A Phase 3, Multicenter, Open-Label Extension Trial of Oral RPC1063 as Therapy for Moderate to Severe Ulcerative Colitis
Phase: PHASE3
Conditions: Ulcerative Colitis
Sponsor: Celgene

Official Title of Study: 
A Phase 3, Multicenter, Open-Label Extension Trial of Oral RPC1063 as Therapy for Moderate to 
Severe Ulcerative Colitis 
 
NCT Number: NCT02531126 
Document Date (Date in which document was last revised): 10 Aug 2022 
 
 
 

Sponsor: Celgene International II Sàrl
Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
1
1
CLINICAL TRIAL PROTOCOL
Protocol Title: 
A Phase 3, Multicenter, Open-Label Extension Trial of 
Oral RPC1063 as Therapy for Moderate to Severe 
Ulcerative Colitis
Protocol Number:
RPC01-3102
Version and Date: 
10.0 dated 10 August 2022
Replaces Version:
9.0 dated 23 August 2021
Product:
RPC1063 (BMS-986374)
IND No.:
115,243
EudraCT No.:
2015-001600-64
Trial Phase:
3
Sponsor:
Celgene International II Sàrl
Route de Perreux 1
2017 Boudry, Switzerland
Tel: + 41 32 729 85 00
Medical Monitor:
Office: 
Cell: 
CONFIDENTIAL
This protocol is provided to you as an Investigator, potential Investigator, or 
consultant for review by you, your staff, and ethics committee/institutional 
review board. The information contained in this document is regarded as 
confidential and, except to the extent necessary to obtain informed consent, 
may not be disclosed to another party unless such disclosure is required by 
law or regulations. Persons to whom the information is disclosed must be 
informed that the information is confidential and may not be further 
disclosed by them.
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Sponsor: Celgene International II Sàrl
Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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Signatures
PROTOCOL TITLE:  A Phase 3, Multicenter, Open-Label Extension Trial of Oral RPC1063 as 
Therapy for Moderate to Severe Ulcerative Colitis
PROTOCOL NO:  RPC01-3102
Receptos Services LLC
Date
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Sponsor: Celgene International II Sàrl
Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
3
1.0
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930190807
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Sponsor: Celgene International II Sàrl
Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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Sponsor:  Celgene International II Sàrl
Signature of Celgene International II 
Sàrl Representative
Date 
Printed Name of Celgene International II Sàrl Representative
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Sponsor: Celgene International II Sàrl
Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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1.0
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Sponsor: Celgene International II Sàrl
Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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OVERALL RATIONALE FOR PROTOCOL AMENDMENT 10.0:
The main reason for this amendment is to extend the duration of the study such that all patients 
complete 5 years (Week 238) of treatment. 
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 10.0
Section Number & Title
Description of Change
Brief Rationale
Synopsis;
Section 8.1: Summary of Trial 
Design;
Table 2: Schedule of Events
(footnote d);
Section 8.2: Discussion of Trial 
Design;
Section 8.3.4: Safety Follow-Up;
Section 8.3.6: Trial Duration;
Section 10.1: Treatments 
Administered
Study duration was 
extended such that each
patient completes 5 years 
(Week 238) of treatment 
and follow-up.
Study extended to enable 
5 years of efficacy and 
safety data for all 
ongoing patients.
Table 2: Schedule of Events;
Section 8.3.4: Safety Follow-Up;
Section 9.4: Trial Discontinuation;
Section 10.5.2: Concomitant 
Medications Prohibited Through 
 after Investigational Drug 
Discontinuation;
Section 10.5.3: Concomitant 
Medications Between 
 after 
Investigational Drug 
Discontinuation and the 90-day 
Safety Follow-up Visit;
Section 10.6: Medical Care of 
Patients after End of Trial;
Section 12.3: Patient-Reported 
Outcomes;
Section 13.1.11: Clinical 
Laboratory Evaluations
Removed 
Safety 
Follow-up (SFU) Visit.
Language regarding 
medications prohibited 
through the 
SFU 
visit was updated to indicate 
these medications are 
prohibited through 
 
following treatment 
discontinuation.
The 
 SFU Visit 
removed to streamline 
assessments for ongoing 
patients.
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Sponsor: Celgene International II Sàrl
Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 10.0
Section Number & Title
Description of Change
Brief Rationale
Table 2: Schedule of Events;
 
Table 2: Schedule of Events
Footnote h was updated to 
state that endoscopy 
 
 
visit will not need to be 
repeated if an endoscopy 
has been completed within 
.
To avoid unnecessary 
endoscopies.
Table 2: Schedule of Events
Table 2: Schedule of Events
Added footnote s to indicate 
ulcerative colitis disease 
relapse and related 
symptoms will be monitored 
as trial endpoints and thus 
will not be recorded as 
adverse events (AEs), 
unless it qualifies as a 
serious AE to trigger safety 
reporting.
Added a reminder to sites 
so that ulcerative colitis 
is not recorded as an AE 
unless serious.
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Sponsor: Celgene International II Sàrl
Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 10.0
Section Number & Title
Description of Change
Brief Rationale
Table 2: Schedule of Events
Frequency of additional 
visits for 
 
 and for 
 
 were 
updated from once a year to 
 (as 
indicated).
To align timing with visit 
schedule.
Table 2: Schedule of Events;
 
Table 2: Schedule of Events;
Section 13.1.1: Physical 
Examination
Removed interim physical 
examination at 90-day SFU.
Complete physical 
examination should be 
performed at 90-day
SFU.
Table 2: Schedule of Events
Table 2: Schedule of Events
Updated blood volumes in 
footnote n past 
.
Updated blood volumes 
to align with frequency 
and type of blood draws.
Section 8.3.2: Trial Visits
To clarify that patients who 
have completed 5 years of 
treatment (Week 238) 
should come in at the time 
of their next scheduled visit. 
At this visit, these patients 
will complete the 
 
 procedures and 
then enter the SFU period.
Clarified procedures for 
patients who have 
completed 5 years of 
treatment at the time this 
amendment is 
implemented.
Section 8.3.6: Trial Duration
Added information 
regarding how patients may 
Outlined options for 
treatment post study.
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Sponsor: Celgene International II Sàrl
Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 10.0
Section Number & Title
Description of Change
Brief Rationale
continue to receive 
treatment after the trial.
Section 10.5.4: Allowed Vaccines
Removed the following text:
If non-live vaccinations are 
to be completed during the 
study, vaccine titers should 
be measured 4 to 8 weeks 
following the last 
administration of the 
vaccine.
Measuring titers 
following vaccination is 
not necessary for this 
trial.
Section 13.2.7: 
 
Pandemic
Language regarding 
reporting of vaccine 
administration was updated.
Updated to align with 
electronic case report 
forms.
All
Minor formatting and 
typographical corrections.
Minor, therefore have not 
been summarized.
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Sponsor: Celgene International II Sàrl
Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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SYNOPSIS
Sponsor/Company: Celgene International II Sàrl
Investigational Product: RPC1063 (BMS-986374)
Name of Active Ingredient: RPC1063
Protocol Title:
A Phase 3, Multicenter, Open-Label Extension Trial of Oral RPC1063 as Therapy 
for Moderate to Severe Ulcerative Colitis
Protocol No:
RPC01-3102
Trial Sites:
Approximately 
 sites
Regions:
North America, Europe, Asia Pacific, South America, South Africa
Trial Duration:  
Estimated date of first patient enrolled:  August 2015
Estimated date of last patient last visit completed: March 2025 
Phase:  3
Main Objectives:

Evaluate the long-term safety of RPC1063 for the treatment of all patients with moderate to severe UC.

Evaluate the long-term efficacy of RPC1063 for the treatment of adult patients with moderate to severe 
UC.
Methodology:
This is an open-label, multicenter, extension trial to evaluate the long-term safety and efficacy of RPC1063 in 
patients with moderately to severely active ulcerative colitis (UC). Only those patients who have previously 
participated in a trial of RPC1063 (eg, RPC01-3101 or completed at least 1 year of the open-label period of 
RPC01-202) and meet eligibility criteria will be eligible for entry in this trial.
Patients entering the trial from the open-label period of RPC01-202
 of RPC01-3101 will continue to 
receive RPC1063/ozanimod HCl at 1 mg (equivalent to ozanimod 
mg) daily. All patients entering the trial 
from a blinded parent trial or treatment period of RPC1063
 of RPC01-3101) will initiate RPC1063 
treatment in accordance with a 7-day dose escalation regimen starting with RPC1063/ozanimod HCl 
 mg 
(equivalent to ozanimod 
 mg) on Days 
, followed by RPC1063/ozanimod HCl 
mg (equivalent to 
ozanimod 
 mg) on Days 
, and reaching the final dose level, RPC1063/ozanimod HCl 1 mg on Day . 
Each patient will receive RPC1063 at 1 mg/day as part of this clinical trial until they complete 5 years (Week 
238) and the Safety Follow-up Visit, unless the Sponsor discontinues the development program.  Patients who are 
not in clinical response or remission at trial entry may be discontinued from investigational drug if they do not 
show clinical improvement from the Baseline Visit of the RPC01-3102 by 
.
Safety Monitoring/Follow-up:
The safety of patients will be monitored by collection of treatment-emergent adverse events (TEAEs), serious 
adverse events (SAEs), TEAEs leading to discontinuation, and TEAEs of special interest, as well as, physical 
examination findings, vital signs measures, electrocardiograms (ECGs) findings, 
results, 
results, clinical laboratory test results (blood chemistry including liver 
transaminases, hematology). White blood cell (WBC) and 
 will be centrally 
monitored. 
Patients entering the trial from the open-label period of RPC01-202 or from the open-label 
 of RPC01-
3101 will continue to receive RPC1063/ozanimod HCl at 1 mg daily and no additional cardiac monitoring is 
required. All patients who enter this trial from a parent blinded trial or treatment period of RPC1063
 
 of RPC01-3101) will undergo 
 
   
Patients who discontinue from treatment for any reason, including lack of response and AE, even if alternative 
treatment is given, will be followed for 90 days for collection of safety data and for assessment of their disease 
status.
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Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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In the event that commercial ozanimod becomes available prior to end of the study, patients may discontinue and 
transition to the commercial product after discussion with the Investigator at his/her discretion.  Patients who 
transition to commercial ozanimod prior to completing the study are not required to attend the Safety Follow-up 
(SFU) Visit after their 
 visit as long as commercial ozanimod is started within 14 days of 
discontinuation of study drug.
Patients who complete 5 years (Week 238) of treatment may transition to commercial RPC1063/ozanimod HCl if 
approved and available in their country. In countries where commercial ozanimod is not available, patients may 
be eligible for a country-specific support program where available (see Section 8.3.6 for details).  
Endoscopy:
All endoscopies will be recorded and read by a central reader. 
Number of patients:  Up to 
Diagnosis and main criteria for inclusion: 
Inclusion Criteria:
Patients are eligible if they fulfill all of the following:
1.
Previously participated in a trial of RPC1063 (eg, RPC01-3101 or completed at least 1 year of the open-
label period of RPC01-202) and meet the criteria for participation in the open-label extension as outlined in 
the prior trial.
2.
Females of childbearing potential (FCBP):
Must agree to practice a highly effective method of contraception throughout the trial until completion of 
the 90-day SFU Visit. Highly effective methods of contraception are those that alone or in combination 
result in a failure rate of a Pearl index of less than 1% per year when used consistently and correctly. 
Acceptable methods of birth control in the trial are the following:

combined hormonal (oestrogen and progestogen containing) contraception, which may be oral, 
intravaginal, or transdermal 

progestogen-only hormonal contraception associated with inhibition of ovulation, which may be oral, 
injectable, or implantable

placement of an intrauterine device (IUD)

placement of an intrauterine hormone-releasing system (IUS)

bilateral tubal occlusion

vasectomized partner

complete sexual abstinence

Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), 
spermicides only, and lactational amenorrhea method are not acceptable methods of contraception.
3.
Must provide written informed consent prior to any trial-related procedures and have the ability to be 
compliant with the schedule of protocol assessments.
Diagnosis and main criteria for exclusion: 
Exclusion Criteria:
Patients are not eligible for this trial if they fulfill any of the following:
Exclusions Related to Medications:
1.
Have received any of the following therapies since the first dose of investigational drug in the prior 
RPC1063 trial:

Treatment with a biologic agent 

Treatment with an investigational agent other than RPC1063

Treatment with a live vaccine or live attenuated vaccine within 4 weeks prior to Visit of this trial

Treatment with D-penicillamine, leflunomide, thalidomide, natalizumab, fingolimod, etrasimod, or 
tofacitinib
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Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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
Treatment with lymphocyte-depleting therapies (eg, Campath, anti-CD4, cladribine, rituximab, 
ocrelizumab, cyclophosphamide, mitoxantrone, total body irradiation, bone marrow transplantation, 
alemtuzumab, daclizumab)
2.
Are currently receiving or require initiation of any of the following therapies:

Treatment with corticosteroids at a dose that exceeds the prednisone equivalent of 40 mg per day

Treatment with immunosuppressive agents (eg, azathioprine, 6-MP, or methotrexate)

Chronic non-steroidal anti-inflammatory drug (NSAID) use (Note: occasional use of NSAIDs and 
acetaminophen [eg, headache, arthritis, myalgias, or menstrual cramps] and aspirin up to 325 mg/day is 
permitted)

Treatment with Class Ia or Class III anti-arrhythmic drugs or treatment with two or more agents in 
combination known to prolong PR interval 
3.
Are receiving treatment with any of the following drugs or interventions within the corresponding 
timeframe:

At Day 
CYP2C8 inhibitors (eg, gemfibrozil or clopidogrel) or inducers (eg, rifampicin)

Two weeks prior to Day 
Monoamine oxidase inhibitors (eg, selegiline, phenelzine) 
4.
Are receiving treatment with breast cancer resistance protein (BCRP) inhibitors (eg, cyclosporine, 
eltrombopag)
Exclusions Related to General Health:
5.
Pregnancy, lactation, or a positive serum beta human chorionic gonadotropin (hCG) 
6.
Clinically relevant hepatic, neurological, pulmonary, ophthalmological, endocrine, psychiatric or other 
major systemic disease making implementation of the protocol or interpretation of the trial difficult or that 
would put the patient at risk by participating in the trial or that would have required a patient to discontinue 
treatment in the previous RPC1063 trial
7.
Clinically relevant cardiovascular conditions, including history or presence of recent myocardial infarction, 
unstable angina, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization, 
Class III/IV heart failure, sick sinus syndrome, or severe untreated sleep apnea
Exclusions Related to Laboratory Results:
Duration of treatment:
As part of this clinical trial, until the patient completes 5 years (Week 238) and the Safety Follow-up Visit, unless
the Sponsor discontinues the development program.
Endpoints:
Definitions:
Complete Mayo score: the sum of the RBS, SFS, PGA subscore, and the MES.  Each subscore has a range 
of 0-3 points and the complete Mayo score has a range of 0-12 points
9-point Mayo score: the sum of the RBS, SFS, and the MES.  The 9-point Mayo score has a range of 0-9 
points
Partial Mayo score: the sum of the RBS, SFS, and the PGA subscore.  The Partial Mayo score has a range 
of 0-9 points
Clinical Remission
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Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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Three-component Mayo: RBS = 0 and SFS ≤ 1 (and a decrease of ≥ 1 point from the Baseline SFS) and 
MES ≤1
Clinical Response
Three-component Mayo: A reduction from Baseline in the 9-point Mayo score of ≥ 2 points and ≥ 35%, 
and a reduction from Baseline in the RBS of ≥ 1 point or an absolute RBS of ≤ 1 point
Corticosteroid-free Remission: Clinical remission while off corticosteroids for ≥12 weeks
Endoscopic Improvement: MES of ≤ 1 point
Mucosal Healing: MES of ≤ 1 point and a Geboes index score < 2.0
Histologic Remission: Geboes index score < 2.0
For statistical analysis purposes, clinical remission and clinical response will be calculated using the Three-
component Mayo definition. 
Efficacy Endpoints:

Proportion of patients in clinical remission

Proportion of patients with a clinical response

Proportion of patients with endoscopic improvement

Proportion of patients with mucosal healing

Proportion of patients with corticosteroid-free remission

Change from Baseline in complete Mayo score, partial Mayo score, and 9-point Mayo score

Proportion of patients with histologic remission

Proportion of patients with clinical response, clinical remission, or endoscopic improvement in patients 
who had previously received anti-TNF therapy
Safety Endpoints:

The incidence, severity, and relationship of treatment-emergent adverse events (TEAEs), serious AEs 
(SAEs), TEAEs leading to discontinuation of investigational drug, and TEAEs of special interest
Statistical Methods:
All patients who receive at least one dose of investigational drug in this trial will comprise both the Intent-to-
Treat population and the Safety population.  These populations will be used to summarize all efficacy and safety 
data.
Each efficacy endpoint will be summarized with the number and percent of patients for proportion-based 
endpoints, and with the number of patients, mean, standard deviation, median, minimum, and maximum for 
continuous endpoints.   For both types of endpoints, 95% confidence intervals around the estimates may also be 
presented.  Due to the open-label nature of the trial and the lack of a control group, all data will be summarized,
and no hypothesis testing will be performed.  All efficacy data will be listed.
All safety data will be listed and summarized.  All TEAEs will be coded and tabulated by System Organ Class 
and Preferred Term.  Incidence of TEAEs, SAEs, AEs leading to discontinuation, and AEs of special interest will 
be summarized and presented in descending order of frequency.  Associated clinical laboratory parameters such 
as hepatic enzymes, renal function, and hematology values will be grouped and presented together.  Individual 
patient values will be listed and values outside of the standard reference range will be flagged.  Shift tables and 
analyses of changes from Baseline will be produced.  The change from Baseline for each of the vital signs and 
ECG parameters will be summarized. Incidence of abnormal vital signs parameters and outlier ECG results will 
be tabulated.
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Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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Sample Size Justification:
As this is an open-label extension trial for patients who previously participated in a trial of RPC1063 for UC, 
there is no statistical basis for the sample size.  It is anticipated that up to 
 patients who participated in prior 
studies of RPC1063 in UC may be eligible for treatment in this trial.
Version and Date:  Version 10.0 dated 10 August 2022
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Sponsor: Celgene International II Sàrl
Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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3
TABLE OF CONTENTS
1
CLINICAL TRIAL PROTOCOL..............................................................................1
OVERALL RATIONALE FOR PROTOCOL AMENDMENT 10.0:..........................................6
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 10.0 ..............................6
2
SYNOPSIS.............................................................................................................10
3
TABLE OF CONTENTS........................................................................................15
4
LIST OF TABLES..................................................................................................18
5
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ...........................19
6
INTRODUCTION..................................................................................................22
6.1
Ulcerative Colitis....................................................................................................22
6.2
RPC1063................................................................................................................23
6.2.1
Nonclinical Studies.................................................................................................24
6.2.2
Clinical Studies.......................................................................................................25
6.3
Rationale for the Current Trial................................................................................25
25
25
28
29
7
TRIAL OBJECTIVES AND ENDPOINTS ............................................................30
7.1
Objectives...............................................................................................................30
7.2
Efficacy Endpoints .................................................................................................30
7.2.1
Definitions..............................................................................................................30
7.2.2
Efficacy Endpoints..................................................................................................30
7.3
Safety Endpoints.....................................................................................................31
31
8
INVESTIGATIONAL PLAN .................................................................................32
8.1
Summary of Trial Design........................................................................................32
8.2
Discussion of Trial Design......................................................................................37
8.3
Trial Periods...........................................................................................................37
8.3.1
Visit .....................................................................................................................37
8.3.2
Trial Visits..............................................................................................................38
38
8.3.4
Safety Follow-Up....................................................................................................38
8.3.5
Study Stopping Rules ..............................................................................................39
8.3.6
Trial Duration ........................................................................................................39
9
SELECTION AND WITHDRAWAL OF PATIENTS............................................40
9.1
Inclusion Criteria....................................................................................................40
9.2
Exclusion Criteria...................................................................................................41
9.3
Considerations for Patients with Comorbid Conditions ...........................................42
9.3.1
Patients with Type 2 Diabetes Mellitus ...................................................................42
9.3.2
Patients with History of Cardiac Disease................................................................42
9.4
Trial Discontinuation..............................................................................................42
10
INVESTIGATIONAL DRUGS ..............................................................................45
10.1
Treatments Administered........................................................................................45
10.1.1
Instructions for Missed Dose(s) ..............................................................................45
10.2
Method of Assigning Patients to Treatment ............................................................45
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Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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10.3
Selection of Dose in the Trial..................................................................................46
10.4
Selection and Timing of Dose for Each Patient .......................................................46
10.5
Prior and Concomitant Treatments..........................................................................46
10.5.1
Allowed Medications ..............................................................................................46
10.5.2
Concomitant Medications Prohibited Through 
 After Investigational 
Drug Discontinuation .............................................................................................47
10.5.3
Concomitant Medications Between 
 After Investigational Drug 
Discontinuation and the 90-day Safety Follow-up Visit...........................................47
10.5.4
Allowed Vaccinations .............................................................................................48
10.6
Medical Care of Patients after End of Trial.............................................................48
10.7
Treatment Compliance............................................................................................48
10.8
Blinding..................................................................................................................49
11
INVESTIGATIONAL DRUG MATERIALS AND MANAGEMENT ...................50
11.1
Investigational Drug ...............................................................................................50
11.2
Packaging and Labelling.........................................................................................50
11.3
Investigational Drug Accountability .......................................................................50
12
ASSESSMENT OF EFFICACY.............................................................................52
12.1
Complete Mayo Score, Partial Mayo Score, 9-Point Mayo Score, and Mayo 
Subscores ...............................................................................................................52
12.2
Flexible Sigmoidoscopy/Colonoscopy....................................................................53
12.3
Patient-Reported Outcomes ....................................................................................53
13
ASSESSMENTS OF SAFETY...............................................................................55
13.1
Safety Parameters ...................................................................................................55
13.1.1
Physical Examination .............................................................................................55
13.1.2
Height and Weight..................................................................................................55
13.1.3
Vital Signs ..............................................................................................................55
13.1.4
Electrocardiogram..................................................................................................55
13.1.5
Ophthalmological Examination ..............................................................................56
13.1.6
Dermatological Examination..................................................................................56
56
13.1.8
Monitoring of Adverse Events and Serious Adverse Events.....................................57
13.1.9
Monitoring of Concomitant Therapy.......................................................................57
13.1.10
Guidelines for Cardiac Monitoring.........................................................................57
13.1.11
Clinical Laboratory Evaluations.............................................................................59
13.2
Adverse Events and Serious Adverse Events...........................................................61
13.2.1
Definition of Adverse Events...................................................................................61
13.2.2
Definition of Serious Adverse Events ......................................................................61
13.2.3
Assessment of Adverse Event Severity .....................................................................62
13.2.4
Assessment of Adverse Event Relationship to Investigational Drug.........................62
13.2.5
Reporting of Serious Adverse Events.......................................................................63
13.2.6
Adverse Events of Special Interest ..........................................................................64
13.2.7
 Pandemic..............................................................................................67
13.2.8
Monitoring of Patients with Adverse Events, Serious Adverse Events, and 
Adverse Events of Special Interest ..........................................................................67
13.2.9
Overdose of Investigational Drug ...........................................................................67
13.2.10
Procedures in Case of Pregnancy ...........................................................................68
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13.2.11
Data Safety Monitoring Board................................................................................68
68
13.4
Appropriateness of Measurements ..........................................................................69
14
PLANNED STATISTICAL METHODS ................................................................70
14.1
Determination of Sample Size.................................................................................70
14.2
Statistical Methods .................................................................................................70
14.2.1
General Considerations..........................................................................................70
14.2.2
Analysis Populations ..............................................................................................70
14.3
Disposition, Demographics, and Baseline Characteristics .......................................70
14.4
Efficacy..................................................................................................................70
14.4.1
Handling Missing Data...........................................................................................70
14.5
Safety Analyses ......................................................................................................71
14.6
Interim Analyses.....................................................................................................71
15
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS.......................................72
15.1
Monitoring .............................................................................................................72
15.2
Data Management/Coding ......................................................................................72
15.3
Quality Assurance and Inspections .........................................................................73
16
QUALITY CONTROL AND QUALITY ASSURANCE........................................74
16.1
Study Monitoring and Source Data Verification......................................................74
16.2
Investigational Medicinal Product Quality Issues....................................................74
17
ETHICS..................................................................................................................76
17.1
Institutional Review Board or Independent Ethics Committee.................................76
17.2
Ethical Conduct of the Trial....................................................................................76
17.3
Patient Information and Informed Consent..............................................................76
17.4
Patient Data Protection ...........................................................................................77
17.5
Investigator Obligations..........................................................................................77
17.6
Protocol Signatures.................................................................................................77
18
DATA HANDLING AND RECORD KEEPING....................................................78
18.1
Inspection of Records .............................................................................................78
18.2
Retention of Records ..............................................................................................78
19
PUBLICATION POLICY, FINANCING, AND INSURANCE ..............................79
20
REFERENCES.......................................................................................................80
21
APPENDICES........................................................................................................83
APPENDIX 1
INVESTIGATOR SIGNATURE............................................................84
APPENDIX 2
INVESTIGATOR RESPONSIBILITIES................................................85
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4
LIST OF TABLES
.....................................................................................26
Table 2:
Schedule of Events .................................................................................33
.................47
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5
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS
Abbreviation
Definition
5-ASA
5-aminosalicylic acid
6-MP
6-mercaptopurine
ADR
Adverse drug reaction
AE
Adverse event
AESI
Adverse event of special interest
ALT
Alanine aminotransferase
AST
Aspartate aminotransferase
AZA
Azathioprine
β-hCG
Beta-human chorionic gonadotropin
BCRP
Breast Cancer Resistance Protein
CFR
Code of Federal Regulations
CMV
Cytomegalovirus
CRO
Contract research organization
CYP
Cytochrome P450
DDI
Drug-drug interaction
DSMB
Data Safety Monitoring Board
ECG
Electrocardiogram
eCRF
Electronic case report form
EDC
Electronic data capture
FCBP
Females of Child Bearing Potential
FDA
Food and Drug Administration
GCP
Good Clinical Practice
GGT
Gamma glutamyl transferase
Hb
Hemoglobin
HbA1c
Glycosylated hemoglobin
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Abbreviation
Definition
HR
Heart rate
IB
Investigator’s Brochure
ICF
Informed Consent Form
ICH
International Council on Harmonization
IEC
Independent Ethics Committee
IP
Investigational Product
IRB
Institutional Review Board
ITT
Intent-to-treat
IUD
Intrauterine device
IUS
Intrauterine hormone releasing system
IV
Intravenous
IV Ig
Intravenous immunoglobulin
IXRS
Interactive voice / web-based activated response system 
MedDRA
Medical Dictionary for Regulatory Activities
MES
Mayo Endoscopy Score
MMF
Mycophenolate mofetil
MS
Multiple sclerosis
NOAEL
No-Observed-Adverse Effect Level
NSAID
Non-steroidal anti-inflammatory drug
OLE
Open-label extension
PD
Pharmacodynamic(s)
P-gp
P-glycoprotein
PGA
Physician Global Assessment
PK
Pharmacokinetic(s)
RBS
Rectal Bleeding Score
RMS
Relapsing multiple sclerosis
S1P
Sphingosine-1-phosphate
S1P1
Sphingosine-1-phosphate 1 receptor 
S1P5
Sphingosine-1-phosphate 5 receptor
SAE
Serious adverse event
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Abbreviation
Definition
SD
Standard deviation
SFS
Stool Frequency Score
SFU
Safety Follow-up
SOP
Standard operating procedures
TDAR
T-cell-dependent antibody response
TEAE
Treatment-emergent adverse event
TNF
Tumor necrosis factor
UC
Ulcerative colitis
WBC
White blood cell
WHO
World Health Organization
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6
INTRODUCTION
6.1
Ulcerative Colitis
Ulcerative colitis (UC) is a chronic gastrointestinal inflammatory disorder that involves the surface 
mucosa, the crypt epithelium, and the submucosa of the colon (Schroeder et al, 1987; Stenson, 
2000).  The etiology of UC is multifactorial, but likely includes a dysregulated mucosal immune 
response against commensal non-pathogenic bacteria of the colon, resulting in bowel inflammation 
(Ordas et al, 2012).
Patients with UC suffer from diarrhea, rectal bleeding, weight loss, abdominal pain, and fever 
(Schroeder et al, 1987; Stenson, 2000; Hyams, 1994).  Ulcerative colitis is characterized by a life-
long chronic course of remissions and exacerbations.  In 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 (Glickman, 1998). Toxic megacolon commonly requires an 
urgent colectomy to avoid perforation, peritonitis, and sepsis.  Within 10 years of diagnosis, 19.9% 
of adults with UC had undergone colectomy for their UC (van Limbergen et al, 2008).
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% of patients with UC for 10 years, to 8% of patients with UC for 20 
years, and to 18% of patients with UC for 30 years (Eaden et al, 2001; Bernstein et al, 2001).
The overall goal of treatment for patients with active UC is to induce and maintain remission and 
to induce and maintain mucosal healing (Ng and Kamm, 2009; Sandhu et al, 2010; Heyman et al, 
2005).  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 (Kornbluth and Sachar, 
2010; Ng and Kamm, 2009; Sandhu et al, 2010).  While agents used to treat mild to moderate UC 
are generally well tolerated, as the severity of UC disease increases, so do the potential toxicities 
of the medications required to manage the disease.  Treatment for mild to moderate UC treatment 
typically starts with topical agents (5-aminosalicylate [5-ASA] or corticosteroids administered via 
suppository or enema).  In patients unresponsive to local therapy or in patients with more severe 
or more extensive disease, systemic treatment with an oral 5-ASA, such as mesalamine, olsalazine, 
sulfasalazine, and balsalazide, with or without antibiotics, is commonly required (Rosenberg and 
Peppercorn, 2010; Ng and Kamm, 2009; Sandhu et al, 2010).  Initially, up to 90% of patients with 
mild to moderate UC can be maintained in remission using once-daily oral administration of 5-
ASA, and treatment with 5-ASA is generally safe and well tolerated (Ng and Kamm, 2009).
For those patients who do not respond or lose response to treatment with 5-ASA or those with 
more severe, 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.
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In pediatric patients with more severe, extensive disease at presentation, corticosteroids are 
effective for short-term flare-ups, but are not recommended to maintain remission due to 
undesirable long-term side effects, including stunted growth. Thus, corticosteroids are usually 
administered for short periods of time and are not recommended for frequent use. Furthermore, it 
has been shown in pediatric populations that although effective in induction of response, after 
1 year, approximately 45% of patients who initially responded to corticosteroids have either 
become steroid-dependent (Hyams et al, 2006) or have required surgery (Tung et al, 2006).  
For those patients who are unresponsive to, or intolerant of corticosteroids, immunomodulators 
including azathioprine (AZA), 6-mercaptopurine (6-MP), and cyclosporine (Rosenberg and 
Peppercorn, 2010), or biologics (such as infliximab or vedolizumab), are used to induce and/or 
maintain remission (Kornbluth and Sachar, 2010; Sandhu et al, 2010).  However, these 
medications have multiple limitations including toxicities.  The use of 6-MP and AZA can result 
in neutropenia, pancytopenia, pancreatitis, nephrotoxicity, hepatotoxicity, and in rare cases, 
hepatosplenic T-cell lymphoma (Carter et al, 2004; Turner and Griffiths, 2011; Bousvaros, 2010; 
Chaparro et al, 2009), as well as a delay in onset of action (AZA and 6-MP take as long as 3 months 
to work).  This class of therapy has a similar benefit-risk profile in children as in adults and have 
been widely prescribed as maintenance therapy for children with UC.  However, reluctance to use 
thiopurines in children, especially males, has increased with the recognition of these potentially 
severe complications. Infliximab is indicated for pediatric UC, but comes with the potential risk 
of infusion reactions, 
, autoimmunity, and psoriasis known for the tumor 
necrosis factor (TNF) blocker medication class.  A requirement for intravenous medication is 
disruptive to school and family economics.  Adalimumab, also a TNF blocker, is currently 
indicated for UC in adults only.  Therefore, there remains an unmet need for a UC treatment that 
is highly effective, well-tolerated, and orally active in both the adult and pediatric/adolescent 
populations.
6.2
RPC1063
RPC1063 (also known as ozanimod or BMS-986374) is a small molecule compound that 
selectively and potently activates the sphingosine-1-phosphate 1 receptor (S1P1) and the S1P 5 
receptor (S1P5), although it is more selective towards S1P1 over S1P5. In vitro, RPC1063 has 
little activity on the other sphingosine-1-phosphate (S1P) receptors, showing half maximal 
effective concentration (EC50) greater than 10,000 nM for S1P2, > 5000 nM for S1P3, and > 2000 
nM for S1P4.  RPC1063 is extensively metabolized in humans with up to 13 metabolites identified 
in plasma, urine, and feces, including 2 active selective major metabolites and one inactive major 
metabolite found in human plasma at steady state. The 2 active metabolites (CC112273 and 
CC1084037) have similar structures to ozanimod and similar selectivity across the S1P receptor 
family.
Many cell types express S1P1, including vascular endothelial cells, brain cells, and lymphocytes 
(Rosen et al, 2009).  Stimulation (agonism) of this receptor results in biological activities that 
includes lymphocyte retention in peripheral lymphoid organs (eg, lymph nodes and gastrointestinal 
Peyer’s patches), resulting in reversible systemic reduction in circulating lymphocytes (Mandala 
et al, 2002).  Given the immune dysregulation observed in UC (Ordas et al, 2012), prevention of 
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trafficking of disease-exacerbating, self-reactive lymphocytes to the gut is likely to have salutary 
immunomodulatory effects with a consequent dampening of disease processes.
The potential for ozanimod to adversely affect the immune system was evaluated in a rat model 
for T-cell-dependent antibody response (TDAR) using keyhole limpet hemocyanin (KLH) as the 
antigenic stimulation (ITR Report No. 72864).  The TDAR model is well-characterized and 
provides a functional evaluation of potential immunotoxic responses as it relies on the coordinated 
participation of antigen presenting cells, T cells, and B cells.  Ozanimod, tested in a dose range of 
0.2 to 2 mg/kg/day, resulted in a dose-dependent decrease in circulating T cell and B cell counts 
and in the primary and recall antibody responses with a no-observed-adverse-effect level 
(NOAEL) of 0.2 mg/kg/day.  The NOAELs for juvenile and adult animals were 0.3 and 0.2 
mg/kg/day, respectively, correlating to ≥ 10 times the exposure for ozanimod that was achieved 
with the clinical administration of 
 mg and > 15 times compared to the 
 mg dose (RPC01-
1001).  Therefore, the clinical doses of 
 mg and 
 mg are unlikely to result in clinically 
meaningful effects on novel or recall immune responses.  Importantly from a safety perspective, 
there are still a significant number of lymphocytes in the circulation in patients treated with even 
the highest dose (
 mg) of ozanimod such that serious infection rates are not increased to date, 
which suggests that the risk for 
 should not be 
significantly increased.  
 has been reported in patients treated with S1P receptor modulators 
and immunomodulatory therapies for multiple sclerosis (MS).
6.2.1
Nonclinical Studies
RPC1063 has been shown to pharmacologically induce rapid and reversible lymphocyte reduction 
in rodents, rabbits, dogs, nonhuman primates, and humans. Extensive nonclinical in vivo safety 
studies of up to a 6-month (rat) or 9-month (monkey) duration have shown that RPC1063 is well 
tolerated in animals at doses that generate robust pharmacodynamic (PD) effects (0.2 mg/kg in rats 
and 0.1 mg/kg in monkeys). RPC1063 has also been examined in reproductive toxicity studies (rat 
and rabbit) carcinogenicity studies (Tg.rasH2 mouse and rat), immunotoxicology (rat) and juvenile 
toxicity studies (rat). RPC1063 is extensively metabolized in humans and animals, with all active 
moieties having similar selective and potent activity at the S1P1 and S1P5 receptors. Doses 
examined in the toxicology studies thoroughly examined the on-target pharmacology (S1P1 and 
S1P5), where effects are similar across species (decreases in absolute lymphocyte counts). 
Differences in metabolism and clearance of these metabolites, however, results in disproportionate 
active metabolites in humans (such as CC112273). Coverage of some of these active metabolites 
(including CC112273) in rodent studies is projected to reach only 1 to 2 fold over efficacious 
human exposure due to rodent-specific differences in production and clearance. Coverage of 
CC112273 in nonhuman primate studies is projected to have reached 10 to 20 fold over efficacious 
human exposure. The data from the entire nonclinical program (including the juvenile rat 
toxicology study and the juvenile rat immunotoxicology study) with RPC1063 do not suggest that 
there are any specific sensitivities or new toxicities in pediatric populations that are not present in 
the adult population.
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6.2.2
Clinical Studies
Phase 1 trials completed with RPC1063 in healthy volunteers include, but are not limited to, the 
first-in-human trial (RPCS 001), a thorough QT trial (RPC01-102), a food-effect trial (RPC01-
1901), a drug-drug interaction (DDI) trial with a potent inhibitor and potent inducer of cytochrome 
P450 3A (RPC01-1902), a DDI trial with a strong inhibitor of P-glycoprotein and Breast Cancer 
Resistance Protein (RPC01-1903), a trial to evaluate the PK and safety of RPC0163 in Japanese 
and Caucasian patients (RPC01-1905), a DDI trial with an oral contraceptive (RPC01-1907), and 
a DDI trial with a calcium channel blocker or a beta blocker (RPC01-1908).
A Phase 2/3 randomized, double-blind, controlled trial (RPC01-201) in patients with relapsing 
multiple sclerosis (RMS) has been completed. In ulcerative colitis, the induction phase of a Phase 
2 trial in adult patients with moderate to severe UC (RPC01-202) was completed in October 2014.  
At the conclusion of the induction phase, the proportion of patients achieving clinical response and 
clinical remission with RPC1063 1 mg was greater than placebo and the difference was both 
clinically meaningful and statistically significant.  In addition, all secondary endpoints at the 
conclusion of the induction phase, including clinical response, change in the Mayo score, 
and mucosal improvement on endoscopy, were also positive and statistically significant for the 
RPC1063 1 mg dose. The maintenance phase of this trial ended in March 2015 and the open-label 
extension period was completed in November 2019, with eligible patients continuing in this study 
(RPC01-3102). The Phase 3 pivotal study (RPC01-3101) completed in May 2020, and eligible 
patients entered into this study. In addition, a Phase 2/3 study in UC patients in Japan (RPC01-
3103) is ongoing.
Additional information regarding company-sponsored trials in the RPC1063 clinical development 
program is provided in the Investigator’s Brochure (IB).
6.3
Rationale for the Current Trial
The objective of the RPC1063 clinical development program in UC is to demonstrate that 
RPC1063 administered orally is safe and effective for treating patients with moderate to severe 
UC.  The positive results obtained in the Phase 2 (RPC01-202) and the Phase 3 pivotal trial 
(RPC01-3101) for the primary and all secondary endpoints led to the approval of the marketing 
application in the United States on 27 May 2021. Continued treatment with ozanimod 1 mg daily 
will provide greater long-term safety and durability data.
The objective of the current trial is to evaluate the long-term safety and efficacy of RPC1063 for 
the treatment of patients with moderate to severe UC.
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7
TRIAL OBJECTIVES AND ENDPOINTS
7.1
Objectives

