Phase III Study of Evobrutinib in Relapsing Multiple Sclerosis

INTERVENTION: Intervention1: Evobrutinib (M2951) 45mg administered orally twice daily: Blinding will be accomplished using a double dummy design given the differences in tablet characteristics between Evobrutinib and Aubagio®. For the purpose of this study, Evobrutinib matching placebo tablets and Aubagio® matching placebo tablets have been developed. Placebo tablets have the same visual appearance as the active tablets. Control Intervention1: Teriflunomide 14 mg film‐coated tablet once a day orally: Teriflunomide 14 mg film‐coated tablets (Aubagio® manufactured by Sanofi‐Genzyme) once a day orally. CONDITION: Health Condition 1: G00‐G99‐ Diseases of the nervous system PRIMARY OUTCOME: To demonstrate superior efficacy with evobrutinib compared to teriflunomide in terms of Annualized Relapse Rate (ARR)Timepoint: ARR based on qualified relapses at Week 96 in participants with RMS SECONDARY OUTCOME: To characterize the safety and tolerability of evobrutinibTimepoint: up to Week 108 To demonstrate the efficacy of evobrutinib relative to that of ; teriflunomide on MRI lesion parameterTimepoint: T1 Gd lesions based on assessments at Week 24, Week 48, and Week 96.T2 lesions based on assessments at Week 24, Week 48, and Week 96 To demonstrate the efficacy of evobrutinib relative to that of teriflunomide on disability progressionTimepoint: 12‐week confirmed disability progression (CDP) as measured by the Expanded Disability Status Scale (EDSS) over 96 weeks. Time to first occurrence of 24‐week CDP as measured by the EDSS over 96 weeks To demonstrate the efficacy of evobrutinib relative to that of teriflunomide on patient reported symptoms and functional statusTimepoint: Change from Baseline (CFB) in Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue score at 96 weeks INCLUSION CRITERIA: Age 1. Are 18 to 55 years of age at the time of signing the informed consent. Type of Participant and Disease Characteristics 2. Are diagnosed with RMS (relapsing‐remitting multiple sclerosis [RRMS] or SPMS with relapses) in accordance with 2017 Revised McDonald criteria (Thompson 2018). 3. One or more documented relapses within the 2 years before Screening with either: a. one relapse which occurred within the last year prior to randomization, OR b. the presence of at least 1 Gd+ T1 lesion within 6 months prior to randomization. 4. Have an EDSS score of 0 to 5.5 at Screening and Baseline (Day 1) a. Participants with an EDSS score â?¤ 2 at Screening and Baseline (Day 1) are only eligible for participation if their disease duration (time since onset of symptoms) is no more than 10 years. 5. Are neurologically stable for â?¥ 30 days prior to both Screening and