A Phase 3b, Multicenter, Open-label Study to Evaluate the Immune Response to, and the Safety of, Vaccines in Participants With Relapsing Forms of Multiple Sclerosis Who Receive Oral Ozanimod Compared to Non-pegylated Interferon (IFN)-β or No Disease Modifying Therapy
Phase: PHASE3
Conditions: Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting
Sponsor: Celgene

Official Title of Study: 
A Phase 3b, Multicenter, Open-label Study to Evaluate the Immune Response to, and the Safety of, 
Vaccines in Participants With Relapsing Forms of Multiple Sclerosis Who Receive Oral Ozanimod 
Compared to Non-pegylated Interferon (IFN)-β or No Disease Modifying Therapy 
 
NCT Number: NCT05028634 
Document Date (Date in which document was last revised): 29 November 2022 
 
 

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
1
A PHASE 3B, MULTICENTER, OPEN-LABEL STUDY TO EVALUATE THE IMMUNE
RESPONSE TO, AND THE SAFETY OF, VACCINES IN PARTICIPANTS WITH 
RELAPSING FORMS OF MULTIPLE SCLEROSIS WHO RECEIVE ORAL 
OZANIMOD COMPARED TO NON-PEGYLATED INTERFERON-Β OR NO DISEASE 
MODIFYING THERAPY
PROTOCOL NUMBER:
RPC-1063-MS-010 
DATE FINAL:
28 APR 2021
AMENDMENT No 1.0 DATE
29 NOV 2022
EudraCT NUMBER:
2021-001847-28
IND NUMBER:
109,159
SPONSOR NAME/ ADDRESS:
Celgene International II Sàrl
Route de Perreux 1, 
2017 Boudry, Switzerland
Tel: 
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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Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
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MEDICAL MONITOR / EMERGENCY CONTACT INFORMATION 
Contact Information:
Name:
Title:
 Clinical Trial Physician
Address: 
Phone:
E-mail:
Note: The back-up 24-hour global emergency contact call center should only be used if you 
are not able to reach the Clinical Research Physician(s) or Medical Monitor or designee for 
emergency calls.
Back-up 24-hour Global Emergency Contact Call Center: 
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RPC-1063-MS-010 Amendment 1.0
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CELGENE THERAPEUTIC AREA HEAD SIGNATURE PAGE
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Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
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SPONSOR: CELGENE INTERNATIONAL II SÀRL
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Protocol RPC-1063-MS-010
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RPC-1063-MS-010 Amendment 1.0
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SITE PRINCIPAL INVESTIGATOR SIGNATURE PAGE
Signature of Site Principal Investigator
dd mmm yyyy
Printed Name of Site Principal Investigator
Institution Name:_______________________________________
By my signature, I agree to personally supervise the conduct of this study at my study site and 
to ensure its conduct is in compliance with the protocol, informed consent, Institutional Review 
Board (IRB)/Ethics Committee (EC) procedures, instructions from Celgene representatives, the 
Declaration of Helsinki, International Council for Harmonisation (ICH) Good Clinical Practices 
Guidelines, and local regulations governing the conduct of clinical studies.
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Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
6
OVERALL RATIONALE FOR THE PROTOCOL AMENDMENT 1.0
The main rationale for this amendment is to revise the age of participants to be enrolled in the 
study. The table below highlights the key changes made to the protocol.
SUMMARY OF CHANGES OF PROTOCOL AMENDMENT 1.0
Section Number 
& Title
Description of Change
Brief Rationale
Protocol 
Summary
Section 4.2:
Inclusion Criteria 
for All Subjects
Changed the age range of 
participants to be enrolled 
from “18 to 55, inclusive” to 
“18 to 65, inclusive”.
To include a wider range of participants 
based on feedback received from sites and 
enrollment challenges. There is no 
sufficient immune response data to exclude 
subjects 55-65 years old.
Section 6.7:
Additional and 
Optional 
Research
Added section with template 
language.
Template language was added, which had 
previously been inadvertently removed 
during the approval process.
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PROTOCOL SUMMARY
Study Title
A Phase 3b, multicenter, open-label study to evaluate the immune response to, and the safety of,
vaccines in participants with relapsing forms of multiple sclerosis who receive oral ozanimod 
compared to non-pegylated interferon (IFN)-β or no disease modifying therapy.
Indication
Relapsing forms of multiple sclerosis
Background
Multiple sclerosis (MS) is a chronic autoimmune and neurodegenerative disease of the central 
nervous
system (CNS) characterized by inflammation, demyelination, neuronal and 
oligodendrocyte loss, and disruption of the blood-brain barrier, leading to irreversible deficits in 
physical function and cognition and an impaired quality of life (Lassmann, 2019). The prevalence 
of MS is increasing and is currently estimated to affect 2.3 million individuals worldwide (Multiple 
Sclerosis International Foundation, 2013).
Ozanimod is a sphingosine 1-phosphate (S1P) receptor modulator, which binds with high affinity 
selectively to sphingosine 1-phosphate receptor subtypes 1 and 5 (S1P1 and S1P5). Ozanimod 
causes lymphocyte retention in lymphoid tissues. The mechanism by which ozanimod exerts 
therapeutic effects in MS is unknown but may involve reduction of lymphocyte migration into the 
CNS (Scott, 2016; Chaudry, 2017). Ozanimod is approved for the treatment of relapsing forms of 
multiple sclerosis (RMS) in adults in the United States (US) and for the treatment of adult subjects 
with relapsing-remitting MS (RRMS) with active disease as defined by clinical or imaging features 
in European Medicines Agency (EMA) jurisdictions.
Based on its mechanism of action ozanimod has the potential to reduce the immune response to
vaccinations; however, the effect of ozanimod on vaccination response has not been measured. 
Because many subjects with MS receive disease modifying therapies (DMT) chronically and 
receive vaccinations while being treated with DMTs, the effect of ozanimod on the vaccination 
response of MS subjects is of interest to patients and prescribers. This study will evaluate the 
immune response to vaccines in subjects with RMS taking ozanimod compared to RMS subjects 
not taking ozanimod. 
The vaccines chosen to investigate in this study allow for the assessment of the humoral immune 
response and are of clinical relevance to MS populations. 
Objectives
Primary Objective
To evaluate the proportion of subjects meeting serologic response criteria against the tetanus 
toxoid antigen after vaccination with the Tetanus Toxoid, Reduced Diphtheria Toxoid and 
Acellular Pertussis, Adsorbed (Tdap) vaccine in subjects with RMS receiving ozanimod or
receiving non-pegylated interferon-β (IFN-β) or no DMT.
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Secondary Objectives
To evaluate the following in subjects with RMS undergoing vaccination and receiving ozanimod 
or receiving non-pegylated IFN-or no DMT:

Proportion of subjects meeting tetanus seroprotective criteria

Proportion of subjects meeting pneumococcus serologic response and seroprotective criteria

Safety and tolerability
Exploratory Objectives
To evaluate the following in subjects with RMS undergoing vaccination and receiving ozanimod 
or receiving non-pegylated IFN-or no DMT:

Immune response to the seasonal inactivated influenza vaccine

Proportion of subjects meeting diphtheria serologic response, seroprotective criteria, and the
Geometric Mean Concentration (GMC) ratio of anti-diphtheria immunoglobulin G (IgG) and
immunoglobulin M (IgM)

Proportion of subjects meeting pertussis serologic response, seroprotective criteria, and the
GMC ratio of anti-pertussis IgG and IgM

GMC ratios of IgG and IgM against tetanus antigens

GMC ratios of IgG and IgM against antigens contained in the pneumococcal polysaccharide
vaccine (PPSV23)

Pharmacokinetic (PK) and pharmacodynamic (PD) parameters of ozanimod and its active
metabolites (ie, CC112273) in subjects who receive ozanimod as their standard of care
Study Design
The proposed study is a Phase 3b, multicenter, open-label study to evaluate the immune response 
to and the safety of vaccines administered in subjects with RMS who receive either oral ozanimod 
0.92 mg or IFN-β or no DMT.
All enrolled subjects will be vaccinated on Day 1 and followed until Day 28 (±3 days) to evaluate 
immune response via serological endpoints. 
The study will include two cohorts differentiated by the vaccines administered. Cohort 1 comprises
subjects who receive Tdap, PPSV23, and the seasonal inactivated influenza vaccine. Cohort 2 
comprises subjects who have already received the seasonal inactivated influenza vaccine and will
therefore receive Tdap and PPSV23 only. Initiation of Cohort 2 will be based on the availability 
of eligible subjects who have not previously been vaccinated with the seasonal inactivated 
influenza vaccine. Cohort 2 may be opened for enrollment at any time determined by the Sponsor
but is estimated to occur after no less than 60% of subjects of the planned total enrollment have 
been recruited into Cohort 1. Subjects who meet all eligibility criteria will continue to be enrolled 
in Cohort 1 throughout the time both cohorts are open for enrollment at the discretion of the 
Sponsor.
The study will be conducted in compliance with International Conference on Harmonisation (ICH) 
Good Clinical Practices (GCPs).
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RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
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Study Population
Approximately 60 ambulatory subjects between the ages of 18 to 65, inclusive, with RMS will be 
enrolled. Approximately 30 of these subjects will have been continuously treated with ozanimod
at least 
 days prior to the Day 1 (Baseline) Visit, and approximately 30 subjects will either be
treated with a non-pegylated IFN-β or will not be receiving any DMT.
Length of Study
This study will include a screening period of up to 14 days. The study period is from Day 1 
vaccination to the 28-day assessment visit. The maximum potential length from screening to end 
of trial is 45 days. Screening and Day 1 may occur on the same day in eligible subjects. 
The End of Trial is defined as either the date of the last visit of the last subject to complete the 
post-treatment follow-up, or the date of receipt of the last data point from the last subject that is 
required for primary, secondary and/or exploratory analysis, as prespecified in the protocol, 
whichever is the later date.
Study Treatments
Tdap, Influenza Vaccine, and Pneumococcal Vaccine, Polyvalent
For all vaccines the pre-filled syringe (0.5 ml) dosage form must be used. 
Ozanimod and Non-pegylated IFN-β
Ozanimod and non-pegylated IFN-β will be considered standard of care DMT medications
prescribed by the Investigator in this study. Standard of care DMTs are not provided as part of this 
study, and the Sponsor will not reimburse sites or subjects for the cost of the standard of care 
medication. During the study, subjects should continue their medication according to their regular 
schedule and as prescribed in the label of their respective countries.  
Overview of Key Efficacy Assessments
This study will evaluate immune response, measured by comparing post-vaccination to pre-
vaccination titers or concentrations of IgG and IgM antibodies against the Tdap, PPSV23, and 
seasonal influenza vaccines in serum samples. 
Primary Endpoint:

Proportion of subjects with serologic response to tetanus toxoid
Secondary Endpoints:

Tetanus:

Proportion of subjects with serological protection against tetanus toxoid

Pneumococcus

Proportion of subjects with serologic response to at least 5 of the following pneumococcal
serotypes: 3, 6B, 9N, 11A, 14, 19A, 19F, 22F and 23F

Proportion of subjects with serological protection against the following pneumococcal
serotypes: 3, 6B, 9N, 11A, 14, 19A, 19F, 22F and 23F
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Exploratory Endpoints:

Influenza

Proportion of subjects with serologic response to the seasonal influenza vaccine

Proportion of subjects with serological protection against seasonal influenza

Geometric Mean Titer (GMT) ratio of anti-influenza antibodies

Assessment if at least one of the specified criteria is met for each treatment arm for each
influenza strain

GMC ratio of anti-tetanus toxoid IgG and IgM

GMC ratio of anti-pneumococcus IgG and IgM for each pneumococcal serotype in PPSV23

Diphtheria

Proportion of subjects with serologic response to reduced diphtheria toxoid

Proportion of subjects with serological protection against reduced diphtheria toxoid

