploading diary data. If adequate entries have not been made, the subject 
should be counseled about proper study procedures.
For eligibility and efficacy analysis purposes, the 3 most recent (not necessarily consecutive), 
valid, electronic subject diary entries recorded from the 7 days prior to a study visit will be 
used to calculate the SF and RB subscores. For study visits that include an endoscopy (eg, 
screening, Weeks 12, 52 and ET or unscheduled visit [if applicable]), the 3 most recent (not 
necessarily consecutive), valid, electronic subject diary entries recorded from the 7 days 
prior to the day a subject starts bowel preparation for the endoscopy will be used to calculate 
the SF and RB subscores. If fewer than 3 days of daily SF and RB data have been recorded in the 
7 day window described above, the modified Mayo score cannot be calculated for that timepoint.
The SF and RB values used to establish eligibility will also be used for calculation of the baseline 
modified Mayo score.
The following will be considered invalid data and excluded from SF and RB subscore calculations:

A day that medication(s) for constipation, diarrhea, or bowel irregularity are taken
Formal calculation of SF and RB subscores will be performed using the electronic subject diaries.
For the preendoscopy screening visit (ie, prior to the availability of electronic subject diary data):
The baseline SF will be determined based on the number of stools a subject has in a 24-hour period 
when in remission from UC symptoms; or if a subject has not been in remission, they should be 
asked to identify the number of stools they had in a 24-hour period before initial onset of signs and 
symptoms of UC (Table 2).
This baseline SF is used as the reference for subsequent SF subscores.
For the endoscopy screening visit:
Best practice is to complete the other screening investigations first and check results to ensure that 
a subject continues to be potentially eligible for the study prior to commencing bowel preparation 
for the endoscopy. When the endoscopy is scheduled, SF and RB data in the electronic subject 
diary from the 7 days prior to the bowel preparation day for the endoscopy will be evaluated to 
ensure eligibility is maintained.
Following endoscopy, the ES subscore will be received via email from the central reader 
 
. This centrally-read screening ES subscore will be entered into the eCRF, in 
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addition to the SF and RB subscores, and the modified Mayo score will be calculated to determine 
subject eligibility.
For subsequent study visits at which Mayo scores are calculated:
For the Week 12 study visit, endoscopy timing should be reviewed prior to the visit to ensure 
adequate diary entries are available for SF and RB subscore determination. The averages of the 
3 most recent (not necessarily consecutive), valid, electronic diary entries for SF and RB data from 
the 7 days prior to the bowel preparation day for the endoscopy will be used. If adequate entries 
have not been made, the site should contact the subject to reschedule the visit, and the subject 
should be counseled about proper study procedures. Following endoscopy, ES subscores will be 
emailed from the central vendor as noted above and entered into the eCRF together with the SF 
and RB subscores to calculate the modified Mayo score for a given visit.
Missing Data:
Assessments with fewer than 3 valid, daily diary entries for SF and RB from the 7 days prior to 
the bowel preparation day for endoscopy are considered missing data and will not count toward 
assessment of disease activity during the screening period or for endpoint assessment at Week 12.
MAYO SCORES: ELECTRONIC SUBJECT DIARY ENTRY INSTRUCTIONS
Standardized instructions for recording SF and RB data (based on draft FDA Guidance for UC 
clinical endpoints)38 are in Table 2.
Table 2:
Standardized Instructions for Recording Number of Stools and 
Worst Rectal Bleeding (for the Mayo Scores) (Each Over a 24-hour 
Period)
Completion of electronic subject diary
Subjects will be trained on the completion of the electronic 
subject diary.
SF
Definition of stool
A stool is defined as a trip to the toilet when the subject has 
either a bowel movement or passes blood alone, blood and 
mucus, or mucus only.
Determine baseline SF 
(over 24 hours)
At the screening visit, the number of stools the subject has in a 
24-hour period when in remission from UC symptoms or prior to 
diagnosis of UC should be asked by the site and entered in the 
electronic patient diary.
If the subject has not been in remission, then the subject should 
be asked to identify the number of stools he/she had in a 24-hour 
period before initial onset of signs and symptoms of UC.
Record whether the baseline SF is based on the reported SF when 
the subject was in remission OR the reported SF before initial 
onset of signs and symptoms of UC.
Recording of SF assessments
Subjects are to record the total number of stools for the previous 
24-hour period in the electronic subject diary on a daily basis. 
Subjects should make diary entries at the same time each day.
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Table 2:
Standardized Instructions for Recording Number of Stools and 
Worst Rectal Bleeding (for the Mayo Scores) (Each Over a 24-hour 
Period)
Completion of electronic subject diary
Subjects will be trained on the completion of the electronic 
subject diary.
NOTE: For eligibility and efficacy analysis purposes, the 
established baseline SF (defined above) will be used to calculate 
the number of stools above normal and subsequently assign a 
Mayo SF component score. This will be done automatically by 
the electronic diary and will not need to be calculated by the 
subject or study team. 
RB
Most severe category of RB 
(in a given 24-hour period)
Subjects should enter into the electronic subject diary the most 
severe category that describes the amount of blood they had in 
their stools for that given day.
Categories (subscore) of RB are defined as follows:

No blood seen (0)

Streaks of blood with stool less than half the time (1)

Obvious blood (more than just streaks) or streaks of blood 
with stool most of the time (2)

Blood alone passed (3)
Subjects should enter “No Blood Seen” in the RB section if they 
do not have stool during a given day. 
Recording of RB assessments
Subjects are to record their RB assessments in the electronic 
subject diary on a daily basis. Subjects should make diary entries 
at the same time each day.
RB = rectal bleeding; SF = stool frequency; UC = ulcerative colitis
Adapted from: Draft Guidance for Industry, Ulcerative Colitis: Clinical Trial Endpoints US Department of Health and 
Human Services, Food and Drug Administration, Center for Drug Evaluation and Research. Draft August 2016. 
Publication UCM515143.
ES Subscore
ES subscores will be provided via email by the independent central endoscopy vendor 
 
 for all eligibility and efficacy assessments, at all time points. The endoscopy 
procedure from screening (central read) will be used to determine the baseline ES subscore 
component of the Mayo score. The ES subscores of the Mayo score will be modified so that the 
value 1 does not include friability.
PGA
The investigator will provide the PGA at every required visit. Categories of the PGA are listed in 
Table 1, above.
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APPENDIX 10
ULCERATIVE COLITIS ENDOSCOPIC INDEX OF SEVERITY 
(UCEIS): SCORES AND DEFINITIONS
Descriptor
Likert scale anchor points
Definition
Vascular pattern
Normal (0)
Normal vascular patterns with arborization of 
capillaries clearly
Patchy obliteration (1)
Patchy obliteration of vascular pattern
Obliterated (2)
Complete obliteration of vascular pattern
Bleeding
None (0)
No visible blood
Mucosal (1)
Some spots or streaks of coagulated blood on the 
surface of the mucosa ahead of the scope that 
can be washed away
Luminal mild (2)
Some free liquid blood in the lumen
Luminal moderate or 
severe (3)
Frank blood in the lumen ahead of the 
endoscope or visibly oozing from the mucosa 
after washing intraluminal blood, or visibly 
oozing from a hemorrhagic mucosa
Erosions and
ulcers
None (0)
Normal mucosa, no visible erosions, or ulcers
Erosions (1)
Tiny (≤5 mm) defects in the mucosa of a white 
or yellow color with
a flat edge
Superficial ulcer (2)
Larger (> 5 mm) defects in the mucosa, which 
are discrete fibrin-covered ulcers when 
compared with erosions but remain superficial
Deep ulcer (3)
Deeper excavated defects in the mucosa with 
slightly raised edge
Source: Travis SP, Schnell D, Krzeski P, et al. Reliability and initial validation of the ulcerative colitis endoscopic 
index of severity. Gastroenterology 2013;145(5):987-95.
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APPENDIX 11
INFLAMMATORY BOWEL DISEASE QUESTIONNAIRE (IBDQ)
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APPENDIX 12
ULCERATIVE COLITIS-RELATED HEALTHCARE UTILIZATION
Protocol Amendment No.: 02
Date: 24-Feb-2022
174
5.0
Approved
930153893
4.0
v
Approved
1.0
v


Clinical Protocol
IM011127
BMS-986165
TYK2 Inhibitor
APPENDIX 13
VACCINE GUIDANCE INCLUDING SARS-COV-2 VACCINES
The following outlines general vaccine guidance for the study:

Administration of a live vaccine is prohibited 90 days prior to the randomization visit, during 
the induction period or maintenance period, or within 2 months after the last dose of IP.

Administration of a nonlive vaccine is allowed during the study. However, the efficacy and 
safety of nonlive vaccines (including nonlive SARS-CoV-2 vaccines) in subjects receiving 
BMS-986165 is unknown.

The following are NOT live vaccines: inactivated vaccines (eg, heat-killed and formalin-killed 
vaccines), subunit vaccines (eg, influenza and pneumococcal vaccines), toxoid vaccines, 
nucleic acid vaccines that do not encode potentially infectious virus (eg, Pfizer/BioNTech and 
Moderna COVID-19 vaccines) and replication-incompetent recombinant vector vaccines (eg, 
AstraZeneca/University of Oxford SARS-CoV-2 vaccine).
The following outlines specific SARS-CoV-2 vaccine guidance for the study:

For SARS-CoV-2 vaccines requiring more than 1 dose, the full series (eg, both doses of a 
2-dose series) should be completed prior to enrollment when feasible, and when a delay in 
enrollment would not put the study subject at risk.

SARS-CoV-2 vaccination during the study should be considered for subjects who were not 
vaccinated or who have not completed eligible booster vaccinations prior to study entry.