Evaluate the long-term safety of RPC1063 for the treatment of all patients with moderate to 
severe UC.

Evaluate the long-term efficacy of RPC1063 for the treatment of adult patients with moderate 
to severe UC.

 
7.2
Efficacy Endpoints
7.2.1
Definitions
Complete Mayo score: the sum of the RBS, SFS, PGA subscore, and the MES.  Each subscore 
has a range of 0-3 points and the complete Mayo score has a range of 0-12 points
9-point Mayo score: the sum of the RBS, SFS, and the MES.  The 9-point Mayo score has a range 
of 0-9 points
Partial Mayo score: the sum of the RBS, SFS, and the PGA subscore.  The Partial Mayo score 
has a range of 0-9 points
Clinical Remission
Three-component Mayo: RBS = 0 and SFS ≤ 1 (and a decrease of ≥ 1 point from the baseline SFS) 
and MES ≤1
Clinical Response
Three-component Mayo: A reduction from Baseline in the 9-point Mayo score of ≥ 2 points and 
≥35%, and a reduction from Baseline in the RBS of ≥ 1 point or an absolute RBS of ≤ 1 point
Corticosteroid-free Remission: Clinical remission while off corticosteroids for ≥12 weeks
Endoscopic Improvement: MES of ≤ 1 point
Mucosal Healing: MES of ≤ 1 point and a Geboes index score < 2.0
Histologic Remission: Geboes index score < 2.0
For statistical analysis purposes, clinical remission and clinical response will be calculated using 
the Three-component Mayo definition. 
7.2.2
Efficacy Endpoints

Proportion of patients in clinical remission

Proportion of patients with a clinical response
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
Proportion of patients with endoscopic improvement

Proportion of patients with mucosal healing

Proportion of patients with corticosteroid-free remission

Change from Baseline in complete Mayo score, partial Mayo score, and 9-point Mayo score

Proportion of patients with histologic remission

Proportion of patients with clinical response, clinical remission, or endoscopic improvement 
in patients who had previously received anti-TNF therapy
For statistical analysis purposes, clinical remission and clinical response will be calculated using 
the Three-component Mayo definition. 
7.3
Safety Endpoints

The incidence, severity, and relationship of treatment-emergent adverse events (TEAEs), 
serious AEs (SAEs), TEAEs leading to discontinuation of investigational drug, AEs of special 
interest (AESIs), and TEAEs of special interest will be summarized.
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8
INVESTIGATIONAL PLAN
8.1
Summary of Trial Design
The Schedule of Events is provided in Table 2
 
This is an open-label, multicenter, extension trial to evaluate the long-term efficacy and safety of 
RPC1063 in patients with moderately to severely active UC. Patients who have previously 
participated in a trial of RPC1063 (eg, RPC01-3101 or completed at least 1 year of the open-label 
period of RPC01-202) for UC and meet the eligibility criteria will be eligible for entry in this trial.
Patients entering the trial from the open-label period of RPC01-202 
 of RPC01-3101 
will continue to receive RPC1063/ozanimod HCl at 1 mg/day.  All patients entering the trial from 
a blinded parent trial or treatment period 
 of RPC01-3101) will initiate RPC1063 
treatment in accordance with a 7-day dose escalation regimen starting with RPC1063/ozanimod 
HCl 
 mg on Days 
, followed by RPC1063/ozanimod HCl 
mg on Days 
, and 
reaching the final dose level, 1 mg, on Day .  Patients will then receive RPC1063 at 1 mg/day as 
part of this clinical trial until the patient completes 5 years (Week 238) and the Safety Follow-up
Visit, unless the Sponsor discontinues the development program (see Section 8.3.6 for details on 
treatment options post study). Adult patients who are not in clinical response or remission at trial
entry may be discontinued from investigational drug if they do not show clinical improvement
from the Baseline Visit of the RPC01-3102 by 
.  
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Table 2:
Schedule of Events
Trial Procedures
Informed consent
Inclusion/exclusion 
criteria
Dispense investigational 
drug
Administer 
investigational drug at 
clinic
Review drug compliance
Prior and concomitant 
medications
Safety Assessments
Adverse eventss
12-Lead ECG
Vital signs
Hematology
Blood chemistryn,p
Urine pregnancy teste
Contraception education
Urinalysis
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Table 2:
Schedule of Events
Trial Procedures
Complete Physical 
Examf
Interim Physical Examf
Height and Weight 
 
PD and PK Assessments
 
PK blood draw
 
Efficacy Assessments
Endoscopy and colonic 
biopsyg
Mayo patient diary
Complete Mayo score
Partial Mayo score
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Abbreviations:  AE = adverse event; 
 ECG = electrocardiogram; 
 
 PD = pharmacodynamics; 
; PK = pharmacokinetic;
; SFU = Safety Follow up; UC = ulcerative colitis.
a
Patients will be entering the trial from a parent RPC1063 trial (eg, RPC01-3101 or completed at least 1 year of the open-label period of RPC01-202). In general, the last visit of 
the prior trial will serve as Visit
 of this trial.  Patients entering the trial from the open-label period of RPC01-202 
 of RPC01-3101 will continue to receive 
RPC1063/ozanimod HCl at 1 mg/day and will not require dose escalation and 
.  All patients entering the trial from a blinded parent trial or treatment 
period 
 of RPC01-3101) will undergo dose escalation and 
. 
 
 
b
Visit  should be scheduled in the morning, when possible, and patients should be instructed not to take the investigational drug from the prior trial until Visit  during which they 
will receive RPC01-3102 investigational drug.
c
Patients should enter the trial within 
 of the last visit of the prior trial. Procedures completed at the last visit of the prior trial do not need to be repeated if Visit  occurs 
within 14 days of the last visit of the prior trial. All Visit  procedures, including the endoscopy, must be completed prior to first dose except for 
 and 
. If indicated, 
patients must complete the 
 and 
 no later than 14 days after Visit .
d
Patients who continue past Visit 
will have additional visit assessments performed at 
. Patients entering from the open-label period of RPC01-202 
will begin visits at 
. The trial will continue until the patient completes 5 years (Week 238) and the Safety Follow-up Visit, unless the Sponsor discontinues the 
development program.
e
In addition to the scheduled pregnancy tests in the clinic, monthly urine pregnancy tests should be performed by the patient between scheduled visits up until the 90-day SFU
Visit.  If a urine pregnancy test is positive, the Investigator will instruct the patient to suspend further RPC1063 dosing, if applicable, and schedule a follow-up appointment as 
soon as possible.  A serum pregnancy test has to be performed for confirmation, even if the test is done after the 90-day SFU Visit.
f
For all patients, a complete physical examination (which includes height and weight) will be performed at Visit , 90-day SFU, and 
. The complete physical examination 
at 
Visit also includes height and weight (See section 13.1.2). The complete physical examination consists of a full examination of the skin for lesions as well as a check 
for visual symptoms (ie, blurred vision or decreased visual acuity).  A check for visual symptoms and a full examination of the skin should be repeated 
.  At all 
other visits, an interim physical examination may be performed.  The interim physical examination will include body systems with previously noted abnormalities and/or those 
body systems associated with any new complaints from the patient.
g
Endoscopy at Day  does not need to be repeated if an endoscopy has been completed within 
of Visit . All subsequent endoscopies should be performed either on day 
of visit or within 
 of the visit date.
h
After the endoscopy at the 
 visit, an endoscopy will be performed at 
 and a Complete Mayo score will be calculated for 
those visits. Endoscopy at the 
 visit will not need to be repeated if an endoscopy has been completed within
 of the 
 visit.
j
The SFU Visit should occur 90 days (± 10 days) after the last dose of investigational drug in the RPC01-3102 trial. Patients who transition to commercial ozanimod within 14 
days of the last dose of investigational drug will not require an SFU Visit.
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Sponsor: Celgene International II Sàrl
Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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n
The following amounts of blood will be taken per visit: At 
, approximately 18.5 mL; at 
, approximately 6.5 mL; at every 
 visit after 
, approximately 5.5 mL; at 
 visit after 
, approximately 21 mL; at 
, approximately 26 mL, and at the 90-day 
SFU Visit, up to approximately 11.5 mL.
p
HbA1c will be assessed at Baseline, 
.
s Ulcerative colitis disease relapse and related symptoms will be monitored as trial endpoints and thus will not be recorded as AEs, unless it qualifies as a serious AE to trigger 
safety reporting as described in Section 13.2.5.
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Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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8.2
Discussion of Trial Design
This trial is designed to evaluate the long-term safety and efficacy of RPC1063 for the treatment 
of patients with moderate to severe UC.  All patients will receive RPC1063 at 1 mg/day as part of 
this clinical trial until the patient completes 5 years (Week 238) and the Safety Follow-up Visit,
unless the Sponsor discontinues the development program (see Section 8.3.6 for treatment options 
post study).  
Patients entering the trial from the open-label period of RPC01-202 
 of RPC01-3101
will continue to receive RPC1063/ozanimod HCl at 1 mg daily. All patients entering this trial from 
a blinded parent trial or treatment period (
 of RPC01-3101) of RPC1063 will initiate 
RPC1063 treatment in accordance with a 7-day dose escalation regimen (in order to maintain the 
blind of the parent trial) starting with RPC1063/ozanimod HCl 
 mg on Days 
, followed 
by RPC1063/ozanimod HCl 
mg on Days 
, and reaching the final dose level, 1 mg, on 
Day .
Patients entering this trial from an open-label trial of RPC01-202 will not undergo dose escalation.
The dosing regimen for RPC1063 is based on previous clinical studies with RPC1063 
(see Section 10.3).
8.3
Trial Periods
It is recommended that the trial visits are scheduled in the morning.  
Whenever possible, the sequence of when assessments are done should remain constant and at 
approximately the same time of day throughout the trial.
It is recommended that procedures are performed in the following order (note that not all 
procedures are performed at every visit):

Spontaneous or solicited AE reporting

ECG

Vital signs

Clinical laboratory tests

Physical examination

Efficacy assessments

Investigational drug administration (Visit )
8.3.1
Visit
Patients must start this trial within 
of their final visit in the prior RPC1063 trial in which 
they participated.  
In general, procedures completed at the final visit of the prior trial will not need to be repeated if 
Visit  occurs on the same day as the final visit of the prior trial. All patients undergoing dose 
escalation will follow the 
 procedures as outlined in Section 13.1.10 and in
 
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Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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8.3.2
Trial Visits
Visits, assessments, and procedures will be performed according to the Schedule of Events
(Table 2).
Adult patients who are not in clinical response or remission at trial entry may be discontinued from 
investigational drug if they do not show clinical improvement from the Baseline Visit of the 
RPC01-3102 by 
  
At the time this amendment is approved, patients who have completed 5 years of treatment
(Week 238) should come in at the time of their next scheduled visit. At this visit, these patients 
will complete the 
 procedures and then enter the SFU period.
8.3.4
Safety Follow-Up
For patients who discontinue the trial for any reason, every attempt should be made to complete 
the assessments detailed at
the 90-day
SFU
Visit in the Schedule of Events
(Table 2).  In the event that commercial ozanimod or an access program becomes available prior 
to end of the study, patients may transition to the commercial product after discussion with the 
Investigator at his/her discretion.  Patients who transition to commercial ozanimod are not required 
to attend a 90-day SFU Visit after their 
 as long as commercial ozanimod is 
started within 14 days of discontinuation of study drug. A 90-day (±10 days) SFU Visit was added 
to ensure adequate collection of adverse events that could be associated with investigational drug. 
  Additional safety 
assessments may be required for patients who have an ongoing AE or safety issue at the 90-day
SFU Visit, at the Investigator’s discretion. Patients may be followed as necessary for an additional 
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Sponsor: Celgene International II Sàrl
Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
39
period of time after the 90-day SFU Visit to review the results of any assessments which were 
conducted at the 90-day SFU Visit.
8.3.5
Study Stopping Rules
The Sponsor has the right to terminate the trial for safety reasons.  In addition, the Sponsor may 
terminate the trial for administrative reasons.  In all cases, all necessary measures must be taken 
to guarantee appropriate SFU of all patients already included in the trial.
The Institutional Review Board (IRB) or Independent Ethics Committee (IEC) and the Regulatory 
Authorities will be informed in writing about any termination of the trial.
8.3.6
Trial Duration
Patients will receive open-label treatment as part of this clinical trial until the patient completes 5 
years (Week 238) and the Safety Follow-up Visit, unless the Sponsor discontinues the 
development program. 
In countries where ozanimod is approved, the treating physician may elect to transfer the patient 
to commercially available ozanimod.
In countries were ozanimod is not commercially available, patients who continue to demonstrate 
clinical benefit may be eligible to receive ozanimod through a country-specific patient support 
program where available.
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Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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9
SELECTION AND WITHDRAWAL OF PATIENTS
9.1
Inclusion Criteria
Patients are eligible if they fulfill all of the following:
1) Previously participated in a trial of RPC1063 (eg, RPC01-3101 or completed at least 1 year of
the open-label period of RPC01-202) and meet the criteria for participation in the open-label 
extension as outlined in the prior trial
2) Females of childbearing potential (FCBP) Y:
Must agree to practice a highly effective method of contraception£ throughout the trial until 
completion of the 90-day SFU Visit. Highly effective methods of contraception are those that 
alone or in combination result in a failure rate of a Pearl index of less than 1% per year when 
used consistently and correctly. Acceptable methods of birth control in the trial are the 
following:

combined hormonal (oestrogen and progestogen containing) contraception, which may be 
oral, intravaginal, or transdermal 

progestogen-only hormonal contraception associated with inhibition of ovulation, which 
may be oral, injectable, or implantable

placement of an intrauterine device (IUD)

placement of an intrauterine hormone-releasing system (IUS)

bilateral tubal occlusion

vasectomized partner

complete sexual abstinence 

Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal 
(coitus interruptus), spermicides only, and lactational amenorrhea method are not 
acceptable methods of contraception.
3) Must provide written informed consent prior to any trial-related procedures and have the ability 
to be compliant with the schedule of protocol assessments. 
                                                       
Y For the purposes of this study, a female patient is considered to be of childbearing potential if she has reached 
menarche, and 1) has not undergone a hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy 
(the surgical removal of both ovaries) or 2) has not been postmenopausal for at least 24 consecutive months (that 
is, has had menses at any time during the preceding 24 consecutive months).
£ Contraception Education: Counselling about pregnancy precautions and the potential risks of fetal exposure must 
be conducted for FCBP.  The Investigator will educate all FCBP about the different options of contraceptive 
methods or abstinence, as appropriate, at the Screening and Baseline Visits.  The patient will be re-educated every 
time her contraceptive measures/methods or ability to become pregnant changes.  The female patient’s chosen form 
of contraception must be effective by the time the female patient is randomized into the study (for example, 
hormonal contraception should be initiated at least 
 before baseline).
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Sponsor: Celgene International II Sàrl
Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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9.2
Exclusion Criteria
Patients are not eligible for this trial if they fulfill any of the following:
Exclusions Related to Medications:
1) Have received any of the following therapies since the first dose of investigational drug in the 
prior RPC1063 trial:

Treatment with a biologic agent 

Treatment with an investigational agent other than RPC1063

Treatment with D-penicillamine, leflunomide, thalidomide, natalizumab, fingolimod, 
etrasimod, or tofacitinib