GMC ratio of anti-diphtheria toxoid IgG and IgM

Pertussis

Proportion of subjects with serologic response to pertussis

Proportion of subjects with serological protection against pertussis

GMC ratio of anti-pertussis IgG and IgM

PK/PD sampling to determine plasma concentration of ozanimod and active metabolites
Overview of Key Safety Assessments
Safety assessments in the study include adverse events (AE), vital signs, physical examination, 
clinical laboratory evaluations, and relapses. The incidence, severity, relationship, and type of 
treatment-emergent AEs, serious adverse events (SAEs), AEs leading to study discontinuation, 
and relapses will be summarized, as well as clinically meaningful changes from baseline for 
clinical laboratory measures, vital signs, and physical examinations. 
Statistical Methods
This is a non-randomized, open-label study in which all subjects remain on their pre-study 
(baseline) treatment per protocol. Subjects will be recruited by investigators from MS clinical 
practice patients and prospectively assessed for immune response to vaccination. The statistical 
analyses will focus on estimating immune response rates, adjusting for baseline subject-level 
characteristics. No formal statistical hypothesis is evaluated. To mitigate for potential differences 
in the recruited subject population in the ozanimod and non-ozanimod arms that potentially could 
affect immune response, response rates will be estimated based on a logistic regression model 
adjusting for several factors, eg, age, sex, body mass index (BMI), and baseline absolute
lymphocyte count (ALC). The results of the statistical analyses for immune response endpoints 
will be summarized for subjects receiving ozanimod (ozanimod arm) and subjects not receiving 
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RPC-1063-MS-010 Amendment 1.0
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ozanimod (non-ozanimod arm) as their standard of care DMT for MS. Analyses of safety will be
summarized by descriptive statistics separately for the ozanimod and non-ozanimod arms.
The primary endpoint is the proportion of subjects with serologic response to vaccination with 
tetanus toxoid. The primary endpoint analysis and all analyses for immune response to vaccination 
will be performed in the per-protocol population, ie, in subjects who received the correctly 
assigned vaccinations, had no systemic use of corticosteroids, and did not receive any other 
vaccines throughout the study. Sensitivity analyses will be conducted within the modified intent-
to-treat population consisting of all subjects who received at least one vaccination and summarized 
according to their initial arm status (ozanimod vs. non-ozanimod) regardless of steroid use. 
The sample size of the study is 60 subjects with an estimated 30 subjects expected to have received 
ozanimod and 30 subjects expected to not have received ozanimod as standard of care DMT. It is 
expected that approximately 60% of the subjects in the IFN-β or no DMT control group will have 
a serologic response to vaccination with Tdap (Kappos, 2015).
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TABLE OF CONTENTS
TITLE PAGE..............................................................................................................................1
OVERALL RATIONALE FOR THE PROTOCOL AMENDMENT 1.0.....................................6
SUMMARY OF CHANGES OF PROTOCOL AMENDMENT 1.0............................................6
PROTOCOL SUMMARY ..........................................................................................................7
TABLE OF CONTENTS..........................................................................................................12
LIST OF TABLES....................................................................................................................15
LIST OF FIGURES ..................................................................................................................16
1
INTRODUCTION..................................................................................................17
1.1
MS Disease Background.........................................................................................17
1.2
Compound Background ..........................................................................................17
1.3
Rationale ................................................................................................................20
1.3.1
Purpose of Study.....................................................................................................20
1.3.2
Rationale to Study Vaccine Response in Ozanimod Subjects ...................................20
1.3.3
Effects of DMTs on Vaccine Response ....................................................................20
1.3.4
Rationale for Selected Study Design .......................................................................21
1.3.5
Rationale for Selected Vaccines..............................................................................22
1.3.6
Rationale for Selected Endpoints ............................................................................23
2
STUDY OBJECTIVES AND ENDPOINTS...........................................................26
3
OVERALL STUDY DESIGN ................................................................................36
3.1
Study Design ..........................................................................................................36
3.2
Study Duration for Subjects....................................................................................39
3.3
End of Trial ............................................................................................................39
4
STUDY POPULATION.........................................................................................40
4.1
Number of Subjects ................................................................................................40
4.2
Inclusion Criteria for All Subjects...........................................................................40
4.3
Exclusion Criteria for Cohort 1...............................................................................41
4.4
Exclusion Criteria for Cohort 2...............................................................................43
5
TABLE OF EVENTS.............................................................................................44
6
PROCEDURES......................................................................................................46
6.1
Screening Period.....................................................................................................46
6.2
Treatment Period - Day 1/Baseline .........................................................................47
6.2.1
Post Vaccination/End of Study................................................................................47
6.2.2
Relapse Assessments...............................................................................................48
6.3
Follow-up Period....................................................................................................49
6.4
Efficacy Assessment...............................................................................................49
6.5
Pharmacokinetics....................................................................................................49
6.6
Biomarkers, Pharmacodynamics, Pharmacogenomics.............................................50
6.7
Additional and Optional Research...........................................................................50
6.7.1
Additional Research ...............................................................................................50
6.7.2
Optional Research..................................................................................................50
7
DESCRIPTION OF STUDY TREATMENTS........................................................50
7.1
Description of Investigational Products...................................................................50
7.2
Treatment Administration and Schedule .................................................................51
7.3
Method of Treatment Assignment...........................................................................53
7.4
Packaging and Labeling..........................................................................................53
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7.5
Investigational Product Accountability and Disposal ..............................................53
7.6
Investigational Product Compliance........................................................................54
8
CONCOMITANT MEDICATIONS AND PROCEDURES....................................54
8.1
Prohibited Concomitant Medications and Procedures..............................................54
8.2
Required Concomitant Medications and Procedures................................................55
9
STATISTICAL CONSIDERATIONS ....................................................................56
9.1
Overview................................................................................................................56
9.2
Study Population Definitions ..................................................................................56
9.3
Sample Size and Power Considerations...................................................................56
9.4
Background and Demographic Characteristics........................................................57
9.5
Subject Disposition.................................................................................................57
9.6
Immune Response Analysis....................................................................................57
9.7
Safety Analysis.......................................................................................................58
9.8
Interim Analysis .....................................................................................................58
10
ADVERSE EVENTS..............................................................................................59
10.1
Monitoring, Recording and Reporting of Adverse Events .......................................59
10.2
Evaluation of Adverse Events.................................................................................59
10.2.1
Seriousness.............................................................................................................59
10.2.2
Severity/Intensity ....................................................................................................60
10.2.3
Causality ................................................................................................................61
10.2.4
Duration.................................................................................................................61
10.2.5
Action Taken...........................................................................................................61
10.2.6
Outcome .................................................................................................................61
10.3
Abnormal Laboratory Values..................................................................................62
10.4
Pregnancy...............................................................................................................63
10.4.1
Females of Childbearing Potential .........................................................................63
10.4.2
Male Subjects .........................................................................................................63
10.5
Reporting of Serious Adverse Events......................................................................63
10.6
Expedited Reporting of Adverse Events..................................................................64
11
DISCONTINUATIONS .........................................................................................66
11.1
Study Discontinuation ............................................................................................66
11.2
Emergency Contact.................................................................................................66
11.3
Emergency Identification of Investigational Products .............................................66
12
REGULATORY CONSIDERATIONS...................................................................67
12.1
Good Clinical Practice............................................................................................67
12.2
Investigator Responsibilities ...................................................................................67
12.3
Subject Information and Informed Consent.............................................................68
12.4
Confidentiality........................................................................................................68
12.5
Protocol Amendments.............................................................................................68
12.6
Institutional Review Board/Independent Ethics Committee Review and 
Approval ................................................................................................................68
12.7
Ongoing Information for Institutional Review Board/ Ethics Committee ................69
12.8
Termination of the Study ........................................................................................69
13
DATA HANDLING AND RECORDKEEPING.....................................................70
13.1
Data/Documents .....................................................................................................70
13.2
Data Management...................................................................................................70
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13.3
Record Retention....................................................................................................70
14
QUALITY CONTROL AND QUALITY ASSURANCE........................................71
14.1
Study Monitoring and Source Data Verification......................................................71
14.2
Audits and Inspections............................................................................................71
14.3
Product Quality Complaint .....................................................................................72
15
PUBLICATIONS ...................................................................................................73
16
REFERENCES.......................................................................................................74
APPENDIX A
TABLE OF ABBREVIATIONS.............................................................83
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LIST OF TABLES
Table 1:
Study Objectives ....................................................................................26
Table 2:
Study Endpoints .....................................................................................27
Table 3:
Table of Events ......................................................................................44
Table 4:
Route and Anatomical Site of Vaccine Administration ...........................52
Table 5:
Recommended Needle Lengths for Intramuscular Vaccination in 
the Deltoid Muscle (Adults)....................................................................52
Table 6:
Examples of Prohibited Cardiac Medications (Systemic Use) .................55
Table 7:
Abbreviations and Specialist Terms........................................................83
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LIST OF FIGURES
Figure 1:
Overall Study Design..............................................................................37
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1
INTRODUCTION 
1.1
MS Disease Background 
Multiple Sclerosis
Multiple sclerosis (MS) is an idiopathic, chronic inflammatory demyelinating disease of the 
Central Nervous System (CNS). The disease is characterized pathologically by inflammatory 
lesions of CNS myelin with resultant edema, demyelination, and oligodendrocyte and neuronal 
loss. Acute inflammatory lesions are initiated by activated peripheral lymphocytes that enter the 
CNS through a breached blood-brain barrier (Lucchenetti, 2000; Popescu, 2012; Lassmann 2007,
Lassman, 2019; Frisher, 2015)
The prevalence of MS is increasing and is currently estimated to affect 2.3 million individuals 
worldwide (Multiple Sclerosis International Foundation, 2013). In Europe (EU), the highest 
prevalence of MS occurs in countries with high latitude, including Sweden (188.9 per 100,000), 
Norway (203 per 100,000), and Denmark (232 per 100,000) (Ahlgren, 2011; Grytten, 2015; Koch-
Henriksen, 2015). Estimates that 300,000 to 400,000 individuals have MS in the United States
(US) are based largely on revisions of estimates from older data (Baum, 1981; Anderson, 1992; 
Evans, 2013).  In an algorithm applied to private, military, and public Administrative Health 
Claims datasets, the estimated 2010 prevalence of MS in the US was 727,344 cases and may have 
been as high as 913,925 in 2017 (Wallin, 2019). The median age at onset is approximately 30 years 
of age and there is a consistent, 3:1 female to male ratio (McKay, 2015; Ribbons, 2015).
Relapsing MS (RMS) has an initial presentation of an acute attack which accounts for the initial 
presentation of approximately 85% of all subjects with MS (Confavreux, 2003; Reich, 2018). 
Typical symptoms include numbness and weakness in the legs leading to difficulty walking, vision 
loss, incoordination, cognitive dysfunction, fatigue, and pain. Almost half of relapses may result 
in incomplete recovery of function and leave permanent disability and impairment that 
accumulates over time (Lublin, 2003). 
There are several Disease Modifying Therapies (DMTs) available for the treatment of MS with 
different mechanisms of action and differentiated efficacy and safety profiles. These include (1) 
the first-approved DMTs (interferon [IFN] β-1a, IFN β-1b, glatiramer acetate [GA]), (2) oral 
therapies (fingolimod, siponimod, ozanimod, dimethyl fumarate, teriflunomide, and cladribine), 
and (3) monoclonal antibodies (alemtuzumab, ocrelizumab, ofatumumab, and natalizumab).
1.2
Compound Background 
Ozanimod 
Ozanimod is approved for the treatment of RMS in adults in the US and for the treatment of adult 
subjects with relapsing-remitting multiple sclerosis (RRMS) with active disease as defined by 
clinical or imaging features in European Medicines Agency (EMA) jurisdictions.
Ozanimod is a sphingosine 1-phosphate (S1P) receptor modulator, which binds with high affinity 
selectively to sphingosine 1-phosphate receptor subtypes 1 and 5 (S1P1 and S1P5). This leads to 
reversible sequestration of lymphocytes in lymphoid tissues. The mechanism by which ozanimod 
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exerts therapeutic effects in MS is unknown but may involve the reduction of lymphocyte 
migration into the CNS (Scott, 2016; Chaudry, 2017). 
Ozanimod was evaluated in two large, randomized, double-blind, double-dummy, parallel-group, 
active controlled clinical trials of similar design and endpoints, in subjects with RMS. SUNBEAM 
was a 1-year study with subjects continuing assigned treatment beyond month 12 until the last 
enrolled subject completed the study (Comi, 2019). RADIANCE was a 2-year study (Cohen, 
2019). The active comparator was IFN β-1a 30 µg intramuscularly (IM) once a week in both 
studies. The primary endpoint, annualized relapse rate (ARR), was met for ozanimod 1 mg versus 
IFN-β-1a in each study. In Study RPC01-301, a statistically significantly (p < 0.0001) lower 
adjusted ARR was observed for ozanimod 1 mg (0.181; [95% confidence interval (CI): 0.140, 
0.236]) compared with IFN-β-1a (0.350; [95% CI: 0.279, 0.440]), corresponding to a 48.2% 
reduction in ARR over 12+ months. In Study RPC01-201B, a statistically significantly (p < 
0.0001) lower adjusted ARR was observed for the ozanimod 1 mg group (0.172; [95 % CI: 0.142, 
0.208]) compared with the IFN-β-1a group (0.276; [95% CI: 0.234, 0.324]), corresponding to a 
37.7% reduction in ARR over 24 months. Key secondary endpoints of new or enlarging T2 lesions 
and the number of gadolinium-enhancing (GdE) lesions were met for ozanimod 1mg versus IFN
β-1a. 
The safety profile of ozanimod is well-characterized by a phase 2 and two large phase 3 studies
and their ongoing open label extension and is consistent with the known safety profile of S1P 
modulators (Novartis Pharmaceuticals Corporation, 2010; 2019). Treatment initiation with S1P 
receptor modulators results in a transient, dose-dependent bradyarrhythmia in both healthy 
subjects and in subjects with RMS mediated through the S1P1 receptor in humans (Gergely, 2009; 
Horga, 2010; Juif, 2016; Scott, 2016). Ozanimod treatment requires a dose escalation regimen at 
treatment initiation, to minimize transient reduction in heart rate (Celgene Corporation, 2020).
IFN-β 
Interferons are naturally occurring proteins produced by eukaryotic cells in response to viral 
infection and other agents. The type I family of interferons includes the IFN-βs, which are used to
treat MS; however, the mechanism of action of IFN-β in the treatment of MS is not completely 
understood.
After the Interferon Beta Study Group demonstrated IFN β-1b efficacy (INFB SG, 1993), the drug 
was approved for the treatment of RMS in the US almost 30 years ago and is approved for the 
treatment of RRMS in EMA jurisdictions. Forms of IFN-β for the treatment of MS include IFN β-
1a (administered IM once per week or subcutaneously [SC] 3 times per week) and IFN β-1b 
(administered SC every other day).
Tdap
In this study BOOSTRIX®, a booster vaccine containing tetanus toxoid, reduced diphtheria toxoid 
and acellular pertussis antigens (Tdap), that confer protection against tetanus, diphtheria, and 
pertussis diseases, will be administered. The acellular pertussis vaccine adsorbed component of 
the Tdap vaccine contains 5 bacterial antigens: pertussis toxoid and 4 adhesion proteins of 
filamentous hemagglutinin, pertactin and fimbriae types 2 and 3 (Dewan, 2020).
1.0
Approved
930197032
1.0
v
Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
19
The Centers for Disease Control (CDC) in the US recommends receiving the Tdap vaccine every 
10 years for adults, or more frequently if clinically indicated. The Tdap vaccine can be safety 
administered at the same time as other vaccines. Additional information about the tetanus vaccine 
can be found at https://www.cdc.gov/vaccines/vpd/dtap-tdap-td/hcp/index.html.  The World 
Health Organization (WHO) currently recommends primary vaccination against tetanus during 
childhood administering 3-4 doses of the tetanus vaccine in the first 2 years of life, followed by 
booster vaccinations throughout adulthood every 10-20 years (Weinberger, 2017). Most European 
countries follow the WHO recommendations. For example, in Germany, the Tdap vaccine is 
recommended every 10 years in adults and should be administered as a vaccine that also vaccinates 
against diphtheria and pertussis (https://www.rki.de/DE/Content/Infekt/EpidBull/Archiv/2019/
Ausgaben/34_19.pdf?__blob=publicationFile). 
PPSV23
In this study the PNEUMOVAX23® vaccine will be used. PNEUMOVAX23® is a sterile, liquid 
vaccine consisting of a mixture of purified capsular polysaccharides from Streptococcus 
pneumoniae types (1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 
20, 22F, 23F, and 33F) (Merck & Co., Inc, 1983).  Pneumococcal polysaccharide vaccine 
(PPSV23) contains antigens to 23 pneumococcal serotypes providing protection against 80-90% 
of capsular serotypes causing disease (Daniels, 2016).  The CDC recommends routine PPSV23 in 
all adults 65 years and older and in adults 19 through 64 years of age with certain medical 
conditions. (https://www.cdc.gov/vaccines/vpd/pneumo/hcp/index.html.)  In Germany, PPSV23 
vaccine is recommended in adults ≥ 60 years of age and in adults with chronic diseases including 
neurological diseases (https://www.rki.de/DE/Content/Infekt/EpidBull/Archiv/2019/ Ausgaben/ 
34_19.pdf?__blob= publication File) (https://www.rki.de/EN/Content/infections/Vaccination/ 
recommandations/34_2017_engl.pdf?__blob=publicationFile). Additionally, routine booster 
vaccination for the PPSV23 vaccine can be considered in immunocompromised and at-risk 
