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

NCT05397470 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: 1821-FSH-301
• Study Type: interventional
• Target: 260
• Locations: 9 countries
• Sites: 33

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.

Conditions

Facioscapulohumeral Muscular Dystrophy (FSHD)

Keywords

Facioscapulohumeral muscular dystrophy (FSHD); Facioscapulohumeral muscular dystrophy type 1 (FSHD 1); Facioscapulohumeral muscular dystrophy type 2 (FSHD 2); Muscular Dystrophy; Facioscapulohumeral Muscular Disorders; Musculoskeletal Diseases; Neuromuscular Diseases; REACH

Outcome Measures

Primary Outcomes (8)

• 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.

  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.

  Week 48 to Week 127

• Part B: Number of Participants With Clinically Significant Changes in Chemistry Parameters

  Blood samples were collected for the analysis of chemistry parameters: Glucose, sodium, potassium, calcium, inorganic phosphate, total protein, albumin, blood urea nitrogen, creatinine, total bilirubin, direct bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase and creatine phosphokinase.

  Week 48 to Week 127

• Part B: Number of Participants With Clinically Significant Changes in Hematology Parameters

  Blood samples were collected for the analysis of hematology parameters: hemoglobin (including mean corpuscular volume), mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, hematocrit, red blood cell count, total white blood cell count, platelet count. Differential blood counts, including basophils, eosinophils, neutrophils, lymphocytes, and monocytes

  Week 48 to Week 127

• Part B: Number of Participants With Clinically Significant Changes in Urinalysis

  Urine samples were collected for the analysis of urinalysis parameters: Leucocytes, blood, nitrite, protein, urobilinogen, bilirubin, potential of Hydrogen (pH), specific gravity, ketones, glucose.

  Week 48 to Week 127

• Part B: Number of Participants With Clinically Significant Changes in Vital Parameters

  Vital parameters including pulse rate, respiration rate, blood pressure, and temperature were measured in seated or recumbent for at least 5 minutes. Data for number of participants with abnormal clinically significant changes for vital signs have been presented.

  Week 48 to Week 127

• Part B: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters

  Twelve-lead ECGs were performed after participants has been recumbent for at least 5 minutes.

  Week 48 to Week 127

• Part B: Number of Participants With Clinically Significant Changes in Physical Examinations

  Physical examinations included an evaluation of body systems, including but not limited to the following: skin; head, eyes, ears, nose, and throat; respiratory system; cardiovascular system; abdomen (liver, spleen); lymph nodes; neurological system; and musculoskeletal system.

  Week 48 to Week 127

Secondary Outcomes (11)

• Part A: Change From Baseline in Quality of Life in Neurologic Disorders Upper Extremity (Neuro-QoL UE) Scale at Week 48

  Baseline (Day 1) and at Week 48

• Part A: Number of Participants With Response to Patient's Global Impression of Change (PGIC) at Week 48

  At Week 48

• Part A: Change From Baseline in Whole Body (WB) Longitudinal Composite Muscle Fat Infiltration (MFI) of B Muscles at Week 48

  Baseline (Day 1) and at Week 48

• Part A: Relative Change From Baseline in Average Shoulder Abductor Strength by Hand-held Quantitative Dynamometry at Week 48

  Baseline (Day 1) and at Week 48

• Part A: Number of Participants Serious TEAEs and TEAEs

  Up to Week 48

Study Arms (3)

Part A: Placebo-controlled treatment period: Losmapimod

EXPERIMENTAL

Participants will be randomized to receive losmapimod.

Drug: Losmapimod

Part A: Placebo-controlled treatment period: Placebo

PLACEBO COMPARATOR

Participants will be randomized to receive placebo

Drug: Placebo oral tablet

Part B: Open-label extension

EXPERIMENTAL

Participants will receive losmapimod, upon completion of all assessments for Part A.

Drug: Losmapimod

Interventions

Losmapimod DRUG

Losmapimod 15 mg will be administered BID by mouth along with food.

Part A: Placebo-controlled treatment period: Losmapimod; Part B: Open-label extension

Placebo oral tablet DRUG

Placebo will be administered BID by mouth along with food.

