A 12-month, Open-label, Prospective, Multicenter, Interventional, Single-arm Study Assessing the Efficacy and Safety of Ofatumumab 20 mg Subcutaneous (s.c.) Injection in Relapsing Multiple Sclerosis (RMS) Patients in China
Phase: PHASE4
Conditions: Relapsing Multiple Sclerosis
Sponsor: Novartis Pharmaceuticals

Novartis Research and Development 
OMB157/Ofatumumab 
Clinical Trial Protocol COMB157G2402 / NCT05199571
A 12-month, open-label, prospective, multicenter, 
interventional, single-arm study assessing the efficacy and 
safety of ofatumumab 20mg s.c. injection in relapsing 
multiple sclerosis (RMS) patients in China 
Document type: 
Clinical Trial Protocol 
EUDRACT number: 
NA 
Version number: 
00 (Original Protocol) 
Clinical Trial Phase: 
IV 
Release date: 
08-Nov-2021 (content final)
Property of Novartis 
Confidential 
May not be used, divulged, published, or otherwise disclosed 
without the consent of Novartis 
Clinical Trial Protocol Template Version 4.0 dated 15-Feb-2021 

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Clinical Trial Protocol (Version No. 00) 
 
Protocol No. COMB157G2402 
 
Table of contents 
Table of contents ................................................................................................................. 2 
List of tables ........................................................................................................................ 5 
List of figures ...................................................................................................................... 5 
List of abbreviations ............................................................................................................ 6 
Glossary of terms ................................................................................................................. 9 
Protocol summary .............................................................................................................. 11 
1 
Introduction ....................................................................................................................... 13 
1.1 
Background ............................................................................................................ 13 
1.2 
Purpose .................................................................................................................. 15 
2 
Objectives and endpoints ................................................................................................... 15 
3 
Study design ...................................................................................................................... 16 
4 
Rationale ............................................................................................................................ 17 
4.1 
Rationale for study design ..................................................................................... 17 
4.2 
Rationale for dose/regimen and duration of treatment .......................................... 17 
4.3 
Rationale for choice of control drugs (comparator/placebo) or combination 
drugs ...................................................................................................................... 18 
4.4 
Purpose and timing of interim analyses/design adaptations .................................. 18 
4.5 
Risks and benefits .................................................................................................. 18 
4.5.1 
Imaging Risk ......................................................................................... 19 
4.6 
Rationale for Public Health Emergency mitigation procedures ............................ 19 
5 
Study Population ............................................................................................................... 19 
5.1 
Inclusion criteria .................................................................................................... 20 
5.2 
Exclusion criteria ................................................................................................... 20 
6 
Treatment ........................................................................................................................... 23 
6.1 
Study treatment ...................................................................................................... 23 
6.1.1 
Investigational and control drugs .......................................................... 24 
6.1.2 
Additional study treatment .................................................................... 24 
6.1.3 
Treatment arms...................................................................................... 24 
6.1.4 
Treatment duration ................................................................................ 24 
6.2 
Other treatment(s) .................................................................................................. 24 
6.2.1 
Concomitant therapy ............................................................................. 24 
6.2.2 
Prohibited medication ........................................................................... 25 
6.2.3 
Recommended treatment for MS relapses ............................................ 26 
6.3 
Preparation and dispensation ................................................................................. 26 
6.3.1 
Handling of study treatment and other treatment .................................. 27 
6.3.2 
Instruction for prescribing and taking study treatment ......................... 27 

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6.4 
Participant numbering, treatment assignment, randomization .............................. 28 
6.4.1 
Participant numbering ........................................................................... 28 
6.4.2 
Treatment assignment, randomization .................................................. 29 
6.5 
Treatment blinding ................................................................................................ 29 
6.6 
Dose escalation and dose modification.................................................................. 29 
6.7 
Additional treatment guidance ............................................................................... 29 
6.7.1 
Treatment compliance ........................................................................... 29 
7 
Informed consent procedures ............................................................................................ 29 
8 
Visit schedule and assessments ......................................................................................... 31 
8.1 
Screening ............................................................................................................... 38 
8.1.1 
Information to be collected on screening failures ................................. 38 
8.2 
Participant demographics/other baseline characteristics ....................................... 38 
8.3 
Efficacy .................................................................................................................. 39 
8.3.1 
Efficacy assessment 1 ........................................................................... 39 
8.3.2 
Efficacy assessment 2 ........................................................................... 40 
8.3.3 
Efficacy assessment 3 ........................................................................... 41 
8.3.4 
Appropriateness of efficacy assessments .............................................. 41 
8.4 
Safety ..................................................................................................................... 41 
8.4.1 
Laboratory evaluations .......................................................................... 42 
8.4.2 
Electrocardiogram (ECG) ..................................................................... 43 
8.4.3 
Pregnancy and assessments of fertility ................................................. 44 
8.4.4 
Appropriateness of safety measurements .............................................. 45 
8.5 
Additional assessments .......................................................................................... 45 
8.5.1 
Clinical Outcome Assessments (COAs) ............................................... 45 
9 
Discontinuation and completion ........................................................................................ 45 
9.1 
Discontinuation from study treatment and from study .......................................... 45 
9.1.1 
Discontinuation from study treatment ................................................... 45 
9.1.2 
Discontinuation from study ................................................................... 46 
9.1.3 
Lost to follow-up ................................................................................... 46 
9.2 
Withdrawal of informed consent/Opposition to use data/biological samples ....... 47 
9.3 
Study completion and post-study treatment .......................................................... 47 
9.4 
Early study termination by the sponsor ................................................................. 48 
10 Safety monitoring, reporting and committees ................................................................... 48 
10.1 
Definition of adverse events and reporting requirements ...................................... 48 
10.1.1 
Adverse events ...................................................................................... 48 
10.1.2 
Serious adverse events .......................................................................... 50 

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10.1.3 
SAE reporting........................................................................................ 51 
10.1.4 
Pregnancy reporting .............................................................................. 52 
10.1.5 
Reporting of study treatment errors including misuse/abuse ................ 52 
10.2 
Additional Safety Monitoring ................................................................................ 53 
10.2.1 
Liver safety monitoring ......................................................................... 53 
10.2.2 
Renal safety monitoring ........................................................................ 53 
10.3 
Committees ............................................................................................................ 54 
11 Data Collection and Database management ...................................................................... 54 
11.1 
Data collection ....................................................................................................... 54 
11.2 
Database management and quality control ............................................................ 54 
11.3 
Site monitoring ...................................................................................................... 55 
12 Data analysis and statistical methods ................................................................................ 56 
12.1 
Analysis sets .......................................................................................................... 56 
12.2 
Participant demographics and other baseline characteristics ................................. 56 
12.3 
Treatments ............................................................................................................. 56 
12.4 
Analysis supporting primary objectives ................................................................ 57 
12.4.1 
Definition of primary endpoint(s) ......................................................... 57 
12.4.2 
Statistical model, hypothesis, and method of analysis .......................... 57 
12.4.3 
Handling of missing visits/censoring/discontinuation .......................... 57 
12.4.4 
Supportive analysis ............................................................................... 58 
12.5 
Analysis supporting secondary objectives ............................................................. 58 
12.5.1 
Efficacy and/or Pharmacodynamic endpoint(s) .................................... 58 
12.5.2 
Safety endpoints .................................................................................... 58 
 
 60 
12.7 
Interim analyses ..................................................................................................... 60 
12.8 
Sample size calculation.......................................................................................... 60 
12.8.1 
Primary endpoint(s) ............................................................................... 60 
13 Ethical considerations and administrative procedures ...................................................... 61 
13.1 
Regulatory and ethical compliance ........................................................................ 61 
13.2 
Responsibilities of the investigator and IRB/IEC .................................................. 61 
13.3 
Publication of study protocol and results............................................................... 61 
13.4 
Quality Control and Quality Assurance ................................................................. 62 
13.5 
Participant Engagement ......................................................................................... 62 
14 Protocol adherence ............................................................................................................ 62 
14.1 
Protocol amendments............................................................................................. 63 
15 References ......................................................................................................................... 64 

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16 Appendices ........................................................................................................................ 66 
16.1 
Appendix 1: Liver event and laboratory trigger definitions & follow-up 
requirements .......................................................................................................... 66 
16.2 
Appendix 2: Specific Renal Alert Criteria and Actions and Event Follow-up ...... 68 
16.3 
Appendix 3: The 2017 McDonald criteria for diagnosis of multiple sclerosis 
in patients with an attack at onset .......................................................................... 68 
16.4 
Appendix 4: Guidance on safety monitoring and immunization ........................... 69 
16.4.1 
Guidance on monitoring of participants with symptoms of 
neurological deterioration suggestive of PML ...................................... 69 
16.4.2 
Guidance on monitoring participants with infections ........................... 70 
16.4.3 
Guidance on monitoring of participants with low immunoglobulin 
levels ..................................................................................................... 70 
16.4.4 
Guidance on immunization ................................................................... 71 
List of tables 
Table 2-1 
Objectives and related endpoints .......................................................... 15 
Table 6-1 
Investigational drug ............................................................................... 24 
Table 6-2 
Prohibited medication ........................................................................... 25 
Table 8-1 
Assessment Schedule, Screening and treatment ................................... 33 
Table 8-2 
Assessment Schedule, Post-Treatment Follow-up ................................ 36 
Table 8-3 
Assessments & Specifications............................................................... 42 
Table 8-4 
Laboratory assessments ......................................................................... 42 
Table 10-1 
Guidance for capturing the study treatment errors including 
misuse/abuse ......................................................................................... 53 
Table 16-1 
Follow up requirements for liver laboratory triggers ............................ 66 
Table 16-2 
Follow up requirements for isolated total bilirubin elevation ............... 67 
Table 16-3 
Specific Renal Alert Criteria and Actions ............................................. 68 
Table 16-4 
2017 McDonald criteria for diagnosis of multiple sclerosis in 
patients with an attack at onset.............................................................. 68 
List of figures 
Figure 3-1 
Study Design ......................................................................................... 17 
Figure 8-1 
Timing of study procedures .................................................................. 43 
 

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List of abbreviations 
 
  
AE 
Adverse Event 
AEP 
Accelerated Elimination Procedure 
AIDS 
Acquired Immune Deficiency Syndrome 
AKI 
Acute Kidney Injury  
ALP 
Alkaline Phosphatase 
ALT 
Alanine Aminotransferase 
ARR 
Annualized Relapse Rate  
AST 
Aspartate Aminotransferase 
ATC 
Anatomical Therapeutic Chemical 
BIL 
Bilirubin 
BL 
Baseline 
BTK 
Bruton's Tyrosine Kinase 
BUN 
Blood Urea Nitrogen 
CDP 
Confirmed Disability Progression  
CFR 
Code of Federal Regulations 
CIS 
Clinically Isolated Syndrome  
CK 
Creatine Kinase 
CKD 
Chronic Kidney Disease 
cm 
centimeter 
CMO&PS  
Chief Medical Office and Patient Safety 
CNS 
Central Nervous System  
CO 
Country Organization 
COA 
Clinical Outcome Assessment 
COVID 
Corona Virus Disease 
CRA 
Clinical Research Associate 
CRF 
Case Report/Record Form (paper or electronic) 
CRO 
Contract Research Organization 
CSF 
Cerebrospinal Fluid 
CSR 
Clinical Study Report 
CT 
Computerized Tomography 
CTCAE 
Common Terminology Criteria for Adverse Events  
DDE 
Direct Data Entry 
DMTs 
Disease-Modifying Therapies  
ECG 
Electrocardiogram 
EDC 
Electronic Data Capture 
EDSS 
Expanded Disability Status Scale  
eGFR 
estimated Glomerular Filtration Rate 
EMA 
European Medicines Agency 
EOS 
End of Study 
eSAE 
electronic Serious Adverse Event 
eSource 
electronic Source 
FAS 
Full Analysis Set  
FDA 
Food and Drug Administration 
FS 
Functional Systems  
FSH 
Follicle Stimulating Hormone 

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GBCA 
Gadolinium-Based Contrast Agent  
GCP 
Good Clinical Practice 
Gd 
Gadolinium 
GGT 
Gamma-glutamyl transferase 
GLDH 
Glutamate Dehydrogenase 
HA 
Health Authority 
HBcAb 
Hepatitis B core Antibody  
HBsAg 
Hepatitis B surface Antigen 
HBV 
Hepatitis B Virus 
hCG 
human Chorionic Gonadotropin 
HIV 
Human Immunodeficiency Virus 
i.v. 
intravenous 
IA 
Interim Analysis  
IB 
Investigator's Brochure 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonization of Technical Requirements for Pharmaceuticals for 
Human Use 
ID 
Identification 
IEC 
Independent Ethics Committee 
IFNβ-1a 
Interferon β-1a 
IFNβ-1b 
Interferon β-1b 
IgG 
Immunoglobin G 
IgM 
Immunoglobin M 
IMP 
Investigational Medicinal Product 
IN 
Investigator Notification 
INR 
International Normalized Ratio 
IRB 
Institutional Review Board 
kg 
kilogram 
LFT 
Liver Function Test 
LLN 
Lower Limit of Normal 
M 
Month 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
milligram 
MHRA 
Medicines and Healthcare products Regulatory Agency 
mL 
milliliter 
MRI 
Magnetic Resonance Imaging 
mRNA 
messenger Ribonucleic Acid 
MS 
Multiple Sclerosis  
NFS 
Nephrogenic Systemic Fibrosis  
NMOSD 
Neuromyelitis Optica Spectrum Disorder  
NMPA 
National Medical Products Administration  
Nrf2 
Nuclear Factor (erythroid-derived 2)-like 2 
NYHA 
New York Heart Association 
PAC 
Post-Approval Commitment 
PCR 
Protein-creatinine Ratio 
PML 
Progressive Multifocal Leukoencephalopathy 
PMS 
Progressive Multiple Sclerosis  

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PPMS 
Primary Progressive Multiple Sclerosis  
PRO 
Patient Reported Outcome 
PT 
Prothrombin Time 
PT FU 
Post-treatment Follow-up 
PTA 
Post Trial Access 
QMS  
Quality Management System 
QTcF 
QT interval corrected by Fridericia's formula 
RMS 
Relapsing Multiple Sclerosis  
RRMS 
Relapsing Remitting Multiple Sclerosis 
s.c. 
subcutaneous 
SAE 
Serious Adverse Event 
SAF 
Safety Set  
SAP 
Statistical Analysis Plan  
Sars-CoV-2 
Severe acute respiratory syndrome Coronavirus 2 
SD 
Standard Deviation 
SOP 
Standard Operating Procedure 
SPMS 
Secondary Progressive Multiple Sclerosis  
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
TB 
Tuberculosis 
TBL 
Total Bilirubin Level 
TFQ 
Trial Feedback Questionnaire 
UK 
United Kingdom 
ULN 
Upper Limit of Normal 
UTI 
Urinary Tract Infection 
W 
Week 
WHO 
World Health Organization  
WoC 
Withdrawal of Consent 

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Glossary of terms 
Assessment 
A procedure used to generate data required by the study 
Biologic Samples 
A biological specimen including, for example, blood (plasma, serum), saliva, 
tissue, urine, stool, etc. taken from a study participant  
Clinical Outcome 
Assessment (COA) 
A measure that describes or reflects how a participant feels, functions, or survives 
Clinical Trial Team 
A group of people responsible for the planning, execution and reporting of all 
clinical trial activities. Examples of team members include the Study Lead, 
Medical Monitor, Trial Statistician etc. 
Coded Data 
Personal Data which has been de-identified by the investigative center team by 
replacing personal identifiers with a code. 
Discontinuation from 
study 
Point/time when the participant permanently stops receiving the study treatment 
and further protocol required assessments or follow-up, for any reason. No 
specific request is made to stop the use of their samples or data. 
Discontinuation from 
study treatment 
Point/time when the participant permanently stops receiving the study treatment 
for any reason (prior to the planned completion of study drug administration, if 
any). Participant agrees to the other protocol required assessments including 
follow-up. No specific request is made to stop the use of their samples or data. 
Dosage 
Dose of the study treatment given to the participant in a time unit (e.g. 100 mg 
once a day, 75 mg twice a day) 
Electronic Data Capture 
(EDC) 
Electronic data capture (EDC) is the electronic acquisition of clinical study data 
using data collection systems, such as Web-based applications, interactive voice 
response systems and clinical laboratory interfaces. EDC includes the use of 
Electronic Case Report Forms (eCRFs) which are used to capture data 
transcribed from source data/documents used at the point of care 
End of the clinical trial 
The end of the clinical trial is defined as the last visit of the last participant 
Enrollment 
Point/time of participant entry into the study at which informed consent must be 
obtained. The action of enrolling one or more participants 
eSource (DDE) 
eSource Direct Data Entry (DDE) refers to the capture of clinical study data 
electronically, at the point of care. eSource Platform/Applications combines 
source documents and case report forms (eCRFs) into one application, allowing 
for the real time collection of clinical trial information to sponsors and other 
oversight authorities, as appropriate 
Investigational drug/ 
treatment 
The drug whose properties are being tested in the study 
Medication number 
A unique identifier on the label of medication kits 
Off-site 
Describes trial activities that are performed at remote location by an off-site 
healthcare professional, such as procedures performed at the participant's home. 
Off-site healthcare 
Professional (OHP) 
A qualified healthcare professional, such as include those used in the study e.g. 
Nurse, Phlebotomist, Physician, who performs certain protocol procedures for the 
participant in an off-site location such as a participant's home. 
Other treatment 
Treatment that may be needed/allowed during the conduct of the study (i.e. 
concomitant or rescue therapy) 
Participant 
A trial participant (can be a healthy volunteer or a patient). "Participant" 
terminology is used in the protocol whereas term "Subject" is used in data 
collection 
Participant number 
A unique number assigned to each participant upon signing the informed consent. 
This number is the definitive, unique identifier for the participant and should be 
used to identify the participant throughout the study for all data collected, sample 
labels, etc. 
Period 
The subdivisions of the trial design (e.g. Screening, Treatment, Follow-up) which 
are described in the Protocol. Periods define the study phases and will be used in 
clinical trial database setup and eventually in analysis 

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Personal data 
Participant information collected by the Investigator that is coded and transferred 
to Novartis for the purpose of the clinical trial. This data includes participant 
identifier information, study information and biological samples. 
Premature participant 
withdrawal 
Point/time when the participant exits from the study prior to the planned 
completion of all study drug administration and/or assessments; at this time all 
study drug administration is discontinued and no further assessments are planned 
Re-screening 
If a participant fails the initial screening and is considered as a Screen Failure, 
he/she can be invited once for a new Screening visit after medical judgment and 
as specified by the protocol 
Remote 
Describes any trial activities performed at a location that is not the investigative 
site where the investigator will conduct the trial, but is for example a home or 
another appropriate location 
Screen Failure 
A participant who did not meet one or more criteria that were required for 
participation in the study 
Source Data/Document 
Source data refers to the initial record, document, or primary location from where 
data comes. The data source can be a database, a dataset, a spreadsheet or 
even hard-coded data, such as paper or eSource 
Start of the clinical trial 
The start of the clinical trial is defined as the signature of the informed consent by 
the first participant 
Study treatment 
Any drug or combination of drugs or intervention administered to the study 
participants as part of the required study procedures; includes investigational 
drug(s), control(s) or background therapy 
Study treatment 
discontinuation 
When the participant permanently stops taking any of the study drug(s) prior to 
the defined study treatment completion date (if any) for any reason; may or may 
not also be the point/time of study discontinuation  
Tele-visit 
Procedures or communications conducted using technology such as telephone or 
video-conference, whereby the participant is not at the investigative site where 
the investigator will conduct the trial. 
Variable (or endpoint) 
A measured value or assessed response that is determined in specific 
assessments and used in data analysis to evaluate the drug being tested in the 
study. 
Withdrawal of study 
consent (WoC) / 
Opposition to use of data 
/biological samples 
Withdrawal of consent from the study occurs when the participant explicitly 
requests to stop use of their data and biological samples (opposition to use data 
and biological samples) AND no longer wishes to receive study treatment, AND 
does not agree to further protocol required assessments. This request should be 
in writing (depending on local regulations) and recorded in the source 
documentation. 
Opposition to use data/biological samples occurs in the countries where collection 
and processing of personal data is justified by a different legal reason than 
consent. 