subjects with repeat vaccinations of intervals of at least 6 years in Germany and 5 years in the US 
after the last vaccination for subjects with increased risk for pneumococcal disease. 
Seasonal influenza vaccine
In this study a seasonal inactivated influenza vaccine will be administered.
The CDC recommends that people 6 months and older should receive a licensed age-appropriate 
influenza vaccine each year at the start of the influenza season. Vaccination is particularly 
important in subjects who are at high risk of developing influenza complications. These subjects 
include those with neurologic conditions and subjects requiring chronic medications that suppress 
the immune system. The CDC recommends that the influenza vaccine is administered by end of 
October in the US; however, getting vaccinated later can still be beneficial and vaccination should 
continue to be offered throughout the influenza season (https://www.cdc.gov/vaccines/v
pd/flu/hcp/index.html.)
In Europe, the seasonal influenza vaccine is recommended in all individuals older than 6 months 
of age with certain chronic diseases. Administration of a tetravalent vaccine is recommended 
before the influenza season begins (World Health Organization, 2021).
1.0
Approved
930197032
1.0
v
Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
20
1.3
Rationale
1.3.1
Purpose of Study
Based on its mechanism of action, ozanimod has the potential to reduce the immune response to 
vaccinations. However, the effect of ozanimod on vaccination response has not been assessed. This 
study is designed to provide data on the immune response and safety of administering vaccines to 
RMS subjects taking ozanimod compared to controls taking IFN-βs or receiving no DMT. The 
data of this study will support the labels for ozanimod in MS because the effect of ozanimod on 
the vaccination response of MS subjects is of interest to patients and prescribers.
In this study, we do not anticipate the risks of receiving vaccines to be different than the risks of 
receiving vaccines in the general population. Several clinical studies have been conducted using 
multiple vaccines in MS subjects, providing no evidence that receiving multiple vaccinations is 
unsafe for MS subjects (Ufer, 2017; Bar-Or, 2020; Ciotti, 2020)
1.3.2
Rationale to Study Vaccine Response in Ozanimod Subjects
Persons with MS should receive vaccinations to avoid preventable diseases (Reyes, 2020; Riva,
2021). In persons with MS not receiving immunotherapy, the disease itself does not appear to 
affect the ability of individuals to mount an immune response to antigenic stimulation, and the 
vaccine response is similar to those who do not have MS (Moriabadi, 2001). Infections may trigger 
MS relapses, increase MS radiologic and immunologic activity, and accelerate disease progression 
(Pannitch, 1994; Buljevac, 2002; Correale, 2006; Farez, 2019). Multiple sclerosis subjects
receiving immunotherapies as part of MS treatment may be at an increased risk of infection,
including pneumococcal pneumonia and influenza infection, which carry the potential to cause 
significant morbidity and mortality in individuals with chronic debilitating diseases (De Keyser, 
1998; Noseworthy, 2000). The vaccines administered in this study have not been associated with 
an increased risk of developing MS, with an increased risk of relapse, or with an increased risk of 
MS disease activity in MS subjects; however, MS subjects are not recommended to receive 
vaccines during a relapse (Confavreux, 2001; Farez, 2019; DeStefano, 2003; Loebermann, 2013). 
The availability of vaccine immune response and safety data in subjects treated with ozanimod 
will help guide practitioners on the impact of ozanimod on vaccine responses in MS subjects.
1.3.3
Effects of DMTs on Vaccine Response
Several studies have evaluated the impact of DMTs on vaccine response, including studies of two 
other S1P modulators, fingolimod and siponimod. Multiple sclerosis subjects and healthy 
volunteers treated with fingolimod showed significantly lower response rates to influenza, 
PPSV23, and tetanus toxoid vaccines at multiple timepoints post-vaccination compared to placebo
(Boulton, 2012; Kappos, 2015). Healthy volunteers treated with siponimod met seroprotective 
criteria similar to those in other treatment groups to influenza after vaccination, but titer ratios 
were generally lower in siponimod groups (Ufer, 2017).
Non-pegylated IFN-βs in MS subjects produce immune responses comparable to controls and do
not reduce response to vaccination (Schwid, 2005; Olberg 2014; Bar-Or, 2013; von Hehn, 2017).
A few studies suggest a trend of potential increased humoral immune response in MS subjects
1.0
Approved
930197032
1.0
v
Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
21
treated with IFN-βs compared to controls (Mehling 2013; Olberg, 2014). However, this trend is 
not consistent across studies, and IFN-β has not proven to be a vaccine adjuvant (Toporovski, 
2010; Rizza, 2011; Ye, 2019). Pegylated IFN-β has not been studied for effect on vaccine response
in MS subjects.
Ocrelizumab demonstrated a significantly reduced immune response to several vaccines with 
some subjects not achieving seroprotection (Bar-Or, 2020). Both dimethyl fumarate and 
teriflunomide showed no significant differences in response rates; similarly, natalizumab-treated 
subjects showed no significant differences in antigen-specific immunoglobulin G (IgG) response, 
but generally had lower titers, leading to an inadequate response in some subjects (von Hehn, 
2017; Bar-Or, 2013; Kaufman, 2014). Glatiramer acetate vaccine studies show mixed results on 
immune response (Olberg 2014; Olberg, 2018).
1.3.4
Rationale for Selected Study Design
This study will use a prospective, open-label design with subjects receiving vaccines at a single 
visit followed by immune response and safety assessments 28 days later in subjects on steady state
ozanimod compared to subjects receiving IFN-β as a reference control or not receiving DMT 
treatment. Using a control group of subjects treated with IFN-β is supported by vaccination studies 
in MS subjects on IFN-βs which show similar post-vaccination immune responses to MS subjects
receiving no DMT (Olberg, 2014; Olberg, 2018; Mehling, 2013) and subjects on IFN-βs have been 
successfully used as controls in other MS DMT vaccine response studies (Bar-Or, 2013; Olberg,
2020; Von Hehn, 2018).  Multiple vaccines administered during a single visit are well established 
in children and recommended for adults as safe, tolerable, and are not likely to reduce immune 
response (King, 1994; Broderick, 2016; Ferlito, 2021). Open-label designs are acceptable to assess 
the effects of immune modulating therapies on vaccine response and by vaccine manufacturers to 
assess vaccine immunogenicity (Schwid, 2005; Bar-Or, 2013; Olberg, 2018; Von Hehn, 2018). 
Laboratory studies, including the immunological correlates that assess the humoral response to 
vaccines (eg, serum antibody concentrations or antibody titers) provide objective assessments of 
vaccine response as substitute endpoints for longer term studies that measure clinical protective 
effect (Madore, 2010). The specific laboratory criteria used to establish vaccine immunogenicity 
is vaccine dependent.  In general, vaccine responses are assessed by comparing post-vaccination
to pre-vaccination antibody levels and by determining whether responses surpass a minimum 
threshold for seroprotection or an increase in antibody titers/concentrations to produce a serologic 
response (WHO, 2013). The laboratory criteria used in this study are based on guideline 
recommendations and correlates of humoral immunity (EMA, 1997; Qin, 2007; FDA, 2007; 
Plotkin, 2008). To mitigate the differences in the recruited subject population, this study will define 
eligibility criteria to reduce potential confounding variables affecting immune response to
vaccination. Despite well-defined eligibility criteria, to account for potential confounders that
could affect immune responses, serological response criteria will be compared based on a model 
adjusting for appropriate factors (eg, age, sex, body mass index [BMI], and baseline absolute 
lymphocyte count [ALC]). 
1.0
Approved
930197032
1.0
v
Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
22
To mitigate the risk of potential enrollment challenges surrounding influenza season, the study is 
designed to allow the addition of a second cohort of subjects that may have already received the 
seasonal influenza vaccine. Subjects in Cohort 2 will only receive Tdap and PPSV23. As of 13 
May 2022, Cohort 1 is closed, and study subjects are only able to enroll in Cohort 2. 
Some subjects in either treatment arm may have discontinued S1P modulators due to lymphopenia
and may have ongoing profound lymphopenia that could affect immune response to vaccination.
To avoid skewing the recruited subject population, no greater than 25% of enrolled subjects who 
discontinued any S1P modulator due to associated lymphopenia can have an ALC <0.5 x 109/L on 
steady state ozanimod or in the control group prior to Day 1. This threshold corresponds to 
approximately the 25th percentile of ALC levels observed in the ozanimod pivotal trials. Subjects 
enrolled who discontinued any S1P modulator due to associated lymphopenia must have an ALC
assessment performed within the 6 months prior to enrollment (and if on ozanimod, the lab must 
have been performed after being on ozanimod for a minimum of 
 days). Subsequent subjects 
enrolled who discontinued an S1P modulator due to associated lymphopenia must have an ALC ≥ 
0.5 x 109/L within 6 months prior to enrollment. 
1.3.5
Rationale for Selected Vaccines
This study will examine response to Tdap, PPSV23, and seasonal influenza vaccines by measuring
responses that act through different immune response pathways. Both T cell-dependent and T cell-
independent humoral responses will be assessed in this study. 
Tdap
The tetanus toxoid component of Tdap, which has remained unchanged over time, has been used
consistently in trials with other DMTs, including fingolimod, and serves a “benchmark” 
vaccination (Boulton, 2012; Kappos, 2015). Vaccination against tetanus is recommended on a 
recurring 10-year basis except following certain potential exposures to Clostridium tetani or its 
toxoid (CDC, 2020; STIKO, 2017). The inactivated tetanus toxoid is a peptide antigen that induces 
a T-cell dependent response (Lesinski, 2001; Przedpelski, 2020). Most individuals in the US and 
Germany have been vaccinated with tetanus toxoid (Poethko-Muller, 2013; Williams, 2016). The
tetanus vaccine is commonly administered in adults as a booster vaccine along with pertussis and 
diphtheria vaccines and can be administered as early as 1 year after previous vaccination as well 
as safely administered at the same time as other vaccines (Halperin 2006; Pool, 2020). Response
to tetanus toxoid will serve as the primary endpoint for this study. Information about Tdap can be 
found at https://www.cdc.gov/vaccines/vpd/dtap-tdap-td/hcp/index.html and https://www.who.int
/health-topics/tetanus#tab=tab_1. 
PPSV23
PPSV23 is a mixture of purified capsular polysaccharides from 23 Streptococcus pneumoniae 
serotypes and allow for assessment of a T-cell independent immune response (Malley, 2005).
Immune response to the PPSV23 in this study will be based on response to serotypes that are 
associated with an increased risk of invasive and/or severe disease (Malley, 2005). In subjects 
with certain neurological diseases older than 16 and less than 65 years of age, PPSV23 is
recommended as a single dose by the Standing Committee on Vaccination at the Robert Koch 
1.0
Approved
930197032
1.0
v
Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
23
Institute (STIKO) vaccination guidelines 
(https://www.rki.de/EN/Content/infections/Vaccination/recommandations/34_2017_engl.pdf?__
blob=publicationFile). Individuals with MS are at increased risk of pneumonia and the American 
Academy of Neurology (AAN) recommends pneumococcal vaccination in specific subgroups of 
MS subjects (eg, those with compromised pulmonary function) and those with more severe 
disease, who may derive greater benefits from pneumococcal vaccination (Reyes, 2020).
Seasonal Influenza Vaccine
Seasonal influenza vaccine generates a T-cell dependent recall for vaccine response (Korenkov, 
2018). The seasonal influenza vaccine is recommended for all MS subjects by the AAN and by
STIKO guidelines (STIKO, 2017; Farez, 2019).
1.3.6
Rationale for Selected Endpoints
Primary Endpoint
Tetanus Toxoid Immune Response - The proportion of subjects with serologic response to 
tetanus toxoid in the Tdap vaccine will serve as the primary endpoint in this study. Serologic 
response to tetanus toxoid is measured by comparing the anti-tetanus toxoid IgG antibody titers at 
4 weeks post-vaccination compared to the pre-vaccination titers. The antibody titers will be 
measured by an ELISA method. Subjects with a pre-vaccination IgG antibody titer level 
≤0.10 IU/mL will have a serologic response if post-vaccination titer levels are ≥0.40 IU/mL. To 
demonstrate a serologic response if pre-vaccination titer levels are > 0.10 IU/mL and ≤2.7 IU/mL, 
subjects will have at least a 4-fold increase in post-vaccination titers. If subjects have a pre-
vaccination titer level > 2.7 IU/mL, they will have at least a 2-fold increase in titers to demonstrate 
a response. This endpoint is supported by the recommendations to manufactures of tetanus 
vaccines to establish immune response which stipulates 0.10 IU/mL as a seroprotective level 
against tetanus and establishes increased Ab titers needed to demonstrate immune response based 
on pre-vaccination titer level (WHO Technical Report Series, No. 980, Annex 5). The requirement 
for a serologic response above the upper baseline level of 2.7 IU/mL as a 2-fold increase is 
supported by the WHO recommendations to establish tetanus vaccine efficacy, as well as by 
research demonstrating subjects with higher baseline titers are associated with less than a 4-fold 
response to vaccination (Petras, 2018; Halperin, 2018). Assessing the tetanus toxoid vaccine 
immune response at 4 weeks is also recommended by the WHO Technical Report Series, No. 980,
Annex 5 and coincides with peak humoral immune response in adults (Blatter, 2009).
Secondary Endpoints
Tetanus Toxoid Immune Response – The proportion of subjects with anti-tetanus toxoid IgG 
≥0.1 indicative of seroprotection.
Pneumococcal PPSV23- The proportion of subjects with a serologic response and serological 
protection to PPSV23 will be assessed in this study. Serologic response to PPSV23 is demonstrated 
by comparing the IgG antibody titers at 4 weeks post vaccination to the pre-vaccination
concentration. The antibody titers will be measured by an ELISA method. Of the 23 serotypes
contained in PPSV23, there is a subset associated with increased risk of invasive and/or severe 
1.0
Approved
930197032
1.0
v
Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
24
disease, including death: Serotypes 3, 6B, 9N, 11A, 14, 19A, 19F, 22F and 23F (Sjöström, 2006; 
Weinberger, 2010). These subtypes will be assessed in this study for pneumococcal vaccination 
immune response. The proportion of subjects with at least a 2-fold increase in post-vaccination 
anti-pneumococcal polysaccharide IgG titers in at least 5 of these serotypes will constitute the 
primary analysis for serologic response to PPSV23.  Serologic response will also be determined 
separately for all selected serotypes. Additional secondary endpoints to assess PPSV23 vaccine 
response are the proportion of subjects with anti-pneumococcal polysaccharide IgG concentration 
≥1.3 μg/mL for the selected serotypes indicative of seroprotection. The increase in antibody 
polysaccharide vaccine criteria (ie, 2-fold increase) is substantiated by studies that show most 
subjects with a pre-vaccination titer of ≥1.3 mg/mL can mount a 2-fold increase in titer on 
immunization but only a minority of subjects with high initial titers will be capable of mounting a 
4-fold increase in antibody titers after vaccination (Orange, 2012; LaFon, 2018). A normal
response to vaccination in unprotected subjects has been defined as conversion to a protected
concentration (1.3 μg/mL) with a 2-fold rise in antibody concentration in at least 70% of serotypes
tested (Orange, 2012; LaFon, 2018). In addition, in a study comparing anti-pneumococcal vaccine
antibody titers from the same specimens tested across multiple reference laboratories, the results
for algorithms using a 2-fold cutoff were consistent between laboratories but a 4-fold increase
criteria led to disparity across labs with low concordance (Daly, 2015).
Exploratory Endpoints
2021-2022 Seasonal Influenza –– The proportion of subjects with a serologic response to the 
influenza vaccine will be assessed in this study. Serologic response to the influenza vaccine is 
measured by comparing the anti-influenza IgG and immunoglobulin M (IgM) antibody titers to 
each strain at 4 weeks post-vaccination to the pre-vaccination concentration. The antibody titers 
will be measured by hemagglutination inhibition (HI). Subjects with a pre-vaccination IgG 
antibody titer < 1:10 will have a serologic response if their post-vaccination level is ≥1:40. To 
demonstrate a serologic response if pre-vaccination titer levels ≥ 1:10, subjects will have at least 
a 4-fold titer increase in post-vaccination titers. The assessment will be calculated separately for 
each antigen/strain, and combined, ie, for proportions of subjects who meet responder criteria for 
at least one antigen. Additional endpoints are HI antibody titers ≥ 1:40 indicative of seroprotection 
and the Geometric Mean Titer (GMT) ratio of pre- and post-vaccination titers for each strain. 
These criteria are supported by the Guidance on Harmonization of Requirements for Influenza 
vaccines, EMA, 1997 and FDA Guidance, 2007. The EMA guidance also recommends for 
demonstrating overall vaccine immunologic response to determine if a proportion of subjects meet 
specified criteria based on the endpoints. Successful vaccination is achieved for each treatment 
arm and for each influenza strain if at least one of the following three criteria is achieved: 1) The 
number of subjects with serologic response > 40%; 2) The Geometric Mean Concentration (GMC)
ratio of post-vaccination antibody titers compared to pre-vaccination is > 2.5; or, 3) The proportion 
of subjects achieving a hemagglutinin titer ≥1:40 is > 70%. Results of successful vaccination for 
each treatment group per strain will be reported.
Tetanus Toxoid Immune Response- GMC ratio of pre- and post-vaccination anti-tetanus toxoid 
IgG and IgM titers will be measured.
1.0
Approved
930197032
1.0
v
Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
25
Pneumococcal PPSV23- GMC ratio of pre and post anti-pneumococcal IgG and IgM titers to each 
selected strain.
Diphtheria Toxoid Immune Response - The proportion of subjects with serologic response to 
the diphtheria toxoid in the Tdap vaccine will be assessed in this study. Serologic response to 
diphtheria toxoid is measured by comparing the IgG anti-diphtheria antibody titers at 4 weeks post-
vaccination to the pre-vaccination titers. The antibody titers will be measured by ELISA. Subjects 
with a pre-vaccination IgG antibody titer level of ≤0.10 IU/mL will have a serologic response if 
post-vaccination levels are ≥0.40 IU/mL. To demonstrate a serologic response if pre-vaccination 
titer levels are > 0.10 IU/mL and ≤ 2.56 IU/mL, subjects will have at least a 4-fold increase in 
post-vaccination titers. If subjects have a pre-vaccination titer > 2.56 IU/mL, they will have at least 
a 2-fold post-vaccination increase in titers to demonstrate a response. This endpoint to assess 
diphtheria vaccine response is supported by the recommendations to manufacturers of diphtheria 
vaccines (WHO Technical Report Series, No. 980, Annex 4) which stipulates 0.10 IU/mL as a 
seroprotective level against diphtheria and established the demonstration of the increased Ab titers 
needed to demonstrate immune response based on pre-vaccination titer level. The use of an upper 
baseline level above which a 2-fold increase is  required to demonstrate serologic response is 
supported by the WHO recommendations to establish diphtheria as well vaccine efficacy and by 
research that demonstrates subjects with higher baseline diphtheria titers are associated with less 
than a 4-fold increase in titers (Halperin, 2018). 
Additional secondary endpoints to assess diphtheria vaccine serologic response are the proportion 
of subjects with anti-diphtheria toxoid IgG ≥0.1 indicative of seroprotection, and the GMC ratio 
of pre- and post-vaccination anti-diphtheria toxoid IgG and IgM titers.
Pertussis – The proportion of subjects with a serologic response to pertussis toxoid in the Tdap 
vaccine will be assessed in this study. Serologic response to the pertussis toxoid component of the 
pertussis vaccine is demonstrated by comparing the IgG antibody titers at 4 weeks post-vaccination 
to the pre-vaccination concentration. The antibody titers will be measured by ELISA. Pertussis 
toxin is a key virulence factor that is specific for B. pertussis and responsible for most systemic 
symptoms associated with pertussis disease (Carbonetti, 2010; Dewan, 2020) and the pertussis 
toxoid will be assessed for vaccine response in this study. Subjects with a pre-vaccination level of 
< 5 EL.U./mL will have a serologic response to pertussis toxoid if post-vaccination antibody 
concentrations are ≥20 EL.U./mL. To demonstrate a serologic response if pre-vaccination titer 
levels ≥5 EL.U./mL and < 20 EL.U./mL, subjects will have at least a 4-fold increase in post-
vaccination titers. If subjects have a pre-vaccination titer level ≥20 EL.U./mL, they will have at 
least a 2-fold post-vaccination increase in titers to demonstrate a response. The baseline levels and 
subsequent response have been validated in clinical studies for the assessment of response to 
pertussis vaccine (Blatter, 2009). Additional secondary endpoints to assess pertussis vaccine 
serologic response are the proportion of subjects with anti-pertussis toxoid IgG ≥5 EL.U./mL 
indicative of seroprotection, and the GMC ratio of pre- and post-vaccination anti-pertussis toxoid 
IgG and IgM titers.
1.0
Approved
930197032
1.0
v
Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
26
Pharmacokinetics and Pharmacodynamics 
Pharmacokinetic (PK) samples will only be collected in subjects who receive ozanimod as their 
DMT to characterize the plasma levels of ozanimod and its main major active metabolite (ie,
CC112273). Plasma concentrations of ozanimod and metabolites will be determined in plasma 
using a validated bioanalytical method.
One PK sample should be collected early during the Day 1 and Day 28 Visits, and the time of 
sample collection must be recorded. In addition, the time of the most recent ozanimod dose prior 
to PK sample collection must be recorded. For subjects who stay at the site for  hours or more 
after the first PK sample collection, a second PK sample should be collected immediately prior to 
visit completion and the time of collection should be recorded. For subjects receiving an ozanimod 
dose after the first PK sample collection and before visit completion, a second PK sample should 
be collected immediately prior to visit completion and the time of collection should be recorded.
Pharmacodynamic (PD) samples will be collected in all subjects at the Day 1 and Day 28 visits.
Pharmacokinetic and PD results may be analyzed for subject medication compliance, concomitant 
effects, and other analyses related to immune response.
2
STUDY OBJECTIVES AND ENDPOINTS
Table 1:
Study Objectives
Primary Objective
To evaluate the proportion of subjects meeting serologic response criteria against the tetanus 
toxoid antigen after vaccination with Tdap in subjects with relapsing forms of MS receiving 
ozanimod or receiving non-pegylated IFN-β or no DMT
Secondary Objectives
To evaluate the following in subjects with relapsing forms of MS undergoing vaccination and 
receiving ozanimod or receiving IFN-β or no DMT:

Proportion of subjects meeting tetanus seroprotective criteria

Proportion of subjects meeting pneumococcus serologic response and seroprotective criteria

Safety and tolerability
Exploratory Objectives
1.0
Approved
930197032
1.0
v
Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
27
Table 1:
Study Objectives
To evaluate the following in subjects with relapsing forms of MS undergoing vaccination and 
receiving ozanimod or receiving non-pegylated IFN-β or no DMT:

Immune response to the seasonal, inactivated influenza vaccine

Proportion of subjects meeting diphtheria serologic response, seroprotective criteria, and the
GMC ratio of anti-diphtheria IgG and IgM

Proportion of subjects meeting pertussis serologic response, seroprotective criteria, and the
GMC ratio of anti-pertussis IgG and IgM

GMC ratios of IgG and IgM against tetanus antigens

GMC ratios of IgG and IgM against antigens contained in PPSV23

PK and PD parameters of ozanimod and its active metabolites (ie, CC112273) in subjects
who receive ozanimod as their standard of care
Abbreviations: DMT = disease modifying therapy; GMC = geometric mean concentration; IFN = interferon; IgG =
immunoglobulin G; IgM = immunoglobulin M; MS = multiple sclerosis; PD = pharmacodynamic; PK =
pharmacokinetic; PPSV23 = pneumococcal polysaccharide vaccine; Tdap = tetanus toxoid, reduced diphtheria toxoid, 
and acellular pertussis vaccine.     
Table 2:
Study Endpoints
Endpoint
Name
Description
Time frame
Primary 
Proportion of subjects 
with serologic 
response to tetanus
toxoid
Serologic response to 
tetanus toxoid: 
If pre-vaccination 
antibody titer is 
≤0.10 IU/mL, post-
vaccination level
≥0.40 IU/mL;
if pre-vaccination 
antibody titer is 
> 0.10 IU/mL and
≤2.7 IU/mL, at least
a 4-fold increase in
titer; if pre-
vaccination antibody
titer is > 2.7 IU/mL,
at least a 2-fold
increase in titer
At the Day 28 post-
vaccination visit
1.0
Approved
930197032
1.0
v
Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
28
Table 2:
Study Endpoints
Endpoint
Name
Description
Time frame
Secondary
Proportion of subjects 
with serological 
protection against 
tetanus toxoid
Subjects with 
serological protection 
have:
Anti-tetanus toxoid 
IgG concentration 
≥0.1 IU/mL
At the Day 28 post-
vaccination visit
Proportion of subjects 
with serologic 
response to at least 5 
of the following 
pneumococcal 
serotypes: 3, 6B, 9N, 
11A, 14, 19A, 19F, 
22F and 23F
Serologic response to 
PPSV23:
The proportion of 
subjects with a ≥2-
fold increase in anti-
pneumococcal 
polysaccharide 
vaccine titer in > 5 of 
the indicated
serotypes
At the Day 28 post-
vaccination visit
Proportion of subjects 
with serological 
protection against the 
following 
pneumococcal 
serotypes: 3, 6B, 9N, 
11A, 14, 19A, 19F, 
22F and 23F 
Subjects with 
serological protection 
have:
Anti-pneumococcal 
polysaccharide IgG 
concentration ≥1.3
µg/mL for indicated
serotypes
At the Day 28 post-
vaccination visit
Safety of concomitant 
vaccine 
administration in 
subjects taking 
ozanimod
(S)AE incidence,
severity, causality,
type
Change from baseline 
in clinical lab values 
and incidence of 
abnormal lab values
Listing of subjects 
with Investigator-
confirmed relapses
Over the study
1.0
Approved
930197032
1.0
v
Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
29
Table 2:
Study Endpoints
Endpoint
Name
Description
Time frame
Exploratory 
Proportion of subjects 
with serologic 
response to the 
seasonal influenza 
vaccine 
Subjects with 
serologic response 
have: 
At least a four-fold 
titer increase in titer 
if the pre-vaccination 
titer ≥1:10, or an 
increase 
hemagglutination 
titer ≥1:40 in 
subjects with a pre-
vaccination titer 
< 1:10. 
To be calculated 
separately for each 
antigen/strain, and 
combined (ie, for 
proportions of 
subjects who meet 
responder criteria for 
at least one antigen)
At the Day 28 post-
vaccination visit
Proportion of subjects 
with serological 
protection against 
seasonal influenza
Subjects with 
serological protection 
have:
Hemagglutination 
inhibition antibody 
titers ≥1:40
To be calculated 
separately for each 
antigen/strain, and 
combined (ie, for the 
proportion of subjects 
who have serological 
protection against at 
least one influenza 
strain)
At the Day 28 post-
vaccination visit
1.0
Approved
930197032
1.0
v
Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
30
Table 2:
Study Endpoints
Endpoint
Name
Description
Time frame
Geometric Mean 
Titer (GMT) ratio of 
anti-influenza 
antibodies
The ratio of the 
geometric mean of 
the post-vaccination 
anti-hemagglutination 
inhibition titer (at the 
post vaccination day 
28 visit) divided by 
the geometric mean 
of the pre-vaccination 
anti-hemagglutination 
inhibition titer 
To be calculated 
separately for each 
antigen/strain.
At the Day 28 post-
vaccination visit
Assessment if at least 
one of the specified 
criteria is met for 
each treatment arm 
for each influenza 
strain 
For each treatment 
arm, at least one 
criterion is met for 
each strain:
Number of subjects 
with serologic 
response > 40%
The ratio of 
geometric mean post 
vaccination 
antibodies titers 
compared to pre-
vaccination is > 2.5
The proportion of 
subjects achieving a 
hemagglutinin titer 
> 40 is > 70%
At the Day 28 post-
vaccination visit
1.0
Approved
930197032
1.0
v
Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
31
Table 2:
Study Endpoints
Endpoint
Name
Description
Time frame
GMC ratio of anti-
tetanus toxoid IgG
The ratio of the 
geometric mean of 
the post-vaccination 
anti-tetanus toxoid 
IgG concentration (at 
the post vaccination 
day 28 visit) divided 
by the geometric 
mean of the pre-
vaccination anti-
tetanus toxoid IgG 
concentration
At the Day 28 post-
vaccination visit 
GMC ratio of anti-
tetanus toxoid IgM
The ratio of the 
geometric mean of 
the post-vaccination 
anti-tetanus toxoid
IgM concentration (at 
the post vaccination 
day 28 visit) divided 
by the geometric 
mean of the pre-
vaccination anti-
tetanus toxoid IgM 
concentration
At the Day 28 post-
vaccination visit
GMC ratio of anti-
pneumococcus IgG 
for each 
pneumococcal 
serotype in PPSV23
The ratio of the 
geometric mean of 
the post-vaccination 
anti-pneumococcus
IgG concentration (at 
the post vaccination 
day 28 visit) divided 
by the geometric 
mean of the pre-
vaccination anti-
pneumococcus IgG 
concentration.
To be calculated 
separately for each 
pneumococcal
serotype.
At the Day 28 post-
vaccination visit 
1.0
Approved
930197032
1.0
v
Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
32
Table 2:
Study Endpoints
Endpoint
Name
Description
Time frame
GMC ratio of anti-
pneumococcus IgM  
for each 
pneumococcal 
serotype in PPSV23
The ratio of the 
geometric mean of 
the post-vaccination 
anti-pneumococcus
IgM concentration (at 
the post vaccination 
day 28 visit) divided 
by the geometric 
mean of the pre-
vaccination anti-
pneumococcus IgM 
concentration.
At the Day 28 post-
vaccination visit
Proportion of subjects 
with serologic 
response to reduced
diphtheria toxoid
Serologic response to 
diphtheria toxoid: 
If pre-vaccination 
antibody titer is ≤0.10 
IU/mL, post-
vaccination level 
≥0.40 IU/mL; if pre-
vaccination antibody 
titer is > 0.10 IU/mL 
and ≤2.56 IU/mL, at  
least a  four-fold rise 
in titer; if pre-
vaccination IgG 
concentration is 
> 2.56 IU/mL, at least 
a two-fold increase in 
titer
At the Day 28 post-
vaccination visit
Proportion of subjects 
with serological 
protection against 
reduced diphtheria 
toxoid
Subjects with 
serological protection 
have:
Anti-diphtheria 
toxoid IgG 
concentration ≥0.1 
IU/mL
At the Day 28 post-
vaccination visit
1.0
Approved
930197032
1.0
v
Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
33
Table 2:
Study Endpoints
Endpoint
Name
Description
Time frame
GMC ratio of anti-
diphtheria toxoid IgG 
The ratio of the 
geometric mean of 
the post-vaccination 
anti-diphtheria toxoid 
IgG concentration (at 
the post vaccination 
day 28 visit) divided 
by the geometric 
mean of the pre-
vaccination anti-
diphtheria toxoid IgG
concentration
At the Day 28 post-
vaccination visit
GMC ratio of anti-
diphtheria toxoid IgM
The ratio of the 
geometric mean of 
the post-vaccination 
anti-diphtheria toxoid 
IgM concentration (at 
the post vaccination 
day 28 visit) divided 
by the geometric 
mean of the pre-
vaccination anti-
diphtheria toxoid IgM 
concentration
At the Day 28 post-
vaccination visit
1.0
Approved
930197032
1.0
v
Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
34
Table 2:
Study Endpoints
Endpoint
Name
Description
Time frame
Proportion of subjects 
with serologic 
response to pertussis 
Serologic response:
In initially 
seronegative subjects 
(< 5 EL.U/mL), post-
vaccination level 
≥20 EL.U/mL; if  
pre-vaccination 
antibody titer ≥5 
EL.U/mL and < 20 
EL.U/mL, at least a 
4-fold increase in 
titer; if pre-
vaccination antibody 
titer ≥20 EL.U/mL, 
at least a 2-fold in 
titer
To be calculated 
separately for each 
pertussis antigen
At the Day 28 post-
vaccination visit
Proportion of subjects 
with serological 
protection against 
pertussis
Subjects with 
serological protection 
have:
Anti-pertussis antigen 
IgG concentration ≥ 5 
EL.U/mL
To be calculated 
separately for each 
pertussis antigen
At the Day 28 post-
vaccination visit
1.0
Approved
930197032
1.0
v
Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
35
Table 2:
Study Endpoints
Endpoint
Name
Description
Time frame
GMC ratio of anti-
pertussis IgG 
The ratio of the 
geometric mean of 
the post-vaccination 
anti-pertussis antigen 
IgG concentration (at 
the post vaccination 
day 28 visit) divided 
by the geometric 
mean of the pre-
vaccination anti-
pertussis antigen IgG 
concentration.
To be calculated 
separately for each 
pertussis antigen
At the Day 28 post-
vaccination visit
GMC ratio of anti-
pertussis IgM
The ratio of the 
geometric mean of 
the post-vaccination 
anti-pertussis antigen 
IgM concentration (at 
the post vaccination 
day 28 visit) divided 
by the geometric 
mean of the pre-
vaccination anti-
pertussis antigen IgM 
concentration
To be calculated 
separately for each 
antigen
At the Day 28 post-
vaccination visit
PK
Plasma 
concentrations of 
ozanimod and its 
metabolites (ie,
CC112273)
At baseline and end 
of study
PD and Plasma 
biomarker analysis 
Cytokines, 
chemokines, 
inflammatory 
markers, and 
COVID-19
antibodies
At baseline and end 
of study
1.0
Approved
930197032
1.0
v
Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
36
3
OVERALL STUDY DESIGN
3.1
Study Design
The proposed study is a Phase 3b, multicenter, open-label, study to evaluate the immunological 
response to, and the safety of, vaccines in subjects with RMS who receive oral ozanimod 0.92 mg, 
non-pegylated IFN-β, or no DMT. The overall study design is presented in Figure 1. The schedule 
of events is presented in Table 3.
The study will include two cohorts differentiated by the vaccines administered. Cohort 1 
comprises subjects who receive Tdap, PPSV23, and the seasonal inactivated influenza vaccine. 
Cohort 2 comprises subjects who have already received the seasonal influenza vaccine. As a 
result, Cohort 2 subjects will receive Tdap and PPSV23, only.  Initiation of Cohort 2 will be 
based on the availability of eligible subjects who have not previously been vaccinated with the 
seasonal inactivated influenza vaccine. Subjects who meet all eligibility criteria but have already 
received the influenza vaccine as described in Exclusion Criterion #13, will be enrolled in 
Cohort 2. Subjects who meet all eligibility criteria, including Exclusion Criterion #13, will 
continue to be enrolled in Cohort 1 throughout the time both cohorts are open for enrollment.
Cohort 2 may be opened for enrollment at any time determined by the Sponsor, but is estimated 
to occur after no less than 60% of subjects of the planned of the planned total enrollment have 
been recruited into Cohort 1.
No greater than 25% of subjects in either treatment arm who discontinued an S1P modulator due 
to S1P modulator-associated lymphopenia will be enrolled who have an ALC <0.5 X 109/L. This 
threshold corresponds to approximately the 25th of ALCs mean levels observed in the ozanimod 
pivotal trials.
The study will be conducted in compliance with the International Council on Harmonisation 
(ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use/Good 
Clinical Practice (GCP) and applicable regulatory requirements.
1.0
Approved
930197032
1.0
v
Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
37
Figure 1:
Overall Study Design
Cohort 1:
Cohort 2:
Abbreviations: Tdap = Tetanus, diphtheria, and acellular pertussis vaccine; PPSV23 = Pneumococcal polysaccharide 
vaccine; IFN = Interferon; DMT = Disease modifying therapy.
1.0
Approved
930197032
1.0
v
Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
38
Screening Period
Subjects who have signed the informed consent form (ICF) will undergo screening evaluations to 
determine eligibility. The screening period may last from -14 to Day 1 (Baseline). Eligible subjects 
can enter the active treatment/vaccination period.
The Screening requirements can be performed on the same day as Day 1, provided that all 
Screening requirements are completed before any Day 1 assessments and vaccine administration
is performed. In this case, Day 1 assessments that are also conducted as Screening assessments do 
not have to be duplicated, including pregnancy screening.
Because the vaccines administered in this study are approved vaccines, they do not require 
laboratory testing prior to administration and are typically administered on the same day without 
a prior monitoring period in a broad range of the general population. Conducting Screening and 
Day 1 assessments on the same day is considered acceptable.
Active Treatment/Vaccination Period
At the Day 1 Visit, eligible subjects in Cohort 1 will have pre-vaccination blood samples collected 
(for titer determination), followed by administration of the following three vaccines:

Tdap booster vaccine

PPSV23

Seasonal influenza vaccine
At the Day 1 Visit, eligible subjects in Cohort 2 will have pre-vaccination blood samples collected
(for titer determination), followed by administration of the following two vaccines:

Tdap booster vaccine

PPSV23
The vaccines administered in this study are commercially available and approved in the
jurisdictions of the clinical sites, and administration will occur in accordance with the drug label.
After Day 1, the post-treatment follow-up period starts.
Post-Treatment Follow Up Period
The post treatment follow-up period spans 28 days, with one visit at post-vaccination Day 28, 
during which subjects will return to the site to have blood samples collected (for serological 
determinations) and adverse events (AE) recorded. Upon completion of the Day 28 Visit, subjects 
have completed the study.
Relapse Assessments
Subjects who experience worsening neurological symptoms during the study should contact the 
Investigator and describe their symptoms, ideally within 48 hours of symptom onset. The 
Investigator will also inquire about worsening neurological symptoms at the Day 28 Visit. If, in 
the opinion of the Investigator, the worsening neurological symptoms are potentially due to an MS 
relapse, a relapse visit should be scheduled within 7 days of site contact. The following 
manifestations are considered consistent with an MS relapse: monophasic clinical episode with 
1.0
Approved
930197032
1.0
v
Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
39
subject-reported neurologic symptoms and objective findings typical of multiple sclerosis, 
reflecting a focal or multifocal inflammatory demyelinating event in the CNS, developing acutely 
or sub acutely, with a duration of at least 24 hours, with or without recovery, and in the absence 
of fever or infection (Thompson, 2018). The relapse visit can take place at the same day as the Day 
28 Visit. 
3.2
Study Duration for Subjects 
This study will include a screening period of up to 14 days. The study period is from Day 1 
Vaccination to the 28-day assessment visit. The maximum potential length from screening to end 
of trial 45 days. Screening and Day 1 may occur on the same day in eligible subjects. 
3.3
End of Trial
The End of Trial is defined as either the date of the last visit of the last subject to complete the 
post-treatment follow-up, or the date of receipt of the last data point from the last subject that is 
required for primary, secondary and/or exploratory analyses, as prespecified in the protocol, 
whichever is the later date.
1.0
Approved
930197032
1.0
v
Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
40
4
STUDY POPULATION
4.1
Number of Subjects 
Approximately 60 subjects with relapsing forms of MS will be enrolled; approximately 30 of these 
subjects will be taking ozanimod for at least
days prior to the Day 1 Visit, and approximately 
30 subjects will be taking non-pegylated IFN-β or not receiving any DMT.
4.2
Inclusion Criteria for All Subjects
Subjects must satisfy the following criteria to be enrolled in the study:
1. Male or female subjects 18 to 65 years of age, inclusive, at the time of signing the ICF.
2. Subject must understand and voluntarily sign an ICF prior to any study-related 
assessments/procedures being conducted. 
3. Subject is willing and able to adhere to the study visit schedule and other protocol 
requirements.
4. Subject has a diagnosis of MS according to the 2017 revision of the McDonald diagnostic 
criteria and has RMS: RRMS or secondary progressive MS with active disease based on 
recent clinical relapse or MRI lesion activity (Thompson, 2018)
5. At Screening, subjects must be on one of the following three treatment options and willing 
to remain on the same treatment for the duration of the study:
a.
Treatment with ozanimod (0.92 mg maintenance dose). Ozanimod treatment must 
have been initiated at least 
 days prior to the Day 1 Visit. Subjects should be 
compliant with the ozanimod label.  In addition, in the  days prior to Day 1, 
ozanimod treatment must not have been interrupted for more than 1 day. 
b. Treatment with a non-pegylated form of IFN-β and compliant with dosing within  
 of Day 1 per the manufacturer’s label
c.
No treatment with a DMT for RMS
6. Subject is ambulatory (with or without walking aid) at Screening.
7. Subject is relapse-free in the 30 days prior to Day 1; during this period, subjects must have 
been clinically stable, without systemic corticosteroid or adrenocorticotrophic hormone 
treatment.
8. Subjects who receive ozanimod or non-pegylated IFN-β as their standard of care 
medication must do so in accordance with the local drug label.
9. Females of childbearing potential (FCBP) who receive ozanimod as their standard of care 
medication must agree to use contraception according to the approved local label. 
All Subjects:
Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus 
interruptus), spermicides only, and lactational amenorrhoea method (LAM) are not acceptable
methods of contraception. Female condom and male condom should not be used together. 
1.0
Approved
930197032
1.0
v
Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
41
4.3
Exclusion Criteria for Cohort 1
The presence of any of the following will exclude a subject from enrollment:
1. Subject is pregnant, lactating, or has a positive urine β-subunit of human chorionic
gonadotropin (β-hCG) measured during screening or on Day 1
2. Subject has any infections, including:
a. Infection requiring hospitalization or treatment with intravenous (IV) antibiotics,
antivirals, antifungal medication, anti-parasite medication within 30 days prior to Day 1
b. Infection requiring treatment with oral antibiotics, antivirals, antifungal medication,
anti-parasite medication within 14 days prior to Day 1
c. Fever ≥40ºC within 14 days of enrollment
d. SARS-CoV-2 infection with symptoms that have not completely resolved, and based on
Investigator assessment in consultation with the Clinical Trial Physician/Medical
Monitor, there are no sequelae that would place the participant at a higher risk of
receiving investigational treatment.
e. Any ongoing infection at Day 1
3. Subject has history of cancer, including solid tumors and hematological except for basal cell
cancer of the skin and carcinoma in situ of the cervix, which are exclusionary if they have not
been excised and resolved
4. Subject has a BMI ≥35 kg/m2
5. Subject has known contraindication against Tdap, PPSV23, or quadrivalent seasonal influenza
vaccine (Cohort 1 only), including, but not limited to:
a.
a history of anaphylactic/anaphylactoid or severe allergic reaction to any component of
the vaccines, including egg as contained in the influenza vaccine, or a history of an
Arthus-type hypersensitivity reaction against tetanus or diphtheria toxoid containing
vaccines
b. Encephalopathy or neurological complication following prior vaccinations containing
pertussis antigens
c.
Thrombocytopenia following prior vaccination against tetanus, diphtheria, or pertussis
6. Subject has a history of or currently active primary or secondary immunodeficiency
7. Subjects has a history of Guillain-Barré Syndrome
8. Subject has severely compromised cardiac or pulmonary function for which a systemic
hypersensitivity reaction to any of the vaccines would pose a significant risk
9. Subject has any moderate or severe acute illness, as assessed by the investigator
10. Subject has a history of alcohol abuse or drug abuse within 1 year prior to Screening
11. Subject has received any vaccine within 30 days prior to Day 1 including any SARS-CoV-2
(COVID-19) vaccine (first or second dose), or planned vaccines including COVID vaccine
throughout the study period.
12. Subject has received any tetanus vaccine within 1 year prior to Screening.
13. Subject has received the seasonal influenza vaccine for the 2021/2022 influenza season prior
to Day 1, or history of influenza vaccine for the 2020/2021 influenza season within 6 months
prior to Day 1.
1.0
Approved
930197032
1.0
v
Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
42
14. Subject has received PPSV23 within 5 years prior or PCV13 within 1 year of the Day 1.
15. For subjects receiving ozanimod: known contraindication against receiving ozanimod,
according to product label.
16. For subjects on IFN-β: known contraindication against IFN-β or ongoing tolerability issues
that might jeopardize compliance during the study (eg, injection site reactions requiring
treatment, intolerable influenza-like symptoms, etc).
17. Subject has previous treatment with one of the following medications or interventions within
the corresponding timeframe described as follows:
a.
Previous treatment with lymphocyte-depleting therapies (eg, Campath®, anti-CD4,
cladribine, cyclophosphamide, mitoxantrone, total body irradiation, bone marrow
transplantation, stem cell transplantation, alemtuzumab, or daclizumab)
b. Previous treatment with teriflunomide within 8 months prior to randomization (unless
teriflunomide plasma concentration is less than 0.02 mg/L [20 ng/mL]) or the subject
had successfully followed the accelerated elimination procedure as described in the
product label.
c.
180 Days prior to Day 1 or 5 half-lives, whichever is longer: any investigational agent
or interventional therapy (excluding life-style interventions)
d. 180 Days prior to Day 1: azathioprine, methotrexate, cyclosporine, mycophenolate
anti-CD20 mAbs (including rituximab, ocrelizumab, ofatumumab), Bruton’s tyrosine
kinase (BTK) inhibitors. After discontinuation of anti-CD20 mAbs, subjects must have
documentation of ALC and gamma globulin levels within the normal range.
e.
60 Days prior to Day 1: fingolimod, dimethyl fumarate
f.
Subjects who discontinued an S1P modulator due to lymphopenia must have a
documented ALC >0.2 X 109/L within 6 months prior to baseline and for subjects on
ozanimod, documented after a minimum of 
days of treatment with ozanimod.
g. 30 Days prior to Day 1: Systemic corticosteroids or adrenocorticotropic hormone
(ACTH).
h. 14 Days prior to Day 1: Pegylated IFNβ-1a, glatiramer acetate, siponimod
i.
Planned start of IFN-β or other MS disease modifying therapy after Day 1 throughout
the study period.
j.
Use of anti-pyretic treatments, including acetaminophen, aspirin, and other non-
steroidal anti-inflammatory drugs (NSAIDs), for a period of 24 hours prior to
administration of the vaccine and for a minimum of 6 hours after.
k. Any systemic immunosuppressive treatments with potential overlapping effects with
the baseline of this study. Corticosteroids that are by non-systemic routes (eg, topical,
inhaled, intra-articular) are allowed.
18. History of treatment with IV immunoglobulin (IVIg) or plasmapheresis within 4 weeks prior
to Day 1.
19. Any significant medical condition, laboratory abnormality, or psychiatric illness that places
the subject at unacceptable risk if he/she were to participate in the study in the opinion of the
investigator.
20. Any condition that confounds the ability to interpret data from the study.
1.0
Approved
930197032
1.0
v
Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
43
4.4
Exclusion Criteria for Cohort 2
All exclusion criteria that applies to Cohort 1 applies to Cohort 2, with the exception of Exclusion 
Criterion #13.
1.0
Approved
930197032
1.0
v
Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
44
5
TABLE OF EVENTS
Table 3:
Table of Events
Screening
Baseline
Post-Vaccination/
End of study
Relapse
Visit Number
1
2
3
Unscheduled
Relapse visita
Study Day
-14 to 1
1a
28 (± 3 days)
Informed consent
X
Inclusion/Exclusion criteria
X
X
Demographics
X
Medical history
X
Vaccination history
X
MS history
X
Prior/concomitant medications
X
X
X
X
Ozanimod/IFN-β compliance
X
X
X
X
Clinical and Laboratory Assessments
Adverse events
X
X
X
X
Pregnancy testb and contraception 
education
X
X
X
X
Vital signsc
X
X
X
X
Heightd
X
Weightd
X
X
X
Physical/neurological examinatione
X
X
Symptom-oriented physical examinatione
X
X
Clinical laboratory evaluationsf
Xg
X
X
X
Efficacy Assessment(s)
Blood draw for antibody concentration or 
titer determinationsh
X
X
X
Blood draw for PK/PD, Plasma 
biomarkers, and COVID-19 antibodies
Xi
Xi
IP
Administer vaccinesj
Xk
Abbreviations: ALC = absolute lymphocyte count, β-hCG = beta-human chorionic gonadotropin, BMI = body mass 
index,COVID-19 = SARS-CoV-2, IP = investigational product, IFN = interferon, N-SAID = nonsteroidal anti-
inflammatory drug, PD = pharmacodynamic, PK = pharmacokinetic, PPSV23 = pneumococcal polysaccharide 
vaccine, S1P = sphingosine-1-phosphate, Tdap = tetanus toxoid, reduced diphtheria toxoid and acellular pertussis 
vaccine, adsorbed. 
1.0
Approved
930197032
1.0
v
Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
45
a. If the assessments for the Screening and Baseline Visits are performed on the same day, assessments do not have
to be duplicated. If the assessments of the Relapse visit are performed on the same day as any other visit,
assessments do not have to be duplicated.
b. Urine β-hCG test at each visit for women of childbearing potential only. If a urine pregnancy test result is positive,
a serum pregnancy test will be performed for confirmation.
c. Vital signs include sitting blood pressure, body temperature and resting pulse. A subject should have rested in
sitting position, preferably for at least 5 minutes before measuring blood pressure and pulse. The same arm should
be used for blood pressure measurement throughout the study. Body temperature is measured by oral, tympanic,
or with temporal thermometer. Manual and digital thermometers are allowed. Resting pulse should be determined
by manual palpation according to standard clinical practice. The method for measuring blood pressure, pulse, and
temperature should be documented and the same method should be used consistently throughout all visits.
d. Height is measured at the Screening Visit with the subject not wearing shoes. Weight is measured at all Visits with
the subject wearing no shoes and light clothing. BMI should be calculated prior to enrollment.
e. Both physical examination and symptom-oriented physical examination will include neurological examination.
f. Day 1 (baseline) and End of Study (Day 28) clinical laboratory tests include serologic antibody testing for COVID-
19 (baseline only), chemistry (full panel), hematology, and urinalysis
g. If needed, ALC may be measured for subjects with prior S1P modulator-related lymphopenia if no laboratory data
are recorded meeting protocol criteria. Clinical laboratory testing, while not required for screening eligibility
except as described in the protocol, may be performed for valid medical concerns after discussion with the medical
monitor.
h. Blood draw for titer determinations at relapse visit should occur prior to administration of any steroids.
i. For subjects on ozanimod only.  Record the time of PK sample collection and the time of the most recent ozanimod
dose administration prior to PK sample collection. If  hours or more pass between (first) PK sample collection
and visit completion, draw a second PK sample immediately prior to visit completion and record time. If an
ozanimod dose is administered after the first PK sample collection, record time of administration and collect second
PK sample immediately prior to visit completion and record time. For all subjects, plasma sample for biomarker
evaluation will be included (eg, inflammatory markers) and COVID-19 antibodies.
j.
Cohort 1 will receive Tdap, PPSV23, and influenza vaccine; Cohort 2 will receive Tdap and PPSV23.
k. Subjects should refrain from using anti-pyretic treatments, including acetaminophen, aspirin, and other NSAIDs
for a minimum of 6 hours post-vaccination.
1.0
Approved
930197032
1.0
v
Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
46
6
PROCEDURES
6.1
Screening Period
Screening evaluations will be performed for all subjects to determine study eligibility. These 
evaluations must be completed within 14 days prior to the Day 1 visit. If screening procedures 
cannot be completed within 14 days, the Medical Monitor must be contacted to discuss whether 
any Screening procedures must be repeated prior to enrollment. All screening assessments and 
procedures are to be performed by the Principal Investigator (PI) or a qualified designee.
Written, signed, and dated informed consent from the subject prior to the performance of any
study-related procedures must be obtained by the PI or designee. A copy of the signed informed 
consent or second original informed consent, signed by both parties (depending on local 
requirements), must be given to the subject for his/her records. 
Safety laboratory analyses and all assessments will be performed centrally. Screening laboratory 
values must demonstrate subject eligibility, but may be repeated within the screening window, if 
necessary.
The following will be performed at screening as specified in Table 3, after informed consent has 
been obtained:

Review of eligibility criteria

Confirmation and source documentation by the PI that subjects have taken ozanimod or IFN-
β as prescribed by the manufacturer label and as required in the inclusion criteria

Demographics (initials, date of birth, sex, race)

Complete medical history (all relevant medical conditions diagnosed/occurring prior to
screening should also be included)

Vaccination History

MS History

Prior and concomitant medication evaluation (including those taken ≤ 30 days before
screening, except for those taken for disease)

Urine pregnancy test confirmed negative and contraception education

Collection of adverse events

Vital signs (including blood pressure, temperature, and heart rate)

Height and weight

Complete physical examination: including evaluation of heart, lung, head, neck, abdominal,
neurological, skin, and extremities

Blood sampling for ALC evaluation, if needed

The Screening requirements can be performed on the same day as the Day 1 assessments,
provided that all Screening assessments for eligibility are completed before any Day 1
assessments and vaccine administration is performed. In this case, Day 1 assessments that are
also conducted as Screening assessments do not have to be duplicated, including urine
pregnancy screening.
1.0
Approved
930197032
1.0
v
Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
47

A screen failure is defined as a subject who has given informed consent and has failed to meet
one or more inclusion criteria and/or has met one or more exclusion criteria.
6.2
Treatment Period - Day 1/Baseline
The following evaluations will be performed at the frequency specified in Table 3. The evaluations 
should be performed prior to vaccine administration on Day 1, unless otherwise specified.

Review of subject eligibility

Confirmation and source documentation by the PI that subjects have taken ozanimod or IFN-
β as prescribed by the manufacturer label and as required in the inclusion criteria

Concomitant medications evaluation

AE evaluation

Urine pregnancy test confirmed negative for pregnancy

Vital signs (including blood pressure, temperature, and heart rate)

Symptom oriented physical examination

Urinalysis and blood sampling for the follow laboratory tests:

Serologic antibody testing for COVID-19 and other PD parameters

Hematology: red blood cell (RBC) count, total and differential white blood cell (WBC)
count (basophils, eosinophils, lymphocytes, monocytes, and neutrophils), platelet count,
hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular
hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC).

Blood Chemistry: sodium, potassium, chloride, calcium, magnesium, phosphate, blood
urea nitrogen, glucose, albumin, alkaline phosphatase, creatinine, alanine
aminotransferase (ALT) (SGPT), aspartate aminotransferase (AST) (SGOT), gamma-
glutamyl transferase (GGT), total bilirubin, and conjugated bilirubin. Abnormal
laboratory parameters inconsistent with clinical presentation of MS or suspicious of
underlying medical condition should be repeated for accuracy.

Efficacy assessments, including blood draw for pre-vaccination antibody titer determination,
and blood draw for PK (see Section 6.4)

Administration of Tdap, PPSV23, and influenza vaccine (Cohort 1 only), (intramuscularly or
subcutaneously, as described in Table 4 )
6.2.1
Post Vaccination/End of Study
An end of study (EOS) evaluation will be performed for subjects who are withdrawn from 
treatment for any reason as soon as possible after the decision to permanently discontinue 
treatment has been made. 
The following evaluations will be performed as specified in the Table 3:

Confirmation and source documentation of subject-described compliance with ozanimod and
IFN-β dosing as prescribed by the manufacturer label

Concomitant medications evaluation (including whether any additional vaccines were
administered)

AE evaluation
1.0
Approved
930197032
1.0
v
Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
48

Urine pregnancy test

Vital signs (including blood pressure, temperature, and heart rate)

Physical/neurological examination and weight

Urinalysis and blood sampling for the follow laboratory tests:

Serologic antibody testing for COVID-19 and other PD parameters

Hematology: RBC count, total and differential WBC count (basophils, eosinophils,
lymphocytes, monocytes, and neutrophils), platelet count, hemoglobin, hematocrit, MCV,
MCH, and MCHC.

Blood Chemistry: sodium, potassium, chloride, calcium, magnesium, phosphate, blood
urea nitrogen, glucose, albumin, alkaline phosphatase, creatinine, ALT (SGPT), AST
(SGOT), GGT, total bilirubin, and conjugated bilirubin. Abnormal laboratory parameters
inconsistent with clinical presentation of MS or suspicious of underlying medical condition
should be repeated for accuracy.

Efficacy assessments, including blood draw for antibody titer determination, and blood draw
for PK
6.2.2
Relapse Assessments
A relapse is defined as a monophasic clinical episode with subject-reported symptoms and 
objective findings typical of multiple sclerosis, reflecting a focal or multifocal inflammatory 
demyelinating event in the CNS, developing acutely or sub acutely, with a duration of at 
least 24 hours, with or without recovery, and in the absence of fever or infection (Thompson, 
2018). Subjects who experience worsening neurological symptoms during the study should 
contact the Investigator site and describe their symptoms, ideally within 48 hours of symptom 
onset. If, in the opinion of the Investigator, the worsening neurological symptoms are potentially 
due to a MS relapse, an unscheduled relapse visit should be planned as soon as possible, ideally 
within 7 days of symptom onset. The unscheduled relapse visit will be conducted if a possible 
relapse is suspected at any time prior to the Day 28 visit. The Investigator will also inquire about 
worsening neurological symptoms at the Day 28 Visit. The following evaluations will be 
performed as specified in Table 3:

Confirmation and source documentation of subject-described compliance with ozanimod and
IFN-β dosing as prescribed by the manufacturer label

Concomitant medications evaluation (including whether any additional vaccines were
administered)

AE evaluation

Urine pregnancy test

Vital signs (including blood pressure, temperature, and heart rate)

Symptom-oriented physical examination and weight

Urinalysis and blood sampling for the follow laboratory tests:

Hematology: RBC count, total and differential WBC count (basophils, eosinophils,
lymphocytes, monocytes, and neutrophils), platelet count, hemoglobin, hematocrit, MCV,
MCH, and MCHC.
1.0
Approved
930197032
1.0
v
Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
49

Blood Chemistry: sodium, potassium, chloride, calcium, magnesium, phosphate, blood
urea nitrogen, glucose, albumin, alkaline phosphatase, creatinine, ALT (SGPT), AST
(SGOT), GGT, total bilirubin, and conjugated bilirubin.

