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

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

Study Overview

• Status: Recruiting
• Conditions: Relapsing Multiple Sclerosis
• Intervention / Treatment: Drug: Remibrutinib; Drug: Teriflunomide

Detailed Description

The study CLOU064C12301 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 (CLOU064C12302) 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 (Estimated): 800
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: 1-888-669-6682; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals; Phone Number: +41613241111

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1012AAR
    • Recruiting
    • Novartis Investigative Site
  • Caba, Argentina, C1424BYD
    • Recruiting
    • Novartis Investigative Site
  • Capital Federal, Argentina, C1023AAB
    • Recruiting
    • Novartis Investigative Site
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1122AAK
      • Recruiting
      • Novartis Investigative Site
    • Capital Federal, Buenos Aires, Argentina, 1424
      • Recruiting
      • Novartis Investigative Site
  • Santa Fe
    • Rosario, Santa Fe, Argentina, 2000
      • Recruiting
      • Novartis Investigative Site
• Belgium
  • Antwerpen, Belgium, 2018
    • Recruiting
    • Novartis Investigative Site
  • Ath, Belgium, 7800
    • Recruiting
    • Novartis Investigative Site
  • Brasschaat, Belgium, 2930
    • Recruiting
    • Novartis Investigative Site
  • Brugge, Belgium, 8000
    • Recruiting
    • Novartis Investigative Site
  • Lier, Belgium, 2500
    • Recruiting
    • Novartis Investigative Site
  • Melsbroek, Belgium, 1820
    • Recruiting
    • Novartis Investigative Site
  • Pelt, Belgium, 3900
    • Recruiting
    • Novartis Investigative Site
  • Antwerpen
    • Edegem, Antwerpen, Belgium, 2650
      • Recruiting
      • Novartis Investigative Site
  • Brussel
    • Jette, Brussel, Belgium, 1090
      • Recruiting
      • Novartis Investigative Site
• Bulgaria
  • Pleven, Bulgaria, 5800
    • Recruiting
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1431
    • Recruiting
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1113
    • Recruiting
    • Novartis Investigative Site
• Chile
  • Region Metropolitana
    • Santiago, Region Metropolitana, Chile, 7650568
      • Recruiting
      • Novartis Investigative Site
    • Santiago, Region Metropolitana, Chile, 8431657
      • Recruiting
      • Novartis Investigative Site
• China
  • Beijing, China, 100730
    • Recruiting
    • Novartis Investigative Site
  • Beijing, China, 100029
    • Recruiting
    • Novartis Investigative Site
  • Chongqing, China, 400016
    • Recruiting
    • Novartis Investigative Site
  • Tianjin, China, 300052
    • Recruiting
    • Novartis Investigative Site
  • Beijing
    • Beijing, Beijing, China, 100000
      • Recruiting
      • Novartis Investigative Site
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Recruiting
      • Novartis Investigative Site
    • Guangzhou City, Guangdong, China, 510000
      • Recruiting
      • Novartis Investigative Site
  • Henan
    • Zhengzhou, Henan, China, 450052
      • Recruiting
      • Novartis Investigative Site
  • Hunan
    • Changsha, Hunan, China, 410008
      • Recruiting
      • Novartis Investigative Site
  • Inner Mongolia
    • Baotou, Inner Mongolia, China, 014040
      • Recruiting
      • Novartis Investigative Site
    • Hohhot, Inner Mongolia, China, 010017
      • Recruiting
      • Novartis Investigative Site
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Recruiting
      • Novartis Investigative Site
  • Jilin
    • Changchun, Jilin, China, 130021
      • Recruiting
      • Novartis Investigative Site
• Colombia
  • Bogota, Colombia, 110110
    • Recruiting
    • Novartis Investigative Site
  • Atlantico
    • Puerto Colombia, Atlantico, Colombia, 080012
      • Recruiting
      • Novartis Investigative Site