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Clinical Trial Protocol (Version No. 00) 
 
Protocol No. COMB157G2402 
 
Protocol summary 
Protocol 
number 
COMB157G2402 
Full Title 
A 12-month, open-label, prospective, multicenter, interventional, single-arm study assessing 
the efficacy and safety of ofatumumab 20 mg subcutaneous (s.c.) injection in relapsing 
multiple sclerosis (RMS) patients in China 
Brief title 
Study of efficacy and safety of ofatumumab in relapsing multiple sclerosis (RMS) patients in 
China 
Sponsor and 
Clinical phase 
Novartis; Phase IV 
Investigation 
type 
Biological 
Study type 
Interventional 
Purpose 
The purpose of this study is to evaluate the efficacy and safety of ofatumumab s.c. in adult 
participants with relapsing multiple sclerosis (RMS) in China, as part of a post-approval 
commitment to the Health Autorithy in China. The study will also be used for ofatumumab's 
license renewal. 
Primary 
Objective(s)  
The primary objective of this trial is to evaluate the effect of ofatumumab 20 mg monthly s.c. 
on annualized relapse rate (ARR) in participants with RMS  
Secondary 
Objectives 
● To evaluate the safety and tolerability of ofatumumab 20 mg monthly s.c. in participants 
with RMS 
● To evaluate the effect of ofatumumab 20 mg monthly s.c. on MRI lesions in participants 
with RMS  
Study design 
Prospective, open-label, single arm, multi-center, interventional study. 
The study is composed of 3 periods with around 100 enrolled participants: 
● Screening period (up to 30 days) 
● Treatment period (12 months) 
● Post-treatment Follow-up period (6 months) 
Rationale 
The clinical development program of ofatumumab has demonstrated efficacy and safety of 
ofatumumab 20 mg monthly s.c. for the treatment of participants with RMS globally in two 
pivotal clinical studies, COMB157G2301 and COMB157G2302. Chinese participants were 
not enrolled into these studies. To support the local approval of ofatumumab as a treatment 
for RMS in China, the National Medical Products Administration (NMPA) in China requested 
a post-approval study to collect efficacy and safety data of ofatumumab 20 mg monthly s.c. 
in adult Chinese RMS participants. 
Study 
population 
Adult participants with RMS 
Key Inclusion 
criteria 
1. Signed informed consent must be obtained prior to participation in the study. 
2. Male or female Chinese aged 18-55 years (inclusive) at their enrollment of the study 
(signing the study consent form). 
3. Clinical definite diagnosis of RMS according to the 2017 Revised McDonald criteria 
(Thompson et al 2018）,  
and the documentation prior to their enrollment to the study (signing the study consent form) 
of: 
 
● Two documented relapses during the past 2 years, or 
 
● One documented relapse during the last year, or 
 
● A positive Gd-enhancing MRI scan during the year prior to Screening. Note: Screening 
MRI scan may be used if no positive Gd-enhancing scan exists from prior year. 
4. Disability status with an EDSS score of 0 - 5.5 (inclusive) at Screening. 
5. Neurologically stable within 1 month prior to both Screening and Baseline (including no 
MS relapse in this period). 
Key Exclusion 
criteria 
1. Participants with primary progressive MS (PPMS) or secondary progressive MS (SPMS) 
without disease activity 
2. Participants meeting criteria for neuromyelitis optica spectrum disorder (NMOSD) 
3. Pregnant or nursing (lactating) women 
4. Women of child-bearing potential unless using effective methods of contraception while 

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taking study treatment and for at least 6 months after stopping medication 
5. Participants with an active chronic disease of the immune system other than MS 
6. Participants with neurological findings consistent with PML or confirmed PML 
7. Participants with active hepatitis B disease 
8. Participants with active systemic infections (including but not limited to active COVID-19 
infection) or known to have AIDS or to test positive for HIV antibody at Screening 
9. Participants at high risk of developing or having reactivation of syphilis or tuberculosis 
10. Have received any live or live-attenuated vaccines within four weeks prior to first study 
drug administration 
11. Have been treated with medications as specified or within timeframes specified in the 
protocol 
12. Any other disease or condition that could interfere with participation in the study 
according to the study protocol, or with the ability of the participants to cooperate and 
comply with the study procedures. 
Study 
treatment 
Ofatumumab 20 mg sc injections at Week 0, 1, 2 and monthly thereafter starting at Week 4, 
administered using an autoinjector 
Efficacy 
assessments 
● MS relapse 
● Expanded Disability Status Scale (EDSS) 
● Magnetic Resonance Imaging (MRI) 
Key safety 
assessments 
● Adverse events 
● Physical/neurological examinations (including skin) 
● Vital signs 
● Laboratory evaluations (blood and urine) 
Other 
assessment 
Trial Feedback Questionnaire (TFQ) (optional) 
Data analysis 
Data will be analyzed using summaries and/or statistical models on different analysis sets as 
appropriate. Annualized relapse rate (ARR) will be analyzed using a negative binomial 
model. The number of Gd-enhancing T1 lesions per MRI scan as well as the annualized rate 
of new or enlarging T2 lesions will also be analyzed using a negative binomial model. 
Change in T2 lesion volume will be summarized by visit. All safety endpoints as well as the 
 will be statistically summarized appropriately. 
Key words 
Relapsing multiple sclerosis, open-label, interventional, efficacy and safety, ofatumumab. 

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1 
Introduction 
1.1 
Background 
The disease: relapsing multiple sclerosis (RMS) 
Multiple sclerosis (MS) is a chronic, immune-mediated disease of the central nervous system 
(CNS) characterized by inflammation, demyelination, and axonal/neuronal destruction, 
ultimately leading to severe disability. MS is the most common autoimmune demyelinating 
disorder of the CNS, affecting approximately 2.8 million individuals worldwide (MSIF 2020). 
MS typically affects young adults (mean age at onset 30 years) and women are affected more 
often than men. 
Reflecting the current understanding of MS, the disease course is traditionally grouped into 2 
main categories: 
1. Relapsing MS (RMS): clinically isolated syndrome (CIS), relapsing-remitting multiple 
sclerosis (RRMS), active secondary progressive MS (SPMS) 
2. Progressive MS (PMS): SPMS without relapses and primary progressive MS (PPMS) 
At the time of their first MS diagnosis, approximately 80% to 85% of patients present initially 
with RRMS, characterized by recurrent acute exacerbations (relapses) of neurological 
dysfunction followed by a variable state of recovery. Most patients with RRMS may progress 
to SPMS, which is a stage of the disease that is characterized by continuous worsening of 
disability independent of relapses. Approximately 10% of patients suffer from PPMS, 
characterized by accumulation of disability since the beginning of the disease with or without 
superimposed relapses (MSIF 2020, Claes et al 2015, D'Amico et al 2019). MS prevalence in 
China is lower than that in western countries, with approximately 3 cases per 100,000 people 
in China comparing to >200 cases per 100,000 people in North America (MSIF 2020). In recent 
years, with increased awareness and revisions to the diagnostic criteria, there are more patients 
being diagnosed and treated in China. Further, the MS phenotypes, gender ratio and age range 
are comparable to Caucasian MS patients (Lau et al 2008, Cheng et al 2010, Chan et al 2011). 
Although there is currently no cure for MS, several disease-modifying therapies (DMTs) have 
been approved globally including in China. As of May 2021, there are 6 approved DMTs in 
China, including interferon β-1b (IFNβ-1b, Betaseron®), interferon β-1a (IFNβ-1a, Rebif®), 
teriflunomide (Aubagio®), fingolimod (Gilenya®), siponimod (Mayzent®) and dimethyl 
fumarate (Tecfidera®). Beta interferons have multiple immune actions but the means by which 
the drugs are effective in MS remains unknown. High-dosage IFNβ-1b showed modest (~34%) 
effect on relapses compared to placebo in RRMS patients (Goodin et al 2002). Teriflunomide, 
an orally active drug that inhibits lymphocyte proliferation, showed moderate reduction in 
disease activity (~30%) and disability (~20%) compared to placebo in RMS patients 
(O'Connor et al 2011, Gold et al 2012); fingolimod, a sphingosine-1 phosphate  receptor 
modulator, and dimethyl fumarate, which has anti-inflammatory immune response by the 
Nuclear Factor (erythroid-derived 2)-like 2 (Nrf2) dependent and independent pathways 
(Yadav et al 2019), both showed marked effect on relapse rate (~50%) and moderate effect on 
disability 
(~30%) 
compared 
to 
placebo 
in 
RMS 
patients 
(Kappos et al 2010, 
Calabresi et al 2014;Gold et al 2012, Arnold et al 2014). Siponimod, a selective sphingosine-1-

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phosphate (S1P) receptors modulator, showed significant effect on active MRI lesions (~70%) 
compared to placebo at the approved dose in a Phase 2 study in RRMS patients 
(Selmaj et al 2013), marked reduction of ARR (55%) and some effect on disability (~20%) 
relatieve to placebo in SPMS patients in a large Phase 3 trial (Kappos et al 2018). 
Recently, with the discovery of the roles of B-cells in the contribution to the immune-mediated 
histopathology in MS (Archelos et al 2000, Frohman et al 2006, McFarland 2008), B-cell 
targeted therapies have drawn some attention and are regarded as high-efficacy treatments that 
can be applied as first-line therapy early in the disease course. The first FDA-approved, 
humanized anti-CD20 monoclonal antibody, ocrelizumab, for RMS showed that B-cell 
depletion led to significantly reduced relapse rates, reduced MRI disease activity, and delayed 
the time to disability worsening vs interferon β-1a over 2 years in RMS patients. With 
ocrelizumab being administrated via intravenous route with relatively high drug dose and 
volume, the risk of infusion-related reactions and potentially limited access to infusion facilities 
need to be considered when choosing ocrelizumab as a treatment option (Hauser et al 2017). 
Ocrelizumab has not been approved by National Medical Products Administration (NMPA) in 
China. 
Ofatumumab 
Ofatumumab (OMB157) is a fully human monoclonal antibody (mAb), which targets CD20 
expressed on B-cells and a subset of T-cells. To date, ofatumumab is approved for the treatment 
of relapsing forms of MS (RMS) (Kesimpta®) in the US, European Union, Japan, Singapore 
and other countries and is among the highly effective MS DMTs (Samjoo et al 2020). 
Ofatumumab specifically recognizes a unique conformational epitope encompassing both the 
large and small extracellular loops on the human CD20 molecule, which allows ofatumumab 
binding very close to the plasma membrane. This unique composite epitope is separate from the 
epitopes on the large loop of CD20 that other anti-CD20 mAbs bind (e.g. rituximab and 
ocrelizumab) (Teeling et al 2006, Bleeker et al 2008). 
In a human CD20 transgenic mouse model, subcutaneous administration of ofatumumab 
resulted in a more direct access to lymph nodes as compared to intravenous administration of 
the drug. It is expected that the direct access to the lymphatic system, a primary location of MS 
pathology and target for MS therapies (Sabatino et al 2019), may contribute to a lower required 
dose to achieve clinical efficacy, with a corresponding better tolerability and an expected lower 
clinical risk (i.e. fewer adverse drug reactions) when compared to an intravenous route of 
administration. 
The efficacy and safety profile of ofatumumab in MS has been evaluated in different clinical 
studies. The two confirmatory Phase 3 pivotal trials (COMB157G2301 and COMB157G2302) 
consisted of randomized, double-blind, double-dummy, active comparator controlled, parallel-
group, multi-center studies of identical design in a total of 1882 RMS participants. Superiority 
of ofatumumab over teriflunomide was demonstrated independently in the two pivotal trials. 
The annualized relapse rate (ARR) was significantly reduced by >50% in both trials, leading to 
very low annualized relapse rates in participants treated with ofatumumab (ARR of 0.11 and 
0.10, respectively). Further, treatment with ofatumumab compared with teriflunomide 
significantly reduced the mean number of gadolinium (Gd)-enhancing T1 lesions per scan 

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by >90% in each of the trials. A significant reduction in the rate of new or enlarging T2 lesions 
per year by >80% was also observed. Compared to teriflunomide, ofatumumab significantly 
reduced the risk for 3-month confirmed disability progression and 6-month confirmed disability 
progression by >30% in pre-specified pooled analyses of the two trials. The results for the two 
pivotal Phase 3 studies showed that treatment with ofatumumab was well tolerated and the 
safety profile observed for ofatumumab was consistent with the expected risks associated with 
anti-CD20 antibody therapy, but with low rates and with primarily mild to moderate severity 
grades for injection-related reactions including the first injection (Hauser et al 2020). 
In a 24-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter Phase 
2 registry study in participants with RMS in Japan and Russia (COMB157G1301), ofatumumab 
demonstrated superior efficacy versus placebo, meeting the primary endpoint with a statistically 
significant reduction in the mean number of Gd-enhancing T1 lesions per scan up to Week 24 
of 94% and a consistent effect across regions (Japan/Russia). The overall safety observations 
were consistent with the known safety profile of ofatumumab in RMS patients based on the 
global pivotal Phase 3 trials (publication under journal review). 
For further details about ofatumumab and an overview of all completed and ongoing studies, 
please refer to the Investigator’s Brochure. 
As part of a post-approval commitment to the Health Authority in China, as China did not join 
previous global studies, Novartis is conducting this post-approval commitment study (PAC) in 
order to evaluate the efficacy and safety profile of ofatumumab in RMS patients in China.  
1.2 
Purpose 
The purpose of this study is to evaluate the efficacy and safety of ofatumumab 20 mg monthly 
s.c. in adult participants with relapsing multiple sclerosis (RMS) in China, as part of a post-
approval commitment to the Health Authority in China. The study will also be used for 
ofatumumab's license renewal. 
2 
Objectives and endpoints 
Table 2-1 
Objectives and related endpoints 
Objective(s) 
Endpoint(s) 
Primary objective(s) 
Endpoint(s) for primary objective(s) 
● To evaluate the effect of ofatumumab 20 mg 
monthly s.c. on annualized relapse rate (ARR) 
in participants with RMS 
● Annualized relapse rate (ARR, based on 
frequencies of confirmed relapses) 
Secondary objective(s) 
Endpoint(s) for secondary objective(s) 
● To evaluate the safety and tolerability of 
ofatumumab 20 mg monthly s.c. in participants 
with RMS 
● Adverse events, including injection-related 
reactions; 
● Laboratory data and vital signs.  
● To evaluate the effect of ofatumumab 20 mg 
monthly s.c. on MRI lesions in participants with 
RMS  
● Number of Gd-enhancing T1 lesions per MRI 
scan； 
● Number of new/enlarging T2 lesion per year 
(annualized T2 lesion rate); 

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Objective(s) 
Endpoint(s) 
● Change in T2 lesion volume compared to 
baseline. 
3 
Study design 
This is a 12-month, open-label, prospective, multi-center, single-arm, interventional study to 
evaluate the efficacy and safety of ofatumumab (OMB157) in approximately 100 adult 
participants with RMS in China. 
The study consists of three periods (see Figure 3-1): Screening, Treatment, and Post-treatment 
Follow-up. 
Screening (up to 30 days): 
After signing the informed consent, participants will enter the Screening period to determine 
eligibility according to the inclusion and exclusion criteria. The Investigator must ensure that 
participants meet all the inclusion and none of the exclusion criteria to be eligible for the study. 
If a participant is declared a screen failure, he/she may be re-screened and all assessments must 
be repeated, with the possible exception of the MRI (if the initial screening MRI was completed 
within the last 3 months). For details, refer to Section 8.1. 
Treatment (12 months): 
During the Treatment period, all eligible participants will receive initial dosing 
with ofatumumab 20 mg s.c. injection at Baseline/Week 0 (BL/W0), W1 and W2, followed by 
subsequent monthly dosing starting at W4 (Month 1/M1; a study month is defined as 28 days). 
The first s.c. injection at W0 will be administered
 
 
 
. 
All participants will have an End of Study (EOS) visit at the end of the Treatment period, when 
a participant has reached the maximum of 12-month treatment, or at the time a participant 
prematurely discontinues study treatment. After study treatment discontinuation, participants 
may initiate alternative MS therapy according to local standard of care if clinically indicated 
(refer to Section 9.3). 
Post-treatment Follow-up (6 months): 
All participants, except for completers who decide to continue with commercially available 
ofatumumab treatment, will be followed up in the Post-treatment Follow-up period for 6 months 
after last study drug dose (Table 8-2). The Post-treatment Follow-up visits should be scheduled 
relative to the EOS visit and will occur at EOS+3 months and EOS+6 months (End of Post-
treatment Follow-up). If a participant prematurely discontinues from Post-treatment Follow-up, 
the End of Post-treatment Follow-up visit should be arranged as soon as possible. Investigators 

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may continue to follow participants outside of this study at his/her discretion (for example, if 
participants have not repleted their B-cells at the end of Post-treatment Follow-up). 
Throughout the study periods, participants may have unscheduled visits due to a suspected MS 
relapse, an acute illness of undetermined cause, for other reasons, or at the discretion of the 
Investigator (refer to Section 8.3.1). 
Figure 3-1 
Study Design 
 
4 
Rationale 
4.1 
Rationale for study design 
The clinical development program of ofatumumab in MS has demonstrated efficacy and safety 
of ofatumumab 20 mg monthly s.c. for the treatment of patients with RMS globally in two 
pivotal clinical studies, COMB157G2301 and COMB157G2302. As Chinese patients were not 
enrolled into these studies, the NMPA in China requested a post-approval study to collect the 
efficacy and safety data of ofatumumab 20 mg monthly s.c. in adult Chinese RMS patients. 
This study is designed with the aim to obtain efficacy and safety data in Chinese RMS 
participants treated with ofatumumab for up to 12 months. Given the limited population size of 
RMS participants in China and as ofatumumab is an approved RMS therapy and continues to 
be effective and safe for RMS patients across various countries in the world, an open-label, 
single arm design is considered to be adequate for this study. 
Upon the requirement of license renewal in 2026, an interim analysis (IA) based on data 
collected up to the IA cut-off (around Q1 2025) will be performed, unless the final analysis has 
already been completed prior to the license renewal, and the results will be reported to NMPA. 
4.2 
Rationale for dose/regimen and duration of treatment 
The dose regimen for ofatumumab for this study is an initial dosing of 20 mg at BL/W0, W1 
and W2, followed by subsequent monthly dosing of 20 mg starting at W4. 

