A Phase 4, Prospective, Open-label Study of Ozanimod to Explore the Safety, Efficacy, Quality of Life, and Biomarker Response in Participants With Moderate to Severe Ulcerative Colitis in Clinical Practice
Phase: PHASE4
Conditions: Colitis, Ulcerative
Sponsor: Bristol-Myers Squibb

Official Title of Study: 
A Phase 4, Prospective, Open-label Study of Ozanimod to Explore the Safety, Efficacy, Quality 
of Life, and Biomarker Response in Participants with Moderate to Severe Ulcerative Colitis in 
Clinical Practice 
 
NCT Number: NCT05369832 
Document Date (Date in which document was last revised): 22-Aug-2022 
 
 
 

Page:
1
Protocol Number:
IM047029
Date:
31-Mar-2022
Revised Date:
22-Aug-2022
CLINICAL PROTOCOL IM047029
A Phase 4, Prospective, Open-label Study of Ozanimod to Explore the Safety, Efficacy, Quality 
of Life, and Biomarker Response in Participants with Moderate to Severe Ulcerative Colitis in 
Clinical Practice
Brief Title:
Open-label study of ozanimod in moderate to severe UC in clinical practice.
Protocol Amendment 01
Clinical Trial Physician-Medical Monitor
Bristol-Myers Squibb Company
3401 Princeton Pike Lawrenceville, NJ 08648 
Phone 
email: 
 
Clinical Scientist
Bristol-Myers Squibb Company
3401 Princeton Pike Lawrenceville, NJ 08648 
Phone 
email: 
24-hr Emergency Telephone Number
USA: 1-866-470-2267
International: +1-248-844-7390
Celgene International II Sàrl
Route de Perreux 1
2017 Boudry, Switzerland
REGULATORY AGENCY IDENTIFIER NUMBER(S)
IND: 115243
EudraCT Number: 2022-001382-12
UTN: U1111-1276-5969
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 
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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. References to BMS in this protocol may apply to partners to which BMS 
has transferred obligations (eg, a Contract Research Organization [CRO]).
© 2020 Bristol-Myers Squibb Company
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Ozanimod
Protocol Amendment No.: 01
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DOCUMENT HISTORY
Document
Date of Issue
Summary of Change
Protocol Amendment 
01
22-Aug-2022

Removed the term “global” from the protocol title.

Study duration reduced from 3 years to 2 years, 
correspondingly time points for additional endpoints 
common for both Cohort 1 and Cohort 2 after Week 26 
(Table 4-3) have been adjusted.

Revised number of participants in Cohort 1 from 200 to 
150.

Revised number of participants in Cohort 2 from 150 to 
100.

Revised Figure 5.1-1 (Study Design Schema) to reflect 
2-year study duration and revised number of 
participants.

Revised inclusion criterion 2b: Participants must have 
moderate to severely active UC, defined as a score of 4 
through 9 on the 9-point modified Mayo score and an 
SF subscore ≥1 in order to enter the treatment period.

Included a new inclusion criterion 5b: Biologic agents 
should be discontinued at least 8 weeks prior or at least 
5 elimination half lives prior to study intervention
initiation, whichever is shorter. Washout period may be 
waived with the demonstration of absent drug levels on 
a TDM assay.

Renumbered inclusion criterion 5b to 5c and revised: 
Added 3 different criteria related to 
6-marcaptourine/AZA or methortrexate. 

Revised inclusion criterion 7a-ii: WOCBP must have a 
negative pregnancy test during the screening process.

Removed exclusion criterion 2g: UC involving the 
rectum only (UC proctitis).

Deleted PK analysis throughout the protocol.

In the SOA the following changes were made: 
o
Table 2-1: Deleted visit at Week 39 and 78; added 
Demographics and Subject Characteristics at 
baseline 
o
Table 2-2: Deleted the entire Year 3 time points.
o
o
 
 
o
Revised notes for CBC and Differential Count, 
Biochemistry, Pregnancy Test, and Stool 
Collection. 
o
Revised legend notes, as needed.

Revised Table 7.1-1: Packaging and labeling details of 
ozanimod have been updated.
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Document
Date of Issue
Summary of Change

Revised Table 7.7-1: Updated washout period for 
immunomodulatory drugs to 1 day and aligned details 
about biologic agents with inclusion criterion 5b.

Study intervention discontinuation criterion 
(Section 8.1) related to laboratory abnormalities has 
been revised.

Treatment interruption criteria (Section 8.1.1) has been 
revised.

Laboratory test result abnormalities for ALC (Section 
9.2.6) has been revised.

 
 

 
 

Minor administrative and editorial changes were made 
throughout the protocol.

Text in the protocol summary has been updated to 
maintain consistency and to align the text with that in 
the main body.
Original Protocol
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OVERALL RATIONALE FOR PROTOCOL AMENDMENT 01:
The primary reason for Protocol Amendment 01 is to clarify study duration, participants in both 
cohorts, revision of inclusion/exclusion criteria,
References to
Global were deleted throughout the protocol and in the title. Clarifying information and 
administrative changes were made. 
These changes pertain to all participants.
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 01
Section 
Number & 
Title
Description of Change
Brief Rationale
All
Removed the term “global” from 
the protocol title.
Study has been reduced to USA-only.
All
Study duration reduced from 3 
years to 2 years, correspondingly 
time points for additional 
endpoints common for both 
Cohort 1 and Cohort 2 after Week 
26 (Table 4-3) have been adjusted.
Duration reduced due to operational 
feasibility assessment, whilst 
maintaining the scientific integrity of the 
study.
All
Revised number of participants in 
Cohort 1 from 200 to 150.
Duration reduced due to operational 
feasibility assessment, whilst 
maintaining scientific integrity of the 
study.
All
Revised number of participants in 
Cohort 2 from 150 to 100.
Duration reduced due to operational 
feasibility assessment, whilst 
maintaining scientific integrity of the 
study.
Section 5.1: 
Overall 
Design
Revised Figure 5.1-1
Revised Study Design Schema to
reflect the 2-year study duration 
and revised number of 
participants.
Reflect above rationale.
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SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 01
Section 
Number & 
Title
Description of Change
Brief Rationale
Section 6.1: 
Inclusion 
Criteria
Revised inclusion criterion 
2b: Participants must have 
moderate to severely active UC, 
defined as a score of 4 through 9 
on the 9-point modified Mayo 
score and an SF subscore ≥ 1 in 
order to enter the treatment 
period.
Broaden scope of study to include more 
moderate activity patients by reducing 
lower Mayo limit to 4-9 points (from 5-9
points).
Section 6.1: 
Inclusion 
Criteria
Added a new inclusion criterion 
5c: Biologic agents should be 
discontinued at least 8 weeks prior 
or at least 5 elimination The 
washout prior to study 
intervention initiation, whichever 
is shorter. The washout period 
may be waived with the 
demonstration of absent drug 
levels on a TDM assay.
Given different half-lives of biologics, it 
is important to address and offer a 
washout of at least 5 elimination half-
lives prior to intervention” for agents 
with short half-lives to be used sooner.
Section 6.1: 
Inclusion 
Criteria
Added 3 different criteria related 
to 6‑marcaptourine/AZA or 
methortrexate. 
Clarify use of 6-MP/azathioprine prior 
to study entry.
Section 6.1: 
Inclusion 
Criteria
Revised inclusion criterion 7a-ii: 
WOCBP must have a negative 
pregnancy test during the 
screening process.
Clarify timing for negative pregnancy 
test prior to initiating study treatment.
Section 6.2: 
Exclusion 
Criteria
Removed exclusion criterion 2g: 
UC involving the rectum only 
(UC proctitis). 
Amendment to include proctitis patients 
in the trial.
All
Deleted PK analysis throughout 
the protocol.
Duration reduced due to operational 
feasibility assessment, whilst 
maintaining scientific integrity of the 
study.
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SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 01
Section 
Number & 
Title
Description of Change
Brief Rationale
Section 2: 
Schedule of 
Activities
In the SOA the following changes 
were made: 
Table 2-1: Deleted visit at Week 
39 and 78; added Demographics 
and Subject Characteristics at 
baseline.
Table 2-2: Deleted the entire Year 
3 time points.
 
 
 
Revised notes for CBC and 
Differential Count, Biochemistry, 
Pregnancy Test, and Stool 
Collection. 
Revised legend notes, as needed.
Edit SOA to align with alterations as 
detailed above.
Section 7.1:
Study 
Interventions 
Administered
Revised Table 7.1-1: Packaging 
and labeling details of ozanimod 
have been updated.
To align with singular (US) market.
Section 7.7.1:
Prohibited 
and/or 
Restricted 
Treatments
Revised Table 7.7-1: Updated 
washout period for 
immunomodulatory drugs to 1 day 
and aligned details about biologic 
agents with inclusion criterion 5b.
To align with protocol from prior 
ozanimod trials, including True North 
trial.
Section 8.1: 
Discontinuatio
n from Study 
Intervention
Study intervention discontinuation 
criterion (Section 8.1) related to 
laboratory abnormalities has been 
revised.
Clarify lab abnormalities that may lead 
to treatment discontinuation.
Section 8.1.1:
Treatment 
interruption
Treatment interruption criteria 
(Section 8.1.1) has been revised.
Clarify recommended actions in the 
setting of interrupted treatment
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SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 01
Section 
Number & 
Title
Description of Change
Brief Rationale
Section 9.2.6: 
Laboratory 
Test Result 
Abnormalities
Laboratory test result 
abnormalities for ALC (Section 
9.2.6) has been revised.
Clarify any lab abnormalities that may 
be seen as reason to signify an AE
All
Minor administrative and editorial 
changes were made throughout 
the protocol.
Minor, therefore, have not been 
summarized.
Section 1: 
Protocol 
Summary
Text in the protocol summary has 
been updated to maintain 
consistency and to align the text 
with that in the main body.
As per rationale above. 
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TABLE OF CONTENTS 
 
 
TITLE PAGE ................................................................................................................ 
 
DOCUMENT HISTORY .............................................................................................. 
 
OVERALL RATIONALE FOR PROTOCOL AMENDMENT 01: ............................ 
 
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 01 ......................... 
 
TABLE OF CONTENTS .............................................................................................. 
 
1 PROTOCOL SUMMARY ......................................................................................... 
 
2 SCHEDULE OF ACTIVITIES.................................................................................. 
 
3 INTRODUCTION ..................................................................................................... 
 
3.1 Study Rationale ................................................................................................. 
 
3.2 Background ....................................................................................................... 
 
3.2.1 Ulcerative Colitis ..................................................................................... 
 
3.2.2 Ozanimod ................................................................................................. 
 
3.2.3 Ozanimod in UC ...................................................................................... 
 
3.3 Benefit/Risk Assessment .................................................................................. 
 
3.3.1 Risk Assessment ....................................................................................... 
 
3.3.2 Benefit Assessment ................................................................................... 
 
3.3.3 Overall Benefit/Risk Conclusion .............................................................. 
 
4 OBJECTIVES AND ENDPOINTS ........................................................................... 
 
5 STUDY DESIGN....................................................................................................... 
 
5.1 Overall Design .................................................................................................. 
 
5.1.1 Data Monitoring Committee and Other Committees ............................... 
 
5.2 Number of Participants ..................................................................................... 
 
5.3 End of Study Definition .................................................................................... 
 
5.4 Scientific Rationale for Study Design............................................................... 
 
5.5 Justification for Dose ........................................................................................ 
 
6 STUDY POPULATION ............................................................................................ 
 
6.1 Inclusion Criteria .............................................................................................. 
 
6.2 Exclusion Criteria ............................................................................................. 
 
6.3 Lifestyle Restrictions ........................................................................................ 
 
6.4 Screen Failures .................................................................................................. 
 
6.4.1 Retesting During Screening or Lead-in Period ....................................... 
 
7 STUDY INTERVENTION(S) AND CONCOMITANT THERAPY ....................... 
 
7.1 Study Interventions Administered .................................................................... 
 
7.2 Method of Study Intervention Assignment ....................................................... 
 
7.3 Blinding............................................................................................................. 
 
7.4 Dosage Modification ......................................................................................... 
 
7.5 Preparation/Handling/Storage/Accountability .................................................. 
 
7.6 Treatment Compliance ...................................................................................... 
 
7.7 Concomitant Therapy........................................................................................ 
 
7.7.1 Prohibited and/or Restricted Treatments................................................. 
 
7.7.2 Other Restrictions and Precautions ......................................................... 
 
7.7.2.1 Treatment Failure Rules ................................................................. 
 
7.8 Continued Access to Study Intervention After the End of the Study ............... 
 
8 DISCONTINUATION CRITERIA ........................................................................... 
 
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8.1 Discontinuation From Study Intervention ........................................................ 
 
8.1.1 Treatment Interruption ............................................................................. 
 
8.1.2 Post-study Intervention Study Follow-up................................................. 
 
8.2 Discontinuation From the Study ....................................................................... 
 
8.2.1 Individual Discontinuation Criteria ........................................................ 
 
8.3 Lost to Follow-up .............................................................................................. 
 
9 STUDY ASSESSMENTS AND PROCEDURES ..................................................... 
 
9.1 Efficacy Assessments ........................................................................................ 
 
9.1.1 Efficacy Assessments for the Study .......................................................... 
 
9.1.2 Other Efficacy Assessments for the Study ................................................ 
 
9.1.2.1 Histology Assessment ...................................................................... 
 
9.1.2.2 Health-related Quality of Life ......................................................... 
 
9.2 Adverse Events ................................................................................................. 
 
9.2.1 Time Period and Frequency for Collecting AE and SAE Information .... 
 
9.2.1.1 Adverse Events of Interest ............................................................... 
 
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 DILI .......................................................................................... 
 
9.2.8 Other Safety Considerations .................................................................... 
 
9.3 Expedited Reporting of SUSARs...................................................................... 
 
9.4 Overdose ........................................................................................................... 
 
9.5 Safety ................................................................................................................ 
 
9.5.1 Physical Examinations ............................................................................. 
 
9.5.2 Vital Signs ................................................................................................ 
 
9.5.3 12-lead ECG ............................................................................................ 
 
9.5.4 Clinical Safety Laboratory Assessments .................................................. 
 
 
 
9.8 Additional Research .......................................................................................... 
 
 
9.9 Other Assessments ............................................................................................ 
 
9.10 Healthcare Resource Utilization ..................................................................... 
 
10 STATISTICAL CONSIDERATIONS .................................................................... 
 
10.1 Statistical Hypotheses ..................................................................................... 
 
10.2 Sample Size Determination ............................................................................. 
 
10.3 Analysis Sets ................................................................................................... 
 
10.4 Statistical Analyses ......................................................................................... 
 
10.4.1 General Considerations ......................................................................... 
 
10.4.2 Disposition, Demographics, and Baseline Characteristics ................... 
 
10.4.3 Primary Endpoint................................................................................... 
 
10.4.4 Secondary Endpoints ............................................................................. 
 
 
 
10.4.6 Other Safety Analyses ............................................................................ 
 
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10.4.7 Other Analyses ....................................................................................... 
 
 
10.5 Interim Analyses ............................................................................................. 
 
11 REFERENCES ........................................................................................................ 
 
12 APPENDICES ......................................................................................................... 
 
APPENDIX 1 ABBREVIATIONS AND TRADEMARKS ........................................ 
 
APPENDIX 2 STUDY GOVERNANCE CONSIDERATIONS ................................. 
 
APPENDIX 3 SELECTED INSTRUMENT DEFINITIONS (BASED ON 
PERMUTATIONS OF THE MAYO SCORE) ...................................................... 
 
APPENDIX 4 WOMEN OF CHILDBEARING POTENTIAL DEFINITIONS AND 
METHODS OF CONTRACEPTION ..................................................................... 
 
APPENDIX 5 ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS: 
DEFINITIONS AND PROCEDURES FOR RECORDING, EVALUATING, 
FOLLOW-UP, AND REPORTING ....................................................................... 
 
APPENDIX 6 SELECTED ENDPOINT DEFINITIONS ............................................ 
 
 
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1
PROTOCOL SUMMARY
Protocol Title:
A Phase 4, Prospective, Open-label Study of Ozanimod to Explore the Safety, Efficacy, 
Quality of Life, and Biomarker Response in Participants with Moderate to Severe Ulcerative 
Colitis in Clinical Practice
Brief Title: Open -label study of ozanimod in moderate to severe UC in clinical practice
Rationale:
This prospective, open-label, Phase 4 study is designed to explore the safety, efficacy, effects on 
quality of life (QOL), and biomarker response of ozanimod (Zeposia®, RPC1063, BMS-986374) 
in participants with moderate to severely active ulcerative colitis (UC) in clinical practice.
The study population will be consistent with the product label, so that this study may generate data 
that are directly relevant to the labeled indication and that may be used to further inform the clinical 
use of ozanimod in this study population.
The study will include 2 cohorts:

Cohort 1: Participants with moderate to severely active UC who have not been exposed to
biologics or immunomodulators for the treatment of UC (ie, advanced therapy-naïve).

Cohort 2: Participants with moderate to severely active UC who have been exposed to a single
mechanism of action of biologics for the treatment of UC (ie, advanced therapy-exposed).
This study will generate additional data on the effect of ozanimod treatment, including (but not 
limited to) the following: 

Characterization of early response (improvement in signs and symptoms of UC within the first
4 weeks), including rectal bleeding (RB), stool frequency (SF), urgency, and abdominal
symptoms.

Characterization of the endoscopic and histologic response to ozanimod at Week 12 in an
advanced therapy-naïve cohort.

Characterization of the endoscopic and histologic response to ozanimod at Week 26 in an
advanced therapy-exposed cohort.

Characterization of the long-term safety of ozanimod over the duration of the study.

Patient-reported outcome (PRO) measures, including impact on disease-specific QOL and
symptoms, fatigue, patient satisfaction with treatment, and work productivity.

Characterization of the effect of ozanimod treatment on biomarkers of disease activity used in
clinical practice, 
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Objectives and Endpoints: 
Specific to Advanced Therapy-naïve Cohort (Cohort 1)
Objectives
Endpoints
Primary

To explore the efficacy of ozanimod in
inducing clinical response in the advanced
therapy-naïve cohort.

Clinical response at Week 12, as measured by modified
Mayo score.
Secondary

To explore the efficacy of ozanimod in the
advanced therapy-naïve cohort.

Clinical remission at Week 12, as measured by modified
Mayo score.

Endoscopic response at Week 12.

Endoscopic improvement at Week 12.

Histological improvement at Week 12.

To explore the effects of ozanimod on
disease-specific health-related quality of life
(HRQOL)
in the advanced therapy-naïve
cohort.

Change 
in 
the 
Inflammatory 
Bowel 
Disease
Questionnaire (IBDQ) total score from baseline to
Week 12.

IBDQ response (change in total score [≥16 points] from
baseline to Week 12).

IBDQ remission (total score [≥170 points]) at Week 12.
Specific to Advanced Therapy-exposed Cohort (Cohort 2)
Objectives
Endpoints
Primary

To explore the efficacy of ozanimod in
inducing clinical response in the advanced
therapy-exposed cohort.

Clinical response at Week 26, as measured by modified
Mayo score.
Secondary

To explore the efficacy of ozanimod in the
advanced therapy-exposed cohort.

Clinical remission at Week 26, as measured by modified
Mayo score.

Endoscopic response at Week 26.

Endoscopic improvement at Week 26.

Endoscopic remission at Week 26.

Histological improvement at Week 26.

Histological remission at Week 26.

Change in the IBDQ total score from baseline to
Week 26.

IBDQ response (change in total score [≥16 points] from
baseline to Week 26).

IBDQ remission (total score [≥170 points]) at Week 26.

