Efficacy and Safety of Remibrutinib Compared to Teriflunomide in Participants With Relapsing Multiple Sclerosis (RMS)

Relapsing Multiple Sclerosis Clinical Trial

— REMODEL-2  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05156281
• Other study ID #: CLOU064C12302
• Secondary ID: 2020-005929-89
• Status: Recruiting
• Phase: Phase 3
• Start date: December 13, 2021
• Est. completion date: October 30, 2030

Study information

• Verified date: June 2024
• Source: Novartis
• Contact: Novartis Pharmaceuticals
• Phone: 1-888-669-6682
• Email: novartis.email[@]novartis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To compare the efficacy and safety of remibrutinib versus teriflunomide in patients with relapsing multiple sclerosis (RMS)

Description:

The study CLOU064C12302 consists of an initial Core Part (CP) (maximum duration per participant of up to 30 months), followed by an Extension Part (EP, 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 relapsing multiple sclerosis (RMS).

The Extension Part is an open-label, single-arm, fixed-dose design in which eligible participants are treated with remibrutinib for up to 5 years.

A second study of identical design (CLOU064C12301) will be conducted simultaneously. Both studies will be conducted globally and data from the two studies will be pooled for some of the endpoints.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 800
• Est. completion date: October 30, 2030
• Est. primary completion date: April 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• Diagnosis of primary progressive multiple sclerosis (PPMS)

• Disease duration of more than 10 years in participants with EDSS score of 2 or less at screening

• History of clinically significant CNS disease other than MS

• Ongoing substance abuse (drug or alcohol)

• History of malignancy of any organ system (other than complete resection of localized basal cell carcinoma of the skin or in situ cervical cancer),

• Participants with history of confirmed Progressive Multifocal Leukoencephalopathy (PML) or Neurological symptoms consistent with PML

• suicidal ideation or behavior

• 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

• Participants who have had a splenectomy

• Active clinically significant systemic bacterial, viral, parasitic or fungal infections

• Positive results for syphilis or tuberculosis testing

• Uncontrolled disease states, such as asthma, or inflammatory bowel disease, where flares are commonly treated with oral or parenteral corticosteroids

• 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.

• Participants with a known immunodeficiency syndrome (AIDS, hereditary immune deficiency, drug induced immune deficiency), or tested positive for HIV antibody

• 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.

• History of severe renal disease or creatinine level

• Participants at risk of developing or having reactivation of hepatitis

• Hematology parameters at screening:

• Hemoglobin: < 10 g/dl (<100g/L)

• Platelets: < 100000/mm3 (<100 x 109/L)

• Absolute lymphocyte count < 800/mm3 (<0.8 x 109/L)

• White blood cells: <3 000/mm3 (<3.0 x 109/L)

• Neutrophils: < 1 500/mm3 (<1.5 x 109/L)

• 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 use of moderate or strong CYP3A4 inducers within two weeks prior to randomization

Inclusion to Extension part:

• Participants who complete the Core Part of the study on double-blind study treatment and conduct the Accelerated Elimination Procedure (AEP)

Other inclusion and exclusion criteria may apply.

Related Conditions & MeSH terms

• Multiple Sclerosis
• Relapsing Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• Remibrutinib
tablet taken orally
• Teriflunomide
capsule taken orally