  • Valle Del Cauca
    • Cali, Valle Del Cauca, Colombia, 760012
      • Recruiting
      • Novartis Investigative Site
    • Cali, Valle Del Cauca, Colombia, 760001
      • Recruiting
      • Novartis Investigative Site
• Croatia
  • Osijek, Croatia, 31000
    • Recruiting
    • Novartis Investigative Site
  • Zadar, Croatia, 23000
    • Recruiting
    • Novartis Investigative Site
  • Zagreb, Croatia, 10000
    • Recruiting
    • Novartis Investigative Site
  • HRV
    • Rijeka, HRV, Croatia, 51000
      • Recruiting
      • Novartis Investigative Site
• Denmark
  • Slagelse, Denmark, DK-4200
    • Recruiting
    • Novartis Investigative Site
• Guatemala
  • Guatemala, Guatemala, 01015
    • Recruiting
    • Novartis Investigative Site
• Hong Kong
  • Sha Tin, Hong Kong
    • Recruiting
    • Novartis Investigative Site
• India
  • Delhi
    • New Delhi, Delhi, India, 110017
      • Recruiting
      • Novartis Investigative Site
  • Maharashtra
    • Mumbai, Maharashtra, India, 400008
      • Recruiting
      • Novartis Investigative Site
    • Nashik, Maharashtra, India, 422005
      • Recruiting
      • Novartis Investigative Site
  • Punjab
    • Chandigarh, Punjab, India, 160012
      • Recruiting
      • Novartis Investigative Site
    • Ludhiana, Punjab, India, 141008
      • Recruiting
      • Novartis Investigative Site
  • Telangana
    • Hyderabad, Telangana, India, 500082
      • Recruiting
      • Novartis Investigative Site
  • Uttar Pradesh
    • Lucknow, Uttar Pradesh, India, 226014
      • Recruiting
      • Novartis Investigative Site
  • Uttarakhand
    • DehraDun, Uttarakhand, India, 248001
      • Recruiting
      • Novartis Investigative Site
• Ireland
  • Dublin, Ireland, DUBLIN 8
    • Recruiting
    • Novartis Investigative Site
  • Dublin 4, Ireland, DO4
    • Recruiting
    • Novartis Investigative Site
• Italy
  • Napoli, Italy, 80131
    • Recruiting
    • Novartis Investigative Site
  • BS
    • Montichiari, BS, Italy, 25018
      • Recruiting
      • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20132
      • Recruiting
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00133
      • Recruiting
      • Novartis Investigative Site
    • Roma, RM, Italy, 00168
      • Recruiting
      • Novartis Investigative Site
  • VR
    • Verona, VR, Italy, 37134
      • Recruiting
      • Novartis Investigative Site
• Latvia
  • Riga, Latvia, LV 1002
    • Recruiting
    • Novartis Investigative Site
  • LV
    • Riga, LV, Latvia, LV-1005
      • Recruiting
      • Novartis Investigative Site
• Lebanon
  • Beirut, Lebanon, 6301
    • Recruiting
    • Novartis Investigative Site
  • LBN
    • El Chouf, LBN, Lebanon, 1503201002
      • Recruiting
      • Novartis Investigative Site
• Malaysia
  • Kuala Lumpur, Malaysia, 50589
    • Recruiting
    • Novartis Investigative Site
  • Pulau Pinang
    • Seberang Jaya, Pulau Pinang, Malaysia, 13700
      • Recruiting
      • Novartis Investigative Site
  • Terengganu
    • Kuala Terengganu, Terengganu, Malaysia, 20400
      • Recruiting
      • Novartis Investigative Site
• Netherlands
  • Breda, Netherlands, 4818 CK
    • Recruiting
    • Novartis Investigative Site
  • Hertogenbosch, Netherlands, 5200
    • Recruiting
    • Novartis Investigative Site
  • Rotterdam, Netherlands, 3079 DZ
    • Recruiting
    • Novartis Investigative Site
• Poland
  • Kielce, Poland, 25 726
    • Recruiting
    • Novartis Investigative Site
  • Lodz, Poland, 90 324
    • Recruiting
    • Novartis Investigative Site
  • Lodz, Poland, 93-113
    • Recruiting
    • Novartis Investigative Site
  • Piotrkow Trybunalski, Poland, 97300
    • Recruiting
    • Novartis Investigative Site
  • Poznan, Poland, 60-693
    • Recruiting
    • Novartis Investigative Site
  • Rzeszow, Poland, 35-323
    • Recruiting
    • Novartis Investigative Site
  • Szczecin, Poland, 70111
    • Recruiting
