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Study of Evobrutinib in Participants With RMS (evolutionRMS 1)

Sponsor
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04338022
Collaborator
EMD Serono Research & Development Institute, Inc. (Industry)
898
Enrollment
273
Locations
2
Arms
72.4
Anticipated Duration (Months)
3.3
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study is to evaluate the efficacy and safety of evobrutinib administered orally twice daily versus Teriflunomide (Aubagio®), administered orally once daily in participants with Relapsing Multiple Sclerosis (RMS).

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Anticipated Enrollment :
898 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase III, Multicenter, Randomized, Parallel Group, Double Blind, Double Dummy, Active Controlled Study of Evobrutinib Compared With Teriflunomide, in Participants With Relapsing Multiple Sclerosis to Evaluate Efficacy and Safety (evolutionRMS 1)
Actual Study Start Date :
Jun 12, 2020
Anticipated Primary Completion Date :
Sep 4, 2023
Anticipated Study Completion Date :
Jun 26, 2026

Arms and Interventions

Arm Intervention/Treatment
Experimental: Evobrutinib + Teriflunomide matched Placebo: DB Period

Drug: Evobrutinib
Evobrutinib twice daily (BID) in double-blind (DB) treatment period.
Other Names:
  • M2951

    • Drug: Placebo (match to Teriflunomide)
    Placebo match to Teriflunomide once daily in double-blind treatment period.
    Active Comparator: Teriflunomide + Evobrutinib matched Placebo: DB Period

    Drug: Teriflunomide
    Teriflunomide once daily in double-blind treatment period.

    Drug: Placebo (match to Evobrutinib)
    Placebo match to Evobrutinib BID in double-blind treatment period.

    Outcome Measures

    Primary Outcome Measures

    1. Annualized Relapse Rate (ARR) [Up to 156 weeks]

      The annualized relapse rates over 96 weeks will be calculated based on qualified relapses. Qualifying relapse is defined as occurrence of new or worsening neurological symptoms attributable to Multiple Sclerosis (MS) (for more than 24 hours, no fever, infection, injury, adverse events, and preceded by a stable or improving neurological state for greater than or equal to (=>) 30 days).

    Secondary Outcome Measures

    1. Time to First Occurrence of 12-Week Confirmed Expanded Disability Status Scale (EDSS) Progression [Up to 156 weeks]

    2. Time to First Occurrence of 24-Week Confirmed Expanded Disability Status Scale (EDSS) Progression [Up to 156 weeks]

    3. Time to First Occurrence of 24-Weeks Confirmed Expanded Disability Status Scale (EDSS) Improvement [Up to 156 weeks]

    4. Change from Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) MS Physical Function (PF) Short Form Score [Baseline up to 96 weeks]

    5. Change from Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) MS Fatigue Short Form Score [Baseline up to 96 weeks]

    6. Total Number of Gadolinium-Enhancing (Gd+) T1 Lesions Assessed by all Available Magnetic Resonance Imaging (MRI) Scans [Up to Week 156]

    7. Total Number of New or Enlarging T2 Lesions Assessed on the Last Available Magnetic Resonance Imaging (MRI) Scans [Up to Week 156]

    8. Neurofilament light chain (NfL) Serum Concentration [At Week 12]

    9. Number of Participants With Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) [Baseline up to 156 weeks]

      An AE is any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal relationship with this treatment.

    10. Number of Participants With Clinically Significant Change From Baseline in Vital Signs, Laboratory Parameters and Electrocardiogram Findings [Baseline up to 156 weeks]

      Number of participants with clinically significant change from baseline in vital signs, laboratory parameters and electrocardiogram findings will be reported.

    11. Absolute Concentrations of Immunoglobulin (Ig) Levels [Baseline up to 156 weeks]

    12. Change From Baseline in Immunoglobulin (Ig) Levels [Baseline up to 156 weeks]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 55 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Participants are diagnosed with RMS (relapsing-remitting multiple sclerosis [RRMS] or secondary progressive multiple sclerosis [SPMS] with relapses) in accordance with 2017 Revised McDonald criteria (Thompson 2018)

    • Participants with 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-enhancing (Gd+) T1 lesion within 6 months prior to randomization

    • Participants have Expanded Disability Status Scale (EDSS) score of 0 to 5.5 at Screening and Baseline (Day 1). Participants with an EDSS score <= 2 at Screening and Baseline (Day 1) are only eligible for participation if their disease duration (time since onset of symptoms) is no more than 10 years

    • Participants are neurologically stable for >= 30 days prior to both screening and baseline (Day 1)

    • Female participants must be neither pregnant nor breast-feeding or must lack child-bearing potential (as defined by either: post-menopausal or surgically sterile), or use an effective method of contraception for the duration of the study and at least 2 years after study intervention due to the long elimination period for teriflunomide of 2 years, unless the participant undergoes an accelerated elimination procedure

    • Male participants must refrain from donating sperm and/or abstain from intercourse with women of child-bearing potential or use an effective method of contraception for the duration of the study and at least 2 years after study intervention due to the long elimination period for teriflunomide of 2 years, unless the participant undergoes an accelerated elimination procedure

    • Participants have given written informed consent prior to any study-related procedure

    • Other protocol defined inclusion criteria could apply.

    Exclusion Criteria:
    • Participants diagnosed with Progressive MS, in accordance with the 2017 Revised McDonald criteria as follows: a). Participants with Primary Progressive MS. b).

    Participants with secondary progressive MS without evidence of relapse

    • Disease duration more than (>) 10 years in participants with an EDSS =< 2.0 at screening and Baseline (Day 1)

    • Immunologic disorder other than MS, or any other condition requiring oral, intravenous (IV) , intramuscular, or intra-articular corticosteroid therapy, with the exception of well-controlled Type 2 diabetes mellitus or well controlled thyroid disease

    • Other protocol defined exclusion criteria could apply.

    Contacts and Locations

    Locations

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    Sponsors and Collaborators

    • Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
    • EMD Serono Research & Development Institute, Inc.

    Investigators

    • Study Director: Medical Responsible, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
    ClinicalTrials.gov Identifier:
    NCT04338022
    Other Study ID Numbers:
    • MS200527_0080
    • 2019-004972-20
    First Posted:
    Apr 8, 2020
    Last Update Posted:
    Jul 1, 2022
    Last Verified:
    Jun 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
    Evobrutinib
    Teriflunomide
    Aubagio®
    Relapsing Multiple Sclerosis
    Additional relevant MeSH terms:
    Multiple Sclerosis
    Sclerosis
    Teriflunomide

    Study Results

    No Results Posted as of Jul 1, 2022