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This dose regimen is consistent with the dose and regimen in the global Phase 3 development 
program of ofatumumab in RMS and with the approved dosage in the various countries 
worldwide, including China before this study is initiated. 
4.3 
Rationale for choice of control drugs (comparator/placebo) or 
combination drugs 
Not applicable. 
4.4 
Purpose and timing of interim analyses/design adaptations 
One interim analysis is planned around Q1 2025. The efficacy and safety data of IA will be 
submitted to NMPA for local license renewal. 
4.5 
Risks and benefits 
The risk to participants in this trial may be minimized by compliance with the eligibility criteria 
and study procedures, close clinical monitoring, and avoidance of prohibited treatments and 
adherence to investigator guidance regarding specific safety areas.   
Ofatumumab is approved for the treatment of RMS in several countries. In the pivotal Phase 
3 studies COMB157G2301 and COMB157G2302, treatment with ofatumumab significantly 
lowered the annualized relapse rate (ARR; primary endpoint) compared to the 
active comparator teriflunomide by >50%. Ofatumumab also significantly reduced the risk 
of disability progression by >30% and showed significant suppression of both Gd-enhancing 
T1 lesions (>90%) and new/enlarging T2 lesions (>80%) on brain MRI compared to 
teriflunomide. 
The data from the global ofatumumab MS program indicate ofatumumab has an acceptable 
safety profile and is well tolerated at the recommended subcutaneous dose of 20 mg.  
Reported adverse reactions included upper respiratory tract infections, decreased 
immunoglobulin M, injection site reaction, and injection-related reactions. For further details 
about ofatumumab, please refer to the Investigator’s Brochure. 
Overall, the balance of benefit and risk supports the proposed clinical study to evaluate the use 
of ofatumumab sc as an effective and safe therapy in Chinese participants with RMS. 
Women of child-bearing potential must be informed that taking the study treatment may involve 
unknown risks to the fetus if pregnancy were to occur during the study, and agree that in order 
to participate in the study, they must adhere to the contraception requirements outlined in the 
exclusion criteria. If there is any question that the participant will not reliably comply, they 
should not be entered or continue in the study. 
In the context of a Public Health Emergency, additional risks exist for participants taking part 
in any clinical trial cannot be excluded. Eligibility criteria for the study requires the Investigator 
to evaluate infections and exclude participants with ongoing infection. The protocol also 
includes guidance on immunization (see Section 16.4.4). Additionally, this protocol has been 
adapted to include the option to allow for remote visits (on a case-by-case basis), to minimize 
unnecessary risk that would be associated with on-site visits. Other options like home nursing 
and shipment of study drug directly to participants’ home may be considered on case-by-case 

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basis. Participants receiving ofatumumab, who may have been exposed to individuals with 
COVID-19, who are experiencing protracted flu-like symptoms (particularly shortness of 
breath) consistent with COVID-19, or are confirmed to have COVID-19, should inform their 
treatment physician as soon as possible. Whether there will be interruption of the use of 
ofatumumab will be based on Investigator's judgement. 
4.5.1 
Imaging Risk 
A gadolinium-based contrast agent (GBCA) will be administered as an i.v. bolus during each 
MRI session. There is recent evidence of gadolinium deposition in brain tissues following use 
of GBCAs. Although no symptoms or diseases linked to gadolinium accumulation in the brain 
have been identified, health authorities took a precautionary approach (e.g., GBCA EMA 
restriction re brain deposit), noting that data on the long-term effects in the brain are limited. 
This led to the suspension of several linear GBCAs and the recommendation that another class 
of GBCAs known as macrocyclic agents be used as an alternative solution, as they are deemed 
more stable and have a lower propensity to release gadolinium than linear agents. Although this 
is highly debated, the current belief is that such agents, especially the linear gadolinium agents, 
may also increase the risk of a rare but serious disease called nephrogenic systemic fibrosis 
(NFS). Few studies showed that use of linear agents in participants with normal kidney function 
or mild-to-moderate CKD (stage 3; eGFR 30-59 ml/min per 1.73 m2) is without clinically 
significant risk of nephrogenic systemic fibrosis (NFS) (Goldstein et al 2019), however they 
should remain contraindicated in participants with acute kidney injury (AKI) or severe renal 
disease (stage 4 or 5 chronic kidney disease, CKD) (eGFR <30 ml/ min per 1.73 m2). To prevent 
this risk and in accordance with health authority guidance (e.g. GBCA FDA guidance re NFS, 
GBCA MHRA guidance re NFS), people with severe kidney failure, participants with previous 
severe allergic/anaphylactoid reaction to a gadolinium-based contrast agent; participants with 
severe renal disease (eGFR <30 mL/min/1.73 m2), or acutely deteriorating renal function, who 
would be at risk of nephrogenic systemic fibrosis should be excluded from participating in this 
study as stipulated in the exclusion criterion. 
4.6 
Rationale for Public Health Emergency mitigation procedures 
In the event of a Public Health Emergency as declared by local or regional authorities i.e. 
pandemic, epidemic or natural disaster, mitigation procedures may be required to ensure 
participants' safety and trial integrity are listed in relevant sections of the study protocol. 
Notification of the Public Health Emergency should be discussed with Novartis prior to 
implementation of mitigation procedures and permitted/approved by local or regional health 
authorities and ethics committees as appropriate. 
5 
Study Population 
The study population will consist of adult relapsing multiple sclerosis (RMS) participants aged 
18-55 years (inclusive) fulfilling all the eligibility criteria listed below. No additional 
inclusion/exclusion criteria may be applied by the Investigator, in order to ensure that the study 
population will be representative of all eligible participants. 
Approximately 100 participants will be enrolled from study sites in China.  

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5.1 
Inclusion criteria 
Participants eligible for inclusion in this study must meet all of the following criteria: 
1. Signed informed consent must be obtained prior to participation in the study. 
2. Male or female Chinese aged 18-55 years (inclusive) at their enrollment of the study 
(signing the study consent form). 
3. Clinical definite diagnosis of RMS according to the 2017 revised McDonald criteria 
(Thompson et al 2018, refer to Section 16.3), and  
with the documentation prior to their enrollment to the study (signing the study consent 
form) of: 
• Two documented relapses during the past 2 years, or 
• One documented relapse during the last year, or 
• A positive Gd-enhancing MRI scan during the year prior to Screening. Note: 
Screening MRI scan may be used if no positive Gd-enhancing scan exists from prior 
year. 
4. Disability status with an EDSS score of 0 - 5.5 (inclusive) at Screening. 
5. Neurologically stable within 1 month prior to both Screening and Baseline (including no 
MS relapse in this period). 
5.2 
Exclusion criteria 
Participants meeting any of the following criteria are not eligible for inclusion in this study. 
1. Participants suspected of not being able or willing to cooperate or comply with study 
protocol requirements in the opinion of the Investigator. 
2. Participants with primary progressive MS (PPMS) (Thompson et al 2018) or secondary 
progressive MS (SPMS) without disease activity (Lublin et al 2014). 
3. Participants meeting criteria for neuromyelitis optica spectrum disorder (NMOSD; 
Wingerchuk et al 2015). 
4. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female 
after conception and until the termination of gestation, confirmed by a positive hCG 
laboratory test. 
5. Women of childbearing potential, defined as all women physiologically capable of 
becoming pregnant, unless they are using effective contraception while taking study 
treatment and for at least 6 months after stopping medication. 
Note: Women are considered post-menopausal if they have had 12 months of natural 
(spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate history 
of vasomotor symptoms). Women are considered not of child bearing potential if they are 
post-menopausal or have had surgical bilateral oophorectomy (with or without 
hysterectomy), total hysterectomy or bilateral tubal ligation at least six weeks ago. In the 
case of oophorectomy alone, only when the reproductive status of the woman has been 
confirmed by follow up hormone level assessment is she considered not of child bearing 
potential. 

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6. Participants at high risk of developing or having reactivation of syphilis or tuberculosis. 
Testing for syphilis and tuberculosis will be done by the central lab at Screening for 
eligibility. 
NOTE: If test results are suspected to be false positive/negative, an infectious disease 
expert should be consulted. The Investigator must document that the test results are 
considered false positive/negative and may then enroll/exclude the participant. 
For participants with positive or uncertain results but no overall disease activity as 
evaluated by an infectious disease expert and have low risk of disease reactivation, the 
Investigator may consider enrolling such a participant. In this case, the investigator must 
document the assessments by the infectious disease expert, and give appropriate treatment 
and/or monitoring as per local clinical practice. 
7. Participants with active hepatitis B disease: 
Hepatitis B virus (HBV) screening is required in all participants, including hepatitis B 
surface antigen (HBsAg) and hepatitis B core antibody (HBcAb) testing. These can be 
complemented with other appropriate markers as per local practice. 
Participants with positive hepatitis B serology (either HBsAg or HBcAb) should consult a 
liver disease expert before the start of treatment and should be monitored and managed 
following local medical standards to prevent HBV infection or reactivation. 
8. Participants with an active chronic disease (or stable but treated with immune therapy) of 
the immune system other than MS (e.g. rheumatoid arthritis, scleroderma, Sjögren’s 
syndrome, Crohn’s disease, ulcerative colitis, etc.) or with immunodeficiency syndrome 
(hereditary immune deficiency, drug-induced immune deficiency). 
9. Participants with active systemic infections (including but not limited to active COVID-19 
infection) or known to have AIDS or to test positive for HIV antibody at Screening. 
10. Participants with neurological findings consistent with PML or confirmed PML. 
11. History of malignancy of any organ system (other than basal cell carcinoma, in situ 
squamous cell carcinoma of skin, or in situ carcinoma of cervix or the uterus that have 
been radically treated e.g. completely excised with clear margins), within the past 5 years, 
regardless of whether or not there is evidence of local recurrence or metastases.  
12. History of hypersensitivity to the study treatment or its excipients or to drugs of similar 
chemical classes. 
13. Use of other investigational drugs at the time of enrollment (Screening) or within the prior 
30 days, or five elimination half-lives, or until the expected pharmacodynamic effect has 
returned to baseline, whichever is longer; or longer if required by local regulations. 
14. Have received live or live-attenuated vaccines (including but not limited to live or live-
attenuated Sars-CoV-2 vaccines, if any) within 4 weeks prior to first study drug 
administration. 
Note 1: Inactivated vaccines, whenever possible, should be administered at least 2 weeks 
prior to the initiation of study drug. 
Note 2: At the time of development of this protocol, there is no efficacy or safety data on 
Sars-CoV-2 vaccines in immunocompromised persons. Though immunocompromised 
persons, including individuals receiving immunosuppressant therapy, may have a 
diminished immune response to the Sars-CoV-2 vaccines, there is presently no 

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contraindication for the use of an inactivated, viral-vector-, or mRNA based Sars-CoV-2 
vaccine in participants who are immunocompromised. However, different Sars-CoV-2 
vaccines may have various mechanisms of action and different associated potential risks. 
Local prescribing information of any specific Sars-CoV-2 vaccine must be reviewed and 
local prescribing information requirements for specific contraindications and special 
warnings and precautions for use must be followed. Vaccination against Sars-CoV-2 
during whole study course should be considered on a case-by-case basis at the discretion 
of the treating physician taking into account the individual benefit-risk assessment and 
local vaccination recommendations. For details, refer to Section 16.4.4. 
15. Have been treated with any other MS DMT within 5 elimination half-lives (according to 
their labels) or within expected pharmacodynamic effect window. For the medications 
commonly used in MS treatment, wash-out period is suggested to be: 
Medication 
Exclusionary if used/used within required wash-
out period 
Systemic corticosteroids, adrenocorticotropic 
hormone 
30 days prior to Screening MRI scan 
interferon-β or glatiramer acetate 
none 
Intravenous immunoglobulin 
8 weeks prior to baseline 
Plasmapheresis 
8 weeks prior to baseline 
Siponimod and ponesimod 
4 weeks prior to baseline 
Fingolimod 
8 weeks prior to baseline 
Teriflunomide 
3.5 months prior to baseline or 1 month prior to 
baseline if participant undergoes AEP (Accelerated 
Elimination Procedure) before baseline 
B-cell targeted therapies (e.g., rituximab, ocrelizumab, 
obinutuzumab) 
Prior to consideration for trial/at Screening, B-cell 
recovery (LLN as per central lab) needs to be verified 
and documented by the investigator 
Or 
2 years prior to baseline 
BTK inhibitors 
2 weeks prior to baseline 
Natalizumab (Participants who have discontinued 
natalizumab in the 6 months prior to randomization 
should be evaluated to rule out PML) 
12 weeks prior to baseline 
Mild to moderately 
immunosuppressive/chemotherapeutic medications 
(e.g. azathioprine, methotrexate) 
24 weeks prior to baseline 
Highly immunosuppressive/chemotherapeutic 
medications (e.g., mitoxantrone, cyclophosphamide, 
cladribine) 
48 weeks prior to baseline 
Alemtuzumab 
Anytime 
Lymphoid irradiation or bone marrow transplantation 
Any time 
Mitoxantrone (with evidence of cardiotoxicity following 
treatment or cumulative life-time dose > 60 mg/m2) 
Anytime 
Ofatumumab 
Anytime 
16. Any of the following chronic, severe conditions that may impact compliance:  
• History of, or current, significant cardiac disease including cardiac failure (NYHA 
functional class II-IV), myocardial infarction (within 6 months prior to Screening), 
unstable angina (within 6 months prior to Screening), transient ischemic attack 

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(within 6 months prior to Screening), stroke, cardiac arrhythmias requiring treatment 
or uncontrolled arterial hypertension 
• Concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular 
tachycardia and clinically significant second or third degree AV block without a 
pacemaker on screening electrocardiogram (ECG) 
• History of familial long QT syndrome or known family history of Torsades de Pointes 
• History of or active severe respiratory disease, including Chronic Obstructive 
Pulmonary Disease, interstitial lung disease or pulmonary fibrosis 
• Participants with asthma requiring regular treatment with oral steroids 
• Severe hepatic impairment (Child-Pugh class C) or any chronic liver or biliary disease 
• Participants with severe renal impairment (Glomerular Filtration Rate < 30 
ml/min/1.73 m2) or severe hypoproteinemia (e.g. in nephrotic syndrome) 
• Any medically unstable condition as determined by the Investigator 
17. Any of the following abnormal laboratory values as confirmed by the central laboratory 
prior to first study drug administration: 
• Lymphocyte count < 800/mm3 (< 0.8 x 109/L). 
• B-cell count < lower limit of normal (LLN, as per central laboratory range) if 
participants had a history of receiving a B-cell targeted therapy and did not meet the 
suggested wash-out period as detailed in exclusion criterion #15. 
• Serum IgG and/or serum IgM < LLN (according to central laboratory range) 
• Any other clinically significant laboratory assessment as determined by the 
Investigator (e.g. significant anemia, neutropenia, thrombocytopenia, signs of 
impaired bone marrow function) 
18. Current medical or neurological condition that might impact efficacy assessments e.g. 
dementia, schizophrenia, bipolar disorder, major depression, history of multiple traumatic 
brain injuries, alcohol/drug abuse or dependence currently, or dependence within the last 
two years. 
19. Participants intolerant to undergo MRI or presents contraindications to MRI (e.g. metallic 
implants, metallic foreign bodies, pacemaker, defibrillator) and the use of gadolinium-
based agents (e.g. people with severe kidney failure, participants with previous severe 
allergic/anaphylactoid reaction to a gadolinium-based contrast agent; participants with 
severe renal disease (eGFR<30 mL/min/1.73 m2), or acutely deteriorating renal function, 
who would be at risk of nephrogenic systemic fibrosis). 
6 
Treatment 
6.1 
Study treatment 
This is a single-arm, open-label study. The study treatment is 20 mg ofatumumab for 
subcutaneous injection. 

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6.1.1 
Investigational and control drugs 
Table 6-1 
Investigational drug 
Investigational 
Drug  
(Name and 
Strength) 
Pharmaceutical 
Dosage Form 
Route of 
Administration 
Presentation 
Sponsor (global or 
local) 
ofatumumab 20mg 
solution for injection 
subcutaneous use 
Open label; 
autoinjector 
Sponsor (global) 
Ofatumumab (OMB157) will be provided as solution for injection in an autoinjector (also called 
pre-filled pen) containing 20 mg ofatumumab (50 mg/mL, 0.4 mL content) for subcutaneous 
administration. Ofatumumab is a clear to opalescent, colorless to pale yellow, essentially 
particle-fee liquid. 
There is no control drug in this study. 
6.1.2 
Additional study treatment 
No other treatments beyond investigational drug are included in this trial. 
6.1.3 
Treatment arms 
This is an open-label study with one treatment arm (ofatumumab 20 mg s.c. injections at Week 
0, Week 1, Week 2, Week 4 and every month thereafter). 
6.1.4 
Treatment duration 
The planned duration of treatment is 12 months. Participants may be discontinued from 
treatment earlier due to unacceptable toxicity (whether it is related to study drug or not), disease 
progression or serious non-compliance to study protocol, and/or treatment is discontinued at the 
discretion of the Investigator or the participant. For participants who in the opinion of the 
Investigator are still deriving clinical benefit from ofatumumab, every effort will be made to 
continue provision of study treatment. 
Post Trial Access (PTA) is not planned for this study, because this is a PAC study and by the 
time when the first participant completes the 12-month treatment, ofatumumab will have been 
launched and commercially accessible in China. 
6.2 
Other treatment(s) 
6.2.1 
Concomitant therapy 
The Investigator should instruct the participant to notify the study site about any new 
medications he/she takes after study enrollment. 
All medications, procedures, and significant non-drug therapies (including physical therapy and 
blood transfusions) administered after the participant was enrolled into the study must be 
recorded on the appropriate electronic Case Report Forms (eCRFs). 
Each concomitant drug must be individually assessed against all exclusion criteria/prohibited 
medication. If in doubt, the Investigator should contact the Novartis medical monitor before 

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dosing with study drug or allowing a new medication to be started. If the participant is already 
enrolled, contact Novartis to determine if the participant should continue participation in the 
study. 
6.2.1.1 
Permitted concomitant therapy requiring caution and/or action 
Only limited benefit of premedication with steroids, antihistamines, or acetaminophen was seen 
in RMS clinical studies (refer also to the Investigator’s Brochure). Injection-related reactions 
(systemic or local reactions) can be managed with symptomatic treatment, should they occur. 
If Investigators choose to administer premedication, it should be administered 30 to 60 min 
prior to study drug injection. Any administrations of premedication must be recorded in the 
appropriate eCRF. 
A standard short course of intravenous corticosteroids (methylprednisolone) is allowed for the 
treatment of MS relapses (refer to Section 6.2.3). In addition, the restrictions regarding MRI 
assessments during, or within 30 days after termination of steroid therapy, must be followed 
(Section 8.3.2) 
The medications allowed for treatment of adverse reactions and MS relapses are not considered 
study supplies, and therefore, need to be supplied by the study site. 
6.2.2 
Prohibited medication 
Use of the treatments displayed in the below table is not allowed concomitantly with study 
treatment. 
Exclusionary medications for study eligibility are listed in the exclusion criteria (Section 5.2). 
Use of excluded medications is not allowed while the participant is on study treatment. 
Table 6-2 
Prohibited medication 
Medication 
Action taken  
Any immunosuppressive/ chemotherapeutic 
medications or procedures including but not 
limited to cyclosporine, azathioprine, 
methotrexate, cyclophosphamide, mitoxantrone, 
lymphoid irradiation and hematopoietic stem cell 
transplantation; monoclonal antibodies targeting 
the immune system including but not limited to 
natalizumab, alemtuzumab, daclizumab and B-
cell depleting agents such as but not limited to 
rituximab, ocrelizumab, obinutuzumab and BTK 
inhibitors.  
Discontinue study treatment; increase vigilance 
regarding infections. 
NOTE: Restarting study treatment is not 
permitted. 
Systemic corticosteroids except when given for 
symptomatic treatment of MS relapses or as pre-
medication Immunoglobulins 
Interrupt study treatment; increase vigilance 
regarding infections. 
Any other immunomodulatory or disease-
modifying MS treatment, including but not limited 
to fingolimod, siponimod, interferon beta, 
glatiramer acetate, dimethyl fumarate 
Discontinue study treatment; increase vigilance 
regarding infections. 
NOTE: Restarting study treatment is not 
permitted. 

