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

Overview

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

Full Title of Study: “A Randomized, Double-Blind, Placebo-Controlled Phase II Study of M2951 With a Parallel, Open-Label, Active Control Group (Tecfidera), in Patients With Relapsing Multiple Sclerosis to Evaluate Efficacy, Safety, Tolerability, Pharmacokinetics, and Biological Activity.”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Double (Investigator, Outcomes Assessor)
  • Study Primary Completion Date: January 24, 2018

Interventions

  • Drug: M2951
    • M2951 low dose will be administered for 48 weeks
  • Drug: M2951
    • M2951 mid dose will be administered for 48 weeks
  • Drug: M2951
    • M2951 high dose will be administered for 48 weeks
  • Drug: Placebo
    • Placebo will be administered for 24 weeks
  • Drug: Tecfidera
    • Tecfidera; 120 mg hard capsule BID for 7 days then 240 mg hard capsule BID for duration of treatment (47 weeks)
  • Drug: M2951
    • Following Placebo for 24 weeks, M2951 low dose will be administered for 24 weeks

Arms, Groups and Cohorts

  • Experimental: M2951 Low dose
  • Experimental: M2951 Mid dose
  • Experimental: M2951 High dose
  • Experimental: Placebo/M2951
  • Active Comparator: Tecfidera

Clinical Trial Outcome Measures

Primary Measures

  • Total Number of Gadolinium (Gd)-Enhancing T1 Lesions at Week 12
    • Time Frame: Week 12
  • Total Number of Gadolinium (Gd)-Enhancing T1 Lesions at Week 16
    • Time Frame: Week 16
  • Total Number of Gadolinium (Gd)-Enhancing T1 Lesions at Week 20
    • Time Frame: Week 20
  • Total Number of Gadolinium (Gd)-Enhancing T1 Lesions at Week 24
    • Time Frame: Week 24

Secondary Measures

  • Annualized Relapse Rate (ARR)
    • Time Frame: Week 24 and 48
    • A qualifying relapse is defined as new, worsening or recurrent neurological symptoms attributed to Multiple Sclerosis (MS) that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. This relapse must be accompanied by new clinical signs (that is changes in the neurological examination or an increase in Expanded Disability Status Scale score)
  • Proportion of Subjects who Remain Qualified Relapse-Free
    • Time Frame: Week 24 and 48
  • Change From Baseline in Expanded Disability Status Scale (EDSS) at Week 24 and Week 48
    • Time Frame: Baseline, Week 24 and 48
    • The EDSS is an ordinal clinical rating scale ranging from 0 (normal neurological examination) to 10 (death due to MS) in half-point increments and should be administered in person by a neurologist trained in its use. The EDSS score will be calculated after neurologic testing and examination of the following eight functional systems, areas of the central nervous system that control bodily functions: Pyramidal (ability to walk); Cerebellar (coordination); Brain stem (speech and swallowing); Sensory (touch and pain); Bowel and bladder functions; Visual; Mental; Other (includes any other neurological findings due to MS).
  • Number of Subjects With Adverse Events (AEs)
    • Time Frame: Up to Week 52
  • Number of Subjects With Abnormalities in Laboratory Safety Parameters, Vital Signs and Electrocardiograms (ECGs)
    • Time Frame: Up to Week 52
  • Absolute Concentrations of Immunoglobulin (Ig) Levels
    • Time Frame: Baseline (Day 1), Weeks 4, 16, 24 and 48
  • Absolute Numbers of B Cells
    • Time Frame: Baseline (Day 1), Weeks 4, 24, 48 and 52
  • Change From Baseline in Immunoglobulin (Ig) Levels
    • Time Frame: Baseline (Day 1), Weeks 4, 16, 24 and 48
  • Change From Baseline in B Cells
    • Time Frame: Baseline (Day 1), Weeks 4, 24, 48 and 52
  • Number of Gd+ T1 Lesions
    • Time Frame: Week 48
  • Total Number of new Gd+ T1 Lesions
    • Time Frame: Weeks 12, 16, 20, 24
  • Mean per-Scan Number of Gd+ T1 Lesions
    • Time Frame: Weeks 12, 16, 20, and 24
  • Total Number of new or Enlarging T2 Lesions
    • Time Frame: Weeks 12, 16, 20, 24
  • Change From Baseline in the Volume of Gd+ T1 Lesions at Week 24 and Week 48
    • Time Frame: Baseline, Week 24 and 48
  • Change From Baseline in the Volume of T2 Lesions at Week 24 and Week 48
    • Time Frame: Baseline, Week 24 and 48
  • Number of new Gd+ T1 Lesions
    • Time Frame: Week 48
  • Number of new or Enlarging T2 Lesions
    • Time Frame: Week 48

Participating in This Clinical Trial

Inclusion Criteria

  • Subjects with a diagnosis of relapsing multiple sclerosis (may include subjects 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 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 (subject must be able to understand the informed consent) indicating that the subject 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 subjects 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 subject: • 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®
  • Subjects 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
  • Subjects 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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 65 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • EMD Serono Research & Development Institute, Inc.
  • Collaborator
    • Merck KGaA, Darmstadt, Germany
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Medical Responsible, Study Director, EMD Serono Inc., a business of Merck KGaA, Darmstadt, Germany

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