Corticosteroid-free clinical remission at Week 26, as
measured by modified Mayo score.
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Objectives
Endpoints

Histo-endoscopic mucosal improvement (HEMI) at
Week 26
Additional Objectives and Endpoints Common for both the Advanced Therapy-naïve 
Cohort (Cohort 1) and the Advanced Therapy-exposed Cohort (Cohort 2) after Week 26
Objectives
Endpoints
Secondary

To explore the safety and tolerability of
ozanimod in the advanced therapy-naïve
cohort and the advanced therapy-exposed
cohort.

Number and proportion of participants experiencing the
following:

Adverse events (AEs).

Serious adverse events (SAEs).

AEs and SAEs, including adverse event of interest
(AEIs)
and 
other 
select 
AEs,
leading to
discontinuation from study intervention and the
study.

Clinical laboratory values.

To explore the long-term durability of response
to ozanimod in the advanced therapy-naïve
cohort and the advanced therapy-exposed
cohort.

Clinical remission by partial Mayo score at Weeks 52
and 104

Corticosteroid-free clinical remission by partial Mayo
score at Weeks 52 and 104.

Clinical response by partial Mayo score at Weeks 52 and
104.
Overall Design:
Study IM047-029 is a Phase 4, prospective, non-randomized, open-label, multicenter clinical study 
designed to explore the safety, efficacy, effects on QOL, and biomarker response of ozanimod 
0.92 mg once daily (QD) per oral (PO) administration in participants with moderate to severely 
active UC in clinical practice. 
This clinical study will evaluate ozanimod 0.92 mg QD PO in multiple UC disease subtypes, and 
with 2 specific cohorts as described above. 
Participants will undergo screening evaluations to determine eligibility as indicated in the 
Schedule of Activities (SOA; see Table 2-1). Participants must meet the eligibility criteria in order 
to enter the treatment period (see Section 6). Participants must have moderate to severely active 
UC, defined as a score of 4 through 9 on the 9-point modified Mayo score, in order to enter the 
treatment period.
Eligibility assessments, physical examinations, additional screening tests, electronic diary 
dispensing and review, blood, stool, and urine sample collections, 
 
 endoscopies with biopsies, additional efficacy assessments, PRO and HRQOL 
assessments, healthcare resource utilization, investigational product (IP) supply, safety 
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assessments, and other study procedures will be performed as indicated in the SOA (see Table 2-1,
Table 2-2).
All eligible participants will receive open-label ozanimod 0.92 mg QD PO, per product label,
during the treatment period (see Table 7.1-1). Ozanimod titration will occur during the first 7 days 
of study intervention exposure, per label (see Table 7.1-2). Once the study intervention 
(ie, ozanimod) has been titrated up to 0.92 mg QD PO (Day 8), further dose escalation is not 
allowed.
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The study design schematic is presented in Figure 1.
Figure 1:
Study Design Schema
E, endoscopies and biopsies; EDC, electronic data capture; ES, endoscopic subscore; EOT, end of treatment.
a For participants who prematurely discontinue from the study, if possible, the EOT visit and follow-up visit should be conducted so that data can be collected at
the time of study discontinuation and follow-up and for any further evaluations that need to be completed. 
b Screening endoscopy (colonoscopy or sigmoidoscopy) may be performed within 60 days prior to the first study intervention administration. Photographic
evidence of ES >2 must be available for study inclusion, as per eligibility criteria. In the event that historic endoscopic data is used as a part of screening, historic 
histopathologic tissue will not be collected.
c Ozanimod titration will occur during the first 7 days of study intervention exposure, per label (Table 7.1-2). Participants will receive
a phone call on Day 5 (when titrating their dose from 0.23 mg to 0.46 mg) and again on Day 8 (when titrating their dose from 0.46 mg to 0.92 mg) as a reminder 
about the dose adjustment. If required, an unscheduled visit can be planned anytime during the treatment period. Data regarding study procedures conducted at 
such unscheduled visits (eg, blood, stool, and urine tests; safety assessments) will be documented in the EDC tool.
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Number of Participants:
It is estimated that approximately 250 screened participants in Cohort 1 (advanced therapy-naïve
cohort) will be required to achieve 150 treated participants. Similarly, for Cohort 2 (advanced 
therapy-exposed cohort), it is estimated that approximately 165 participants will be required to 
achieve 100 treated participants. These enrollment estimates assume a screen failure rate of 
approximately 40% in each cohort.
If the screen failure rate is higher than expected, enrollment will remain open until the required 
number of treated participants in each cohort is achieved.
The sample size for this study is not based on statistical power for comparisons among treatment 
cohorts; it has been selected to minimize the width of the 95% confidence interval (CI) of the 
estimate of the clinical response rate (primary endpoint) for each.
Study Population:
Prospective approval of protocol deviations to the recruitment and enrollment criteria, also known 
as protocol waivers or exemptions, is not permitted.
Key Inclusion Criteria

Participant must be over 18 years of age (or the legal age of consent in the jurisdiction in which 
the study is taking place) at the time of signing the informed consent.

A diagnosis of UC, with signs and symptoms consistent with UC for at least 3 months prior to 
the first study intervention administration.

Moderate to severely active UC disease activity, defined as a modified Mayo score of 4 through
9, inclusive, with the following minimum subscores:

An SF subscore ≥1, AND

An RB subscore ≥1, AND

An endoscopic subscore (ES) ≥2 (endoscopy performed within 60 days of the first study 
intervention administration).

In order to participate in Cohort 1 (advanced therapy-naïve cohort), a participant must meet 
the eligibility criteria outlined in this inclusion criterion (IC) and must not meet the eligibility 
criteria for Cohort 2.

Participants must be naïve to 6-mercaptopurine/azathioprine (AZA) and any biologics (see 
IC 5[a]) in Section 6.1 for list) for any other medical indication, as well as UC.

In order to participate in Cohort 2 (advanced therapy-exposed cohort), a participant must have 
failed only one mechanism of action of biologics.

Documentation of an inadequate response, loss of response, or intolerance to a treatment 
course of one class of approved biologics (see IC 5[a]) in Section 6.1 for list) and should 
not have been treated with additional classes of approved biologics.

6-mercaptopurine/AZA or methotrexate: 
Participant may have been previously treated with 6-mercaptopurine/AZA or 
methotrexate.
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Participant may not take these agents concomitantly over the course of the study.
These agents must be discontinued prior to day of starting study intervention.

Key Exclusion Criteria

Medical conditions, including the following: 

Recent (within 6 months of screening) myocardial infarction, unstable angina, stroke, 
transient ischemic attack, decompensated heart failure requiring hospitalization, or New 
York Heart Association Class III/IV heart failure.

Presence of Mobitz type II second- or third-degree atrioventricular (AV) block, sick sinus 
syndrome, or sino-atrial block, unless the participant has a functioning pacemaker.

Severe untreated sleep apnea.

Current macular edema. (Note: Participants with diabetes, or a history of uveitis, retinal 
disease, or previous macular edema must have an ophthalmic evaluation of the fundus, 
including the macula, prior to the first study intervention administration.)

Current active infection, and/or any infection requiring oral antibiotics within 14 days of 
screening, or intravenous (IV) antibiotics within 30 days of screening.

Any major infection that required hospitalization.

Immunodeficient state (not including previously mentioned immunosuppressants) leading 
to increased risk of opportunistic infections.

A history of cancer within 5 years, including solid tumors and hematological malignancies 
(except basal cell carcinoma or squamous cell carcinoma of the skin that have been fully 
treated, or cervical dysplasia or carcinoma in situ that have been fully treated).

Severe hepatic impairment (Child-Pugh Class C).

Participant has a current diagnosis of Crohn’s disease (CD), indeterminate colitis, radiation 
colitis or ischemic colitis, a monogenic cause of UC-like intestinal inflammation, colonic 
diverticulitis, or an alternative diagnosis that explains their colonic inflammation. 

Current or recent (within 3 months of screening) evidence of fulminant colitis, toxic 
megacolon, or bowel perforation.

Current need for, or anticipated need for, surgical intervention for UC during the course of the 
study. 

Extensive colonic resection or current stoma.

Colonic dysplasia that has not been removed.

Previous or current use of Janus kinase (JAK) inhibitors (eg, tofacitinib, filgotinib).

Hypersensitivity to active ingredients or excipients of ozanimod.
Intervention Cohorts and Duration:
Intervention cohorts and study duration are described in the study rationale and overall design 
sections above.
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Study Intervention: 
Study Intervention for IM047029
Medication 
Potency 
Ozanimod (Zeposia)
0.23 mg, 0.46 mg, and 0.92 mg
Statistical Methods:
Due to the open-label design of the study and the lack of a control group, all data will be 
summarized, and no hypothesis testing will be performed.
Baseline is defined as the last observed measurement prior to the first dose of study intervention 
on Day 1.
In general, descriptive summaries will be presented for the efficacy and safety variables collected. 
Continuous variables will be summarized using the number of participants (n), mean, standard 
deviation, minimum, median, and maximum. Categorical variables will be summarized using 
frequency counts and percentages and 95% CIs.
The primary endpoint for Cohort 1 is the proportion of participants who achieve a clinical response 
at Week 12. The clinical response rate at Week 12 will be estimated, and the corresponding 95%
CI will be derived based on the Clopper Pearson method. 
The primary endpoint for Cohort 2 is the proportion of participants who achieve clinical response 
at Week 26. An estimate of the clinical response rate at Week 26 will be provided along with the 
corresponding 95% CI derived based on the Clopper Pearson method.
The primary endpoint analysis will be performed when all participants in both cohorts have 
completed the primary endpoint visit (ie, Week 12 for Cohort 1 and Week 26 for Cohort 2). The 
statistical analysis plan (SAP) will describe the planned interim analyses in greater detail.
For proportion-based efficacy endpoints, patients with missing Week 12 efficacy data from 
Cohort 1 and/or participants with missing Week 26 efficacy data from Cohort 2 will be considered 
non-responders, and non-responder imputation will be used. Sensitivity analyses around missing 
data may involve missing data imputed using multiple imputation and may analyze observed cases 
with no imputation. Details of the sensitivity analysis will be provided in the SAP. 
For continuous efficacy endpoints, observed cases will be analyzed with no imputation.
Data Monitoring Committee: No
Other Committee: No
Brief Summary:
The purpose of this study is to explore the safety, efficacy, effects on QOL, and biomarker response 
of ozanimod in participants with moderate to severely active UC in clinical practice. Study details 
include the following:
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Study Duration: Approximately 2.4 years
Study Intervention Duration: 2 years
Study Visit Frequency: Participants will have clinic visits as follows:

Year 1: Screening, Day 1, Week 4 (± 7 days), Week 12 (± 7 days), Week 26 (± 7 days),
Week 52 (± 14 days).

Years 2: Week 104 (± 14 days), Week 116 ( ± 14 days)
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2
SCHEDULE OF ACTIVITIES
The Schedule of Activities (SOA) for the screening and initial on-treatment study period is
provided in Table 2-1. The SOA for the on-treatment period beyond Week 52 is provided in 
Table 2-2.
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Table 2-1:
Schedule of Activities for Year 1 (IM047029)
Procedure
Screening
(Days -28 
to -1)
Week 0
(Day 1)
Week 4
(Day 28)
Week 12
(Day 84)
Week 26
(Day 182)
Week 52
(Day 365)
Unscheduleda
Notes
Visit Window (± n Days)
7
7
7
14
Eligibility Assessments
Informed Consent
X
See APPENDIX 2
Obtain Participant 
Number
X
Medical History
X
UC Disease History
X
Prior Medications
X
X
Concomitant 
Medications
X
X
X
X
X
X
Assessments after screening for 
change in concomitant medications 
(see Section 7.7)
UC Medications
X
X
X
X
X
X
Tobacco / e-cigarette 
Use
X
X
X
X
X
X
Assessments after screening for 
change in use
Review Eligibility 
Criteria
X
See Section 6 for details
Physical Examination
See Section 9.5.1 for details
Weight
X
X
X
X
X
Height
X
Vital Signs (HR, BP, 
Temperature [°C])
X
X
X
X
X
X
Complete Physical 
Examination
X
X
X
X
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Table 2-1:
Schedule of Activities for Year 1 (IM047029)
Procedure
Screening
(Days -28 
to -1)
Week 0
(Day 1)
Week 4
(Day 28)
Week 12
(Day 84)
Week 26
(Day 182)
Week 52
(Day 365)
Unscheduleda
Notes
Visit Window (± n Days)
7
7
7
14
Interim Physical 
Examination
X
X
Additional Screening 
Tests
12-lead ECG
X
See Section 9.5.3 for details
Examination of Ocular 
Fundus and Pulmonary 
Functionb
X
Cardiologist Clearance 
or 6-hour First Dose 
Observationc
X
X
Electronic Diary 
(eCOA)
Dispense and Train 
Participant on Electronic 
Daily Diary
X
Demographics and 
Subject Characteristics
X
Site Review of 
Electronic Daily Diary 
Compliance
X
X
X
X
X
X
Blood and Urine Testsd
See Section 9.5.4 for details
CBC and Differential 
Count
X
X
X
X
X
X
X
Blood test results from anytime 
within 30 days prior to starting first 
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Table 2-1:
Schedule of Activities for Year 1 (IM047029)
Procedure
Screening
(Days -28 
to -1)
Week 0
(Day 1)
Week 4
(Day 28)
Week 12
(Day 84)
Week 26
(Day 182)
Week 52
(Day 365)
Unscheduleda
Notes
Visit Window (± n Days)
7
7
7
14
Biochemistryd
X
X
X
X
X
X
X
dose of study intervention can be 
considered for screening process. 
Results must be documented, if 
obtained locally.  
Varicella IgG
X
Pregnancy Test - Serum 
or Urine beta-hCGe
X
X
See footnotes
FSHf
X
Optional. See footnotes
TDM Testg
X
Optional. See footnotes
Diagnostic Test for 
SARS-CoV-2
X
Participants must have a negative 
SARS-CoV-2 PCR test result prior to 
Day 1, in accordance with site 
standard practices 
Stool Collection
For Clostridium difficile 
Testing (and stool 
infectious screen)
X
Xh
Stool test results from anytime within 
30 days prior to starting first dose of 
study intervention can be considered 
for screening process. Results must 
be documented, if obtained locally.
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Table 2-1:
Schedule of Activities for Year 1 (IM047029)
Procedure
Screening
(Days -28 
to -1)
Week 0
(Day 1)
Week 4
(Day 28)
Week 12
(Day 84)
Week 26
(Day 182)
Week 52
(Day 365)
Unscheduleda
Notes
Visit Window (± n Days)
7
7
7
14
For Culture, Ova, and 
Parasitesi
X
or stool PCR - see footnotes
Endoscopy and Biopsiesj
Cohort 1 (Advanced 
Therapy-naïve Cohort)
X
X
Results from endoscopy 
(colonoscopy or sigmoidoscopy) 
performed within 60 days prior to 
first dose of study intervention may 
be considered for the screening 
process. Images must be documented 
to confirm severity. In the setting of 
historic (prior) endoscopy 
documentation, biopsy tissue will not 
be collected.   
Cohort 2 (Advanced 
Therapy-exposed 
Cohort)
X
X
Results from endoscopy performed 
within 60 days prior to first dose, 
may be considered for the screening 
process. Images must be documented 
to confirm severity.In the setting of 
historic (prior) endoscopy 
documentation, biopsy tissue will not 
be collected.
Additional Efficacy 
Assessmentsk
Site Calculates Modified 
Mayo Score
X
Xl
Xm
Required for eligibility assessment
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Ozanimod
Table 2-1:
Schedule of Activities for Year 1 (IM047029)
Procedure
Screening
(Days -28 
to -1)
Week 0
(Day 1)
Week 4
(Day 28)
Week 12
(Day 84)
Week 26
(Day 182)
Week 52
(Day 365)
Unscheduleda
Notes
Visit Window (± n Days)
7
7
7
14
Baseline (prior to flare) 
SF
X
PGA Collection
X
X
X
X
X
X
Physician-reported
RB Subscore
X
X
X
X
X
X
Recorded for 7 days prior to Day 1, 
daily for the first 12 weeks of the 
study, and 7 days prior to each study 
visit thereafter
SF Subscore
X
X
X
X
X
X
HRQOLn
IBDQ
X
X
X
X
X
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Ozanimod
Table 2-1:
Schedule of Activities for Year 1 (IM047029)
Procedure
Screening
(Days -28 
to -1)
Week 0
(Day 1)
Week 4
(Day 28)
Week 12
(Day 84)
Week 26
(Day 182)
Week 52
(Day 365)
Unscheduleda
Notes
Visit Window (± n Days)
7
7
7
14
Healthcare Resource 
Utilizationo
AE Reporting
Monitor AEs 
X
X
X
X
X
X
Monitor SAEs
X
X
X
X
X
X
X
COVID AEs
X
X
X
X
X
X
X
IP Supply
Dispense IP
Xp
X
X
X
X
X
Review Participant 
Compliance with IP
X
X
X
X
X
AE, adverse event; BP, blood pressure; beta-hCG, beta-subunit of human chorionic gonadotropin; CBC, complete blood count; COVID, coronavirus disease; 
ECG, electrocardiogram; eCOA, electronic clinical outcome assessment; EDC, electronic data capture; 
 FDO, first dose observation; FSH, follicle-stimulating hormone; Hb, hemoglobin; HR, heart rate; 
HRQOL, health-related quality of life; 
 IBDQ, Inflammatory Bowel Disease Questionnaire; IFN, interferon; 
IgG, immunoglobulin G; LFT, liver function test; PCR, polymerase chain reaction; PCR, polymerase chain reaction; PGA, Physician’s Global Assessment; 
RB, rectal bleeding; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; SAE, serious adverse event; SF, stool frequency; TDM, therapeutic drug 
monitoring;
 UC, ulcerative colitis;
 
