Efficacy and Safety of Remibrutinib Compared to Teriflunomide in Participants With Relapsing Multiple Sclerosis (RMS) (REMODEL-2)

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Relapsing Multiple Sclerosis
• Intervention / Treatment: Drug: Remibrutinib; Drug: Teriflunomide

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 1007
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1012AAR
    • Novartis Investigative Site
  • CABA, Argentina, C1181ACH
    • Novartis Investigative Site
  • Córdoba, Argentina, X5004CDT
    • Novartis Investigative Site
  • Mendoza Province
    • Bombal, Mendoza Province, Argentina, M5500DXO
      • Novartis Investigative Site
  • Santa Fe Province
    • Rosario, Santa Fe Province, Argentina, S2000BZL
      • Novartis Investigative Site
    • Rosario, Santa Fe Province, Argentina, S2000DSW
      • Novartis Investigative Site
  • Tucumán Province
    • San Miguel de, Tucumán Province, Argentina, T4000
      • Novartis Investigative Site
• Brazil
  • São Paulo, Brazil, 01240-020
    • Novartis Investigative Site
  • Espírito Santo
    • Vitória, Espírito Santo, Brazil, 29055-450
      • Novartis Investigative Site
  • Federal District
    • Brasília, Federal District, Brazil, 70200-730
      • Novartis Investigative Site
  • Paraná
    • Curitiba, Paraná, Brazil, 81210-310
      • Novartis Investigative Site
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90430-001
      • Novartis Investigative Site
    • Porto Alegre, Rio Grande do Sul, Brazil, 90560-032
      • Novartis Investigative Site
    • Porto Alegre, Rio Grande do Sul, Brazil, 90620-130
      • Novartis Investigative Site
  • Santa Catarina
    • Joinville, Santa Catarina, Brazil, 89202-165
      • Novartis Investigative Site
• Bulgaria
  • Plovdiv, Bulgaria, 4002
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1309
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1431
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1407
    • Novartis Investigative Site
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • Novartis Investigative Site
  • British Columbia
    • Burnaby, British Columbia, Canada, V5G 2X6
      • Novartis Investigative Site
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 4K4
      • Novartis Investigative Site
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Novartis Investigative Site
  • Quebec
    • Lévis, Quebec, Canada, G6W 0M5
      • Novartis Investigative Site
    • Montreal, Quebec, Canada, H4A 3T2
      • Novartis Investigative Site
    • Québec, Quebec, Canada, G1J 1Z4
      • Novartis Investigative Site
    • Saint-Jérôme, Quebec, Canada, J7Z 5T3
      • Novartis Investigative Site
• China
  • Beijing, China, 100034
    • Novartis Investigative Site
  • Shanghai, China, 200025
    • Novartis Investigative Site
  • Shanghai, China, 200040
    • Novartis Investigative Site
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Novartis Investigative Site
    • Wuhan, Hubei, China, 430060
      • Novartis Investigative Site
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Novartis Investigative Site
  • Ningxia
    • Yinchuan, Ningxia, China, 750004
      • Novartis Investigative Site
  • Shanxi
    • Taiyuan, Shanxi, China, 030001
      • Novartis Investigative Site
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310016
      • Novartis Investigative Site
    • Hangzhou, Zhejiang, China, 310006
      • Novartis Investigative Site
    • Wenzhou, Zhejiang, China, 325000
      • Novartis Investigative Site
• Croatia
  • Vukovar, Croatia, 32000
    • Novartis Investigative Site
  • Zagreb, Croatia, 10000
    • Novartis Investigative Site
  • HRV
    • Split, HRV, Croatia, 21000
      • Novartis Investigative Site
    • Varaždin, HRV, Croatia, 42000
      • Novartis Investigative Site
• Czechia
  • Brno, Czechia, 602 00
    • Novartis Investigative Site
  • Hradec Králové, Czechia, 500 05
    • Novartis Investigative Site
  • Teplice, Czechia, 415 29
    • Novartis Investigative Site
• Estonia
  • Tallinn, Estonia, 11315
    • Novartis Investigative Site
  • Tartu, Estonia, 50406
    • Novartis Investigative Site
• France
  • Caen, France, 14033
    • Novartis Investigative Site
  • Clermont-Ferrand, France, 63003
    • Novartis Investigative Site
  • Dijon, France, 21000
    • Novartis Investigative Site
  • Gonesse, France, 95500
