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

NCT05147220 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: CLOU064C123012020-005899-36
• Study Type: interventional
• Target: 1,001
• Locations: 34 countries
• Sites: 200

Brief Summary

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

Conditions

Relapsing Multiple Sclerosis

Keywords

MS; RMS; RRMS; active secondary progressive multiple sclerosis SPMS; remibrutinib; LOU064; teriflunomide; adult; relapse; Expanded Disability Status Scale; T2 lesions; T1 lesions; GD- enhancing MRI; Neurofilament light chain; McDonald diagnostic criteria

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (24)

• Time to 3-month confirmed disability progression (3mCDP) on Expanded Disability Status Scale (EDSS) [Core Part] (pooled data)

  Baseline up to 30 months

• Time to 6-month confirmed disability progression (6mCDP) on EDSS [Core Part] (pooled data)

  Baseline up to 30 months

• Annualized rate of new or enlarging T2 lesion [Core Part]

  Baseline up to 30 months

• Neurofilament light chain (Nfl) [Core Part]

  Baseline up to 30 months

• Number of Gd-enhancing T1 lesions per MRI scan [Core Part]

  Baseline up to 30 months

Study Arms (4)

Remibrutinib - Core

EXPERIMENTAL

Remibrutinib tablet and matching placebo of teriflunomide capsule

Drug: Remibrutinib

Teriflunomide - Core

ACTIVE COMPARATOR

Teriflunomide capsule and matching placebo remibrutinib tablet

Drug: Teriflunomide

Remibrutinib - Extension

EXPERIMENTAL

Participants on remibrutinib in Core will continue on remibrutinib tablet

Drug: Remibrutinib

Remibrutinib - Extension (on teriflunomide in Core)

EXPERIMENTAL

Participants on teriflunomide in Core will switch to remibrutinib tablet

Drug: Remibrutinib

Interventions

Teriflunomide DRUG

capsule taken orally

Teriflunomide - Core

Remibrutinib DRUG

tablet taken orally

Also known as: LOU064

Remibrutinib - Core; Remibrutinib - Extension; Remibrutinib - Extension (on teriflunomide in Core)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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 (including all Child-Pugh classes) or hepatic failure or any chronic liver or biliary disease.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (200)

AZ Integrated Neuro and Spine

Phoenix, Arizona, 85037, United States

Location

Center for Neurosciences

Tucson, Arizona, 85718, United States

Location

The Belinga Clinic

Fort Smith, Arkansas, 72916, United States

Location

The Research and Education Inst. of Alta Bates Summit Med. Grp

Berkeley, California, 94705, United States

Location

The Neuron Clinic

Chula Vista, California, 91910, United States

Location

Glendale Adventist Medical Center

Glendale, California, 91206, United States

Location

Hoag Health System

Newport Beach, California, 92663, United States

Location

SC3 Research Pasadena

Pasadena, California, 91105, United States

Location

Neuro Center

Pomona, California, 91767, United States

Location

Alpine Clinical Research Center

Boulder, Colorado, 80301, United States

Location

Christiana Care Health Services

Newark, Delaware, 19713, United States

Location

Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

Neurology of Central FL Res Ctr

Altamonte Springs, Florida, 32714, United States

Location

Arrow Clinical Trials

Daytona Beach, Florida, 32117, United States

Location

Homestead Assoc In Research Inc

Homestead, Florida, 33033, United States

Location

Reliant Medical Research

Miami, Florida, 33165, United States

Location

Neurological Services of Orlando PA

Orlando, Florida, 32806, United States

Location

Orlando Health Clinical Trials

Orlando, Florida, 32806, United States

Location

Comprehensive Neurology Clinic

Orlando, Florida, 32825, United States

Location

Neurology Associates of Ormond Beach

Ormond Beach, Florida, 32174, United States

Location

Neurostudies Inc

Port Charlotte, Florida, 33952, United States

Location

Accel Research Sites St Pete-Largo

Seminole, Florida, 33777, United States

Location

University Of South Florida

Tampa, Florida, 33612, United States

Location

Conquest Research

Winter Park, Florida, 32789, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

IU Health Inc

Fort Wayne, Indiana, 46815, United States

Location

College Park Family Care Center

Overland Park, Kansas, 66210, United States

Location

Norton Neurology MS Services

Louisville, Kentucky, 40207, United States

Location

American Oncology Partners PA Center for Cancer & Blood Disorders

Bethesda, Maryland, 20817, United States

Location

Neurology Center of New England PC

Foxborough, Massachusetts, 02035, United States

Location

Wayne State University Multiple Sclerosis Clinic

Detroit, Michigan, 48201, United States

Location

The MS Center for Innovation in Care

St Louis, Missouri, 63131, United States

Location

SCL Health

Billings, Montana, 59101, United States

Location

Jersey Shore University Medical Ctr

Neptune City, New Jersey, 07753, United States

Location

Neurological Associates of Long Island PC

Lake Success, New York, 11042, United States

Location

NYU Langone Med Center CV Research

New York, New York, 10016, United States

Location

The Neurological Institute PA

Charlotte, North Carolina, 28204, United States

Location

Velocity Clinical Research

Raleigh, North Carolina, 27607, United States

Location

Columbus Neuroscience

Westerville, Ohio, 43082, United States

Location

Multiple Sclerosis Center of Excellence of OMRF

Oklahoma City, Oklahoma, 73104, United States

Location

Providence St Vincent Med Center

Portland, Oregon, 97225, United States

Location

University Of Pittsburgh Medical Ctr Magee-Womens Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