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Medication 
Action taken  
Any other investigational drugs 
Discontinue study treatment; increase vigilance 
regarding infections. 
NOTE: Restarting study treatment is not 
permitted. 
Administration of any live or live-attenuated 
vaccine on study drug (long-lasting effects of 
ofatumumab should be taken into consideration; 
refer to Investigator’s Brochure). 
They may be administered when participants are 
no longer exposed to study drug 
(Section 16.4.4). 
Consider risk/benefit and follow local labels. 
Note: Restarting study treatment is not 
permitted. 
6.2.3 
Recommended treatment for MS relapses 
The decision to treat MS relapses should be based on the Investigator’s judgement and/or 
local clinical practices. If MS relapses require treatment, the standard treatment should consist 
of a short course of corticosteroids (methylprednisolone). Standard of care will be followed 
during treatment. 
Taper with oral steroids is not permitted. Plasmapheresis may be used only if subject does not 
respond to standard treatment with corticosteroids. 
Investigators should consider the added immunosuppressive effects of corticosteroid 
therapy and increase vigilance regarding infections during such treatment and in the weeks 
following administration. 
Use of steroids for treatment of relapses must be recorded on the Concomitant medications 
eCRF. 
Please refer to restrictions for MRI in Section 8.3.2 concerning the use of steroids and 
performing the MRI. 
6.3 
Preparation and dispensation 
Each study site will be supplied with study drug in packaging as described in Section 6.1.1. 
Ofatumumab is commercially available and will be supplied locally by the Novartis Country 
Organization (CO). Preparation and dispensation should follow the locally approved package 
insert and local practice. 
As per Section 4.6, during a Public Health Emergency as declared by local or regional 
authorities, i.e. pandemic, epidemic or natural disaster, that limits or prevents on-site study 
visits, delivery of IMP directly to a participant’s home may be permitted (if allowed by local or 
regional health authorities and ethics committees as appropriate) in the event the Investigator 
has decided that an on-site visit by the participant is no longer appropriate or possible, and that 
it is in the interest of the participant’s health to administer the study treatment even without 
performing an on-site visit. The dispatch of IMP from the site to the participant’s home remains 
under the accountability of the Investigator. Each shipment/provisioning will be for a maximum 
of 4 months’ supply. In this case, additional phone calls or virtual contacts to replace scheduled 
on-site visits will occur between the site and their participants for instructional purposes, safety 
monitoring, drug accountability, investigation of any adverse events, ensuring participants 

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continue to benefit from treatment and discussion of the participants' health status until the 
participants can resume visits at the study site. 
6.3.1 
Handling of study treatment and other treatment 
6.3.1.1 
Handling of study treatment 
Study treatment must be received 
, handled and stored 
safely and properly and kept in a secured location to which only the investigator and designated 
site personnel have access. Upon receipt, all study treatment must be stored according to the 
instructions specified on the approved label. 
Clinical supplies are to be dispensed only in accordance with the protocol. Technical complaints 
are to be reported to the respective Novartis CO Quality Assurance. 
Medication labels will be in the local language and comply with the legal requirements of each 
country. They will include storage conditions for the study treatment but no information about 
the participant except for the medication number. 
The Investigator must maintain an accurate record of the shipment and dispensing of study 
treatment in a drug accountability log. Monitoring of drug accountability will be performed by 
field monitors during site or remote monitoring visits, and at the completion of the trial. 
If study treatment is administered at home, participants will be asked to return all unused study 
treatment and packaging at the end of the study or at the time of discontinuation of study 
treatment. 
The site may destroy and document destruction of unused study treatment, drug labels and 
packaging as appropriate in compliance with site processes, monitoring processes, and per local 
regulation/guidelines. Otherwise, the investigator will return all unused study treatment, 
packaging, drug labels, and a copy of the completed drug accountability log to the Novartis 
monitor or to the Novartis address provided in the investigator folder at each site. 
6.3.2 
Instruction for prescribing and taking study treatment 
Ofatumumab will be dispensed starting at W0, and then at scheduled visits throughout the 
Treatment period according to Table 8-1. 
Participants will receive 3 initial s.c. injections of ofatumumab at W0, W1 and W2, followed 
by subsequent regular monthly dosing starting at W4 (a month is defined as 28 days). 
The first s.c. injection at W0 will be administered 
 
 
 
 
 
 
 

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Participants, who miss s.c. injections or temporarily interrupt study drug without discontinuing 
from the study or withdrawing consent, will be permitted to resume study drug if determined to 
be safe and appropriate in the opinion of the Investigator. When resuming study drug, the timing 
of the next s.c. injection will be determined based on the original study schedule as follows: 
• If one monthly injection is missed by more than 1 week, the participant should skip the 
dose and take the next dose at the time when the next injection would be due according to 
the original schedule. 
• If two or more consecutive monthly injections are missed, the Investigator should inform 
the local Sponsor Medical Advisor before re-starting dosing. 
• If any initial dose (at W0, W1 or W2), or the W4 dose is missed, then the injection should 
be administered as soon as possible. The next injection should then be administered 
according to the original schedule.  
All dosages prescribed to the participant and all dose administrations and interruptions during 
the study must be recorded on the eCRF. 
6.4 
Participant numbering, treatment assignment, randomization 
6.4.1 
Participant numbering 
Each participant is identified in the study by a Participant Number (Participant No.), that is 
assigned when the participant is enrolled for screening and is retained for the participant 
throughout his/her participation in the trial. A new Participant No. will be assigned at every 
subsequent enrollment if the participant is re-screened. The Participant No. consists of the 
Center Number (Center No.) (as assigned by Novartis to the investigative site) with a sequential 
Participant No. suffixed to it, so that each participant’s participation is numbered uniquely 
across the entire database. Upon signing the informed consent form (ICF), the participant is 
assigned to the next sequential Participant No. available. 

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6.4.2 
Treatment assignment, randomization 
This is a single-arm study and all participants will receive the same treatment (ofatumumab 20 
mg s.c.). 
6.5 
Treatment blinding 
Not applicable. 
6.6 
Dose escalation and dose modification 
Study treatment dose adjustments are not permitted during the study. Interruptions are permitted 
if clinically indicated. 
Conditions/events that may lead to the study drug interruptions based on Investigator judgment 
and overall clinical assessment include: 
• reported serious adverse event; 
• emergency medical condition, unplanned hospitalization, involving use of excluded 
concomitant medications; 
• abnormal laboratory value(s) or abnormal test or examination result(s). 
Should the participant interrupt the study drug for whatever reason, re-start decision should be 
made on a case-by-case basis. Should the Investigator decide, after informing the Sponsor, to 
re-initiate treatment with study drug, depending on the duration of the interruption, the first s.c. 
dose at re-start may need to take place 
 to ensure observation in a similar manner 
as W0. 
The reason for the interruption of treatment and date of interruption should be appropriately 
documented in the source documents as well as in the eCRF. 
6.7 
Additional treatment guidance 
6.7.1 
Treatment compliance 
The Investigator must promote compliance by instructing the participant to take the study 
treatment exactly as prescribed and by stating that compliance is necessary for the participant's 
safety and the validity of the study. The participant must also be instructed to contact the 
Investigator if he/she is unable for any reason to take the study treatment as prescribed. A 
monitor will perform and document drug accountability during site visits and at the end of the 
study. All study treatment dispensed and returned must be recorded in the drug accountability 
log. 
7 
Informed consent procedures 
Eligible participants may only be included in the study after providing (witnessed, where 
required by law or regulation) IRB/IEC-approved informed consent. 
If applicable, in cases where the participant's representative(s) gives consent (if allowed 
according to local requirements), the participant must be informed about the study to the extent 
possible given his/her level of understanding. If the participant is capable of doing so, he/she 

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must indicate agreement by personally signing and dating the written informed consent 
document. 
Informed consent must be obtained before conducting any study-specific procedures (e.g. all of 
the procedures described in the protocol). The process of obtaining informed consent must be 
documented in the participant source documents. 
Novartis will provide to investigators in a separate document a proposed informed consent form 
(ICF) that complies with the ICH E6 GCP guidelines and regulatory requirements and is 
considered appropriate for this study. Any changes to the proposed consent form suggested by 
the investigator must be agreed by Novartis before submission to the IRB/IEC. 
Information about common side effects already known about the investigational treatment can 
be found in the Investigator's Brochure (IB) and the approved label. This information will be 
included in the participant informed consent and should be discussed with the participant during 
the study as needed. Any new information regarding the safety profile of the investigational 
drug that is identified between IB updates will be communicated as appropriate, for example, 
via an investigator notification or an aggregate safety finding. New information might require 
an update to the informed consent and then must be discussed with the participant. 
The following informed consents are included in this study: 
• Main study consent, which also includes:  
• A subsection that requires a separate signature for the ‘Optional Consent for 
Additional Research’ to allow future research on data/samples collected during this 
study 
• As applicable, Pregnancy Outcomes Reporting Consent for female participants who took 
study treatment 
Women of child bearing potential must be informed that taking the study treatment may involve 
unknown risks to the fetus if pregnancy were to occur during the study and agree that in order 
to participate in the study they must adhere to the contraception requirements. 
A copy of the approved version of all consent forms must be provided to Novartis after IRB/IEC 
approval. 
Participants might be asked to complete an optional questionnaire to provide feedback on their 
clinical trial experience. 
As per Section 4.6, during a Public Health Emergency as declared by local or regional 
authorities i.e. pandemic, epidemic or natural disaster, that may challenge the ability to obtain 
a standard written informed consent due to limits that prevent an on-site visit, Investigator may 
conduct the informed consent discussion remotely (e.g. telephone, videoconference) if 
allowable by a local health authority. 
Guidance issued by local regulatory bodies on this aspect prevail and must be implemented and 
appropriately documented (e.g. the presence of an impartial witness, sign/dating separate ICFs 
by trial participant and person obtaining informed consent etc.). 

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8 
Visit schedule and assessments 
The Assessment Schedule (Table 8-1 and Table 8-2) lists all of the assessments and indicates 
with "X" or "S" when they are performed. The “X” in the table denotes the assessments to be 
recorded in the clinical database or received electronically from a vendor. The “S” in the table 
denotes the assessments that are only in the participant’s source documentation and do not need 
to be recorded in the clinical database. All data obtained from these assessments must be 
supported in the participant’s source documentation. 
Participants should be seen for all visits/assessments as outlined in the assessment schedule 
(Table 8-1 and Table 8-2) or as close to the designated day/time as possible, with an allowed 
“injection window” as described in Section 6.3.2. Missed or rescheduled visits should not lead 
to automatic discontinuation. In the study, one month is defined as 28 calendar days.  
For all scheduled visits, any AE or SAE reported by the participant will be recorded according 
to Section 10.1.1 and Section 10.1.2. For women of childbearing potential, urine or serum 
pregnancy test is required prior to each administration of study drug, and drug administration 
can only be conducted with negative pregnancy test result (refer to Section 8.4.3). 
EOS visit is mandatory for all participants. The EOS visit is conducted at the end of the 
Treatment period (i.e. M12), or when participants prematurely discontinue study treatment 
before M12, whether they plan to enter Post-treatment Follow-up period or withdraw from the 
study. Participants who prematurely discontinue study treatment will have their EOS visit as 
soon as possible. At the EOS visit, AEs and concomitant medications not previously reported 
must be recorded on the eCRFs. 
Participant diaries 
During the study, participants will be asked to complete a diary from BL/W0 onwards till EOS 
to record information pertinent to study treatment administration (including date and time of 
s.c. injections), home pregnancy testing (date and results) for women of childbearing potential 
and other information (e.g. AEs). The participant is requested to bring the completed diaries 
with them to each visit and the Investigator/Study Coordinator/Nurse must review these for 
completeness and for potential AEs, injection-related reactions, study treatment interruptions 
etc. and record information obtained from the diaries into the relevant eCRFs. 
Telephone or virtual interviews 
Site personnel will conduct a structured telephone interview (script provided) for W1 and W2 
initial doses, and then every month in between the scheduled site visits following the W4 site 
visit (Table 8-1 and Table 8-2). During the Treatment period, the interview should take place 
around time of the monthly s.c. self/home‑injections to query about any new or worsening 
symptoms warranting an unscheduled visit, compliance with study treatment, changes in 
concomitant medication, injection reactions, results of home pregnancy testing and compliance 
with contraception requirements when applicable. During the Post-treatment Follow-up period, 
the interview should take place regularly every month between scheduled visits to query about 
any new or worsening symptoms warranting an unscheduled visit, changes in MS treatment and 
concomitant medication, compliance with contraception requirements and potential AEs etc.  

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Participants, except for those who will continue with commercially available ofatumumab 
treatment, will enter the 6-month Post-treatment Follow-up period after EOS as described in 
Table 8-2. 
As per Section 4.6, during a Public Health Emergency as declared by local or regional 
authorities i.e. pandemic, epidemic or natural disaster that limits or prevents on-site study visits, 
alternative methods of providing continuing care may be implemented by the investigator as 
the situation dictates. If allowable by a local health authority and depending on operational 
capabilities, phone calls, virtual contacts (e.g. tele consult) or visits by site staff/home nursing 
staff to the participant´s home, can replace on-site study visits, for the duration of the disruption 
until it is safe for the participant to visit the site again. 

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Table 8-1 
Assessment Schedule, Screening and treatment 
Period 
Screening 
Treatment 
Treatment 
Visit Name 
Screening 
BL/W0 
W1 (Phone 
Interview) 
W2 (Phone 
Interview) 
W4 
M3 
M6 
M9 
M12/EOS 
Unscheduled Visit1 
Days 
-30 to -1 
- 
7 
14 
28 
84 
168 
252 
336 
- 
Informed consent 
X 
  
  
  
  
  
  
  
  
  
Demography, Height 
X 
  
  
  
  
  
  
  
  
  
Inclusion / Exclusion criteria 
X 
X2 
  
  
  
  
  
  
  
  
Medical history/current 
medical conditions 
X 
  
  
  
  
  
  
  
  
  
MS History/Treatments 
X 
  
  
  
  
  
  
  
  
  
COVID-19 vaccination status 
X 
X3 
X 
X 
X 
X 
X 
X 
X 
  
Physical Examination  
S 
S3 
  
  
S 
  
S 
  
S 
S 
Weight, Vital Signs 
X 
X4 
  
  
X 
X 
X 
X 
X 
X 
Electrocardiogram (ECG) 
X 
  
  
  
  
  
  
  
  
  
Hematology 
X5 
  
  
  
X 
X 
X 
X 
X 
  
Clinical Chemistry 
X5 
  
  
  
X 
X 
X 
X 
X 
  
Urinalysis 
X5 
  
  
  
X 
  
X 
  
X 
  
Serological markers for 
hepatitis B6 
X5 
  
  
  
  
  
  
  
  
  
HIV antibody screen7 
X5 
  
  
  
  
  
  
  
  
  
Syphilis screen7 
X5 
  
  
  
  
  
  
  
  
  
Tuberculosis screen 7 
X5 
  
  
  
  
  
  
  
  
  
Pregnancy and assessments 
of fertility 8 
X5 
X3 
  
  
X 
X 
X 
X 
X 
  
Contraception Status9 
X 
X3 
X 
X 
X 
X 
X 
X 
X 
  
MS relapse 
X 
X3 
X 
X 
X 
X 
X 
X 
X 
X 
MRI 
X 
  
  
  
  
X 
  
  
X10 
  

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Period 
Screening 
Treatment 
Treatment 
Visit Name 
Screening 
BL/W0 
W1 (Phone 
Interview) 
W2 (Phone 
Interview) 
W4 
M3 
M6 
M9 
M12/EOS 
Unscheduled Visit1 
Days 
-30 to -1 
- 
7 
14 
28 
84 
168 
252 
336 
- 
Adverse Events 
X 
X3 
X 
X 
X 
X 
X 
X 
X 
X 
Prior/Concomitant 
Medications 11 
X 
X3 
X 
X 
X 
X 
X 
X 
X 
X 
Surgical/medical procedures 
X 
X3 
X 
X 
X 
X 
X 
X 
X 
X 
Sample for B-cells12 
X 
X3 
  
  
X 
X 
X 
  
X 
  
Sample for IgG and IgM12 
X 
  
  
  
  
  
X 
  
X 
  
Drug dispensation 
  
S 
  
  
S 
S 
S 
S 
  
  
Drug administration 13 
  
X 
X 
X 
Monthly, except for M12/EOS 
  
Participant diaries14 
  
  
X 
  
Participant Diary Review  
  
  
  
  
X 
X 
X 
X 
X 
  
Phone interview/virtual 
visit15,16 
  
  
X 
X 
Monthly between scheduled visits 
  
Treatment Phase Completion 
  
  
  
  
  
  
  
  
X 
  
X Assessment to be recorded in the clinical database or received electronically from a vendor 
S Assessment to be recorded in the source documentation only 
1 Unscheduled visit: assessments performed as unscheduled visits will depend on the clinical needs of the participant. All participants with neurological symptoms 
suggestive of an MS relapse should at least have the mentioned assessments in table 8-1 performed. Other assessments may be done as appropriate. 
2 Inclusion/exclusion criteria need to be checked again before first dose of study drug. 
3 Assessments to be completed prior to first study drug administration. 
4 Vital signs should be obtained 30-60 min before sc injection (if premedication is administered, pre-injection vital signs should be obtained before premedication is 
administered). 
5 Laboratory results must be available prior to Baseline/Week 0 (BL/W0) to evaluate the Inclusion/Exclusion criteria. 
6 Hepatitis B screening is required in all study participants, including hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (HBcAb) testing. These can be 
complemented with other appropriate markers as per local guidelines. For detailed guidance, refer to Section 16.4.2.   
7 HIV, Syphilis and Tuberculosis testing must be done at central lab as part of eligibility check (Exclusion criterion #6 and #9) for all participants.  
8 Women of childbearing potential only -For Screening and EOS visits, serum pregnancy test will be conducted in central lab. Monthly urine pregnancy tests will be 
conducted between scheduled visits(starting after W4) at home or at site prior to the administration of study treatment. In case of a positive test result, the participant 
must contact the investigator immediately and confirmatory testing should be performed at the investigator's discretion. 
9 Contraception MUST be used during the study treatment period and for at least 6 months after the last dose of study drug. Participant’s contraception status must be 
reviewed and documented to ensure method of contraception continues to be appropriate per protocol requirement for effective contraception. 

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Period 
Screening 
Treatment 
Treatment 
Visit Name 
Screening 
BL/W0 
W1 (Phone 
Interview) 
W2 (Phone 
Interview) 
W4 
M3 
M6 
M9 
M12/EOS 
Unscheduled Visit1 
Days 
-30 to -1 
- 
7 
14 
28 
84 
168 
252 
336 
- 
10 MRI scan at the End of Study (EOS) is needed if there was no MRI scan in the last 3 months. 
11 Including corticosteroids used to treat MS relapse; any newly started MS treatment as applicable (for participants who have discontinued study medication). 
12 The assessments (samples taken for IgG and IgM, B-cells) should be completed prior to study drug administration. 
13 The first s.c. injection at W0 will be administered 
 
. 
14 Study treatment administration (including date and time of s.c. injections) and home pregnancy testing (date and results) for women of childbearing potential will be 
recorded for each home injection. Other information (e.g. AEs) will be recorded continuously.  
15 Phone interview will be performed by site staff for W1 and W2, and then every month starting from W4 between scheduled visits. The interview should take place 
around time of the monthly s.c. self/home injection to query about any new or worsening symptoms warranting an unscheduled visit, injection reactions, results of home 
pregnancy testing and compliance with contraception requirements. 
16 Phone interview/virtual visits are also applicable to the scheduled visits for participants who exceptionally cannot come to the study site for a face-to-face examination 
due to a Public Health Emergency (e.g. restricting the subject’s general access to sites). 

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Table 8-2 
Assessment Schedule, Post-Treatment Follow-up 
Period 
Post-Treatment Follow-Up 
Visit Name 
V11 
End of FU1,2 
Unscheduled Visit3 
Days 
EOS+3 months 
EOS+6 months 
NA 
Weight, Vital Signs 
X 
X 
X 
COVID-19 vaccination status 
X 
X 
  
Physical Examination  
S 
S 
S 
Clinical Chemistry 
X 
X 
  
Hematology 
X 
X 
  
Urinalysis 
X 
X 
  
Pregnancy Test (serum)4 
X 
X 
  
Contraception Status5 
X 
X 
  
Sample for B-cells 
X 
X 
  
Sample for IgG and IgM 
X 
X 
  
MS relapse 
X 
X 
X 
MRI 
  
X6 
  
Concomitant medications7 
X 
X 
X 
Surgical/medical procedures 
X 
X 
X 
Adverse Events 
X 
X 
X 
Phone interview/virtual visit8,9 
Monthly between scheduled visits 
  
Post Treatment Part Completion 
  
X 
  
X Assessment to be recorded in the clinical database or received electronically from a vendor 
S Assessment to be recorded in the source documentation only 
1 Visits 1 and end of FU are applicable to all participants, except for completers of the Treatment period who decide to continue with commercially available ofatumumab 
treatment. 
2  If a participant prematurely discontinues from the Post-Treatment Follow-up (PT FU), the End of PT FU should be done as soon as possible. If scheduled PT FU1 visit 
and the end of PT FU visit occur around the same time, only end of PT FU should be done. 
3 Unscheduled visit: assessments performed at unscheduled visits depend on the clinical needs of the participant. All participants with neurological symptoms suggestive 
of an MS relapse should have an EDSS evaluation. Other assessments may be done as appropriate. 
4 Women of childbearing potential only. Serum pregnancy tests will be conducted on scheduled visits every 3 months by central lab.  