    • Novartis Investigative Site
  • Dolnoslaskie
    • Wroclaw, Dolnoslaskie, Poland, 52 416
      • Recruiting
      • Novartis Investigative Site
  • Woj Kujawsko-pomorskie
    • Bydgoszcz, Woj Kujawsko-pomorskie, Poland, 85-796
      • Recruiting
      • Novartis Investigative Site
• Slovakia
  • Bratislava, Slovakia, 82606
    • Recruiting
    • Novartis Investigative Site
  • Nitra, Slovakia, 94901
    • Recruiting
    • Novartis Investigative Site
  • Trnava, Slovakia, 917 75
    • Recruiting
    • Novartis Investigative Site
  • Slovak Republic
    • Kosice, Slovak Republic, Slovakia, 04066
      • Recruiting
      • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Novartis Investigative Site
  • Las Palmas de Gran Canaria, Spain, 35010
    • Recruiting
    • Novartis Investigative Site
  • Leon, Spain, 24080
    • Recruiting
    • Novartis Investigative Site
  • Madrid, Spain, 28034
    • Recruiting
    • Novartis Investigative Site
  • Madrid, Spain, 28040
    • Recruiting
    • Novartis Investigative Site
  • Madrid, Spain, 28222
    • Recruiting
    • Novartis Investigative Site
  • Andalucia
    • Cadiz, Andalucia, Spain, 11009
      • Recruiting
      • Novartis Investigative Site
    • Cordoba, Andalucia, Spain, 14004
      • Recruiting
      • Novartis Investigative Site
    • Malaga, Andalucia, Spain, 29010
      • Recruiting
      • Novartis Investigative Site
  • Barcelona
    • Sant Joan Despi, Barcelona, Spain, 08970
      • Recruiting
      • Novartis Investigative Site
  • Cataluna
    • Salt, Cataluna, Spain, 17190
      • Recruiting
      • Novartis Investigative Site
  • Galicia
    • La Coruna, Galicia, Spain, 15006
      • Recruiting
      • Novartis Investigative Site
  • Madrid
    • Alcorcon, Madrid, Spain, 28922
      • Recruiting
      • Novartis Investigative Site
    • Getafe, Madrid, Spain, 28905
      • Recruiting
      • Novartis Investigative Site
  • Murcia
    • El Palmar, Murcia, Spain, 30120
      • Recruiting
      • Novartis Investigative Site
  • Vizcaya
    • Baracaldo, Vizcaya, Spain, 48903
      • Recruiting
      • Novartis Investigative Site
• Switzerland
  • Basel, Switzerland, 4031
    • Recruiting
    • Novartis Investigative Site
  • Bern, Switzerland, 3010
    • Recruiting
    • Novartis Investigative Site
• United Kingdom
  • Bristol
    • Westbruy On Trym, Bristol, United Kingdom, BS10 5NB
      • Recruiting
      • Novartis Investigative Site
  • Hampshire
    • Winchester, Hampshire, United Kingdom, SO21 1HU
      • Recruiting
      • Novartis Investigative Site
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Recruiting
      • Novartis Investigative Site
    • Tucson, Arizona, United States, 85718
      • Recruiting
      • Novartis Investigative Site
  • Arkansas
    • Fort Smith, Arkansas, United States, 72916
      • Recruiting
      • Novartis Investigative Site
  • California
    • Berkeley, California, United States, 94705
      • Recruiting
      • Novartis Investigative Site
    • Chula Vista, California, United States, 91910
      • Recruiting
      • Novartis Investigative Site
    • Fullerton, California, United States, 92835
      • Recruiting
      • Novartis Investigative Site
    • Glendale, California, United States, 91206
      • Recruiting
      • Novartis Investigative Site
    • Newport Beach, California, United States, 92663
      • Recruiting
      • Novartis Investigative Site
  • Colorado
    • Basalt, Colorado, United States, 81621
      • Recruiting
      • Novartis Investigative Site
    • Boulder, Colorado, United States, 80301
      • Recruiting
      • Novartis Investigative Site
  • Delaware
    • Newark, Delaware, United States, 19713
      • Recruiting
      • Novartis Investigative Site
  • Florida
    • Altamonte Springs, Florida, United States, 32714
      • Recruiting
      • Novartis Investigative Site
    • Miami, Florida, United States, 33032
      • Recruiting
