Clinical trial NCT04264442: Efficacy and Safety of Losmapimod in Treating Subjects With Facioscapulohumeral Muscular Dystrophy (FSHD) With Open-Label Extension (OLE)
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Facioscapulohumeral Muscular Dystrophy (FSHD)
Keywords: FSHD, FSHD1
Muscular Dystrophy
Muscular Dystrophies
Facioscapulohumeral Muscular Disorders
Musculoskeletal Diseases
Neuromuscular Diseases
Lead sponsor: Fulcrum Therapeutics
Sponsor class: INDUSTRY
First posted: 2020-02-11
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This study is part two of NCT04003974 which was a randomized, double-blind placebo-controlled treatment period for 48 weeks. This study is an open-label extension with losmapimod in patients with FSHD1.
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Safety and Tolerability of Losmapimod
timeFrame: Every 12 Weeks from the date of enrollment through study completion, up to 60 months
Secondary outcomes:
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: 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: 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
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 Washinton Medical Center
state: Washington
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute
state: Ontario
city: Montréal
country: Canada
facility: Montreal Neurological Institute and Hospital
state: Quebec
city: Nice
country: France
facility: CHU de NICE- CHU pasteur2
city: Barcelona
country: Spain
facility: Hospital de la Sta Creu i St Pau
city: Valencia
country: Spain
facility: Hospital UiP La Fe
Study officials:
affiliation: Fulcrum Therapeutics
name: Marie-Helene Jouvin, MD
role: STUDY_DIRECTOR
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: 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.
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.
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: 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.
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.
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.