    • Novartis Investigative Site
  • Grenoble, France, 38043
    • Novartis Investigative Site
  • Lille, France, 59037
    • Novartis Investigative Site
  • Lille, France, 59000
    • Novartis Investigative Site
  • Nice, France, 06001
    • Novartis Investigative Site
  • Nîmes, France, 30029
    • Novartis Investigative Site
  • Poissy, France, 78303
    • Novartis Investigative Site
  • Toulouse, France, 31059
    • Novartis Investigative Site
  • Haute Vienne
    • Limoges, Haute Vienne, France, 87000
      • Novartis Investigative Site
  • Val De Marne
    • Toulon, Val De Marne, France, 83800
      • Novartis Investigative Site
• Germany
  • Essen, Germany, 45147
    • Novartis Investigative Site
  • Hamburg, Germany, 22179
    • Novartis Investigative Site
  • Baden-Wurttemberg
    • Freiburg im Breisgau, Baden-Wurttemberg, Germany, 79106
      • Novartis Investigative Site
• Greece
  • Athens, Greece, 115 28
    • Novartis Investigative Site
  • Athens, Greece, 11526
    • Novartis Investigative Site
  • Chaïdári, Greece, 124 62
    • Novartis Investigative Site
  • Ioannina, Greece, 455 00
    • Novartis Investigative Site
  • Larissa, Greece, 411 10
    • Novartis Investigative Site
  • Thessaloniki, Greece, 54636
    • Novartis Investigative Site
  • Thessaloniki, Greece, 53246
    • Novartis Investigative Site
• India
  • Kerala
    • Kochi, Kerala, India, 682025
      • Novartis Investigative Site
  • Maharashtra
    • Pune, Maharashtra, India, 411013
      • Novartis Investigative Site
  • National Capital Territory of Delhi
    • New Delhi, National Capital Territory of Delhi, India, 110060
      • Novartis Investigative Site
  • Punjab
    • Amritsar, Punjab, India, 143006
      • Novartis Investigative Site
  • Telangana
    • Hyderabad, Telangana, India, 500082
      • Novartis Investigative Site
  • Uttar Pradesh
    • Lucknow, Uttar Pradesh, India, 226007
      • Novartis Investigative Site
  • West Bengal
    • Kolkata, West Bengal, India, 700017
      • Novartis Investigative Site
• Italy
  • Naples, Italy, 80138
    • Novartis Investigative Site
  • BR
    • Brindisi, BR, Italy, 72100
      • Novartis Investigative Site
  • FG
    • Foggia, FG, Italy, 71122
      • Novartis Investigative Site
  • IS
    • Pozzilli, IS, Italy, 86077
      • Novartis Investigative Site
  • ME
    • Messina, ME, Italy, 98124
      • Novartis Investigative Site
  • MO
    • Modena, MO, Italy, 41126
      • Novartis Investigative Site
  • PV
    • Pavia, PV, Italy, 27100
      • Novartis Investigative Site
  • TO
    • Orbassano, TO, Italy, 10043
      • Novartis Investigative Site
• Japan
  • Chiba, Japan, 2608677
    • Novartis Investigative Site
  • Fukuoka, Japan, 810-0022
    • Novartis Investigative Site
  • Fukuoka, Japan, 8128582
    • Novartis Investigative Site
  • Kobe, Japan, 650-0017
    • Novartis Investigative Site
  • Kyoto, Japan, 616-8255
    • Novartis Investigative Site
  • Niigata, Japan, 9518520
    • Novartis Investigative Site
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 4668560
      • Novartis Investigative Site
  • Chiba
    • Ichihara, Chiba, Japan, 2990111
      • Novartis Investigative Site
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 0630005
      • Novartis Investigative Site
  • Hyōgo
    • Nishinomiya, Hyōgo, Japan, 6638501
      • Novartis Investigative Site
  • Kanagawa
    • Isehara, Kanagawa, Japan, 259-1193
      • Novartis Investigative Site
    • Sagamihara, Kanagawa, Japan, 252-0375
      • Novartis Investigative Site
  • Miyagi
    • Sendai, Miyagi, Japan, 9838512
      • Novartis Investigative Site
  • Nara
    • Kashihara, Nara, Japan, 6348522
      • Novartis Investigative Site
  • Osaka
    • Moriguchi, Osaka, Japan, 570-8507
      • Novartis Investigative Site
    • Suita, Osaka, Japan, 565-0871
      • Novartis Investigative Site
  • Saitama
    • Higashi-Matsuyama, Saitama, Japan, 355-0005
      • Novartis Investigative Site
  • Tokyo
    • Itabashi-ku, Tokyo, Japan, 1738610
      • Novartis Investigative Site
    • Kodaira, Tokyo, Japan, 187-8551
      • Novartis Investigative Site
    • Shinjuku Ku, Tokyo, Japan, 160-0023
      • Novartis Investigative Site
    • Shinjuku Ku, Tokyo, Japan, 1628666
      • Novartis Investigative Site
    • Shinjuku-ku, Tokyo, Japan, 1608582
      • Novartis Investigative Site
• Mexico
  • Chihuahua City, Mexico, 31203
