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CTRI Number  CTRI/2022/09/045485 [Registered on: 13/09/2022] Trial Registered Prospectively
Last Modified On: 18/04/2026
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group, Active Controlled Trial 
Public Title of Study   Efficacy and Safety of Remibrutinib Compared to Teriflunomide in Participants With Relapsing Multiple Sclerosis (RMS)  
Scientific Title of Study   A randomized, double-blind, double-dummy, parallel-group study, comparing the efficacy and safety of remibrutinib versus teriflunomide in participants with relapsing multiple sclerosis, followed by extended treatment with open-label remibrutinib 
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
2020-005929-89  EudraCT 
CLOU064C12302-Amended Protocol Version02 18-Jan-2022  Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Murugananthan K 
Designation  Country Monitoring Head 
Affiliation  Novartis Healthcare Pvt Ltd 
Address  Novartis Healthcare Pvt Ltd GDO Trial Monitoring, India 6 & 7 floor , Inspire BKC G Block, BKC Main Road Bandra Kurla Complex Bandra (East)

Mumbai
MAHARASHTRA
400051
India 
Phone    
Fax    
Email  murugananthan.k@novartis.com  
 
Details of Contact Person
Scientific Query  
Name  Murugananthan K 
Designation  Country Monitoring Head 
Affiliation  Novartis Healthcare Pvt Ltd 
Address  Novartis Healthcare Pvt Ltd GDO Trial Monitoring, India 6 & 7 floor , Inspire BKC G Block, BKC Main Road Bandra Kurla Complex Bandra (East)


MAHARASHTRA
400051
India 
Phone    
Fax    
Email  murugananthan.k@novartis.com  
 
Details of Contact Person
Public Query  
Name  Murugananthan K 
Designation  Country Monitoring Head 
Affiliation  Novartis Healthcare Pvt Ltd 
Address  Novartis Healthcare Pvt Ltd GDO Trial Monitoring, India 6 & 7 floor , Inspire BKC G Block, BKC Main Road Bandra Kurla Complex Bandra (East)


MAHARASHTRA
400051
India 
Phone    
Fax    
Email  murugananthan.k@novartis.com  
 
Source of Monetary or Material Support  
Novartis Pharma AG, Novartis Campus 4056 – Basel, Switzerland 
 
Primary Sponsor  
Name  Novartis Healthcare Pvt Ltd 
Address  Novartis Healthcare Pvt Ltd GDO Trial Monitoring, India 6 & 7 floor , Inspire BKC G Block, BKC Main Road Bandra Kurla Complex Bandra (East), Mumbai – 400051 India 
Type of Sponsor  Pharmaceutical industry-Global 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NA 
 
Countries of Recruitment     Australia
Brazil
Canada
China
Denmark
Germany
India
Malaysia
Poland
Russian Federation
Slovakia
South Africa
Switzerland
Taiwan
Thailand
United Kingdom
United States of America
Viet Nam  
Sites of Study
Modification(s)  
No of Sites = 9  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Sunil K Narayan  Jawaharlal Institute of Postgraduate Medical Education & Research  Jipmer Campus Rd, Gorimedu, Dhanvantari Nagar, Puducherry, 605006
Pondicherry
PONDICHERRY 		 04132272380

sunil.narayan@jipmer.edu.in 
Dr Sidharth Shankar Anand  Institute of Neurosciences  185/1 AJC Bose Road, Kolkata 700017 India
Kolkata
WEST BENGAL 		 9641469587

drsidharthsa@gmail.com 
DR Rahul Kulkarni  Lata Mangeshkar Medical Foundations Deenanath Mangeshkar Hospital and Research Centre  Lata Mangeshkar Medical Foundations Deenanath Mangeshkar Hospital and Research Centre, Ooff Karve Road, Erandawane, Pune- 411004, Maharashtra, India
Pune
MAHARASHTRA 		 9822012588