 WOCBP, women of childbearing potential; 
 
a If required, an unscheduled visit can be planned anytime during the treatment period. Data regarding study procedures conducted at such unscheduled visits
(eg, blood, stool, and urine tests; safety assessments) will be documented in the EDC tool.
b Need for fundic examination and pulmonary function is dependent on specific risk factors outlined in the product label.
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c Need for 6-hour FDO is dependent on specific cardiac risk factors outlined in the product label. A cardiologist’s opinion is required in the setting of history of
cardiac arrest, cerebrovascular disease, uncontrolled hypertension, severe untreated sleep apnea, history of recurrent syncope or symptomatic bradycardia; 
pre-existing significant QT interval prolongation (QTc greater than 500 msec) or other risks for QT prolongation, and patients on medicinal products other than 
beta-blockers and calcium channel blockers that may potentiate bradycardia; patients on class Ia (eg, quinidine, disopyramide) or class III (eg, amiodarone, 
sotalol) antiarrhythmic medicinal products, which have been associated with cases of torsades de pointes in patients with bradycardia have not been studied with 
ozanimod.
d Complete list of clinical safety laboratory assessments is provided in Section 9.5.4.
e WOCBP only. Pregnancy test anytime within 7 days prior to day of study intervention initiation is permissable – if pregnancy test is done locally, it must be
documented.  
f Optional test of FSH level may be used to exclude childbearing potential in peri-menopausal females.
g For all biologics, the washout period is 8 weeks or 5 elimination half lives, which ever is shorter, but it may be waived with the demonstration of absent drug
levels on TDM assay.
i
Stool PCR panel may be performed as an alternative to stool culture if that is in routine clinical use at a site.
j
Endoscopy- and biopsy-related procedure details will be provided to the sites in a separate document/manual.
k A brief description about additional efficacy assessments is provided in Section 9.1.
l
Only for Cohort 1.
m Only for Cohort 2.
n A brief description about HRQOL assessments is provided in Section 9.1.2.2.
o A brief description about healthcare resource utilization assessments is provided in Section 9.10.
p Ozanimod titration will occur during the first 7 days of study intervention exposure, per label (Table 7.1-2). Participants will receive a phone call on Day 5
(when titrating their dose from 0.23 mg to 0.46 mg) and again on Day 8 (when titrating their dose from 0.46 mg to 0.92 mg) as a reminder about the dose 
adjustment.
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Table 2-2:
Schedule of Activities for Year 2 (IM047029)
Procedure
Week 104
EOT/ETa
(Day 728)
Week 116
PTFU
(Day 812)
Unscheduledb
Notes
Visit Window (± n Days)
14
14
Concomitant Medications 
X
X
Assess for change in concomitant medications (see 
Section 7.7)
UC Medications
X
X
Tobacco / e-cigarette vape use
X
X
Assess for change in use
Physical Examination
See Section 9.5.1 for details
Weight
X
X
Vital Signs (HR, BP, 
Temperature [°C])
X
X
Complete Physical 
Examination
X
Interim Physical Examination
X
Electronic Diary (eCOA)
Site Review of Electronic Daily 
Diary Compliance
X
X
X
Blood and Urine Testsc
See Section 9.5.4 for details
CBC and Differential Count
X
X
Biochemistryd
X
X
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Ozanimod
Table 2-2:
Schedule of Activities for Year 2 (IM047029)
Procedure
Week 104
EOT/ETa
(Day 728)
Week 116
PTFU
(Day 812)
Unscheduledb
Notes
Visit Window (± n Days)
14
14
Additional Efficacy 
Assessmentse
PGA Collection
X
X
Physician-reported
RB Subscore
X
X
Recorded for 7 days prior to each study visit 
SF Subscore
X
X
HRQOLf
IBDQ
X
X
Healthcare Resource 
Utilizationg
AE Reporting
Monitor AEs 
X
X
X
Monitor SAEs
X
X
X
COVID AEs
X
X
X
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Table 2-2:
Schedule of Activities for Year 2 (IM047029)
Procedure
Week 104
EOT/ETa
(Day 728)
Week 116
PTFU
(Day 812)
Unscheduledb
Notes
Visit Window (± n Days)
14
14
IP Supply
Dispense IP
X
Review Participant Compliance 
with IP
X
X
AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BP, blood pressure; CBC, complete blood count; eCOA, electronic clinical 
outcome assessment; COVID, coronavirus disease; EDC, electronic data capture; 
 EOT, end of treatment; ET, early termination; 
 HR, heart rate; HRQOL, health-related quality of life; 
 
 IBDQ, Inflammatory Bowel Disease Questionnaire; INR, international normalized ratio; IP, investigational product; PGA, Physician’s Global 
Assessment; PTFU, post-treatment follow-up; RB, rectal bleeding; 
 SAE, serious adverse event; 
SF, stool frequency; 
 UC, ulcerative colitis; 
 
 ULN, upper limit of normal;
 
a For participants who prematurely discontinue from the study, if possible, the EOT visit and follow-up visit should be conducted so that data can be collected at 
the time of study discontinuation and follow-up and for any further evaluations that need to be completed.
b If required, an unscheduled visit can be planned anytime during the treatment period. Data regarding study procedures conducted at such unscheduled visits (eg, 
blood, stool, and urine tests; safety assessments) will be documented in the EDC tool.
c Complete list of clinical safety laboratory assessments is provided in Section 9.5.4.
d Per physician discretion, INR may be collected if ALT or AST > 3 × ULN.
e A brief description about additional efficacy assessments is provided in Sections 9.1.
f A brief description about HRQOL assessments is provided in Section 9.1.2.2.
g A brief description about healthcare resource utilization assessments is provided in Section 9.10.
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3
INTRODUCTION
Ozanimod (RPC1063, BMS-986374) is a sphingosine 1-phosphate (S1P) receptor modulator that 
has been approved in the US, Europe, and other countries for the treatment of ulcerative colitis
(UC) and multiple sclerosis (MS). The US Food and Drug Administration (FDA) approval of 
ozanimod (trade name Zeposia®) for the treatment of moderate to severely active UC was received 
in May 2021 and was based on data from the pivotal Phase 3 True North study (RPC01-3101) and 
supported by data from the Phase 2 Touchstone Study (RPC01-202), which evaluated ozanimod 
as an induction and maintenance therapy vs placebo in adult patients with moderate to severe 
UC.1,2
3.1
Study Rationale
This prospective, open-label, Phase 4 study is designed to explore the safety, efficacy, effects on 
quality of life (QOL), and biomarker response of ozanimod in participants with moderate to 
severely active UC in clinical practice.
The study population will be consistent with the product label, so that this study may generate data 
that are directly relevant to the labeled indication and that may be used to further inform the clinical 
use of ozanimod in this study population.
The study will include 2 cohorts:

Cohort 1: Participants with moderate to severely active UC who have not been exposed to 
biologics or immunomodulators for the treatment of UC (ie, advanced therapy-naïve).

Cohort 2: Participants with moderate to severely active UC who have been exposed to a single 
mechanism of action of biologics for the treatment of UC (ie, advanced therapy-exposed).
This study will generate additional data on the effect of ozanimod treatment, including (but not 
limited to) the following: 

Characterization of early response (improvement in signs and symptoms of UC within the first 
4 weeks), including rectal bleeding (RB), stool frequency (SF), urgency, and abdominal 
symptoms. 

Characterization of the endoscopic and histologic response to ozanimod at Week 12 in an 
advanced therapy-naïve cohort.

Characterization of the endoscopic and histologic response to ozanimod at Week 26 in an 
advanced therapy-exposed cohort. 

Characterization of the long-term safety of ozanimod over the duration of the study.

Patient-reported outcome (PRO) measures, including impact on disease-specific QOL and 
symptoms, fatigue, patient satisfaction with treatment, and work productivity.

Characterization of the effect of ozanimod treatment on biomarkers of disease activity used in 
clinical practice, 
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3.2
Background
3.2.1
Ulcerative Colitis
UC is a chronic gastrointestinal (GI) inflammatory disorder that involves the surface mucosa, the 
crypt epithelium, and the submucosa of the colon.3,4 The etiology of UC is multifactorial, but likely 
includes a dysregulated mucosal immune response against commensal nonpathogenic bacteria of 
the colon, resulting in bowel inflammation.5
Patients with UC suffer from diarrhea, RB, weight loss, abdominal pain, and fever.3,4 The 
pathology of UC is characterized by a life-long chronic course of exacerbations and remissions. In 
the case of severe UC, the bowel wall may become thinned, the mucosa denuded, and the 
inflammation may extend to the serosa, leading to dilation, toxic megacolon, and perforation.6
Toxic megacolon, although uncommon, may require an urgent colectomy to avoid perforation, 
peritonitis, and sepsis. Within 10 years of diagnosis, 19.9% of patients with UC have undergone 
colectomy.7
In addition, patients with UC have an increased risk of carcinoma when compared with the general 
population. The estimated risk of colorectal carcinoma increases as the duration and extent of 
disease increases, from 2% in patients with UC for 10 years, to 8% in patients with UC for 20 years, 
and to 18% in patients with UC for 30 years.8,9
The overall goal of treatment for patients with active UC is to induce and maintain both remission 
and mucosal healing.10 Treatment of UC consists of anti-inflammatory and immunosuppressive 
therapies that are chosen to maximize efficacy while minimizing toxicity. The therapy chosen is 
therefore dependent on the patient’s disease severity and their response to therapy.10,11 Although 
agents used to treat mild to moderate UC are generally well -tolerated, as the severity of UC disease 
increases, so too do the potential toxicities related to the medications required to manage the 
disease. Treatment for mild to moderate UC typically starts with topical agents (5-aminosalicylate 
[5-ASA] or corticosteroids administered via suppository or enema). In patients unresponsive to 
local therapy or in those with more severe or more extensive disease, oral 5-ASA, such as 
mesalamine, olsalazine, sulfasalazine, and balsalazide, with or without antibiotics, is commonly 
required.10,12 Initially, up to 90% of patients with mild to moderate UC can maintain their 
remission status using oral administration of 5-ASA, which is generally safe and well -tolerated.10
For those patients who do not respond or lose response to treatment with 5-ASA or for those with 
more severe and extensive disease at presentation, corticosteroids are generally the first-line 
treatment for inducing disease remission. Although effective in inducing disease remission, 
treatment with corticosteroids is associated with multiple adverse effects, including weight gain, 
insomnia, mood swings, osteoporosis, scalp hair loss or facial hair growth, moon face, cataracts, 
acne, hypertension, diabetes, appearance of stretch marks, and increased susceptibility to 
infections and bruising.
For those patients who are unresponsive to, or intolerant of corticosteroids, immunomodulators, 
including azathioprine (AZA), 6-mercaptopurine, and cyclosporine12 are used to induce and/or 
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maintain remission.11 However, these medications have multiple limitations, including toxicities. 
The use of 6-mercaptopurine and AZA can result in neutropenia, pancytopenia, pancreatitis, 
nephrotoxicity, hepatotoxicity, and,
in rare cases, Epstein–Barr virus (EBV) and 
non-EBV-associated lymphoma, as well as the uniformly fatal hepatosplenic T cell 
lymphoma.13,14,15 A Cochrane systematic review concluded that available medical trials do not 
support the use of methotrexate for short- or long-term remission of active UC.16
Updated guidance on treating UC in adult patients emphasizes the role of biologic agents, 
including infliximab, adalimumab, golimumab (anti-tumor necrosis factor [TNF] therapies), 
vedolizumab (anti-integrin antibody), tofacitinib (Janus kinase [JAK] inhibitor), and ustekinumab 
(anti-interleukin [IL]–12/23 antibody).17,18 However, up to one-fifth of patients receiving 
anti-TNF agents may not demonstrate an initial response,17 and an additional 10% to 20% may 
lose response every year despite an initial benefit.19,20 The anti-TNF agents also come with the 
potential risk of infusion reactions or injection site reactions, infections, malignancy, 
autoimmunity, and psoriasis known for that medication class. Although tofacitinib is administered 
orally, the US FDA has approved new warnings on an increased risk of blood clots and death with 
the dose of tofacitinib that is used in patients with UC.21 Therefore, there remains an unmet need 
for a UC treatment that is effective, well-tolerated, and orally active. In this scenario, the US FDA 
approval of ozanimod, a selective S1P receptor modulator, as once daily (QD) per oral (PO)
treatment in adults with moderate to severely active UC could help to fill a treatment gap in this 
disease.
3.2.2
Ozanimod 
Ozanimod is a small molecule compound that selectively binds with high affinity to S1P receptors 
1 and 5. In vitro, ozanimod has little activity on the other S1P receptors, showing half-maximal 
EC50 > 10,000 nM for S1P2, > 5000 nM for S1P3, and > 2000 nM for S1P4.
Many cell types express S1P1, including vascular endothelial cells, brain cells, and lymphocytes. 
Stimulation (agonism) of this receptor results in biological activities that include lymphocyte 
retention in peripheral lymphoid organs (eg, lymph nodes and GI Peyer’s patches), which can 
result in reversible systemic reduction in circulating lymphocytes.22 Given the immune-mediated 
inflammation in UC, prevention of circulation of disease-exacerbating, self-reactive lymphocytes 
to the gut is likely to have salutary immunomodulatory effects with a consequent dampening of 
disease processes.
An open-label, pharmacokinetic (PK)/pharmacodynamic (PD) study in patients with MS examined 
the effect of ozanimod on circulating leukocyte subsets.23 Ozanimod 0.92 mg demonstrated greater 
reduction in CD4+ (helper) T cells than CD8+ (cytotoxic) T cells. Additionally, CD4+ and CD8+ 
central memory T cells were reduced more than CD4+ and CD8+ effector memory T cells, 
respectively. There was minimal impact on monocytes and natural killer cells. It was hypothesized 
that the differential impact on leukocyte subpopulations may provide inhibition of inflammation 
that may lead to pathophysiology in MS, while allowing for maintenance of immune function. 
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Leukocyte subpopulations in patients with UC who have received ozanimod have not yet been 
studied.
Ozanimod is extensively metabolized in humans to form a number of circulating active 
metabolites, including 2 major active metabolites (CC112273 [also referred to as RP112273] and 
CC1084037 [also referred to as RP100798]); other active metabolites, including RP101988, 
RP101075, RP112289, and RP101442; and one circulating inactive metabolite, RP101124. 
Ozanimod and its active metabolites have similar chemical structures, activity, and selectivity for 
S1P1 and S1P5 receptors. Following multiple -dose administration of ozanimod in healthy 
subjects, approximately 94% of circulating total active drug exposure was represented by 
ozanimod (6%), CC112273 (73%), and CC1084037 (15%).
3.2.3
Ozanimod in UC
In the True North study, a total of 645 participants were randomly assigned 2:1 to either ozanimod 
0.92 mg QD PO (n = 429) or placebo (n = 216). The primary induction endpoint of clinical 
remission at Week 10 (18% vs 6%; P<0.0001, for ozanimod vs placebo, respectively) was met, as 
were the key secondary endpoints, including clinical response (48% vs 26%; P<0.0001), 
endoscopic improvement (27% vs 12%; P<0.0001),
and endoscopic-histologic mucosal 
improvement (13% vs 4%; P<0.001). Decreases in RB and SF subscores were observed as early 
as Week 2 (ie, one week after participants completed the required 7-day dosage titration) in 
participants treated with ozanimod.
A total of 457 participants who received ozanimod in the induction period or in an open-label arm 
and achieved clinical response at Week 10 were re-randomized 1:1 and were treated with either 
ozanimod 0.92 mg QD PO (n = 230) or placebo (n = 227) for 42 weeks, for a total of 52 weeks of
treatment. The primary endpoint of clinical remission at Week 52 was met (37% vs 19%; 
P<0.0001), as were the key secondary endpoints, including clinical response (60% vs 41%;
P<0.0001), endoscopic improvement (46% vs 26%; P<0.001), corticosteroid-free clinical 
remission (32% vs 17%; P<0.001), and endoscopic-histologic mucosal improvement (30% vs 
14%; P<0.001). 
The safety and tolerability results from the induction and maintenance periods of the True North 
study demonstrated that ozanimod at a dose of 0.92 mg daily for 8 weeks or for 52 weeks, 
respectively, was well -tolerated and had an acceptable safety profile in patients with moderate to 
severely active UC. There was no evidence of new patterns of treatment-emergent adverse events 
(TEAEs), increased incidence of TEAEs, or unique TEAEs with longer exposure to ozanimod. 
Overall, these results were consistent with safety findings that have previously been reported 
regarding ozanimod therapy in Phase 3 trials involving patients with MS.
A detailed description of the efficacy and safety of ozanimod is provided in the product label.
3.3
Benefit/Risk Assessment
More detailed information about the known and expected benefits and risks and reasonably 
anticipated adverse events (AEs) of ozanimod may be found in the product label.
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3.3.1
Risk Assessment
Table 3.3.1-1:
Risk Assessment
Potential Risk of Clinical Significance
Summary of Data/
Rationale for Risk
Mitigation Strategy
Study Intervention(s)
Infections (eg, herpes viral infection, 
cryptococcal infection, PML)
Per Zeposia product label
Per Zeposia product label
Prior and concomitant treatment with 
anti-neoplastic, immunosuppressive, or 
immune-modulating therapies
Per Zeposia product label
Per Zeposia product label
Vaccinations
Per Zeposia product label
Per Zeposia product label
Bradyarrhythmia and AV conduction 
delays
Per Zeposia product label
Per Zeposia product label
Liver injury
Per Zeposia product label
Per Zeposia product label
Fetal risk
Per Zeposia product label
Per Zeposia product label
Increased blood pressure
Per Zeposia product label
Per Zeposia product label
Respiratory effects
Per Zeposia product label
Per Zeposia product label
Macular edema (eg, in patients with a 
history of uveitis or diabetes mellitus)
Per Zeposia product label
Per Zeposia product label
Posterior reversible encephalopathy 
syndrome
Per Zeposia product label
Per Zeposia product label
Unintended additive immunosuppressive 
effects from prior treatment with 
immunosuppressive or 
immune-modulating drugs
Per Zeposia product label
Per Zeposia product label
Immune system effects after stopping 
ozanimod
Per Zeposia product label
Per Zeposia product label
Study Procedures
Endoscopy and biopsies
While endoscopy is considered 
to be a very safe procedure, rare 
complications may include 
perforation, bleeding, and 
infection. Risk of bleeding 
complications after an 
endoscopy is increased if the 
procedure involves biopsy
Per institutional 
protocol/investigator discretion
Other (if Applicable)
SARS-CoV-2 infection
Current ongoing pandemic
Vaccination prior to enrollment 
is encouraged. The risk of 
enrolling participants with active 
SARS-CoV-2 infection will be 
minimized by testing at 
screening. General risk 
mitigation against SARS-CoV-2 
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Table 3.3.1-1:
Risk Assessment
Potential Risk of Clinical Significance
Summary of Data/
Rationale for Risk
Mitigation Strategy
infection will be implemented in 
accordance with the site’s 
monitoring and prevention 
control measures. 
 
 
 
AV, atrioventricular; PML, progressive multifocal leukoencephalopathy; SARS-CoV-2, severe acute respiratory 
syndrome coronavirus 2
3.3.2
Benefit Assessment
Ozanimod has been approved in the US, Europe, and other countries for the treatment of moderate 
to severely active UC. Data from the Phase 3 True North study suggests that ozanimod is 
efficacious in the treatment of moderate to severe UC, with an acceptable safety profile. In the 
True North study, a significantly greater proportion of patients who received ozanimod achieved 
the primary induction endpoint (ie, clinical remission) as well as key secondary endpoints (ie, 
clinical response, endoscopic improvement, and endoscopic-histologic mucosal improvement)
compared with those who received placebo. Longer exposure to ozanimod did not lead to any new 
safety concerns.
As this is an open-label study, participants are not at risk of receiving placebo, and ozanimod 
therapy is expected to potentially induce clinical remission, endoscopic response and
improvement, histological improvement, and health-related quality of life (HRQOL) in this target 
patient population.
3.3.3
Overall Benefit/Risk Conclusion
Taking into account the measures taken to minimize risk to participants in this study, the potential 
risks identified in association with ozanimod are justified by the anticipated benefits that may be 
afforded to participants with moderate to severe UC.
The Sponsor will evaluate the risk/benefit profile of the study on an ongoing basis. This evaluation 
will be based on all available data with particular attention to i) AEs or other safety trends in this 
or any other clinical study of ozanimod whose character, severity, and/or frequency suggest that 
participants would be exposed to an unreasonable and significant risk of illness or injury; (ii) new 
nonclinical data suggesting unreasonable and significant risk of illness or injury.
If such evaluation suggests that the risk/benefit profile of the study has become unfavorable to 
participants, the Sponsor will pause enrollment and/or treatment until further evaluation of data 
can take place on potential actions. Such actions may include (but are not limited to) study 
continuation, substantial amendment, or termination of the study.
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4
OBJECTIVES AND ENDPOINTS
The study objectives and endpoints are listed in the following 3 tables:

Table 4-1: Objectives and endpoints that are specific to Cohort 1.

Table 4-2: Objectives and endpoints that are specific to Cohort 2.

Table 4-3: Objectives and endpoints that are common for both Cohort 1 and Cohort 2.
Additional endpoints and analyses will be described in the statistical analysis plan (SAP), the 
Endoscopy Image Review Charter, and/or the Histopathology Image Review Charter (as 
applicable). Selected endpoint definitions are provided in APPENDIX 6.
Table 4-1:
Objectives and Endpoints Specific to Advanced Therapy-naïve 
Cohort (Cohort 1)
Objectives
Endpoints
Primary
Primary

To explore the efficacy of ozanimod in 
inducing clinical response in the advanced 
therapy-naïve cohort.

Clinical response at Week 12, as measured by modified 
Mayo score.
Secondary
Secondary

To explore the efficacy of ozanimod in the 
advanced therapy-naïve cohort.

Clinical remission at Week 12, as measured by modified 
Mayo score.

