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Sponsor Decision
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Losmapimod | Experimental | FSHD1 patients with genetic confirmation 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Losmapimod | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Reporting Serious Treatment Emergent Adverse Events (Serious TEAEs) and TEAEs | A TEAE is an adverse event that begins on or after the first dose of study drug and on or before the stop of study drug plus 7 days or begins before the first dose of study drug and worsens on or after the first dose of study drug and on or before the stop of study drug plus 7 days. An adverse event with completely missing onset and end dates was considered as TEAE. An adverse event with missing onset date but the end date is on or after the first dose of study drug and before the stop of study drug plus 7 days was considered a TEAE. | Up to 57 months |
| 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, total bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase and creatine phosphokinase. | Up to 57 months |
| 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 57 months |
| 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, partial thromboplastin time. | Up to 57 months |
| Number of Participants With Clinically Significant Changes in Urinalysis |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Marie-Helene Jouvin, MD | Fulcrum Therapeutics | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California Irvine | Irvine | California | 92868 | United States | ||
| University of California Los Angeles (UCLA) |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23215699 | Background | 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. | |
| 21262998 | Background |
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Participants were analysed according to their original treatment assignment and their entry point into the OLE: Losmapimod 15 mg BID / Losmapimod 15 mg BID (from Week 24 or Week 48) and Placebo BID / Losmapimod 15 mg BID (from Week 24 or Week 48).
Participants who completed either 24 or 48 weeks in the placebo-controlled treatment period of the parent study were eligible to enroll in the Open-Label Extension (OLE) phase. A total 76 participants entered the OLE) phase and received at least 1 dose of losmapimod. Of those, 39 were previously in the losmapimod group and 37 in the placebo group during the double-blind treatment period of study (NCT04003974) and met eligibility criteria for continued treatment.
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| ID | Title | Description |
|---|---|---|
| FG000 | Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Participants will continue to receive Losmapimod 15 mg (2×7.5 mg tablets/dose) BID until 90 days after commercial drug is available post regulatory approval or until the study is discontinued by the Sponsor (up to 60 months). |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 17, 2022 | Sep 10, 2025 |
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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.
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Urine samples were collected for the analysis of urinalysis parameters: Leucocytes, blood, nitrite, protein, urobilinogen, bilirubin, pH, specific gravity, ketones, glucose. |
| Up to 57 months |
| Number of Participants With Clinically Significant Changes in Vital Parameters | Vital parameters including pulse rate, respiration rate, blood pressure, and temperature were measured in seated or recumbent for at least 5 minutes. Data for number of participants with abnormal clinically significant changes for vital signs have been presented. | Up to 57 months |
| Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters | Twelve-lead ECGs was performed after participants has been recumbent for at least 5 minutes. | Up to 57 months |
| Number of Participants With Clinically Significant Changes in Physical Examinations | Physical examinations included an evaluation of body systems, including but not limited to the following: skin; head, eyes, ears, nose, and throat; respiratory system; cardiovascular system; abdomen (liver, spleen); lymph nodes; neurological system; and musculoskeletal system. | Up to 57 months |
| Los Angeles |
| California |
| 90095 |
| United States |
| University of Florida | Gainesville | Florida | 32610 | United States |
| University of Kansas Medical Center | Kansas City | Kansas | 66160 | United States |
| Kennedy Krieger Institute | Baltimore | Maryland | 21205 | United States |
| University of Massachusetts Memorial Medical Center | Worcester | Massachusetts | 01655 | United States |
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
| University of Rochester Medical Center | Rochester | New York | 14642 | United States |
| Ohio State University | Columbus | Ohio | 43221 | United States |
| University of Utah | Salt Lake City | Utah | 84132 | United States |
| Virginia Commonwealth University | Richmond | Virginia | 23298 | United States |
| University of Washinton Medical Center | Seattle | Washington | 98195 | United States |
| Ottawa Hospital Research Institute | Ottawa | Ontario | K1Y 4E9 | Canada |
| Montreal Neurological Institute and Hospital | Montreal | Quebec | H3A 2B4 | Canada |
| CHU de NICE- CHU pasteur2 | Nice | 06001 | France |
| Hospital de la Sta Creu i St Pau | Barcelona | 08041 | Spain |
| Hospital UiP La Fe | Valencia | 46026 | Spain |
| 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. |
| 19728363 | Background | 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. |
| 24828906 | 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. |
| 28171552 | Background | 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. |
| 23873337 | 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. |
| 30312408 | Background | 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. |
| COMPLETED |
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| NOT COMPLETED |
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Open-Label Analysis Set comprised of all participants who completed 24 or 48 weeks of treatment in the placebo-controlled treatment period and received at least 1 dose of open-label losmapimod in the OLE.