Treatment with lymphocyte-depleting therapies (eg, Campath, anti-CD4, cladribine, 
rituximab, ocrelizumab, cyclophosphamide, mitoxantrone, total body irradiation, bone 
marrow transplantation, alemtuzumab, daclizumab)

Treatment with a live vaccine or live attenuated vaccine within 4 weeks prior to Visit  of 
this trial
2) Are currently receiving or require initiation of any of the following therapies:

Treatment with corticosteroids at a dose that exceeds the prednisone equivalent of 40 mg

Treatment with immunosuppressive agents (eg, azathioprine, 6-MP, or methotrexate)

Chronic non-steroidal anti-inflammatory drug (NSAID) use (Note: occasional use of 
NSAIDs and acetaminophen [eg, headache, arthritis, myalgias, or menstrual cramps] and 
aspirin up to 325 mg/day is permitted)

Treatment with Class Ia or Class III anti-arrhythmic drugs or treatment with two or more 
agents in combination known to prolong PR interval
3) Are receiving treatment with any of the following drugs or interventions within the 
corresponding timeframe:

At Day 

CYP2C8 inhibitors (eg, gemfibrozil or clopidogrel) or inducers (eg, rifampicin)

Two weeks prior to Day 

Monoamine oxidase inhibitors (eg, selegiline, phenelzine) 
4) Are receiving treatment with breast cancer resistance protein (BCRP) inhibitors (eg, 
cyclosporine, eltrombopag)
Exclusions Related to General Health:
5) Pregnancy, lactation, or a positive serum beta human chorionic gonadotropin (hCG)
6) Clinically relevant hepatic, neurological, pulmonary, ophthalmological, endocrine, psychiatric 
or other major systemic disease making implementation of the protocol or interpretation of the 
trial difficult or that would put the patient at risk by participating in the trial or that would have 
required a patient to discontinue treatment in previous RPC1063 trial
7) Clinically
relevant 
cardiovascular 
conditions, 
including 
history 
or 
presence 
of 
recent myocardial 
infarction, 
unstable 
angina, 
stroke, 
transient 
ischemic 
attack, 
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Sponsor: Celgene International II Sàrl
Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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decompensated heart failure requiring hospitalization, Class III/IV heart failure, sick sinus 
syndrome, or severe untreated sleep apnea
Exclusions Related to Laboratory Results:
9.3
Considerations for Patients with Comorbid Conditions
9.3.1
Patients with Type 2 Diabetes Mellitus
Patients with type 2 diabetes mellitus were permitted in parent induction/maintenance studies if 
their glycosylated hemoglobin A1c (HbA1c) was ≤ 9% at Screening.  Such patients should receive 
appropriate diabetes management and treatment during this trial.
Gestational diabetes and steroid-induced diabetes occurring in the past and resolved prior to 
Screening are not exclusionary.
The treating Investigator should ensure that diabetic patients who are included in the trial are 
closely monitored for signs or symptoms of 
 (see Section 13.2.6).  Patients with 
diabetic uveitis or diabetic patients with significant comorbid conditions such as retinopathy or 
nephropathy are excluded.
Duration of disease and medication history throughout the trial will be recorded in source 
documents and in the electronic case report form (eCRF).
9.3.2
Patients with History of Cardiac Disease
Patients with some pre-existing cardiac conditions, who have stable disease and would not 
be placed at significant safety risk by participating in a trial of RPC1063, were considered 
for participation in parent induction/maintenance studies and are eligible for enrollment in this 
trial.
Patients entering this trial should continue to be monitored in the manner in which they 
were monitored during the parent trial.  The treating Investigator should ensure these 
patients included in the trial are closely monitored for signs of any 
 
 after the first dose of RPC1063, as these patients may be at higher risk for 
 
All patients will follow the detailed 
 procedures as outlined in Sections 10.5.2
and 13.1.10.
9.4
Trial Discontinuation
Patients may voluntarily withdraw from the trial at any time.  The Investigator will provide a 
written explanation in the source documentation to be entered on the appropriate eCRF page 
describing the reason for discontinuation.  
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Sponsor: Celgene International II Sàrl
Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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The criteria for enrollment are to be followed explicitly.  If a patient who does not meet enrollment 
criteria is inadvertently enrolled, the Medical Monitor must be contacted, and that patient will be 
withdrawn from the trial if continuation is determined to be a safety risk.
Reasons for discontinuation include, but are not limited, to the following:

Physician decision:  The Investigator must discontinue investigational drug if it is determined 
that it is not safe or in the patient’s best interest to receive further treatment.  The Medical 
Monitor should be promptly notified of the decision 

Non-compliance with investigational drug:  After consultation between the Investigator, the 
Medical Monitor, or and the Sponsor when appropriate, a patient may be discontinued from 
the trial for failure to comply with dosing regimen as specified by the protocol

Non-compliance with protocol/protocol deviation:  A patient fails to follow protocol 
procedures, or other event or decision that stands in contrast to the guidelines set in the 
protocol.

Adverse event:  A patient must be discontinued from investigational drug if, in the judgment 
of the Investigator or if specified in the protocol, the patient develops an AE such as an 
intercurrent illness or complication that justifies discontinuation of investigational drug.

Lack of efficacy: Decision by the patient and/or the Investigator to discontinue treatment due 
to a lack of expected or desired effect related to a therapy.

Withdrawal by Patient:  The patient may choose to discontinue investigational drug at any 
time.  Patients who discontinue investigational drug will be withdrawn from the trial.  Every 
effort should be made within the bounds of safety and patient choice to have each patient 
complete the 
 Visit and 90-day SFU Visit.  If a patient withdraws consent, 
the only additional trial data to be collected will be the follow up of SAEs as mandated by the 
protocol.

Pregnancy: If the patient becomes pregnant investigational drug must be discontinued 
(see Section 13.2.10)

Trial termination by Sponsor

Other (including discontinuation criteria described as part of AESIs in Section 13.2.6)
All patients who discontinue investigational drug should complete an 
 
 
 
 
 Alternative treatment for UC can be started, if 
needed, 
 after discontinuing investigational drug. With the exception of patients who
withdraw consent or are lost to follow-up, patients should complete the 90-day SFU Visit for the 
collection of safety data and to assess their disease status.  
The reason for discontinuation of investigational drug will be recorded in the clinical records and 
the patient’s eCRF.  For those patients whose status is unclear because they fail to appear for trial 
visits without stating an intention to withdraw, the Investigator should show due diligence by 
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Sponsor: Celgene International II Sàrl
Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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documenting in the source documents steps taken to contact the patient (eg, dates of telephone 
calls, registered letters) prior to withdrawing the patient from the trial.
Patients who withdraw from the trial will not be replaced.
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Sponsor: Celgene International II Sàrl
Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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10
INVESTIGATIONAL DRUGS
10.1
Treatments Administered
The Investigator must ensure that the investigational drug will be used only in accordance with the 
protocol.
Patients should be instructed to take investigational drug orally at approximately the same time 
each day with or without food.  
Patients entering the trial from the open-label period of RPC01-202 will continue to receive 
RPC1063/ozanimod HCl 1 mg daily. All patients entering the trial from a blinded parent trial or 
treatment period (
 of RPC01-3101) of RPC1063 will initiate RPC1063 treatment in 
accordance with a 7-day dose escalation regimen of RPC1063/ozanimod HCl at 
mg 
 on 
Days 
(one RPC1063/ozanimod HCl at 
 mg/day 
 capsule), RPC1063/ozanimod HCl 
at 
mg 
 on Days
(two RPC1063/ozanimod HCl 
 mg capsules), and reaching 
RPC1063/ozanimod HCl 1 mg one RPC1063/ozanimod 1 mg capsule) on Day .  Patients will 
continue to take open-label RPC1063/ozanimod HCl 1 mg once daily (one RPC1063/ozanimod 1 
mg capsule) as part of this clinical trial until the patient completes 5 years (Week 238) and the 
Safety Follow-up Visit, unless the Sponsor discontinues the development program. See Section 
8.3.6 for details on treatment options post study. Patients entering this trial from a prior open-label 
trial of RPC1063 will not undergo dose escalation.
10.1.1
Instructions for Missed Dose(s)
Patients should be instructed that if they forget to take a dose, they can take the dose 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 patient vomits the capsule, they should be instructed not to take another 
capsule on the same day, but to take the next dose at the regular time on the following day. Patients 
will record whether they took the daily dose of medication in a diary that will be reviewed 
periodically by site staff and the site monitor.
If a dose is missed during the first 2 weeks of treatment, or for more than 7 consecutive days during 
Days 
, reinitiate treatment using the 7-day titration regimen.  If a patient misses a dose during 
dose escalation, the Medical Monitor should be contacted to discuss completing the dose escalation 
schedule.
If a dose is missed after the first 2 weeks of treatment, continue with the treatment as planned. 
If the patient misses more than 14 consecutive doses for any reason including AE/SAE, the 
Medical Monitor must be contacted to discuss procedures for resuming therapy, which may 
include dose escalation and Day
 procedures on the first day that the patient 
resumes dosing.
10.2
Method of Assigning Patients to Treatment 
Patients must provide proper informed consent before any trial procedures are performed. Refer 
to Section 17.3 for further details regarding obtaining patients informed consent.
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Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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Consented patients meeting all eligibility criteria will be enrolled using the Interactive voice/web-
based activated response system (IXRS) which will also be used to log distribution of 
investigational drug.  Further instructions on the use of the system will be provided in a separate 
IXRS manual.  
10.3
Selection of Dose in the Trial
The dose of RPC1063 1 mg once each day was based on the completed Phase 1 (RPCS-001 and 
RPC01-102) and Phase 2 (RPC01-202) and Phase 2/3 (RPC01-201) trials (see Section 6.2.2 and 
subsections).  The 1 mg/day dose demonstrated better efficacy than the 
 mg/day dose across 
various clinical and endoscopic endpoints in these clinical trials.  Furthermore, the expected 
magnitude of the pharmacodynamic effect on peripheral lymphocyte reduction was observed and 
this dose demonstrated an acceptable safety profile.
A dose escalation over the first 7 days (
 mg/day on Days 
 and 
 mg/day on Days
) 
will be implemented, as results from the Phase 1 study (RPCS 001) and preliminary results from 
the Phase 2 study (RPC01-202) indicate that use of a dose escalation regimen appears to mitigate 
the magnitude of reduction in heart rate (HR).  Preliminary evidence from these studies suggested 
that patients who increase their dose progressively over the first week are less likely to have a 
profound decrease in HR or blood pressure; therefore, a dose escalation starting with 
 mg 
RPC1063 for the first 4 days of dosing followed by 
 mg on Days 
 before progressing 
to the 1 mg/day dose will be used.
10.4
Selection and Timing of Dose for Each Patient
Patients will self-administer RPC1063 orally once daily.  Investigational drug should be taken at 
approximately the same time each day with or without food.  See Section 10.1.1 for instructions 
regarding missed doses. 
10.5
Prior and Concomitant Treatments
All treatments, other than RPC1063, being taken by the patients on entry to the trial or at any time 
during the trial including through the 90-day SFU Visit are regarded as concomitant medications 
and must be documented on the appropriate section of the eCRF.  All ongoing medications 
indicated at the completion of RPC01-3101 and RPC01-202 must be recorded in the RPC01-3102 
concomitant treatment eCRF.
Administration of concomitant medications must be reported in the appropriate section of 
the eCRF along with dosage information, dates of administration, and reasons for use.  For 
medications with a single active ingredient, generic names for concomitant medication should be 
used, if possible.  For combination products, brand names should be used.  The total daily dose 
should be filled in whenever possible.
10.5.1
Allowed Medications
All prior medications (including over-the-counter medications) administered 
 prior to the 
date of informed consent and any concomitant therapy administered to the patient during the 
course of the trial (including any ongoing medications at the end of the parent study and new 
medication started after the completion of the parent study or medications that were initiated in 
1.0
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930190807
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Sponsor: Celgene International II Sàrl
Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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the prior study) until 
 after the final dose of investigational drug will be recorded.  Any 
medication that is considered necessary for the patient’s health and that is not expected to interfere 
with the evaluation of or interact with investigational drug may be continued during the trial.
10.5.2
Concomitant Medications Prohibited Through 
 After 
Investigational Drug Discontinuation
The following medications cannot be used during the trial through 
 after investigational 
drug discontinuation:

Treatment with Class Ia or Class III anti-arrhythmic drugs 
 
or treatment with 2 or more agents in combination 
known to prolong PR interval (eg, combination of a beta blocker and calcium channel blocker 
such as verapamil) are prohibited during the study unless approved by the Sponsor’s 
representative.

Marketed biologic therapies such as abatacept, infliximab, etanercept, adalimumab, 
golimumab, certolizumab, anakinra, rituximab, vedolizumab, and ustekinumab 

Immunomodulatory agents (eg, etrasimod, natalizumab, fingolimod, or tofacitinib)

Immunosuppressive agents (eg, AZA, 6-MP, cyclosporine, methotrexate, oral cyclosporine, 
tacrolimus, sirolimus or MMF) or other antineoplastic therapies or immune-modulating 
therapies

Any investigational treatment other than the investigational drug specified in this trial

Live vaccines or live attenuated vaccines

Intravenous immunoglobulin (IV-Ig) or plasmapheresis 

D-penicillamine, leflunomide, or thalidomide 

Breast cancer resistance protein (BCRP) inhibitors (eg, cyclosporine, eltrombopag)

Monoamine oxidase inhibitors (eg, selegiline, phenelzine)

CYP2C8 inducers (eg, rifampicin). For patients who are currently enrolled and are receiving 
monoamine oxidase inhibitors or CYP2C8 inducers, an individual safety assessment will be 
conducted and, if indicated, either the concomitant medication will be discontinued and the 
patient will continue in the study or investigational drug will be discontinued and the patient 
will be withdrawn from the study.
10.5.3
Concomitant Medications Between 
 After Investigational Drug 
Discontinuation and the 90-day Safety Follow-up Visit
The following medications should not be used between 
 after investigational drug 
discontinuation and the 90-day SFU Visit:
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Sponsor: Celgene International II Sàrl
Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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
Treatment with Class Ia or Class III anti-arrhythmic drugs or treatment with 2 or more agents 
in combination known to prolong PR interval (eg, combination of a beta blocker and calcium 
channel blocker such as verapamil) are prohibited during the study unless approved by the 
Sponsor’s representative.

Natalizumab, fingolimod, or etrasimod

Immunosuppressive agents that deplete lymphocytes

Monoamine oxidase inhibitors (eg, selegiline, phenelzine)

Live vaccines or live attenuated vaccines
10.5.4
Allowed Vaccinations

The vaccinations administered during the trial will be recorded in EDC (Electronic Data 
Capture). 
10.6
Medical Care of Patients after End of Trial
Patients who leave the trial and complete their end of trial assessments, including the 90-day SFU
Visit, do not require any additional care provided by the sponsor; they will return to the care of 
their personal physician(s).
10.7
Treatment Compliance 
It is the Investigator’s responsibility to ensure that patients are correctly instructed on how to take 
their investigational drug and that each patient is fully compliant with their assigned dosage 
regimen.  Records of investigational drug used and intervals between visits will be kept during the 
trial.  Drug accountability will be noted by the monitor during site visits and at the completion of 
the trial.  Patients will be asked to return any remaining unused investigational drug at the end of 
the trial.  The investigational drug should be dispensed by the Investigator, or by a qualified 
individual under the Investigator’s supervision.  An up-to-date treatment inventory/dispensing 
record must be maintained as described below in Section 11.3.
Patients who take less than 80% or more than 120% of investigational drug during the entire 
treatment period are considered non-compliant.
At each visit, previously dispensed investigational drug capsules will be collected by the 
Investigator and compliance assessed.  Patients will record whether they took the daily dose of 
investigational drug in a diary that will be reviewed periodically by site staff and the Clinical 
Monitor.  Patients exhibiting poor compliance as assessed by investigational drug counts (ie, 2 or 
more missed investigational drug days in 1 week) should be counseled on the importance of good 
compliance to the trial dosing regimen.  Patients who are persistently non-compliant (< 80% or > 
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Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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120%) should be discussed with the Medical Monitor to determine whether they should be 
withdrawn from the trial.
10.8
Blinding
This is an open-label extension trial.  However, to maintain the blind from the parent trial from 
which a patient may be entering, certain procedures such as dose escalation and cardiac monitoring 
and certain laboratory values such as leukocytes for all patients entering from a blinded parent trial 
(eg, end of the Induction Period 
 or end of the Maintenance Period of RPC01-3101)
will be conducted as outlined in this protocol. 
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Sponsor: Celgene International II Sàrl
Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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11
INVESTIGATIONAL DRUG MATERIALS AND MANAGEMENT
11.1
Investigational Drug
RPC1063 capsules will be manufactured, quality control tested, and released in accordance with 
Good Manufacturing Practices (GMP).  A clinical distribution vendor will supply the
investigational drug (RPC1063 capsules). 
RPC1063 will be provided as powder-filled capsules.  RPC1063 drug substance is blended with 
microcrystalline cellulose, silicon dioxide, croscarmellose sodium, and magnesium stearate in
Swedish orange opaque hard-gelatin capsules.  Two RPC1063 dosage strengths have been 
prepared for the clinical investigations; 
 mg 
 and  mg 
  
All investigational drug must be stored in a secure location.
11.2
Packaging and Labelling
RPC1063 capsules will be packaged in 
 