Endoscopic response at Week 12.

Endoscopic improvement at Week 12.

Histological improvement at Week 12.

To explore the effects of ozanimod on 
disease-specific HRQOL in the advanced 
therapy-naïve cohort.

Change in the IBDQ total score from baseline to
Week 12.

IBDQ response (change in total score [≥16 points] from 
baseline to Week 12).

IBDQ remission (total score [≥170 points]) at Week 12.
 IBDQ, Inflammatory Bowel Disease Questionnaire.
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Table 4-2:
Objectives and Endpoints Specific to Advanced Therapy-exposed 
Cohort (Cohort 2)
Objectives
Endpoints
Primary
Primary

To explore the efficacy of ozanimod in 
inducing clinical response in the advanced 
therapy-exposed cohort.

Clinical response at Week 26, as measured by modified 
Mayo score.
Secondary
Secondary

To explore the efficacy of ozanimod in the 
advanced therapy-exposed cohort.

Clinical remission at Week 26, as measured by modified 
Mayo score.

Endoscopic response at Week 26.

Endoscopic improvement at Week 26.

Endoscopic remission at Week 26.

Histological improvement at Week 26.

Histological remission at Week 26.

Change in the IBDQ total score from baseline to 
Week 26.

IBDQ response (change in total score [≥16 points] from 
baseline to Week 26).

IBDQ remission (total score [≥170 points]) at Week 26.

Corticosteroid-free clinical remission at Week 26, as 
measured by modified Mayo score.

HEMI at Week 26.
HEMI, histo-endoscopic mucosal improvement; IBDQ, Inflammatory Bowel Disease Questionnaire. 
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Table 4-3:
Additional Objectives and Endpoints Common for both the 
Advanced Therapy-naïve Cohort (Cohort 1) and the Advanced 
Therapy-exposed Cohort (Cohort 2) after Week 26
Objectives
Endpoints
Secondary
Secondary

To explore the safety and tolerability of
ozanimod in the advanced therapy-naïve cohort
and the advanced therapy-exposed cohort.

Number and proportion of participants experiencing the
following:

AEs.

SAEs.

AEs and SAEs, including AEIs and other select
AEs, leading to discontinuation from the study
intervention and the study.

Clinical laboratory values.

To explore the long-term durability of response
to ozanimod in the advanced therapy-naïve
cohort and the advanced therapy-exposed
cohort.

Clinical remission by partial Mayo score at Weeks 52
and 104.

Corticosteroid-free clinical remission by partial Mayo
score at Weeks 52 and 104.

Clinical response by partial Mayo score at Weeks 52
and 104.
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Table 4-3:
Additional Objectives and Endpoints Common for both the 
Advanced Therapy-naïve Cohort (Cohort 1) and the Advanced 
Therapy-exposed Cohort (Cohort 2) after Week 26
Objectives
Endpoints
AEI, adverse event of interest; 
 
 
 SAE, serious adverse event; 
 
 
5
STUDY DESIGN
5.1
Overall Design
Study IM047029 is a Phase 4, prospective, non-randomized, open-label, multicenter clinical study
designed to explore the safety, efficacy, effects on QOL, and biomarker response of ozanimod 
0.92 mg QD PO administration in participants with moderate to severely active UC in clinical 
practice.
This clinical study will evaluate ozanimod 0.92 mg QD PO in multiple UC disease subtypes, and 
with 2 specific cohorts as described in Section 3.1 and Figure 5.1-1.
Participants will undergo screening evaluations to determine eligibility as indicated in the SOA;
see Table 2-1). Participants must meet the eligibility criteria outlined in Section 6 in order to enter 
the treatment period. Participants must have moderate to severely active UC, defined as a score of 
4 through 9 on the 9-point modified Mayo score, in order to enter the treatment period. 
Assessments of medical and UC disease history, prior medications, concomitant and UC 
medications, tobacco/e-cigarette use, baseline (prior to flare) SF, physical examinations, 12-lead 
electrocardiograms (12-lead ECGs), blood, stool, and urine sample collections, endoscopies with 
biopsies, Physician’s Global Assessment (PGA) ratings, PRO and HRQOL instruments, and other 
study procedures will be performed as indicated in the SOA (Table 2-1, Table 2-2). Additional 
risk-based assessment of cardiac conduction abnormalities, pulmonary function, and/or visual 
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acuity (including evaluation of the fundus and macula) may also be performed during screening 
and as appropriate thereafter.
Disease activity assessment for the purpose of eligibility and evaluation of the primary endpoints 
in both cohorts will be performed using the modified Mayo score instrument (APPENDIX 3). The 
modified Mayo score will be calculated using data from the following sources: baseline (prior to 
flare) SF (patient-reported and recorded by the investigator), daily assessments of SF and RB
(PROs recorded in the participant’s electronic daily diary), and assessment of mucosal 
inflammation at endoscopy. The PGA of disease activity (physician-reported) will also be captured 
at various time points (Table 2-1, Table 2-2).
Screening will include the assessment of pre-existing cardiac conduction abnormalities by 12-lead 
ECG. Investigators should consider cardiology consultation if conduction abnormalities are 
identified on the 12-lead ECGs, or if the participant is receiving concomitant medications 
(see Table 7.7-2) that have the potential to decrease their heart rate (HR).
Participants who have a history of uveitis, diabetes mellitus, macular edema or other retinal disease
will have ophthalmic evaluation of the fundus, including the macula, prior to study intervention, 
in order to exclude macular edema.
Antibodies to varicella zoster virus (VZV) will be tested during the screening period. Participants 
must have documentation of positive VZV immunoglobulin G (IgG) antibody status at screening 
or complete VZV vaccination prior to the first study intervention administration.
1) No live or live-attenuated vaccine within 4 weeks prior to study intervention administration.
Pregnancy will be excluded in women of childbearing potential (WOCBP) prior to the first 
study intervention administration. 
All eligible participants will receive open-label ozanimod 0.92 mg QD PO, per product label,
during the treatment period (Table 7.1-1). Ozanimod titration will occur during the first 7 days of 
study intervention exposure, per label (Table 7.1-2). Once study intervention (ie, ozanimod) has 
been titrated up to 0.92 mg QD PO (Day 8), further dose escalation is not allowed.
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The study design schematic is presented in Figure 5.1-1.
Figure 5.1-1:
Study Design Schema
E, endoscopies and biopsies; ES, endoscopic subscore; EOT, end of treatment.
a For participants who prematurely discontinue from the study, if possible, the EOT visit and follow-up visit should be conducted so that data can be collected at 
the time of study discontinuation and follow-up and for any further evaluations that need to be completed. 
b Screening endoscopy (colonoscopy or sigmoidoscopy) may be performed within 60 days prior to the first study intervention administration. Photographic 
evidence of ES >2 must be available for study inclusion, as per eligibility criteria. In the event that historic endoscopic data is used as a part of screening, historic 
histopathologic tissue will not be needed to be collected.
c Ozanimod titration will occur during the first 7 days of study intervention exposure, per label (Table 7.1-2). Participants will receive a phone call on Day 5 
(when titrating their dose from 0.23 mg to 0.46 mg) and again on Day 8 (when titrating their dose from 0.46 mg to 0.92 mg) as a reminder about the dose 
adjustment. If required, an unscheduled visit can be planned anytime during the treatment period. Data regarding study procedures conducted at such unscheduled 
visits (eg, blood, stool, and urine tests; safety assessments) will be documented in the EDC tool.
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5.1.1
Data Monitoring Committee and Other Committees
A Data Monitoring Committee or other review committee will not be used in the study.
5.2
Number of Participants
It is estimated that approximately 250 screened participants in Cohort 1 (advanced therapy-naïve 
cohort) will be required to achieve 150 treated participants. Similarly, for Cohort 2 (advanced 
therapy-exposed cohort), it is estimated that approximately 165 participants will be required to 
achieve 100 treated participants. These enrollment estimates assume a screen failure rate of 
approximately 40% in each cohort.
If the screen failure rate is higher than expected, enrollment will remain open until the required 
number of treated participants in each cohort is achieved.
5.3
End of Study Definition
The start of the trial is defined as the first participant’s first visit. 
The end of the trial is defined as the last participant’s last visit or scheduled procedure shown in 
the SOA (Table 2-2) for the last participant. 
Study completion is defined as the final date on which data for the primary endpoint were or are
expected to be collected, if this is not the same.
A participant is considered to have completed the study if he/she has completed the last procedure 
shown in the SOA (Table 2-2).
5.4
Scientific Rationale for Study Design
Ozanimod is approved in the US for the treatment of moderate to severely active UC in adults. 
This approval was based on safety and efficacy data from the induction and maintenance periods 
of the Phase 3 True North study (NCT02435992)24 and supported by safety and efficacy data from 
the Phase 2 Touchstone study (NCT01647516)25 and by safety data from 2 randomized, 
double-blind, double-dummy, active comparator-controlled clinical trials in patients with 
relapsing forms of MS (NCT02294058 and NCT02047734).26,27,28,29 The eligibility criteria for 
the cohorts within this clinical protocol will be consistent with the approved product label (in the 
US and other countries, as applicable). The cohorts within this clinical protocol will generate novel 
data on safety, efficacy, effects on QOL, and biomarker response of ozanimod, as listed in 
Section 3.1. Consequently, this study will extend the evidence base supporting ozanimod, and 
these data may be used to further inform the clinical use of ozanimod in the approved UC patient 
population. 
The results of the True North and Touchstone studies demonstrate that equivalence between 
ozanimod and placebo is no longer present for the multiplicity of controlled endpoints evaluated 
in those clinical trials.28,29 Consequently, Cohort 1 and Cohort 2 will not use placebo control. 
The primary endpoint of Cohort 1 and Cohort 2 is assessed using the modified Mayo score 
instrument, which is a composite of the Mayo score SF, RB, and endoscopic findings subscores. 
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Consistent with regulatory draft guidance, the instrument is modified from the original description 
of the Mayo score by the exclusion of friability from an ES of 1 (ES = 1), and the exclusion of the 
Mayo score’s PGA.3,30,31 Permutations of the Mayo score are listed in APPENDIX 3. Clinical 
response, the primary endpoint of Cohort 1 and Cohort 2, has been accepted as a primary endpoint 
in clinical trials that have supported prior approvals of treatments for UC.31 Additional endpoints 
based on permutations of the Mayo score that will be evaluated in Cohort 1 and Cohort 2 are listed 
in Table 4-1, Table 4-2, and Table 4-3.
Additional instruments to be assessed in Cohort 1 and Cohort 2 will include (but not be limited to) 
the following: Geboes score, 
 
 Inflammatory Bowel Disease Questionnaire (IBDQ), 
 
 
 
 
(Section 2). 
Taken together, the data collected using the instruments described above will facilitate a 
comprehensive exploration of the effect of ozanimod on UC disease activity (clinical, endoscopic,
and histologic), additional UC symptoms, QOL, fatigue, work productivity, and treatment 
satisfaction.
5.5
Justification for Dose
Ozanimod 0.92 mg QD PO has been approved in the US, Europe, and other countries for the 
treatment of moderate to severely active UC, following a 7-day titration with 0.23 mg and 0.46 mg 
QD PO.1,2
6
STUDY POPULATION
Prospective approval of protocol deviations to the recruitment and enrollment criteria, also known 
as protocol waivers or exemptions, is not permitted.
6.1
Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
1) Signed Written Informed Consent
a) Participants must have signed and dated an Institutional Review Board (IRB)/Independent 
Ethics Committee (IEC)-approved written informed consent form (ICF) in accordance with 
regulatory, local, and institutional guidelines. This must be obtained before the 
performance of any protocol-related procedures that are not part of normal patient care.
2) Type of Participant and Target Disease Characteristics
a) A diagnosis of UC, with signs and symptoms consistent with UC for at least 3 months prior 
to the first study intervention administration.
b) Moderate to severely active UC disease activity, defined as a modified Mayo score of 
4 through 9, inclusive, with the following minimum subscores:
i)
An SF subscore ≥1, 
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AND
ii) An RB subscore ≥1, 
AND
iii) An ES ≥2 (endoscopy performed within 60 days of the first study intervention
administration).
c) Must be up to date with screening for colorectal neoplasia and surveillance for dysplasia, 
according to local standard of care.
d) Must have documentation of positive VZV IgG antibody status at screening or complete 
VZV vaccination prior to the first study intervention administration.
e) Report of a previous colonoscopy that documents extent of disease (Note: If performed in 
the prior 60 days, this data may be used for study inclusion.)
f)
UC disease distribution (including ulcerative proctitis) extending proximal to the rectum 
(ie, approximately ≥5 cm from anal margin).
3) Age of Participant
a) Participant must be over 18 years of age (or the legal age of consent in the jurisdiction in 
which the study is taking place) at the time of signing the informed consent.
4) Cohort 1 (Advanced Therapy-naïve Cohort): Disease Distribution and Prior UC 
Medication Exposure
In order to participate in Cohort 1, a participant must meet the eligibility criteria outlined in 
this inclusion criterion (IC) and must not meet the eligibility criteria outlined in IC 5.
a) Participants must be naïve to 6-mecaptopurine/AZA and any biologics (see IC 5[a] for list)
for any other medical indication, as well as UC.
5) Cohort 2 (Advanced Therapy-exposed Cohort): Disease Distribution and Prior UC 
Medication Exposure
In order to participate in Cohort 2, a participant must have failed only one mechanism of 
action of biologics.
a) Documentation of an inadequate response, loss of response, or intolerance to a treatment 
course of one class of approved biologics (and should not have been treated with additional 
classes of approved biologics), including:
i)
Anti-TNF agents (eg, infliximab, adalimumab, golimumab, certolizumab, anti-TNF 
biosimilars).
ii) Anti-integrin inhibitors (eg, vedolizumab).
iii) Anti-IL-12p40 biologics (eg, ustekinumab).
iv) Anti-IL-23p19 biologics (eg, mirikizumab, risankizumab).
v) Other biologics that may become approved for clinical use in this UC study during the 
course of the study (please discuss with Medical Monitor).
b) Not Applicable Per Protocol Amendment 01: Patient may have been previously treated 
with 6-mercaptopurine/AZA, but not concomitantly over the course of the study, and not 
for at least 30 days prior to the first study intervention administration.
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c) Biologic agents should be discontinued at least 8 weeks prior or at least 5 elimination half 
lives prior to study intervention initiation, whichever is shorter. Washout period may be 
waived with the demonstration of absent drug levels on a therapeutic drug monitoring 
(TDM) assay.
d) 6-mercaptopurine/AZA or methotrexate: 
i)
Participant may have been previously treated: with 6-mercaptopurine/AZA or 
methotrexate.
ii) Participant may not take these agents concomitantly over the course of the study.
iii) These agents must be discontinued prior to day of starting study intervention.
6) Dose Stabilization and Prohibited Concomitant Medications
a) Compliance with the washout periods for prohibited concomitant medications, as listed in 
Table 7.7-1.
b) Must meet the dose stabilization criteria for permitted concomitant medications, as listed 
in Table 7.7-3.
7) Reproductive Status

Investigators shall counsel WOCBP participants 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 Participants:
i)
Women who are not of childbearing potential are exempt from contraceptive 
requirements. Evidence to support this status must be included in source documents.
ii) WOCBP must have a negative highly sensitive serum or urine pregnancy test 
(minimum sensitivity of 25 IU/L or equivalent units of human chorionic gonadotropin 
[hCG]) during the baseline as outline in the SOA (Section 2).

