Efficacy and Safety of Losmapimod in Treating Participants With Facioscapulohumeral Muscular Dystrophy (FSHD) (REACH)

March 7, 2024 updated by: Fulcrum Therapeutics

A Phase 3 Global, Randomized, Double-Blind, Placebo-Controlled, 48-Week, Parallel-Group Study of the Efficacy and Safety of Losmapimod in Treating Patients With Facioscapulohumeral Muscular Dystrophy (FSHD) (REACH)

This is a study to evaluate the safety and efficacy of losmapimod in treating participants with Facioscapulohumeral Muscular Dystrophy (FSHD). Participants diagnosed with Facioscapulohumeral muscular dystrophy type 1 (FSHD1) or Facioscapulohumeral muscular dystrophy type 2 (FSHD2) will participate in Part A (Placebo-controlled treatment period) and will be randomized in a 1:1 ratio to receive losmapimod 15 milligrams (mg) or placebo orally twice daily (BID). Upon completion of Part A, participants will have the option to rollover into Part B (open-label extension) to evaluate the long-term safety, tolerability, and efficacy of losmapimod and will receive losmapimod 15 mg orally BID.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Patients diagnosed with FSHD 1 and FSHD 2 will participate in this study for approximately 53 weeks. This will include a 4-week screening period, a 48-week, placebo-controlled treatment period and a 7-day safety follow-up period. Patients will be randomized to receive 15 mg of losmapimod or placebo twice daily by mouth for 48 weeks.

Study Type

Interventional

Enrollment (Actual)

260

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 4Z6
        • University of Calgary
    • Ontario
      • Ottawa, Ontario, Canada, K1Y 4E9
        • The Ottawa Hospital Research Institute
    • Quebec
      • Montréal, Quebec, Canada, H3A 2B4
        • Montreal Neurological Institute and Hospital
  • Denmark
      • Aarhus, Denmark, 8200
        • Aarhus Universitetshospital
      • Copenhagen, Denmark, 2100
        • Rigshospitalet
  • France
      • Paris, France, 75013
        • Institute de Myologie, Groupe Hospitalier Pitié-Salpêtrière
    • Paca
      • Nice, Paca, France, 06001
        • Nice University Hospital - CHU Nice
  • Germany
      • Bonn, Germany, 53127
        • University Hospital Bonn
      • München, Germany, 80336
        • LMU Klinikum Ludwig-Maximilians-Universität München
      • Ulm, Germany, 89081
        • Universitätsklinikum Ulm
  • Italy
      • Milano, Italy, 20133
        • Fondazione IRCCS Istituto Neurologico Carlo Besta
    • Lombardia
      • Milano, Lombardia, Italy, 20162
        • Fondazione Serena Onlus- Centro Clinico NEMO
  • Netherlands
    • Gelderland
      • Nijmegen, Gelderland, Netherlands, 9101
        • Radboudumc
    • Southern Holland
      • Leiden, Southern Holland, Netherlands, 2333 ZA
        • Leiden University Medical Centre
  • Spain
      • Barcelona, Spain, 08035
        • Hospital Universitario Vall d'Hebron
      • Valencia, Spain, 46026
        • Hospital Universitari i Politecnic La Fe
    • Guipuzkoa
      • San Sebastián, Guipuzkoa, Spain, 20014
        • Hospital Universitario Donostia
  • United Kingdom
      • London, United Kingdom, WC1N 3BG
        • University College of London Hospitals
      • Newcastle upon Tyne, United Kingdom, NE1 3BZ
        • Newcastle upon Tyne NHS Foundation Trust
  • United States
    • California
      • Irvine, California, United States, 92868
        • University of California Irvine
      • Los Angeles, California, United States, 90095
        • University of California Los Angeles (UCLA)
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Anschutz Medical Campus
    • Florida
      • Gainesville, Florida, United States, 32610
        • University of Florida
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Medical Center
    • Maryland
      • Baltimore, Maryland, United States, 21205
        • Kennedy Krieger Institute
    • Massachusetts
      • Worcester, Massachusetts, United States, 01655
        • University of Massachusetts Memorial Medical Center
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • New York
      • Rochester, New York, United States, 14642
        • University of Rochester Medical Center
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Ohio State University Medical Center
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • University of Utah
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Virginia Commonwealth University
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Participants must be between 18 and 65 years of age, inclusive.
  • Genetically confirmed diagnosis of FSHD 1 or FSHD 2.
  • Clinical severity score of 2 to 4 (Ricci Score; Range 0-5), at screening. Participants who are wheelchair-dependent or dependent on walker or wheelchair for activities are not permitted to enroll in the study.
  • Screening total RSA (Q1-Q4) without weight in the dominant UE assessed by RWS ≥ 0.2 and ≤ 0.7.
  • No contraindications to MRI.