    • Novartis Investigative Site
  • Mexico City, Mexico, 14050
    • Novartis Investigative Site
  • Querétaro, Mexico, 76070
    • Novartis Investigative Site
  • Mexico City
    • Mexico City, Mexico City, Mexico, 06700
      • Novartis Investigative Site
• Poland
  • Bialystok, Poland, 15-704
    • Novartis Investigative Site
  • Glogow Wielkopolski, Poland, 36-060
    • Novartis Investigative Site
  • Katowice, Poland, 40-081
    • Novartis Investigative Site
  • Katowice, Poland, 40-571
    • Novartis Investigative Site
  • Katowice, Poland, 40-686
    • Novartis Investigative Site
  • Katowice, Poland, 40-689
    • Novartis Investigative Site
  • Lublin, Poland, 20-701
    • Novartis Investigative Site
  • Wroclaw, Poland, 51-685
    • Novartis Investigative Site
  • Zabrze, Poland, 41-800
    • Novartis Investigative Site
  • Poznan
    • Plewiska, Poznan, Poland, 62-064
      • Novartis Investigative Site
• Portugal
  • Braga, Portugal, 4710243
    • Novartis Investigative Site
  • Coimbra, Portugal, 3004-561
    • Novartis Investigative Site
  • Leiria, Portugal, 2410-197
    • Novartis Investigative Site
  • Lisbon, Portugal, 1649-035
    • Novartis Investigative Site
  • Lisbon, Portugal, 1169-050
    • Novartis Investigative Site
  • Matosinhos Municipality, Portugal, 4454-513
    • Novartis Investigative Site
  • Santa Maria da Feira, Portugal, 4520-211
    • Novartis Investigative Site
• Puerto Rico
  • Guaynabo, Puerto Rico, 00968
    • Caribbean Center for Clinical Research Inc
• Romania
  • Campulung Muscel, Romania, 115100
    • Novartis Investigative Site
  • Constanța, Romania, 900591
    • Novartis Investigative Site
  • ROM
    • Brasov, ROM, Romania, 500123
      • Novartis Investigative Site
    • Constanța, ROM, Romania, 900123
      • Novartis Investigative Site
• Slovakia
  • Banská Bystrica, Slovakia, 975 17
    • Novartis Investigative Site
  • Banská Bystrica, Slovakia, 974 04
    • Novartis Investigative Site
  • Bratislava, Slovakia, 833 05
    • Novartis Investigative Site
• Slovenia
  • Celje, Slovenia, 3000
    • Novartis Investigative Site
  • Ljubljana, Slovenia, 1000
    • Novartis Investigative Site
  • Maribor, Slovenia, 2000
    • Novartis Investigative Site
• South Africa
  • Pretoria, South Africa, 0041
    • Novartis Investigative Site
  • Rosebank, South Africa, 2196
    • Novartis Investigative Site
  • Free State
    • Bloemfontein, Free State, South Africa, 9301
      • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08041
    • Novartis Investigative Site
  • Lleida, Spain, 25198
    • Novartis Investigative Site
  • Madrid, Spain, 28040
    • Novartis Investigative Site
  • Madrid, Spain, 28009
    • Novartis Investigative Site
  • Málaga, Spain, 29016
    • Novartis Investigative Site
  • Seville, Spain, 41009
    • Novartis Investigative Site
  • Valencia, Spain, 46026
    • Novartis Investigative Site
  • A Coruna
    • Santiago Compostela, A Coruna, Spain, 15706
      • Novartis Investigative Site
  • Araba
    • Vitoria-Gasteiz, Araba, Spain, 01009
      • Novartis Investigative Site
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Novartis Investigative Site
  • Castille-La Mancha
    • Albacete, Castille-La Mancha, Spain, 02006
      • Novartis Investigative Site
  • Catalonia
    • Barcelona, Catalonia, Spain, 08003
      • Novartis Investigative Site
  • La Rioja
    • Logroño, La Rioja, Spain, 26006
      • Novartis Investigative Site
  • Madrid
    • Pozuelo de Alarcón, Madrid, Spain, 28223
      • Novartis Investigative Site
    • Torrejón de Ardoz, Madrid, Spain, 28850
      • Novartis Investigative Site
  • Principality of Asturias
    • Gijón, Principality of Asturias, Spain, 33394
      • Novartis Investigative Site
  • Valencia
    • Valencia, Valencia, Spain, 46017
      • Novartis Investigative Site
• Sweden
  • Stockholm, Sweden, 102 35
    • Novartis Investigative Site
• Turkey (Türkiye)
  • Kocaeli, Turkey (Türkiye), 41380
    • Novartis Investigative Site
  • Konya, Turkey (Türkiye), 42130
    • Novartis Investigative Site
  • Atakum
    • Samsun, Atakum, Turkey (Türkiye), 55200
      • Novartis Investigative Site
  • Balcova
    • Izmir, Balcova, Turkey (Türkiye), 35340
      • Novartis Investigative Site
  • Fatih
    • Istanbul, Fatih, Turkey (Türkiye), 34098
      • Novartis Investigative Site
