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

Facioscapulohumeral Muscular Dystrophy (FSHD) Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05397470
• Other study ID #: 1821-FSH-301
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 16, 2022
• Est. completion date: January 2026

Study information

• Verified date: March 2024
• Source: Fulcrum Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 260
• Est. completion date: January 2026
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Facioscapulohumeral Muscular Dystrophy (FSHD)
• Muscular Dystrophies
• Muscular Dystrophy, Facioscapulohumeral

Intervention

Drug:
• Losmapimod
Losmapimod 15 mg will be administered BID by mouth along with food.
• Placebo oral tablet
Placebo will be administered BID by mouth along with food.

Locations

Country	Name	City	State
Canada	University of Calgary	Calgary	Alberta
Canada	Montreal Neurological Institute and Hospital	Montréal	Quebec
Canada	The Ottawa Hospital Research Institute	Ottawa	Ontario
Denmark	Aarhus Universitetshospital	Aarhus
Denmark	Rigshospitalet	Copenhagen
France	Nice University Hospital - CHU Nice	Nice	Paca
France	Institute de Myologie, Groupe Hospitalier Pitié-Salpêtrière	Paris
Germany	University Hospital Bonn	Bonn
Germany	LMU Klinikum Ludwig-Maximilians-Universität München	München
Germany	Universitätsklinikum Ulm	Ulm
Italy	Fondazione IRCCS Istituto Neurologico Carlo Besta	Milano
Italy	Fondazione Serena Onlus- Centro Clinico NEMO	Milano	Lombardia
Netherlands	Leiden University Medical Centre	Leiden	Southern Holland
Netherlands	Radboudumc	Nijmegen	Gelderland
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Hospital Universitario Donostia	San Sebastián	Guipuzkoa
Spain	Hospital Universitari i Politecnic La Fe	Valencia
United Kingdom	University College of London Hospitals	London
United Kingdom	Newcastle upon Tyne NHS Foundation Trust	Newcastle upon Tyne
United States	University of Colorado Anschutz Medical Campus	Aurora	Colorado
United States	Kennedy Krieger Institute	Baltimore	Maryland
United States	Ohio State University Medical Center	Columbus	Ohio
United States	University of Florida	Gainesville	Florida
United States	University of California Irvine	Irvine	California
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	University of California Los Angeles (UCLA)	Los Angeles	California
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Rochester Medical Center	Rochester	New York
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	University of Utah	Salt Lake City	Utah
United States	University of Washington Medical Center	Seattle	Washington
United States	University of Massachusetts Memorial Medical Center	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Fulcrum Therapeutics

Countries where clinical trial is conducted

United States,  Canada,  Denmark,  France,  Germany,  Italy,  Netherlands,  Spain,  United Kingdom, 

References & 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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Primary	Part B: Number of participants reporting Adverse events (AEs)		Up to Week 192
Primary	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	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
Secondary	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
Secondary	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
Secondary	Part A: Change from Baseline in average shoulder abductor strength by hand-held quantitative dynamometry 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
Secondary	Part A: Number of participants reporting Adverse events (AEs)		Up to Week 48
Secondary	Part A: Number of participants with clinically significant changes in clinical laboratory parameters, ECG, vital signs and physical examinations		Up to Week 48