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Period 
Post-Treatment Follow-Up 
Visit Name 
V11 
End of FU1,2 
Unscheduled Visit3 
Days 
EOS+3 months 
EOS+6 months 
NA 
5 Contraception MUST be used during the study and for at least 6 months after stopping study drug. Participant’s contraception status must be reviewed and 
documented to ensure method of contraception continues to be appropriate per protocol requirement for highly effective contraception. 
6 For treatment period completers, MRI at the end of PT FU is not needed. For participants that prematurely discontinue from study treatment, MRI scan at the End of FU 
is needed if there has been no MRI scan in the last 3 months. 
7 Including corticosteroids used to treat MS relapse; any newly started MS treatment as applicable (for participants who have discontinued study medication).  
8 Phone interview/virtual visits are also applicable to the scheduled visits for participants who exceptionally cannot come to the study site for a face-to-face examination 
due to a Public Health Emergency (e.g. restricting the subject’s general access to sites). 
9 Phone interview will be performed by site staff regularly every month between scheduled visits to query about any new or worsening symptoms warranting an 
unscheduled visit, changes in MS treatment and concomitant medication, compliance with contraception requirements and potential AEs. 

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8.1 
Screening 
Screening 
If a participant does not meet Inclusion/Exclusion criteria, he/she may be re-screened. In 
general, a participant may not be re-screened more than once. All assessments must be repeated 
at re-screening, with the possible exception of MRI if the previous screening MRI scan was 
performed within 3 months of re-screening. If a participant is re-screened, a new ICF must be 
obtained and re-screening will be documented in the participant’s source documents.  
A new participant ID will be allocated and the site will record the data in a new eCRF. 
In the case where a laboratory assessment at screening is outside of the range specified in the 
exclusion criteria, the assessment may be repeated at the discretion of the Investigator within 
the Screening period time window, and the participant may be included if the criteria are then 
met. In this instance, it is not considered as re-screening; the participant will not be required to 
sign another ICF and the original Participant Number assigned by the Investigator will be used. 
In the event that the laboratory tests cannot be performed within the Screening visit window, or 
the re-tests do not meet the entrance criteria, or other eligibility criteria have changed and are 
not met anymore, the participant is considered a screen failure. 
8.1.1 
Information to be collected on screening failures 
Participants who sign an ICF and are subsequently found to be ineligible prior to starting 
treatment will be considered as a screen failure. The reason for screen failure should be recorded 
on the appropriate eCRF. The disposition, demographic information, informed consent, and 
inclusion/exclusion, withdrawal of consent (if the participant withdrew consent) pages must 
also be completed for screen failure participants. No other data is required to be entered into the 
clinical database for participants who are screen failures, unless the participant experienced a 
serious adverse event (SAE) during the screening phase (see Section 10.1.3 for SAE reporting 
details).  
Adverse events that are not SAEs will be followed by the Investigator and recorded only in the 
source data. 
Participants who sign an informed consent and are considered eligible but fail to be started on 
treatment for any reason will be considered an early terminator. The reason for early termination 
should be captured on the appropriate disposition eCRF. 
8.2 
Participant demographics/other baseline characteristics 
Participant demographic and baseline characteristic data to be collected on the appropriate 
eCRF from the participant will include age, race, sex, ethnicity, height and weight.  
Relevant medical history (including alcohol and smoking history), current medical conditions 
present before signing informed consent and any medication taken to treat these conditions will 
be captured on the corresponding eCRF. Where possible, the diagnosis and not symptoms 
should be recorded. Investigators will have discretion to record abnormal test findings on the 

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eCRF capturing medical history whenever in their medical judgment, the test abnormality 
occurred prior to the informed consent signature.  
MS disease history including date of diagnosis, history of relapses and previous MS treatment 
will also be collected on the corresponding eCRFs. 
8.3 
Efficacy 
MS relapse activity and neurological impairment of MS as measured by Expanded Disability 
Status Scale (EDSS) will be obtained in order to characterize the clinical disease activity.  Brain 
MRI will be used to assess radiological disease activity. 
8.3.1 
Efficacy assessment 1 
Annualized relapse rate (ARR) 
MS relapse definition: Appearance of a new neurological abnormality or worsening of 
previously stable or improving pre-existing neurological abnormality, separated by at least 30 
days from onset of a preceding clinical demyelinating event. The abnormality must be present 
for at least 24 hours and occur in the absence of fever (< 37.5 °C) or known infection. 
Diagnosing MS relapses during the study: The assessment, management and reporting of MS 
relapse is made by the Treating Investigator. A participant may report symptoms indicative of 
a relapse at a scheduled visit or at any other time. Participants will be instructed to immediately 
contact the Investigator if he/she develops new or re-occurring or worsening neurological 
symptoms. At each scheduled visit, the participant will also be asked whether any such 
symptoms have occurred. If a participant reports new neurological symptoms or worsening of 
previous symptoms, an unscheduled visit should be performed as soon as possible, ideally 
within 7 days. During this visit, the Investigator will first assess whether the new/worsening 
neurological abnormality is consistent with the definition of MS relapse above. If so, the 
standard neurological examination (for the EDSS score) should be performed by the 
Investigator or a qualified designator. If fever or infection cannot be excluded, the neurological 
examination will be postponed until the fever or the infection has ceased (provided that the 
symptoms indicative of a relapse are still present). Treatment with steroids should not begin 
prior to the assessment by the Investigator.  
Confirmation of MS relapse: A relapse is confirmed when it is accompanied by an increase 
of at least half a step (0.5) on the EDSS score or an increase of 1 point on two different 
Functional Systems (FS) of the EDSS or 2 points on one of the FS (excluding Bowel/Bladder 
or Cerebral FS) compared to the previously available rating (the last EDSS rating that did not 
occur during a relapse).  
All MS relapses, regardless if they meet definition for confirmation based on EDSS or not, are 
reported on the appropriate eCRF.  

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8.3.2 
Efficacy assessment 2 
MRI parameters: Gd- enhancing T1 lesions; new or enlarging T2 lesions; T2 
lesion volume 
All participants will undergo MRI scanning of the brain according to the schedule in the 
schedule of assessment (Table 8-1 and Table 8-2). MRI scans will be read by the central 
MRI reading center as part of the efficacy analysis (central reading not needed for eligibility). 
Each site Investigator will be responsible to have a qualified neuro-radiologist review each MRI 
scan to determine if there may be any incidental findings unrelated to the planned observations 
within the study protocol detected on the images. Refer to Section 16.4.1 for Guidance on safety 
monitoring. 
Additional MRI scans in participants with suspected MS relapse is not required per study 
protocol and is at the discretion of the Investigator. 
Scanning 
The gadolinium contrast medium may occasionally cause nausea and vomiting. Allergic 
reactions may also occur very rarely and, in extremely rare instances, can be potentially serious 
and require immediate anti-anaphylactic treatment. 
T1-weighted images before and after administration of gadolinium contrast medium as well as 
T2-weighted images will be performed. 
Prior to the start of the study, the neuroradiologist and MRI technician from each center will 
receive an MRI manual, outlining technical implementation, image quality requirements and 
MRI administrative procedures. Each site will be asked to program the MRI scanner that is 
designated for evaluation of the study participants and perform and submit a qualification scan 
to the MRI reading center to assess the image quality and to evaluate the compatibility of the 
electronic data carrier. Once the qualification scan has been accepted, all the parameter 
settings for the study specific MRI sequences must remain unchanged for the duration of the 
study. 
During the study, the quality of each scan performed on scheduled visits will be assessed by the 
central MRI reading center. The MRI scan should be sent to the central MRI reading center 
upon completion. As soon as the scan is received by the central MRI reading center, it will be 
evaluated for quality, completeness and adherence to the protocol. Confirmation of MRI quality 
or a description of the quality problems, if detected, will be communicated to the site. If a scan 
is incomplete or incorrectly performed, the study center will be asked to repeat it as soon as 
possible. After completion of the quality check, all scans will be analyzed according to the MRI 
manual. 
As per Section 4.6, during a Public Health Emergency as declared by local or regional 
authorities i.e. pandemic, epidemic, or natural disaster, that limits or prevents on-site study 
visits, the collection of images may be modified by Novartis and will be communicated to the 
Investigator. 

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Restrictions for MRI schedule 
To avoid potential interference caused by steroids used for the treatment of MS relapses, the 
following restrictions will be applied for this study: 
• In case of relapse, if an MRI would have been scheduled within 30 days of the initiation of 
steroid treatment, this MRI should be performed before steroid treatment is initiated 
• No MRI scan should be performed while a participant is on steroid therapy and within 30 
days after termination of steroid therapy 
8.3.3 
Efficacy assessment 3 
 
Expanded Disability Status Scale (EDSS) will be determined, based on neurological 
examination at scheduled visits (Table 8-1 and Table 8-2) and in case of a suspected MS 
relapse. 
The EDSS is an ordinal scale used for assessing neurologic impairment in MS based on a 
neurological examination. It consists of scores in each of seven functional systems (FSs) that 
are then combined to determine the EDSS steps [ranging from 0 (normal) to 10 (death due to 
MS)]. The FSs are Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel & Bladder, and 
Cerebral functions (fatigue contributes). The FSs and EDSS steps will be assessed in a 
standardized manner. EDSS is a widely used and accepted instrument to evaluate disability 
status at a given time and, longitudinally, to assess disability progression in clinical studies in 
MS. 
 
 
 
 
 
 
 
8.3.4 
Appropriateness of efficacy assessments 
MS relapse, EDSS assessments as well as MRI parameters in this patient population are 
standard efficacy assessments in MS and serve to characterize the patient population included 
in this study as well as their disease activity and neurological status over the study.  
8.4 
Safety 
Safety assessments are specified as below with the assessment schedule detailing when each 
assessment is to be performed. 
• Physical/neurological examination (including skin) 
• Vital signs 

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• Laboratory evaluations 
• Adverse events 
For details on AE collection and reporting, refer to Section 10.1. 
Table 8-3 
Assessments & Specifications 
Assessment 
Specification 
Physical  
A physical examination includes an assessment of skin, head and neck, lymph nodes, 
breast, heart, lungs, abdomen, back and/or comments on general appearance. A 
neurological examination may also be a part of the physical examination.  
Information for all physical examinations must be included in the source documentation at 
the study site. Clinically relevant findings that are present prior to signing informed 
consent must be recorded on the appropriate eCRF that captures medical history. 
Significant findings made after signing informed consent which meet the definition of an 
adverse event must be recorded on the Adverse Event eCRF. 
Vital signs 
Vital signs include temperature, blood pressure and pulse measurements. 
Sitting pulse rate and blood pressure should be obtained after the participant has 5 
minutes of rest. The pulse should be measured just prior to obtaining the blood pressure 
measurement. After the participant has been sitting for five minutes, with back supported 
and both feet placed on the floor, systolic and diastolic blood pressure will be measured 
using a validated device, e.g. OMRON, with an appropriately sized cuff. For any abnormal 
reading, the repeated sitting measurements will be made at 1 - 2 minute intervals and the 
mean of the measurements will be used. 
Height and weight 
Height in centimeters (cm) and body weight (to the nearest 0.1 kilogram (kg) in indoor 
clothing, but without shoes) will be measured. 
8.4.1 
Laboratory evaluations 
A central laboratory will be used for analysis of all specimens (except for urine pregnancy 
tests) collected as described in Table 8-1 and Table 8-2. Details on the collections, shipment of 
samples and reporting of results by the central laboratory are provided to Investigators in the 
laboratory manual. 
All abnormal lab results must be evaluated for criteria defining an adverse event and reported 
as such if the criteria are met (see also Section 10.1.1). Clinically significant abnormalities 
should be recorded in the eCRF as either AEs or as medical history/current medical conditions 
as appropriate. For AEs related to laboratory abnormalities, repeated evaluations are 
recommended until normalization of the test result(s) or until the result is no longer considered 
clinically significant. 
In case of increases in liver function test (LFT), refer to Section 16.1. 
If a Public Health Emergency as declared by local or regional authorities, i.e. pandemic, 
epidemic or natural disaster limits or prevents on-site study visits, the method of collection and 
testing of samples may be modified by Novartis if applicable and if modified, will be 
communicated to the Investigator.  
Table 8-4 
Laboratory assessments  
Test Category 
Test Name 
Hematology 
Hematocrit, hemoglobin, platelets, red blood cell count, total white blood cell count 
and differential counts (Basophils, Eosinophils, Lymphocytes, Monocytes, 
Neutrophils) 

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Test Category 
Test Name 
Chemistry 
Albumin, ALP, ALT, AST, gamma-glutamyl transferase (GGT), sodium, potassium, 
creatinine, total and conjugated bilirubin (BIL), blood urea nitrogen (BUN) 
B-cell 
CD19+ B-cell counts 
Immunoglobulin 
Immunoglobulin (IgG and IgM) 
Urinalysis 
Macroscopic Panel (Color, Bilirubin, Blood, Glucose, Ketones, Leukocytes 
esterase, Nitrite, pH, Protein, Specific Gravity, Urobilinogen) 
If clinical notable findings of macroscopic panel, then Microscopic Panel 
(Erythrocytes, Leukocytes, Casts, Crystals, Bacteria, Epithelial cells) 
Hepatitis markers 
HBV screening is required in all participants, including Hepatitis B surface antigen 
(HBsAg) and hepatitis B core antibody (HBcAb) testing. 
Participants with positive hepatitis B serology (either HBsAg or HBcAb) should 
consult a liver disease expert before the start of treatment and should be 
monitored and managed following local medical standards to prevent HBV 
infection or reactivation.  
NOTE: If the infectious disease expert finds no evidence of acute or chronic 
hepatitis infection and considers the serology results false positive and not 
clinically relevant, the Investigator must document that the serology results are 
considered false positive and may then enroll the participant. 
Pregnancy Test1 (women 
of childbearing potential) 
Serum / Urine pregnancy test (refer to Section 8.4.3) 
Additional tests2 
HIV antibodies, syphilis and TB screening test. Serology markers for other 
hepatitis, as appropriate; 
Follicle Stimulating Hormone (FSH) (for female participants with unclear fertility 
status). 
Cerebrospinal fluid (CSF) aliquot in the event of suspected CNS infection (PML) 
1 Serum pregnancy test analyzed in Central lab is required for Screening, EOS visits and for 
scheduled visits during Post-treatment Follow-up period. For the other scheduled visits, urine 
pregnancy test is to be analyzed with pregnancy kits provided by the central lab; monthly urine 
pregnancy test is to be conducted with pregnancy kits prior to every study drug administration. Urine 
pregnancy tests by local lab at site can be considered if pregnancy kit is not allowed per site 
requirement. 
2 HIV, syphilis and tuberculosis testing must be done as part of eligibility check (Exclusion criterion #6 
and #9) for all participants. These screening tests should be done by the central lab. 
8.4.2 
Electrocardiogram (ECG) 
An ECG will be obtained and reviewed locally for the eligibility assessment at Screening. 
Additional unscheduled ECGs may be performed at Investigator’s discretion if clinically 
indicated. 
ECGs must be recorded after 10 minutes rest in the supine position to ensure a 
stable baseline/according to the ECG investigator manual. In the case of a series of assessments, 
ECG should be the first assessment obtained while the participant is at rest (refer to Figure 8-1). 
Figure 8-1 
Timing of study procedures 
 

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The QT interval corrected by Fridericia's formula (QTcF) is suggested for use of clinical 
decisions. The Investigator should calculate QTcF if it is not auto-calculated by the ECG 
machine. 
Single 12-lead ECGs are collected and results are entered into the appropriate eCRF page. The 
original ECGs, appropriately signed and labeled, must be collected and archived at the study 
site. The Investigator should document clinical evaluation in source. 
Clinically significant abnormalities must be recorded in the eCRF as either medical 
history/current medical conditions or AEs as appropriate. 
8.4.3 
Pregnancy and assessments of fertility 
All pre-menopausal women who are not surgically sterile will have pregnancy testing. 
Additional pregnancy testing might be performed if requested by local requirements. 
Serum pregnancy tests will be conducted by central lab at Screening, EOS visit and the 
scheduled visits in the Post-treatment Follow-up period. Urine pregnancy tests will be 
conducted for all women of childbearing potential at all the remaining scheduled visits and 
monthly starting after W4 between the scheduled visits (with urine pregnancy testing kits 
provided by the central lab unless not permitted per site requirement) prior to study drug 
administration. The participants will document the date and results of each home pregnancy test 
in a diary provided for the study. A monthly site contact (refer to Table 8-1) will also be 
conducted with the participants, which includes questions to confirm that the home urine 
pregnancy testing is done and the result is correctly documented. In case of a positive test result, 
the participant must contact the Investigator immediately for confirmatory testing at the 
Investigator's discretion. It is important that participants are instructed to perform the urine 
pregnancy test first and only if the test result is negative then proceed with the administration 
of the study treatment. The communication process described above as part of the monthly site 
contacts with the participant should be followed so that the site is informed and can verify the 
pregnancy test results. 
If participants cannot visit the site to have serum pregnancy tests during a Public Health 
emergency as declared by Local or Regional authorities i.e. pandemic, epidemic or natural 
disaster, that limits or prevents on-site study visits, urine pregnancy test kits may be used. 
Relevant participants can perform the urine pregnancy test at home and report the result to the 
site. It is important that participants are instructed to perform the urine pregnancy test first and 
only if the test result is negative proceed with the administration of the study treatment. A 
communication process should be established with the participant so that the Site is informed 
and can verify the pregnancy test results (e.g., following country specific measures). 
In addition, the Investigator will review the contraception status with the participant at each 
visit to ascertain that the participant continues to comply with protocol requirements for 
effective contraception as applicable. 
Contraception must be used during the study treatment period and for at least 6 months after 
the last dose of study drug. 
Assessments of fertility 

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Medical documentation of oophorectomy, hysterectomy, or tubal ligation must be retained as 
source documents. Subsequent hormone level assessment to confirm the woman is not of child-
bearing potential must also be available as source documentation in the following cases: 
1. Surgical bilateral oophorectomy without a hysterectomy 
2. Reported 12 months of natural (spontaneous) amenorrhea with an appropriate clinical 
profile. 
In the absence of the above medical documentation, FSH testing is required of any female 
participant regardless of reported reproductive/menopausal status at screening/baseline. 
8.4.4 
Appropriateness of safety measurements 
The safety assessments selected are standard for this indication/participant population and 
appropriate based on the current safety profile of ofatumumab (see Investigator's Brochure). 
8.5 
Additional assessments 
8.5.1 
Clinical Outcome Assessments (COAs) 
Trial Feedback 
This study is including an optional questionnaire, the “Trial Feedback Questionnaire” for trial 
participants to provide feedback on their clinical trial experience. Individual trial participant 
responses will not be reviewed by Investigators. Responses may be used by the Sponsor to 
understand where improvements can be made in the clinical trial process. This questionnaire 
does not ask questions about the trial participant's disease, symptoms, treatment effect, or 
adverse events, and therefore is not considered as trial data. 
9 
Discontinuation and completion 
9.1 
Discontinuation from study treatment and from study 
9.1.1 
Discontinuation from study treatment 
Discontinuation of study treatment for a participant occurs when study treatment is permanently 
stopped for any reason (prior to the planned completion of study drug administration, if any) 
and can be initiated by either the participant or the Investigator. 
The Investigator must discontinue study treatment for a given participant if he/she believes that 
continuation would negatively impact the participant's well-being. 
Discontinuation from study treatment is required under the following circumstances: 
• Participant/guardian decision (Section 9.1.2) 
• Pregnancy (Section 8.4.3 and Section 10.1.4)  
• Use of prohibited treatment as per recommendations in the prohibited treatment section 
(Section 6.2.2) 
• Diagnosis of PML (Section 16.4.1) 
• Hypersensitivity to the study drug 