    • Istanbul, Fatih, Turkey (Türkiye), 34093
      • Novartis Investigative Site
  • Karabaglar
    • Izmir, Karabaglar, Turkey (Türkiye), 35150
      • Novartis Investigative Site
  • Melikgazi
    • Kayseri, Melikgazi, Turkey (Türkiye), 38039
      • Novartis Investigative Site
  • Nilufer
    • Bursa, Nilufer, Turkey (Türkiye), 16140
      • Novartis Investigative Site
  • Pendik
    • Istanbul, Pendik, Turkey (Türkiye), 34899
      • Novartis Investigative Site
  • Sancaktepe
    • Istanbul, Sancaktepe, Turkey (Türkiye), 34785
      • Novartis Investigative Site
• United Kingdom
  • Invernesshire
    • Inverness, Invernesshire, United Kingdom, IV2 3RE
      • Novartis Investigative Site
  • Kent
    • Canterbury, Kent, United Kingdom, CT1 3NG
      • Novartis Investigative Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85018
      • Ctr for Neurology and Spine
  • California
    • Hanford, California, United States, 93230
      • Vladimir Royter MD APMC
    • Los Angeles, California, United States, 90073
      • VA Greater LA Healthcare System
    • West Hollywood, California, United States, 90048
      • Regina Berkovich MD PhD Inc
  • Colorado
    • Aurora, Colorado, United States, 80045
      • CU Anschutz Med Campus
    • Denver, Colorado, United States, 80210
      • Colorado Neurological Research PC
  • Connecticut
    • Stamford, Connecticut, United States, 06905
      • New England Institute for Clinical Research
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • Georgetown University Hospital
    • Washington D.C., District of Columbia, United States, 20007
      • Georgetown University Hospital Research
  • Florida
    • Bradenton, Florida, United States, 34209
      • Nova Clinical Research LLC
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Hollywood, Florida, United States, 33021
      • Memorial Healthcare System
    • Maitland, Florida, United States, 32751
      • Neurology Associates PA
    • Miami, Florida, United States, 33136
      • UM Department Of Neurology
    • Miami, Florida, United States, 33133
      • Gables Neurology
    • Naples, Florida, United States, 34105
      • Aqualane Clinical Research
    • Orlando, Florida, United States, 32803
      • Advent Health Orlando
    • Pembroke Pines, Florida, United States, 33024
      • Humanity Clinical Research
    • Pensacola, Florida, United States, 32514
      • Emerald Coast Neurology
    • Port Orange, Florida, United States, 32127
      • Brain and Spine Institute
    • Vero Beach, Florida, United States, 32960
      • Vero Beach Neurology
    • Winter Park, Florida, United States, 32789
      • Conquest Research
  • Indiana
    • Merrillville, Indiana, United States, 46410
      • Methodist Neuroscience Institute
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Hospital
  • Kentucky
    • Nicholasville, Kentucky, United States, 40356
      • Baptist Physicians Lexington
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation
  • Maryland
    • Frederick, Maryland, United States, 21702
      • Clinre Comprehensive Neurology
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • Missouri
    • Kansas City, Missouri, United States, 64128
      • Kansas City VA Medical Center
  • New York
    • Patchogue, New York, United States, 11772
      • South Shore Neurologic Associates
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599 9500
      • University Of NC At Chapel Hill
    • Charlotte, North Carolina, United States, 28210
      • Piedmont Healthcare
  • Ohio
    • Columbus, Ohio, United States, 43235
      • The Boster Ctr for MS
    • Dayton, Ohio, United States, 45408
      • Neurology Diagnostics Inc
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Hershey Medical Center
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Premier Neurology
    • Old Point Station, South Carolina, United States, 29707
      • Metrolina Neurological Associates PA
  • Tennessee
    • Knoxville, Tennessee, United States, 37922
      • Sibyl Wray MD Neurology PC
  • Texas
    • Dallas, Texas, United States, 75231
      • Neurology Consultants of Dallas PA
    • El Paso, Texas, United States, 79935
      • Med Research Inc
    • Frisco, Texas, United States, 75035
      • Lone Star Neurology
    • San Antonio, Texas, United States, 78258
      • Lonestar Neurology of San Antonio
    • San Antonio, Texas, United States, 78229