, apart from the dose escalation kits), closed with a 
 
.  The 
 on the treatment 
 will be 
, and 
 
The labelling will be in accordance with GMP and Good Clinical Practice (GCP) and any other 
local regulatory requirements. The label(s) for Investigational Product (IP) will include Sponsor 
name, address and telephone number, the protocol number, IP name, dosage form and strength 
(where applicable), amount of IP per container, lot number, expiry date (where applicable), 
medication identification/kit number, dosing instructions, storage conditions, and required caution 
statements and/or regulatory statements as applicable. Additional information may be included on 
the label as applicable per local regulations.
11.3
Investigational Drug Accountability
Investigational drug should not be used for purposes other than as defined in this protocol.
All supplies of investigational drug will be accounted for in accordance with GCP.  There will be 
an individual investigational drug accountability record for each patient and the Investigator 
should maintain accurate records of the disposition of all investigational drug supplies received 
during the trial.  These records should include the amounts and dates clinical drug supplies were 
received, dispensed to the patient, returned by the patient, and returned to the Sponsor.  If errors 
or damages in the clinical drug supply shipments occur, the Investigator should contact the clinical 
supply distribution vendor and the Site Monitor immediately.  The Site Monitor will periodically 
check the supplies of investigational drug held by the Investigator or pharmacist to verify 
accountability of all medication used.
The Investigator will provide the investigational drug only to the identified patients of this trial, 
according to the procedures described in this trial protocol.  After the end of the trial, the Site
Monitor will perform final accountability, package, seal, and prepare for shipment. Investigational 
drug and all investigational drug containers will be returned to the clinical supply distribution 
vendor and documentation will be returned to the contract research organization (CRO).  The CRO 
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Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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will verify that a final report of drug accountability is prepared and maintained in the Investigator’s 
Trial Master File.
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Sponsor: Celgene International II Sàrl
Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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12
ASSESSMENT OF EFFICACY
12.1
Complete Mayo Score, Partial Mayo Score, 9-Point Mayo Score, and 
Mayo Subscores 
The Complete Mayo Score is a composite of four assessments, each rated from 0 to 3:  SFS, RBS, 
MES, and PGA (Schroeder et al, 1987).  The MES of the complete Mayo score is derived from an 
evaluation of findings on endoscopy based on central reading by a qualified central laboratory.  
The 9-Point Mayo score eliminates the PGA, resulting in a composite of the RBS, SFS, and MES. 
The Partial Mayo Score eliminates the MES, resulting in a composite of the RBS, SFS, and PGA
subscores.  The complete Mayo score has a range of 0 to 12 and the 9-Point Mayo score and Partial 
Mayo Score each have a range of 0 to 9.
The complete Mayo score consists of four subscores, each ranging from (0-3) for a total score that 
ranges from 0 to 12:
1) Stool frequencya
a) 0 = Normal number of stools for this patient
b) 1 = 1 to 2 stools more than normal
c) 2 = 3 to 4 stools more than normal
d) 3 = 5 or more stools more than normal
2) Rectal bleedingb
a) 0 = No blood seen
b) 1 = Streaks of blood with stool less than half the time
c) 2 = Obvious blood with stool most of the time
d) 3 = Blood alone passes
3) Findings on endoscopy
a) 0 = Normal or inactive disease
b) 1 = Mild disease (erythema, decreased vascular pattern, does not include friability)
c) 2 = Moderate disease (marked erythema, lack of vascular pattern, friability, erosions)
d) 3 = Severe disease (spontaneous bleeding, ulceration)
4) Physician’s Global Assessmentc
a) 0 = Normal
b) 1 = Mild disease
c) 2 = Moderate disease
d) 3 = Severe disease
a Each patient serves as his or her own control to establish the degree of abnormality of the SFS.
b The daily RBS represents the most severe bleeding of the day.
c The PGA acknowledges the 3 other criteria, the patient’s daily recollection of abdominal discomfort and general 
sense of well-being, and other observations, such as physical findings and the patient’s performance status.
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Sponsor: Celgene International II Sàrl
Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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See Section 6.2.1 for definitions of clinical remission, clinical response, corticosteroid-free 
remission, endoscopic improvement, mucosal healing, and histologic remission.
Partial Mayo Scores are calculated using data from Items 1, 2, and 4 only and are calculated using 
the SFS and RBS data from the most recent consecutive 3-day period prior to the visit, excluding 
the following:

The day(s) of a procedure or preparation for a procedure (eg, enemas, other laxative, clear 
liquid diet) that would affect bowel frequency or blood content of the stool
12.2
Flexible Sigmoidoscopy/Colonoscopy
To ensure quality data and standardization, the same endoscopist should be used throughout the 
trial wherever possible. Endoscopy images will be obtained during each endoscopy and will be 
sent for central reading and determination of the Mayo MES. A detailed image review charter 
from the central reading laboratory will outline the endoscopic procedures, video recordings and 
equipment. For each patient, video recording of the entire endoscopic procedure will be performed 
using an acceptable storage medium. The endoscopic recordings will be read centrally in a blinded 
manner for mucosal lesions and endoscopic severity by a qualified gastroenterologist according to 
the image review charter. The MES will be determined both at the Investigator site and centrally 
as described above.  The complete and 9-point Mayo score used for clinical endpoints in the trial 
will utilize the MES derived from the central reader.
Biopsy
Each patient entered into the trial will have colonic biopsies obtained during flexible 
sigmoidoscopy/full colonoscopy as follows (see Table 2):

One biopsy pair will be taken from the most inflamed area of the left colon.  Biopsies will be 
placed in formalin.  These biopsies will be analyzed centrally.

ONLY if there is suspicion for clinically significant cytomegalovirus (CMV) colitis, one 
biopsy should be taken from the base of an ulcer to evaluate for histological presence of CMV, 
but otherwise is not necessary for inclusion in the trial.  Analysis will be performed locally.

Only if there is suspicion for dysplasia or malignancy, appropriate biopsies should be taken to 
exclude malignancy or assess dysplasia.  Analysis should be performed locally.
Necrotic areas of ulcerated mucosa should be avoided during biopsy.  The original location 
(colonic segment and endoscopic depth) of biopsy specimens should be clearly indicated.  
In all cases, the video recordings are to be taken prior to biopsy and sent to central reading 
center of the study.
12.3
Patient-Reported Outcomes
Patient-reported outcomes (SFS and RBS components of the complete, 9-point, and partial Mayo 
score), and the clinician-reported PGA will be collected in an electronic diary.  Patients will 
complete the SFS and RBS components of the Mayo subscore daily from the Baseline Visit until 
the 
 Visit.
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Sponsor: Celgene International II Sàrl
Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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Patients will be instructed on the use and completion of questions on the electronic diary.  The 
patients’ baseline SFS is to be recorded in RPC01-3102 using data collected on the first day of 
Screening from the RPC01-3101 or RPC01-202 trial.  This is defined as the number of stools the 
patient passed in a 24-hour period prior to having UC or when the patient is in remission.  
The diary entries will be reviewed by site personnel during screening (prior to dosing, if applicable) 
and during all trial visits, through the 
 Visit.  The SFS and RBS diary entries 2 weeks prior 
to each trial visit will be used to calculate the complete, 9-point, and partial Mayo score.
Because the colonoscopy/flexible sigmoidoscopy preparations can interfere with the assessment 
of other clinical parameters, diary entries used to calculate the complete Mayo Score and Partial 
Mayo Score will not correspond to day(s) of bowel preparation or endoscopy.  
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Sponsor: Celgene International II Sàrl
Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
55
13
ASSESSMENTS OF SAFETY
13.1
Safety Parameters
13.1.1
Physical Examination 
A complete physical examination will include evaluation of the heart, lungs, head and neck, 
abdomen, skin, and extremities, as well as a check for visual symptoms.  All significant findings 
that are present at the Baseline Visit must be reported on the relevant medical history/current 
medical conditions eCRF.  A check for visual symptoms and a full examination of the skin should 
be repeated 
. Significant findings made after Baseline that meet the definition of 
an AE must be recorded on the AEs eCRF.
At all other visits following the Baseline Visit (except 
and 90-day SFU), an interim 
physical examination will be performed (Table 2).  The interim physical examination will include 
body systems with previously noted abnormalities and/or those body systems associated with any 
new complaints from the patient.
13.1.2
Height and Weight
For all patients, height and weight will be measured at Visit and at the 
 visit. Height and 
weight can also be measured at the SFU Visit at the discretion of the Investigator (eg, in the case 
of ongoing AEs that need to be further evaluated).
13.1.3
Vital Signs
Systolic and diastolic blood pressure and pulse will be assessed in a sitting position.  An automated 
validated device may be used, if available. In case the cuff sizes available are not large enough for 
the patient’s arm circumference, a sphygmomanometer with an appropriately sized cuff may 
be used. 
 
 
13.1.4
Electrocardiogram
The 12-lead digital ECG devices will be provided to each clinical site by the central ECG 
laboratory for the duration of the trial.  Detailed instructions describing the process for recording 
and transmission of the digital ECGs will be outlined in the trial-specific manual and provided to 
the site before the start of the trial.  Paper versions of ECG tracings recorded at the times specified 
in the Schedule of Events (Table 2) will be printed and photocopied to preserve the ink if necessary, 
and kept at the site as source documentation. 
An ECG will be performed while resting.  Electrocardiograms will be performed 
 
 
 will be evaluated by the treating 
physician, with input if needed from a local cardiologist or a central reader to confirm if extended 
monitoring is required.  Additional ECG monitoring will be performed on Days 
 if cardiac 
issues are identified on the prior day of dose escalation, as described in Section 13.1.10.
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Sponsor: Celgene International II Sàrl
Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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Only clinically significant abnormalities should be reported in the medical history/current medical 
conditions or the AE eCRF.  Clinically significant findings must be discussed with the Medical 
Monitor before enrolling the patient in the trial. 
13.1.5
Ophthalmological Examination
 will be performed in patients with a history of uveitis or 
diabetes mellitus or underlying/coexisting retinal disease or in all patients if deemed necessary by 
local or national requirements, as scheduled in Table 2.  All original 
 images (colored 
printouts) are considered source documents that should be made available to the site upon request, 
or otherwise at the end of the study.
 
 
 The 
 images may be reviewed by an independent panel of ophthalmologists assigned to this trial.
13.1.6
Dermatological Examination
Dermatological evaluations will be performed by the treating Investigator or designee as part of 
the physical exam, as scheduled in Table 2.  Patients with any suspicious finding noted during the 
examination will be referred to an appropriately qualified dermatologist for evaluation and 
treatment, if warranted.
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Sponsor: Celgene International II Sàrl
Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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13.1.8
Monitoring of Adverse Events and Serious Adverse Events
Throughout the course of the trial, every effort must be made to remain alert to possible AEs or 
SAEs.  Refer to Section 13.2 for definitions of AEs/SAEs, monitoring, and reporting.  Refer to 
Section 13.2.6 for AEs of special interest.
13.1.9
Monitoring of Concomitant Therapy
The use of concomitant medication and procedures will be monitored throughout the trial. Refer 
to Section 10.5.2 for prohibited concomitant therapies.
13.1.10
Guidelines for Cardiac Monitoring 
Patients entering the trial from the open-label period of RPC01-202 will continue to receive 
RPC1063 and no additional cardiac monitoring is required.
 
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Sponsor: Celgene International II Sàrl
Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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Sponsor: Celgene International II Sàrl
Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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13.1.11
Clinical Laboratory Evaluations
The central laboratory will analyze the samples.  Further details of the procedures to be followed 
for sample collection, storage, and shipment will be documented in a laboratory manual.
Additional and repeat laboratory safety testing may be performed at the discretion of the 
Investigator and analyzed by the local laboratory. Approval from the Medical Monitor must be 
obtained if any lab test is required to be repeated > 2 times.

Hematology:  Red blood cell count, total and differential WBC count (basophils, eosinophils, 
lymphocytes, monocytes, and neutrophils), platelet count, hemoglobin (Hb), hematocrit, mean 
corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin 
concentration.  Total WBC count and all differential WBC counts will not be disclosed for 
Visit  only and will be monitored centrally throughout the trial.
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930190807
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Sponsor: Celgene International II Sàrl
Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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
Chemistry:  

Full chemistry panel at Baseline: sodium, potassium, chloride, calcium, magnesium, 
phosphate, blood urea nitrogen, glucose, HbA1c, albumin, alkaline phosphatase, 
creatinine, ALT, AST, gamma glutamyl transferase (GGT), total bilirubin, conjugated 
bilirubin, total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, 
and 
.
HbA1c will be repeated annually

All other visits – blood urea nitrogen, albumin, alkaline phosphatase, creatinine, ALT, 
AST, GGT, total bilirubin, conjugated bilirubin, 
.  Of note, 
 
 will not be disclosed for Visit  to maintain the blind from the parent trial from 
which a patient may be entering.

Urinalysis:  Leukocytes, specific gravity, bilirubin, blood, glucose, ketones, pH, protein, and 
urobilinogen

The central laboratory will analyze routine 
.  Details regarding collection of 
samples, shipment of samples, reporting of results, laboratory reference ranges, and alerting 
abnormal values will be supplied to the site before site initiation in a trial laboratory manual.  
The results of the analysis will be made available to each site by the central laboratory.

Investigators will be asked to comment on those abnormalities on the respective laboratory 
result page, including a notation of the clinical significance of each abnormal finding in the 
patient’s source documents.  The laboratory sheets will be filed with the patient’s source 
documents.  

Pregnancy test:  Serum β-hCG must be performed in females of childbearing potential at 
Baseline if more than 1 month has elapsed from the last pregnancy test in the parent trial. Urine
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930190807
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Sponsor: Celgene International II Sàrl
Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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β-hCG will be performed in females of childbearing potential at each scheduled visit. Between 
scheduled visits up until the 90-day SFU Visit, monthly home urine pregnancy tests should be 
performed by the patient. If a urine pregnancy test result is positive, the Investigator will 
instruct the patient to suspend further RPC1063 dosing, if applicable, and schedule a follow-
up appointment as soon as possible. A serum pregnancy test will be performed for 
confirmation, including after the 90-day SFU Visit, if needed.
13.2
Adverse Events and Serious Adverse Events
13.2.1
Definition of Adverse Events
An AE is any untoward medical occurrence in a patient or clinical investigation patient 
administered a pharmaceutical product, which does not necessarily have a causal relationship with 
this treatment.  An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of 
a medicinal product, whether or not considered related to the medicinal product (ICH E2A, II.A.1).
Ulcerative colitis disease relapse and related symptoms will be monitored as trial endpoints and 
thus will not be recorded as AEs, unless it qualifies as a serious AE to trigger safety reporting as 
described in Section 13.2.5.
In cases of surgical or diagnostic procedures, the condition/illness leading to such a procedure is 
considered as the AE rather than the procedure itself.
An Adverse Drug Reaction (ADR) is defined as all noxious and unintended responses to 
a medicinal product causally related to any dose (ICH E2A, II.A.2).  
An Unexpected ADR is defined as an adverse reaction, the nature of which is not consistent with 
the applicable product information (ICH E2A, II.A.3).
Each AE is to be evaluated for duration, severity, seriousness, and causal relationship to the 
investigational drug.  The action taken and the outcome must also be recorded.
13.2.2
Definition of Serious Adverse Events
Definition of Serious Adverse Event (SAE):  An SAE (experience) or reaction is any untoward 
medical occurrence that at any dose (ICH E2A, II.B):

Results in death 

Is life-threatening 
NOTE:  The term life-threatening” in the definition of “serious” refers to an event in which the 
patient was at risk of death at the time of the event; it does not refer to an event which 
hypothetically might have caused death if it were more severe.

Requires inpatient hospitalization or prolongation of existing hospitalization

Results in persistent or significant disability/incapacity, or

Is a congenital abnormality/birth defect
Medical and scientific judgment should be exercised in deciding whether expedited reporting is 
appropriate in other situations, such as important medical events that may not be immediately life-
threatening or result in death or hospitalization but jeopardize the patient or may require 
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Sponsor: Celgene International II Sàrl
Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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intervention to prevent one of the other outcomes listed in the definition above.  These should also 
usually be considered serious.  
Examples of such events may be related to CNS (Central Nervous System), cardiovascular, 
pulmonary, ophthalmic, gastrointestinal, genitourinary or other body systems and include events 
such as intensive treatment in an emergency room or at home for allergic bronchospasm; blood 
dyscrasias or convulsions that do not result in hospitalization; or development of drug dependency 
or drug abuse.
In case of a fatality, the cause of death is considered as the SAE, and the death is considered as its 
OUTCOME.
13.2.3
Assessment of Adverse Event Severity
The severity of the AE will be characterized as “mild, moderate, or severe” according to the 
following definitions:

Mild events are usually transient and do not interfere with the patient’s daily activities.

Moderate events introduce a low level of inconvenience or concern to the patient and may 
interfere with daily activities.

Severe events are incapacitating and interrupt the patient’s usual daily activity.
13.2.4
Assessment of Adverse Event Relationship to Investigational Drug
The causal relationship between the investigational drug and the AE has to be characterized as 
unrelated, unlikely, possible, probable, or related.  This medical assessment should be made as 
soon as feasible when reporting an SAE.
The Investigator is requested to assess the relationship of any AEs to treatment using the following 
definitions:

Unrelated:  Those AEs which are clearly and incontrovertibly due to extraneous causes 
(concurrent drugs, environment, etc.) and do not meet the criteria for drug relationship listed 
under Unlikely, Possible, Probable, or Related.

Unlikely:  An AE may be considered unlikely if it includes at least the first two features:

It does not follow a reasonable temporal sequence from administration of the drug 

It could readily have been produced by the patient’s clinical state, environmental or toxic 
factors, or other modes of therapy administered to the patient 

It does not follow a known pattern to the suspected drug 

It does not reappear or worsen when the drug is re-administered 

Possible: an AE may be considered possible if it includes at least the first two features:

It follows a reasonable temporal sequence from administration of the drug

It could readily have been produced by the patient’s clinical state, environment or toxic 
factors, or other modes of therapy administered to the patient

It follows a known response pattern to the suspected drug
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Sponsor: Celgene International II Sàrl
Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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
Probable: an AE may be considered probable if it includes at least the first three features:

It follows a reasonable temporal sequence from administration of the drug

It could not be reasonably explained by the known characteristics of the patient’s clinical 
state, environmental or toxic factors or other modes of therapy administered to the patient

It disappears or decreased on cessation or reduction in dose.  There are exceptions when 
an AE does not disappear upon discontinuation of the drug (eg, bone marrow depression, 
fixed drug eruptions, tardive dyskinesia, etc.)