Blood draw for antibody titer determination prior to the administration of any steroid treatment
The relapse visit can take place at the same day as the Day 28 Visit. If relapse occurs at Day 28
visit, assessments do not have to be duplicated.
Subjects who experience a relapse may receive treatment with IV corticosteroids, if judged to be 
clinically appropriate by the Investigator. The following standardized treatment regimen should 
be used: as warranted, up to 1.0 g IV methylprednisolone per day for a maximum of 5 consecutive 
days. No deviation from the standardized treatment regimen is allowed unless approved by the 
Medical Monitor. The Investigator is asked to draw antibody titers prior to steroid administration 
during an unscheduled relapse visit, regardless of its proximity to the Day 28 Visit. Blood draw 
for antibody titers will also occur at the Day 28 Visit. 
The analysis of any relapses captured during the study will be descriptive.
6.3
Follow-up Period
Not applicable.
6.4
Efficacy Assessment
The immunological response is measured by comparing post- to pre-vaccination titers or 
concentrations of and IgG and IgM antibodies against vaccine antigens as described in detail in 
Table 2.
Serological response to vaccines is generally characterized as a 2 or 4-fold increase in titers if 
subjects are above levels of seroprotection at baseline. If subjects are below levels of 
seroprotection at baseline, serologic response is generally measured by demonstrating a response 
above seroprotection criteria. The specific levels are based on vaccine guidelines and are consistent 
with other studies of immune response with concomitant immunomodulatory treatments. 
Additional assessments would include evaluation of the GMT ratio post- to pre-vaccination 
antibody titers. 
For vaccines utilized in the study containing a single component, the response of that component 
will be measured. For PPSV23 and pertussis vaccines, important subcomponents will be assessed 
in the primary analysis of these vaccines for immune response. All antigens contained within the 
seasonal influenza vaccine will be assessed for immune responses. 
6.5
Pharmacokinetics
PK samples will only be collected in subjects who receive ozanimod as their standard of care 
treatment, to characterize the plasma levels of ozanimod and its main metabolites (ie, CC112273). 
Plasma concentrations of ozanimod and metabolites will be determined in plasma using a validated 
bioanalytical method.
One PK sample should be collected early during the Day 1 and Day 28 Visits, and the time of 
sample collection must be recorded. In addition, the time of the most recent ozanimod dose prior 
1.0
Approved
930197032
1.0
v
Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
50
to PK sample collection must be recorded. For subjects who stay at the site for  hours or more 
after the first PK sample collection, a second PK sample should be collected immediately prior to 
visit completion and the time of collection should be recorded. For subjects receiving an ozanimod 
dose after the first PK sample collection and before visit completion, a second PK sample should 
be collected immediately prior to visit completion and the time of collection should be recorded.
6.6
Biomarkers, Pharmacodynamics, Pharmacogenomics 
Blood samples will be analyzed by the central laboratory upon receipt, subject to national and 
local requirements. PD blood biomarkers include but are not limited to markers of inflammation 
and possible measurements of SARS-CoV-2 serologic status. 
One PD sample should be collected early during the Day 1 and Day 28 Visits, and the time of 
sample collection must be recorded. The total amount of blood collected for biomarker and 
safety evaluations will be specified in the Informed Consent Form. In addition to the required 
biomarker analyses described above, if the subject has granted consent where allowed by the 
regulatory authorities and local ethics committee, residual samples will be stored for up to 
15 years and may be used for additional analyses.
6.7
Additional and Optional Research
Additional and optional research as described below may be performed using left-over samples 
originally collected for another test required in this study or using samples collected specifically 
for biomarker testing. The research may involve genetic tests using DNA or RNA and may lead to 
the development of new diagnostic tests.
6.7.1
Additional Research
Additional research related to the study drug and/or disease may be performed. The results of this 
additional research could help to improve the diagnosis and/or the treatment of this disease in the 
future. 
6.7.2
Optional Research
Optional research not related to the study drug or the subject’s disease may be performed. The 
subject’s decision to participate in this optional research will not impact their ability to participate 
in the main study. 
7
DESCRIPTION OF STUDY TREATMENTS
7.1
Description of Investigational Products
Tdap, PPSV23, and Seasonal Influenza Vaccines
All vaccines used in this study will be provided to the clinical sites. The commercial names of the 
Tdap and pneumococcal vaccines are BOOSTRIX® and PNEUMOVAX®.  The seasonal 
inactivated influenza vaccine will be determined based on supply for the 2021/2022 influenza 
season. For all vaccines, the pre-filled syringe (0.5 ml) dosage form must be used. Vaccines must 
be stored in a secure location at the site at 2ºC to 8ºC (36ºF to 46ºF) and protected from light until 
1.0
Approved
930197032
1.0
v
Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
51
used for vaccine administration. Prior to the administration of vaccines, sites should check the 
vaccine expiration date and vigorously shake the pre-filled syringes. The contents of the syringe 
should appear as a homogeneous solution without particulate matters or discoloration. Vaccine 
batch and lot number must be documented. 
7.2
Treatment Administration and Schedule 
At the Day 1 Visit, eligible subjects will have pre-vaccination blood samples collected (for 
serological determinations), followed by parenteral administration of Tdap, PPSV23, and seasonal 
inactivated influenza vaccine (Cohort 1), or Tdap and PPSV23 (Cohort 2). 
The vaccines administered in this study are commercially available and approved in the 
jurisdictions of the clinical sites, and administration will occur in accordance with the product
labels. After Day 1 the post-treatment follow-up period starts.
Post-vaccination 
After vaccination, subjects should be observed for approximately 15 minutes, or as per 
recommended local guidelines, whichever is longer, for development of hypersensitivity reactions. 
Should hypersensitivity reactions occur, the Investigator should record the event as an AE and
should monitor pulse and blood pressure. The Investigator must determine if treatment with 
steroid, antihistamines, epinephrine/adrenaline, or hospital admission is warranted and act 
accordingly. If no hypersensitivity reactions develop or a mild to moderate hypersensitivity 
reaction has stabilized, subjects can leave the site. Subjects should be informed that over the 
counter ibuprofen or acetaminophen (paracetamol) can be used to treat post-vaccination pain or 
fever, but subjects should refrain from using anti-pyretic treatments, including acetaminophen, 
aspirin, and other NSAIDs for a minimum of 6 hours post-vaccination (Scheifele, 2018; Doedee, 
2014).
Vaccine administration must conform with the label requirements and must be performed by 
someone who is experienced in intramuscular and subcutaneous administration of medicinal 
products. Sites must have epinephrine or adrenaline medication available that can be administered 
in case of anaphylactic reactions. Subjects should be stably seated or reclined before and during 
vaccine administration to avoid injuries from falls or in case of syncopal reactions. Standard 
hygiene practices should be applied during vaccine administration, including skin disinfection with 
alcohol swaps at the site of vaccine administration and hand cleaning or wearing gloves by the 
person administering the vaccine. The seasonal influenza vaccine and Tdap must be administered 
intramuscularly, and PPSV23 should be administered subcutaneously. The recommended 
anatomical site of administration for each vaccine is listed in Table 4 . Only one vaccine must be 
administered per anatomical site. On the day that the vaccine is administered, subjects who receive 
IFN-β injections must not have IFN-β administered at a site of vaccine administration.
1.0
Approved
930197032
1.0
v
Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
52
Table 4:
Route and Anatomical Site of Vaccine Administration
Vaccine
Route of 
Administration
Recommended Anatomical Site of 
Administration
BOOSTRIX®
Intramuscular
Left deltoid muscle
PNEUMOVAX®
Intramuscular or 
Subcutaneous
Lateral mid-thigh (either cohort) or right deltoid 
muscle (Cohort 2 only) 
Cohort 1 Only:
Seasonal inactivated influenza 
vaccine
Intramuscular
Right deltoid muscle
Intramuscular administration 
A sterile needle for intramuscular injection (28 to 25 gauge) of appropriate length should be 
attached to the prefilled syringe and a separate needle must be used for each vaccine. The needle 
should enter the skin at a 90-degree angle and the vaccine should be administered at approximately 
the center of the deltoid muscle. Deeper administration in the muscle mass is generally associated 
with fewer adverse reactions compared with injections close to the subcutaneous tissue. Table 5
lists the needle length for adults based on weight, which is based on CDC recommendations 
(https://www.immunize.org/catg.d/p3084.pdf). Once the needle is inserted to the muscle tissue, 
the vaccine is injected, followed by withdrawal of the needle. A simple band aid can be used to 
cover the injection site. 
Subcutaneous administration 
A sterile needle for subcutaneous injection (23 to 25 gauge; 16 mm [5/8 inch] length) should be 
attached to the prefilled syringe and a separate needle must be used for each vaccine. The skin at 
the injection site should be elevated between thumb and index finger of the vaccinator and the 
needle should enter the skin at approximately a 45-degree angle. Once the needle is inserted in the 
subcutaneous tissue, the vaccine is injected, followed by withdrawal of the needle. A simple band 
aid can be used to cover the injection site.
Table 5:
Recommended Needle Lengths for Intramuscular Vaccination in 
the Deltoid Muscle (Adults)
Weight Range
Recommended Needle Length
Men and Women < 60 kg (<130 lbs)
5/8 to 1-inch (16 to 25 mm) – when using 5/8-inch (16 
mm) length, stretch skin over deltoid muscle (do not
bunch muscle)
Men and Women 60 to 70 kg (130 to 152 lbs) 
1 inch (25 mm)
Men 70 to 118 kg (152 to 260 lbs)
1 to 1.5 inches (25 to 38 mm)
Women 70 to 90 kg (152 to 200 lbs)
Men > 118 kg (260 lbs)
1.5 inches (38 mm)
Women > 90 kg (200 lbs)
1.0
Approved
930197032
1.0
v
Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
53
Ozanimod and Non-pegylated IFN-β
Ozanimod and non-pegylated IFN-β are provided as standard of care medication by the 
Investigator. They are not provided as part of this study, and the Sponsor will not reimburse sites 
or subjects for the cost of the standard of care medication. During the study, subjects should 
continue their standard of care medication according to their regular schedule. Drug compliance 
will be based on subject report and recorded in source documents. 
7.3
Method of Treatment Assignment
All subjects who meet all eligibility criteria, including Exclusion Criterion #13, will be enrolled 
into Cohort 1. All Cohort 1 subjects will receive the following vaccines:

Tdap

PPSV23

Seasonal Influenza Vaccine
Cohort 2 may be opened for enrollment at any time determined by the Sponsor. Subjects who meet 
all eligibility criteria, with the exception of Exclusion Criterion #13 will be enrolled in Cohort 2.
Subjects who meet all eligibility criteria, including Exclusion Criterion #13, will continue to be 
enrolled in Cohort 1 throughout the time both cohorts are open for enrollment. All Cohort 2 
subjects will receive the following vaccines:

Tdap

PPSV23
7.4
Packaging and Labeling
Not applicable
7.5
Investigational Product Accountability and Disposal 
All vaccine supply will be accounted for in accordance with GCP. If errors or damages in the 
vaccine supply shipments occur, the Investigator should contact the Clinical Monitor immediately. 
Each Investigator will provide copies of the vaccine accountability records for inclusion in the 
Trial Master File after database lock. The Clinical Monitor will periodically check the supplies of 
vaccine held by the Investigator or pharmacist to verify accountability of all supply used.
The Investigator will provide the vaccines only to the identified subjects of this study, according 
to the procedures described in this study protocol. After the end of the study, the Clinical Monitor 
will perform final accountability.
Celgene (or designee) will review with the Investigator and relevant site personnel the process for 
investigational product return, disposal, and/or destruction including responsibilities for the site 
versus Celgene (or designee).
1.0
Approved
930197032
1.0
v
Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
54
7.6
Investigational Product Compliance
It is the Investigator’s responsibility to ensure subjects are fully compliant with their DMT. Drug 
compliance will be based on subject report and recorded in source documents. 
8
CONCOMITANT MEDICATIONS AND PROCEDURES
All concomitant treatments, including blood and blood products, used from 30 days prior to Day
1 until Day 28, must be reported on the CRF 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.
Treatment for symptoms related to MS (eg, spasticity, incontinence, pain, fatigue, and depression) 
is not restricted, but Investigators should attempt to keep therapies or treatments reasonably 
constant throughout the study period. Changes may be made if appropriate for a subject’s well-
being in the clinical judgment of the Investigator.
8.1
Prohibited Concomitant Medications and Procedures
The following medications cannot be used during the trial through the End of Treatment 
Visit:

Any medications prohibited by the product labels of country for ozanimod and IFN-β
compounds

Any approved and unapproved disease-modifying MS agents, excluding ozanimod and IFN-β

Treatment with Class Ia or Class III anti-arrhythmics (examples of prohibited systemic cardiac
medications are provided in Table 6 ) or treatment with a combination of 2 or more agents
known to prolong PR interval (eg, combination of a beta blocker and verapamil) are prohibited
during the study unless approved by the Sponsor’s representative. Note that Table 6 does not
provide a comprehensive list. The Medical Monitor should be contacted for further guidance
if needed.

Systemic corticosteroid therapy or ACTH, except for treatment of protocol-defined treatment
of relapses. Corticosteroids that are by non-systemic routes (eg, topical, inhaled, intra-articular)
are allowed.

Any vaccine, including first or second dose of COVID-19 vaccine

Intravenous immunoglobulin (IVIg) or plasmapheresis

Immunosuppressive agents known to deplete lymphocytes

Breast cancer resistance protein inhibitors (eg, cyclosporine, eltrombopag)

Monoamine oxidase inhibitors (eg, selegiline, phenelzine)

CYP2C8 inhibitors (eg, gemfibrozil and clopidogrel) or inducers (eg, rifampicin)
1.0
Approved
930197032
1.0
v
Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
55
Table 6:
Examples of Prohibited Cardiac Medications (Systemic Use)
Pharmaceutical Class
Example Medications
Class Ia or Class III Antiarrhythmic
drugs
amiodarone, bepridil hydrochloride, disopyramide, 
dofetilide, dronedarone, flecainide, sotalol, ibutilide, 
lidocaine, procainamide, propafenone, quinidine, 
tocainide
8.2
Required Concomitant Medications and Procedures
Not applicable 
1.0
Approved
930197032
1.0
v
Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
56
9
STATISTICAL CONSIDERATIONS
Detailed methodology for summary and statistical analyses of the data collected in this study will 
be documented in a Statistical Analysis Plan, which will be maintained by the Sponsor. 
9.1
Overview
This is a non-randomized, open-label study in which all subjects remain on their pre-study 
(baseline) treatment per protocol. Subjects will be recruited by investigators from MS clinical 
practice patients and prospectively assessed for immune response to vaccination.  The statistical 
analyses will focus on estimating immune response rates, adjusting for baseline subject-level 
characteristics. No formal statistical hypothesis is evaluated. To mitigate for potential differences 
in the recruited subject population in the ozanimod and non-ozanimod arms that potentially could 
affect immune response, response rates will be estimated based on a logistic regression model 
adjusting for several factors, eg, age, sex, body mass index (BMI), and baseline absolute 
lymphocyte count (ALC). The results of the statistical analyses for immune response endpoints 
will be summarized for subjects receiving ozanimod (ozanimod arm) and subjects not receiving 
ozanimod (non-ozanimod arm) as their standard of care disease modifying therapy for MS.
Analyses of safety will be summarized by descriptive statistics separately for the ozanimod and 
non-ozanimod arms.
9.2
Study Population Definitions
The study will include two cohorts differentiated by the vaccines administered. Cohort 1 comprises 
subjects who receive Tdap, PPSV23, and the seasonal inactivated influenza vaccine. Cohort 2 
comprises subjects who receive Tdap and PPSV23 only. Initiation of Cohort 2 will be based on 
the availability of eligible subjects who have not previously been vaccinated with the seasonal 
inactivated influenza vaccine.
The modified intent-to-treat (mITT) population consists of all subjects who received at least one 
vaccination and summarized according to their initial treatment status (ozanimod vs. non-
ozanimod) regardless of systemic use of corticosteroids.
The per-protocol (PP) population consists of all subjects who received the correctly assigned 
vaccinations, had no steroid use, and did not receive any other vaccines throughout the study.
9.3
Sample Size and Power Considerations
The sample size of the study is 60 subjects with an estimated 30 subjects expected to have received
ozanimod and 30 subjects expected to not have received ozanimod as standard of care DMT. It is 
expected that approximately 60% of the subjects not receiving ozanimod as standard of care 
therapy will have a serologic response to vaccination with Tdap (Kappos, 2015). 
With a sample size of 30 subjects for the ozanimod arm, assuming the response rate is 45%, the 
expected half width of the 95% confidence interval (based on normal approximation) is 
approximately 0.175. We note that in simulations (assuming a true response rate of 0.45), the 
estimated response rate falls within 0.267 and 0.633 among 95% of the simulated trials (across 
100,000 simulations).
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Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
57
9.4
Background and Demographic Characteristics
The following summaries will be provided by treatment status (ozanimod vs non-ozanimod) based 
on the mITT population:
Subject’s age, height, weight, and baseline characteristics will be summarized using descriptive 
statistics, while sex, race and other categorical variables will be provided using frequency 
tabulations.  Medical history data will be summarized using frequency tabulations by Medical 
Dictionary for Regulatory Activities (MedDRA) system organ class and preferred term.
9.5
Subject Disposition
The following summaries will be provided by treatment status (ozanimod vs non-ozanimod) based 
on the mITT population.
The number and percentage of subjects will be summarized. Subject disposition, including the 
number of subjects who enrolled, completed the trial, and discontinued the trial with reasons for 
discontinuation. Subject demographics include age, sex, race, ethnicity, height, weight, and body 
mass index.
Baseline characteristics include age at MS symptom onset, age at MS diagnosis, years since MS 
symptom onset, years since MS diagnosis, number of relapses within the last 12 months, number 
of relapses within the last 24 months, and number of GdE lesions.
9.6
Immune Response Analysis
The primary endpoint analysis and all analyses for immune-response to vaccination will be 
performed in the per-protocol population, ie, in subjects who received the correctly assigned 
vaccinations and had no major protocol violations. Sensitivity analyses will be conducted within 
the mITT population consisting of all subjects who received at least one vaccination and 
summarized according to their initial treatment status (ozanimod vs non-ozanimod) regardless of 
protocol violations 
If Cohort 2 is initiated, then not all subjects will receive the seasonal inactivated influenza vaccine.   
For the purposes of summarizing the Tdap and PPSV23 vaccines, all subjects in Cohorts 1 and 2 
will be combined, since they generally would have had the opportunity to receive all three 
vaccines.  For evaluating the seasonal inactivated influenza vaccine, the analyses will be based on 
Cohort 1 subjects. 
The ozanimod and non-ozanimod treatment group immune response rates and differences will be 
estimated based on a model adjusting for baseline demographics (eg, age, gender, BMI, baseline 
ALC, etc). We note the estimates of treatment differences should be interpreted with caution, since, 
in addition to the limited sample size, the ozanimod and non-ozanimod arms are not randomized. 
Some or all of the aforementioned factors may not be feasible to include in the analysis model. 
Analysis details will be provided in the statistical analysis plan such as the required number of 
subjects within each factor stratum (eg, if within a factor stratum level there are less than 10 
subjects, then that factor will be excluded from the model).
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Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
58
9.7
Safety Analysis
All subjects who receive at least 1 vaccine, the mITT population, will be included in the safety 
analyses. Adverse events will be summarized by worst severity grade. Adverse events, with 
particular focus on treatment-emergent AEs, will be summarized by MedDRA system organ class, 
and preferred term.  This will include vaccine-related adverse events, adverse events leading to 
death or to discontinuation from treatment, serious adverse events, and events of interest.
Associated laboratory parameters such as hepatic enzymes, renal function, and hematology values 
will be grouped and presented together. Individual subject 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 blood pressure monitoring, each of the vital signs 
and physical examination parameters will be summarized. The incidence of abnormal vital signs 
parameters and outlier physical examination results will be tabulated. 
By-subject listings will be provided for all relevant safety data.  Graphical displays and figures 
will be provided where useful to assist in the interpretation of results.
9.8
Interim Analysis
Not applicable
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Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
59
10
ADVERSE EVENTS
10.1
Monitoring, Recording and Reporting of Adverse Events
An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in 
a subject during the course of a study. It may be a new intercurrent illness, a worsening 
concomitant illness, an injury, or any concomitant impairment of the subject’s health, including 
laboratory test values (as specified by the criteria in Section 10.3), regardless of etiology. Any 
worsening (ie, any clinically significant adverse change in the frequency or intensity of a pre-
existing condition) should be considered an AE.  A diagnosis or syndrome should be recorded on 
the AE page of the CRF rather than the individual signs or symptoms of the diagnosis or syndrome. 
All subjects will be monitored for AEs during the study.  Assessments may include monitoring of 
any or all of the following parameters:  the subject’s clinical symptoms, laboratory, pathological,
physical examination findings, or findings from other tests and/or procedures.
All AEs will be recorded by the Investigator from the time the subject signs informed consent until 
28 days after the vaccine administration, as well as those serious adverse events (SAEs) made 
known to the Investigator at any time thereafter that are suspected of being related to IP.  All AEs
(serious/non-serious) will be recorded on the CRF and in the subject’s source documents.  Refer 
to Section 10.5 for instructions on how to report SAEs to Drug Safety. 
All AEs related to SARS-CoV-2 must be collected continuously during the study including at the 
safety follow visit(s). After the initial AE/SAE report, the investigator is required to proactively 
follow each participant at subsequent visits/contacts. All SAEs and non-serious AEs, including 
SARS-COV-2 will be followed until resolution, until the condition stabilizes, until the event is 
otherwise explained, or until the participant is lost to follow-up. COVID-19 related AEs/SAEs 
will be captured in specific clinical safety program CRF pages
10.2
Evaluation of Adverse Events
A qualified Investigator will evaluate all AEs as to: 
10.2.1
Seriousness 
An SAE is any AE occurring at any dose that:

Results in death;

Is life-threatening (ie, in the opinion of the Investigator, the subject is at immediate risk of
death from the AE);

Requires inpatient hospitalization or prolongation of existing hospitalization (hospitalization
is defined as an inpatient admission, regardless of length of stay);

Results in persistent or significant disability/incapacity (a substantial disruption of the subject’s
ability to conduct normal life functions);

Is a congenital anomaly/birth defect;

Constitutes an important medical event.
Important medical events are defined as those occurrences that may not be immediately life-
threatening or result in death, hospitalization, or disability, but may jeopardize the subject or
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Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
60
require medical or surgical intervention to prevent one of the other outcomes listed above.  Medical 
and scientific judgment should be exercised in deciding whether such an AE should be considered
serious.
Events not considered to be SAEs are hospitalizations for:

routine treatment or monitoring of the studied indication not associated with any deterioration 
in condition.

a procedure for protocol/disease-related investigations (eg, sampling for laboratory tests) 
However, hospitalization or prolonged hospitalization for a complication of such procedures 
remains a reportable SAE.

hospitalization or prolongation of hospitalization for technical, practical, or social reasons, in 
absence of an AE.

a procedure that is planned (ie, planned prior to start of treatment on study); must be 
documented in the source document and the CRF.  Hospitalization or prolonged hospitalization 
for a complication remains a reportable SAE.

an elective treatment of or an elective procedure for a pre-existing condition, unrelated to the 
studied indication, that has not worsened from baseline. 

emergency outpatient treatment or observation that does not result in admission, unless 
fulfilling other seriousness criteria above.
For each AE, the Investigator will provide information on severity, start and stop dates, 
relationship to the IP, action taken regarding the IP, and outcome.
10.2.2
Severity/Intensity
For each AE, the Investigator must assess the severity/ intensity of the event. 
Mild

Asymptomatic or mild symptoms; clinical or diagnostic observations only

Intervention not indicated

Activities of daily life (ADLs) minimally or not affected

No or minimal intervention/therapy may be required 
Moderate 

Symptom(s) cause moderate discomfort

Local or noninvasive intervention indicated

More than minimal interference with ADLs but able to carry out daily social and functional 
activities.

Drug therapy may be required
Severe (could be non-serious or serious) 

Symptoms causing severe discomfort/pain

Symptoms requiring medical/surgical attention/intervention
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Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
61

Interference with ADLs including inability to perform daily social and functional activities (eg, 
absenteeism and/or bed rest)

Drug therapy is required
The term “severe” is often used to describe the intensity of a specific event (as in mild, moderate,
or severe myocardial infarction); the event itself, however, may be of relatively minor medical 
significance (such as severe headache).  This criterion is not the same as “serious” which is based 
on subject/event outcome or action criteria associated with events that pose a threat to a subject’s 
life or functioning.  
Seriousness, not severity, serves as a guide for defining regulatory obligations.
10.2.3
Causality
The Investigator must determine the relationship between the administration of the IP and the 
occurrence of an AE as Not Suspected or Suspected as defined below:
Not suspected:
a causal relationship of the adverse event to IP administration is 
unlikely or remote, or other medications, therapeutic interventions, 
or underlying conditions provide a sufficient explanation for the 
observed event.
Suspected:
there is a reasonable possibility that the administration of IP caused 
the adverse event.  ‘Reasonable possibility’ means there is evidence 
to suggest a causal relationship between the IP and the adverse event.
Causality should be assessed and provided for each AE based on currently available information.  
Causality is to be reassessed and provided as additional information becomes available.
If an event is assessed as suspected of being related to a comparator, ancillary or additional IP that 
has not been manufactured or provided by Celgene, please provide the name of the manufacturer 
when reporting the event.
10.2.4
Duration
For each AE, the Investigator will provide a record of the start and stop dates of the event.
10.2.5
Action Taken
The Investigator will report the action taken with IP as a result of each AE, as applicable (eg, 
discontinuation, interruption, or dose reduction of IP, as appropriate) and report if concomitant 
and/or additional treatments were given for the event. 
10.2.6
Outcome
The Investigator will report the outcome of the event for each AE.
All SAEs that have not resolved upon discontinuation of the subject’s participation in the study 
must be followed until recovered (returned to baseline), recovered with sequelae, or death (due to 
the SAE).
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1.0
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1.0
v

Oza ni m o d
Pr ot oc ol R P C - 1 0 6 3-M S - 0 1 0
Cel ge ne C or p orati o n
R P C - 1 0 6 3-M S -0 1 0 A me n d me nt 1. 0
Date 2 9 N O V 2 0 2 2
6 2
1 0. 3
A b n or m al L a b or at or y V al u e s
A n a b n or mal la b orat or y  val ue is c o nsi dere d t o be a n A E if t he a b n or malit y:

res ults i n disc o nti n uati on fr o m t he st u d y;

re q uires treat me nt, m o dificati on/ i nterr u pti o n of I P d ose, or a n y ot her t hera pe utic i nter ve nt i on;
or

is j u d ge d t o be of sig nifica nt cli nic al i m p orta nce, e g, o ne t hat i n dicates a ne w disease pr ocess
a n d/ or or ga n t o xicit y or is a n e xacer bati on or w orse ni n g of a n e xist i n g c o n diti on.
Re gar dless o f se verity gra de, o nl y la b orat or y a b n or malit ies t hat f ulfill a seri o us ness criteri o n nee d 
t o be d oc u me nt e d as a seri o us a d verse e ve nt.
If a la b orat or y a b n or malit y is o ne c o mp o ne nt of a di a g n osis or s y n dr o me, t he n o nl y t he dia g n osis 
or s y n dr ome s h o uld be rec or de d as t he A E .  If t he a b n or malit y was n ot a part of  a dia gn osis or 
s y n dr ome, t he n t he la b orat or y a b n or malit y sh o ul d be rec or de d as t he A E. If p ossi ble, t he lab orat or y 
a b n or malit y s h o uld be rec or de d as a me dical ter m a n d n ot si m pl y as a n a b n or mal la b orat or y res ult  
(e g, rec or d t hr o m b oc yt o pe nia rat her t ha n decrease d platelets).
If a n y of the f oll owi n g r es ults are o bser ve d d uri n g t he treat me nt peri o d, t he I n vesti gat or will be 
n otifie d a n d as ke d t o re peat t he la b orat or y  t ests wit h a p pr o xi matel y 7 da ys :

A bs ol ute l y m p h oc y te c o u nt ( A L C) < 2 0 0 cells/ µ L

A bs ol ute ne utr o p hil c o u nt ( A N C) < 1 0 0 0 cells/ µ L

T ot al  W B C > 2 0, 0 0 0 cells/ µ L
If t he re peat val ues als o e xcee d t hese li mits, t he I n vesti gat or will be i nf or me d t hat t he s u bject’s
res ults for t he a b n or m al para meter ha ve falle n o utsi de t he acce pta ble t hres h o l ds.
If A N C or t otal W B C c o u nts are c o nfir me d o utsi de t he acce pta ble li mits, t he Me dical M o nit or will 
c o ntact t he treat me nt i n vesti gat or t o re q uest cl ose m onit ori n g f or ri s k of i nfecti on a n d a p pr o priate 
f oll ow- u p, at t he discreti o n o f t he i n vest i gat or. 
If A L C res ults are c o nfir me d o n re peat as bel o w 2 0 0 cells/ µ L, t he i n vesti gat or will be i nstr ucte d 
t e mp oraril y disc o nt i n ue oza ni m o d a n d re peat A L C la b orat or y testi n g e ver y wee k u ntil A L C le vel 
is > 5 0 0 cells/ µ L. T he i n vest i gat or ma y res u me oza ni m o d at t hat p oi nt per t he pr o d uct la bel.
Li ver F u ncti o n Tests
If a s u bject is fo u n d t o ha ve ele vat i ons i n A L T a n d/ or A S T ≥3 x t he u p per li mit of n or mal ( U L N)
fr om baseli ne la bs or d uri n g t he st u d y , a retest s h o ul d be perf or me d wit hi n 7 da ys after t he ori gi nal 
test. If t he a b n or malit y is c o nfir me d, wee kl y testi n g s h o uld c o nti n ue, an d t he Me di cal Mo ni t or 
s h o uld be c o ns ul te d. T he I n vestigat or s h o ul d esta blis h ca usa lity.  
At  an y time, if a n y of t he f oll owi n g occ ur a n d t here are n o a p pare nt alt er nati ve ca uses f or t he 
fi n di n g, t he i n vesti gati onal dr u g m ust be per m a ne ntl y disc o nt i n ue d, a nd a n A E re p orte d:

A L T or A S T > 8 x U L N or

A L T or A S T > 5 x U L N wit h c o nfir mat i on, wi t hi n 2 wee ks or

A L T or A S T > 3 x U L N a n d (t otal bilir u bi n > 2 x U L N or I N R > 1. 5) or
1 . 0
A p p r o v e d
9 3 0 1 9 7 0 3 2
1 . 0
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Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
63

ALT or AST > 3x ULN with the appearance of fatigue, nausea, vomiting, right upper quadrant
pain or tenderness, fever, rash, and/or eosinophilia (>5%).
The Investigator should establish causality further and liver function evaluation should be 
performed (for example, coagulation panel and alkaline phosphatase) in consultation with the 
Medical Monitor.
10.4
Pregnancy
All pregnancies or suspected pregnancies occurring in either a female subject of childbearing 
potential or partner of childbearing potential of a male subject are immediately reportable events.
Any subject with a suspected or confirmed pregnancy should discontinue ozanimod and consult 
the medical monitor.  
10.4.1
Females of Childbearing Potential
Pregnancies and suspected pregnancies (including elevated β-hCG or positive pregnancy test in a 
female subject of childbearing potential regardless of disease state) occurring while the subject is 
enrolled in the study are considered immediately reportable events.  A pregnancy, suspected 
pregnancy, or positive pregnancy test must be reported to Celgene Drug Safety immediately by 
email, phone or facsimile, or other appropriate method, using the Pregnancy Initial Report Form, 
or approved equivalent form.  
The female subject may be referred to an obstetrician-gynecologist or another appropriate 
healthcare professional for further evaluation.
The Investigator will follow the female subject until completion of the pregnancy and must notify 
Celgene Drug Safety immediately about the outcome of the pregnancy (either normal or abnormal 
outcome) using the Pregnancy Follow-up Report Form or approved equivalent form.
If the outcome of the pregnancy was abnormal (eg, spontaneous abortion), the Investigator should 
report the abnormal outcome as an AE. If the abnormal outcome meets any of the serious criteria, 
it must be reported as an SAE to Celgene Drug Safety within 24 hours of the Investigator’s 
knowledge of the event.
All neonatal deaths that occur within 28 days of birth should be reported, without regard to 
causality, as an SAE.  In addition, any infant death after 28 days that the Investigator suspects is 
related to the in-utero exposure to the IP should also be reported as an SAE to Celgene Drug Safety 
within 24 hours of the Investigator’s knowledge of the event.
10.4.2
Male Subjects
If a female partner of a male subject enrolled in the study becomes pregnant, the male subject 
should notify the Investigator, and the pregnant female partner should be advised to call their 
healthcare provider immediately.  
10.5
Reporting of Serious Adverse Events
Any AE that meets any serious criterion requires reporting as an SAE within 24 hours of the 
Investigator’s knowledge of the event. This instruction pertains to initial SAE reports as well as 
any follow-up reports.
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Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
64
This requirement applies to all SAEs (regardless of relationship to IP) that occur during the study 
(from the time the subject signs informed consent until 28 days after vaccine administration) or 
any SAE made known to the Investigator at any time thereafter that are suspected of being related 
to IP.  Serious adverse events occurring prior to treatment (after signing the ICF) are to be recorded 
within the CRF, but do not require reporting to Celgene Drug Safety.
Where required by local legislation, the Investigator is responsible for informing the Institutional 
Review Board/Ethics Committee (IRB/EC) of the SAE and providing them with all relevant initial 
and follow-up information about the event. The Investigator must keep copies of all SAE 
information on file including correspondence with Celgene and the IRB/EC.
The SAE is recorded within the CRF, and the data is transmitted electronically to Celgene Drug
Safety. In the event electronic transmission is not available, a paper SAE Report Form will be
completed and sent directly to Celgene Drug Safety, ensuring the event is recorded on the CRF as 
well.
10.6
Expedited Reporting of Adverse Events
For the purpose of regulatory reporting, Celgene Drug Safety will determine the expectedness of 
events suspected of being related to ozanimod based on the Investigator Brochure.
In the United States, expedited reports sent to the FDA by the sponsor based on the reasonable 
possibility threshold are known as ‘IND safety reports’ and will be reported in accordance with 21 
CFR 312.32.
For reporting to the FDA, events that are not suspected to be causally related to IP by the sponsor 
will not be considered adverse reactions. 
For countries within the European Economic Area (EEA), Celgene or its authorized representative 
will report in an expedited manner to Regulatory Authorities and Ethics Committees concerned, 
suspected unexpected serious adverse reactions (SUSARs) in accordance with Directive 
2001/20/EC and the Detailed Guidance on collection, verification and presentation of adverse 
reaction reports arising from clinical trials on investigational products for human use (ENTR/CT3) 
and also in accordance with country-specific requirements. 
For the purpose of regulatory reporting in the EEA, Celgene Drug Safety will determine the 
expectedness of events suspected of being related to BOOSTRIX®, PNEUMOVAX23®, and the 
seasonal inactivated influenza vaccine based on the US Prescribing Information (USPI) or EU 
Summary of Product Characteristics (SmPC).
Serious adverse reactions and nonserious adverse reactions will be reported to the Regulatory 
Authorities, in accordance with Regulation (EC) No. 726/2004 and/or Directive 2001/83/EC as 
amended, and also in accordance with country-specific requirements for countries within the EEA.
Celgene or its authorized representative shall notify the Investigator of the following information 

Any AE suspected of being related to the use of IP in this study or in other studies that is both 
serious and unexpected (ie, SUSAR);
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Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
65

Any finding from tests in laboratory animals that suggests a significant risk for human subjects
including reports of mutagenicity, teratogenicity, or carcinogenicity.
Where required by local legislation, the Investigator shall notify his/her IRB/EC promptly of these 
new serious and unexpected AE(s) or significant risks to subjects.
The Investigator must keep copies of all pertinent safety information on file including 
correspondence with the IRB/EC. (See Section 13.3 for record retention information).
1.0
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Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
66
11
DISCONTINUATIONS
11.1
Study Discontinuation
The following events are considered acceptable reasons for discontinuing a subject from the study:

Screen Failure

Adverse Event

Withdrawal by subject

Death

Lost to follow-up

Other (to be specified on the CRF)

Physician Decision

Site terminated by Sponsor: An indication that a clinical study was stopped at a particular site 
by its Sponsor. 