rahulneuro@gmail.com 
Dr Sireesha Yareeda  Nizams Institute of Medical Sciences  Department of Neurology, Ground floor, Millenium block, Nizams Institute of Medical Sciences, Panjagutta, Hyderabad-500082, Telangana, India
Hyderabad
TELANGANA 		 9966406827

mailforsiree@gmail.com 
Dr Shripad Pujari  Noble Hospital  Noble Hospital Clinical Research Department, Noble Annex, Noble Hospital Pvt Ltd, 153A, Magarpatta City Road, Hadapsar, Pune-411013 Maharashtra, India
Pune
MAHARASHTRA 		 9881009233

drshripadpujari@gmail.com 
Dr Suresh Kumar Radhakrishnan  Polakulath Narayanan Renai Medicity  Central lab, Polakulath Narayanan Renai Medicity, Post Box No 2259, Palarivattom PO Kochi Kerela 682025
Thiruvananthapuram
KERALA 		 914842880000

drsuresh@renaimedicity.org 
Dr Anshu Rohatgi  Sir Ganga Ram Hospital  Sir Ganga Ram Hospital Marg, Rajinder Nagar, New Delhi-110060, India
New Delhi
DELHI 		 9810159046

rohatgianshu@yahoo.com 
Dr Dinesh Kumar  Sri Guru Ram Das Institute of Medical Sciences and Research  VPO Vallah, Mehta Road, Amritsar, Punjab-143006
Amritsar
PUNJAB 		 8427158005

drdineshkumar0508@gmail.com 
Dr Usha Kant Misra  Vivekanand Polyclinic and Institute of Medical Sciences  Department of Neurology, Vivekanand Polyclinic and Institute of Medical Sciences, Lucknow-226007, UP
Lucknow
UTTAR PRADESH 		 9450453685

drukmisra@rediffmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 9  
Name of Committee  Approval Status 
Ethics Committee- Dr Sunil Narayan  Approved 
IEC-Institute of Neurosciences Kolkatta- Dr Santosh Trivedi  Approved 
Institutional Ethics Committee-Dr Dinesh  Approved 
Institutional Ethics Committee-Dr UK Misra  Approved 
Lata Mangeshkar Medical Foundations Deenanath Mangeshkar Hospital and Research Centre  Approved 
NIMS Institutional Ethics Committee-Dr Sireesha  Approved 
Noble Hospital Institutional Ethics Committee-Dr Pujari  Approved 
PolakulathNarayananRenai Medicity  Approved 
Sir Ganga Ram Hospital Ethics Committee-Dr Anshu  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: G35||Multiple sclerosis,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Remibrutinib   100 mg/ matching placebo Tablet 100 mg b.i.d. oral use (blinded) for 30 months 
Comparator Agent  Teriflunomide   14 mg/ matching placebo Capsule 14 mg q.d. oral use (blinded)for 30 months 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  55.00 Year(s)
Gender  Both 
Details  •18 to 55 years of age
•Diagnosis of RMS according to the 2017 McDonald diagnostic criteria
•At least: 1 documented relapse within the previous year. OR 2 documented relapses within the previous 2 years, OR 1 active Gadolinium (Gd)-enhancing lesion in the 12 months.
•EDSS score of 0 to 5.5 (inclusive)
•Neurologically stable within 1 month
 
