Study of Evobrutinib in Participants With RMS

NCT04032171 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: MS200527_00742018-004700-19
• Study Type: interventional
• Target: 1
• Locations: 2 countries
• Sites: 2

Brief Summary

The study was to evaluate the efficacy and safety of evobrutinib administered orally twice daily versus Interferon-beta-1a (Avonex®), once a week intramuscularly in participants with Relapsing Multiple Sclerosis (RMS).

Conditions

Relapsing-remitting Multiple Sclerosis

Keywords

Evobrutinib; Avonex®; Interferon-beta 1a; Relapsing Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• Annualized Relapse Rate (ARR)

  The annualized relapse rate at 96 weeks was to be calculated based on qualified relapses. A qualifying relapse is the occurrence of new or worsening neurological symptoms attributable to MS. The relapse should be accompanied by an increase of 0.5 points or more on Expanded Disability Status Scale (EDSS), or 2 points increase on one of the Functional System Scores (FSS), or 1 point increase on at least two of the FSS. The increase in FSS scores must be related to the neurological symptoms which were reported as new or worsening.

  At Week 96

Secondary Outcomes (23)

• Time to First Occurrence of 12-Week Confirmed Expanded Disability Status Scale (EDSS) Progression

  Baseline up to 96 weeks

• Time to First Occurrence of 24-Week Confirmed Expanded Disability Status Scale (EDSS) Progression

  Baseline up to 96 weeks

• Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) Short Form Score at Week 96

  Baseline, Week 96

• Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form Score at Week 96

  Baseline, Week 96

• Total Number of Gadolinium-Enhancing (Gd+) Time Constant 1 (T1) Lesions Assessed by Magnetic Resonance Imaging (MRI) Scans at Week 24, 48, and 96

  At Week 24, 48 and 96

Study Arms (2)

Evobrutinib + Avonex® matched Placebo

EXPERIMENTAL

Participants received active evobrutinib twice daily (BID) along with concomitant intramuscular (IM) injection of placebo matched to Avonex® once a week. Treatment period was planned to be of 96 weeks.

Drug: Evobrutinib; Drug: Avonex® matched Placebo

Avonex® + Evobrutinib matched Placebo

ACTIVE COMPARATOR

Participants received IM injection of active Avonex® once a week along with concomitant placebo matched to evobrutinib BID. Treatment period was planned to be of 96 weeks.

Drug: Avonex®; Drug: Evobrutinib matched Placebo

Interventions

Evobrutinib DRUG

Participants received evobrutinib twice daily (BID).

Also known as: M2951

Evobrutinib + Avonex® matched Placebo

Avonex® DRUG

Participants received avonex® IM injection once a week.

Avonex® + Evobrutinib matched Placebo

Avonex® matched Placebo DRUG

Participants received IM injection of placebo matched to avonex® once a week.

Evobrutinib + Avonex® matched Placebo

Evobrutinib matched Placebo DRUG

Participants received placebo matched to evobrutinib twice a day.

Avonex® + Evobrutinib matched Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Participants 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 EDSS score of 0 to 5.5 at Baseline. Participants with an EDSS score \<= 2 at screening 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.
• Female participants must be neither pregnant nor breast-feeding and 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.
• Participants have given written informed consent prior to any study-related procedure.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• EMD Serono Research & Development Institute, Inc.: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (2)

Please Contact U.S. Medical Information

Rockland, Massachusetts, 02370, United States

Location

Please Contact the Communication Center

Darmstadt, 64293, Germany

Location

Related Links

• Trial Awareness and Transparency website
• US Medical Information website, Medical Resources

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting

Interventions

evobrutinib; Interferon beta-1a

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Interferon-beta; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Limitations and Caveats

Following analysis of open label extension (OLE) data from RMS phase 2 study (MS200527- 0086), it was determined that a change in active comparator warranted in phase 3 RMS comprised of trial MS200527-0074. Consequently, this trial terminated early, therefore, it was decided as per Statistical Analysis Plan not to report the efficacy data for this study.

Results Point of Contact

• Title: Communication Center
• Organization: Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany

service@emdgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2019
• First Posted: July 25, 2019
• Study Start: September 10, 2019
• Primary Completion: May 20, 2020
• Study Completion: May 20, 2020
• Last Updated: August 5, 2021
• Results First Posted: August 5, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will share

Locations

US (1); DE (1)