Efficacy and Safety of Losmapimod in Treating Subjects With Facioscapulohumeral Muscular Dystrophy (FSHD) With Open-Label Extension (OLE)

Facioscapulohumeral Muscular Dystrophy (FSHD) Clinical Trial

Official title:

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, 48-Week, Parallel-Group Study of the Efficacy and Safety of Losmapimod in Treating Subjects With Facioscapulohumeral Muscular Dystrophy (FSHD) With Open-Label Extension (OLE)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04264442
• Other study ID #: FIS-002-2019 OLE
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: February 13, 2020
• Est. completion date: January 2026

Study information

• Verified date: July 2023
• Source: Fulcrum Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is an open-label extension to evaluate the safety and tolerability of long-term dosing of Losmapimod in patients with FSHD1 who participated in the ReDux4 study.

Description:

This study is an open-label extension study to evaluate the safety and tolerability of long-term dosing of Losmapimod in patients with FSHD1 who participated in the ReDux4 study. This study is a multi-center clinical trial. It will be conducted in North America, Canada and Europe. Only patients who participated and competed all study procedures in the ReDUX4 Study treatment period will be eligible to participate in this open label extension study. Patients who complete the randomized, placebo-controlled portion of the study will have the option to roll over into the open-label extension study. Patients will receive 15 mg of losmapimod by mouth twice daily for a total of 30 mg by mouth daily. All patients will attend clinic visits approximately every 12 weeks. Participation in this open-label extension study will continue until 90 days after losmapimod becomes commercially available, the patient withdraws from the study, or the Sponsor decides to close the study. The primary endpoint of the study is to evaluate the safety and tolerability of long-term dosing of losmapimod in patients with FSHD.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 76
• Est. completion date: January 2026
• Est. primary completion date: October 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• The patient must have consented to participate and must have provided signed, dated and witnessed an IRB-approved informed consent form that conforms to federal and institutional guidelines.
• Male or female subjects
• Patients must be between 18 and 65 years of age, inclusive
• Must be will and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines and other study procedures.
• Will practice an approved method of birth control

Exclusion Criteria:

• Has a history of any illness or any clinical condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject. This may include, but is not limited to, a history of relevant drug or food allergies; history of cardiovascular or central nervous system disease; neuromuscular diseases except FSHD (eg, myopathy, neuropathy, neuromuscular junction disorders); or clinically significant history of mental disease.
• For subjects who are on drug(s) or supplements that may affect muscle function, as determined by the treating physician, or that are included in the list of drugs presented in the protocol, subjects 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. Changes to the dose or treatment discontinuation during the study can only be done for strict medical reasons by the treating physician with clear documentation and notification to the sponsor.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Losmapimod
Patients will receive Losmapimod 15 mg by mouth twice daily for a total of 30 mg daily until 90 days after commercial drug is available post regulatory approval or until the study is discontinued by the Sponsor. The study drug should be taken with food and the date and time of each dose taken should be recorded in the subject diary.

Locations

Country	Name	City	State
Canada	Montreal Neurological Institute and Hospital	Montréal	Quebec
Canada	Ottawa Hospital Research Institute	Ottawa	Ontario
France	CHU de NICE- CHU pasteur2	Nice
Spain	Hospital de la Sta Creu i St Pau	Barcelona
Spain	Hospital UiP La Fe	Valencia
United States	Kennedy Krieger Institute	Baltimore	Maryland
United States	Ohio State University	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	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 Washinton 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,  France,  Spain, 

References & Publications (7)

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

Cheriyan J, Webb AJ, Sarov-Blat L, Elkhawad M, Wallace SM, Maki-Petaja KM, Collier DJ, Morgan J, Fang Z, Willette RN, Lepore JJ, Cockcroft JR, Sprecher DL, Wilkinson IB. Inhibition of p38 mitogen-activated protein kinase improves nitric oxide-mediated vasodilatation and reduces inflammation in hypercholesterolemia. Circulation. 2011 Feb 8;123(5):515-23. doi: 10.1161/CIRCULATIONAHA.110.971986. Epub 2011 Jan 24. — View Citation

de Greef JC, Lemmers RJ, van Engelen BG, Sacconi S, Venance SL, Frants RR, Tawil R, van der Maarel SM. Common epigenetic changes of D4Z4 in contraction-dependent and contraction-independent FSHD. Hum Mutat. 2009 Oct;30(10):1449-59. doi: 10.1002/humu.21091. — 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

Jagannathan S, Shadle SC, Resnick R, Snider L, Tawil RN, van der Maarel SM, Bradley RK, Tapscott SJ. Model systems of DUX4 expression recapitulate the transcriptional profile of FSHD cells. Hum Mol Genet. 2016 Oct 15;25(20):4419-4431. doi: 10.1093/hmg/ddw271. — View Citation

Statland JM, Tawil R. Risk of functional impairment in Facioscapulohumeral muscular dystrophy. Muscle Nerve. 2014 Apr;49(4):520-7. doi: 10.1002/mus.23949. Epub 2014 Feb 10. — View Citation

Wang LH, Friedman SD, Shaw D, Snider L, Wong CJ, Budech CB, Poliachik SL, Gove NE, Lewis LM, Campbell AE, Lemmers RJFL, Maarel SM, Tapscott SJ, Tawil RN. MRI-informed muscle biopsies correlate MRI with pathology and DUX4 target gene expression in FSHD. Hum Mol Genet. 2019 Feb 1;28(3):476-486. doi: 10.1093/hmg/ddy364. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and Tolerability of Losmapimod	Safety and tolerability of losmapimod will be evaluated by the following: a. Type, frequency, severity and relationship of adverse events (AEs) to losmapimod	Every 12 Weeks from the date of enrollment through study completion, up to 60 months