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Bombal	Mendoza
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	San Miguel De	Tucuman
Brazil	Novartis Investigative Site	Brasilia	DF
Brazil	Novartis Investigative Site	Curitiba	PR
Brazil	Novartis Investigative Site	Joinville	Santa Catarina
Brazil	Novartis Investigative Site	Porto Alegre	Rio Grande Do Sul
Brazil	Novartis Investigative Site	Porto Alegre	RS
Brazil	Novartis Investigative Site	Porto Alegre	RS
Brazil	Novartis Investigative Site	Sao Paulo
Brazil	Novartis Investigative Site	Vitoria	ES
Bulgaria	Novartis Investigative Site	Plovdiv
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Canada	Novartis Investigative Site	Burnaby	British Columbia
Canada	Novartis Investigative Site	Edmonton	Alberta
Canada	Novartis Investigative Site	Greenfield Park	Quebec
Canada	Novartis Investigative Site	Halifax	Nova Scotia
Canada	Novartis Investigative Site	Levis	Quebec
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Ottawa	Ontario
Canada	Novartis Investigative Site	Quebec
Canada	Novartis Investigative Site	St Jerome	Quebec
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Fuzhou	Fujian
China	Novartis Investigative Site	Hangzhou	Zhejiang
China	Novartis Investigative Site	Hangzhou	Zhejiang
China	Novartis Investigative Site	Nanjing	Jiangsu
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Taiyuan	Shanxi
China	Novartis Investigative Site	Wenzhou	Zhejiang
China	Novartis Investigative Site	Wuhan	Hubei
China	Novartis Investigative Site	Wuhan	Hubei
China	Novartis Investigative Site	Yinchuan	Ningxia
Croatia	Novartis Investigative Site	Split	HRV
Croatia	Novartis Investigative Site	Varazdin	HRV
Croatia	Novartis Investigative Site	Vukovar
Croatia	Novartis Investigative Site	Zagreb
Estonia	Novartis Investigative Site	Tallinn
Estonia	Novartis Investigative Site	Tartu
France	Novartis Investigative Site	Caen
France	Novartis Investigative Site	Clermont-Ferrand Cedex 1
France	Novartis Investigative Site	Contamine Sur Arve
France	Novartis Investigative Site	Dijon
France	Novartis Investigative Site	Gonesse
France	Novartis Investigative Site	Grenoble
France	Novartis Investigative Site	Lille
France	Novartis Investigative Site	Lille
France	Novartis Investigative Site	Limoges
France	Novartis Investigative Site	Marseille
France	Novartis Investigative Site	Nantes	Cedex 1
France	Novartis Investigative Site	Nice
France	Novartis Investigative Site	Nimes
France	Novartis Investigative Site	Poissy
France	Novartis Investigative Site	Suresnes
France	Novartis Investigative Site	Toulon Cedex 9	Val De Marne
France	Novartis Investigative Site	Toulouse Cedex 9
Greece	Novartis Investigative Site	Athens	Attica
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Greece
Greece	Novartis Investigative Site	Ioannina	GR
Greece	Novartis Investigative Site	Larissa	GR
Greece	Novartis Investigative Site	Thessaloniki
India	Novartis Investigative Site	Amritsar	Punjab
India	Novartis Investigative Site	Hyderabad	Telangana
India	Novartis Investigative Site	Kochi	Kerala
India	Novartis Investigative Site	Kolkata	West Bengal
India	Novartis Investigative Site	Lucknow	Uttar Pradesh
India	Novartis Investigative Site	New Delhi	Delhi
India	Novartis Investigative Site	Pune	Maharashtra
India	Novartis Investigative Site	Pune	Maharashtra
Italy	Novartis Investigative Site	Brindisi	BR
Italy	Novartis Investigative Site	Firenze	FI
Italy	Novartis Investigative Site	Foggia	FG
Italy	Novartis Investigative Site	Messina	ME
Italy	Novartis Investigative Site	Modena	MO
Italy	Novartis Investigative Site	Napoli
Italy	Novartis Investigative Site	Orbassano	TO
Italy	Novartis Investigative Site	Pavia	PV
Italy	Novartis Investigative Site	Pozzilli	IS
Japan	Novartis Investigative Site	Chiba
Japan	Novartis Investigative Site	Fukuoka
Japan	Novartis Investigative Site	Fukuoka city	Fukuoka
Japan	Novartis Investigative Site	Higashimatsuyama	Saitama
Japan	Novartis Investigative Site	Ichihara-city	Chiba
Japan	Novartis Investigative Site	Isehara	Kanagawa
Japan	Novartis Investigative Site	Itabashi-ku	Tokyo
Japan	Novartis Investigative Site	Kashihara city	Nara
Japan	Novartis Investigative Site	Kobe-shi	Hyogo
Japan	Novartis Investigative Site	Kodaira	Tokyo
Japan	Novartis Investigative Site	Koriyama city	Fukushima
Japan	Novartis Investigative Site	Kyoto-city	Kyoto
Japan	Novartis Investigative Site	Moriguchi	Osaka
Japan	Novartis Investigative Site	Nagoya	Aichi
Japan	Novartis Investigative Site	Niigata
Japan	Novartis Investigative Site	Nishinomiya	Hyogo
Japan	Novartis Investigative Site	Sagamihara	Kanagawa
Japan	Novartis Investigative Site	Sapporo city	Hokkaido
