Efficacy and safety of remibrutinib compared to teriflunomide in participants with relapsing multiple sclerosis, followed by long term treatment with remibrutinib

INTERVENTION: Product Name: remibrutinib Product Code: LOU064 Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: Remibrutinib Current Sponsor code: LOU064C Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100‐ Pharmaceutical form of the placebo: Film‐coated tablet Route of administration of the placebo: Oral use Trade Name: Aubagio Product Name: Teriflunomide Pharmaceutical Form: Capsule, hard INN or Proposed INN: Teriflunomide CAS Number: 108605‐62‐5 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 14‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use CONDITION: Multiple Sclerosis ; MedDRA version: 21.0 Level: PT Classification code 10080700 Term: Relapsing multiple sclerosis System Organ Class: 10029205 ‐ Nervous system disorders Therapeutic area: Diseases [C] ‐ Nervous System Diseases [C10] PRIMARY OUTCOME: Main Objective: Core part:; Demonstrate that remibrutinib is superior to teriflunomide in reducing the frequency of confirmed relapses; Extension part:; To assess long‐term safety, tolerability and efficacy parameters in participants treated with remibrutinib Primary end point(s): Core part:; Annualized relapse rate (ARR) of confirmed relapses; Extension Part:; ‐ Adverse events, laboratory data, vital signs, electrocardiogram (ECG),; Columbia Suicide Severity Rating; ‐ ARR, number of new or enlarging T2 lesions on MRI per year; (annualized T2 lesion rate), time to 6mCDP (EDSS), change in SDMT,; NfL, Patient Reported Outcomes scores Secondary Objective: Core; Assess whether remibrutinib is superior to teriflunomide in; ‐ Delaying disability progression based on the pooled data from both identical pivotal studies; ‐ Reducing new inflammatory activity on MRI, based on MRI cohort data; ‐ Reducing neuronal damage; ‐ Disease‐Activity‐free status based on pooled data from both identical pivotal studies (MRI Cohort); Extension (exploratory); ‐ Explore effect of remibrutinib versus terifunomide on brain MRI, relationship between remibrutinib exposure (PK) and efficacy and safety endpoints and relationship between potential biomarkers and their relationship with disease activity, disease course and treatment response; ‐ Perform exploratory pharmacogenetic analysis based on blood samples for DNA (optional); ‐ Explore the effect of remibrutinib versus teriflunomide on disease activity free status and effect of remibrutinib versus teriflunomide on disability progression independent of relapse activity; See protocol for complete list of objectives Timepoint(s) of evaluation of this end point: Up to 30 months SECONDARY OUTCOME: Secondary end point(s): Core part:; ‐ Time to 3‐month confirmed disability progression (3mCDP) on Expanded Disability Status Scale (EDSS); ‐ Time to 6‐month confirmed disability progression (6mCDP) on EDSS; ‐ Number of new or enlarging T2 lesions on MRI per year (annualized T2 lesion rate); ‐ Total number of Gd‐enhancing T1 lesions per MRI scan; ‐ Neurofilament light chain (NfL) concentration in serum ; ‐ 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; ; Extension part (exploratory); ‐ Annualized rate of brain volume loss (BVL), based on percentage brain volume change from baseline; ‐ Change from baseline in cortical grey matter volume, hemispheric white matter volume and thalamus volume; ‐ Slowly Expanding Lesions (SEL) in MRI; ‐ T2 lesions, ARR, 3mCDP, safety endpoints etc. (as applicable); ‐ NfL, GFAP, total IgG, total IgM, B‐cells, T2 lesions, ARR, 3mCDP etc. (as applicable); ‐ Evaluate the relationship of genetic polymorphisms data with drug metabolism, the indication, the drug target pathway, and treatment response; ‐ Percentage of participants with NEDA‐4, as assessed by the absence of confirmed MS relapses, 6mCDP, new/enlarging T2 lesions on MRI and brain volume loss > ‐0.4%/year; ‐ Time to 3mCDP, 6mCDP Timepoint(s) of evaluation of this end point: Up to 30 months. INCLUSION CRITERIA: 1. Signed informed consent obtained prior to any assessment performed (confirm at screening visit) 2. Male or female participants 18 to 55 years of age (inclusive) at screening 3. Diagnosis of RMS according to the 2017 McDonald diagnostic criteria (this would include relapsing‐remitting course (RRMS) or secondary progressive (SPMS) course with disease activity) as confirmed at screening visit. 4. At least: 1 documented relapse within the previous year, OR 2 documented relapses within the previous 2 years, prior to screening, OR 1 active Gadolinium (Gd)‐enhancing lesion in the 12 months prior to screening 5. EDSS score of 0 to 5.5 (inclusive) at screening and randomization 6. Neurologically stable within 1 month prior to screening and randomization (including no MS relapse in this period) Please see protocol for complete detailed list of inclusion criteria Are the trial subjects under 18? no Number of subjects for this age range: