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

Phase 3TerminatedNCT05397470

Fulcrum Therapeutics260 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

260

Conditions

Facioscapulohumeral Muscular Dystrophy (FSHD)

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Key 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. Key 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.

Locations (33)

University of California Irvine

Irvine, California, United States

University of California Los Angeles (UCLA)

Los Angeles, California, United States

University of Colorado Anschutz Medical Campus

Aurora, Colorado, United States

University of Florida

Gainesville, Florida, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Outcomes

Primary Outcomes

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

Participants are instructed to complete a simple set of standardized movements of each arm centered around the shoulder joint. These arm movements are captured and quantitated with the use of a video camera. 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 is the last non-missing evaluation prior to first dose of study drug. Change from Baseline was calculated as the post-treatment value minus the value at Baseline.

Time frame: Baseline (Day 1) and at Week 48

Part B: Number of Participants Reporting Serious Treatment Emergent Adverse Events (Serious TEAEs) and Non-serious TEAEs > 5%

Treatment-emergent adverse event is an AE that begins on or after the first dose of study drug and on or before the stop of study drug + 35 days or begins before the first dose of study drug and worsens on or after the first dose of study drug and on or before the stop of study drug + 35 days. A SAE is defined as an AE that results in any of the following outcomes: death; life-threatening adverse event; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; congenital anomaly/birth defect.