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• Protocol violation that results in a significant risk to the participant’s safety 
• Emergence of certain adverse events, such as malignancy (except successfully treated 
basal cell carcinoma, in situ squamous cell carcinoma and in situ carcinoma of cervix of 
uterus), liver failure, or serious chronic infection (such as active hepatitis B, HIV) 
• Laboratory abnormalities requiring the action of study drug discontinuation as defined in 
Section 16.1 
• Any laboratory abnormalities that in the judgment of the Investigator, taking into 
consideration the participant’s overall status, prevents the participant from continuing 
participation in the study  
• Any situation in which study participation might result in a safety risk to the participant  
• Non-compliance with study drug or study procedures 
If discontinuation of study treatment occurs, the Investigator should make a reasonable effort 
to understand the primary reason for the participant’s premature discontinuation of study 
treatment and record this information. 
Participants who discontinue study treatment or who decide they do not wish to participate in 
the study further should NOT be considered withdrawn from the study UNLESS they withdraw 
their consent (see Section 9.2, 'Withdrawal of Informed Consent' section). Where possible, they 
should return for the assessments indicated in the Post-treatment Follow-up assessment 
schedule (Table 8-2). If they fail to return for these assessments for unknown reasons, every 
effort (e.g. telephone, e-mail, letter) should be made to contact the participant/pre-designated 
contact as specified in the lost to follow-up section. This contact should preferably be done 
according to the study visit schedule. 
If the participant cannot or is unwilling to attend any visit(s), the site staff should maintain 
regular telephone contact with the participant, or with a person pre-designated by the 
participant. This telephone contact should preferably be done according to the study visit 
schedule. 
After discontinuation from study treatment, at a minimum, the following data should be 
collected: 
• New/concomitant treatments 
• Adverse Events/Serious Adverse Events 
9.1.2 
Discontinuation from study 
Discontinuation from study is when the participant permanently stops receiving the study 
treatment, and further protocol-required assessments or follow-up, for any reason. 
If the participant agrees, a final evaluation at the time of the participant’s study discontinuation 
should be made as detailed in the assessment table (refer to Section 8). 
9.1.3 
Lost to follow-up 
For participants whose status is unclear because they fail to appear for study visits without 
stating an intention to discontinue from study treatment or discontinue from study or withdraw 
consent/oppose to the use of their data/biological samples, the investigator must show "due 

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diligence" by documenting in the source documents steps taken to contact the participant, e.g. 
dates of telephone calls, registered letters, etc. A participant should not be considered as lost to 
follow-up until due diligence has been completed or until the end of the study. 
9.2 
Withdrawal of informed consent/Opposition to use 
data/biological samples 
Withdrawal of consent/opposition to use data/biological samples occurs when a participant: 
• Explicitly requests to stop use of their biological samples and/or data (opposition to use 
participant’s data and biological samples) 
and 
• No longer wishes to receive study treatment 
and 
• Does not want any further visits or assessments (including further study-related contacts) 
This request should be in writing (depending on local regulations) and recorded in the source 
documentation. 
In this situation, the Investigator should make a reasonable effort (e.g. telephone, e-mail, letter) 
to understand the primary reason for the participant’s decision to withdraw their 
consent/opposition to use data/biological samples and record this information. 
Study treatment must be discontinued and no further assessments conducted, and the data that 
would have been collected at subsequent visits will be considered missing. 
Further attempts to contact the participant are not allowed unless safety findings require 
communicating or follow-up. 
If the participant agrees, a final evaluation at the time of the participant’s withdrawal of 
consent/opposition to use data/biological samples should be made as detailed in the assessment 
table (refer to Section 8). 
Novartis 
Further details on withdrawal of consent or the exercise of participants' data privacy rights are 
included in the corresponding informed consent form. 
9.3 
Study completion and post-study treatment 
Study completion is defined as when the last participant finishes their end of Post-treatment 
Follow-up visit and any repeat assessments associated with this visit have been documented 
and followed-up appropriately by the Investigator or, in the event of an early study termination 
decision, the date of that decision. 
During the Post-treatment Follow-up period, the Investigator should consider the benefit/risk 
of initiation of alternative MS therapy in terms of the participant's clinical status, local 
regulations, treatment guidelines and local prescribing information. When initiating other 
immunosuppressive therapies with prolonged immune effects after study drug, the duration and 
mode of action should be taken into account because of potential additive immunosuppressive 
effect.  

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9.4 
Early study termination by the sponsor 
The study can be terminated by Novartis at any time. 
Reasons for early termination may include the benefit/risk assessment of participating in the 
study, practical reasons, or for regulatory or medical reasons. 
In taking the decision to terminate, Novartis will always consider participant welfare and safety. 
Should early termination be necessary, participants must be seen as soon as possible and treated 
as a prematurely withdrawn participant. The Investigator may be informed of additional 
procedures to be followed in order to ensure that adequate consideration is given to the 
protection of the participant’s interests. The Investigator or Sponsor depending on local 
regulation will be responsible for informing IRBs/IECs of the early termination of the trial. 
10 
Safety monitoring, reporting and committees 
10.1 
Definition of adverse events and reporting requirements 
10.1.1 
Adverse events 
An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and 
unintended sign including abnormal laboratory findings, symptom or disease) in a clinical 
investigation participant after providing written informed consent for participation in the study. 
Therefore, an AE may or may not be temporally or causally associated with the use of a 
medicinal (investigational) product. 
The investigator has the responsibility for managing the safety of individual participant and 
identifying adverse events. 
Novartis qualified medical personnel will be readily available to advise on trial-related medical 
questions or problems. 
The occurrence of adverse events must be sought by non-directive questioning of the participant 
at each visit during the study. Adverse events also may be detected when they are volunteered 
by the participant during or between visits or through physical examination findings, laboratory 
test findings, or other assessments. 
Abnormal laboratory values or test results constitute adverse event only if they fulfill at least 
one of the following criteria: 
• they induce clinical signs or symptoms 
• they are considered clinically significant 
• they require therapy 
Clinically significant abnormal laboratory values or test results must be identified through a 
review of values outside of normal ranges/clinically notable ranges, significant changes from 
baseline or the previous visit, or values, which are considered non-typical in participants with 
the underlying disease. Investigators have the responsibility for managing the safety of 
individual participant and identifying adverse events. Clinically notable laboratory findings are 
defined according to the Common Terminology Criteria for Adverse Events (CTCAE) (the 
most current version will be used and can be found on the following web-site: ctep.cancer.gov). 

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Adverse events must be recorded under the signs, symptoms, or diagnosis associated with them, 
accompanied by the following information (as far as possible) (if the event is serious refer to 
Section 10.1.2): 
1. The CTCAE grade (1-4) 
If CTCAE grading does not exist for an adverse event, use: 
• 1 = mild: usually transient in nature and generally not interfering with normal 
activities 
• 2 = moderate: sufficiently discomforting to interfere with normal activities 
• 3 = severe: prevents normal activities 
• 4 = life-threatening 
2. Its relationship to the study treatment. If the event is due to lack of efficacy or progression 
of underlying illness (i.e. progression of disability) the assessment of causality will usually 
be ‘Not suspected.’ The rationale for this guidance is that the symptoms of a lack of 
efficacy or progression of underlying illness are not caused by the trial drug, they happen 
in spite of its administration and/or both lack of efficacy and progression of underlying 
disease can only be evaluated meaningfully by an analysis of cohorts, not on a single 
participant. 
3. Its duration (start and end dates or ongoing) and the outcome must be reported 
4. Whether it constitutes a SAE (see Section 10.1.2 for definition of SAE) and which 
seriousness criteria have been met 
5. Action taken regarding with study treatment. 
All adverse events must be treated appropriately. Treatment may include one or more of the 
following: 
• No action taken (e.g. further observation only) 
• Drug interrupted/permanently discontinued 
6. Its outcome  
• Not recovered/not resolved 
• Recovered/resolved, 
• Recovering/resolving, 
• Recovered/resolved with sequelae 
• Fatal 
• Unknown 
Conditions that were already present at the time of informed consent should be recorded in the 
medical history of the participant. 
Adverse events (including lab abnormalities that constitute AEs) should be described using a 
diagnosis whenever possible, rather than individual underlying signs and symptoms. 
Once an adverse event is detected, it must be followed until its resolution or until it is judged to 
be permanent (e.g. continuing at the end of the study), and assessment must be made at each 
visit (or more frequently, if necessary) of any changes in severity, the suspected relationship to 
the interventions required to treat it, and the outcome. 

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Information about adverse drug reactions for the investigational drug can be found in the 
Investigator's Brochure (IB). 
As per the local requirement, non-serious adverse drug reactions will be collected and reported 
to the health authority in China. 
10.1.2 
Serious adverse events 
An SAE is defined as any adverse event [appearance of (or worsening of any pre-existing)] 
undesirable sign(s), symptom(s), or medical conditions(s) which meets any one of the following 
criteria: 
• fatal 
• life-threatening 
Life-threatening in the context of a SAE refers to a reaction in which the participant was at risk 
of death at the time of the reaction; it does not refer to a reaction that hypothetically might have 
caused death if it were more severe (please refer to the ICH-E2D Guidelines). 
• results in persistent or significant disability/incapacity  
• constitutes a congenital anomaly/birth defect 
• requires inpatient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is for:  
• routine treatment or monitoring of the studied indication, not associated with any 
deterioration in condition 
• elective or pre-planned treatment for a pre-existing condition that is unrelated to the 
indication under study and has not worsened since signing the informed consent 
• social reasons and respite care in the absence of any deterioration in the participant’s 
general condition 
• treatment on an emergency outpatient basis for an event not fulfilling any of the 
definitions of a SAE given above and not resulting in hospital admission 
• is medically significant, e.g. defined as an event that jeopardizes the participant or may 
require medical or surgical intervention to prevent one of the outcomes listed above 
Medical and scientific judgment should be exercised in deciding whether other situations should 
be considered serious reactions, such as important medical events that might not be immediately 
life threatening or result in death or hospitalization but might jeopardize the participant or might 
require intervention to prevent one of the other outcomes listed above. Such events should be 
considered as “medically significant.” Examples of such events are intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias, or convulsions that 
do not result in hospitalization or development of dependency or abuse (please refer to the ICH-
E2D Guidelines). 
All new malignant neoplasms will be assessed as serious under “medically significant” if other 
seriousness criteria are not met. 
Any suspected transmission via a medicinal product of an infectious agent is also considered a 
serious adverse reaction. 

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All reports of intentional misuse and abuse of the product are also considered serious adverse 
event irrespective if a clinical event has occurred. 
10.1.3 
SAE reporting 
To ensure participant safety, every SAE, regardless of causality, occurring after the participant 
has provided informed consent and until the End of Post-treatment FU or EOS (if the participant 
continues with commercial ofatumumab after treatment completion and does not enter Post-
treatment FU) must be reported to Novartis safety immediately, without undue delay, under no 
circumstances later than within 24 hours of learning of its occurrence. Detailed instructions 
regarding the submission process and requirements are to be found in the investigator folder 
provided to each site. Information about all SAEs is collected and recorded on the eSAE with 
paper backup SAE Report Form; all applicable sections of the form must be completed in order 
to provide a clinically thorough report. 
Protocol exempt SAEs  
MS relapses as defined in Section 8.3.1 are part of one of the effectiveness endpoints in this 
study; hence, they are exempt from SAE reporting although they may meet the SAE definition 
on the basis that they are considered medically significant and are frequently associated with 
hospitalization. These events will therefore be reported on the corresponding eCRF instead of 
the SAE form. However, if, in the judgment of the Investigator, a MS relapse is unusually severe 
or medically unexpected and warrants specific notification, then an SAE form should be 
completed and submitted according to SAE reporting procedures outlined above. 
Disability progression as defined in Section 8.3.3 is one of the efficacy endpoints in this study; 
hence it is exempt from SAE reporting although it may meet the SAE definition “results in 
persistent or significant disability/incapacity”.  
However, if, in the judgment of the Investigator the disability progression is unusually severe 
or medically unexpected and warrants specific notification, then an SAE form should be 
completed and submitted according to SAE reporting procedures outlined above. 
All follow-up information for the SAE including information on complications, progression of 
the initial SAE and recurrent episodes must be reported as follow-up to the original episode 
within 24 hours of the investigator receiving the follow-up information. An SAE occurring at a 
different time interval or otherwise considered completely unrelated to a previously reported 
one must be reported separately as a new event. 
If the SAE is not previously documented in the Investigator’s Brochure or Package Insert (new 
occurrence) and is thought to be related to the study treatment, a CMO & PS Department 
associate may urgently require further information from the investigator for health authority 
reporting. Novartis may need to issue an Investigator Notification (IN) to inform all 
investigators involved in any study with the same study treatment that this SAE has been 
reported. 
Suspected Unexpected Serious Adverse Reactions (SUSARs) will be collected and reported to 
the competent authorities and relevant ethics committees in accordance with EU Guidance 
2011/C 172/01 or as per national regulatory requirements in participating countries. 

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Any SAEs experienced after the reporting period should only be reported to Novartis Safety if 
the Investigator suspects a causal relationship to study treatment, unless otherwise specified by 
local law/regulations. 
10.1.4 
Pregnancy reporting 
Pregnancies 
If a female trial participant becomes pregnant, the study treatment should be stopped, and the 
pregnancy consent form should be presented to the trial participant. The participant must be 
given adequate time to read, review and sign the pregnancy consent form. This consent form is 
necessary to allow the Investigator to collect and report information regarding the pregnancy. 
After consent is provided, the pregnancy reporting will occur up to one year after the estimated 
date of delivery to collect information about the pregnancy follow up data and the health of the 
baby (if the pregnancy results in a live birth). To ensure participant safety, each pregnancy 
occurring after signing the informed consent must be reported to Novartis within 24 hours of 
learning of its occurrence. The pregnancy should be followed up to determine outcome, 
including spontaneous or voluntary termination, details of the birth, and the presence or absence 
of any birth defects, congenital abnormalities, or maternal and/or newborn complications. 
Pregnancy should be recorded and reported by the Investigator to the Novartis Chief Medical 
Office and Patient Safety (CMO&PS). Pregnancy follow-up should be recorded on the same 
form and should include an assessment of the possible relationship to ofatumumab any 
pregnancy outcome. Any SAE experienced during pregnancy must be reported. 
10.1.5 
Reporting of study treatment errors including misuse/abuse 
Medication errors are unintentional errors in the prescribing, dispensing, administration or 
monitoring of a medicine while under the control of a healthcare professional, participant or 
consumer (EMA definition). 
Misuse refers to situations where the medicinal product is intentionally and inappropriately used 
not in accordance with the protocol. 
Abuse corresponds to the persistent or sporadic, intentional excessive use of a medicinal 
product, which is accompanied by harmful physical or psychological effects. 
Study treatment errors and uses outside of what is foreseen in the protocol will be recorded on 
the appropriate eCRF irrespective of whether or not associated with an AE/SAE and reported 
to Safety only if associated with an SAE. Misuse or abuse will be collected and reported in the 
safety database irrespective of it being associated with an AE/SAE within 24 hours of 
Investigator’s awareness. 

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Table 10-1 
Guidance for capturing the study treatment errors including 
misuse/abuse 
Treatment error type 
Document in Dosing 
CRF (Yes/No) 
Document in AE eCRF 
Complete SAE form 
Unintentional study 
treatment error 
Yes 
Only if associated with an 
AE 
Only if associated with an 
SAE 
Misuse/Abuse 
Yes 
Yes 
Yes, even if not 
associated with an SAE 
For more information on AE and SAE definition and reporting requirements, please see the 
respective sections. 
10.2 
Additional Safety Monitoring 
10.2.1 
Liver safety monitoring 
To ensure participant safety and enhance reliability in determining the hepatotoxic potential of 
an investigational drug, a standardized process for identification, monitoring and evaluation of 
liver events has to be followed. 
Once a participant is exposed to study treatment, every liver event defined in Table 16-1 and 
Table 16-2 should be followed up by the Investigator or designated personnel at the trial site, 
as summarized below. Additional details on actions required in case of liver events are outlined 
in Table 16-1 and Table 16-2. Repeat liver chemistry tests to confirm elevation. 
• These liver chemistry repeats will be performed using the central laboratory. If results will 
not be available from the central laboratory, then the repeats can also be performed at a 
local laboratory to monitor the safety of the participant. If a liver event is subsequently 
reported, any local liver chemistry tests previously conducted that are associated with this 
event should have results recorded on the appropriate CRF 
• If the initial elevation is confirmed, close observation of the participant will be initiated, 
including consideration of treatment interruption if deemed appropriate. 
• Discontinuation of the investigational drug (refer to Section 9.1.1 Discontinuation from 
study treatment), if appropriate 
• Hospitalization of the participant if appropriate 
• Causality assessment of the liver event 
• Thorough follow-up of the liver event should include:  
• These investigations can include based on investigator’s discretion: serology tests, 
imaging and pathology assessments, hepatologist’s consultancy; obtaining more 
detailed history of symptoms and prior or concurrent diseases, history of concomitant 
drug use, exclusion of underlying liver disease 
All follow-up information and procedures performed must be recorded as appropriate in the 
eCRF. 
10.2.2 
Renal safety monitoring 
Once a participant is exposed to study treatment, the following two categories of abnormal renal 
laboratory alert values should be assessed during the study period: 

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• Serum creatinine increase ≥ 25% compared to baseline during normal hydration status 
• Any one of the following:  
• Urine protein-creatinine ratio (PCR) ≥1g/g or ≥100 mg/mmol, OR 
• New onset dipstick proteinuria ≥ 3+, OR 
• New onset dipstick hematuria ≥ 3+(after excluding menstruation, UTI, extreme 
exercise, or trauma) 
Abnormal renal event findings must be confirmed after ≥24 hours but ≤ 5 days after first 
assessment. 
Once a participant is exposed to study treatment, renal laboratory alerts or renal safety events 
should be monitored and followed up by the investigator or designated trial staff as summarized 
in Table 16-3. 
10.3 
Committees 
Not applicable 
11 
Data Collection and Database management 
11.1 
Data collection 
Designated investigator staff will enter the data required by the protocol into the Electronic 
Case Report Forms (eCRF). The eCRFs have been built using fully validated secure web-
enabled software that conforms to 21 CFR Part 11 requirements, Investigator site staff will not 
be given access to the EDC system until they have been trained. Automatic validation programs 
check for data discrepancies in the eCRFs, allow modification and/or verification of the entered 
data by the investigator staff. 
The Investigator/designee is responsible for assuring that the data (entered into eCRF) is 
complete, accurate, and that entry and updates are performed in a timely manner. The 
Investigator must certify that the data entered are complete and accurate. 
After final database lock, the Investigator will receive copies of the participant data for 
archiving at the investigational site. 
All data should be recorded, handled, and stored in a way that allows its accurate reporting, 
interpretation, and verification. 
11.2 
Database management and quality control 
Novartis personnel (or designated CRO) will review the data entered by investigational staff 
for completeness and accuracy. Electronic data queries stating the nature of the problem and 
requesting clarification will be created for discrepancies and missing values and sent to the 
investigational site via the EDC system. Designated investigator site staff are required to 
respond promptly to queries and to make any necessary changes to the data. 
Concomitant treatments and prior medications entered into the database will be coded using the 
World Health Organization (WHO) Drug Reference List, which employs the Anatomical 

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Therapeutic Chemical classification system. Medical history/current medical conditions and 
adverse events will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
terminology. 
Laboratory samples will be processed centrally and the results will be sent electronically to 
Novartis. MRI scans will be analyzed centrally and the derived results will also be sent 
electronically to Novartis. 
For electronic COAs, devices will be supplied by a vendor, data will be processed centrally, 
and both raw and processed data will be sent electronically to Novartis (or a designated CRO). 
Once all the necessary actions have been completed and the database has been declared to be 
complete and accurate, it will be locked. Any changes to the database after that time can only 
be made after written agreement by Novartis development management. 
11.3 
Site monitoring 
Before study initiation, at a site initiation visit or at an investigator’s meeting, a Novartis 
representative will review the protocol and data capture requirements (i.e. eSource DDE or 
eCRFs) with the investigators and their staff. During the study, Novartis employs several 
methods of ensuring protocol and GCP compliance and the quality/integrity of the sites’ data. 
The field monitor will visit the site to check the completeness of participant records, the 
accuracy of data capture / data entry, the adherence to the protocol and to Good Clinical 
Practice, the progress of enrollment, and to ensure that study treatment is being stored, 
dispensed, and accounted for according to specifications. Key study personnel must be available 
to assist the field monitor during these visits. Continuous remote monitoring of each site’s data 
may be performed by a centralized Novartis CRA organization (or a delegated CRO). 
Additionally, a central analytics organization may analyze data and identify risks and trends for 
site operational parameters, and provide reports to Novartis clinical teams to assist with trial 
oversight. 
The Investigator must maintain source documents for each participant in the study, consisting 
of case and visit notes (hospital or clinic medical records) containing demographic and medical 
information, laboratory data, electrocardiograms, and the results of any other tests or 
assessments. All information on eCRFs must be traceable to these source documents in the 
participant's file. The Investigator must also keep the original ICF signed by the participant (a 
signed copy is given to the participant). 
The Investigator must give the monitor access to all relevant source documents to confirm their 
consistency with the data capture and/or data entry. Novartis monitoring standards require full 
verification for the presence of informed consent, adherence to the inclusion/exclusion criteria, 
documentation of SAEs, and of data that will be used for all primary variables. Additional 
checks of the consistency of the source data with the eCRFs are performed according to the 
study-specific monitoring plan. No information in source documents about the identity of the 
participants will be disclosed. 