Part A: Placebo-controlled treatment period: Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Fulcrum Therapeutics: lead

Study Sites (33)

University of California Irvine

Irvine, California, 92868, United States

Location

University of California Los Angeles (UCLA)

Los Angeles, California, 90095, United States

Location

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Kennedy Krieger Institute

Baltimore, Maryland, 21205, United States

Location

University of Massachusetts Memorial Medical Center

Worcester, Massachusetts, 01655, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

University of Calgary

Calgary, Alberta, T2N 4Z6, Canada

Location

The Ottawa Hospital Research Institute

Ottawa, Ontario, K1Y 4E9, Canada

Location

Montreal Neurological Institute and Hospital

Montreal, Quebec, H3A 2B4, Canada

Location

Aarhus Universitetshospital

Aarhus, 8200, Denmark

Location

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Nice University Hospital - CHU Nice

Nice, PACA, 06001, France

Location

Institute de Myologie, Groupe Hospitalier Pitié-Salpêtrière

Paris, 75013, France

Location

University Hospital Bonn

Bonn, 53127, Germany

Location

LMU Klinikum Ludwig-Maximilians-Universität München

München, 80336, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Fondazione Serena Onlus- Centro Clinico NEMO

Milan, Lombardy, 20162, Italy

Location

Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, 20133, Italy

Location

Radboudumc

Nijmegen, Gelderland, 9101, Netherlands

Location

Leiden University Medical Centre

Leiden, Southern Holland, 2333 ZA, Netherlands

Location

Hospital Universitario Donostia

San Sebastián, Guipuzkoa, 20014, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

Location

University College of London Hospitals

London, WC1N 3BG, United Kingdom

Location

Newcastle upon Tyne NHS Foundation Trust

Newcastle upon Tyne, NE1 3BZ, United Kingdom

Location

Related Publications (3)

• Barbour AM, Sarov-Blat L, Cai G, Fossler MJ, Sprecher DL, Graggaber J, McGeoch AT, Maison J, Cheriyan J. Safety, tolerability, pharmacokinetics and pharmacodynamics of losmapimod following a single intravenous or oral dose in healthy volunteers. Br J Clin Pharmacol. 2013 Jul;76(1):99-106. doi: 10.1111/bcp.12063.

  PMID: 23215699 BACKGROUND

• Han JJ, Kurillo G, Abresch RT, de Bie E, Nicorici A, Bajcsy R. Reachable workspace in facioscapulohumeral muscular dystrophy (FSHD) by Kinect. Muscle Nerve. 2015 Feb;51(2):168-75. doi: 10.1002/mus.24287. Epub 2014 Nov 19.

  PMID: 24828906 BACKGROUND

• Mellion ML, Ronco L, Berends CL, Pagan L, Brooks S, van Esdonk MJ, van Brummelen EMJ, Odueyungbo A, Thompson LA, Hage M, Badrising UA, Raines S, Tracewell WG, van Engelen B, Cadavid D, Groeneveld GJ. Phase 1 clinical trial of losmapimod in facioscapulohumeral dystrophy: Safety, tolerability, pharmacokinetics, and target engagement. Br J Clin Pharmacol. 2021 Dec;87(12):4658-4669. doi: 10.1111/bcp.14884. Epub 2021 May 14.

  PMID: 33931884 BACKGROUND

MeSH Terms

Conditions

Muscular Dystrophy, Facioscapulohumeral; Muscular Dystrophies; Musculoskeletal Diseases; Neuromuscular Diseases

Interventions

6-(5-((cyclopropylamino)carbonyl)-3-fluoro-2-methylphenyl)-N-(2,2-dimethylprpyl)-3-pyridinecarboxamide

Condition Hierarchy (Ancestors)

Muscular Disorders, Atrophic; Muscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Call Center
• Organization: Fulcrum Therapeutics

clinicaltrials@fulcrumtx.com

617-651-8853

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Part B of the study will be performed in an open-label fashion.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2022
• First Posted: May 31, 2022
• Study Start: June 16, 2022
• Primary Completion: November 19, 2024
• Study Completion: November 19, 2024
• Last Updated: November 10, 2025
• Results First Posted: November 10, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share

Locations

US (14); NL (2); CA (3); ES (3); GB (2); IT (2); DE (3); DK (2); FR (2)