Japan	Novartis Investigative Site	Sendai city	Miyagi
Japan	Novartis Investigative Site	Shinjuku ku	Tokyo
Japan	Novartis Investigative Site	Shinjuku-ku	Tokyo
Japan	Novartis Investigative Site	Shinjuku-ku	Tokyo
Japan	Novartis Investigative Site	Suita	Osaka
Mexico	Novartis Investigative Site	Chihuahua
Mexico	Novartis Investigative Site	Ciudad De Mexico
Mexico	Novartis Investigative Site	Ciudad de Mexico	Distrito Federal
Mexico	Novartis Investigative Site	Queretaro
Poland	Novartis Investigative Site	Bialystok
Poland	Novartis Investigative Site	Glogow
Poland	Novartis Investigative Site	Katowice
Poland	Novartis Investigative Site	Katowice
Poland	Novartis Investigative Site	Katowice
Poland	Novartis Investigative Site	Krakow
Poland	Novartis Investigative Site	Plewiska	Poznan
Poland	Novartis Investigative Site	Wroclaw
Poland	Novartis Investigative Site	Zabrze
Portugal	Novartis Investigative Site	Braga
Portugal	Novartis Investigative Site	Coimbra
Portugal	Novartis Investigative Site	Leiria
Portugal	Novartis Investigative Site	Lisboa
Portugal	Novartis Investigative Site	Lisboa
Portugal	Novartis Investigative Site	Matosinhos	Porto
Portugal	Novartis Investigative Site	Santa Maria da Feira
Puerto Rico	Caribbean Center for Clinical Research, Inc. .	Guaynabo
Romania	Novartis Investigative Site	Brasov	ROM
Romania	Novartis Investigative Site	Campulung Muscel
Romania	Novartis Investigative Site	Constanta
Romania	Novartis Investigative Site	Constanta	ROM
Romania	Novartis Investigative Site	Suceava
Romania	Novartis Investigative Site	Targu Mures
Slovakia	Novartis Investigative Site	Banska Bystrica
Slovakia	Novartis Investigative Site	Banska Bystrica
Slovakia	Novartis Investigative Site	Bratislava
Slovenia	Novartis Investigative Site	Celje
Slovenia	Novartis Investigative Site	Ljubljana
Slovenia	Novartis Investigative Site	Maribor
South Africa	Novartis Investigative Site	Bloemfontein	Free State
South Africa	Novartis Investigative Site	Pretoria
South Africa	Novartis Investigative Site	Rosebank
Spain	Novartis Investigative Site	Albacete	Castilla La Mancha
Spain	Novartis Investigative Site	Badalona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Gijon	Asturias
Spain	Novartis Investigative Site	Hospitalet de Llobregat	Barcelona
Spain	Novartis Investigative Site	Logrono	La Rioja
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Malaga
Spain	Novartis Investigative Site	Pozuelo de Alarcon	Madrid
Spain	Novartis Investigative Site	Santiago De Compostela	Galicia
Spain	Novartis Investigative Site	Sevilla	Andalucia
Spain	Novartis Investigative Site	Torrejon de Ardoz	Madrid
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Spain	Novartis Investigative Site	Valencia
Spain	Novartis Investigative Site	Vitoria Gasteiz	Pais Vasco
Sweden	Novartis Investigative Site	Stockholm
Sweden	Novartis Investigative Site	Stockholm
Turkey	Novartis Investigative Site	Bursa
Turkey	Novartis Investigative Site	Istanbul
Turkey	Novartis Investigative Site	Istanbul	TUR
Turkey	Novartis Investigative Site	Izmir
Turkey	Novartis Investigative Site	Izmir
Turkey	Novartis Investigative Site	Kayseri
Turkey	Novartis Investigative Site	Kocaeli
Turkey	Novartis Investigative Site	Meram
Turkey	Novartis Investigative Site	Pendik Istanbul
Turkey	Novartis Investigative Site	Samsun
Turkey	Novartis Investigative Site	Sancaktepe	Istanbul
United Kingdom	Novartis Investigative Site	Canterbury	Kent
United Kingdom	Novartis Investigative Site	Inverness	Invernesshire
United Kingdom	Novartis Investigative Site	London
United States	CU Anschutz Med Campus	Aurora	Colorado
United States	SFM Clinical Research LLC	Boca Raton	Florida
United States	Tufts Medical Center .	Boston	Massachusetts
United States	Nova Clinical Research LLC .	Bradenton	Florida
United States	Medical Uni of South Carolina Medical Univ of SC	Charleston	South Carolina
United States	Piedmont HealthCare	Charlotte	North Carolina
United States	Colorado Springs Neurological Associates	Colorado Springs	Colorado
United States	The Boster Ctr for MS	Columbus	Ohio
United States	Elligo Health Research	Crab Orchard	West Virginia
United States	Neurology Consultants Of Dallas PA Research	Dallas	Texas
United States	Neurology Diagnostics Inc .	Dayton	Ohio
United States	Colorado Neurological Research PC	Denver	Colorado
United States	Med Research Inc	El Paso	Texas
United States	Comprehensive Neurology	Frederick	Maryland
United States	Lone Star Neurology	Frisco	Texas
United States	Univ of Florida College of Medicine Norman Fixel Institute	Gainesville	Florida
United States	Aurora BayCare Medical Center	Green Bay	Wisconsin