      • UT Health MARC Medical Arts and Research Center
    • Sherman, Texas, United States, 75092
      • Texas Institute for Neurological Disorders
    • Temple, Texas, United States, 76508
      • Baylor Scott and White
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Centre
    • Seattle, Washington, United States, 98133
      • University of Washington MS Clinic
  • West Virginia
    • Crab Orchard, West Virginia, United States, 25827
      • Elligo Health Research
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Ascension St Francis Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

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 (including all Child-Pugh classes) or hepatic failure 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 as per central ECG reading at screening visit
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Remibrutinib - Core; Remibrutinib tablet and matching placebo of teriflunomide capsule	Drug: Remibrutinib; tablet taken orally; Other Names: LOU064
Active Comparator: Teriflunomide - Core; Teriflunomide capsule and matching placebo remibrutinib tablet	Drug: Teriflunomide; capsule taken orally
Experimental: Remibrutinib - Extension; Participants on remibrutinib in Core will continue on remibrutinib tablet	Drug: Remibrutinib; tablet taken orally; Other Names: LOU064
Experimental: Remibrutinib - Extension (on teriflunomide in Core); Participants on teriflunomide in Core will switch to remibrutinib tablet	Drug: Remibrutinib; tablet taken orally; Other Names: LOU064

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurofilament light chain (Nfl) [Core Part]	Neurofilament light chain (NfL) concentration in serum	Baseline up to 30 months
Pharmacokinetics of remibrutinib [Core Part]	Blood concentrations of remibrutinib	Month 1, Month 6
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
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
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
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
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
Neurofilament light chain (NfL) [Extension Part]	Neurofilament light chain (NfL) concentration in serum	Day 1 Extension up to 5 years
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
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
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
Annualized rate of new or enlarging T2 lesion [Core Part]	Number of new/newly enlarged T2 lesions per year	Baseline up to 30 months
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
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
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
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
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
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
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
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
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
Change from Baseline in T2 lesion volume [Core Part]	Change from baseline in total T2 lesion volume.	Baseline up to 30 months
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
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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2021
• Primary Completion (Estimated): July 23, 2026
• Study Completion (Estimated): October 30, 2030

Study Registration Dates

• First Submitted: December 1, 2021
• First Submitted That Met QC Criteria: December 1, 2021
• First Posted (Actual): December 14, 2021

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: adult; RRMS; MS; relapse; Neurofilament light chain; teriflunomide; RMS; Expanded Disability Status Scale; active secondary progressive multiple sclerosis SPMS; remibrutinib; LOU064; T2 lesions; T1 lesions; GD- enhancing MRI; McDonald diagnostic criteria
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Pathological Conditions, Signs and Symptoms; Recurrence; Charcot-Marie-Tooth disease, Type 1F; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Antirheumatic Agents; Sensory System Agents; Protein Kinase Inhibitors; Analgesics, Non-Narcotic; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; teriflunomide; remibrutinib
• Other Study ID Numbers: CLOU064C12302; 2023-509372-41-00 (Registry Identifier: EU CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No