Study terminated by Sponsor: An indication that a clinical study was stopped by its Sponsor. 

The details concerning the reason for study discontinuation should be recorded in the CRF and 
in the source documents.

The decision to discontinue a subject remains the responsibility of the treating physician, which 
will not be delayed or refused by the Sponsor.  However, prior to discontinuing a subject, the 
Investigator may contact the Medical Monitor and forward appropriate supporting documents 
for review and discussion.
11.2
Emergency Contact
In emergency situations, the Investigator should contact the responsible Clinical Research
Physician/Medical Monitor or designee by telephone at the number listed on the Emergency 
Contact Information page of the protocol.
In the unlikely event that the Clinical Research Physician/Medical Monitor or designee cannot be 
reached, please contact the global Emergency Call Center by telephone at the number listed on the 
Emergency Contact Information page of the protocol. This global Emergency Call Center is 
available 24 hours a day and 7 days a week. The representatives are responsible for obtaining your 
call-back information and contacting the on-call Celgene/contract research organization Medical 
Monitor, who will then contact you promptly.
Note: The back-up 24-hour global emergency contact call center should only be used if you are 
not able to reach the Clinical Research Physician or Medical Monitor or designee for emergency 
calls. 
11.3
Emergency Identification of Investigational Products
This is an open-label study; therefore, IP will be identified on the package labeling.
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Celgene Corporation
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67
12
REGULATORY CONSIDERATIONS
12.1
Good Clinical Practice
The procedures set out in this study protocol pertaining to the conduct, evaluation, and 
documentation of this study are designed to ensure that Celgene, its authorized representative, and 
Investigator abide by Good Clinical Practice (GCP), as described in International Conference on 
Harmonisation (ICH) Guideline E6 and in accordance with the general ethical principles outlined 
in the Declaration of Helsinki. The study will receive approval from an IRB/EC prior to 
commencement. The Investigator will conduct all aspects of this study in accordance with 
applicable national, state, and local laws of the pertinent regulatory authorities.
12.2
Investigator Responsibilities
Investigator responsibilities are set out in the ICH Guideline for Good Clinical Practice and in the 
local regulations.  Celgene staff or an authorized representative will evaluate and approve all 
Investigators who in turn will select their staff.
The Investigator should ensure that all persons assisting with the study are adequately informed 
about the protocol, amendments, study treatments, as well as study-related duties and functions, 
including obligations of confidentiality of Celgene information. The Investigator should maintain 
a list of Sub-investigators and other appropriately qualified persons to whom he or she has 
delegated significant study-related duties.
The Investigator is responsible for keeping a record of all subjects who sign an informed consent 
form (ICF) and are screened for entry into the study.  Subjects who fail screening must have the 
reason(s) recorded in the subject’s source documents.
The Investigator, or a designated member of the Investigator’s staff, must be available during 
monitoring visits to review data, resolve queries and allow direct access to subject records (eg, 
medical records, office charts, hospital charts, and study-related charts) for source data 
verification.  The Investigator must ensure timely and accurate completion of CRFs and queries.
The information contained in the protocol and amendments (with the exception of the information 
provided by Celgene on public registry websites) is considered Celgene confidential information.  
Only information that is previously disclosed by Celgene on a public registry website may be 
freely disclosed by the Investigator or its institution, or as outlined in the Clinical Trial Agreement.  
Celgene protocol, amendment and IB information is not to be made publicly available (for example 
on the Investigator’s or their institution’s website) without express written approval from Celgene.  
Information proposed for posting on the Investigator’s or their institution’s website must be 
submitted to Celgene for review and approval, providing at least 5 business days for review.
At the time results of this study are made available to the public, Celgene will provide Investigators 
with a summary of the results that is written for the lay person. The Investigator is responsible for 
sharing these results with the subject and/or their caregiver as agreed by the subject.
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Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
68
12.3
Subject Information and Informed Consent
The Investigator must obtain informed consent of a subject and/or a subject’s legal representative 
prior to any study related procedures.
Documentation that informed consent occurred prior to the study subject’s entry into the study and 
of the informed consent process should be recorded in the study subject’s source documents 
including the date.  The original ICF signed and dated by the study subject and by the person 
consenting the study subject prior to the study subject’s entry into the study, must be maintained 
in the Investigator’s study files and a copy given to the study subject.  In addition, if a protocol is 
amended and it impacts on the content of the informed consent, the ICF must be revised.  Study 
subjects participating in the study when the amended protocol is implemented must be re-
consented with the revised version of the ICF.  The revised ICF signed and dated by the study 
subject and by the person consenting the study subject must be maintained in the Investigator’s 
study files and a copy given to the study subject.
12.4
Confidentiality
Celgene affirms the subject's right to protection against invasion of privacy and to be in compliance 
with ICH and other local regulations (whichever is most stringent). Celgene requires the 
Investigator to permit Celgene's representatives and, when necessary, representatives from 
regulatory authorities, to review and/or copy any medical records relevant to the study in 
accordance with local laws.
Should direct access to medical records require a waiver or authorization separate from the 
subject’s signed ICF, it is the responsibility of the Investigator to obtain such permission in writing 
from the appropriate individual.
12.5
Protocol Amendments
Any amendment to this protocol must be approved by the Celgene Clinical Research Physician.  
Amendments will be submitted to the IRB/EC for written approval.  Written approval must be 
obtained before implementation of the amended version occurs.  The written signed approval from 
the IRB/EC should specifically reference the Investigator name, protocol number, study title and 
amendment number that is applicable. Amendments that are administrative in nature do not require 
IRB/IEC approval but will be submitted to the IRB/IEC for information purposes.
12.6
Institutional Review Board/Independent Ethics Committee Review and 
Approval
Before the start of the study, the study protocol, ICF, and any other appropriate documents will be 
submitted to the IRB/EC with a cover letter or a form listing the documents submitted, their dates 
of issue, and the site (or region or area of jurisdiction, as applicable) for which approval is sought. 
If applicable, the documents will also be submitted to the authorities in accordance with local legal 
requirements.
IP can only be supplied to an Investigator by Celgene or its authorized representative after 
documentation on all ethical and legal requirements for starting the study has been received by 
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Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
69
Celgene or its authorized representative. This documentation must also include a list of the 
members of the IRB/EC and their occupation and qualifications. If the IRB/EC will not disclose 
the names, occupations, and qualifications of the committee members, it should be asked to issue 
a statement confirming that the composition of the committee is in accordance with GCP. For 
example, the IRB General Assurance Number may be accepted as a substitute for this list. Formal 
approval by the IRB/EC should mention the protocol title, number, amendment number (if 
applicable), study site (or region or area of jurisdiction, as applicable), and any other documents 
reviewed. It must mention the date on which the decision was made and must be officially signed 
by a committee member. Before the first subject is enrolled in the study, all ethical and legal 
requirements must be met.
The IRB/EC and, if applicable, the authorities, must be informed of all subsequent protocol 
amendments in accordance with local legal requirements. Amendments must be evaluated to 
determine whether formal approval must be sought and whether the ICF should also be revised.
The Investigator must keep a record of all communication with the IRB/EC and, if applicable, 
between a Coordinating Investigator and the IRB/EC. This statement also applies to any 
communication between the Investigator (or Coordinating Investigator, if applicable) and 
regulatory authorities.
Any advertisements used to recruit subjects for the study must be reviewed by Celgene and the 
IRB/EC prior to use.  
12.7
Ongoing Information for Institutional Review Board/ Ethics Committee
If required by legislation or the IRB/EC, the Investigator must submit to the IRB/EC:

Information on serious or unexpected adverse events as soon as possible; 

Periodic reports on the progress of the study;

Deviations from the protocol or anything that may involve added risk to subjects.
12.8
Termination of the Study
Celgene reserves the right to terminate this study prematurely at any time for reasonable medical 
or administrative reasons. Any premature discontinuation will be appropriately documented 
according to local requirements (eg, IRB/EC, regulatory authorities, etc.).
In addition, the Investigator or Celgene has the right to discontinue a single site at any time during 
the study for medical or administrative reasons such as:

Unsatisfactory enrollment;

GCP noncompliance;

Inaccurate or incomplete data collection;

Falsification of records;

Failure to adhere to the study protocol.
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Approved
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Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
70
13
DATA HANDLING AND RECORDKEEPING
13.1
Data/Documents
The Investigator must ensure that the records and documents pertaining to the conduct of the study 
and the distribution of the investigational product are complete, accurate, filed and retained.  
Examples of source documents include: hospital records; clinic and office charts; laboratory notes; 
memoranda; subject’s diaries or evaluation checklists; dispensing records; recorded data from 
automated instruments; copies or transcriptions certified after verification as being accurate copies; 
microfiche; x-ray film and reports; and records kept at the pharmacy, and the laboratories, as well 
as copies of CRFs or CD-ROM.
13.2
Data Management
Data will be collected via CRF and entered into the clinical database per Celgene SOPs. This data 
will be electronically verified through use of programmed edit checks specified by the clinical 
team.  Discrepancies in the data will be brought to the attention of the clinical team, and 
investigational site personnel, if necessary.  Resolutions to these issues will be reflected in the 
database.  An audit trail within the system will track all changes made to the data.
13.3
Record Retention
Essential documents must be retained by the Investigator according to the period of time outlined 
in the clinical trial agreement. The Investigator must retain these documents for the time period 
described above or according to local laws or requirements, whichever is longer. Essential 
documents include, but are not limited to, the following:

Signed ICFs for all subjects;

Subject identification code list, screening log (if applicable), and enrollment log;

Record of all communications between the Investigator and the IRB/EC;

Composition of the IRB/EC;

Record of all communications between the Investigator, Celgene, and their authorized 
representative(s);

List of Sub-investigators and other appropriately qualified persons to whom the Investigator 
has delegated significant study-related duties, together with their roles in the study, curriculum 
vitae, and their signatures;

Copies of CRFs (if paper) and of documentation of corrections for all subjects;

IP accountability records;

Record of any body fluids or tissue samples retained;

All other source documents (subject records, hospital records, laboratory records, etc); 

All other documents as listed in Section 8 of the ICH consolidated guideline on GCP (Essential 
Documents for the Conduct of a Clinical Trial).
The Investigator must notify Celgene if he/she wishes to assign the essential documents to 
someone else, remove them to another location or is unable to retain them for a specified period.  
The Investigator must obtain approval in writing from Celgene prior to destruction of any records. 
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Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
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If the Investigator is unable to meet this obligation, the Investigator must ask Celgene for 
permission to make alternative arrangements. Details of these arrangements should be 
documented. 
All study documents should be made available if required by relevant health authorities. 
Investigator or institution should take measures to prevent accidental or premature destruction of 
these documents.
14
QUALITY CONTROL AND QUALITY ASSURANCE
All aspects of the study will be carefully monitored by Celgene or its authorized representative for 
compliance with applicable government regulations with respect to current GCP and SOPs.
14.1
Study Monitoring and Source Data Verification
Celgene ensures that appropriate monitoring procedures are performed before, during and after the 
study.  All aspects of the study are reviewed with the Investigator and the staff at a study initiation 
visit and/or at an Investigators’ Meeting.  Prior to enrolling subjects into the study, a Celgene 
representative will review the protocol, CRFs, procedures for obtaining informed consent, record 
keeping, and reporting of AEs/SAEs with the Investigator. Monitoring details describing strategy, 
including definition of study critical data items and processes (eg, risk-based initiatives in 
operations and quality such as risk management and mitigation strategies and analytical risk-based 
monitoring), methods, responsibilities, and requirements, including handling of noncompliance 
issues and monitoring techniques (central, remote, or on-site monitoring) are provided in the 
monitoring plan.
Accuracy will be checked by performing source data verification that is a direct comparison of the 
entries made onto the CRFs against the appropriate source documentation.  Any resulting 
discrepancies will be reviewed with the Investigator and/or his/her staff.  Any necessary 
corrections will be made directly to the CRFs or via queries by the Investigator and/or his/her staff. 
Monitoring procedures require that informed consents, adherence to inclusion/exclusion criteria 
and documentation of SAEs and their proper recording be verified.  Additional monitoring 
activities may be outlined in a study-specific monitoring plan.
14.2
Audits and Inspections
In addition to the routine monitoring procedures, a Good Clinical Practice Quality Assurance unit 
exists within Celgene.  Representatives of this unit will conduct audits of clinical research activities 
in accordance with Celgene SOPs to evaluate compliance with Good Clinical Practice guidelines 
and regulations.
The Investigator is required to permit direct access to the facilities where the study took place, 
source documents, CRFs and applicable supporting records of study subject participation for audits 
and inspections by IRB/ECs, regulatory authorities (eg, FDA, EMA) and company authorized 
representatives.  The Investigator should make every effort to be available for the audits and/or 
inspections.  If the Investigator is contacted by any regulatory authority regarding an inspection, 
he/she should contact Celgene immediately.
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930197032
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Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
72
14.3
Product Quality Complaint
Issues that call into question 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 an issue or concern with all sponsor 
supplied IP suspected to have occurred before the product was transferred to the responsibility of 
the investigational site (eg, during manufacturing, packaging, and labeling, storage, and/or 
distribution).
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).
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.
1.0
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930197032
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Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
73
15
PUBLICATIONS
As described in Section 12.2, all protocol- and amendment-related information, with the exception 
of the information provided by Celgene on public registry websites, is considered Celgene 
confidential information and is not to be used in any publications.  Celgene protocol-related 
information proposed for use in a publication must be submitted to Celgene for review and 
approval and should not be utilized in a publication without express written approval from 
Celgene, or as described in the Clinical Trial Agreement.
Celgene will ensure Celgene-sponsored studies are considered for publication in the scientific 
literature in a peer-reviewed journal, irrespective of the results.  At a minimum, this applies to 
results from all Phase 3 clinical studies, and any other study results of significant medical 
importance.  This also includes results relating to investigational medicines whose development 
programs have been discontinued.
Study results may also be presented at one or more medical congresses and may be used for 
scientific exchange and teaching purposes.  Additionally, this study and its results may be 
submitted for inclusion in all appropriate health authority study registries, as well as publication 
on health authority study registry websites, as required by local health authority regulations.
Eligibility for external authorship, as well as selection of first authorship, will be based on several 
considerations, including, but not limited to, contribution to protocol development, study 
recruitment, data quality, participation in data analysis, participation in study steering committee 
(when applicable) and contribution to abstract, presentation and/or publication development.
1.0
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930197032
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Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
74
16
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930197032
1.0
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Approved
1.0
v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
75
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Approved
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v

Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
76
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Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
77
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1.0
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1.0
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Ozanimod
Protocol RPC-1063-MS-010
Celgene Corporation
RPC-1063-MS-010 Amendment 1.0
Date 29 NOV 2022
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APPENDIX A
TABLE OF ABBREVIATIONS
Table 7:
Abbreviations and Specialist Terms
Abbreviation or Specialist 
Term
Explanation
AAN
American Academy of Neurology
ACTH
Adrenocorticotropic hormone
ADL
Activities of daily life
AE
Adverse event
ALC
Absolute lymphocyte count
ALT
Alanine aminotransferase (SGPT)
ANC
Absolute neutrophil count
ARR
Annualized relapse rate
AST
Aspartate aminotransferase (SGOT)
β-hCG
β-subunit of human chorionic gonadotropin
BMI
Body mass index
BTK
Bruton’s tyrosine kinase
CDC
Centers for Disease Control
CI
Confidence interval 
CNS
Central nervous system
COVID-19
SARS-CoV-2
CRF
Case report form
DMT
Disease modifying therapy
EC
Ethics committee
EEA
European economic area
EMA
European Medicines Agency
EOS
End of study
EU
European Union
FCBP
Female of childbearing potential 
FDA
Food and Drug Administration
GA
Glatiramer acetate
GCP
Good Clinical Practice
GdE
Gadolinium-enhancing 
GGT
Gamma-glutamyltransferase
GMC
Geometric mean concentration
GMT
Geometric mean titer
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Table 7:
Abbreviations and Specialist Terms
Abbreviation or Specialist 
Term
Explanation
HI
Hemagglutination
ICF
Informed consent form
ICH
International Council on Harmonisation
IFN
Interferon
IgG
Immunoglobulin G
IgM
Immunoglobulin M
IM
Intramuscular
IND
Investigational new Drug
INR
International normalized ratio
IP
Investigational product
IRB
Institutional review board
IVIg
Intravenous immunoglobulin 
IV
Intravenous
LAM
Lactational amenorrhea method 
MCH
Mean Corpuscular Hemoglobin 
MCHC
Mean corpuscular hemoglobin concentration 
MCV
Mean corpuscular volume 
MedDRA
Medical Dictionary for Regulatory Activities
mITT
Modified intent-to-treat
MS
Multiple sclerosis
NSAID
Non-steroidal anti-inflammatory drug 
PD
Pharmacodynamic 
PI
Principal Investigator 
PK
Pharmacokinetics
PP
Per protocol 
PPSV23
Pneumococcal polysaccharide vaccine
RBC
Red blood cell
RMS
Relapsing multiple sclerosis
RRMS
Relapsing remitting multiple sclerosis
S1P
Sphingosine-1-phosphate
SAE
Serious adverse event
SC
Subcutaneous 
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Table 7:
Abbreviations and Specialist Terms
Abbreviation or Specialist 
Term
Explanation
SGOT
Serum glutamic oxaloacetic transaminase 
SGPT
Serum glutamic pyruvic transaminase
SmPC
Summary of Product Characteristics
SOP
Standard operating procedure
STIKO
Standing Committee on Vaccination at the Robert Koch Institute
SUSAR
Suspected unexpected serious adverse reaction
Tdap
Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine, adsorbed 
ULN
Upper limit of normal
US
United States of America
USPI
US Prescribing Information 
WBC
White blood cell 
WHO
World Health Organization
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