Relapsing Multiple Sclerosis MedDRA version: 19.0 Level: PT Classification code 10028245 Term: Multiple sclerosis System Organ Class: 10029205 - Nervous system disorders MedDRA version: 19.0 Level: PT Classification code 10048393 Term: Multiple sclerosis relapse System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: M2951
Product Code: M2951
Pharmaceutical Form: Tablet
INN or Proposed INN: M2951
Current Sponsor code: M2951
Other descriptive name: M2951
Concentration unit: mg milligram(s)
Concentrati
Sponsors
Merck KGaA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects with a diagnosis of relapsing multiple sclerosis (may include subjects with Secondary PMS [SPMS] with superimposed relapses provided they meet the other criteria) in accordance with revised McDonald criteria for MS and Lublin and Reingold 2. Male or female aged 18 to 65 years 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 would make the patient eligible. 4. Expanded Disability Status Scale score of 0 to 6 at Baseline 5. Women of childbearing potential must use a supplementary barrier method together with a highly effective method of contraception for 4 weeks prior to randomization, throughout the trial, and for 90 days after the last dose of IMP. Male subjects and their female partners must also use the above. 6. 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 248 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
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, daclizumab • 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 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 laborator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate the efficacy and dose-response of M2951 on the number of gadolinium-positive (Gd+) T1 MRI lesions versus placebo after 24 weeks of treatment.;Secondary Objective: The key secondary objectives are as follows: - To evaluate the efficacy and dose-response of M2951 on clinical endpoints over 24 weeks versus placebo - To evaluate the safety of M2951 Additional secondary objectives are as follows: - To evaluate the efficacy of M2951 on additional MRI parameters over 24 weeks versus placebo - To evaluate the efficacy of M2951 on clinical and MRI endpoints from Weeks 24 to 48 - To evaluate the efficacy of Tecfidera on clinical and MRI endpoints over 24 weeks - To evaluate the efficacy of Tecfidera on clinical and MRI endpoints from Weeks 24 to 48 - To evaluate the safety of Tecfidera;Primary end point(s): Total number of gadolinium-enhancing T1 lesions at Weeks 12, 16, 20, and 24;Timepoint(s) of evaluation of this end point: Weeks 12, 16, 20 and 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key secondary endpoints to evaluate the efficacy and safety of M2951 compared to placebo: • Annualized relapse rate (ARR), based on protocol-defined qualified relapses, at Week 24 • Proportion of subjects who remain qualified relapse-free at Week 24 • Change from Baseline in Expanded Disability Status Scale (EDSS) at Week 24 • Safety as assessed by the nature, severity, and incidence of adverse events (AEs); vital signs; electrocardiograms (ECGs); absolute concentrations and change from Baseline in immunoglobulin (Ig) levels; absolute numbers and change from Baseline in B cells; and clinical laboratory safety parameters (duration of placebo treatment group is limited to 24 weeks).;Timepoint(s) of evaluation of this end point: Week 24 for the key secondary endpoints | — |
Countries
Bulgaria, Croatia, Czech Republic, Poland, Russian Federation, Serbia, Slovakia, Spain, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactCommunication Center Merck KGaA
Merck KGaA
Outcome results
None listed