It follows a known pattern of response to the suspected drug

Related: an AE may be considered related if it includes all of the following features:

It follows a reasonable temporal sequence from administration of the drug

It could not be reasonably explained by the known characteristics of the patient’s clinical 
state, environmental or toxic factors or other modes of therapy administered to the patient

It disappears or decreased on cessation or reduction in dose.  There are exceptions when 
an AE does not disappear upon discontinuation of the drug (eg, bone marrow depression, 
fixed drug eruptions, tardive dyskinesia, etc)

It follows a known pattern of response to the suspected drug

It reappears or worsens if the drug is re-administered
All efforts should be made to classify the AE according to the above categories. 
After initiation of investigational drug, all AEs, regardless of relationship to investigational drug, 
will be recorded until the patient completes his or her last trial visit.
13.2.5
Reporting of Serious Adverse Events
Reporting requirements for SAEs will be managed on behalf of the Sponsor by the CRO.  Full 
details of the procedures to be adopted will be documented in a safety management plan approved 
by responsible parties, in brief:
The Investigator will report any SAE that occurs to any patient from the time written informed 
consent is signed through the last visit.  If an SAE occurs after informed consent and is resolved 
before the first dose of investigational drug in RPC01-3102, the event will be captured in the parent 
trial only (eg, RPC01-3101 or RPC01-202). If the SAE is ongoing at the time of the first dose in 
RPC01-3102, it will be transcribed into the eCRF for RPC01-3102. If an SAE occurs after the 
first dose of investigational drug in RPC01-3102, it will be captured in the eCRF for RPC01-3102.  
All SAEs that occur within 90 days of the last dose of treatment with the investigational drug, 
whether or not considered related to the investigational drug, must also be reported.  Any SAE that 
is ongoing when the patient completes the trial or discontinues from the trial will be followed by 
the Investigator until the event has resolved, stabilized, or returned to Baseline status.
Any AE considered serious by the Investigator or Sub-investigator or that meets serious criteria 
should be reported to the CRO’s Pharmacovigilance group using the designated SAE reporting 
forms as well as eCRF forms and procedures.  Data entry must be completed within 24 hours from 
the time the trial site personnel first learned of the event. 
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Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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The SAE hotline contacts are as follows:
Phone Number: +1 866-599-1341
Fax Number: +1 866-599-1342
Email: QPV_Receptos@iqvia.com 
The initial report should be promptly followed by detailed, written reports, which will include 
copies of hospital case records, discharge summaries, autopsy reports, and other documents when 
requested and applicable.  For unrelated cases, a full detailed case description may negate the need 
for additional hospital case records, discharge summaries, etc.
13.2.5.1
Reporting of Serious Adverse Events to Regulatory Authorities and 
Investigators
Investigators will be notified by the CRO of all SAEs that require prompt submission to their IRB 
or IEC.  Investigators should provide written documentation of IRB/IEC notification for each 
report to the CRO.  The CRO will ensure that all SAEs are reported to the appropriate Regulatory 
Authorities as required.  Reporting of SAEs must comply with ICH E6, 4.11.1.
13.2.6
Adverse Events of Special Interest
Potential AEs that may be a consequence of S1P1 modulation will be closely monitored during the 
trial.  
 
 
 
 
 
 
 
 
  The study team will perform routine safety reviews starting 
after the first patient is dosed with investigational product.
Special considerations regarding monitoring for these events are as follows:
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930190807
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Sponsor: Celgene International II Sàrl
Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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13.2.7
 Pandemic 
 pandemic has been identified as a potential risk 
to clinical trial patients in general and may particularly affect individuals with underlying chronic 
diseases on immunomodulatory therapies. It is not known whether taking ozanimod increases the 
risk of 
 infection, or the duration or severity 
.
Evaluation and management of 
 infections arising during the course of the trial are 
left to the discretion and expertise of the investigator. For patients who exhibit symptoms 
consistent with 
, testing for 
 to inform decisions and clinical care 
during the study should follow local standard practice. The Sponsor advises the Investigator to 
consult the Medical Monitor.
Each study visit will include an assessment for AEs including 
 and other infections. 
In order to facilitate reporting of 
 events that occur during the study, all AEs and 
SAEs related to 
 should be reported from the time of consent until the final study 
visit.
Procedures related 
 
 and treatment (eg, intubation, dialysis) must be reported in the 
appropriate eCRF.
Administration of vaccinations must be reported along with dates of administration, vaccine 
name/trade name, location, and laterality in the appropriate eCRF. A separate logline should be 
entered for each vaccine administered.
13.2.8
Monitoring of Patients with Adverse Events, Serious Adverse Events, 
and Adverse Events of Special Interest

Investigators must carefully monitor each patient for AEs.  This includes clinical laboratory 
variables.  Assessments must be made of the seriousness, severity, and relationship to the 
administration of the investigational drug.  After the initial AE/SAE report, the Investigator is 
required to follow up proactively with each patient and provide further information to the CRO 
on the patient’s condition.  During the trial, all AE/SAEs should be followed up to resolution 
unless the event is considered by the Investigator to be unlikely to resolve due to the patient’s 
underlying disease, or the patient is lost to follow-up.  Safety reporting must comply with ICH 
E6, 4.11.
13.2.9
Overdose of Investigational Drug
An overdose is any dose of investigational drug given to a patient or taken by a patient that exceeds 
the dose described in the protocol. There is no information available regarding overdose with 
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RPC1063. Any overdose, with or without associated AEs, must be promptly reported to the CRO’s 
Medical Monitor or other designated Drug Safety Center. Overdoses need to be recorded in the 
drug log in the eCRF; but only in the case of any AEs associated with the overdose should these
be reported on relevant AE/SAE sections in the eCRF. 
13.2.10
Procedures in Case of Pregnancy
If a urine pregnancy test is positive, the Investigator will instruct the patient to suspend further 
RPC1063 dosing. If the test was performed by the patient between scheduled visits, a follow-up 
appointment will be scheduled as soon as possible. A serum pregnancy test will be performed for 
confirmation.
Pregnancy in itself is not regarded as an AE unless there is a suspicion that an investigational drug 
may have interfered with the effectiveness of a contraceptive medication; however, the outcome 
of all pregnancies (spontaneous miscarriage, elective termination, normal birth, or congenital 
abnormality) must be followed up and documented even if the patient was discontinued from the 
trial.  In cases of live birth, the infant will be followed for up to a year.
Male patients should also be instructed to notify the Investigator in the event that their female 
partner becomes pregnant.  Attempts should be made to follow female partners of trial patients, if 
they should become pregnant.  The Investigator must obtain informed consent from the pregnant 
partner of a trial patient prior to collecting data on her pregnancy and its outcome.
All reports of congenital abnormalities/birth defects are SAEs.  Spontaneous miscarriages should 
also be reported and handled as SAEs.  Elective abortions without complications should not be 
handled as AEs.  All outcomes of pregnancy must be reported to the Sponsor and/or its designee.
In cases of live birth, the infant will be followed for up to a year.
13.2.11
Data Safety Monitoring Board
An independent Data Safety Monitoring Board (DSMB) was charged with monitoring data from 
the trial as part of the ozanimod UC Phase 3 program, as well as general aspects of trial conduct.
The DSMB scope, conduct, processes, and accountabilities are specified in a separate charter.
The committee met periodically during the trial (approximately 4 times each year) to review 
aggregate analyses by treatment group including but not limited to enrollment, treatment 
compliance, adherence to follow-up schedule, and safety data from the trial.  The DSMB
recommended to continue the study without modification and did not recommend modifying or 
stopping the trial early due to safety concerns based on data reviews. 
As the maintenance period has been completed for the RPC01-3101 study, the DSMB will no 
longer meet to review data from the UC Phase 3 program. The internal team will continue to 
monitor the data from this open-label extension study.
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Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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13.4
Appropriateness of Measurements
The efficacy and safety assessments are standard assessments and deemed to be reliable, accurate, 
and relevant for this indication and patient population.
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14
PLANNED STATISTICAL METHODS
14.1
Determination of Sample Size
As this is an open-label extension trial for patients who previously participated in a trial of 
RPC1063 in UC, there is no statistical basis for the sample size.  It is anticipated that up to 
 
patients who participated in prior studies of RPC1063 in UC may be eligible for treatment in this 
trial.
14.2
Statistical Methods
14.2.1
General Considerations
All efficacy and safety data will be listed by patient.  Baseline is defined as the last observed 
measurement prior to the Day receipt of investigational drug.
In general, descriptive summaries will be presented for the efficacy and safety variables collected.  
Continuous variables will be summarized using number of patients (n), mean, standard deviation 
(SD), minimum, median, and maximum.  Categorical variables will be summarized using 
frequency counts and percentages.  
14.2.2
Analysis Populations
All patients who receive at least one dose of investigational drug will comprise both the Intent-to-
Treat (ITT) population and the Safety population.  These populations will be used to summarize 
all efficacy and safety data, respectively.
14.3
Disposition, Demographics, and Baseline Characteristics
The number and percentage of patients in each population will be summarized.  Patient disposition, 
including the number of patients screened, dosed, and not completing trial by reason for dropout 
will be summarized.  Patient demographics will be summarized and will include age, sex, race, 
ethnicity, height, weight, and body mass index.
Baseline characteristics for each patient from their previous trial will be summarized and will 
include age at UC symptom onset, age at UC diagnosis, years since UC symptom onset, years 
since UC diagnosis, prior anti-tumor necrosis factor use, prior corticosteroid use, each component 
of the Mayo score, the complete Mayo score, the partial Mayo score, and the 9-Point Mayo score.
Compliance with investigational drug will be summarized and will include the number of patients 
estimated to be < 80% compliant, 80 to 100% compliant, > 100%, and > 120% compliant. 
14.4
Efficacy
Due to the open-label nature of the trial and the lack of a control group, all data will be summarized,
and no hypothesis testing will be performed.  Each efficacy endpoint will be summarized and 95% 
confidence intervals around the estimates may also be presented.  All efficacy data will be listed.
14.4.1
Handling Missing Data
For all proportion-based efficacy endpoints, patients with missing efficacy data will be considered 
non-responders.
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For continuous efficacy endpoints, patients with missing data will have their last post-baseline 
value carried forward.  
Observed-cases analyses will also be presented for all efficacy endpoints.
14.5
Safety Analyses
Adverse events will be monitored during the trial and the data analyzed with respect to incidence 
within each parent trial treatment group as well as severity and potential relationship of the AEs 
to investigational drug.  
All AEs with a start date before the first dose date in RPC01-3102, which are ongoing from a 
previous trial to RPC01-3102, will be listed in the AE data listing and labeled as “Prior Adverse 
Event.” 
Adverse events with an onset date on or after the first open-label dose date in RPC01-3102, or 
with onset prior to the first open-label dose date in RPC01-3102 that increase in severity on or 
after the first dose of investigational drug
will be considered treatment emergent.  
Treatment-emergent AEs will be summarized for the Safety population by System Organ Class 
and Preferred Term and presented in descending order of frequency within each System Organ 
Class.  Serious AEs and AEs leading to discontinuation will be summarized similarly.
Associated laboratory parameters such as hepatic profile, renal function, and hematology values 
will be grouped and presented together.  For each laboratory test, individual patient 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 highest and to the lowest on-trial value in and out of the 
normal range as well as by visit.  Changes from Baseline to each visit for each numeric 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.
The change from Baseline to each visit for each of the ECG parameters will be summarized. An 
outlier analysis of ECG results will be conducted.
14.6
Interim Analyses
Interim analyses were performed to support regulatory submission activities for the MS and UC 
indications.
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15
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS
15.1
Monitoring
The Sponsor has engaged the services of a CRO to perform all monitoring functions within this 
clinical trial.  The CRO monitors will work in accordance with CRO standard operating procedures 
(SOPs) and have the same rights and responsibilities as monitors from the Sponsor organization.  
Monitors will establish and maintain regular contact with the Investigator.
Monitoring visits will be conducted according to all applicable regulatory requirements and 
standards.  Regular monitoring visits will be made to each site while patients are enrolled in the 
trial.  
15.2
Data Management/Coding
Electronic Data Capture (EDC) will be used for this trial, meaning that all eCRF data will be 
entered in electronic forms at the site.  All EDC systems used in the trial will have access-
controlled security and an audit history available to document any changes made to the data 
throughout the course of the trial.  Data collection recorded in site source documents will be 
entered into the eCRF by authorized site staff designated by the Investigator. Patients will record 
whether they took the daily dose of investigational drug directly into an electronic diary, and this 
will be considered a source document.  Appropriate training and security measures will be 
completed with the Investigator, all authorized site staff, and patients prior to the trial being 
initiated and any data being entered into the system for and/or by any trial patients.
All data entered by the site staff must be entered in English.  The eCRFs should be completed 
contemporaneous to the patient’s visit.  The Investigator may delegate data entry, but is responsible 
for verifying that all data entries in the eCRFs are accurate and correct at the conclusion of the 
trial.  
Source documents are all documents used by the Investigator or hospital that relate to the patient’s 
medical history, that verify the existence of the patient, the inclusion and exclusion criteria, and 
all records covering the patient’s participation in the trial.  They include laboratory notes, ECG 
results, memoranda, pharmacy dispensing records, patient files, etc.
Source documents will be made available for inspection by the trial monitor at each monitoring 
visit.  The Investigator must complete eCRFs for each patient who receives investigational drug.  
Any copy of source document(s) that are provided to the Sponsor or its representatives for any 
purpose (eg, in support of an SAE report) must be redacted such that all patient-identifying 
information is removed, and clearly labeled with the trial and patient number.
All AEs and medical histories recorded in the eCRF will be coded using the Medical Dictionary 
for Regulatory Activities (MedDRA). Concomitant medications will be coded using the World 
Health Organization (WHO) drug dictionary.  Versions of dictionaries to be used will be specified 
in the data management plan for the trial.
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10 August 2022, Version 10.0
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15.3
Quality Assurance and Inspections
Sites, the trial database, and trial documentation may be subject to Quality Assurance audit during 
the course of the trial by the Sponsor or CRO on behalf of the Sponsor.  In addition, inspections 
may be conducted by regulatory bodies at their discretion.  
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Safety and Efficacy of RPC1063 in UC
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16
QUALITY CONTROL AND QUALITY ASSURANCE
16.1
Study Monitoring and Source Data Verification
According to the Guidelines of Good Clinical Practice (CPMP/ICH/135/95), the Sponsor is 
responsible for implementing and maintaining quality assurance and quality control systems with 
written SOPs. Study Monitoring including, risk-based monitoring, risk management and 
mitigation strategies as well as analytical risk-based monitoring, responsibilities, and 
requirements, including handling of noncompliance issues and monitoring techniques (central, 
remote, or on-site monitoring) will be followed as per the monitoring plan.
Quality control will be applied to each stage of data handling.  
The following steps will be taken to ensure the accuracy, consistency, completeness, and reliability 
of the data:

Investigator meeting(s) 

Central laboratories for clinical laboratory parameters and ECGs 

Site initiation visit 

Early site visits post-enrollment 

Routine site monitoring 

Ongoing site communication and training 

Data management quality control checks 

Continuous data acquisition and cleaning 

Internal review of data

Quality control check of the final clinical study report
In addition, Sponsor and/or CRO Clinical Quality Assurance Department may conduct periodic 
audits of the trial processes, including, but not limited to site facilities, central laboratories, 
vendors, clinical database, and final clinical study report.  When audits are conducted, access must 
be authorized for all trial-related documents including medical history and concomitant medication 
documentation to authorized Sponsor’s representatives and regulatory authorities.
16.2
Investigational Medicinal Product Quality Issues
Investigational Medicinal Product Quality Issues such as IP safety, purity, potency, quality and 
identity (eg, evidence of suspected tampering of product) must be reported as soon as possible to 
the study Clinical Trial Monitor and/or Clinical Trial Manager or designee. Report any issue or 
concern of all sponsor-supplied IP (eg, manufacturing, packaging and labelling, storage, and/or 
distribution), if suspected to have occurred before the product was received, becomes the 
responsibility of the investigational site. This includes suspected quality issues of components 
co-packaged with the drug, labelling, and IP device/drug combination products, and medical 
devices. 

