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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Facioscapulohumeral Muscular Dystrophy (FSHD)

Intervention / Treatment
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* Drug: Losmapimod
* Drug: Placebo oral tablet


Participation Criteria
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Eligibility Criteria
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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. Orally administered cytochrome P450 (CYP3A4) substrates and multidrug and toxin extrusion (MATE) and organic anion transporter (OAT)3 substrates are not permitted as concomitant therapy during the administration of losmapimod (defined as Baseline visit through end of study treatment). 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Change from Baseline in total Relative surface area (RSA) Quadrants 1 to 5 (Q1-Q5) with 500 grams (g) wrist weight in dominant arm as assessed by Reachable workspace (RWS) 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 | 
| Part B: Number of participants reporting Adverse events (AEs) |  | Up to Week 192 | 
| 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

| 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 | 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 | 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 | 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) |  | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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REACH, Facioscapulohumeral muscular dystrophy (FSHD), Facioscapulohumeral muscular dystrophy type 1 (FSHD 1), Facioscapulohumeral muscular dystrophy type 2 (FSHD 2), Muscular Dystrophies, Muscular Dystrophy, Facioscapulohumeral Muscular Disorders, Musculoskeletal Diseases, Neuromuscular Diseases