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| ID | Title | Description |
|---|---|---|
| BG000 | Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Participants will continue to receive Losmapimod 15 mg (2×7.5 mg tablets/dose) BID until 90 days after commercial drug is available post regulatory approval or until the study is discontinued by the Sponsor (up to 60 months). |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants Reporting Serious Treatment Emergent Adverse Events (Serious TEAEs) and TEAEs | A TEAE is an adverse event that begins on or after the first dose of study drug and on or before the stop of study drug plus 7 days or begins before the first dose of study drug and worsens on or after the first dose of study drug and on or before the stop of study drug plus 7 days. An adverse event with completely missing onset and end dates was considered as TEAE. An adverse event with missing onset date but the end date is on or after the first dose of study drug and before the stop of study drug plus 7 days was considered a TEAE. | Open-Label Analysis Set. | Posted | Count of Participants | Participants | Up to 57 months |
|
|
| |||||||||||||||||||||||||||||||||
| Primary | 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, total bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase and creatine phosphokinase. | Open-Label Analysis Set. | Posted | Count of Participants | Participants | Up to 57 months |
|
| ||||||||||||||||||||||||||||||||||
| Primary | 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 | Open-Label Analysis Set: | Posted | Count of Participants | Participants | Up to 57 months |
|
| ||||||||||||||||||||||||||||||||||
| Primary | 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, partial thromboplastin time. | Open-Label Analysis Set. | Posted | Count of Participants | Participants | Up to 57 months |
|
| ||||||||||||||||||||||||||||||||||
| Primary | Number of Participants With Clinically Significant Changes in Urinalysis | Urine samples were collected for the analysis of urinalysis parameters: Leucocytes, blood, nitrite, protein, urobilinogen, bilirubin, pH, specific gravity, ketones, glucose. | Open-Label Analysis Set. | Posted | Count of Participants | Participants | Up to 57 months |
|
| ||||||||||||||||||||||||||||||||||
| Primary | Number of Participants With Clinically Significant Changes in Vital Parameters | Vital parameters including pulse rate, respiration rate, blood pressure, and temperature were measured in seated or recumbent for at least 5 minutes. Data for number of participants with abnormal clinically significant changes for vital signs have been presented. | Open-Label Analysis Set. | Posted | Count of Participants | Participants | Up to 57 months |
|
| ||||||||||||||||||||||||||||||||||
| Primary | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters | Twelve-lead ECGs was performed after participants has been recumbent for at least 5 minutes. | Open-Label Analysis Set. | Posted | Count of Participants | Participants | Up to 57 months |
|
| ||||||||||||||||||||||||||||||||||
| Primary | Number of Participants With Clinically Significant Changes in Physical Examinations | Physical examinations included an evaluation of body systems, including but not limited to the following: skin; head, eyes, ears, nose, and throat; respiratory system; cardiovascular system; abdomen (liver, spleen); lymph nodes; neurological system; and musculoskeletal system. | Open-Label Analysis Set. | Posted | Count of Participants | Participants | Up to 57 months |
|
|
Up to 57 months
Serious TEAEs and TEAEs were collected in Open-Label Analysis Set which comprised of all participants who completed 24 or 48 weeks of treatment in the placebo-controlled treatment period and received at least 1 dose of open-label losmapimod in the OLE.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Participants will continue to receive Losmapimod 15 mg (2×7.5 mg tablets/dose) BID until 90 days after commercial drug is available post regulatory approval or until the study is discontinued by the Sponsor (up to 60 months). | 0 | 76 | 7 | 76 | 71 | 76 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute myocardial infarction | Cardiac disorders | MedDRA (23.0) | Non-systematic Assessment |
| |
| Coronary artery disease | Cardiac disorders | MedDRA (23.0) | Non-systematic Assessment |
| |
| Ulcer haemorrhage | General disorders | MedDRA (23.0) | Non-systematic Assessment |
| |
| Anaphylactic reaction | Immune system disorders | MedDRA (23.0) | Non-systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Non-systematic Assessment |
| |
| Endometrial cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (23.0) | Non-systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA (23.0) | Non-systematic Assessment |
| |
| Labile blood pressure | Vascular disorders | MedDRA (23.0) | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Palpitations | Cardiac disorders | MedDRA (23.0) | Non-systematic Assessment |
| |
| Dry eye | Eye disorders | MedDRA (23.0) | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (23.0) | Non-systematic Assessment |
| |
| Food poisoning | Gastrointestinal disorders | MedDRA (23.0) | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (23.0) | Non-systematic Assessment |
| |
| Pain | General disorders | MedDRA (23.0) | Non-systematic Assessment |
| |
| Corona virus infection | Infections and infestations | MedDRA (23.0) | Non-systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA (23.0) | Non-systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (23.0) | Non-systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA (23.0) | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (23.0) | Non-systematic Assessment |
| |
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA (23.0) | Non-systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA (23.0) | Non-systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA (23.0) | Non-systematic Assessment |
| |
| Joint injury | Injury, poisoning and procedural complications | MedDRA (23.0) | Non-systematic Assessment |
| |
| Ligament sprain | Injury, poisoning and procedural complications | MedDRA (23.0) | Non-systematic Assessment |
| |
| Skin abrasion | Injury, poisoning and procedural complications | MedDRA (23.0) | Non-systematic Assessment |
| |
| Skin laceration | Injury, poisoning and procedural complications | MedDRA (23.0) | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Non-systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Non-systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Non-systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Non-systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Non-systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (23.0) | Non-systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA (23.0) | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (23.0) | Non-systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDRA (23.0) | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Non-systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Non-systematic Assessment |
| |
| Sleep apnoea syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (23.0) | Non-systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Call Center | Fulcrum Therapeutics | 617-651-8853 | clinicaltrials@fulcrumtx.com |
| Prot_002.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 8, 2024 | Aug 14, 2025 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D020391 | Muscular Dystrophy, Facioscapulohumeral |
| D009136 | Muscular Dystrophies |
| D009140 | Musculoskeletal Diseases |
| D009468 | Neuromuscular Diseases |
| ID | Term |
|---|---|
| D020966 | Muscular Disorders, Atrophic |
| D009135 | Muscular Diseases |
| D009422 | Nervous System Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
Not provided
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| ID | Term |
|---|---|
| C543534 | 6-(5-((cyclopropylamino)carbonyl)-3-fluoro-2-methylphenyl)-N-(2,2-dimethylprpyl)-3-pyridinecarboxamide |
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| Unknown or Not Reported |
|
| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
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