United States	Premier Neurology	Greenville	South Carolina
United States	Vladimir Royter MD APMC	Hanford	California
United States	Memorial Hospital .	Hollywood	Florida
United States	Neurocare Plus	Houston	Texas
United States	Metrolina Neurological Associates PA .	Indian Land	South Carolina
United States	Kansas City VA Medical Center	Kansas City	Missouri
United States	University of Kansas Medical Center CFTY720D2399E1	Kansas City	Kansas
United States	Hope Neurology	Knoxville	Tennessee
United States	Neurology Associates, PA	Maitland	Florida
United States	Methodist Neuroscience Institute	Merrillville	Indiana
United States	Gables Neurology	Miami	Florida
United States	University of Miami Miller School of Medicine .	Miami	Florida
United States	Ascension St Francis Center	Milwaukee	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Aqualane Clinical Research .	Naples	Florida
United States	Ochsner Clinic Foundation .	New Orleans	Louisiana
United States	Baptist Physicians Lexington .	Nicholasville	Kentucky
United States	Advent Health Orlando	Orlando	Florida
United States	Memorial Healthcare .	Owosso	Michigan
United States	South Shore Neurologic Associates CFTY720D2403	Patchogue	New York
United States	Humanity Clinical Research .	Pembroke Pines	Florida
United States	Emerald Coast Neurology .	Pensacola	Florida
United States	Ctr for Neurology and Spine	Phoenix	Arizona
United States	True North Neurology .	Port Jefferson Station	New York
United States	Brain and Spine Institute	Port Orange	Florida
United States	Lonestar Neurology of San Antonio	San Antonio	Texas
United States	University of Texas Health Science Center San Antonio COMB157G2301	San Antonio	Texas
United States	University of Washington MS Clinic	Seattle	Washington
United States	Virginia Mason Medical Centre Benaroya Research Institute-2	Seattle	Washington
United States	Texas Institute for Neurological Disorders	Sherman	Texas
United States	Georgia Neurology and Sleep Medicine Assoc	Suwanee	Georgia
United States	Vero Beach Neurology .	Vero Beach	Florida
United States	Georgetown University Hospital Research	Washington	District of Columbia
United States	Regina Berkovich MD PhD Inc	West Hollywood	California
United States	Conquest Research	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Bulgaria,  Canada,  China,  Croatia,  Estonia,  France,  Greece,  India,  Italy,  Japan,  Mexico,  Poland,  Portugal,  Puerto Rico,  Romania,  Slovakia,  Slovenia,  South Africa,  Spain,  Sweden,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Annualized relapse rate (ARR) of confirmed relapses [Core Part]	ARR is the average number of confirmed MS relapses in a year	From Baseline, up to 30 months
Secondary	Time to 3-month confirmed disability progression (3mCDP) on Expanded Disability Status Scale (EDSS) [Core Part] (pooled data)	Time to 3-month confirmed disability progression (3mCDP) is defined as an increase in Expanded Disability Status Scale (EDSS) which is sustained for at least 3 months	Baseline up to 30 months
Secondary	Time to 6-month confirmed disability progression (6mCDP) on EDSS [Core Part] (pooled data)	Time to 6-month confirmed disability progression (6mCDP) is defined as an increase in Expanded Disability Status Scale (EDSS) which is sustained for at least 6 months	Baseline up to 30 months
Secondary	Annualized rate of new or enlarging T2 lesion [Core Part]	Number of new/newly enlarged T2 lesions per year	Baseline up to 30 months
Secondary	Neurofilament light chain (Nfl) [Core Part]	Neurofilament light chain (NfL) concentration in serum	Baseline up to 30 months
Secondary	Number of Gd-enhancing T1 lesions per MRI scan [Core Part]	Average number of Gd-enhancing T1 lesions per scan	Baseline up to 30 months
Secondary	Percentage of participants with No Evidence of Disease Activity-3 (NEDA-3) [Core Part] (pooled data)	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	Baseline up to 30 months
Secondary	Time to first confirmed relapse [Core Part]	Change in the Expanded Disability Status Scale (EDSS), an increase of at least 0.5 points on the EDSS (total) score, or an increase of at least 1 point on at least two functional scores (FSs), or an increase of at least 2 points on at least one FS, excluding changes involving bowel/bladder or cerebral FS, compared to the previous available rating.	Baseline up to 30 months
Secondary	Time to 6-month confirmed disability improvement (6mCDI) on EDSS [Core Part] (pooled data)	Decrease in Expanded Disability Status Scale Score (EDSS) which is sustained for at least 6 months	Baseline up to 30 months
