Efficacy and Safety of Losmapimod in Treating Participants With Facioscapulohumeral Muscular Dystrophy (FSHD) (REACH)
- Conditions
- Facioscapulohumeral Muscular Dystrophy (FSHD)
- Interventions
- Drug: Placebo oral tablet
- Registration Number
- NCT05397470
- Lead Sponsor
- Fulcrum Therapeutics
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 260
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part A: Placebo-controlled treatment period: Placebo Placebo oral tablet Participants will be randomized to receive placebo Part A: Placebo-controlled treatment period: Losmapimod Losmapimod Participants will be randomized to receive losmapimod. Part B: Open-label extension Losmapimod Participants will receive losmapimod, upon completion of all assessments for Part A.
- Primary Outcome Measures
Name Time Method Part B: Number of participants reporting Adverse events (AEs) 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 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.
Part B: Number of participants with clinically significant changes in clinical laboratory parameters, Electrocardiogram (ECG), vital signs and physical examinations Up to Week 192
- Secondary Outcome Measures
Name Time Method Part A: Change from Baseline in average shoulder abductor strength by hand-held quantitative dynamometry at Week 48 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.
Part A: Change from Baseline in Whole body (WB) longitudinal composite Muscle Fat Infiltration (MFI) of B muscles at Week 48 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).
Part A: Number of participants reporting Adverse events (AEs) Up to Week 48 Part A: Number of participants with clinically significant changes in clinical laboratory parameters, ECG, vital signs and physical examinations Up to Week 48 Part A: Change from Baseline in Quality of Life in Neurologic Disorders upper extremity (Neuro-QoL UE) Scale at Week 48 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.
Part A: Patient's Global Impression of Change (PGIC) at Week 48 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.
Trial Locations
- Locations (33)
University of California Irvine
🇺🇸Irvine, California, United States
University of California Los Angeles (UCLA)
🇺🇸Los Angeles, California, United States
Kennedy Krieger Institute
🇺🇸Baltimore, Maryland, United States
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
University of Massachusetts Memorial Medical Center
🇺🇸Worcester, Massachusetts, United States
Radboudumc
🇳🇱Nijmegen, Gelderland, Netherlands
University of Calgary
🇨🇦Calgary, Alberta, Canada
Hospital Universitari i Politecnic La Fe
🇪🇸Valencia, Spain
Universitätsklinikum Ulm
🇩🇪Ulm, Germany
Montreal Neurological Institute and Hospital
🇨🇦Montréal, Quebec, Canada
Newcastle upon Tyne NHS Foundation Trust
🇬🇧Newcastle upon Tyne, United Kingdom
Leiden University Medical Centre
🇳🇱Leiden, Southern Holland, Netherlands
University College of London Hospitals
🇬🇧London, United Kingdom
The Ottawa Hospital Research Institute
🇨🇦Ottawa, Ontario, Canada
Fondazione IRCCS Istituto Neurologico Carlo Besta
🇮🇹Milano, Italy
University Hospital Bonn
🇩🇪Bonn, Germany
LMU Klinikum Ludwig-Maximilians-Universität München
🇩🇪München, Germany
Institute de Myologie, Groupe Hospitalier Pitié-Salpêtrière
🇫🇷Paris, France
Hospital Universitario Donostia
🇪🇸San Sebastián, Guipuzkoa, Spain
University of Florida
🇺🇸Gainesville, Florida, United States
Ohio State University Medical Center
🇺🇸Columbus, Ohio, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Nice University Hospital - CHU Nice
🇫🇷Nice, Paca, France
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
Aarhus Universitetshospital
🇩🇰Aarhus, Denmark
Rigshospitalet
🇩🇰Copenhagen, Denmark
Fondazione Serena Onlus- Centro Clinico NEMO
🇮🇹Milano, Lombardia, Italy
University of Colorado Anschutz Medical Campus
🇺🇸Aurora, Colorado, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States