Reading Hospital

Reading, Pennsylvania, 19611, United States

Location

Palmetto Clinical Research

Summerville, South Carolina, 29485, United States

Location

Texas Neurology

Dallas, Texas, 75206, United States

Location

John Peter Smith Hospital

Fort Worth, Texas, 76104, United States

Location

Neuro Eye Clinical Trials Inc

Houston, Texas, 77074, United States

Location

DHR Health Institute

McAllen, Texas, 78503, United States

Location

Saturn Research Solutions LLC

Plano, Texas, 75024, United States

Location

MS Center of Greater Washington, P.C.

Vienna, Virginia, 22182, United States

Location

University of Wisconsin Madison

Madison, Wisconsin, 53792, United States

Location

Neuroscience Group

Neenah, Wisconsin, 54956, United States

Location

Novartis Investigative Site

Capital Federal, Buenos Aires, 1424, Argentina

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Novartis Investigative Site

Rosario, Santa Fe Province, 2000, Argentina

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Novartis Investigative Site

Buenos Aires, C1012AAR, Argentina

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Novartis Investigative Site

Buenos Aires, C1055AAF, Argentina

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Novartis Investigative Site

Caba, C1424BYD, Argentina

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Novartis Investigative Site

Capital Federal, C1023AAB, Argentina

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Novartis Investigative Site

Santiago del Estero, 4200, Argentina

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Novartis Investigative Site

Linz, Upper Austria, 4020, Austria

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Novartis Investigative Site

Linz, 4020, Austria

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Novartis Investigative Site

Brussels, Brussels Capital, 1070, Belgium

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Novartis Investigative Site

Bruges, 8000, Belgium

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Novartis Investigative Site

Edegem, 2650, Belgium

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Novartis Investigative Site

Melsbroek, 1820, Belgium

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Novartis Investigative Site

Overpelt, 3900, Belgium

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Novartis Investigative Site

Porto Alegre, Porto Alegre RS, 90610 000, Brazil

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Novartis Investigative Site

Santo André, São Paulo, 09040 010, Brazil

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Novartis Investigative Site

São Paulo, São Paulo, 01244-030, Brazil

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São Paulo, São Paulo, 04076-004, Brazil

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Novartis Investigative Site

São Paulo, 01321001, Brazil

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Novartis Investigative Site

São Paulo, 04550-000, Brazil

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Pleven, 5800, Bulgaria

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Novartis Investigative Site

Sofia, 1113, Bulgaria

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Novartis Investigative Site

Sofia, 1431, Bulgaria

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Novartis Investigative Site

Sofia, 1680, Bulgaria

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Santiago, Santiago Metropolitan, 7650568, Chile

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Santiago, Santiago Metropolitan, 8431657, Chile

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Guangzhou, Guangdong, 510030, China

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Zhengzhou, Henan, 450003, China

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Changsha, Hunan, 410008, China

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Baotou, Inner Mongolia, 014040, China

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Hohhot, Inner Mongolia, 010017, China

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Nanchang, Jiangxi, 330006, China

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Changchun, Jilin, 130021, China

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Beijing, 100053, China

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Novartis Investigative Site

Beijing, 100730, China

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Chongqing, 400016, China

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Tianjin, 300052, China

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Puerto Colombia, Atlántico, 080012, Colombia

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Cali, Valle del Cauca Department, 760001, Colombia

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Cali, Valle del Cauca Department, 760032, Colombia

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Bogotá, 111411, Colombia

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Medellín, 050001, Colombia

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Novartis Investigative Site

Medellín, 050034, Colombia

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Osijek, 31000, Croatia

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Rijeka, 51000, Croatia

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Zagreb, 10000, Croatia

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Slagelse, 4200, Denmark

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Tbilisi, 114, Georgia

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Tbilisi, 141, Georgia

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Tbilisi, 159, Georgia

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Tbilisi, 160, Georgia

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Tbilisi, 172, Georgia

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Tbilisi, 179, Georgia

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Guatemala City, 01015, Guatemala

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Shatin, Hong Kong

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Mangalore, Karnataka, 575003, India

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Mangalore, Karnataka, 575018, India

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Mumbai, Maharashtra, 400008, India

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Nashik, Maharashtra, 422005, India

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New Delhi, National Capital Territory of Delhi, 110017, India

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Chandigarh, Punjab, 160012, India

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Ludhiana, Punjab, 141008, India

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Lucknow, Uttar Pradesh, 226014, India

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Dehradun, Uttarakhand, 248001, India