 
ExclusionCriteria 
Details  1-Diagnosis of primary progressive multiple sclerosis (PPMS)
2-Disease duration of more than 10 years in participants with EDSS score of 2 or less at screening
3-History of clinically significant CNS disease other than MS
4-Ongoing substance abuse (drug or alcohol)
5-History of malignancy of any organ system (other than complete resection of localized basal cell carcinoma of the skin or in situ cervical cancer),
6-Participants with history of confirmed Progressive Multifocal Leukoencephalopathy (PML) or Neurological symptoms consistent with PML
7-suicidal ideation or behavior
8-Evidence of clinically significant cardiovascular, neurological, psychiatric, pulmonary , renal, hepatic, endocrine, metabolic, hematological disorders or gastrointestinal disease that can interfere with interpretation of the study results or protocol adherence
9-Participants who have had a splenectomy
10-Active clinically significant systemic bacterial, viral, parasitic or fungal infections
11-Positive results for syphilis or tuberculosis testing
12-Uncontrolled disease states, such as asthma, or inflammatory bowel disease, where flares are commonly treated with oral or parenteral corticosteroids
13-Active, chronic disease of the immune system (including stable disease treated with immune therapy (e.g. Leflunomide, Methotrexate)) other than MS (e.g. rheumatoid arthritis, systemic lupus erythematosus, etc.) with the exception of well-controlled diabetes or thyroid disorder.
14-Participants with a known immunodeficiency syndrome (AIDS, hereditary immune deficiency, drug induced immune deficiency), or tested positive for HIV antibody
15-History or current treatment for hepatic disease including but not limited to acute or chronic hepatitis, cirrhosis or hepatic failure or participants with moderate or severe hepatic impairment (Child-Pugh class C) or any chronic liver or biliary disease.
16-History of severe renal disease or creatinine level
17-Participants at risk of developing or having reactivation of hepatitis

Hematology parameters at screening:
1-Hemoglobin: < 10 g/dl (<100g/L)
2-Platelets: < 100000/mm3 (<100 x 109/L)
3-Absolute lymphocyte count < 800/mm3 (<0.8 x 109/L)
4-White blood cells: <3 000/mm3 (<3.0 x 109/L)
5-Neutrophils: < 1 500/mm3 (<1.5 x 109/L)
6-B-cell count < 50% lower limit of normal (LLN) or total IgG & total IgM < LLN (only required for participants who had a history of receiving B-cell therapies, such as rituximab, ocrelizumab or ofatumumab, prior to screening)

History or current diagnosis of significant ECG abnormalities
Resting QTcF ≥450 msec (male) or ≥460 msec (female) at pre-treatment (prior to randomization)
Use of other investigational drugs
Requirement for anticoagulant medication or use of dual anti-platelet therapy Significant bleeding risk or coagulation disorders,
History of gastrointestinal bleeding
Major surgery within 8 weeks prior to screening
History of hypersensitivity to any of the study drugs or excipients
Pregnant or nursing (lactating) female participants, prior to randomization
Women of childbearing potential not using highly effective contraception
Sexually active males not agreeing to use condom
Have received any live or live-attenuated vaccines within 6 weeks of randomization or requirement to receive these vaccinations during study
Use of strong CYP3A4 inhibitors or strong CYP3A4 inducers within two weeks prior to randomization

Inclusion to Extension part:

patient who complete the Core Part of the study on double-blind study treatment and conduct the Accelerated Elimination Procedure (AEP) 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Centralized 
Blinding/Masking   Double Blind Double Dummy 
Primary Outcome  
Outcome  TimePoints 
To demonstrate that remibrutinib (100 mg b.i.d. p.o.) is superior to teriflunomide (14 mg q.d. p.o.) in reducing the frequency of confirmed relapses  Annualized relapse rate (ARR) of confirmed relapses( the number of confirmed relapses per year). Symptoms will be reported by participants at at a scheduled visit or at any other time and confirmation of relapses will be assessed by EDSS Rater 
 
Secondary Outcome  
Outcome  TimePoints 
Key secondary objectives (Core Part): To assess whether remibrutinib is superior to teriflunomide in
1.Delaying disability progression based on the pooled data from both identical pivotal studies 		 1. Time to 3-month confirmed disability progression (3mCDP) on Expanded Disability Status Scale (EDSS)
2. Time to 6-month confirmed disability progression (6mCDP) on EDSS
 
1. Key secondary objectives (Core Part): To assess whether remibrutinib is superior to teriflunomide in
Reducing new inflammatory activity on MRI, based on MRI cohort data 		 1. Number of new or enlarging T2 lesions on MRI per year (annualized T2 lesion rate)
Total number of Gd-enhancing T1 lesions per MRI scan
 
Key secondary objectives (Core Part): To assess whether remibrutinib is superior to teriflunomide in
● Reducing neuronal damage 		 Neurofilament light chain (NfL) concentration in serum  
Key secondary objectives (Core Part): To assess whether remibrutinib is superior to teriflunomide in
● Disease-Activity-free status based on pooled data from both identical pivotal studies (MRI Cohort) 		 Percentage of participants with No Evidence of Disease Activity-3 (NEDA-3), as assessed by absence of confirmed MS relapses, 6mCDP and new/enlarging T2 lesions on MRI 
Other secondary objectives (Core Part):
To assess the effects of remibrutinib relative to teriflunomide on additional clinical and MRI endpoints [pooled data from both identical pivotal studies will be used as indicated in the endpoint column] 		 Time to first confirmed relapse
Time to 6-month confirmed disability improvement(6mCDI)on EDSS (pooled data)
Change from baseline in (SDMT) (pooled data)
Time to 6-month confirmed worsening by at least 20% in the:
(T25FW) (pooled data)
Timed 9-hole peg test (9HPT) (pooled data)
Time to composite 6-month confirmed disability progression,as evaluated by 6mCDP or 6-month confirmed worsening by at least 20% in T25FW or 9HPT (pooled data)
Change from baseline in T2 lesion volume 
Other secondary objectives (Core Part):
To assess the effect of remibrutinib relative to teriflunomide on MS symptoms (fatigue, anxiety, depression, pain), activity limitations, and health-related quality of life (HRQoL) 		 Patient Reported Outcomes (PROs): Fatigue Symptoms and Impacts Questionnaire - Relapsing Multiple Sclerosis (FSIQ-RMS); Generalized Anxiety Disorder Scale (GAD-7); Patient Health Questionnaire-9 (PHQ-9); Brief Pain Inventory - short form (BPI-SF); Health Utilities Index (HUI-III); Multiple Sclerosis Impact Scale (MSIS-29) 
Other secondary objectives (Core Part):
To assess the safety and tolerability of remibrutinib compared to teriflunomide 		 Adverse events, laboratory data, vital signs, electrocardiogram (ECG), Columbia Suicide Severity Rating 
Other secondary objectives (Core Part):
To assess the pharmacokinetics (PK) of remibrutinib 		 Remibrutinib blood concentrations 
 
Target Sample Size   Total Sample Size="800"
Sample Size from India="28" 
Final Enrollment numbers achieved (Total)= "0"
Final Enrollment numbers achieved (India)="0" 
Phase of Trial   Phase 3 
Date of First Enrollment (India)   17/10/2022 
Date of Study Completion (India) Date Missing 
Date of First Enrollment (Global)  31/12/2021 
Date of Study Completion (Global) Date Missing 
Estimated Duration of Trial   Years="7"
Months="5"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  		 Completed 
Recruitment Status of Trial (India)  Completed 
Publication Details   NIL 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
Brief Summary   The purpose of the study is to provide efficacy, safety and tolerability data for remibrutinib, to support regulatory approval worldwide as a treatment for relapsing multiple sclerosis (RMS). Two identical Phase III trials (CLOU064C12301 and CLOU064C12302) will be conducted simultaneously. The primary objective of this study is to demonstrate that remibrutinib  is superior to teriflunomide  in reducing the frequency of confirmed relapses.Remibrutinib has a  favorable pharmacological profile in terms of potency, selectivity for BTK and safety (as observed in available Phase II data) in different indications at relevant doses and may offer a novel therapeutic option for participants with RMS. This study consists of an initial Core Part (CP) (maximum duration per participant of up to 30 months), followed by an Extension Part (of up to 5 years duration) for eligible participants.
The Core Part is a randomized, double-blind, double-dummy, active comparator-controlled, fixed-dose, parallel-group, multi-center study in approximately 800 participants with RMS. The treatment duration of the Core Part for individual participants will be variable based on when the Core Part End of Study (EOS) criteria are met. The maximal duration of the Core Part for an individual participant will be 30 months (~2.5 years).

 
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