A Study of Efficacy and Safety of M2951 in Participants With Relapsing Multiple Sclerosis
NCT ID: NCT02975349
Last Updated: 2025-05-14
Study Results
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View full resultsBasic Information
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TERMINATED
PHASE2
267 participants
INTERVENTIONAL
2017-03-07
2024-04-02
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
DOUBLE
Study Groups
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Placebo then Evobrutinib 25 mg QD (Period 2)
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.
Evobrutinib
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Evobrutinib
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Evobrutinib
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Evobrutinib
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Tecfidera (Period 1, 2 and 3)
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 received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Tecfidera
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 received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Placebo
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
Placebo
Placebo were administered for 24 weeks in active treatment period.
Placebo + Evobrutinib 25 mg QD (Period 3)
Participants who received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1 received Evobrutinib 25 mg orally, QD from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Evobrutinib
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Interventions
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Evobrutinib
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Evobrutinib
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Evobrutinib
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Placebo
Placebo were administered for 24 weeks in active treatment period.
Tecfidera
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 received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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
18 Years
65 Years
ALL
No
Sponsors
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Merck KGaA, Darmstadt, Germany
INDUSTRY
EMD Serono Research & Development Institute, Inc.
INDUSTRY
Responsible Party
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Principal Investigators
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Medical Responsible
Role: STUDY_DIRECTOR
EMD Serono Inc., a business of Merck KGaA, Darmstadt, Germany
Locations
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Research Site
Blagoevgrad, , Bulgaria
Research Site
Dupnitsa, , Bulgaria
Research Site 1
Pleven, , Bulgaria
Research Site 2
Pleven, , Bulgaria
Research Site
Rousse, , Bulgaria
Research Site
Sofia, , Bulgaria
Research Site
Sofia, , Bulgaria
Research Site
Sofia, , Bulgaria
Research Site
Sofia, , Bulgaria
Research Site
Sofia, , Bulgaria
Research Site
Sofia, , Bulgaria
Research Site
Sofia, , Bulgaria
Research Site
Brno, , Czechia
Research Site
Hradec Králové, , Czechia
Research Site
Hradec Králové, , Czechia
Research Site
Jihlava, , Czechia
Research Site
Prague, , Czechia
Research Site
Teplice, , Czechia
Research Site
Bydgoszcz, , Poland
Research Site
Katowice, , Poland
Research Site
Katowice, , Poland
Research Site
Lodz, , Poland
Research Site
Lublin, , Poland
Research Site
Oświęcim, , Poland
Research Site
Plewiska, , Poland
Research Site
Poznan, , Poland
Research Site
Rzeszów, , Poland
Research Site
Warsaw, , Poland
Research Site
Kazan', , Russia
Research Site
Krasnoyarsk, , Russia
Research Site
Krasnoyarsk, , Russia
Research Site
Moscow, , Russia
Research Site
Novosibirsk, , Russia
Research Site
Perm, , Russia
Research Site
Saransk, , Russia
Research Site
Belgrade, , Serbia
Research Site
Kragujevac, , Serbia
Research Site
Niš, , Serbia
Research Site
Užice, , Serbia
Research Site
Banská Bystrica, , Slovakia
Research Site
Bratislava, , Slovakia
Research Site
Dubnica nad Váhom, , Slovakia
Research Site
A Coruña, , Spain
Research Site
Barcelona, , Spain
Research Site
Barcelona, , Spain
Research Site
Chernivtsi, , Ukraine
Research Site
Ivano-Frankivsk, , Ukraine
Research Site
Kharkiv, , Ukraine
Research Site
Kharkiv, , Ukraine
Research Site
Kharkiv, , Ukraine
Research Site
Kyiv, , Ukraine
Research Site
Kyiv, , Ukraine
Research Site
Lviv, , Ukraine
Research Site
Poltava, , Ukraine
Research Site
Zaporizhzhia, , Ukraine
Research Site
Zaporizhzhia, , Ukraine
Countries
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References
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Montalban X, Arnold DL, Weber MS, Staikov I, Piasecka-Stryczynska K, Willmer J, Martin EC, Dangond F, Syed S, Wolinsky JS; Evobrutinib Phase 2 Study Group. Placebo-Controlled Trial of an Oral BTK Inhibitor in Multiple Sclerosis. N Engl J Med. 2019 Jun 20;380(25):2406-2417. doi: 10.1056/NEJMoa1901981. Epub 2019 May 10.
Arnold DL, Elliott C, Martin EC, Hyvert Y, Tomic D, Montalban X. Effect of Evobrutinib on Slowly Expanding Lesion Volume in Relapsing Multiple Sclerosis: A Post Hoc Analysis of a Phase 2 Trial. Neurology. 2024 Mar 12;102(5):e208058. doi: 10.1212/WNL.0000000000208058. Epub 2024 Feb 9.
Papasouliotis O, Mitchell D, Girard P, Dangond F, Dyroff M. Determination of a clinically effective evobrutinib dose: Exposure-response analyses of a phase II relapsing multiple sclerosis study. Clin Transl Sci. 2022 Dec;15(12):2888-2898. doi: 10.1111/cts.13407. Epub 2022 Sep 30.
Montalban X, Wallace D, Genovese MC, Tomic D, Parsons-Rich D, Le Bolay C, Kao AH, Guehring H. Characterisation of the safety profile of evobrutinib in over 1000 patients from phase II clinical trials in multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus: an integrated safety analysis. J Neurol Neurosurg Psychiatry. 2023 Jan;94(1):1-9. doi: 10.1136/jnnp-2022-328799. Epub 2022 Nov 23.
Bar-Or A, Cross AH, Cunningham AL, Hyvert Y, Seitzinger A, Guhring H, Drouin EE, Alexandri N, Tomic D, Montalban X. Antibody response to SARS-CoV-2 vaccines in patients with relapsing multiple sclerosis treated with evobrutinib: A Bruton's tyrosine kinase inhibitor. Mult Scler. 2023 Oct;29(11-12):1471-1481. doi: 10.1177/13524585231192460. Epub 2023 Aug 25.
Montalban X, Wallace D, Genovese MC, Tomic D, Parsons-Rich D, Bolay CL, Kao AH, Guehring H. A plain language summary of what clinical studies can tell us about the safety of evobrutinib - a potential treatment for multiple sclerosis. Neurodegener Dis Manag. 2023 Aug;13(4):207-213. doi: 10.2217/nmt-2023-0003. Epub 2023 Jun 22.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Related Links
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Trial Awareness and Transparency website
Medical Information Location Map - Med Info Contacts
Other Identifiers
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2016-001448-21
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
MS200527-0086
Identifier Type: -
Identifier Source: org_study_id
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