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Dublin, D03 VX82, Ireland

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Dublin, DO4, Ireland

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Ashkelon, 7830604, Israel

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Hadera, 3820302, Israel

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Haifa, 3109601, Israel

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Jerusalem, 9112001, Israel

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Sefad, 1311300, Israel

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Milan, MI, 20132, Italy

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Roma, RM, 00133, Italy

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Roma, RM, 00168, Italy

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Novartis Investigative Site

Roma, RM, 00189, Italy

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Verona, VR, 37134, Italy

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Novara, 28100, Italy

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Amman, 11942, Jordan

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Riga, LV, LV-1005, Latvia

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Riga, LV 1002, Latvia

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El Chouf, LBN, 1503201002, Lebanon

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Beirut, 166830, Lebanon

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Tripoli, 1434, Lebanon

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Šiauliai, LTU, 76231, Lithuania

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Klaipėda, LT-92288, Lithuania

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Kuala Lumpur, Kuala Lumpur, 50586, Malaysia

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Seberang Jaya, Pulau Pinang, 13700, Malaysia

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Kuching, Sarawak, 93586, Malaysia

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Kuala Terengganu, Terengganu, 20400, Malaysia

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Guadalajara, Jalisco, 44600, Mexico

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San Pedro G G, 66278, Mexico

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Veracruz, 91900, Mexico

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Rotterdam, South Holland, 3079 DZ, Netherlands

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Wroclaw, Lower Silesian Voivodeship, 52-416, Poland

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Bydgoszcz, Woj Kujawsko Pomorskie, 85-796, Poland

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Kielce, 25 726, Poland

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Lodz, 90 324, Poland

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Lodz, 93-113, Poland

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Lublin, 20-410, Poland

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Piotrkow Trybunalski, 97-300, Poland

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Poznan, 60-693, Poland

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Rzeszów, 35-323, Poland

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Szczecin, 70-111, Poland

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Jeddah, 21423, Saudi Arabia

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Jeddah, 21499, Saudi Arabia

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Riyadh, 11426, Saudi Arabia

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Bratislava, 826 06, Slovakia

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Košice, 041 90, Slovakia

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Nitra, 950 01, Slovakia

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Trnava, 917 02, Slovakia

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Cadiz, Andalusia, 11009, Spain

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Seville, Andalusia, 41014, Spain

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Sant Joan Despí, Barcelona, 08970, Spain

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Salt, Girona, 17190, Spain

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Alcorcón, Madrid, 28922, Spain

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Getafe, Madrid, 28905, Spain

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Majadahonda, Madrid, 28222, Spain

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El Palmar, Murcia, 30120, Spain

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Vigo, Pontevedra, 36212, Spain

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Castilleja de la Cuesta, Sevilla, 41950, Spain

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A Coruña, 15006, Spain

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Barcelona, 08035, Spain

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Córdoba, 14004, Spain

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Novartis Investigative Site

Las Palmas GC, 35010, Spain

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León, 24080, Spain

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Madrid, 28006, Spain

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Madrid, 28034, Spain

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Madrid, 28040, Spain

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Málaga, 29010, Spain

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Valladolid, 47011, Spain

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Basel, 4031, Switzerland

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Bern, 3010, Switzerland

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Kaohsiung City, 83301, Taiwan

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Novartis Investigative Site

Tainan, 704302, Taiwan

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Novartis Investigative Site

Taipei, 11220, Taiwan

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Novartis Investigative Site

Taoyuan District, 33305, Taiwan

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Ankara, Bilkent-Cankaya, 06800, Turkey (Türkiye)

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Izmir, Karsiyaka, 35575, Turkey (Türkiye)

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Istanbul, Sultangazi, 34295, Turkey (Türkiye)

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Ankara, Yenimahalle, 06500, Turkey (Türkiye)

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Mersin, Yenisehir, 33110, Turkey (Türkiye)

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Istanbul, 34147, Turkey (Türkiye)

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Izmir, 35100, Turkey (Türkiye)

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Abu Dhabi, 00000, United Arab Emirates

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Dubai, United Arab Emirates

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Westbruy on Trym, Bristol, BS10 5NB, United Kingdom

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Winchester, Hampshire, SO23 8SR, United Kingdom

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Glasgow, Scotland, G51 4TF, United Kingdom

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MeSH Terms

Conditions

Recurrence; Charcot-Marie-Tooth disease, Type 1F

Interventions

remibrutinib; teriflunomide

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: In order to maintain blinding, a double-dummy design will be used
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Eligible participants will be randomized in a 1:1 ratio

Study Record Dates

• First Submitted: November 24, 2021
• First Posted: December 7, 2021
• Study Start: December 16, 2021
• Primary Completion: April 30, 2026
• Study Completion (Estimated): October 30, 2030
• Last Updated: March 10, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

IE (2); LE (3); LI (2); GE (6); CH (2); TW (4); CO (6); IL (5); US (52); DK (1); HK (1); AR (7); IT (6); SL (4); ES (20); AE (2); BR (6); NL (1); JO (1); CN (11); IN (9); LA (2); TU (7); AU (2); CR (3); MY (4); ME (3); BU (4); BE (5); GU (1); SA (3); GB (3); CL (2); PL (10)