In the event of a suspected product quality issue, the immediate action to be taken by site is to 
quarantine the affected product. Do not dispose of the product unless retention presents a risk 
to personnel (eg, cytotoxic, risk of injury from broken glass or sharps).
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
When reporting, provide as much product information as possible. Suspected IP quality issues 
will be investigated, and a response will be provided back to the investigational site.
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17
ETHICS
17.1
Institutional Review Board or Independent Ethics Committee
An IEC should approve the final protocol, including the final version of the Informed Consent 
Form (ICF), and any other written information and/or materials to be provided to the patients.  The 
Investigator will provide the Sponsor or CRO with documentation of IRB/IEC approval of the 
protocol and ICF before the trial may begin at the site(s).  The Investigator should submit the 
written approval to the Sponsor or representative before enrollment of any patient into the trial.
The Sponsor or representative should approve any modifications to the ICF that are needed to meet 
local requirements.
The Investigator will supply documentation to the Sponsor or CRO of required IRB/IEC’s annual 
renewal of the protocol, and any approvals of revisions to the ICF document or amendments to the 
protocol.
The Investigator will report promptly to the IRB/IEC, any new information that may adversely 
affect the safety of patients or the conduct of the trial.  Similarly, the Investigator will submit 
written summaries of the trial status to the IRB/IEC annually, or more frequently if requested by 
the IRB/IEC.  Upon completion of the trial, the Investigator will provide the Ethics Committee 
with a brief report of the outcome of the trial, if required.
17.2
Ethical Conduct of the Trial
This trial will be conducted and the informed consent will be obtained according to the ethical 
principles stated in the applicable version of the Declaration of Helsinki, the applicable guidelines 
for Good Clinical Practice (GCP; CPMP/ICH/135/95), or the applicable drug and data protection
laws and regulations of the countries where the trial will be conducted.
Good Clinical Practice is an international ethical and scientific quality standard for designing, 
conducting, recording and reporting studies that involve the participation of human patients.  The 
trial will be conducted in compliance with GCP and the applicable national regulations so as to 
assure that the rights, safety and well-being of the participating trial patients are protected 
consistent with the ethical principles that have their origin in the Declaration of Helsinki.
17.3
Patient Information and Informed Consent
The Investigator will explain the benefits and risks of participation in the trial to each patient and/or 
the impartial witness and obtain written informed consent.  Written informed consent must be 
obtained prior to the patient entering the trial and before initiation of any trial-related procedure.  
The final, version dated form must be agreed to by the IRB/IEC and must be provided in language 
readily understood by the patient.  In case the patient is unable to read or write, an impartial witness 
should be present during the entire informed consent discussion.  After the patient has orally 
consented to participation in the trial, the witness’ signature on the form will attest that the 
information in the consent form was accurately explained and understood.  The Investigator or 
designee will retain an original consent form for each patient, signed and dated by the patient, or 
witness, and by the person who conducted the informed consent discussion.  The Investigator will 
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Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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supply all enrolled patients with either a copy of their signed informed consent or, depending upon 
local requirements, a second original informed consent, signed by both parties.
The consent form may need to be revised during the trial due to a protocol amendment or should 
important new information become available that may be relevant to the safety of the patient.  In 
this instance, approval should always be given by the IRB/IEC and existing patients informed of 
the changes and re-consented, as directed by the IRB/IEC and in accordance with its policies and 
procedures; however, in some instances where an immediate change is necessary to eliminate an 
apparent hazard to patients, then it would not be necessary for a protocol amendment to receive 
IRB/IEC review and approval before being implemented.  Those patients who are presently 
enrolled and actively participating in the trial should be informed of the change if it might relate 
to the patients’ willingness to continue their participation in the trial. 
With the consent of the patient, the Investigator should inform the patient’s primary physician 
about participation in the clinical trial.   
17.4
Patient Data Protection
The ICF will incorporate (or, in some cases, be accompanied by a separate document 
incorporating) wording that complies with relevant data protection and privacy legislation.
17.5
Investigator Obligations
This trial will be conducted in accordance with the International Council on Harmonization (ICH)
Harmonized Tripartite Guideline for GCP (GCP, 1997); the US Code of Federal Regulations 
(CFR) Title 21 parts 50, 56, and 312; and European Legislation; and the ethical principles that 
have their origin in the Declaration of Helsinki.  
A summary of Investigator Obligations is provided in (Appendix 2).
The Investigator agrees to conduct the clinical trial in compliance with this protocol after the 
approval of the protocol by the IRB/IEC in compliance with local regulatory requirements.  The 
Investigator and the Sponsor will sign the protocol to confirm this agreement.
17.6
Protocol Signatures
After reading the protocol, each Investigator will sign the protocol signature page and send a copy 
of the signed page to the Sponsor or representative (Appendix 1).  By signing the protocol, the 
Investigator confirms in writing that they have read, understand, and will strictly adhere to the trial
protocol and will conduct the trial in accordance with ICH Tripartite Guidelines for Good Clinical 
Practice and applicable regulatory requirements.  The trial will not be able to start at any site where 
the Investigator has not signed the protocol.
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Safety and Efficacy of RPC1063 in UC
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18
DATA HANDLING AND RECORD KEEPING
18.1
Inspection of Records
The Investigator will prepare and maintain adequate and accurate source documents to record all 
observations and other pertinent data for each patient enrolled in the trial.
The Investigator will allow the Sponsor, CRO, and authorized regulatory authorities to have direct 
access to all documents pertaining to the trial, including individual patient medical records, as 
appropriate.
18.2
Retention of Records
It is the Investigator’s responsibility to maintain essential trial documents (protocol and protocol 
amendments, completed eCRFs, signed ICFs, relevant correspondence, and all other supporting 
documentation).  The trial site should plan on retaining such documents for approximately 15 years 
after trial completion.  The trial site should retain such documents until at least 2 years after the 
last approval of a marketing application in an International Conference on Harmonization (ICH)
region and until there are no pending or contemplated marketing applications in an ICH region or 
at least 2 years after the formal discontinuation of clinical development of the investigational drug.  
These documents should be retained for a longer period if required by the applicable regulatory 
requirements or the hospital, institution, or private practice in which the trial is being conducted.  
Patient identification codes (patient names and corresponding trial numbers) will be retained for 
this same period of time.  These documents may be transferred to another responsible party, 
acceptable to Sponsor, who agrees to abide by the retention policies.  Written notification of 
transfer must be submitted to Sponsor.  The Investigator must contact Sponsor prior to disposing 
of any trial records.  
No records should be disposed of without the written approval of the Sponsor.
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Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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19
PUBLICATION POLICY, FINANCING, AND INSURANCE
The data generated by this trial are confidential information of the Sponsor.  The Sponsor will 
make the results of the trial publicly available.  The publication policy, financing, and insurance 
information with respect to the Investigator and the site will be set forth in the Clinical Trial 
Agreement.
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Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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20
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Schroeder et al, 1987
Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly 
to moderately active ulcerative colitis. A randomized study. N Engl J Med. 1987;317(26):1625-9.
Stenson, 2000
Stenson WF. Inflammatory bowel disease. In: Goldman l, Bennett, JC, eds. Cecil Textbook of 
Medicine, 21st ed. Philadelphia, PA: WB Saunders Co; 2000;722-729.
Tung et al, 2006
Tung J, Loftus EV Jr, Freese DK, et al. A population-based study of the frequency of corticosteroid 
resistance and dependence in pediatric patients with Crohn's disease and ulcerative colitis. Inflamm 
Bowel Dis 2006;12(12):1093-1100.
Turner and Griffiths, 2011
Turner D, Griffiths AM. Acute severe ulcerative colitis in children: a systematic review. Inflamm 
Bowel Dis 2011;17(1):440-449.
van Limbergen et al, 2008
van Limbergen J, Russell RK, Drummond HE, et al. Definition of phenotypic characteristics of 
childhood-onset inflammatory bowel disease. Gastroenterology 2008; 135(4):1114-1122.
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21
APPENDICES
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APPENDIX 1
INVESTIGATOR SIGNATURE
PROTOCOL TITLE:  A Phase 3, Multicenter, Open-Label Extension Trial of Oral RPC1063 as 
Therapy for Moderate to Severe Ulcerative Colitis
PROTOCOL NO:
RPC01-3102
This protocol is a confidential communication of Celgene International II Sàrl.  I confirm that I 
have read this protocol, I understand it, and I will work according to this protocol.  I will also work 
consistently with the ethical principles that have their origin in the Declaration of Helsinki and that 
are consistent with good clinical practices and the applicable laws and regulations.  Acceptance of 
this document constitutes my agreement that no unpublished information contained herein will be 
published or disclosed without prior written approval from Celgene International II Sàrl.
Instructions to the Investigator:  Please SIGN and DATE this signature page.  PRINT your name, title, 
and the name of the site in which the study will be conducted. 
I have read this protocol in its entirety and agree to conduct the study accordingly:
Signature of Investigator:
______________________________
Date:
________
Printed Name:
______________________________
Investigator Title: 
______________________________
Name/Address of Site:
______________________________
______________________________
______________________________
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Safety and Efficacy of RPC1063 in UC
10 August 2022, Version 10.0
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APPENDIX 2
INVESTIGATOR RESPONSIBILITIES
Per Good Clinical Practices 21CFR312.53
The Investigator:

Will conduct the study in accordance with the relevant, current protocol and will only make 
changes in the protocol after notifying the Sponsor, except when necessary to protect the 
safety, the rights, or welfare of patients;

Will comply with all requirements regarding the obligations of clinical Investigators and all 
other pertinent requirements;

Will personally conduct or supervise the described investigation;

Will inform any potential patients that the drugs are being used for investigational purposes 
and will ensure that the requirements relating to obtaining informed consent and IEC review 
and approval are met;

Will report to the Sponsor adverse experiences that occur in the course of the investigation in 
accordance with Section 312.64;

Has read and understands the information in the Investigator’s Brochure, including the 
potential risks and side effects of the drug; and

Will ensure that all associates, colleagues, and employees assisting in the conduct of the study 
are informed about their obligations in meeting the above commitments.
Per Good Clinical Practices 21CFR312.60
General Responsibilities of Investigators:
An Investigator is responsible for ensuring that an investigation is conducted according to the 
signed Investigator statement, the investigational plan, and applicable regulations; for protecting 
the rights, safety, and welfare of patients under the Investigator’s care; and for the control of drugs 
under investigation.  An Investigator shall, in accordance with the provisions of part 50, obtain the 
informed consent of each human patient to whom the drug is administered, except as provided in 
21CFR50.23.
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EDMS Doc. Number: 25770494 - 23199434
Sponsor: Celgene International II Sàrl
Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC—Summary of Changes 
23 August 2021, Version 9.0
(replaces 12 June 2020, Version 8.0)
CONFIDENTIAL
Page 4 of 114
This document summarizes the changes to Protocol RPC01-3102 from Version 8.0 (12 June 
2020) to Version 9.0 (dated 23 August 2021). 
1.
OVERVIEW OF KEY CHANGES (JUSTIFICATION FOR
AMENDMENT)
Main reason/purpose for amendment: Significant changes and rationale for the changes 
included in the amendment are briefly summarized below in Section 1 with detailed description 
in Section 2.
1. Extension of the duration of trial to evaluate the long-term safety and durable
efficacy in UC patients treated with ozanimod.
To ensure that a patient’s preference for commercially available Zeposia (in the country
of approval) is respected and a smooth transition is provided in the event that commercial
ozanimod or an access program becomes available prior to March 2023, patients may
transition to the commercial product after discussion with the Investigator.  Patients who
transition to commercial ozanimod are not required to attend safety follow-up visits after
their 
 as long as commercial ozanimod is started within 14 days of
discontinuation of study drug.
Revised Sections: Protocol Synopsis and Section 8.3.4 Safety Follow-Up
2. Safety evaluation criteria to justify less frequent visit schedule, decreasing the
burden on the patient.
Given the well-established safety profile and to simplify the visit schedule in this long-
term extension, frequency of visits after 
 was reduced from 
 intervals, with the exception for patients with specific safety concerns who
require more frequent visits.
Revised Sections:  Protocol Synopsis, Section 8.3.4 Safety Follow-Up and Schedule of
Events (Table 1) footnote (j),
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Safety and Efficacy of RPC1063 in UC—Summary of Changes 
23 August 2021, Version 9.0
(replaces 12 June 2020, Version 8.0)
CONFIDENTIAL
Page 5 of 114
5. Cardiac Monitoring requirement revision.
Revised Section:  Section 13.1.10 Guidelines for Cardiac Monitoring was updated
6.
.
Updated 
 to align with risk-based monitoring and current ozanimod 
prescribing information.
      Revised Sections:  Section 13.1.5 Ophthalmological Examination and Schedule of Events 
      Table 1-
7. Guidance on 
(following pandemic).
Provided additional guidance on 
infection, risk, 
and vaccinations in accordance with Sponsor-wide and ozanimod specific 
recommendations.
      Revised Section:  New Objective 7.1 and Section 13.2.7
 Pandemic were 
      added
8. Prohibited Medication Revisions (to ease restrictions and simplify):
a.
Removed prohibition of antimotility medications (minimal impact on disease activity)
b. Removed prohibition of chronic NSAID (Non-steroidal anti-inflammatory drugs) use, 
as these medications are rarely used in UC
c.
Removed CYP2C8 inhibitors as a prohibited medication during the study given that 
there is no meaningful impact on ozanimod metabolism; CYP2C8 inducers are 
prohibited through 
 SFU (Safety Follow-up) only (no longer through 90 Day 
SFU)
d. Consolidated medications of the same type/class
Revised Sections:  Section 10.5.2 Concomitant Medications Prohibited Through the 
 Safety Follow-up Visit, Section 10.5.3 Concomitant Medications Between the 
 Safety Follow-up Visit and the 90-day Safety Follow-up Visit, and Section 12.1
Complete Mayo Score, Partial Mayo Score, 9-Point Mayo Score, and Mayo Subscores
9. Packaging and Labelling
Details were updated as appropriate to reflect the information shown on the package and 
labelling for IP.
Revised Section: 11.2 Packaging and Labelling
10.
 
 
 
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Protocol No. RPC01-3102
Safety and Efficacy of RPC1063 in UC—Summary of Changes 
23 August 2021, Version 9.0
(replaces 12 June 2020, Version 8.0)
CONFIDENTIAL
Page 6 of 114
Revised Section:  Section 13.2.6 Adverse Events of Special Interest
11. Study Monitoring.
Updated new language for Study Monitoring, which also allows for a risk-based
approach and remote monitoring where possible.
Revised Section:  Section 16.1 Study Monitoring and Source Data Verification
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EDMS Doc. Number: 24787315 - 23199434
Sponsor: Celgene International II Sàrl
Protocol No. RPC01-3102
Efficacy and Safety of RPC1063 in UC—Summary of Changes 
12 June 2020, Version 8.0
(replaces 22 May 2019, Version 7.0)
CONFIDENTIAL
Page 3 of 110
This document summarizes the changes to Protocol RPC01-3102 from Version 7.0 (dated 
22 May 2019) to Version 8.0 (dated 12 June 2020).
1.
OVERVIEW OF KEY CHANGES
The following bulleted list identifies the key changes to the protocol and provides the rationale 
for each change:

 
 
 
 
 

Section 10.5.2 and 10.5.3: Concomitant medications has been updated to specify that 
calcium channel blockers, when combined with beta blockers, increase the risk of 
prolonged QT interval. This was previously implied by giving the example of 
verapamil.

 
 
 
 
 

 
 
 
 
 

 
 

References to Cohort 3 (
) have 
been removed throughout the protocol, as no adolescents were enrolled in parent 
study RPC01-3101. 

Drug dependence and withdrawal assessments have been removed from the protocol. 
These assessments were originally included to complement the abuse liability data 
being collected in the Ozanimod multiple sclerosis (MS) program.
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Protocol No. RPC01-3102
Efficacy and Safety of RPC1063 in UC—Summary of Changes 
12 June 2020, Version 8.0
(replaces 22 May 2019, Version 7.0)
CONFIDENTIAL
Page 4 of 110

An additional notation was added to Section 13.2.10 to indicate that the Data Safety 
Monitoring Board (DSMB) no longer needs to review the data from this open-label 
extension study. As RPC01-3101 (blinded parent study) is now complete, the internal 
study team will continue to monitor the data for the duration of the study.

Additional instructions for missed doses were added to Section 10.1.1, in accordance 
with the prescribing information for ozanimod.

Section 6.2.2 now includes updated information on the status of ozanimod clinical 
studies under the ulcerative colitis indication.

Section 10.5.2 Concomitant Medications Prohibited: Antineoplastic therapies and
immune-modulating therapies were added to be consistent with the Investigator’s 
Brochure, in order to avoid additive immunosuppressive effects.

Section 10.5.1 on allowed medications section was updated per a previous protocol 
clarification letter. This clarification now specifies to include any ongoing 
medications at the end of the parent study and new medication started after the 
completion of the parent study or medications that were initiated in the prior study.

The text in Section 14.6 was updated to indicate that interim analyses were performed 
to support regulatory submission activities for the MS and ulcerative colitis (UC)
indications.

 
 
.
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Sponsor: Celgene International II Sàrl
Protocol No. RPC01-3102
Efficacy and Safety of RPC1063 in UC—Summary of Changes 
22 May 2019, Version 7.0 (replaces Version 6.0)
CONFIDENTIAL
Page 3 of 104
This document summarizes the changes to Protocol RPC01-3102 from Version 6.0 (dated 18 
Dec 2018) to Version 7.0 (dated 22 May 2019).
1.
OVERVIEW OF KEY CHANGES
The following bulleted list identifies the key changes to the protocol and provides the rationale 
for each change:

The 75-day (±10 days) Safety Follow-up Visit was extended to a 90-day (±10 days) 
Safety Follow-up Visit. 
 
 

Extended the requirements for contraception in females after treatment 
discontinuation from the 75-day Safety Follow-up Visit to the 90-day Safety Follow-
up Visit.

Extended the requirements for reporting of adverse events (AEs) after treatment 
discontinuation from the 75-day Safety Follow-up Visit to the 90-day Safety Follow-
up Visit. 

The requirement for male contraception was removed. Using safety factor 
assumptions of tenfold higher concentration in the semen than plasma, a twofold 
higher dose of ozanimod, and semen levels at the maximum concentration (Cmax), 
exposure ratio estimates were negligible for female partners of male patients and do 
not represent a meaningful risk.

Added the following Safety Follow-up Visits for up to approximately 80 adult
patients: Last dose +1, 4 (±1 day), 7 (±2 days), 14 (±3 days), 21 (±3 days), and 90
(±10 days) days. Relevant assessments at these visits include AEs, vital signs, 
concomitant medications, and the following newly added assessments: Physician’s 
Withdrawal Checklist (PWC-20), Hospital Anxiety and Depression Scale (HADS), 
and Epworth Sleepiness Scale (ESS). These assessments will also be performed at the 
 and in all adult patients at the first 
scheduled visit on study treatment after approval of Protocol Amendment Version 7, 
in order to provide a baseline assessment while on study drug. 

As described in the “Assessment of Abuse Potential of Drugs” FDA guidance 
document, an evaluation of abuse potential is most relevant for New Molecular 
Entities with Central Nervous System activity that have not previously been assessed 
by the Food and Drug Administration (FDA) for abuse potential. Considering this 
general guidance, the dependence and withdrawal questionnaires are being included 
in this protocol to complement the abuse liability data being collected and generated 
in the Ozanimod Multiple Sclerosis program.

Updated the section for safety assessments to include newly added dependence and 
withdrawal assessments.
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EDMS Doc. Number: 23762531 - 23199434
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Protocol No. RPC01-3102
Efficacy and Safety of RPC1063 in UC—Summary of Changes 
22 May 2019, Version 7.0 (replaces Version 6.0)
CONFIDENTIAL
Page 4 of 104

Updated safety endpoints section(s) to include newly added assessments for 
withdrawal/dependence.

Updated statistics section(s) to include planned summaries for newly added 
assessments.

Updated the Table of Events for additional visits such that the reference point is Day 
 (versus the last visit). Also clarified that HbA1c assessments will be performed at 
Baseline, 
.

 
, as the Safety Follow-up Period follows this visit before the 
 
 will be declared.

Removed language regarding consultation with the Medical Monitor for medications 
prohibited between 
 and 90 days for the Safety Follow-up Period.

Removed tofacitinib as a prohibited medication between 
 and 90 days for the 
Safety Follow-up Period.

Clarified that patients who enter as adolescents should continue with assessments for 
adolescents for continuity purposes, and that they do not need to complete 
assessments specific only for adults.

Removed 
 from discontinuation criteria,
 

Removed reference to adult partner pregnancies, as partner pregnancies should be 
followed for all male patients.

Clarified language around scope and duration of the Data Safety Monitoring Board 
(DSMB).

