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

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ClinicalTrials.gov Identifier: NCT02975349

Recruitment Status : Active, not recruiting

First Posted : November 29, 2016

Last Update Posted : January 17, 2019

Sponsor:

Collaborator:

Merck KGaA, Darmstadt, Germany

Information provided by (Responsible Party):

EMD Serono ( EMD Serono Research & Development Institute, Inc. )

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Relapsing-remitting Multiple Sclerosis	Drug: M2951 Drug: Placebo Drug: Tecfidera	Phase 2

Study Design


Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	267 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	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.
Actual Study Start Date :	March 7, 2017
Actual Primary Completion Date :	January 24, 2018
Estimated Study Completion Date :	August 12, 2020

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Multiple sclerosis

MedlinePlus related topics: Multiple Sclerosis

Drug Information available for: Dimethyl fumarate

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: M2951 Low dose	Drug: M2951 M2951 low dose will be administered for 48 weeks Other Name: Evobrutinib
Experimental: M2951 Mid dose	Drug: M2951 M2951 mid dose will be administered for 48 weeks Other Name: Evobrutinib
Experimental: M2951 High dose	Drug: M2951 M2951 high dose will be administered for 48 weeks Other Name: Evobrutinib
Experimental: Placebo/M2951	Drug: Placebo Placebo will be administered for 24 weeks Drug: M2951 Following Placebo for 24 weeks, M2951 low dose will be administered for 24 weeks Other Name: Evobrutinib
Active Comparator: Tecfidera	Drug: Tecfidera Tecfidera; 120 mg hard capsule BID for 7 days then 240 mg hard capsule BID for duration of treatment (47 weeks)

Outcome Measures

Primary Outcome 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 Outcome 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 ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 65 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02975349

Show 56 Study Locations

Sponsors and Collaborators

EMD Serono Research & Development Institute, Inc.

Merck KGaA, Darmstadt, Germany

Investigators


Study Director:	Medical Responsible	EMD Serono Inc., a business of Merck KGaA, Darmstadt, Germany

More Information


Responsible Party:	EMD Serono Research & Development Institute, Inc.
ClinicalTrials.gov Identifier:	NCT02975349 History of Changes
Other Study ID Numbers:	MS200527-0086 2016-001448-21 ( EudraCT Number )
First Posted:	November 29, 2016 Key Record Dates
Last Update Posted:	January 17, 2019
Last Verified:	January 2019


Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by EMD Serono ( EMD Serono Research & Development Institute, Inc. ):


M2951 Relapsing Multiple Sclerosis Bruton's Tyrosine Kinase inhibitor

Additional relevant MeSH terms:


Sclerosis Multiple Sclerosis Multiple Sclerosis, Relapsing-Remitting Pathologic Processes Demyelinating Autoimmune Diseases, CNS Autoimmune Diseases of the Nervous System Nervous System Diseases Demyelinating Diseases	Autoimmune Diseases Immune System Diseases Dimethyl Fumarate Dermatologic Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs

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