Exclusion Criteria:

  • Previously diagnosed cancer that has not been in complete remission for at least 5 years. Localized carcinomas of the skin and carcinoma in situ of the cervix that have been resected or ablated for cure are not exclusionary.
  • Participants who are on drug(s) or supplements that may affect muscle function, as determined by the Investigator: participants must be on a stable dose of that drug(s) or supplement for at least 3 months prior to the first dose of study drug and remain on that stable dose for the duration of the study.
  • Known active opportunistic or life-threatening infections including Human Immunodeficiency virus (HIV) and hepatitis B or C.
  • Known active or inactive tuberculosis infection.
  • Acute or chronic history of liver disease.
  • Known severe renal impairment.
  • History of cardiac dysrhythmias requiring anti-arrhythmia treatment(s); or history or evidence of abnormal ECGs.
  • Use of another investigational product within 30 days or 5 half-lives (whichever is longer) or currently participating in a study of an investigational device.
  • Current or anticipated participation in a natural history study. Previous participation is allowed but participants cannot continue after enrollment in Study 1821-FSH-301.
  • Known hypersensitivity to losmapimod or any of its excipients.
  • Previous participation in a Fulcrum-sponsored FSHD losmapimod study (FIS-001-2019 or FIS-002-2019).

Note that all other inclusion and exclusion criteria are listed in the protocol and only key are presented.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part A: Placebo-controlled treatment period: Losmapimod
Participants will be randomized to receive losmapimod.
Drug: Losmapimod
Losmapimod 15 mg will be administered BID by mouth along with food.
Placebo Comparator: Part A: Placebo-controlled treatment period: Placebo
Participants will be randomized to receive placebo
Drug: Placebo oral tablet
Placebo will be administered BID by mouth along with food.
Experimental: Part B: Open-label extension
Participants will receive losmapimod, upon completion of all assessments for Part A.
Drug: Losmapimod
Losmapimod 15 mg will be administered BID by mouth along with food.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part B: Number of participants reporting Adverse events (AEs)
Time Frame: Up to Week 192
Up to Week 192
Part B: Number of participants with clinically significant changes in clinical laboratory parameters, Electrocardiogram (ECG), vital signs and physical examinations
Time Frame: Up to Week 192
Up to Week 192
Part A: Change from Baseline in total Relative surface area (RSA) Quadrants 1 to 5 (Q1-Q5) with 500 grams (g) wrist weight averaged over both arms as assessed by Reachable workspace (RWS) at Week 48
Time Frame: Baseline and at Week 48
The RWS is a clinical outcome measure that measures the relative surface area that a participant may reach with an outstretched arm. Responses are rated on a scale of 0 (no reachable workspace) to 1.25 (maximal reachable workspace). Higher scores indicate better outcomes.
Baseline and at Week 48

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part A: Change from Baseline in Quality of Life in Neurologic Disorders upper extremity (Neuro-QoL UE) Scale at Week 48
Time Frame: Baseline and at Week 48
The Neuro-QoL UE will be used to measure change(s) from Baseline in the participants upper extremity function. The Neuro-QoL UE is a questionnaire that measures the participants self-reported upper extremity function including activities of daily living (ADLs) involving digital, manual, and reach-related function and self-care. Responses are rated from 1 (unable to do) to 5 (without any difficulty). Lower scores indicate worse symptoms.
Baseline and at Week 48
Part A: Patient's Global Impression of Change (PGIC) at Week 48
Time Frame: At Week 48
The Patient Global Impression of Change (PGIC) is a standard and validated participant-report outcome that measures the participant's self-reported change in health status compared to the start of the study. The PGIC uses a single question and 7-point patient self-reporting scale of overall improvement during treatment ranging from 1 (very much improved) to 7 (very much worse). Higher scores indicate worse symptoms.
At Week 48
Part A: Change from Baseline in Whole body (WB) longitudinal composite Muscle Fat Infiltration (MFI) of B muscles at Week 48
Time Frame: Baseline and at Week 48
Change from Baseline in skeletal muscle tissue replacement by fat will be measured by WB musculoskeletal (MSK) magnetic resonance imaging (MRI).
Baseline and at Week 48
Part A: Number of participants reporting Adverse events (AEs)
Time Frame: Up to Week 48
Up to Week 48
Part A: Number of participants with clinically significant changes in clinical laboratory parameters, ECG, vital signs and physical examinations
Time Frame: Up to Week 48
Up to Week 48
Part A: Change from Baseline in average shoulder abductor strength by hand-held quantitative dynamometry at Week 48
Time Frame: Baseline and at Week 48
Quantitative: isometric dynamometry (hand-held dynamometer) will be used to assess the skeletal muscle strength. Isometric dynamometry measures the static muscle strength without any movement.
Baseline and at Week 48

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fulcrum Therapeutics

Investigators

  • Study Director: Marie-Helene Jouvin, MD, Fulcrum Therapeutics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 16, 2022

Primary Completion (Estimated)

October 1, 2024

Study Completion (Estimated)

January 1, 2026

Study Registration Dates

First Submitted

May 4, 2022

First Submitted That Met QC Criteria

May 25, 2022

First Posted (Actual)

May 31, 2022

Study Record Updates

Last Update Posted (Actual)

March 12, 2024

Last Update Submitted That Met QC Criteria

March 7, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1821-FSH-301

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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