If a subject has received a specific SARS-CoV-2 vaccination, the COVID-19 vaccination 
information, including type of vaccine and date(s) received, will be recorded in the 
COVID-19 vaccination form.
Please contact the Medical Monitor with any questions related to SARS-CoV-2 vaccines.
Protocol Amendment No.: 02
Date: 24-Feb-2022
175
5.0
Approved
930153893
4.0
v
Approved
1.0
v


Clinical Protocol
IM011127
BMS-986165
TYK2 Inhibitor
APPENDIX 14
PROTOCOL AMENDMENT SUMMARY OF CHANGE HISTORY
Overall Rationale for the Protocol Amendment 01, 06-May-2021
The primary purposes of this protocol amendment are to apply revisions relating to SARS-CoV-2 
infection and add clarification regarding additional research collection.
Key additions and clarifications include:

Adding information, instructions, and measures to be taken in relation to SARS-CoV-2 
infection

Adding clarification regarding additional research sample collection and use

Removing prohibition of medical marijuana

Adding assessments of mean corpuscular volume and mean corpuscular hemoglobin to the list 
of hematology laboratory tests to be conducted.

Removing the endoscopic global severity score. This was included in error, and is not being 
collected in the study.

Clarifying the definitions of steroid-dependent and steroid-resistant UC, to aid eCRF 
completion.

Clarifying the definition of the Ulcerative Colitis Endoscopic Index of Severity (UCEIS).

Clarifying male contraception requirements
This protocol amendment will be implemented after the investigator receives all appropriate 
agency and Investigational Review Board/Independent Ethics Committee approvals.
All changes applied to the body were applied to the synopsis, as necessary, and synopsis changes 
are not included in the list below.
Only major additions and deletions are provided in this summary document, and all minor 
grammatical, formatting, rephrasing, stylistic changes, or clarifications, as well as reorganizational 
changes are not included.
The rationales for changes to this protocol amendment are provided in the summary of key changes 
table, as shown below:
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 01
Section Number & Title
Description of Change
Brief Rationale
2 Schedule of Activities, Table 1
3.2 Benefit/Risk Assessment
4 Objectives and Endpoints
6.1 Inclusion Criteria
6.2 Exclusion Criteria
7.7.1 Prohibited Treatments
Added information, instructions, 
and measures to be taken related to 
SARS-CoV-2 infection/COVID-19, 
including the following:
Replaced the following Exclusion 
Criteria:
5)c) → 5)e)
Provide guidance 
to investigators 
related to 
SARS-CoV-2.
Protocol Amendment No.: 02
Date: 24-Feb-2022
176
5.0
Approved
930153893
4.0
v
Approved
1.0
v


Clinical Protocol
IM011127
BMS-986165
TYK2 Inhibitor
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 01
Section Number & Title
Description of Change
Brief Rationale
8.1.1 Temporary Discontinuation (new section)
9.1.2 Disease Activity and Quality of Life Indices Used in 
this Study
9.2.1 Time Period and Frequency for Collecting AE and 
SAE Information
9.4.3 Clinical Safety Laboratory Assessments
9.6 Biomarkers
9.6.1 Additional Research Collection
9.8 SARS-CoV-2 Testing (new section)
Appendix 1 Abbreviations and Trademarks
Appendix 5 Criteria to Define Inadequate Response 
(Primary), Loss of Response (Secondary), and Intolerance 
To Previous Standard Of Care Medication(s)
Appendix 10 Ulcerative Colitis Endoscopic Index of 
Severity (UCEIS): Scores and Definitions
Appendix 13 COVID-19 Vaccines (new appendix)
Removed exclusion of medical 
marijuana, including the following:
Replaced the following Exclusion 
Criteria:
9)j) Ѝ 9)p)
Facilitate study 
feasibility.
Removed inclusion criteria 5b ii and 
iii, added clarifying language to 5b 
iv (now ii) to clarify male 
contraception requirement
Clarify male 
contraception 
requirements.
Added text regarding additional 
research sample collection and use.
Clarify additional 
research sample 
collection and 
use.
Added assessments of mean 
corpuscular volume (MCV) and 
mean corpuscular hemoglobin 
(MCH) to the list of hematology 
laboratory tests to be conducted.
Estimation of 
MCV and MCH 
will assist in the 
characterization 
of red blood cell 
morphology.
Removed the endoscopic global 
severity score.
This score was 
included in error, 
and is not being 
collected in the 
study.
Clarification of the definitions of 
"steroid-refractory" and 
"steroid-dependent" disease for the 
purpose of eCRF completion 
Additionally 
clarify the 
corticosteroids 
criteria.
Clarified the definition of the 
Ulcerative Colitis Endoscopic Index 
of Severity (UCEIS).
Additionally 
clarify the 
classification of 
erosions and 
ulcers.
Protocol Amendment No.: 02
Date: 24-Feb-2022
177
5.0
Approved
930153893
4.0
v
Approved
1.0
v