Evaluation of Safety, Tolerability, and Changes in Biomarker and Clinical Outcome Assessments of Losmapimod for FSHD1 With Extension

NCT04004000 | Terminated Phase 2 Results

• 1 other identifier: FIS-001-2019
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial is a study to evaluate the safety, tolerability, and changes in biomarker and clinical outcome assessments of Losmapimod for patients with Facioscapulohumeral Muscular Dystrophy 1 (FSHD1) with an open-label extension.

Conditions

Facioscapulohumeral Muscular Dystrophy 1

Keywords

FSHD, FSHD1; Muscular Dystrophies; Facioscapulohumeral Muscular Disorders; Atrophic Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases

Outcome Measures

Primary Outcomes (4)

• Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. A TEAE is an AE that begins on or after the first dose of study drug and before the stop of study drug + 7 days or begins before the first dose of study drug and worsens on or after the first dose of study drug and before the stop of study drug + 7 days. A Serious adverse event (SAE) is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment.

  Up to 68 Weeks

• 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, uric acid, total bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, lactate dehydrogenase and creatine phosphokinase.

  Up to 68 Weeks

• 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

  Up to 68 Weeks

• Number of Participants With Clinically Significant Changes in Serum Coagulation Parameters

  Blood samples were collected for the analysis of Serum coagulation parameters: International normalized ratio, prothrombin time, activated partial thromboplastin time and fibrinogen.

  Up to 68 Weeks

Secondary Outcomes (4)

• Percent Change From Baseline in the Ratio of Phosphorylated HSP27 (pHSP27) /Total HSP27 in Sorbitol-stimulated Whole Blood

  Baseline and at Week 44

• Percent Change From Baseline in Ratio of pHSP27/Total HSP27 in Muscle

  Baseline and at Week 8

• Plasma Concentration of Losmapimod

  Post-dose at Baseline, Week 4, Week 8, Week 20, Week 32, Week 44, and Week 56

• Muscle Concentration of Losmapimod

  Post dose at Baseline, Week 4, Week 8 and Week 44

Study Arms (1)

Treatment

EXPERIMENTAL

FSHD1 subjects with genetic confirmation will receive 15 mg of losmapimod twice daily given by mouth; for a total of 30 mg daily until 90 days after commercial drug is available post regulatory approval or study termination.

Drug: Losmapimod

Interventions

Losmapimod DRUG

The main study includes a treatment period of approximately one year. Subjects will receive 15 mg of losmapimod twice daily by mouth; for a total of 30 mg daily. The study drug should be taken with food and the date and time of each dose taken recorded in the subject diary. Only subjects who participated in and completed all procedures for the main study (Week 60) will be eligible to participate in the extension. For the extension, subjects will receive 15 mg of losmapimod by mouth twice daily for a total of 30 mg by mouth daily. Participation will continue until 90 days after commercial drug is available post regulatory approval or study termination.

Treatment

Eligibility Criteria

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

You may qualify if:

• FSHD1 subjects age 18-65 years.
• Subject will sign and date an informed consent form (ICF).
• Confirmed diagnosis of FSHD1 with 1 to 9 repeats via assessment of the size of the D4Z4 array on chromosome 4. Genetic confirmation must be obtained prior to the screening MRI and baseline muscle biopsy; genetic confirmation can come from previous testing if verified with appropriate documentation.
• Must be willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines, scheduled needle muscle biopsies, and other study procedures.
• Both male and female subjects must be willing to practice an approved method of birth control.
• Clinical Severity Score between 2 and 4 on Ricci's Scale (scale range is from 0 to 5). Subjects that use a wheelchair or walker for any activity are not permitted to enroll in the study.
• Commitment to complete the 2 visits for skeletal muscle needle biopsy and all visits for whole-body MRI.
• Able to complete the RWS, TUG, and FSHD PROs (FSHD-RODS and FSHD-HI) at the screening visit.
• Must have an MRI-eligible muscle for biopsy as determined by the central reader.
• Subject must complete the main study through the Week 60 visit in order to participate in the open-label extension study.