      • Novartis Investigative Site
    • Miami, Florida, United States, 33175
      • Recruiting
      • Novartis Investigative Site
    • Orlando, Florida, United States, 32806
      • Recruiting
      • Novartis Investigative Site
    • Orlando, Florida, United States, 32825
      • Recruiting
      • Novartis Investigative Site
    • Ormond Beach, Florida, United States, 32174
      • Recruiting
      • Novartis Investigative Site
    • Port Charlotte, Florida, United States, 33952
      • Recruiting
      • Novartis Investigative Site
    • Seminole, Florida, United States, 33777
      • Recruiting
      • Novartis Investigative Site
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Novartis Investigative Site
    • Tampa, Florida, United States, 33609
      • Recruiting
      • Novartis Investigative Site
  • Georgia
    • Savannah, Georgia, United States, 31406
      • Recruiting
      • Novartis Investigative Site
  • Hawaii
    • Honolulu, Hawaii, United States, 96817
      • Withdrawn
      • Novartis Investigative Site
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Recruiting
      • Novartis Investigative Site
    • Chicago, Illinois, United States, 60616
      • Recruiting
      • Novartis Investigative Site
    • Park Ridge, Illinois, United States, 60068
      • Recruiting
      • Novartis Investigative Site
  • Indiana
    • Fort Wayne, Indiana, United States, 46845
      • Recruiting
      • Novartis Investigative Site
  • Kansas
    • Overland Park, Kansas, United States, 66210
      • Recruiting
      • Novartis Investigative Site
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Recruiting
      • Novartis Investigative Site
    • Lutherville, Maryland, United States, 21093
      • Recruiting
      • Novartis Investigative Site
  • Massachusetts
    • Foxboro, Massachusetts, United States, 02035
      • Recruiting
      • Novartis Investigative Site
  • Missouri
    • Saint Louis, Missouri, United States, 63131
      • Recruiting
      • Novartis Investigative Site
  • Montana
    • Billings, Montana, United States, 59101
      • Recruiting
      • Novartis Investigative Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Recruiting
      • Novartis Investigative Site
    • Raleigh, North Carolina, United States, 27607
      • Recruiting
      • Novartis Investigative Site
  • Ohio
    • Westerville, Ohio, United States, 43082
      • Completed
      • Novartis Investigative Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Recruiting
      • Novartis Investigative Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107-5098
      • Recruiting
      • Novartis Investigative Site
    • Reading, Pennsylvania, United States, 19611
      • Recruiting
      • Novartis Investigative Site
  • South Carolina
    • Summerville, South Carolina, United States, 29485
      • Recruiting
      • Novartis Investigative Site
  • Texas
    • Dallas, Texas, United States, 75206
      • Recruiting
      • Novartis Investigative Site
    • Dallas, Texas, United States, 75390-9034
      • Withdrawn
      • Novartis Investigative Site
    • El Paso, Texas, United States, 79912
      • Withdrawn
      • Novartis Investigative Site
    • Houston, Texas, United States, 77074
      • Recruiting
      • Novartis Investigative Site
    • McAllen, Texas, United States, 78503
      • Recruiting
      • Novartis Investigative Site
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Withdrawn
      • Novartis Investigative Site
  • Virginia
    • Vienna, Virginia, United States, 22182
      • Recruiting
      • Novartis Investigative Site
  • Washington
    • Seattle, Washington, United States, 98122
      • Recruiting
      • Novartis Investigative Site
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Recruiting
      • Novartis Investigative Site
    • Neenah, Wisconsin, United States, 54956
      • Recruiting
      • Novartis Investigative Site

