Clinical trial NCT05397470: Efficacy and Safety of Losmapimod in Treating Participants With Facioscapulohumeral Muscular Dystrophy (FSHD) (REACH)
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
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 Dystrophies
Muscular Dystrophy
Facioscapulohumeral Muscular Disorders
Musculoskeletal Diseases
Neuromuscular Diseases
REACH
Lead sponsor: Fulcrum Therapeutics
Sponsor class: INDUSTRY
First posted: 2022-05-31
Enrollment: 260
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: Baseline and at Week 48
measure: Part B: Number of participants reporting Adverse events (AEs)
timeFrame: Up to Week 192
measure: Part B: Number of participants with clinically significant changes in clinical laboratory parameters, Electrocardiogram (ECG), vital signs and physical examinations
timeFrame: Up to Week 192
Secondary outcomes:
measure: Part A: Change from Baseline in Quality of Life in Neurologic Disorders upper extremity (Neuro-QoL UE) Scale at Week 48
timeFrame: Baseline and at Week 48
measure: Part A: Patient's Global Impression of Change (PGIC) at Week 48
timeFrame: At Week 48
measure: Part A: Change from Baseline in Whole body (WB) longitudinal composite Muscle Fat Infiltration (MFI) of B muscles at Week 48
timeFrame: Baseline and at Week 48
measure: Part A: Change from Baseline in average shoulder abductor strength by hand-held quantitative dynamometry at Week 48
timeFrame: Baseline and at Week 48
measure: Part A: Number of participants reporting Adverse events (AEs)
timeFrame: Up to Week 48
measure: Part A: Number of participants with clinically significant changes in clinical laboratory parameters, ECG, vital signs and physical examinations
timeFrame: Up to Week 48
Other outcomes:
Locations:
city: Irvine
country: United States
facility: University of California Irvine
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles (UCLA)
state: California
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: Kennedy Krieger Institute
state: Maryland
city: Worcester
country: United States
facility: University of Massachusetts Memorial Medical Center
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Ottawa
country: Canada
facility: The Ottawa Hospital Research Institute
state: Ontario
city: Montréal
country: Canada
facility: Montreal Neurological Institute and Hospital
state: Quebec
city: Aarhus
country: Denmark
facility: Aarhus Universitetshospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Nice
country: France
facility: Nice University Hospital - CHU Nice
state: Paca
city: Paris
country: France
facility: Institute de Myologie, Groupe Hospitalier Pitié-Salpêtrière
city: Bonn
country: Germany
facility: University Hospital Bonn
city: München
country: Germany
facility: LMU Klinikum Ludwig-Maximilians-Universität München
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Milano
country: Italy
facility: Fondazione Serena Onlus- Centro Clinico NEMO
state: Lombardia
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Neurologico Carlo Besta
city: Nijmegen
country: Netherlands
facility: Radboudumc
state: Gelderland
city: Leiden
country: Netherlands
facility: Leiden University Medical Centre
state: Southern Holland
city: San Sebastián
country: Spain
facility: Hospital Universitario Donostia
state: Guipuzkoa
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: London
country: United Kingdom
facility: University College of London Hospitals
city: Newcastle upon Tyne
country: United Kingdom
facility: Newcastle upon Tyne NHS Foundation Trust
Study officials:
References:
citation: 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.
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.
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.