You may not qualify if:

• 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, history of relevant drug or food allergies; history of cardiovascular or central nervous system disease; history or presence of clinically significant pathology; clinically significant history of mental disease; and history of cancer, except for squamous cell skin cancer, basal cell skin cancer, and Stage 0 cervical carcinoma in situ (all 3 with no recurrence for the last 5 years).
• Subject has a known or clinically suspected infection with human immunodeficiency virus or hepatitis B or C viruses.
• Subject has current clinically significant liver (alanine aminotransferase \> 2X upper limit of normal or total bilirubin \>1.5 X upper limit of normal) or kidney (GFR \< 30 mL/min/1.73m2) dysfunction.
• Subject screens positive for hepatitis B surface antigen, hepatitis C virus (HCV) antibody, or antibodies against human immunodeficiency viruses 1 and 2 (HIV 1/HIV 2 antibodies).
• Subject has any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy, or other gastrointestinal tract surgery, except appendectomy).
• Subject has a standard 12-lead ECG demonstrating QT interval by Fredericia (QTcF) \>450 msec for male subjects and QTcF \>470 msec for female subjects at Screening. If QTcF exceeds 450 msec for males or 470 msec for females, the ECG will be repeated 2 more times, and the average of the 3 QTcF values will be used to determine the subject's eligibility.
• Subject has a history of cardiac dysrhythmias requiring anti-arrhythmia treatment(s); or history or evidence of abnormal ECGs that, in the opinion of the investigator or Medical Monitor, would preclude the subject's participation in the study.
• Male subject has a female partner who is planning to become pregnant during the study or within 90 days after the last study drug dose.
• Subject has donated blood (of approximately 1 pint \[500 mL\] or more) or has had any significant loss of blood within 90 days before the first study drug dose, as determined by the investigator.
• Vaccination with a live attenuated vaccine within 6 weeks of randomisation.
• Subject has a history of alcohol, analgesic/opioid, and/or illicit drug abuse as defined by the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, in the last 6 months before screening, or a positive test for drugs of abuse at screening.
• Subject has participated in a clinical trial in which they have received an investigational product within the following time period prior to enrolment in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever was longer).
• For subjects that are on drug(s) or supplements that may affect muscle function as determined by the treating physician or included in the list of drugs presented in Section 15: subjects must be on a stable dose of that drug(s) or supplement for at least 3 months prior to enrollment in the study and remain on that stable dose for the duration of the study (list of drugs presented in Section 15). 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.
• Subject has a history of sensitivity to any of the study medications or components thereof, or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicated their participation.
• Female subject is pregnant as determined by positive urine Human Chorionic Gonadotropin (HCG) test at Screening or prior to dosing.

Sponsors & Collaborators

• Fulcrum Therapeutics: lead

Study Sites (1)

Radboud University Medical Center

Nijmegen, 9101, Netherlands

Location

Related Publications (5)

• 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

• 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.

  PMID: 21262998 BACKGROUND

• de Greef JC, Frants RR, van der Maarel SM. Epigenetic mechanisms of facioscapulohumeral muscular dystrophy. Mutat Res. 2008 Dec 1;647(1-2):94-102. doi: 10.1016/j.mrfmmm.2008.07.011. Epub 2008 Aug 3.

  PMID: 18723032 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

• 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.

  PMID: 23873337 BACKGROUND

MeSH Terms

Conditions

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
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a single-centre, open-label pilot study with open-label extension

Study Record Dates

• First Submitted: June 25, 2019
• First Posted: July 1, 2019
• Study Start: August 23, 2019
• Primary Completion: October 31, 2024
• Study Completion: October 31, 2024
• Last Updated: December 2, 2025
• Results First Posted: December 2, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)