The investigator is responsible for the review of medical history, menstrual history, and recent 
sexual activity to decrease the risk for inclusion of a woman with an early undetected 
pregnancy.
iii) WOCBP must agree to follow the instructions for method(s) of contraception defined 
in APPENDIX 4, as described below, and included in the ICF.
iv) WOCBP are permitted to use hormonal contraception methods (as described in 
APPENDIX 4).
v) A female participant 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 that is highly effective (with a 
failure rate of < 1% per year), with low user dependency, as described in 
APPENDIX 4, during the intervention period and for at least 90 days, and agrees 
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not to donate eggs (ova, oocytes) for the purpose of reproduction for the same time 
period.
6.2
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
1) Medical Conditions
a) Recent (within 6 months of screening) myocardial infarction, unstable angina, stroke, 
transient ischemic attack, decompensated heart failure requiring hospitalization, or New 
York Heart Association Class III/IV heart failure.
b) Presence of Mobitz type II second- or third-degree atrioventricular (AV) block, sick sinus 
syndrome, or sino-atrial block, unless the participant has a functioning pacemaker.
c) Severe untreated sleep apnea.
d) Current macular edema. (Note: Participants with diabetes, or a history of uveitis, retinal 
disease, or previous macular edema must have an ophthalmic evaluation of the fundus, 
including the macula, prior to the first study intervention administration.)
e) Current active infection, and/or any infection requiring oral antibiotics within 14 days of 
screening, or intravenous (IV) antibiotics within 30 days of screening.
f)
Any major infection that required hospitalization.
g) Immunodeficient state (not including previously mentioned immunosuppressants) leading 
to increased risk of opportunistic infections.
h) A history of cancer within 5 years, including solid tumors and hematological malignancies 
(except basal cell carcinoma or squamous cell carcinoma of the skin that have been fully 
treated, or cervical dysplasia or carcinoma in situ that have been fully treated).
i)
Severe hepatic impairment (Child-Pugh Class C).
2) UC-related Exclusion Criteria
a) Participant has a current diagnosis of Crohn’s disease (CD), indeterminate colitis, radiation 
colitis or ischemic colitis, a monogenic cause of UC-like intestinal inflammation, colonic 
diverticulitis, or an alternative diagnosis that explains their colonic inflammation. 
b) Current or recent (within 3 months of screening) evidence of fulminant colitis, toxic 
megacolon, or bowel perforation.
c) Current need for, or anticipated need for, surgical intervention for UC during the course of 
the study.
d) Extensive colonic resection or current stoma.
e) Colonic dysplasia that has not been removed.
f)
Previous or current use of JAK inhibitors (eg, tofacitinib, filgotinib).
g) Not applicable per Protocol Amendment 1: UC involving the rectum only (UC proctitis).
h) Women who are pregnant, planning on becoming pregnant during the study, breastfeeding, 
or who have a positive serum or urine beta-hCG test during screening or on Day 1.
3) Not applicable per Protocol Amendment 1: Reproductive Satus
a) Women who are pregnant, planning on becoming pregnant during the study, breastfeeding, 
or who have a positive serum or urine beta-hCG test during screening or on Day 1. 
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4) Prior/Concomitant Therapy
a) Prior participation in an ozanimod clinical trial.
b) Prior exposure to ozanimod or other S1P receptor modulators.
c) Current immunomodulators for the treatment of UC.
d) Previous or current JAK inhibitors for the treatment of UC.
e) Current biologics for the treatment of UC.
f)
Current use of a monoamine oxidase inhibitor.
g) Live or live-attenuated vaccine within 4 weeks prior to study intervention administration.
h) Current or recent (without B cell recovery) use of alemtuzumab.
i)
Current use of beta interferon.
j)
Current use of glatiramer acetate.
Note: A detailed summary of prohibited concomitant medications and washout periods is listed 
in Table 7.7-1.
5) Physical and Laboratory Test Findings
If any of the following stool or blood tests were performed in the prior 30 days and can be 
documented, this data may be used for study inclusion.
a) Evidence of organ dysfunction or any clinically significant deviation from normal in 
physical examination, vital signs, 12-lead ECGs, or clinical laboratory determinations 
beyond what is consistent with the target population.
b) Positive stool test for Clostridium difficile. If positive, participants may be rescreened after 
appropriate treatment and retested no earlier than 7 days after completion of treatment.
c) Positive stool test for pathogenic bacteria, ova, or parasites. If positive, participants may 
be rescreened after completion of treatment. 
d) Clinically significant abnormalities in laboratory testing during the screening period.
e) Severe anemia (ie, hemoglobin [Hb] <8 g/dL) at screening visit.
f)
Liver function impairment or persisting elevations of aspartate aminotransferase (AST) or 
alanine aminotransferase (ALT) > 2 × upper limit of normal (ULN), or direct bilirubin 
> 1.5 × ULN.
6) Allergies and Adverse Drug Reaction
a) Hypersensitivity to active ingredients or excipients of ozanimod.
7) Other Exclusion Criteria
a) Prisoners or participants who are involuntarily incarcerated. (Note: Under certain specific 
circumstances and only in countries where local regulations permit, a person who has been 
imprisoned may be included or permitted to continue as a participant. Strict conditions 
apply, and Bristol-Myers Squibb [BMS] approval is required.)
b) Inability to comply with study procedures, including study visits, venipunctures, 
endoscopies, etc.
c) Participation in another clinical trial concurrent with this study.
d) Any other sound medical, psychiatric, and/or social reason as determined by the 
investigator.
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Eligibility criteria for this study have been carefully considered to ensure the safety of the study 
participants and that the results of the study can be used. It is imperative that participants fully 
meet all eligibility criteria. Further criteria will follow the product label.
6.3
Lifestyle Restrictions
Female participants (WOCBP only) should use highly effective contraception during the treatment 
period and for 90 days after discontinuing study intervention.
Aged, fermented, cured, smoked, and pickled foods containing large amounts of exogenous amines 
(eg, aged cheese, pickled herring) may cause release of norepinephrine, resulting in a rise of blood 
pressure (tyramine reaction). Consequently, participants will be counselled to avoid foods 
containing a large amount of tyramine during the treatment period.
6.4
Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but who 
are not subsequently entered in the study/included in the analysis population. 
A minimal set of screen failure information is required to ensure transparent reporting of screen 
failure participants, to meet the Consolidated Standards of Reporting Trials 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 serious adverse events (SAEs).
6.4.1
Retesting During Screening or Lead-in Period
Participant re-enrollment: This study permits the re-enrollment of a participant who has 
discontinued the study as a pretreatment failure (ie, participant has not been treated). If re-enrolled, 
the participant must be re-consented and given a distinct patient identification number (PID).
Retesting of laboratory parameters and/or other assessments within any single screening or lead-in 
period will be permitted (in addition to any parameters that require a confirmatory value).
The most current result prior to the is the value by which study inclusion will be assessed, because 
it represents the participant’s most current clinical state.
Laboratory parameters and/or assessments that are included in Table 2-1, the SOA for Year 1, may 
be repeated in an effort to find all possible well-qualified participants. Discussion with the Medical 
Monitor is needed to identify whether repeat testing of any particular parameter is clinically 
relevant.
7
STUDY INTERVENTION(S) AND CONCOMITANT THERAPY 
Study intervention is defined as any investigational intervention(s), marketed product(s), placebo,
procedure(s), or medical device intended to be administered to a study participant according to the 
study protocol.
Study intervention includes investigational (medicinal) product (IP/IMP) as indicated in Table 7.1-
1.
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An IP, also known as 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 that 
already have a marketing authorization but are used or assembled (formulated or packaged) 
differently from the authorized form, used for an unauthorized indication, or used to gain further 
information about the authorized form.
7.1
Study Interventions Administered
Details of the IP used for both cohorts are provided in Table 7.1-1:
Table 7.1-1:
Study Interventions
Study Intervention Details (for Cohort 1 and Cohort 2)
Intervention Name
Ozanimod (Zeposia)
Type 
Drug
Dose Formulation
Capsule
Unit Dose Strength(s)
0.23 mg, 0.46 mg, and 0.92 mg
Dosage Level(s)
Days 1–4: 1 × 0.23 mg (QD)
Days 5–7: 1 × 0.46 mg (QD)
Day 8 and thereafter : 1 × 0.92 mg (QD)
Route of Administration
Oral
Use
Active
Sourcing
Provided by the Sponsor
Packaging and Labeling
Ozanimod will be packaged and labelled per country requirements.
Current/Former Name(s) or 
Alias(es)
RPC1063, BMS-986374
Table 7.1-2Participants will receive a phone call on Day 5 (when titrating their dose from 0.23 mg 
to 0.46 mg) and again on Day 8 (when titrating their dose from 0.46 mg to 0.92 mg) as a reminder 
about the dose adjustment (see Table 2-1).
Table 7.1-2:
Ozanimod Dose Titration Regimen
Days
Regimen
Days 1–4
0.23 mg QD PO
Days 5–7
0.46 mg QD PO
Day 8 and thereafter
0.92 mg QD PO
7.2
Method of Study Intervention Assignment
Study using interactive response technology (IRT): All participants will be centrally assigned 
using IRT. Before the study is initiated, each user will receive log-in information and directions 
on how to access the IRT.
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The study intervention will be dispensed at the study visits as listed in the SOA (Section 2). 
During the screening visit, the investigative site will access the screening option of the IRT
designated by BMS for the assignment of a 5-digit participant number that will be unique across 
all sites. Enrolled participants, including those who are not dosed, will be assigned sequential 
participant numbers starting with 
. The PID will 
ultimately comprise the site number and participant number. For example, the first participant
screened (ie, enrolled) at site number 1 will have a PID of 
. Once it is determined that 
the participant meets the eligibility criteria, he or she will be assigned to the applicable cohort
during the screening visit.
7.3
Blinding
This is an open-label study. Participants, site personnel (eg, monitors and investigators), and 
Sponsor personnel will not be blinded to therapy.
7.4
Dosage Modification
Additional dose modification after the 7-day titration is not allowed.
7.5
Preparation/Handling/Storage/Accountability
The IP must be stored in a secure area according to local regulations. It is the responsibility of the 
investigator or the designee, where permitted, to ensure that the IP is only dispensed to study 
participants. 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 intervention is stored in accordance with 
the environmental conditions (temperature, light, and humidity) determined by BMS. If concerns 
regarding the quality or appearance of the study intervention arise, the study intervention should 
not be dispensed, and BMS should be contacted immediately.
Documentation of IP must be maintained that includes all processes required to ensure the drug is 
accurately administered. This includes documentation of drug storage, administration, and, as 
applicable, storage temperatures, etc.

The investigator or designee must confirm that appropriate temperature conditions have been
maintained during transit for all study intervention received and that any discrepancies are
reported and resolved before use of the study intervention.

The investigator, institution, or the head of the medical institution (where applicable) is
responsible for study intervention accountability, reconciliation, and record maintenance
(ie, receipt, reconciliation, and final disposition records).

Further guidance and information for the final disposition of unused study interventions are
provided in the Study Reference Manual.
7.6
Treatment Compliance
Study intervention compliance will be periodically (see Table 2-1 and Table 2-2) monitored for
drug accountability. Drug accountability should be reviewed by the site study staff at each visit to 
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confirm treatment compliance. Sites should discuss discrepancies with the participants at each on-
treatment study visit. 
When participants self-administer study intervention(s) at home, compliance with the study 
intervention will be assessed at each visit. Compliance will be assessed by counting returned 
capsules during site visits and will be documented in the source documents and relevant form. 
Deviation(s) from the prescribed dosage regimen should be recorded in the electronic case report 
form (eCRF).
A record of the quantity of study intervention dispensed to and taken by each participant must be 
maintained and reconciled with study intervention and compliance records. Intervention start and 
stop dates, including dates of intervention delays and/or dose reductions, will also be recorded in 
the eCRF.
7.7
Concomitant Therapy
7.7.1
Prohibited and/or Restricted Treatments
Prohibited and/or restricted medications taken prior to study intervention administration in the 
study are described below. Medications taken prior to study intervention administration must be 
recorded on the eCRF.

Prior exposure to ozanimod is prohibited.

Exposure to any investigational drug or placebo within 4 weeks of study intervention
administration is prohibited. 

Prohibited concomitant medications are listed in Table 7.7-1.
Table 7.7-1:
Summary of Prohibited Concomitant Medications
Immunomodulatory Drugs

eg, Thiopurines, methotrexate, cyclosporin, tacrolimus.

Prohibited, with a required washout period of at least 1 day.
Advanced Therapies for the Treatment of 
UC

Biologic agents and small molecules.

Prohibited with required washout periods prior to study 
initiation of at least 8 weeks or 5 elimination half lives, 
whichever is shorter.

Washout period may be waived with the demonstration of 
absent drug levels on a TDM assay.
Monoamine Oxidase Inhibitors

Prohibited during ozanimod treatment.

14-day washout period prior to the first study intervention
administration.
Live or Live-attenuated Vaccines

Prohibited during ozanimod treatment.

30-day washout period prior to the first study intervention
administration.

Avoid use for up to 3 months after discontinuation of the study 
intervention.
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Table 7.7-1:
Summary of Prohibited Concomitant Medications
Therapy for Current Active or Any Major 
Infections

Patients who require antibiotic treatment (oral or IV) for 
current active or any major infections are excluded.
Alemtuzumab

Prohibited during ozanimod treatment.

Confirm B cell recovery prior to the first study intervention
administration.
Beta Interferon

Prohibited during ozanimod treatment.
Glatiramer Acetate

Prohibited during ozanimod treatment.
Restricted concomitant medications and foods are listed in Table 7.7-2.
Table 7.7-2:
Summary of Restricted Concomitant Medications and Foods
NSAIDs

May be used as clinically indicated during the study.

Oral NSAIDs may be associated with GI toxicity, including mucosal 
injury. Consequently, their use is not recommended.
Inactivated or Subunit Vaccines

May be used as clinically indicated during the study.

The effect of ozanimod treatment on responses to vaccination is not 
known.
Antiarrhythmic Drugs with 
Known Arrhythmogenic 
Properties

Ozanimod has not been studied in patients taking QT-prolonging drugs.

Class Ia (eg, quinidine, procainamide) and Class III (eg, amiodarone, 
sotalol) antiarrhythmic drugs have been associated with cases of 
torsades de pointes in patients with bradycardia.

Advice from a cardiologist should be sought prior to the initiation of 
treatment with ozanimod.
Combination Beta Blocker and a 
Calcium Channel Blocker 

Co-administration of ozanimod with both a beta blocker and a calcium 
channel blocker has not been studied. However, there is potential for 
additive effects on HR.

Advice from a cardiologist should be sought prior to the initiation of 
treatment with ozanimod.
Adrenergic and Serotoninergic 
Drugs

Co-administration of ozanimod with drugs or over-the-counter 
medications that can increase norepinephrine or serotonin (eg, opioid 
drugs, SSRIs, SNRIs, tricyclic antidepressants, tyramine) will be per 
product label.

Monitor participants for hypertension with concomitant use.
Foods Containing a Large 
Amount of Tyramine

Participants should be advised to avoid foods containing a large amount 
of tyramine during the treatment period.

Aged, fermented, cured, smoked, and pickled foods containing large 
amounts of exogenous amines (eg, aged cheese, pickled herring) may 
cause the release of norepinephrine, resulting in an increase in blood 
pressure (tyramine reaction).
Strong CYP2C8 Inducers

Use of strong CYP2C8 inducers (eg, rifampicin) should be avoided.
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Table 7.7-2:
Summary of Restricted Concomitant Medications and Foods

Co-administration of ozanimod with strong CYP2C8 inducers reduces 
the exposure of the major active metabolites of ozanimod, which may 
decrease the efficacy of ozanimod.
CYP2C8, cytochrome P4502C8; NSAID, non-steroidal anti-inflammatory drugs; SNRI, serotonin-norepinephrine 
reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor.
Dose stabilization rules for permitted concomitant medications are listed in Table 7.7-3.
Table 7.7-3:
Summary of Dose Stabilization Rules for Permitted Concomitant 
Medications
Oral and Rectal 5-ASAs

Oral and rectal 5-ASAs are permitted.

Stable doses are encouraged after the first study intervention
administration, particularly up to the assessment of the primary 
endpoint.
Rectal Corticosteroids

Rectal corticosteroids are permitted as clinically indicated.

After assessment of the primary endpoint, rectal corticosteroids are only 
allowed for a maximum of 3 months per year (eg, rectal corticosteroids 
are permitted during induction, and one other course is permitted as 
indicated within Year 1; only one 3-month course is permitted per year 
thereafter).
Oral Prednisone

Cannot be on oral prednisone continuously for more than 28 days prior 
to Day 1.

Oral prednisone ≤40 mg QD PO (or equivalent) is permitted at Day 1, if 
clinically indicated, and is permitted at that dose for no more than 
14 days prior.

Tapering schedule will be as follows: Reduce dose by 5 mg weekly until 
20 mg is reached, then reduce by 2.5 mg weekly to 0 mg. Tapering can 
occur more rapidly at the investigator’s discretion. Patient should be on 
prednisone continuously for no more than 12 weeks.

One rescue course of prednisone (up to 40 mg QD PO with subsequent 
tapering, as described above) will be permitted per year, not including 
prednisone use in the first 12 weeks of the study. The maximum duration 
of each course is 12 weeks.
Oral Budesonide 

Budesonide ≤9 mg QD PO is permitted at Day 1, if clinically indicated.

Dose should be stable for 14 days prior to the first study intervention
administration.

One rescue course of budesonide will be permitted each year with a 
maximum course duration of 12 weeks and tapering at the investigator’s
discretion.

The investigator may switch between prednisone and budesonide for the 
rescue treatment. The maximum duration of 12 weeks applies, 
irrespective of steroid switching.
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7.7.2
Other Restrictions and Precautions
Participants are prohibited from joining another interventional clinical trial while they are 
participating in this study.
7.7.2.1
Treatment Failure Rules
Treatment failure rules will be applied to the primary analyses of all efficacy endpoints. 
Participants will be considered to have failed treatment if any of the following occur:

Any protocol-prohibited change in medications, including:

Post-baseline initiation of or increase in total daily dose to a level higher than the 40 mg 
maximum permitted dose of corticosteroid to treat UC. 

Prolonged course of systemic corticosteroids (ie, > 12 consecutive weeks) for treatment of 
UC.

Initiation of an immune-suppressing therapy,
including 6-mercaptopurine, AZA, 
methotrexate, anti-TNF agents, anti-integrin, anti-IL-12/23 agents, or JAK inhibitors.

A colectomy (partial or total) or an ostomy.

Discontinuation of the study intervention due to lack of therapeutic effect before primary or 
secondary efficacy evaluations.
7.8
Continued Access to Study Intervention After the End of the Study
At the end of the study, BMS will not continue to provide BMS-supplied study interventions to 
participants or investigators unless BMS chooses to extend the study. The investigator should 
ensure that the participant receives the appropriate standard of care to treat the condition under 
study.
8
DISCONTINUATION CRITERIA
8.1
Discontinuation From Study Intervention
Participants MUST discontinue IP for any of the following reasons:

Participant’s or investigator’s request to stop study intervention. Participants who request to 
discontinue study intervention will remain in the study and must continue to be followed for 
the protocol-specified follow-up procedures. The only exception to this is when a participant 
specifically withdraws consent for any further contact with him/her or persons previously 
authorized by the participant to provide this information.

Any clinical AE, laboratory abnormality, intercurrent illness, or other appropriate reason(s), 
which, in the opinion of the investigator, indicates that continued administration of study 
intervention is not in the best interest of the participant.

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.)
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
Pregnancy (refer to Section 9.2.5).

Significant non-compliance with the protocol (eg, procedures, assessments, medications). The 
investigator should discuss such issues with the Medical Monitor.

Participant meets one of the following criteria for laboratory abnormalities in 2 sequential 
laboratory measurements taken up to 14 days apart:

Hb < 7.0 g/dL or a decrease of >30% from baseline

Lymphocyte count < 0.2 × 109/L (< 200/mm3) – see Section 9.2.6 for temporary 
discontinuation guidance.

Participant meets any of the following criteria for liver-related laboratory abnormalities. If 
these abnormalities are identified, repeat testing should occur within 48 to 72 hours, and these 
results should be discussed with the BMS Medical Monitor or designee. Additional 
recommendations on the recognition and investigation of potential drug-induced liver injury 
(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%).
Refer to the SOA for the data that will be collected at the time of treatment discontinuation and 
follow-up and for any further evaluations that can be completed.
All participants who discontinue study intervention should comply with the protocol-specified 
follow-up procedures, as outlined in Section 2. The only exception to this requirement is when a 
participant withdraws consent for all study procedures, including post-treatment study follow-up,
or loses the ability to consent freely (eg, is imprisoned or involuntarily incarcerated for the 
treatment of either a psychiatric or physical illness).
If study intervention is discontinued prior to the participant’s completion of the study, the reason 
for the discontinuation must be documented in the participant’s medical records, per local 
regulatory requirements in each region/country, as applicable, and entered on the appropriate 
eCRF page.
8.1.1
Treatment Interruption
Participants should be instructed that if they forget to take a dose, they can take it within 4 hours 
of the normal dosing time; otherwise, they should take their next dose at the regular time on the 
following day. If the participant vomits the dose, he/she should be instructed not to take another 
dose on the same day, but to take the next dose at the regular time on the following day. Participants
will record whether they took the daily dose of medication in an electronic diary that will be 
reviewed periodically by the site staff and the site monitor.
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If a dose is missed during the first 2 weeks of treatment, re-iniate treatment using dose escalation 
regimen. If a dose of study intervention is missed after the first 2 weeks of treatment, continue 
with the treatment as planned. If more than 7 consecutive days between Day 15 and Day 28 of 
treatment, or more than 14 consecutive days after Day 28 of treatment, re-initiate treatment using 
the dose escalation regimen. The Medical Monitor should be contacted to discuss completing the 
dose escalation schedule.
8.1.2
Post-study Intervention Study Follow-up
Participants who discontinue study intervention may continue to be followed.
8.2
Discontinuation From the Study
Participants who request to discontinue study intervention will remain in the study and must 
continue to be followed for the protocol-specified follow-up procedures. The only exception to 
this is when a participant specifically withdraws consent for any further contact with him/her or 
persons previously authorized by the participant to provide this information. 

Participants should notify the investigator of the decision to withdraw consent from future 
follow-up.

The investigator should explain the withdrawal of consent in detail in the medical records, 
including whether the withdrawal is from further treatment with study intervention only or 
whether it is also from study procedures and/or post-treatment study follow-up, and should 
enter this on the appropriate eCRF page.

In the event that vital status (whether the participant 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 participant withdraws consent for disclosure of future information, the Sponsor may 
retain and continue to use any data collected before such a withdrawal of consent.
8.2.1
Individual Discontinuation Criteria

A participant may withdraw completely from the study at any time at his/her own request, or 
may be withdrawn at any time at the discretion of the investigator for safety, behavioral, 
compliance, or administrative reasons; this is expected to be uncommon. Stopping study 
intervention is not considered withdrawal from the study.

At the time of discontinuing from the study, the end of treatment and follow-up visits should 
be conducted, if possible, as shown in the SOA. See the SOA (Table 2-1 and Table 2-2) for 
the data to be collected at the time of study discontinuation and follow-up and for any further 
evaluations that need to be completed.

The participant will be permanently discontinued both from the study intervention and from 
the study at that time.

If the participant withdraws consent for disclosure of future information, the Sponsor may 
retain and continue to use any data collected before such a withdrawal of consent.
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8.3
Lost to Follow-up
The following actions must be taken if a participant fails to return to the clinic for a required study 
visit:

All reasonable efforts must be made to locate the participant to determine and report their 
ongoing status. This includes follow-up with persons authorized by the participant.

Lost to follow-up is defined by the inability to reach the participant after a minimum of 
three (3) documented phone calls, faxes, or emails, as well as a lack of response by the 
participant to one (1) registered mail letter. All attempts should be documented in the 
participant’s medical records.

If it is determined that the participant has died, the site will use permissible local methods to 
obtain the date and cause of death.

