A Study of Efficacy and Safety of M2951 in Participants With Relapsing Multiple Sclerosis
Condition: Relapsing-remitting Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis
Intervention: Evobrutinib; Evobrutinib; Evobrutinib; Placebo; Tecfidera; Evobrutinib
Intervention description: Participants received Evobrutinib 75 milligrams (mg) orally, twice daily (BID) up to Week 48; Participants received Evobrutinib 25 mg orally, once daily (QD) up to Week 48; Participants received Evobrutinib 75 mg orally, QD up to Week 48; Placebo were administered for 24 weeks; Tecfidera; 120 mg hard capsule BID for 7 days then 240 mg hard capsule BID for duration of treatment (48 weeks).; Following Placebo for 24 weeks, participants received Evobrutinib 25 milligram (mg) orally, once daily (QD) from Week 24 to 48 weeks.
Intervention MeSH terms: Dimethyl Fumarate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Enrollment: 267.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: M2951; Relapsing Multiple Sclerosis; Bruton's Tyrosine Kinase inhibitor

Summary:

      The aim of this protocol is to find out about the safety and effectiveness of M2951 in
      participants with relapsing multiple sclerosis. Participants were placed into 1 of 3 groups
      to receive M2951, placebo or tecfidera for 24 weeks. After 24 weeks, the participants on
      placebo were given M2951.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants with a diagnosis of relapsing multiple sclerosis (may include
             participants with Secondary Progressive Multiple Sclerosis (SPMS) with superimposed
             relapses provided they meet the other criteria) in accordance with revised McDonald
             criteria for MS and Lublin and Reingold

          -  Male or female aged 18 to 65 years

          -  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 gadolinium-positive (Gd+) T1 lesion within 6 months prior to
             randomization would make the patient eligible.

          -  Expanded Disability Status Scale score of 0 to 6 at Baseline

          -  Women of childbearing potential must use a supplementary barrier method together with
             a highly effective method of contraception (according to International Council for
             Harmonisation [ICH] guidance M3[R2]) for 4 weeks prior to randomization, throughout
             the trial, and for 90 days after the last dose of IMP.

          -  Signed and dated informed consent (participant must be able to understand the informed
             consent) indicating that the participant has been informed of all the pertinent
             aspects of the trial prior to enrolment and will comply with the requirements of the
             protocol.

        Exclusion Criteria:

          -  Progressive MS

          -  Disease duration > 15 years in participants with EDSS of 2 or less

          -  Use of the following, as determined in the protocol ; rituximab, ocrelizumab,
             mitoxantrone, or lymphocyte-depleting therapies, lymphocyte trafficking blockers (eg,
             natalizumab, fingolimod), intravenous (IV) immunoglobulins (Ig), plasmapheresis,
             immunosuppressive treatments, B-interferons or glatiramer acetate, Systemic
             glucocorticoids, teriflunomide

          -  Exposure to Tecfidera within 6 months prior to randomization

          -  Any allergy, contraindication, or inability to tolerate Tecfidera

          -  Treatment with dalfampridine (fampridine, Ampyra) unless on a stable dose for ≥ 30
             days prior to randomization

          -  Inability to comply with MRI scanning

          -  Immunologic disorder other than MS, with the exception of secondary well-controlled
             diabetes or thyroid disorder, or any other condition requiring oral, IV,
             intramuscular, or intra-articular corticosteroid therapy

          -  Vaccination with live or live-attenuated virus vaccine within 1 month prior to
             Screening

          -  Severe drug allergy or history of anaphylaxis, or allergy to the IMP or any of its
             incipients

          -  Active, clinically significant viral, bacterial, or fungal infection, or any major
             episode of infection requiring hospitalization or treatment with parenteral
             anti-infectives within 4 weeks of Screening, or completion of oral anti-infectives
             within 2 weeks before or during Screening, or a history of recurrent infections (ie, 3
             or more of the same type of infection in a 12-month rolling period). Vaginal
             candidiasis, onychomycosis, and genital or oral herpes simplex virus considered by the
             Investigator to be sufficiently controlled would not be exclusionary.

          -  History of or positive testing for human immunodeficiency virus (HIV), hepatitis C
             (HCV) antibody and/or polymerase chain reaction, hepatitis B surface antigen (HBsAg)
             (+) and/or hepatitis B core total, and/or immunoglobulin M (IgM) antibody (+) at
             Screening.

          -  The participant: • Has a history of or current diagnosis of active tuberculosis (TB)
             or • Is currently undergoing treatment for latent TB infection (LTBI) or • Has an
             untreated LTBI or • Has a positive QuantiFERON®-TB test at Screening.

          -  Indeterminate QuantiFERON®

          -  Participants with current household contacts with active TB will also be excluded

          -  History of splenectomy or any major surgery within 2 months prior to Screening

          -  History of myocardial infarction or cerebrovascular event as per the protocol

          -  History of attempted suicide within 6 months prior to Screening or a positive response
             to items 4 or 5 of Columbia-Suicide Severity Rating Scale (C-SSRS)

          -  An episode of major depression within the last 6 months prior to Screening

          -  On anticoagulation, fish oil supplements, or antiplatelet therapy other than daily
             aspirin for cardioprotection and treatment of Tecfidera induced flushing

          -  History of cancer, except adequately treated basal cell or squamous cell carcinoma of
             the skin

          -  Breastfeeding/lactating or pregnant women

          -  Participation in any investigational drug trial within 1 month or 5 half-lives of the
             investigational drug, whichever is longest, prior to Screening

          -  Participants currently receiving (or unable to stop using prior to receiving the first
             dose of IMP) medications or herbal supplements known to be potent inhibitors of
             cytochrome P450 3A (CYP3A)

          -  History of or current alcohol or substance abuse

          -  Clinically significant abnormality on electrocardiogram or screening chest X-ray

          -  Clinically significant laboratory abnormality