Secondary	Time to 3-months confirmed disability progression (3mCDP) and 6-month confirmed disability progression (6mCDP) independent of relapse activity (PIRA) [Core Part] (pooled data)	Time to 3-month confirmed disability progression (3mCDP) and 6-month confirmed disability progression (6mCDP) is defined as an increase in Expanded Disability Status Scale (EDSS) which is sustained for at least 3 months or 6 months, respectively, without an on-study relapse before or on the day of a progression eve	Baseline up to 30 months
Secondary	Change from baseline in the Symbol Digit Modalities Test (SDMT) [Core Part] (pooled data)	Symbol Digit Modalities Test (SDMT), an array of symbols paired with empty spaces, measures processing in speed; participants verbally match the number for each symbol as rapidly as possible. The score is the number of correctly coded items in 90 seconds. Higher scores indicate improvement. Lower scores indicate worsening	Baseline up to 30 months
Secondary	Time to 6-month confirmed worsening by at least 20% in the Timed 25-foot walk test (T25FW) [Core Part] (pooled data)	The patient walking speed to cover 25-foot distance is recorded in seconds. Longer time indicates poorer lower limb function. 20% worsening is defined as 20% increase from baseline T25FW score	Baseline, up to 30 months
Secondary	Time to 6-month confirmed worsening by at least 20% in the Timed 9-hole peg test (9HPT) (pooled data) [Core Part] (pooled data)	The patient's right and left arm function to peg 9 holes measured in seconds. Longer time indicates poorer upper limb function. 20% worsening is defined as 20% increase from baseline 9HPT score in at least one hand (average of two trials per hand)	Baseline up to 30 months
Secondary	Time to composite 6-month confirmed disability Progression (CDP) [Core Part] (pooled data)	The composite involves CDP and worsening by at least 20% in T25FW and 9HPT	Baseline up to 30 months
Secondary	Change from Baseline in T2 lesion volume [Core Part]	Change from baseline in total T2 lesion volume.	Baseline up to 30 months
Secondary	Change from baseline in Multiple Sclerosis Impact Scale (MSIS-29) [Core Part]	29-item, self-administered questionnaire that includes 2 domains, physical and psychological. Responses are captured on a 4-point scale ranging from "not at all" (1) to "extremely" (4), where higher scores reflect greater impact on day to day life	Baseline up to 30 months
Secondary	Number of participants with Adverse events and Serious adverse events(SAE) [Core Part]	Adverse events and SAEs including clinically significant, laboratory data, vital signs, electrocardiogram (ECG), Columbia Suicide Severity Rating	Baseline up to 30 months
Secondary	Pharmacokinetics of remibrutinib [Core Part]	Blood concentrations of remibrutinib	Month 1, Month 6
Secondary	Number of participants with Adverse events and Serious adverse events (SAE) [Extension Part]	Adverse events and SAEs including clinically significant, laboratory data, vital signs, electrocardiogram (ECG), Columbia Suicide Severity Rating	Day 1 Extension up to 5 years
Secondary	Annualized relapse rate (ARR) of confirmed relapses [Extension Part]	ARR is the average number of confirmed MS relapses in a year	Day 1 Extension up to 5 years
Secondary	Annualized rate of new or enlarging T2 lesion [Extension Part]	Number of new/newly enlarged T2 lesions per year	Day 1 Extension up to 5 years
Secondary	Time to 6-month confirmed disability progression (6mCDP) on EDSS [Extension Part]	Time to 6-month confirmed disability progression (6mCDP) is defined as an increase in Expanded Disability Status Scale (EDSS) which is sustained for at least 6 months	Day 1 Extension up to 5 years
Secondary	Change from baseline in the Symbol Digit Modalities Test (SDMT) [Extension Part]	Symbol Digit Modalities Test (SDMT), an array of symbols paired with empty spaces, measures processing in speed; participants verbally match the number for each symbol as rapidly as possible. The score is the number of correctly coded items in 90 seconds. Higher scores indicate improvement. Lower scores indicate worsening	Day 1 Extension up to 5 years
Secondary	Neurofilament light chain (NfL) [Extension Part]	Neurofilament light chain (NfL) concentration in serum	Day 1 Extension up to 5 years
Secondary	Change from baseline in Multiple Sclerosis Impact Scale (MSIS-29) [Extension Part]	29-item, self-administered questionnaire that includes 2 domains, physical and psychological. Responses are captured on a 4-point scale ranging from "not at all" (1) to "extremely" (4), where higher scores reflect greater impact on day to day life	Day 1 Extension up to 5 years