Clarified that WBC counts and WBC differentials, as well as 
, will 
not be disclosed for Visit  only (to maintain the blind from the parent trial from 
which the patient is entering). In addition,
 and 
 values of interest were 
updated to include SI units.

Added references, abbreviations, and other minor edits as appropriate.
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EDMS Doc. Number: 23200101 - 23199434
RPC1063
Summary of Changes RPC01-3102
Celgene International II Sàrl
Confidential and Proprietary
3
RPC01-3102 Amendment 6.0 Final: 13 Dec 2018
1.
JUSTIFICATION FOR AMENDMENT
Significant changes included in this amendment are summarized below:

 this protocol is being 
amended to include adolescent patients in Study RPC01-3102. Eligible adolescent patients 
will enter the trial from parent study PRC01-3101.

Throughout the protocol, 
, and 
Definition 2 is now referred to as the Three-component Mayo to better describe the 
constituents of the definition.

For statistical analysis purposes, clinical remission and clinical response will be calculated 
using the Three-component Mayo definition for all regions. This is in accordance with the 
recent FDA and European Medicines Agency (EMA) guidelines, and removes the 
subjectivity of the Physician’s Global Assessment (PGA) from the calculation.
Newly added language or revised text appears in the following sections of the protocol:

Synopsis; Throughout the Synopsis

Section 7.1; Objectives

Section 7.2; Efficacy Endpoints 

Section 8.1.; Summary of Trial Design

Section 8.2.; Discussion of Trial Design

Section 8.3.2.; Trial Visits

Section 10.1.; Treatments Administered

Section 10.3.1.; Selection of Dose in the Trial for Adolescent Patients

Section 10.8.; Blinding

Section 12.1; Assessment of Efficacy; Mayo Score, Partial Mayo Score, and 9-Point 
Mayo Score, Pediatric Ulcerative Colitis Activity Index

Section 13.1.2.; Assessments of Safety; Height and Weight

Section 13.1.10.; Assessments of Safety; Guidelines for Monitoring Patients at 
Baseline Visit (Day )

Section 14.3; Planned Statistical Methods; Disposition, Demographics, and Baseline 
Characteristics

Other updates and additions related to the adolescent cohort include:

Section 4. List of Tables  

Section 6.1. Ulcerative Colitis 

Section 6.2. RPC1063
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EDMS Doc. Number: 23200101 - 23199434
RPC1063
Summary of Changes RPC01-3102
Celgene International II Sàrl
Confidential and Proprietary
4
RPC01-3102 Amendment 6.0 Final: 13 Dec 2018

Section 6.2.1. Nonclinical Studies

Updated footnote d in Table 2 (Section 8.1 Summary of Trial Design).

Added Table 4 (Section 12.1) to include Pediatric Ulcerative Colitis Activity Index 
(PUCAI) and included PUCAI in Schedule of Events (Section 8.1 Summary of Trial 
Design/Table 1 Schedule of Events).

Updated Table 1, Schedule of Events, to include specific adolescent patient 
assessments. (Section 8.1 Summary of Trial Design).

Guidelines on informed consent/assent, early discontinuation guidelines, and 
withdrawal were included for the adolescents in Cohort 3. (Section 9.1 Inclusion 
Criteria, Section 9.4 Trial Discontinuation, Section 10.2; Method of Assigning 
Patients to Treatment, and Section 17.3 Patient Information and Informed 
Consent/Assent)

Other important updates and their rationale include:

The volume of blood taken at each visit, added 
 (Section 8.1
Summary of Trial Design/Table 1 Schedule of Events, footnote n).

Updated language in Section 9.4. (Trial Discontinuation) to clarify when alternative 
treatments for UC can begin.

Section 10.5.2; Cholestyramine was removed as a prohibited medication because bile 
acid malabsorption is not known to have an effect on ulcerative colitis disease status.

Updated language in Section 12.3 (Patient Reported Outcomes) to clarify when the 
questionnaires are to be completed, and updated Table 1, Schedule of Events, Mayo 
patient diary line to be consistent with Section 12.3.

Updated language in Section 13.1.1. (Physical Examination) to clarify the difference 
between the complete physical examination and interim physical examination, and at 
which visits each is conducted. Footnote f in Table 1, and Schedule of Events were
also updated to be consistent with Section 13.1.1.

A separate line was added in Table 1, Schedule of Events, for interim physical 
examination to clarify the visits when the interim physical examinations would be 
conducted, consistent with Section 13.1.1. 

 

 
 
 

Added footnote e in Table 2 and updated Section 10.1 (Treatments Administered) to 
specify which subjects would undergo first dose escalation and cardiac monitoring. 
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EDMS Doc. Number: 23200101 - 23199434
RPC1063
Summary of Changes RPC01-3102
Celgene International II Sàrl
Confidential and Proprietary
5
RPC01-3102 Amendment 6.0 Final: 13 Dec 2018

Additional height and weight assessments for adolescent patients added 
 
(Section 8.1 Summary of Trial Design/Table 1 Schedule of Events and Section 
13.1.2 Height and Weight).

Added hematology blood draw and optional safety assessments at the 75-day Safety 
Follow-up Visit to monitor safety (Section 8.1 Summary of Trial Design/Table 1
Schedule of Events and Section 8.3.4 Safety Follow-Up).

 
 

Updated Section 6.2 with additional information regarding metabolites of ozanimod.

 

HbA1c was added at the Baseline Visit and annually thereafter (Section 8.1/Table 1 
Schedule of Events, Section 13.1.11 Clinical Laboratory Evaluations) in order for 
subjects to receive appropriate diabetes management and treatment during this trial.

Etrasimod and tofacitinib were added to the list of excluded and prohibited UC 
medications during the study (Section 2 Synopsis, Section 9.2 Exclusion Criteria, 
Section 10.5.2 Concomitant Medications Prohibited Through the 
 Safety 
Follow-up Visit, and Section 10.5.3 Concomitant Medications Between the 
 
Safety Follow-up Visit and the 75-Day Safety Follow-up Visit).

Section 13.1.5 (Ophthalmological Examination) was updated with details regarding 
source documentation and review of 
.

 

Minor updates include the following:

Updated Section 6.2.1 to include nonclinical study information, which was previously 
referenced to the IB.

 

Updated language in Section 13.2.9. (Procedures in Case of Pregnancy) to specify 
that only adult patients are required to follow pregnancy partner procedures.

Added “/assent” to the word “consent” throughout the protocol.

Updated signature page.

Updated List of Abbreviations and Definitions of Terms.
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EDMS Doc. Number: 23200101 - 23199434
RPC1063
Summary of Changes RPC01-3102
Celgene International II Sàrl
Confidential and Proprietary
6
RPC01-3102 Amendment 6.0 Final: 13 Dec 2018

Corrected date for last patient completed in Synopsis.

Added definition for females of childbearing potential (FCBP) including
contraception educational language (Section 9.1 Patient Inclusion Criteria).
Contraception education was also added to Table 1, Schedule of Events.


Added notation to Section 10.8 Blinding and Section 13.1.11 Clinical Laboratory
Evaluations such that certain laboratory results will not be disclosed to maintain the
blind from the parent trial from which a patient may be entering.

Removed requirement for collection of nontrial diagnostic, therapeutic, or surgical
procedures relating to UC (Section 10.5.1 Allowed Medications).

Separated Table of Contents and List of Tables into 2 separate sections (Section 3 and
Section 4, respectively).

Specified throughout that patients will receive treatment as part of this trial until the
end of 2021, or until marketing approval of RPC1063 for UC is obtained in their
country, or until the Sponsor discontinues the development program, whichever
comes first.

Updated acronym for ICH to International Council on Harmonisation (Section 5,
Section 17.5)

References (Section 20. REFERENCES) were updated.
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Sponsor: Celgene International II Sàrl 
Protocol No. RPC01-3102 
Efficacy and Safety of RPC1063 in UC —Summary of Changes 
29 May 2018, Version 5.0 (replaces Version 4.0) 
CONFIDENTIAL 
Page 3 of 22 
This document summarizes the changes that were made between Protocol RPC01-3102 Version 
5.0 (dated 07 Jun 2017) and Version 5.0 (dated 29 May 2018). 
1.
OVERVIEW OF KEY CHANGES
The following bulleted list identifies the key changes to the protocol and provides the rationale 
for each change: 

Updated description of RPC1063 to include metabolite CC112273.

A 75-day (±10 days) Safety Follow-up Visit was added to ensure adequate collection
of adverse events that could be associated with investigational drug. 



.

Added details regarding previous RPC1063 trial participation requirement to
inclusion criterion #1.

Added dosing instructions and timing of visits for patients entering the study from the
open-label period of Study RPC01-202.

Added breast cancer resistance protein (BCRP) inhibitors to the list of medications
that are prohibited during the trial until the 
 Safety Follow-up Visit. In a
Phase 1 drug-drug interaction study, a strong inhibitor of BCRP, cyclosporine, had no
effect on ozanimod exposure, while it approximately doubled the exposure of its
active metabolites, RP101988 and RP101075. While the major active metabolite
CC112273 is not a substrate of drug transporters, it is unknown if the increase in
RP101075 (via RP101988) may also lead to a similar increase in CC112273, which is
formed directly from RP101075.

Added monoamine oxidase inhibitors to the list of excluded medications and the list
of medications that are prohibited during the trial and safety follow-up period because
in vitro data show that the major active metabolite CC112273 is formed by and
inhibits MAO-B.  The potential for clinical interaction with MAO inhibitors has not
been studied.

Added CYP2C8 inducers or inhibitors to the list of excluded medications and the list
of medications that are prohibited during the trial and safety follow-up period because
in vitro data show that the major active metabolite CC112273 is further metabolized
by CYP2C8 (and by carbonyl reductase). The potential for clinical interactions with
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Sponsor: Celgene International II Sàrl 
Protocol No. RPC01-3102 
Efficacy and Safety of RPC1063 in UC —Summary of Changes 
29 May 2018, Version 5.0 (replaces Version 4.0) 
CONFIDENTIAL 
Page 4 of 22 
CYP2C8 inhibitors or inducers has not been studied and therefore co-administration 
is not recommended. 

Changed “titration” to “dose escalation” throughout the protocol for consistency with
other ongoing RPC1063 protocols.

Added nomenclature and dose equivalency between RPC1063/ozanimod HCl
(
 mg, 
 mg, and 1 mg) and ozanimod (
 mg, 
 mg, and 
 mg) for
consistency across RPC1063 protocols.

Removed hemoglobin A1c from the chemistry panel because it is not needed for
routine evaluation of patient safety.

Updated protocol to add new protocol template language regarding handling of
product quality complaints for any drug product manufactured by or on behalf of
Celgene.

Updated Sponsor’s address.

Made minor editorial changes and changes for clarification.
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Celgene International II Sàrl  
Summary of Changes: Protocol Number: RPC01-3102 
7 June 2017 
Drug Name: RPC1063 
Version 4.0 
Page 3 of 15 
This document summarizes the changes that were made between Protocol RPC01-3102 Version 
3.0 (dated 7 June 2016) and Version 4.0 (dated 7 June 2017). 
1.
OVERVIEW OF KEY CHANGES
The following bulleted list identifies the key changes to the protocol and provides the rationale 
for each change: 

Contraception methods and the frequency of pregnancy testing were aligned with the
“Recommendations related to contraception and pregnancy testing in clinical trials”
(15 Sep 2014) by the Clinical Trial Facilitation Group. Additionally, the requirement for
male contraception was maintained from Inclusion Criterion #2 from the previous version of
the protocol.

The prohibition on concomitant use of CYP3A4 inhibitors and inducers was removed based
on the results of the clinical pharmacology study RPC01-1902.

The prohibition on concomitant 
 was
removed based on the results of the clinical pharmacology study RPC01-1908.

Timing windows were extended for select visits. These changes were made to provide
operational flexibility to the study sites.

A number of changes were made to clarify previously existing instructions and improve
readability.
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Celgene International II Sàrl 
 
Summary of Changes: Protocol Number: RPC01-3102 
 
7 June 2016 
Drug Name: RPC1063 
 
Version 3.0 
Page 2 of 22 
 
This document summarizes the changes that were made between Protocol RPC01-3102 
Version 2.0 (dated 08 May 2015) and Version 3.0 (dated 7 June 2016). 
Receptos, Inc. was acquired by Celgene Corporation, and, effective 29 Jan 2016, Celgene 
International II Sàrl (“CIS II”), a subsidiary of Celgene Corporation, has assumed responsibility 
as the sponsor of record for all RPC1063 clinical studies for which Receptos, Inc. was previously 
named sponsor. Receptos Services LLC (“Receptos”), a wholly owned subsidiary of Celgene 
Corporation, is and will serve as an authorized representative for CIS II, supporting RPC1063 
clinical studies. 
Overview of Changes: 
 Corrections were made to remove reference to a “maintenance trial” and in some 
instances replaced with “extension trial” 
 The Introduction was updated to include the relevant trial, RPC01-1901 (to support 
removal of the fasting restriction prior to dosing with RPC1063), to include a third 
metabolite of RPC1063 due to the addition of RPC01-1901 results, to update the status of 
completed trials, and to reference the Investigator’s Brochure as the most up-to date 
source of information about studies within the RPC1063 clinical development program. 
 The definition of mucosal healing and histologic remission was updated. 
 For the purposes of clarity, complete Mayo score, partial Mayo score, and 9-point Mayo 
score were listed in the description of other efficacy endpoints.  
 Physical examinations and 
 were removed from the list of 
safety endpoints as they will not be summarized as change from Baseline. 
 The section “Pharmacodynamic Endpoints” was added to include the description of 
 
and 
. Text regarding markers of inflammation have been 
revised throughout the protocol to include examples. 
 The required window to complete vital signs was removed. 
 Instruction to take RPC1063 in a fasted state was removed based on results of the food 
effect study (Study RPC01-1901).  
 The requirement that patients should enter the trial 
 
.  
 Instruction for patients not to take study medication from the prior trial until Visit  
during which they will receive RPC01-3102 study medication was added. 
 The timepoint after which patients will begin to have additional visit assessments at 
. 
 A full examination of the skin for lesions was added as a procedure required for the 
interim physical examination. 
 The window to complete endoscopies was changed from 
 to 
within 
 of the visit date to allow adequate time for completion of procedures. The 
Day  endoscopy does not need to be repeated if an endoscopy has been completed 
within 
. 
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Celgene International II Sàrl 
 
Summary of Changes: Protocol Number: RPC01-3102 
 
7 June 2016 
Drug Name: RPC1063 
 
Version 3.0 
Page 3 of 22 
 
 
 
 
 
 Table 2 - footnote d describing pulse monitoring guidelines was updated.   
 Inclusion criterion #4 removed “Are capable of providing” to emphasize that the subject 
must provide informed consent. 
 Added a time window for which treatment with a live vaccine should be exclusionary for 
exclusion criteria #1. 
 For clarification purposes and to maintain consistency with protocol RPC01-3101, 
additional detail (P450 3A4) was added to the CYP3A4 description. 
 “Calcium channel blockers” was replaced with examples of calcium channel blockers in 
exclusion criteria #2. QT interval prolonging drugs with a known risk of torsades de 
pointes were removed from the exclusion. 
 
 
 
 
 
. 
 For clarification purposes, the statement patients will be encouraged to complete the trial 
was revised to only note that the patient may voluntarily withdraw from the trial at any 
time. 
 The definition of “withdrawal by patient” was clarified to note that patients who 
discontinue study medication will be withdrawn from the study. 
 Additional clarity was added to describe dosing (added 
 to be taken). 
 Correction was made to ensure that prior medication history is captured starting at the 
date of informed consent. The phrase “date of informed consent” was removed from the 
description of concomitant medications. 
 QT prolonging drugs were removed from the list of excluded medications 
 
 
 Methotrexate was added as an example of an immunosuppressive agents. 
 Tofacitinib was added as an excluded medication. 
 Proprietary names for components (eg, chemical excipients or capsules) and packaging of 
investigational and commercial drug products have been removed in favor of using 
generic terms. This has been done to simplify the text and limit the use of trademarked or 
registered names. 
 Instructions to the Investigator regarding investigational drug accountability along with 
record transfer and on site destruction were deleted. 
 For clarification purposes, 
 was changed 
 for documentation of 
history of prior medications. 
 Details regarding colonic biopsies have been revised. 
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Celgene International II Sàrl 
 
Summary of Changes: Protocol Number: RPC01-3102 
 
7 June 2016 
Drug Name: RPC1063 
 
Version 3.0 
Page 4 of 22 
 
 For the purpose of clarity, the time period in which stool frequency and rectal bleeding 
diary entries will be used to calculate Mayo Score was further defined. Additional details 
regarding calculation of Mayo Score was deleted since this will be outlined in the 
Statistical Analysis Plan. 
 The details of the condition in which ECGs will be performed were revised. 
 
 
 
 Criteria #2 for additional extended monitoring of first dose heart rate was revised. 
 An additional directive for the requirement of Medical Monitor approval if retest is 
required to be repeated > 2 times was added. Additional text was added to clarify that 
repeat laboratory safety testing would be analyzed by the local laboratory. 
 Criteria for repeating hematology laboratory results were added. 
 A correction was made to section titled “Handling Missing Data” to delete instructions if 
no post-baseline values are available since all patients in this study will have post-
baseline values available from the parent study (RPC01-3101).   
 Details on the version of Declaration of Helsinki were removed since the version varies 
based on region. 
Global Changes: 
 The Sponsor name and address were changed. 
 Confidentiality language was modified. 
 The Medical Monitor’s company was updated. 
 A Celgene International II Sàrl signatory was added. 
 The list of abbreviations was updated, as appropriate. 
 References to “Receptos, Inc.” and “Receptos” were modified. 
 Minor typographical corrections 
 
 
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Sponsor: Receptos, Inc. 
 
 
Protocol No. RPC01-3102 
Open-Label Extension of RPC1063 in UC—Summary of Changes 
08 May 2015, Version 2.0 
 
This document summarizes the changes that were made between Protocol RPC01-3102 
Version 1.0 (dated 20 April 2015) and Version 2.0 (dated 08 May 2015). 
Overview of Changes: 
• Vitals signs assessment was added to Safety Follow-up visit 
• Erroneous text relating to questionnaires was removed. 
• Minor corrections 
 
 
Page 2 of 3 
 
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