If the investigator’s use of a third-party representative to assist in the follow-up portion of the 
study has been included in the participant’s informed consent, then the investigator may use a 
Sponsor-retained third-party representative to assist site staff with obtaining the participant’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, in order to obtain updated contact information.

If, after all attempts, the participant remains lost to follow-up, then the last known alive date,
as determined by the investigator, should be reported and documented in the participant’s 
medical records.
9
STUDY ASSESSMENTS AND PROCEDURES

Study procedures and timing are summarized in the SOA (Section 2). 

Protocol waivers or exemptions are not allowed.

All immediate safety concerns must be discussed with the Sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue 
treatment.

Adherence to the study design requirements, including those specified in the SOA (Section 2), 
is essential and required for study conduct.

All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria before study intervention administration on Day 1. 
The investigator will maintain a screening log to record details of all participants screened and 
to confirm eligibility or record reasons for screening failure, as applicable.

Procedures that are conducted as part of the participant’s routine clinical management 
(eg, blood count) and obtained before signing of informed consent may be utilized for 
screening or baseline purposes, provided the procedure meets the protocol-defined criteria and 
has been performed within the timeframe defined in the SOA (Section 2).
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9.1
Efficacy Assessments
9.1.1
Efficacy Assessments for the Study
Study evaluations will take place in accordance with the SOA (Section 2). Endoscopy- and 
biopsy-related procedure details will be provided to the sites in a separate document/manual.
A brief description about additional efficacy assessments is provided in Sections 5.1 and 5.4.
9.1.2
Other Efficacy Assessments for the Study
9.1.2.1
Histology Assessment 
A histology assessment will be done using the Geboes score. This instrument has been used to 
characterize the histological appearance of the mucosa in registrational UC studies.32
9.1.2.2
Health-related Quality of Life 
HRQOL
will be captured using the following
questionnaires: 
 IBDQ, 
.
 
The IBDQ was developed to measure the patient’s 
experience of inflammatory bowel diseases (UC and CD). It consists of 32 questions divided into 
4 dimensions: bowel symptoms (10 items), systemic symptoms (5 items), emotional function 
(12 items), and social function (5 items). Each question ranges from 1 “worst situation” to 7 “best 
situation”; and the total score ranges from 32 to 224, with higher scores representing better 
QOL.34,35
 
The timing of HRQOL collection is provided in the SOA (Section 2).
9.2
Adverse Events
The definitions of an AE or an SAE can be found in APPENDIX 5.
AEs will be reported by the participants
The investigator and any qualified designees are responsible for detecting, documenting, and 
reporting events that meet the definition of an AE or SAE and remain responsible for following up
on AEs that are serious, considered related to the study intervention or the study, or that caused 
the participant to discontinue before completing the study. 
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Refer to APPENDIX 5 for SAE reporting.
9.2.1
Time Period and Frequency for Collecting AE and SAE Information
The collection of nonserious AE and coronavirus disease (COVID) AE information should begin 
at screening until the follow-up visit, at the time points specified in the SOA (Section 2). 
All SAEs must be collected from the time of signing the ICF, including those thought to be 
associated with protocol-specified procedures, and within 30 days following discontinuation of 
dosing.
The investigator must report any SAE that occurs after these time periods and that is believed to 
be related to study intervention or a protocol-specified procedure (eg, endoscopy, biopsy).

Medical occurrences that begin before the start of study intervention but after obtaining 
informed consent will be recorded in the appropriate section of the eCRF.

All SAEs will be recorded and reported to the Sponsor or designee within 24 hours, as indicated 
in APPENDIX 5. 

The investigator will submit any updated SAE data to the Sponsor or designee within 24 hours
of the updated information being available.
Investigators are not obligated to actively seek AEs or SAEs in former study participants. 
However, if the investigator learns of any SAE, including a death, at any time after a participant 
has been discharged from the study, and he/she considers the event to be reasonably related to the 
study intervention or study participation, the investigator must promptly notify the Sponsor.
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 5.
9.2.1.1
Adverse Events of Interest
Because of the characteristics of the disease under study and ozanimod in particular, some AEs 
are considered adverse event of interest (AEI). AEIs may be serious or nonserious. Such events 
may require further investigation to better characterize and understand them. In the ozanimod 
clinical development program, potential AEIs that may be a result of S1P1 modulation will be 
closely monitored during the study. These AEIs include bradycardia, heart conduction 
abnormalities (second degree and higher AV block), macular edema, malignancy, serious or 
opportunistic infection, pulmonary effects, hepatic effects, posterior reversible encephalopathy 
syndrome, progressive multifocal leukoencephalopathy (PML), and events associated with 
orthostatic hypotension (eg, dizziness, lightheadedness, syncope, seizure). The Sponsor may 
request additional medical information concerning AEIs that are nonserious.

Bradycardia and heart conduction abnormalities (eg, symptomatic bradycardia, 2nd degree AV 
block, QT prolongation) will be screened for per the SOA (Section 2). First dose observation
or cardiologist opinion will be per the SOA (Section 2). Investigators should be particularly 
cautious with participants with pulse rates < 55 beats per minute prior to administration of 
ozanimod. Atropine IV is recommended as first-line treatment for bradycardia, up to a 
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maximum daily dose of 3 mg. In general, common guidelines for treatment of bradycardia 
(eg, advanced cardiac life support) should be followed as appropriate.

Macular edema

For participants with symptoms of new-onset macular edema that develop following 
initiation of treatment, a general ophthalmologic examination, including eye history, visual 
acuity, and dilated ophthalmoscopy must be performed.

Ozanimod must be discontinued in any participant who has a confirmed diagnosis of 
new-onset macular edema.

Participants with a diagnosis of macular edema must be followed up monthly and more 
frequently, if needed, based on the ophthalmologist’s clinical judgment.

Malignancy: Participants should be carefully monitored for malignancies (including 
dermatologic malignancy). The investigator will complete dermatological examinations to 
monitor the potential development of new cutaneous malignancies during the study. 
Participants with any suspicious finding noted during the examination will be referred to an 
appropriately qualified dermatologist for evaluation and treatment, if warranted.

Serious or opportunistic infection: Tuberculosis, serious bacterial infections, systemic fungal 
infections, viral infections, such as herpes infections (including herpes zoster and disseminated 
herpes simplex), and protozoan infections will be considered AEIs.

Pulmonary effects: If a participant discontinues due to a respiratory AE, the investigator should 
ensure that the participant has had adequate evaluations, as clinically indicated by a 
pulmonologist (consider pulmonary function tests, chest X-ray, or high-resolution computed 
tomography, based on findings of the other examinations), at the time of the AE.

Hepatic effects: If participants have elevations in liver function tests (LFTs; ALT or/and AST) 
≥3 × ULN, a retest should be performed as soon as possible but no later than 14 days after the 
original test. Upon confirmation of the abnormality, retests should be performed weekly until 
the elevated LFT decreases to below 3 × ULN. At any time, if any of the following occur and 
there are no apparent alternative causes for the finding, the study intervention must be 
permanently discontinued:

ALT or AST > 8 × ULN or

ALT or AST > 5 × ULN with confirmation within 2 weeks or

ALT or AST > 3 × ULN and (total bilirubin > 2 × ULN or INR > 1.5) or

ALT or AST > 3 × ULN with the appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash, and/or eosinophilia (> 5%).

The investigator should establish causality.

After discontinuation due to elevation of ALT or AST > 5 × ULN or concurrent elevations of 
ALT or AST > 3 × ULN and bilirubin > 2 × ULN, further liver function evaluations should be 
performed (for example, coagulation panel and alkaline phosphatase) in consultation with the 
Medical Monitor.

Posterior reversible encephalopathy syndrome (PRES) is a syndrome characterized by sudden 
onset of severe headache, confusion, seizures, and visual loss. If a participant develops any 
unexpected neurological or psychiatric symptoms/signs (eg, cognitive deficits, behavioral 
changes, cortical visual disturbances, or any other neurological cortical symptoms/signs), any 
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symptom/sign suggestive of an increase of intracranial pressure, or accelerated neurological 
deterioration, the physician should promptly schedule a complete physical and neurological 
examination and should consider magnetic resonance imaging (MRI). If PRES is suspected, 
treatment with study intervention should be discontinued.

PML: In the event of any neurological decline while on ozanimod, the participant should be 
urgently evaluated by a neurologist. 

PML is an opportunistic viral infection of the brain caused by the John Cunningham virus 
that typically occurs in patients who are immunocompromised and may lead to death or 
severe disability. John Cunningham virus infection resulting in PML has been associated 
with some risk factors (eg, polytherapy with immunosuppressants, severely 
immunocompromised patients). PML has been observed in patients treated with 
immunomodulators, including ozanimod.

Typical symptoms associated with PML are diverse, progress over days to weeks, and 
include progressive weakness on one side of the body or clumsiness of limbs, disturbance 
of vision, and changes in thinking, memory, and orientation leading to confusion and 
personality changes.

Investigators should be vigilant for clinical symptoms or other findings that may be 
suggestive of PML. If PML is suspected, a neurologist consultation should be obtained,
and an MRI scan should be requested. Treatment with ozanimod should be suspended until 
PML has been excluded. If confirmed, treatment with ozanimod should be discontinued.
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 participant. Care should be taken not to introduce bias when collecting AEs and/or 
SAEs. Inquiry about specific AEs should be guided by clinical judgment in the context of known 
AEs, when appropriate for the program or protocol.
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 5).

Follow-up is also required for nonserious AEs that cause interruption or discontinuation of 
study intervention and for those present at the end of study intervention, as appropriate.

All identified nonserious AEs must be recorded and described on the nonserious AE page of 
the eCRF. Completion of supplemental eCRFs may be requested for AEs and/or laboratory 
abnormalities that are reported/identified during the course of the study.
All SAEs will be followed until resolution, until the condition stabilizes, until the event is 
otherwise explained, or until the participant is lost to follow-up (as defined in Section 8.3).
Further information on follow-up procedures is given in APPENDIX 5.
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9.2.4
Regulatory Reporting Requirements for SAEs

Prompt notification of SAEs by the investigator to the Sponsor is essential so that legal 
obligations and ethical responsibilities toward the safety of participants 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 will file it along with 
the product label and will notify the IRB/IEC, if appropriate according to local requirements.
The Sponsor or designee must report AEs to regulatory authorities and ethics committees 
according to local applicable laws and regulations. A SUSAR (suspected, unexpected serious 
adverse reaction) is a subtype of SAE and must 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 intervention, it is subsequently discovered that a participant is 
pregnant or may have been pregnant at the time of study exposure, including for at least 
intervention after study product administration, the investigator must immediately notify the BMS 
Medical Monitor/designee of this event. Then, they must complete and forward a Pregnancy 
Surveillance Form to the BMS designee within 24 hours of awareness of the event and in 
accordance with SAE reporting procedures described in APPENDIX 5.
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 with the participant.
9.2.6
Laboratory Test Result Abnormalities
The following laboratory test result abnormalities should be captured on the nonserious AE eCRF 
page or SAE eCRF, as appropriate. Paper forms are only intended as a back-up option when the 
electronic system is not functioning.

Reductions in absolute lymphocyte count (ALC) levels for participants in this study are an 
expected primary PD effect. If ALC < 200 cells/µL results are observed during the study, the 
investigator will be notified and asked to repeat the laboratory tests within 14 days. If the repeat 
ALC is confirmed below the 200 cells/μL limit, the investigator will temporarily discontinue 
study intervention. Laboratory testing will be repeated weekly until the ALC is > 500 cells/μL. 
For participants who have a confirmed ALC below the 200 cells/μL limit and decide to 
permanently discontinue study intervention, central laboratory testing will continue every 14 
days (± 3 days) after the end of treatment visit until it is above the lower limit of normal or 
until the ALC is considered to have stabilized and/or reached a level that is not clinically 
significant. Reductions in ALC, in general, need not be reported as AEs unless there are clinical 
consequences. The decision to report decreased ALC as an AE is at the investigator’s 
discretion.

Any laboratory test result that is clinically significant or meets the definition of an SAE.
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
Any laboratory test result abnormality that required the participant to have study intervention
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 term would be used by the reporting investigator 
rather than the laboratory term (eg, anemia vs low Hb value).
9.2.7
Potential DILI
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 5 for reporting 
details).
A potential DILI is defined as: 

Aminotransferase (AT; ALT or AST) elevation > 3 × ULN
AND

Total bilirubin > 2 × ULN, without initial findings of cholestasis (elevated serum alkaline 
phosphatase)
AND

No other immediately apparent possible causes of AT elevation and hyperbilirubinemia, 
including, but not limited to, viral hepatitis, pre-existing chronic or acute liver disease, or the 
administration of other drug(s) known to be hepatotoxic.
9.2.8
Other Safety Considerations
Any significant worsening of conditions noted during interim or final physical examinations, 
12-lead ECG, X-ray filming, or any other potential safety assessment required or not required by 
the protocol should also be recorded as a nonserious AE or SAE, as appropriate, and reported 
accordingly.
9.3
Expedited Reporting of SUSARs
For regulatory reporting, the BMS Drug Safety team is responsible for determining the 
expectedness of reported events that are suspected to be related to ozanimod based on the product 
label. Upon assessment and confirmation, SUSARs will be distributed per agreed contractual 
obligations between BMS and PPD.

Reporting to global regulatory authorities/agencies will be handled by the BMS Drug Safety 
team.

Reporting to Ethics Committees will be handled as follows:

For countries where reporting obligations to the IEC/IRB are delegated to PPD, the 
pharmacovigilance (PVG) team will ensure distribution to the appropriate IEC/IRB.
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
For countries where reporting obligations to the IEC/IRB fall under the responsibility of 
the principal investigators (PIs), the PPD PVG team will distribute the reports to the PIs 
via PPD’s LifeSphere system. The PIs will retrieve the safety reports from LifeSphere and 
perform onward submission to their corresponding IECs/IRBs per current local 
regulations.
This also applies for distribution of aggregate reports (eg, 6-monthly SUSAR line listings and 
Development Safety Update Report), based on the delegation of reporting tasks between PPD and 
BMS.
9.4
Overdose
An overdose is any dose of IP given to a participant or taken by a participant that exceeds the dose 
described in the protocol. Any overdose, with or without associated AEs, must be promptly 
reported to the Medical Monitor or other designated Drug Safety Center. The overdose should be 
recorded in the study exposure eCRF. AEs associated with an overdose should be reported in 
relevant AE/SAE sections in the eCRF.
In the event of an overdose, the investigator should:

Contact the Medical Monitor immediately.

Closely monitor the participant for AEs/SAEs and laboratory abnormalities, as deemed 
appropriate by investigator.

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 Medical Monitor based on the clinical evaluation of the participant.
9.5
Safety
Planned time points for all safety assessments are listed in the SOA (Section 2).
9.5.1
Physical Examinations
Physical examinations will be performed at the time points specified in the SOA (Section 2).
Physical examinations will be performed by an investigator-designated medical doctor or 
advanced practitioner (eg nurse practitioner, physician assistant). Findings must be recorded in the 
appropriate section of the eCRF.
9.5.2
Vital Signs
Vital signs will be measured at the time points specified in the SOA (Section 2).
9.5.3
12-lead ECG
12-lead ECG will be performed at screening, as specified in the SOA (Section 2). ECG will be 
read locally. Clinically significant 12-lead ECG findings must be recorded in the appropriate 
section of the eCRF and should be discussed with the BMS Medical Monitor or designee.
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9.5.4
Clinical Safety Laboratory Assessments

Investigators must document their review of each laboratory safety report.

Refer to Table 9.5.4-1 for details related to the clinical safety laboratory assessments and to 
the SOA (Section 2) for their time points.
A central laboratory will perform the analyses and will provide reference ranges for these tests.
Results of the clinical laboratory tests must be available prior to the first dose of study intervention 
on Day 1.
Table 9.5.4-1:
Clinical Safety Laboratory Assessments
CBC and Differential Count
Hb
Hematocrit
Total leukocyte count, including differential
Platelet count
Biochemistry
ALT 
AST 
Total bilirubin
Direct bilirubin
Alkaline phosphatase
Lactate dehydrogenase 
Creatinine
BUN
Uric acid 
Fasting glucose
Total protein
Albumin
Sodium
Potassium
Chloride
Calcium
Phosphorus
Magnesium
Urinalysis
Protein
Glucose
Blood
Leukocyte esterase
Specific gravity
pH
Microscopic examination of the sediment if blood, protein, or leukocytes esterase are positive on the dipstick
Other Analyses
Pregnancy test (screening only; serum or urine)
Varicella IgG (screening only)
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Table 9.5.4-1:
Clinical Safety Laboratory Assessments
Urine beta-hCG test (WOCBP only)
FSH (optional; screening only [may be used to exclude childbearing potential in peri-menopausal females]) 
BUN, blood urea nitrogen; CBC, complete blood count; FSH, follicle-stimulating hormone; 
 
 IgG, immunoglobulin G.
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9.8
Additional Research
Additional research related to the study intervention and/or disease may be performed. The results 
of this additional research could help to improve the diagnosis and/or the treatment of this disease 
in the future. This research 
 
 
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9.9
Other Assessments
Not applicable.
9.10
Healthcare Resource Utilization 
Healthcare resource utilization data associated with medical encounters will be collected in the 
eCRF by the investigator and study site personnel for all participants throughout the study (see 
Table 2-1 and Table 2-2). Protocol-mandated procedures, tests, and encounters will be excluded. 
The data collected may be used to conduct exploratory economic analyses and will include:

Number and duration of medical care encounters
, 
including surgeries and other selected procedures (inpatient and outpatient).