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 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 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)

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 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 month
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 month
Annualized rate of new or enlarging T2 lesion [Core Part]	Number of new/newly enlarged T2 lesions per year	Baseline up to 30 month
Neurofilament light chain (Nfl) [Core Part]	Neurofilament light chain (NfL) concentration in serum	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 month
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 month
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 month
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 month
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 month
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 month
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 month
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 month
Change from Baseline in T2 lesion volume [Core Part]	Change from baseline in total T2 lesion volume.	Baseline up to 30 month
Change from baseline in Fatigue Symptoms and Impacts Questionnaire - Relapsing Multiple Sclerosis (FSIQ-RMS) [Core Part]	20-item, self-administered questionnaire. Global score ranges from 0 to 100 where higher score represents greater fatigue	Baseline up to 30 month
Change from baseline in Generalized Anxiety Disorder Scale (GAD-7) [Core Part]	7-item, self-administered scale. It has a global score ranging from 0-21. Higher score means higher severity of anxiety symptoms	Baseline up to 30 month
Change from baseline in Patient Health Questionnaire-9 (PHQ-9) [Core Part]	9-item, self-administered scale. Scores can range from 0 to 27. PHQ-9 scores of 5, 10, 15, and 20 represent mild, moderate, moderately severe, and severe depression, respectively	Baseline up to 30 month
Change from baseline in Brief Pain Inventory- short form (BPI-SF) [Core Part]	15-item, self-administered questionnaire to assess the severity of pain and the impact of pain on daily functions. Includes seven-item interference scale. It has a 10-point response option, ranging from 0 (does not interfere) to 10 (completely interferes). Global score ranges from 0 to 10, where lower scores represent lower pain	Baseline up to 30 month
Change from baseline in Health Utilities Index (HUI-Ill) [Core Part]	15-item, self-administered index that measures eight health-related quality of life areas including vision, hearing, speech, ambulation/mobility, pain, dexterity, emotion, and cognition	Baseline up to 30 month
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 month
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 month
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 Fatigue Symptoms and Impacts Questionnaire - Relapsing Multiple Sclerosis (FSIQ-RMS) [Extension Part]	20-item, self-administered questionnaire. Global score ranges from 0 to 100 where higher score represents greater fatigue	Day 1 Extension up to 5 years
Change from baseline in Generalized Anxiety Disorder Scale (GAD-7) [Extension Part]	7-item, self-administered scale. It has a global score ranging from 0-21. Higher score means higher severity of anxiety symptoms	Day 1 Extension up to 5 years
Change from baseline in Patient Health Questionnaire-9 (PHQ-9) [Extension Part]	9-item, self-administered scale. Scores can range from 0 to 27. PHQ-9 scores of 5, 10, 15, and 20 represent mild, moderate, moderately severe, and severe depression, respectively	Day 1 Extension up to 5 years
Change from baseline in Brief Pain Inventory- short form (BPI-SF) [Extension Part]	15-item, self-administered questionnaire to assess the severity of pain and the impact of pain on daily functions. Includes seven-item interference scale. It has a 10-point response option, ranging from 0 (does not interfere) to 10 (completely interferes). Global score ranges from 0 to 10, where lower scores represent lower pain	Day 1 Extension up to 5 years
Change from baseline in Health Utilities Index (HUI-Ill) [Extension Part]	15-item, self-administered index that measures eight health-related quality of life areas including vision, hearing, speech, ambulation/mobility, pain, dexterity, emotion, and cognition	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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2021
• Primary Completion (Estimated): April 30, 2026
• Study Completion (Estimated): October 30, 2030

Study Registration Dates

• First Submitted: November 24, 2021
• First Submitted That Met QC Criteria: November 24, 2021
• First Posted (Actual): December 7, 2021

Study Record Updates

• Last Update Posted (Actual): October 3, 2023
• Last Update Submitted That Met QC Criteria: September 29, 2023
• Last Verified: September 1, 2023

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; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Protein Kinase Inhibitors; Teriflunomide; Remibrutinib
• Other Study ID Numbers: CLOU064C12301; 2020-005899-36 (EudraCT Number)

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