A Study of Efficacy and Safety of M2951 in Participants With Relapsing Multiple Sclerosis

Merck KGaA (EMD Serono)

Status and phase: Terminated; Phase 2

Conditions: Relapsing-remitting Multiple Sclerosis

Treatments: Drug: Evobrutinib; Drug: Placebo; Drug: Tecfidera

Study type: Interventional

Funder types: Industry

Identifiers

NCT02975349

2016-001448-21 (EudraCT Number)

MS200527-0086

Details and patient eligibility

About

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.

Enrollment: 267 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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267 participants in 6 patient groups, including a placebo group

Placebo then Evobrutinib 25 mg QD

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: Evobrutinib

Evobrutinib 25 mg QD

Experimental group

Description:

Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period.

Treatment:

Drug: Evobrutinib

Evobrutinib 75 mg QD

Experimental group

Description:

Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period.

Treatment:

Drug: Evobrutinib

Evobrutinib 75 mg BID

Experimental group

Description:

Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period.

Treatment:

Drug: Evobrutinib

Tecfidera

Active Comparator group

Description:

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.

Treatment:

Drug: Tecfidera

Placebo

Placebo Comparator group

Description:

Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.

Treatment:

Drug: Placebo