Duration of hospitalization (total length of stay in days, including duration by wards; 
eg, intensive care unit).
10
STATISTICAL CONSIDERATIONS
10.1
Statistical Hypotheses
Due to the open-label design of the study and the lack of a control group, all data will be 
summarized, and no hypothesis testing will be performed.
10.2
Sample Size Determination 
The sample size for this study is not based on statistical power for comparisons among treatment 
cohorts; it has been selected to minimize the width of the 95% confidence interval (CI) of the 
estimate of the clinical response rate (primary endpoint) for each cohort. 
An estimated total of 250 participants will be enrolled to achieve a total sample of 150 treated 
participants in Cohort 1, and approximately 165 participants will be enrolled to achieve a total 
sample of 100 treated participants in Cohort 2. The methods for determining each cohort’s sample 
size are described below.
Cohort 1 (Advanced Therapy-naïve Cohort)
Due to the lack of published data evaluating the proportion of subjects achieving clinical response 
at Week 12, sample size estimates are based on clinical response rates at Week 10 in the 
biologic-naïve population from Study RPC01-3101 (ie, patients who have not been exposed to at 
least one biologic prior to study entry). Based on those results, it is anticipated that at least 50% of 
Cohort 1 will achieve clinical response at Week 12. Under these assumptions, a sample size of 
150 participants would estimate exact binomial 95% CIs ranging between 41.7% and 58.3%.
Cohort 2 (Advanced Therapy-exposed Cohort)
The proportion of patients with clinical response in Cohort 2 is estimated to be 35% to 45% at 
Week 26 based on the clinical response rate at Weeks 10 and 52, as well as symptomatic response 
(as a surrogate variable) in the biologic-exposed population of Study RPC01-3101 (ie, patients 
who have been exposed to at least one biologic prior to study entry). Assuming a 45% clinical 
response rate at Week 26, a sample size of 100 participants is needed to provide a half-width of 
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the 95% CI of 10.5% (ie, 95% CI: 35%, 55.3%) using the exact CI formula for binomial 
probabilities.
10.3
Analysis Sets
For the purposes of analysis, the populations are defined as follows:
Population
Description
Enrolled 
All participants who signed an ICF and were registered into IRT.
Cohort 1 Treated 
Analysis Population 
All Cohort 1 participants who received at least one dose of study intervention. This 
population will be used for both the efficacy and safety analyses for Cohort 1.
Cohort 2 Treated 
Analysis Population 
All Cohort 2 participants who received at least one dose of study intervention. This 
population will be used for both the efficacy and safety analyses for Cohort 2.
Defined Analysis Data 
Sets
Description
Analysis set for primary 
estimand (Cohort 1)
All Cohort 1–treated participants. Participants who discontinued study intervention 
and/or received prohibited concomitant medications prior to Week 12 will be 
considered non-responders.
Analysis set for primary 
estimand (Cohort 2)
All Cohort 2–treated participants. Participants who discontinued study intervention
and/or received prohibited concomitant medications prior to Week 26 will be 
considered non-responders.
10.4
Statistical Analyses
Detailed methodology for the summary and statistical analyses of the data collected in this study 
will be documented in an SAP, which will be written and finalized prior to the study database lock.
The plans outlined in this protocol may be modified in the SAP; however, any major modifications 
of the key endpoint definitions and/or related analyses will also be reflected in a protocol 
amendment.
10.4.1
General Considerations
Baseline is defined as the last observed measurement prior to the first dose of study intervention 
on Day 1.
In general, descriptive summaries will be presented for the efficacy and safety variables collected. 
Continuous variables will be summarized using the number of participants (n), mean, standard 
deviation, minimum, median, and maximum. Categorical variables will be summarized using 
frequency counts and percentages, and 95% CIs. Analyses will be performed separately for each 
cohort, unless otherwise stated.
10.4.2
Disposition, Demographics, and Baseline Characteristics
Participant disposition, including the number of participants screened and dosed, will be 
summarized for the enrolled population. Participant demographics will be summarized for the 
treated population and will include age, sex, race, ethnicity, height, weight, and body mass index.
Baseline characteristics will be summarized for the treated population and will include age at UC 
symptom onset, age at UC diagnosis, years since UC symptom onset, years since UC diagnosis, 
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prior anti-TNF use, corticosteroid use at screening, concomitant UC medication use at baseline, 
each component of the Mayo score, the complete Mayo score, the partial Mayo score, and the 
9-point Mayo score.
10.4.3
Primary Endpoint
The primary endpoint for each cohort, their corresponding descriptions, and prespecified time 
points are listed in Table 10.4.3-1.
The primary endpoint for Cohort 1 is the proportion of participants who achieve a clinical response 
at Week 12. The clinical response rate at Week 12 will be estimated, and the corresponding 95% 
CI will be derived based on the Clopper Pearson method.
The primary endpoint for Cohort 2 is the proportion of participants who achieve a clinical response 
at Week 26. An estimate of the clinical response rate at Week 26 will be provided, along with the 
corresponding 95% CI derived based on the Clopper Pearson method.
For proportion-based efficacy endpoints, patients with missing Week 12 efficacy data from 
Cohort 1 and/or participants with missing Week 26 efficacy data from Cohort 2 will be considered 
non-responders, and non-responder imputation will be used. Sensitivity analyses around missing 
data may involve missing data imputed using multiple imputation and may analyze observed cases 
with no imputation. Details of the sensitivity analysis will be provided in the SAP.
For continuous efficacy endpoints, observed cases will be analyzed with no imputation.
Table 10.4.3-1:
Endpoints 
Primary 
Description
Timeframe
Clinical Response (modified Mayo 
score)
Proportion of participants achieving the following:

Decrease from baseline in the modified Mayo 
score of ≥2 points, and

Decrease from baseline in the modified Mayo 
score of ≥35%, and

Decrease in RB subscore of ≥1 point or 
absolute RB subscore ≤1.
Week 12 (Cohort 1)
Week 26 (Cohort 2)
Secondary
Description
Timeframe
Clinical Remission (modified Mayo 
score)
Proportion of treated participants achieving the 
following in each component of the modified Mayo 
score:

SF subscore ≤1, with ≥1-point decrease from 
baseline, and

RB subscore = 0, and

ES ≤1.
Week 12 (Cohort 1)
Week 26 (Cohort 2)
Endoscopic Response
Proportion of treated participants with a decrease 
from baseline of ≥1 point in Mayo ES
Week 12 (Cohort 1)
Week 26 (Cohort 2)
Endoscopic Improvement
Proportion of treated participants with Mayo ES ≤1 
Week 12 (Cohort 1) 
Week 26 (Cohort 2)
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Table 10.4.3-1:
Endpoints 
Endoscopic Remission
Proportion of treated participants with Mayo ES = 0
Week 26 (Cohort 2)
IBDQ Response
Proportion of participants with a change from 
baseline in total score of ≥16 points
Week 12 (Cohort 1)
Week 26 (Cohort 2)
IBDQ Remission
Proportion of patients with a total score ≥170 points
Week 12 (Cohort 1)
Week 26 (Cohort 2)
Corticosteroid-free 
Clinical 
Remission (modified Mayo score)
Proportion of treated participants with:

Clinical remission (modified Mayo score) and

No oral systemic steroid use in prior 90 days
Week 26 (Cohort 2)
HEMI
Proportion of participants with endoscopy subscore 
of ≤1 point and a Geboes index score < 3.1
Week 26 (Cohort 2)
HEMI, histo-endoscopic mucosal improvement.
10.4.4
Secondary Endpoints
All secondary endpoints, their corresponding descriptions, and prespecified time points are listed 
in Table 10.4.3-1 for each cohort.
For all binary response secondary endpoints in each cohort, the response rate at the prespecified 
time point will be estimated and a corresponding 95% CI will be derived based on the Clopper 
Pearson method. Details of the analysis for each secondary endpoint will be specified in the SAP.
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10.4.6
Other Safety Analyses
All safety analyses will be carried out for the treated population.
AEs will be monitored during the study, and the data will be analyzed with respect to incidence,
severity, and the potential relationship of the AEs and study intervention. AEs with onset on or 
after the first dose of study intervention, or with onset prior to the first dose of study intervention
that increase in severity on or after the first dose of study intervention will be considered treatment-
emergent. TEAEs will be summarized for the safety population by system organ class (SOC) and 
preferred term, and presented in descending order of frequency within each SOC. SAEs, including 
AEIs, and AEs leading to discontinuation of study intervention will be summarized similarly.
Laboratory parameters will also be summarized. For each laboratory test, individual participant 
values outside the standard reference range will be flagged and listed. Shift tables will be produced 
showing the frequency of shifts from baseline to the lowest and to the highest on-trial value in and 
out of the normal range, as well as by visit. Changes from baseline to each visit for each laboratory 
parameter will also be summarized.
The change from baseline to each visit for each of the vital sign variables will be summarized. 
Abnormal vital sign values will be flagged and listed.
10.4.7
Other Analyses 
Additional endpoints collected during the study, such as 
 
 IBDQ (QOL), 
 
 will be summarized. All collected values will 
be listed for all participants.
10.5
Interim Analyses 
Pre-planned interim analyses may be performed when all participants in both cohorts have 
completed the primary endpoint visit (ie, Week 12 for Cohort 1 and Week 26 for Cohort 2), and 
again when all participants in both cohorts have completed the 52-week visit. The final study 
analysis will be performed when all participants have completed the 116-week study (including 
the safety follow-up visit) or discontinued early from the study. Additionally, optional datacuts at 
other time points will be planned, if required. Details of all planned analyses will be provided in 
the SAP.
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11
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1
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Stenson WF. Inflammatory bowel disease. In: Goldman L, Bennett JC, editors. Cecil textbook 
of medicine. Philadelphia: W.B. Saunders; 2000. pp. 722-29.
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Ordás I, Eckmann L, Talamini M, et al. Ulcerative colitis. Lancet. 2012;380(9853):1606-19.
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Glickman RM. Inflammatory bowel disease: ulcerative colitis and Crohn’s disease. In: Fauci
AS, Braunwald E, editors. Harrison’s principles of internal medicine. New York: McGraw-
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Van Limbergen J, Russell RK, Drummond HE, et al. Definition of phenotypic characteristics 
of childhood-onset inflammatory bowel disease. Gastroenterology 2008;135(4):1114-22.
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Bernstein CN, Blanchard JF, Kliewer E, Wajda A. Cancer risk in patients with inflammatory 
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Eaden JA, Abrams KR, Mayberry JF. The risk of colorectal cancer in ulcerative colitis: a 
meta-analysis. Gut 2001;48(4):526-35.
10 Ng SC, Kamm MA. Therapeutic strategies for the management of ulcerative colitis. Inflamm 
Bowel Dis 2009;15(6):935-50.
11 Kornbluth A, Sachar DB, Practice Parameters Committee of the American College of 
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Gastroenterology, Practice Parameters Committee. Am J Gasteroenterol 2010;105(3):501-23.
12 Rosenberg LN, Peppercorn MA. Efficacy and safety of drugs for ulcerative colitis. Expert 
Opinion Drug Saf 2010;9(4):573-92.
13 Carter MJ, Lobo AJ, Travis SP. Guidelines for the management of inflammatory bowel disease 
in adults. Gut 2004;53(Suppl 5):1-6.
14 Chaparro M, Trapero-Marugan M, Moreno-Otero R, Gisbert JP. Azathioprine plus ribavirin 
treatment and pancytopenia. Aliment Pharmacol Ther 2009;30(9):962-3.
15 Bousvaros A. Use of immunomodulators and biologic therapies in children with inflammatory 
bowel disease. Expert Rev Clin Immunol 2010;6(4):659-66.
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16 Chande N, Wang Y, MacDonald JK, McDonald JW. Methotrexate for induction of remission 
in ulcerative colitis. Cochrane Database Syst Rev 2014;(8)CD006618.
17 Rubin DT, Ananthakrishnan AN, Siegel CA, et al. ACG clinical guideline: ulcerative colitis in 
adults. Am J Gastroenterol 2019;114(3):384-413.
18 Feuerstein JD, Isaacs KL, Schneider Y, et al. AGA clinical practice guidelines on the 
management of moderate to severe ulcerative colitis. Gastroenterology 2020;158(5):1450-61.
19 Gisbert JP, Panés J. Loss of response and requirement of infliximab dose intensification in 
Crohn's disease: a review. Am J Gastroenterol. 2009;104(3):760-7.
20 Billioud V, Sandborn WJ, Peyrin-Biroulet L. Loss of response and need for adalimumab dose 
intensification 
in 
Crohn's 
disease: 
a 
systematic 
review. 
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Gateroenterol 
2011;106(4):674-84.
21 XELJANZ® (tofacitinib) US Prescribing Information. Pfizer Labs, NY. May 2018.
22 Mandala S, Hajdu R, Bergstrom J, et al. Alteration of lymphocyte trafficking by sphingosine-
1-phosphate receptor agonists. Science 2002;296(5566):346-9.
23 Harris S, Tran JQ, Southworth H, et al. Effect of the sphingosine-1-phosphate receptor 
modulator ozanimod on leukocyte subtypes in relapsing MS. Neurol Neuroimmunol 
Neuroinflamm 2020;7(5)e839.
24 Celgene. A phase 3, multicenter, randomized, double-blind, placebo-controlled trial of oral 
RPC1063 as induction and maintenance therapy for moderate to severe ulcerative colitis 
[Internet]. clinicaltrials.gov; 2021 Sep [cited 2022 Mar 25]. Report No.: NCT02435992. 
Available from: https://clinicaltrials.gov/ct2/show/NCT02435992.
25 Celgene. A phase 2, multi-center, randomized, double-blind, placebo controlled parallel-group 
study to evaluate the clinical efficacy and safety of induction therapy with RPC1063 in patients 
with moderately to severely active ulcerative colitis [Internet]. clinicaltrials.gov; 2021 May 
[cited 
2021 
Nov 
1]. 
Report 
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NCT01647516. 
Available 
from: 
https://clinicaltrials.gov/ct2/show/NCT01647516.
26 Celgene. A phase 2/3, multi-center, randomized, double-blind, placebo-controlled (Part A) and 
double-blind, double-dummy, active-controlled (Part B), parallel group study to evaluate the 
efficacy and safety of RPC1063 administered orally to relapsing multiple sclerosis patients 
[Internet]. clinicaltrials.gov; 2021 Feb [cited 2022 Mar 25]. Report No.: NCT02047734. 
Available from: https://clinicaltrials.gov/ct2/show/NCT02047734.
27 Celgene. A phase 3, multi-center, randomized, double-blind, double-dummy, active controlled, 
parallel group study to evaluate the efficacy and safety of RPC1063 administered orally to 
relapsing multiple sclerosis patients [Internet]. clinicaltrials.gov; 2020 Nov [cited 2021 Nov 1]. 
Report 
No.: 
NCT02294058. 
Available 
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https://clinicaltrials.gov/ct2/show/NCT02294058.
28 Sandborn WJ, Feagan BG, Wolf DC, et al. Ozanimod induction and maintenance treatment for 
ulcerative colitis. N Engl J Med 2016;374(18):1754-62.
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29 Sandborn WJ, Feagan BG, D’Haens G, et al. Ozanimod as induction and maintenance therapy 
for ulcerative colitis. N Engl J Med 2021;385(14):1280-91.
30 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.
31 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 (CDER). 2016.
32 Geboes K, Riddell R, Ost A, et al. A reproducible grading scale for histological assessment of 
inflammation in ulcerative colitis. Gut 2000;47(3):404-9.
34 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.
35 Mitchell A, Guyatt G, Singer J, et al. Quality of life in patients with inflammatory bowel 
disease. J Clin Gastroenterol 1988;10(3):306-10.
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APPENDICES
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APPENDIX 1
ABBREVIATIONS AND TRADEMARKS
Term
Definition
5-ASA
5-aminosalicylate
AE
adverse event
AEI
adverse event of interest
ALC
absolute lymphocyte count
ALT
alanine aminotransferase
AST
aspartate aminotransferase
AT
aminotransferase
AV
atrioventricular
AZA
azathioprine
BMS
Bristol-Myers Squibb
CD
Crohn’s disease
CI
confidence interval
COVID
coronavirus disease
CSR
clinical study report
CTAg
Clinical Trial Agreement
DILI
drug-induced liver injury
EBV
Epstein–Barr virus
ECG
electrocardiogram
eCRF
electronic case report form
EDC
electronic data capture
ES
endoscopic subscore
EU
European Union
FDA
Food and Drug Administration
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
GI
gastrointestinal
Hb
hemoglobin
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Term
Definition
hCG
human chorionic gonadotropin
HEMI
histo-endoscopic mucosal improvement
HIPAA
Health Insurance Portability and Accountability Act
HR
heart rate
HRQOL
health-related quality of life
HRT
hormone replacement therapy
IBDQ
Inflammatory Bowel Disease Questionnaire
IC
inclusion criterion
ICF
informed consent form
ICH
International Council on Harmonisation
ICMJE
International Committee of Medical Journal Editors
IEC
Independent Ethics Committee
IgG
immunoglobulin G
IL
interleukin
IMP
investigational medicinal product
INR
international normalized ratio
IP
investigational product
IRB
Institutional Review Board
IRT
interactive response technology
IT
information technology
IUS
intrauterine system
IV
intravenous
JAK
Janus kinase
LAM
lactational amenorrhea method
LFT
liver function test
MRI
magnetic resonance imaging
MS
multiple sclerosis
PD
pharmacodynamics
PGA
Physician’s Global Assessment
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Term
Definition
PI
principal investigator
PID
patient identification number
PML
progressive multifocal leukoencephalopathy
PO
per oral
PRES
posterior reversible encephalopathy syndrome
PRO
patient-reported outcome
PVG
pharmacovigilance
QD
once daily
QOL
quality of life
RB
rectal bleeding
S1P
sphingosine 1-phosphate
SAE
serious adverse event
SAP
statistical analysis plan
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
SF
stool frequency
SOA
Schedule of Activities
SOC
system organ class
SUSAR
suspected, unexpected serious adverse reaction
TEAE
treatment-emergent adverse event
TNF
tumor necrosis factor
UC
ulcerative colitis
ULN
upper limit of normal
VZV
varicella zoster virus
WOCBP
women of childbearing potential
 
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APPENDIX 2
STUDY GOVERNANCE CONSIDERATIONS
The terms “participant” and “subject” refer to a person who has consented to participate in the 
clinical research study. Typically, the term “participant” is used in the protocol and the term 
“subject” is used in the eCRF.
REGULATORY AND ETHICAL CONSIDERATIONS
This study will be conducted in accordance with:

Consensus ethical principles derived from international guidelines, including the Declaration 
of Helsinki and Council for International Organizations of Medical Sciences international 
ethical guidelines

Applicable International Council for Harmonisation (ICH) Good Clinical Practice (GCP) 
guidelines

Applicable laws, regulations, and requirements
The study will be conducted in compliance with the protocol. The protocol, any 
revisions/amendments, and the participant ICF will receive approval/favorable opinion by the 
IEC/IRB, and regulatory authorities according to applicable regulations prior to initiation of the 
study.
All potential serious breaches must be reported to the Sponsor or designee immediately. A 
potential serious breach is defined as a quality issue (eg, protocol deviation) that is likely to affect, 
to a significant degree, 1 or more of the following: (1) the rights, physical safety, or mental integrity 
of one or more participants; (2) the scientific value of the clinical 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, product labeling information, ICF, participant recruitment 
materials (eg, advertisements), and any other written information to be provided to participants.
The investigator, Sponsor, or designee should provide the IRB/IEC with reports, updates, and other 
information (eg, expedited safety reports, amendments, administrative letters) annually, or more 
frequently, in accordance with regulatory requirements or institutional procedures.
The investigator is responsible for providing oversight of the conduct of the study at the site and 
adherence to requirements of the following where applicable:

ICH guidelines 
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
United States Code of Federal Regulations, Title 21, Part 50 (21CFR50)

European Union (EU) Directive 2001/20/EC

European Regulation 536/2014 for clinical studies (if applicable) 

European Medical Device Regulation 2017/745 for clinical device research (if applicable)

the IRB/IEC

all other applicable local regulations.
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, by the local Health Authority), except where necessary to eliminate an immediate 
hazard(s) to study participants. 
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 the following:

IRB/IEC

Regulatory authority(ies), if applicable according to 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, by the local Health Authority, must be sent to BMS.
If an amendment substantially alters the study design or increases the potential risk to the 
participant: (1) the ICF 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 participants 
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 participants prior to enrollment.
FINANCIAL DISCLOSURE
Investigators and sub-investigators will provide the Sponsor with sufficient, accurate financial 
information, in accordance with 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 study and for 1 year 
after completion of the study.
INFORMED CONSENT PROCESS
Investigators must ensure that participants are clearly and fully informed about the purpose, 
potential risks, and other critical issues regarding clinical studies in which they volunteer to 
participate. 
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The Sponsor or designee will provide the investigator with an appropriate sample ICF, which will 
include all elements required by the ICH GCP, and applicable regulatory requirements. The sample 
ICF will adhere to the ethical principles that have their origin in the Declaration of Helsinki.
The investigator or his/her representative must:

Obtain IRB/IEC written approval/favorable opinion of the written ICF and any other 
information to be provided to the participant prior to the beginning of the study and after any 
revisions are completed for new information.

Provide a copy of the ICF and written information about the study in the language in which 
the participant is proficient prior to clinical study participation. The language must be 
nontechnical and easily understood. 

Explain the nature of the study to the participant and answer all questions regarding the study.

Inform the participant that his/her participation is voluntary. The participant will be required 
to sign a statement of informed consent that meets the requirements of 21 CFR Part 50, local 
regulations, ICH guidelines, Health Insurance Portability and Accountability Act (HIPAA) 
requirements, where applicable, and the IRB/IEC or study center.

Allow time necessary for the participant to inquire about the details of the study.

Obtain an ICF signed and personally dated by the participant and by the person who conducted 
the informed consent discussion. 

Include a statement in the participant’s medical record that written informed consent was 
obtained before the participant was enrolled in the study and the date the written consent was 
obtained. The authorized person obtaining the informed consent must also sign the ICF.

Re-consent the participant to the most current version of the ICF(s) during his/her participation.
Revise the ICF whenever important new information becomes available that is relevant to the 
participant’s consent. The investigator, or a person designated by the investigator, should fully 
inform the participant of all pertinent aspects of the study and of any new information relevant to 
the participant’s willingness to continue participation in the study. This communication should be 
documented. 
The confidentiality of records that could identify participants must be protected, respecting the 
privacy and confidentiality rules applicable to regulatory requirements, the participant’s signed 
ICF, and, in the US, the participant’s signed HIPAA authorization.
The ICF must also include a statement that BMS and local and foreign regulatory authorities have 
direct access to participant records. 
Participants who are unable to give their written informed consent (eg, due to stroke or participants 
with severe dementia) may only be enrolled in the study with the consent of a legally acceptable 
representative. The participant must also be informed about the nature of the study to the extent 
compatible with his or her understanding, and should this participant become capable, he or she 
should personally sign and date the ICF as soon as possible. The explicit wish of a participant who 
is unable to give his or her written consent, but who is capable of forming an opinion and assessing 
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information to refuse participation in, or to be withdrawn from, the clinical study at any time, 
should be considered by the investigator.
The rights, safety, and well-being of the study participants are the most important considerations 
and should prevail over interests of science and society.
BMS COMMITMENT TO DIVERSITY IN CLINICAL TRIALS
The mission of BMS is to transform patients’ lives through science by discovering, developing, 
and delivering innovative medicines that help them prevail over serious diseases. 
BMS is committed to doing its part to ensure that patients have a fair and just opportunity to 
achieve optimal health outcomes.
BMS is working to improve the recruitment of a diverse participant population with the goal that 
the clinical trial becomes more reflective of the real-world population and the people impacted by 
the diseases studied.
DATA PROTECTION, DATA PRIVACY, AND DATA SECURITY
BMS collects and processes personal data of study participants, patients, health care providers,
and researchers for biopharmaceutical research and development to advance innovative, 
high-quality medicines that address the medical needs of patients. BMS ensures the privacy, 
protection, and confidentiality of such personal data to comply with applicable laws. To achieve 
these goals, BMS has internal policies that indicate measures and controls for processing personal 
data. BMS adheres to these standards to ensure that collection and processing of personal data are
limited and proportionate to the purpose for which BMS collects such personal data. This purpose 
is clearly and unambiguously notified to the individual at the time of collection of personal data. In 
the true spirit of science, BMS is dedicated to sharing clinical trial information and data with 
participants, medical/research communities, the media, policy makers, and the general public. This 
is done in a manner that safeguards participant privacy and informed consent while respecting the 
integrity of national regulatory systems. Clinical trial data, health-related research, and PVG
activities on key-coded health data transferred by BMS across national borders are done in 
compliance with the relevant data protection laws in the country and GCP requirements.
BMS protects personal information with adequate and appropriate security controls as indicated 
under the data protection laws. To align with the recommended security standards, BMS has 
adopted internal security standards and policies to protect personal data at every stage of 
its processing.
To supplement these standards, BMS enters into Clinical Trial Agreements (CTAgs) with 
confidentiality obligations to ensure proper handling and protection of personal data by third 
parties accessing and handling personal data.
BMS takes unauthorized access and disclosure of personal information very seriously. BMS has 
adopted the security standards that include National Institute of Standards and Technology 
Cybersecurity Framework for studies in the US. BMS aligns with these standards to continuously 
assess and improve its ability to protect, detect, and respond to cyber attacks and other 
unauthorized attempts to access personal data. These standards also aid in mitigating possible 
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adverse effects. Furthermore, BMS information technology (IT) has defined 6 principles to protect 
our digital resources and information: 
1) Responsibilities of IT personnel
2) Securing the BMS digital infrastructure
3) Identity and access management
4) External partner connections
5) Cyber threat detection and response
6) Internal cyber incident investigation
SOURCE DOCUMENTS
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator’s site.
Data reported on the case report form or entered in the eCRF that are transcribed from source 
documents must be consistent with the source documents or the discrepancies must be explained. 

The investigator may need to request previous medical records or transfer records depending 
on the study. Also, current medical records must be available.

Definition of what constitutes source data and its origin can be found in the source data location 
list/map or equivalent document.
The investigator is responsible for ensuring that the source data are accurate, legible, 
contemporaneous, original, and attributable, whether the data are handwritten 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 records/electronic health 
records, AE tracking/reporting, protocol-required assessments, and/or drug accountability records.
When paper records from such systems are used in place of an 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. 
STUDY INTERVENTION RECORDS
Records for study intervention (whether supplied by BMS, its vendors, or the site) must 
substantiate study intervention integrity and traceability from receipt, administration, and through 
destruction or return. Records must be made available for review at the request of BMS/designee 
or a Health Authority.
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If
Then
Supplied by BMS (or its vendors)
Records or logs must comply with applicable 
regulations and guidelines and should include
(but are not limited to) the following:

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 participant, including unique 
participant identifiers

Amount transferred to another area/site 
for dispensing or storage

Non-study disposition (eg, lost, wasted) 

Amount destroyed at study site, if 
applicable

Amount returned to BMS

Dates and initials of person responsible 
for IP

Dispensing/accountability per the 
Delegation of Authority Form
Note: BMS or its 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 eCRF 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. Electronic case report forms may be requested for AEs and/or 
laboratory test result abnormalities that are reported or identified during the study.
For sites using the Sponsor or designee electronic data capture (EDC) tool, eCRFs 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 Pregnancy Surveillance Form, respectively. If the 
electronic SAE form is not available, a paper SAE form can be used. 
The confidentiality of records that could identify participants must be protected, respecting the 
privacy and confidentiality rules in accordance with the applicable regulatory requirement(s).
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The investigator will maintain a signature sheet to document signatures and initials of all persons 
authorized to make entries and/or corrections on eCRFs. 
The completed eCRF and SAE/pregnancy CRFs must be promptly reviewed, signed, and dated by 
the investigator or qualified physician who is a sub-investigator and who is delegated this task on 
the Delegation of Authority Form. The investigator must retain a copy of the eCRFs, including 
records of the changes and corrections.
Each individual electronically signing eCRFs must meet Sponsor or designee training 
requirements and must only access the BMS EDC tool using the unique user account provided by 
the 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 
mitigation strategies and analytical risk-based monitoring), methods, responsibilities, and 
requirements, including handling of non-compliance 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.
In addition, the study may be evaluated by the 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 the Sponsor or designee. 
RECORDS RETENTION
The investigator 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 its designee, whichever is longer. The investigator must contact BMS prior 
to destroying any records associated with the study.
BMS or its designee will notify the investigator 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/IEC). 
Notice of such transfer will be given in writing to BMS or its designee. 
RETURN OF STUDY INTERVENTION
For this study, study intervention, such as partially used study intervention titration blistercard or 
bottles, may be destroyed on-site. 
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If
Then
Study interventions supplied by BMS (or
vendors)
Any unused study interventions can only be 
destroyed after being inspected and reconciled 
by the responsible Study Monitor, unless study 
intervention titration blistercards or bottles
must be immediately destroyed as required for 
safety, or to meet local regulations (eg, 
cytotoxic or biologic agents).
Partially used study interventions and/or 
titration blistercard or bottles may be destroyed 
after proper reconciliation and documentation. 
However, unused IMP must be reconciled by 
the site monitor/clinical research associate 
prior to destruction.
If study interventions will be returned, the 
return will be arranged by the responsible 
study monitor.
It is the investigator’s or designee’s responsibility to arrange for disposal of study interventions, 
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 study intervention.

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 standard operating procedures and a copy provided to BMS upon request.

Records are maintained that allow for traceability of each blistercard or bottle, including the
date disposed of, quantity disposed, and identification of the person disposing the blistercards
or bottles. The method of disposal (eg, 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 Study
Monitor to review throughout the clinical study period.
It is the investigator’s or designee’s responsibility to arrange for disposal of all empty blistercards 
or bottles.
If conditions for destruction cannot be met, the responsible study monitor will make 
arrangements for return of study interventions provided by BMS (or its vendors). 
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STUDY AND SITE CLOSURE
The Sponsor/designee reserves the right to close the study site or to terminate the study at any 
time for any reason at the sole discretion of the Sponsor. Study sites will be closed upon 
study completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study site closure visit has been performed.
The investigator may initiate study site closure at any time, provided there is reasonable cause and 
sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study site by the Sponsor or investigator may include, but are 
not limited to, the following:
For study termination:

Discontinuation of further development of study intervention

For site termination:

Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC or
local Health Authorities, the Sponsor’s procedures, or GCP guidelines

Inadequate or no recruitment (evaluated after a reasonable amount of time) of participants by
the investigator

Discontinuation of further study intervention development
If the study is prematurely terminated or suspended, the Sponsor shall promptly inform the 
investigators, the IECs/IRBs, the regulatory authorities, and any contract research organization(s) 
used in the study of the reason for termination or suspension, as specified by the applicable 
regulatory requirements. The investigator shall promptly inform the participant and should ensure
appropriate participant therapy and/or follow-up.
DISSEMINATION OF CLINICAL STUDY DATA
To benefit potential study participants, patients, health care 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 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.
In the EU, the summary of results and summary for laypersons will be submitted within 1 year of 
global end of trial.
CLINICAL STUDY REPORT
A signatory investigator must be selected to sign the clinical study report (CSR). 
For each CSR related to this protocol, the following criteria will be used to select the signatory 
investigator:

External PI designated at protocol development

National coordinating investigator
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
Study Steering Committee chair or designee

Participant recruitment (eg, among the top quartile of enrollers)

Involvement in study design

Regional representation (eg, among top quartile of enrollers from a specified region or country)
SCIENTIFIC PUBLICATIONS
The data collected during this study are confidential and proprietary to the Sponsor or designee. 
Any publications or abstracts arising from this study must adhere to the publication requirements 
set forth in the CTAg governing (study site or investigator) participation in the study. These 
requirements include, but are not limited to, submitting proposed publications to the Sponsor or 
designee at the earliest practicable time prior to submission or presentation and otherwise within 
the period set forth in the CTAg.
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 
PI, sub-investigator, or any other member of the study staff without the prior written consent of 
the Sponsor.
Authorship of publications by the Sponsor or its designees is aligned with the criteria of the 
International Committee of Medical Journal Editors (ICMJE; www.icmje.org). Authorship 
selection is based on 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 participants with quality data), analysis, or interpretation of data for the 
work (eg, problem solving, advice, evaluation, insights and conclusion)
2) Drafting the work or revising it critically for important intellectual content
3) Final approval of the version to be published
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 the 
Sponsor for authorship of the primary publication. Sub-investigators 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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Participants must be informed that their study-related data (including but not limited to), such as 
endoscopy images, may be used for the publication of results, if required.
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APPENDIX 3
SELECTED INSTRUMENT DEFINITIONS (BASED ON 
PERMUTATIONS OF THE MAYO SCORE)
Modified Mayo Score
Sum of the following components of the Mayo score (Range 0-9):

SF subscore: Range 0-3

RB subscore: Range 0-3

ES: Range 0-3
ES is modified from the original description: Friability is not included 
in ES = 1.
Partial Mayo Score
Sum of the following components of the Mayo score (Range 0-9): 

SF subscore: Range 0-3

RB subscore: Range 0-3

PGA: Range 0-3
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APPENDIX 4
WOMEN OF CHILDBEARING POTENTIAL DEFINITIONS AND 
METHODS OF CONTRACEPTION
Appendix 4 provides general information and definitions related to 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 participants, refer to Section 6.1 of the 
protocol. Only the contraception methods described in Section 6.1 are acceptable for this study.
DEFINITIONS
Woman of Childbearing Potential 
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

Pre-menopausal female with one of the following:

Documented hysterectomy

Documented bilateral salpingectomy

Documented bilateral oophorectomy
Note: Documentation can come from the site personnel’s review of the participant’s medical 
records, medical examination, or medical history interview.

Post-menopausal female

A post-menopausal state is defined as 12 months of amenorrhea in a woman over the age 
of 45 years in the absence of other biological or physiological causes. In addition, females 
under the age of 55 years must have a serum follicle-stimulating hormone (FSH) level 
> 40 mIU/mL to confirm menopause.
Note: Females treated with hormone replacement therapy (HRT) are likely to have artificially 
suppressed FSH levels and may require a washout period to obtain a physiologic FSH level. The 
duration of the washout period is a function of the type of HRT used. Suggested guidelines for the 
duration of the washout periods for HRT types are presented below. Investigators should use their 
judgment in checking serum FSH 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 FSH 
level is > 40 mIU/mL at any time during the washout period, the woman can be considered 
postmenopausal.
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End of Relevant Systemic Exposure
End of relevant systemic exposure is the time point at which the study intervention (IMP and other 
study interventions, ie, non-IMP/auxiliary medicinal product required for study) or any active 
major metabolites have decreased to a concentration that is no longer considered relevant for 
human teratogenicity or fetotoxicity. This should be evaluated in the context of safety margins 
from the no-observed-adverse-effect level or the time required for 5 half-lives of the study 
intervention 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 in which hormonal contraception is permitted by the 
study protocol.)b

Oral (birth control pills)

Intravaginal (rings)

Transdermal

Combined (estrogen- and progestogen-containing) hormonal contraception must begin at 
least 30 days prior to initiation of study intervention.

Progestogen-only hormonal contraception associated with inhibition of ovulation. (This 
method of contraception can only be used by WOCBP participants in studies in which 
hormonal contraception is permitted by the study protocol.)b

Oral

Injectable

Progestogen-only hormonal contraception must begin at least 30 days prior to initiation of 
study intervention.
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 in which hormonal contraception is permitted by the study protocol.)b

Intrauterine device.

Intrauterine system (IUS). (This method of contraception can only be used by WOCBP 
participants in studies in which 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 intervention. 
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 participant.

Continuous abstinence must begin at least 30 days prior to initiation of study intervention.

It is not necessary to use any other method of contraception when complete abstinence is 
elected.

WOCBP participants who choose complete abstinence must continue to have pregnancy 
tests, as specified in Section 2 of the protocol.

Acceptable alternate methods of highly effective contraception must be discussed in the 
event that the WOCBP participant chooses to forego complete abstinence.

Periodic abstinence (including, but not limited to, calendar, symptothermal, post-ovulation 
methods), withdrawal (coitus interruptus), spermicides only, and lactation amenorrhea 
method (LAM) are not acceptable methods of contraception for this study.
NOTES: 
a Typical use failure rates may differ from failure rates when contraceptive methods are used consistently and
correctly. Use should be consistent with local regulations regarding the use of contraceptive methods for 
participants in clinical studies. 
b Hormonal contraception may be susceptible to interaction with the study intervention, 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 Sections 6.1 Inclusion Criteria and 7.7.1 Prohibited and/or Restricted 
Treatments of the protocol.
c IUS 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 Sections 6.1 Inclusion Criteria and 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.
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
Cervical cap with spermicide.

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 in which hormonal contraception is prohibited.)
Unacceptable Methods of Contraception

Periodic abstinence (calendar, symptothermal, post-ovulation 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: Pregnancy of the protocol and APPENDIX 4.
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APPENDIX 5
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS: 
DEFINITIONS AND PROCEDURES FOR RECORDING, 
EVALUATING, FOLLOW-UP, AND REPORTING
ADVERSE EVENTS
AE Definition
An AE is defined as any new untoward medical occurrence or worsening of a pre-existing 
medical condition occurring in a clinical investigation participant after signing of informed 
consent, whether or not considered related to the study intervention. 
An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory 
test result), symptom, or disease temporally associated with the study intervention.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
results from other safety assessments (eg, ECGs, radiological scans, vital sign 
measurements), including those that worsen from baseline, considered clinically significant 
in the medical and scientific judgment of the investigator. Note that abnormal laboratory test
results or other safety assessment findings 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 pre-existing condition, including either an increase 
in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study intervention administration, even though 
the condition 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 the definition above, then it cannot be an SAE, even if serious 
conditions are met.
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SERIOUS ADVERSE EVENTS
A SAE is defined as 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 that 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 department or other hospital department < 24 hours that does not 
result in admission (unless considered an important medical or life-threatening event).

Elective surgery that was planned prior to signing consent.

Admissions 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 enrollment 
in 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/incapacity.
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 results 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 department
or at home for allergic bronchospasm and blood dyscrasias or convulsions that do not result in 
hospitalization. Potential DILI is also considered an important medical event. (See Section 9.2.7:
Potential DILI of the protocol for the definition of a potential DILI.) 
Pregnancy and DILI must follow the same transmission timing and processes to BMS as those 
used for SAEs. (See Section 9.2.5: Pregnancy of the protocol for reporting pregnancies.)
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EVALUATING AES AND SAES
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, evidence, 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 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 the 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 the Sponsor.

The investigator may change his/her opinion of causality in light of follow-up information 
and send an SAE follow-up report with the updated causality assessment.

The causality assessment is one of the criteria used when determining regulatory reporting 
requirements.

Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported during the 
study and assign it to one of the following categories: 

Mild: An event that is easily tolerated by the participant, 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.
An event is defined as “serious” when it meets at least one of the pre-defined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe.
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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 intervention or if new 
information becomes available, the SAE report must be updated and submitted within 24 hours 
to BMS (or the designee) using the same procedure used for transmitting the initial SAE report.
All AEs/SAEs must be followed to resolution or stabilization.
REPORTING OF SAES TO SPONSOR OR DESIGNEE

SAEs, whether related or not related to study intervention, and pregnancies must be reported 
to BMS (or the designee) promptly and not to exceed 24 hours of awareness of the event.

SAEs must be recorded on the SAE Report Form.

The required method for SAE data reporting is through the eCRF.

The paper SAE Report Form is intended only as a back-up option when the EDC system 
is unavailable/not functioning for transmission of the eCRF to BMS (or the designee).
In this case, the paper form is transmitted via email or confirmed fax transmission.
When paper forms are used, the original paper forms are to remain on site.

Pregnancies must be recorded on paper Pregnancy Surveillance Forms and transmitted via 
email or confirmed fax transmission.
SAE Email Address: SAE reporting contact information will be provided locally
SAE Fax Number: SAE reporting contact information will be provided locally.
SAE Telephone Contact (required for SAE and pregnancy reporting): SAE reporting contact 
information will be provided locally.
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APPENDIX 6
SELECTED ENDPOINT DEFINITIONS
Clinical 
Response 
(modified Mayo 
score, primary 
endpoint)
Achieving the following changes 
from baseline in the modified Mayo 
score:

A decrease from baseline in the 
modified Mayo score ≥2 points, 
and

A decrease from baseline in the 
modified Mayo score ≥35% , and

A decrease from baseline in RB 
subscore ≥1 point or absolute RB
subscore ≤1. 
Clinical 
Remission
(modified Mayo 
score)
A modified Mayo score with the 
following:

SF subscore ≤1, with ≥1 point 
decrease from baseline, and

RB subscore = 0, and

ES ≤1
Clinical 
Remission
(partial Mayo)
Partial Mayo score < 2.5
Endoscopic 
Response
A decrease from baseline of ≥1 point 
in Mayo ES
Endoscopic 
Improvement
Mayo ES ≤1
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Endoscopic 
Remission
Mayo ES = 0
Histological 
Improvement


Achieving a Geboes score < 3.1
Histologic 
Remission
Achieving Geboes score < 2
HEMI 
Mayo ES ≤1 and a Geboes score 
< 3.1
Corticosteroid-
free Clinical 
Remission
(modified 
Mayo score)
Clinical remission (by modified 
Mayo criteria), and no oral systemic 
steroid use in prior 90 days. 
Corticosteroid-
free Clinical 
Remission
(partial Mayo 
score)
Clinical remission (by partial Mayo 
criteria), and no oral systemic steroid 
use in prior 90 days.
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