A Study of Efficacy and Safety of M2951 in Participants With Relapsing Multiple Sclerosis
Relapsing-remitting Multiple Sclerosis
About this trial
This is an interventional treatment trial for Relapsing-remitting Multiple Sclerosis focused on measuring M2951, Relapsing Multiple Sclerosis, Bruton's Tyrosine Kinase inhibitor
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
Sites / Locations
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Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Experimental
Experimental
Experimental
Experimental
Active Comparator
Placebo Comparator
Placebo then Evobrutinib 25 mg QD
Evobrutinib 25 mg QD
Evobrutinib 75 mg QD
Evobrutinib 75 mg BID
Tecfidera
Placebo
Participants who received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1 received Evobrutinib 25 milligram (mg) orally, once daily (QD) in blinded extension (BE) period from week 25 to week 48.
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period.
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period.
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period.
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period.
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.