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12 
Data analysis and statistical methods 
The analyses (summaries or listings) will be conducted on all participant data at the time of end 
of study (i.e. including data from the Post-treatment Follow-up part). 
Interim analysis will be performed at the planned time point with details defined in Section 12.7. 
There will be no hypothesis testing performed in this study. Data will be summarized 
descriptively. In general, categorical data will be presented as frequency and percentage; 
continuous data will be summarized by mean, standard deviation (SD), median, minimum, and 
maximum. For primary efficacy endpoints, the point estimate and confidence interval will be 
model-based. Additional analysis populations may be defined and sensitivity analyses may be 
conducted to evaluate the impact of COVID-19 pandemic. 
Any data analysis carried out independently by the investigator should be submitted to Novartis 
before publication or presentation. 
12.1 
Analysis sets 
The Full Analysis Set (FAS) comprises all participants who have signed the Informed Consent 
and who have received at least one dose of study treatment. The FAS will be used for the 
summary of demography and baseline characteristics as well as for all efficacy analyses. 
The Safety Set (SAF) is identical to FAS in this study. The Safety Set will be used for all safety 
analyses. 
12.2 
Participant demographics and other baseline characteristics 
Demographics, MS disease history, MRI baseline characteristics and MS medication history 
will be summarized descriptively and/or listed for the FAS as appropriate. 
Categorical data will be presented as frequencies and percentages. For continuous data, mean, 
standard deviation, median, minimum, and maximum will be presented. For selected 
parameters, 25th and 75th percentiles will also be presented. 
Relevant medical histories and current medical conditions at baseline will be summarized by 
system organ class and preferred term. 
12.3 
Treatments 
The summary of exposure and time-at-risk will be based on the SAF. 
Exposure to investigational study medication is defined as the number of days spent on study 
treatment divided by 365.25 days. Intermediate treatment interruptions will be subtracted from 
drug exposure. Exposure to investigational study medication will be summarized with number 
and percentage of participants by time category, and with summary statistics of the number of 
participant years of exposure. Further details will be included in the statistical analysis plan 
(SAP). 
Time-at-risk is defined as the number of days spent in the study, from first dose to the last dose 
of study medication, plus the safety data cut-off of 100 days (or until EOS for participants 
continue with commercial ofatumumab immediately after EOS, or until last dose of study 

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medication plus 100 days or one day before switching to another DMT, whichever comes 
earlier, for participants who have such switch in the PT FU). Intermediate treatment 
interruptions will be included in time-at-risk calculations. Time-at-risk corresponds to the time 
window used for adverse event reporting and can serve as a denominator to safety (e.g. in 
exposure-adjusted incidence rates). Time-at-risk will be summarized in a similar way to 
exposure to investigational study medication. Further details will be specified in the SAP. 
Concomitant medications and significant non-drug therapies prior to and after the start of the 
study treatment will be summarized and/or listed according to the Anatomical Therapeutic 
Chemical (ATC) classification system. 
12.4 
Analysis supporting primary objectives 
12.4.1 
Definition of primary endpoint(s) 
The primary endpoint is the annualized relapse rate (ARR), which is defined as the average 
number of confirmed MS relapses in a year. In the primary analysis, the ARR is estimated based 
on the FAS which follows the intent-to-treat principle using a negative binomial model by 
including individual cumulative confirmed relapse counts as the response variable with 
participants' time in study as an offset variable. 
Two variables are required for the calculation of the ARR (excluding covariates): 
• The cumulative number of confirmed MS relapses by participant is the response variable 
in the negative binomial model. The confirmation based on EDSS will be derived as 
defined in Section 8.3.1. 
• The time-in-study by participant will be used as an offset variable to adjust for the various 
length participants have been observed and at-risk of a confirmed MS relapse in the study. 
12.4.2 
Statistical model, hypothesis, and method of analysis 
In the primary analysis, the ARR will be estimated by a negative binomial regression model 
with log-link function, the cumulative number of confirmed MS relapses per participant as the 
response variable, number of relapses in the previous year (or two years) before enrollment, 
baseline EDSS, baseline age and baseline number of Gd-enhancing T1 lesions as continuous 
covariates. Natural log of time on study in years will be used as the offset variable to account 
for the varying lengths of participants' time in the study. The adjusted ARR (i.e., model-based 
estimate adjusted for covariates) and the corresponding 95% confidence interval will be 
obtained. 
The primary analysis will be performed for FAS. 
12.4.3 
Handling of missing visits/censoring/discontinuation 
For participants who withdraw early from the study, the number of relapses up to the study 
discontinuation will be used for the primary analysis. No imputation will be applied to the 
incomplete study duration. 

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The primary negative binomial regression model with an offset for the time in study adjusts for 
missing information (drop-out) under the assumption of non-informative drop-out, information 
is missing at random, and constant relapse rate over time. 
12.4.4 
Supportive analysis 
The primary analysis will be repeated based on all reported MS relapses (rather than on only 
the confirmed ones) for FAS population. 
A summary of ARR time-based and ARR participant-based will also be given. Time-based 
ARRs are calculated by taking the total number of relapses observed for all participants in FAS 
divided by the total number of days in study of those participants and multiplied by 365.25 
days. Also, participant-based ARR is presented, where individual ARRs are computed and 
summarized over participants for FAS population. ­For above ARR calculations, the analysis 
will consider confirmed relapses only.  
Additional sensitivity analyses may be defined in the statistical analysis plan. 
12.5 
Analysis supporting secondary objectives 
12.5.1 
Efficacy and/or Pharmacodynamic endpoint(s) 
The following MRI efficacy variables will be analyzed based on FAS: 
• The analysis of the number of Gd-enhancing T1 lesions per MRI-scan will be done using a 
negative binomial regression model with log-link function. The total number of Gd-
enhancing lesions (cumulative count of Gd-enhancing lesions across all the MRI-scans per 
participant) will be used as the response variable, using baseline age and baseline number 
of Gd-enhancing T1 lesions as continuous covariates. Natural log of the number of MRI-
scans will serve as the offset variable to account for the varying lengths of participants' 
time in the study. The number of Gd-enhancing lesions per scan will be estimated and the 
corresponding 95% confidence interval will be obtained. 
• The analysis of the annualized rate of new or enlarging T2 lesions will be done using a 
negative binomial regression model with log-link function. The number of new or 
enlarging T2 lesions on the last available MRI scan relative to baseline will be used as the 
response variable, using baseline age and baseline volume of T2 lesions as continuous 
covariates. Natural log of the time (in years) of the MRI-assessment from the 
baseline/Screening scan will serve as the offset variable to account for the varying lengths 
of participants' time in the study. The number of new or enlarging T2 lesions per year will 
be estimated and the corresponding 95% confidence interval will be obtained. 
• Change from baseline in T2 lesion volume on MRI will be summarized by visit. 
12.5.2 
Safety endpoints 
For all safety analyses, the safety set will be used. Unless explicitly stated otherwise, only data 
up to and including the safety cut-off of 100 days after permanent study treatment 
discontinuation or treatment completion (or EOS for participants continue with commercial 
ofatumumab immediately after EOS, or min(last dose of study medication + 100 days, date of 
switching to another DMT - 1) for participants who have such switch in the PT FU) will be 

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included in the analysis and data beyond this time point for a participant will be excluded from 
safety analysis. 
The assessment of safety data will be primarily based on the frequency and percentage of 
adverse events (including death and non-fatal serious adverse events). Additional safety 
assessments such as laboratory tests, physical examination (including examination of skin), and 
vital signs will be analyzed. Clinically significant findings in these additional safety 
assessments will be reported as adverse events and analyzed as such. The detailed analyses of 
additional safety assessments will be defined in the SAP. 
Adverse events 
Treatment-emergent adverse events including serious adverse events and deaths will be 
summarized up to and including the safety cut-off. 
The number (and percentage) of participants with treatment emergent adverse events (events 
started after the first dose of study medication or events present prior to start of treatment but 
increased in severity based on preferred term) will be summarized in the following ways: 
· by primary system organ class and preferred term. 
· by primary system organ class, preferred term and maximum severity. 
Separate summaries will be provided for adverse events related to study treatment, death, 
serious adverse events, and other significant adverse events leading to interruption or 
discontinuation, if appropriate. 
Specific risks of interest will be defined by combinations of adverse event and/or other relevant 
safety data (e.g. lab data). The number (and proportion) of participants fulfilling such risk 
definitions will be summarized. 
A participant with multiple adverse events within a primary system organ class will only be 
counted once towards the total of the primary system organ class. 
Given the flexible follow-up of the study, treatment-emergent adverse events will also be 
summarized by reporting exposure-adjusted incidence rates (assuming a Poisson-process for 
adverse events). This will be done for all treatment-emergent adverse events, and for serious 
treatment-emergent adverse events, by primary system organ class and preferred term. 
Vital signs 
Vital sign measurements and their change from baseline will be summarized with descriptive 
statistics (mean, median, standard deviation, min, max) by visit. The number and percentage of 
participants with clinically notable vital signs will be presented, if appropriate. The clinically 
notable definitions will be provided in SAP as needed. 
Clinical laboratory evaluations 
The summary of laboratory evaluations will be presented for 2 groups of laboratory tests: 
hematology and chemistry. 

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Laboratory measurements and their change from baseline will be summarized with descriptive 
statistics (mean, median, standard deviation, min, max) by visit. The number and percentage of 
participants with clinically notable vital signs will be presented, if appropriate. The clinically 
notable definitions will be provided in SAP as needed. 
Other safety evaluations 
All clinically significant safety findings based on additional safety evaluations (e.g. physical 
examination, urinalysis etc.) must be reported as adverse events on the appropriate eCRF. The 
statistical analysis of these findings will be done in the analysis of adverse events. Other safety 
data will be summarized or listed as appropriate. 
12.7 
Interim analyses 
One interim analysis is planned in approximately Q1 2025, unless the final analysis will have 
already been completed. The efficacy and safety data (including summaries on key efficacy and 
safety endpoints) will be submitted to NMPA for local license renewal for Kesimpta. 
12.8 
Sample size calculation 
12.8.1 
Primary endpoint(s) 
The ARR of Chinese RMS participants treated with ofatumumab is assumed based on the 
pivotal studies, COMB157G2301 and COMB157G2302. Since the participants are treated up 
to 12 months in the current study, the cumulative ARR from Month 0 to Month 12 from the 
pivotal studies is adopted: 
 
Ofatumumab 20mg 
Teriflunomide 14mg 
Cumulative ARR from Month 0 to Month 12 in 
COMB157G2301 & COMB157G2302 
0.145 
0.307 
Under the assumption of a negative binomial distribution (~ NB(µ, k)) for the ARR, where µ is 
the true ARR which we assume to be 0.15 based on the reference above, and k is the dispersion 
parameter which we assume to be 0.82 based on historical trialdata in MS. For different sample 
sizes, the following can be calculated using normal approximation: the 95% lower and upper 
ranges of the estimated ARR (point estimate), and the probability of showing the ARR on 
ofatumumab is significantly lower than 0.30 (i.e. lower than the historical reference value for 
the ARR in patients treated with teriflunomide based on the COMB157G2301 & 
COMB157G2302 trial data)). Note that this probability is equivalent to the probability that the 
upper limit of 95% CI is lower than 0.3. The results are showed below. 
µ (true 
ARR) 
k 
Sample 
size 
95% lower range 
of estimated ARR 
95% upper range 
of estimated ARR 
Probability that the upper limit 
of 95% CI is lower than 0.30 
0.15 
0.82 
60 
0.05 
0.25 
80.8% 
0.15 
0.82 
65 
0.05 
0.25 
83.8% 

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µ (true 
ARR) 
k 
Sample 
size 
95% lower range 
of estimated ARR 
95% upper range 
of estimated ARR 
Probability that the upper limit 
of 95% CI is lower than 0.30 
0.15 
0.82 
70 
0.05 
0.25 
86.4% 
0.15 
0.82 
75 
0.06 
0.24 
88.6% 
0.15 
0.82 
80 
0.06 
0.24 
90.5% 
0.15 
0.82 
85 
0.06 
0.24 
92.1% 
0.15 
0.82 
90 
0.07 
0.23 
93.4% 
Based on the calculation, a sample with 85 participants will provide an estimated ARR in [0.06, 
0.24] with 95% probability. In addition, with a probability of 92.1%, a sample with this size 
will also provide a 95% CI with upper limit lower than 0.30, i.e. it would be strongly suggestive 
of a higher efficacy of ofatumumab compared with the historical teriflunomide data. Therefore, 
a sample size of 85 completers is considered adequate. Allowing for a dropout rate of 15% 
(dropout rate was 10.3% in COMB157G2301 and 17.3% in COMB157G2302), the sample size 
for this study will be approximately 100 participants. 
Sample size calculation was performed in nQuery 8, Version 8.4.1.0, Statistical Solutions Ltd. 
13 
Ethical considerations and administrative procedures 
13.1 
Regulatory and ethical compliance 
This clinical study was designed and shall be implemented, executed and reported in accordance 
with the ICH Harmonized Tripartite Guidelines for Good Clinical Practice, with applicable 
local regulations, and with the ethical principles laid down in the Declaration of Helsinki. 
13.2 
Responsibilities of the investigator and IRB/IEC 
Before initiating a trial, the investigator/institution must obtain approval/favorable opinion from 
the Institutional Review Board/Independent Ethics Committee (IRB/IEC) for the trial protocol, 
written ICF, consent form updates, participant recruitment procedures (e.g. advertisements) and 
any other written information to be provided to participants. Prior to study start, the investigator 
is required to sign a protocol signature page confirming his/her agreement to conduct the study 
in accordance with these documents and all of the instructions and procedures found in this 
protocol and to give access to all relevant data and records to Novartis monitors, auditors, 
Novartis Quality Assurance representatives, designated agents of Novartis, IRBs/IECs, and 
regulatory authorities as required. If an inspection of the clinical site is requested by a regulatory 
authority, the investigator must inform Novartis immediately that this request has been made. 
13.3 
Publication of study protocol and results 
The protocol will be registered in a publicly accessible database such as clinicaltrials.gov. In 
addition, after study completion (defined as last patient last visit) and finalization of the study 
report the results of this trial will be submitted for publication and posted in a publicly accessible 
database of clinical trial results, such as the Novartis clinical trial results website and all required 
health authority websites (e.g. clinicaltrials.gov) . 

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For details on the Novartis publication policy including authorship criteria, please refer to the 
Novartis publication policy training materials that were provided to you at the trial investigator 
meetings. 
13.4 
Quality Control and Quality Assurance 
Novartis maintains a robust Quality Management System (QMS) that includes all activities 
involved in quality assurance and quality control, to ensure compliance with written Standard 
Operating Procedures as well as applicable global/local GCP regulations and ICH Guidelines. 
Audits of investigator sites, vendors, and Novartis systems are performed by auditors, 
independent from those involved in conducting, monitoring or performing quality control of the 
clinical trial. The clinical audit process uses a knowledge/risk-based approach. 
Audits are conducted to assess GCP compliance with global and local regulatory requirements, 
protocols and internal SOPs, and are performed according to written Novartis processes. 
13.5 
Participant Engagement 
The following participant engagement initiatives are included in this study and will be provided, 
as available, for distribution to study participants at the timepoints indicated. If compliance is 
impacted by cultural norms or local laws and regulations, sites may discuss modifications to 
these requirements with Novartis. 
• Thank You letter 
• Plain language trial summary - after CSR publication 
• Trial Feedback Questionnaires (TFQ)  
14 
Protocol adherence 
This protocol defines the study objectives, the study procedures and the data to be collected on 
study participants. Additional assessments required to ensure safety of participants should be 
administered as deemed necessary on a case by case basis. Under no circumstances including 
incidental collection is an investigator allowed to collect additional data or conduct any 
additional procedures for any purpose involving any investigational drugs under the protocol, 
other than the purpose of the study. If despite this interdiction prohibition, data, information, 
observation would be incidentally collected, the investigator shall immediately disclose it to 
Novartis and not use it for any purpose other than the study, except for the appropriate 
monitoring on study participants. 
Investigators ascertain they will apply due diligence to avoid protocol deviations. If an 
investigator feels a protocol deviation would improve the conduct of the study this must be 
considered a protocol amendment, and unless such an amendment is agreed upon by Novartis 
and approved by the IRB/IEC and Health Authorities, where required, it cannot be 
implemented. 

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14.1 
Protocol amendments 
Any change or addition to the protocol can only be made in a written protocol amendment that 
must be approved by Novartis, health authorities where required, and the IRB/IEC prior to 
implementation. 
Only amendments that are required for participant safety may be implemented immediately 
provided the health authorities are subsequently notified by protocol amendment and the 
reviewing IRB/IEC is notified. 
Notwithstanding the need for approval of formal protocol amendments, the investigator is 
expected to take any immediate action required for the safety of any participant included in this 
study, even if this action represents a deviation from the protocol. In such cases, Novartis should 
be notified of this action and the IRB/IEC at the study site should be informed according to 
local regulations. 

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15 
References 
References are available upon request 
Archelos JJ, Storch MK, Hartung HP (2000) The role of B cells and autoantibodies in 
multiple sclerosis. Ann Neurol; 47(6):694-706. 
Arnold DL, Gold R, Kappos L, et al (2014) Effects of delayed-release dimethyl fumarate on 
MRI measures in the Phase 3 DEFINE study. J Neurol; 261:1794-802. 
Bleeker WK, Munk ME, Mackus WJ, et al (2008) Estimation of dose requirements for 
sustained in vivo activity of a therapeutic human anti-CD20 antibody. Br J Haematol; 
140:303-12. 
Calabresi PA, Radue EW, Goodin D, et al (2014) Safety and efficacy of fingolimod in 
patients with relapsing-remitting multiple sclerosis (FREEDOMS II): a double-blind, 
randomised, placebo-controlled, phase 3 trial. Lancet Neurol; 13:545-56. 
Chan KH, Tsang KL, Ho PW, et al (2011) Clinical outcome of relapsing remitting multiple 
sclerosis among Hong Kong Chinese. Clin Neurol Neurosurg; 113:617-22. 
Cheng XJ, Cheng Q, Xu LZ, et al (2010) Evaluation of multiple sclerosis diagnostic criteria in 
Suzhou, China--risk of under-diagnosis in a low prevalence area. Acta Neurol Scand; 121:24-
9. 
Claes N, Fraussen J, Stinissen P, et al (2015) B Cells Are Multifunctional Players in Multiple 
Sclerosis Pathogenesis: Insights from Therapeutic Interventions. Front Immunol; 6:642. 
D'Amico E, Zanghì A, Gastaldi M, et al (2019) Placing CD20-targeted B cell depletion in 
multiple sclerosis therapeutic scenario: Present and future perspectives. Autoimmun Rev; 
18:665-72. 
Frohman EM, Racke MK, Raine CS (2006) Multiple sclerosis--the plaque and its 
pathogenesis. N Engl J Med; 354(9):942-55. 
Gold R, Kappos L, Arnold DL, et al (2012) Placebo-controlled phase 3 study of oral BG-12 
for relapsing multiple sclerosis. N Engl J Med; 367(12):1098-107. 
Gold R, Radue EW, Giovannoni G, et al (2016) Safety and efficacy of daclizumab in 
relapsing-remitting multiple sclerosis: 3-year results from the SELECTED open-label 
extension study. BMC Neurol; 16:117. 
Goldstein KM, Lunyera J, Mohottige D, et al (2019) Risk of Nephrogenic Systemic Fibrosis 
after Exposure to Newer Gadolinium Agents [Internet]. Washington (DC): Department of 
Veterans Affairs (US); 2019 Oct. 
Goodin DS, Frohman EM, Garmany GP, et al (2002) Disease modifying therapies in multiple 
sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the 
American Academy of Neurology and the MS Council for Clinical Practice Guidelines. 
Neurology; 58:169-78. 
Hauser SL, Bar-Or A, Cohen JA, et al (2020) Ofatumumab versus Teriflunomide in Multiple 
Sclerosis. N Engl J Med; 383(6):546-557. 

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Hauser SL, Bar-Or A, Comi G, et al (2017) Ocrelizumab versus Interferon Beta-1a in 
Relapsing Multiple Sclerosis. N Engl J Med; 376(3):221-34. 
Kappos L, Bar-Or A, Cree BAC, et al (2018) Siponimod versus placebo in secondary 
progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study. Lancet; 
391:1263-73. 
Kappos L, Radue EW, O'Connor P, et al (2010) A placebo-controlled trial of oral fingolimod 
in relapsing multiple sclerosis. N Engl J Med; 362(5):387-401. 
Lau KK, Wong WW, Sheng B, et al (2008) The clinical course of multiple sclerosis patients 
in Hong Kong. J Neurol Sci; 268:78-82. 
Lublin FD, Reingold SC, Cohen JA, et al (2014) Defining the clinical course of multiple 
sclerosis: the 2013 revisions. Neurology; 83:278-86. 
MSIF Multiple Sclerosis International Federation. Atlas of MS 3rd edition; available at: 
atlasofms.org/map/global/epidemiology/number-of-people-with-ms. 
McFarland HF (2008) The B cell--old player, new position on the team. N Engl J Med; 
358(7):664-5. 
O'Connor P, Wolinsky JS, Confavreux C, et al (2011) Randomized trial of oral teriflunomide 
for relapsing multiple sclerosis. N Engl J Med; 365(14):1293-303. 
Sabatino JJ, Pröbstel AK, Zamvil SS (2019) B cells in autoimmune and neurodegenerative 
central nervous system diseases. Nat Rev Neurosci; 20:728-45. 
Samjoo IA, Worthington E, Drudge C, et al (2020) Comparison of ofatumumab and other 
disease-modifying therapies for relapsing multiple sclerosis: a network meta-analysis. J Comp 
Eff Res; 9(18):1255-74. 
Selmaj K, Li DK, Hartung HP, et al (2013) Siponimod for patients with relapsing-remitting 
multiple sclerosis (BOLD): an adaptive, dose-ranging, randomised, phase 2 study. Lancet 
Neurol; 12:756-67. 
Teeling JL, Mackus WJ, Wiegman LJ, et al (2006) The biological activity of human CD20 
monoclonal antibodies is linked to unique epitopes on CD20. J Immunol; 177:362-71. 
Thompson AJ, Banwell BL, Barkhof F, et al (2018) Diagnosis of multiple sclerosis: 2017 
revisions of the McDonald criteria. Lancet Neurol; 17:162-73. 
Wingerchuk DM, Banwell B, Bennett JL, et al (2015) International consensus diagnostic 
criteria for neuromyelitis optica spectrum disorders. Neurology; 85:177-89. 
Yadav SK, Soin D, Ito K, et al (2019) Insight into the mechanism of action of dimethyl 
fumarate in multiple sclerosis. J Mol Med; 97:463-72. 

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16 
Appendices 
16.1 
Appendix 1: Liver event and laboratory trigger definitions & 
follow-up requirements 
Tables below provide the clinically notable liver function test results and the required actions. 
When the laboratory abnormality is deemed clinically significant, AEs must be reported. 
Clinical symptoms with a diagnosis must be reported as AEs. 
Table 16-1 
Follow up requirements for liver laboratory triggers 
ALT or AST 
TBL 
Liver 
Symptoms 
Action 
ALT/AST increase without bilirubin increase: 
If normal at baseline: 
ALT/AST > 3 x ULN 
Normal; 
For participants with 
Gilbert’s syndrome: 
No clinically 
significant change in 
baseline TBL 
None 
• 
No change to study 
treatment 
• 
Measure ALT, AST, ALP, 
GGT, TBIL, INR, albumin, 
CK, and GLDH in 48-72 
hours. 
• 
Follow-up for 
symptoms/etiology to 
establish causality 
If elevated at baseline: 
ALT/AST > 2 x baseline 
If normal at baseline: 
ALT/AST > 5 x ULN for more 
than two weeks 
Normal; 
For participants with 
Gilbert’s syndrome: 
No clinically 
significant change in 
baseline TBL 
None 
• 
Interrupt study drug 
• 
Measure ALT, AST, ALP, 
GGT, TBIL, INR, albumin, 
CK, and GLDH in 48-72 
hours. 
• 
Follow-up for 
symptoms/etiology to 
establish causality. 
• 
Study drug can be 
restarted only if another 
etiology is identiﬁed and 
liver enzymes return to 
baseline. 
If elevated at baseline: 
ALT/AST > 3 x baseline for 
more than two weeks 
If normal at baseline: 
ALT/AST > 8 x ULN 
Normal 
None 
ALT/AST increase with bilirubin increase: 
If normal at baseline: 
ALT/AST > 3 x ULN 
TBL > 2 x ULN (or 
INR > 1.5) 
For participants with 
Gilbert’s syndrome: 
Doubling of direct 
bilirubin at baseline 
None 
If elevated at baseline: 
ALT/AST > 2 x baseline 
If normal at baseline: 
ALT/AST > 3 x ULN 
Normal or elevated 
Severe fatigue, 
nausea, 
vomiting, right 
upper quadrant 
pain 
If elevated at baseline: 
ALT/AST > 2 x baseline 
Hy’s Law cases: 
- ALT or AST > 3 × ULN and TBL > 2 × ULN, without notable increase in ALP 
to > 2 × ULN, and 
- Absence of any alternative cause likely explaining the combination of 
increased ALT or AST and TBL (such as viral hepatitis A, B, C, or E); pre-
existing acute liver disease; or another drug capable of causing the observed 
injury 
• 
Interrupt study drug 
• 
Report to Novartis as SAE 
• 
Treat the condition and 
measure ALT, AST, ALP, 
GGT, TBL, INR, albumin, 
CK, and GLDH at the 
frequency per 
Investigator’s discretion 

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Table 16-2 
Follow up requirements for isolated total bilirubin elevation 
Criteria 
Actions required 
Follow-up monitoring 
Total Bilirubin (isolated) 
>1.5 – 3.0 ULN 
• 
Repeat LFTs within 48-72 
hours 
Monitor LFTs weekly until 
resolution to ≤ Grade 1 or to 
baseline 
> 3 - 10 × ULN (in the absence of 
known Gilbert syndrome) 
• 
Interrupt treatment 
• 
Repeat LFT within 48-72 
hours 
• 
Hospitalize if clinically 
appropriate 
• 
Establish causality 
• 
Record the AE and 
contributing factors (e.g. 
conmeds, med hx, lab) in the 
appropriate eCRFs 
Monitor LFTs weekly until 
resolution to ≤ Grade 1 or to 
baseline (ALT, AST, total bilirubin, 
Alb, PT/INR, ALP and GGT) 
Test for hemolysis (e.g. 
reticulocytes, haptoglobin, 
unconjugated [indirect] bilirubin) 
> 10 x ULN 
• 
Discontinue the study 
treatment immediately 
• 
Hospitalize the participant 
• 
Establish causality 
• 
Record the AE and 
contributing factors(e.g. 
conmeds, med hx, lab)in the 
appropriate eCRFs 
ALT, AST, total bilirubin, Alb, 
PT/INR, ALP and GGT until 
resolution* (frequency at 
investigator discretion) 
* Resolution is defined as an outcome of one of the following: (1) return to baseline values, (2) 
stable values at three subsequent monitoring visits at least 2 weeks apart, (3) remain at elevated 
level after a maximum of 6 months, (4) liver transplantation, and (5) death. 
For any AE potentially indicative of a liver toxicity, consider study drug interruption or 
discontinuation and hospitalization if clinically appropriate. Establish causality and record the 
AE and contributing factors in the appropriate eCRFs. Based on Investigator’s discretion, 
investigation(s) for contributing factors for the liver event can include: Serology tests, imaging 
and pathology assessments, hepatologist’s consultancy; obtaining more detailed history of 
symptoms and prior or concurrent diseases, history of concomitant drug use, exclusion of 
underlying liver disease. 

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16.2 
Appendix 2: Specific Renal Alert Criteria and Actions and Event 
Follow-up 
Table 16-3 
Specific Renal Alert Criteria and Actions 
Serum Event 
Action 
Serum creatinine (sCr) increase ≥25% 
compared to baseline during normal 
hydration status 
• 
Confirm 25% increase ≥24 hours but within 5 days 
• 
Consider causes and possible interventions (including study 
drug interruption) 
Urine Event 
Action 
Urine protein-creatinine ratio(PCR) ≥1g/g 
or ≥100 mg/mmol 
OR 
New onset dipstick proteinuria ≥ 3+ 
OR 
New onset dipstick hematuria ≥ 3+ (after 
excluding menstruation, urinary tract 
infection, extreme exercise, or trauma) 
• 
Confirm value* after ≥24 hours but within 5 days 
• 
Perform urine microscopy 
• 
Consider causes and possible interventions (including study 
drug interruption/discontinuation) 
Follow-up of Renal Events 
• 
Document contributing factors in the eCRF: co-medication, other comorbid conditions, and additional 
diagnostic procedures 
• 
Monitor participant at Investigator’s discretion 
*urine PCR can be used as a follow-up of a positive urine dipstick proteinuria. 
16.3 
Appendix 3: The 2017 McDonald criteria for diagnosis of multiple 
sclerosis in patients with an attack at onset 
Table 16-4 
2017 McDonald criteria for diagnosis of multiple sclerosis in patients 
with an attack at onset 
Number of lesions with objective clinical evidence 
Additional data needed for a diagnosis of multiple 
sclerosis 
≥2 clinical attacks 
≥2  
None* 
≥2 clinical attacks 
1 (as well as clear-cut 
historical evidence of a 
previous 
attack involving a lesion in a 
distinct anatomical location) 
None* 
≥2 clinical attacks 
1 
Dissemination in space demonstrated by an additional 
clinical attack implicating a different CNS site or by 
MRI 
1 clinical attack 
≥2  
Dissemination in time demonstrated by an additional 
clinical attack or by 
MRI OR demonstration of CSF-specific oligoclonal 
bands¶ 
1 clinical attack 
1 
Dissemination in space demonstrated by an additional 
clinical attack 
implicating a different CNS site or by MRI 
AND 
Dissemination in time demonstrated by an additional 
clinical attack or by 

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MRI OR demonstration of CSF-specific oligoclonal 
bands¶ 
If the 2017 McDonald Criteria are fulfilled and there is no better explanation for the clinical presentation, the 
diagnosis is multiple sclerosis. If multiple sclerosis is suspected by virtue of a clinically isolated syndrome but 
the 2017 McDonald Criteria are not completely met, the diagnosis is possible multiple sclerosis. If another 
diagnosis arises during the evaluation that better explains the clinical presentation, the diagnosis is not multiple 
sclerosis.  
*No additional tests are required to demonstrate dissemination in space and time. However, unless MRI is not 
possible, brain MRI should be obtained in all patients in whom the diagnosis of multiple sclerosis is being 
considered. In addition, spinal cord MRI or CSF examination should be considered in patients with insufficient 
clinical and MRI evidence supporting multiple sclerosis, with a presentation other than a typical clinically 
isolated syndrome, or with atypical features. If imaging or other tests (eg, CSF) are undertaken and are 
negative, caution needs to be taken before making a diagnosis of multiple sclerosis, and alternative diagnoses 
should be considered. †Clinical diagnosis based on objective clinical findings for two attacks is 
most secure. Reasonable historical evidence for one past attack, in the absence of documented objective 
neurological findings, can include historical events with symptoms and evolution characteristic for a previous 
inflammatory demyelinating attack; at least one attack, however, must be supported by objective findings. In 
the absence of residual objective evidence, caution is needed.  
¶The presence of CSF-specific oligoclonal bands does not demonstrate dissemination in time per se but can 
substitute for the requirement for demonstration of this measure. 
16.4 
Appendix 4: Guidance on safety monitoring and immunization 
16.4.1 
Guidance on monitoring of participants with symptoms of 
neurological deterioration suggestive of PML 
Should a participant develop any unexpected neurological or psychiatric symptom/signs in the 
opinion of Investigator (e.g. cognitive deficit, behavioral changes, cortical visual 
disturbances or any other neurological cortical symptoms/signs any symptom/sign suggestive 
of an increase of intracranial pressure) or accelerated neurological deterioration, the 
Investigator should schedule a complete physical and neurological examination and an MRI as 
soon as possible before beginning any steroid treatment. Conventional MRI, as defined in the 
protocol, as well as additional scanning such as Fluid-attenuated Inversion Recovery (FLAIR) 
and Diffusion weighted imaging (DWI) sequences should be performed to aid in differential 
diagnosis. The MRI must be evaluated by the local neuroradiologist. The Investigator will 
contact the Medical Advisor at Novartis to discuss findings and diagnostic possibilities as soon 
as possible. A copy of the unscheduled MRI should be sent to the MRI Evaluation Center 
designated by Novartis as soon as possible. SAEs need to be reported and filed as appropriate. 
If the MRI shows (new) lesions consistent with a MS relapse assessment and treatment of the 
relapse will be performed as described in the protocol (Section 6.2.3 ). In case of new findings 
in the MRI images, in comparison with the previously available MRI, which are not compatible 
with lesions consistent with a MS relapse, the study drug will be interrupted and other diagnostic 
evaluations need to be performed at the discretion of the Investigator. If new lesions are detected 
on the MRI, which may be infectious in origin, it is recommended to collect a cerebrospinal 
fluid (CSF) sample if indicated. Analysis of the CSF sample including cellular, biochemical, 
PCR, and microbiological analysis (e.g. herpes virus, JC virus, cryptococcus) to 
confirm/exclude an infection should be performed. In the event of suspected CNS infection 
(PML), a CSF aliquot should be sent to a qualified laboratory (designated by Novartis) for 
confirmatory testing. Only after the evaluations have excluded diagnoses other than MS and 

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after discussion with the Medical Advisor at Novartis and a Global Study Team member, the 
study drug may be restarted. 
16.4.2 
Guidance on monitoring participants with infections 
All infections that develop during the study will be reported as adverse events on the 
respective eCRF pages. Treatment and additional evaluations will be performed at Investigator 
discretion. The Investigator should remind the participant of the risk of infections and instruct 
them to report any symptoms of infections promptly. In the case of suspected or confirmed 
serious (CTCAE, Grade 3-4) or atypical infection, study drug interruption should be considered. 
The Investigator should inform the Novartis Medical Advisor and/or a Study Team member of 
any such cases. When evaluating a participant with a suspected infection, the most sensitive 
tests available should be used (i.e. that directly detect the pathogen, as with PCR). The 
Investigator should consider early treatment with specific antimicrobial therapy based on 
clinical diagnosis or suspicion thereof in consultation with infectious disease experts, as 
appropriate. The Investigator should inform the Novartis Medical Advisor and Global Study 
Team of any such cases. Investigators should consider the added immunosuppressive effects of 
corticosteroid therapy for treatment of clinical relapses/attack and increase vigilance regarding 
infections during such therapy and in the weeks following administration. 
Hepatitis B Virus (HBV) 
There were no reports of HBV reactivation in patients with MS treated with 
ofatumumab. However, HBV reactivation, in some cases resulting in fulminant hepatitis, 
hepatic failure, and death, has occurred in patients being treated with ofatumumab for chronic 
lymphocytic leukemia (CLL) (at significantly higher intravenous doses than the 20 mg dose in 
this study) and in patients treated with other anti-CD20 antibodies. HBV screening is required 
in all study participants, including hepatitis B surface antigen (HBsAg) and hepatitis B core 
antibody (HBcAb) testing. These can be complemented with other appropriate markers as per 
local guidelines. Participants with positive hepatitis B serology (either HBsAg or HBcAb) 
should consult a liver disease expert before the start of treatment and should be monitored and 
managed following local medical standards to prevent HBV infection or reactivation. In 
participants with suspicion of HBV infection (active/reactivation) during the study, laboratory 
testing for HBV should be done. For participants with positive hepatitis B serology (either 
HBsAg or HBcAb), the Investigator should consult a liver disease expert and participants 
should be monitored and managed following local medical standards to prevent HBV infection 
or reactivation. In participants who develop infection or reactivation of HBV while receiving 
study drug, immediately discontinue study drug and institute appropriate treatment and follow-
up. 
16.4.3 
Guidance on monitoring of participants with low immunoglobulin 
levels 
During the study, immunoglobulin levels (IgG and IgM) will be measured according to 
the schedule in Table 8-1. If IgG levels drop below 300mg/dL (Agarwal and Cunningham-
Rundles 2007), the Investigator should evaluate participant for any potential infections and 
monitor on a regular basis (refer to Section 16.4.2). Consider interrupting or discontinuing study 
treatment if a participant with low IgG as defined above develops a serious opportunistic 

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infection or recurrent infections, or if prolonged hypogammaglobinemia requires treatment with 
intravenous immunoglobulins. Immunoglobulin substitution therapy as per local medical 
practice is allowed and all relevant data must be recorded on the appropriated eCRFs. In case 
of treatment interruption, re-initiation of the study drug is subject to Investigator's discretion. 
Care should be taken to re-initiate study treatment according to planned dosing schedule in 
relation to the participant's W0 injection to ensure continuity and regularity of study visits and 
assessments. Participants that are prematurely discontinued should have the EOS visit as early 
as possible and continue into the Post-treatment Follow-up, please refer to assessment schedule 
Table 8-2.  
16.4.4 
Guidance on immunization 
The safety of and ability to generate a primary or anamnestic response to immunization 
with live, live-attenuated or inactivated vaccines during ofatumumab treatment has not been 
investigated. The response to vaccination could be impaired when B-cells are depleted. It is 
recommended that the Investigator reviews the participant’s immunization history as part of the 
initial Screening procedure for a participant being considered for treatment with ofatumumab. 
Because vaccination with live-attenuated or live vaccines is not recommended during treatment 
with ofatumumab and after treatment discontinuation until B-cell repletion, all immunizations 
must be administered according to immunization guidelines at least 4 weeks prior to initiation 
of ofatumumab for live or live-attenuated vaccines, and whenever possible, at least 2 weeks 
prior to initiation of ofatumumab for inactivated vaccines（including Sars-CoV-2 vaccines）. 
Hepatitis B vaccination should be considered prior to administration of ofatumumab in 
participants with risk factors for hepatitis B infection or in areas with a high prevalence of 
hepatitis B, as per local area treatment guidelines. Immune suppression of B cells is expected 
to affect the response to vaccination, and thus during treatment with ofatumumab, vaccination 
(non-live vaccines) may be less effective. 
Sars-CoV-2 Vaccinations 
SARS-CoV-2 vaccinations (e.g. inactivated, viral-vector-, or mRNA) that have been permitted 
for use by a local Health Authority are allowed. Permitted use includes full approval, 
conditional 
approval, 
emergency 
use 
authorization, 
provisional/temporary/interim 
authorization by Health Authority that are administered outside of a SARS-CoV-2 clinical trial 
to evaluate the effectiveness or safety of a SARS-CoV-2 vaccine. 
Additional guidance on permitted use of SARS-CoV-2 vaccinations may be made available 
separately taking into consideration the SARS-CoV-2 vaccine prescribing information, 
ofatumumab/SARS-CoV-2 vaccination recommendations and health authority guidance. 
Risk/benefit ratio for SARS-CoV-2 vaccination must be evaluated on a case-by-case basis by 
the Investigator. 
SARS-CoV-2 vaccination status is to be recorded on appropriate eCRF.