ong-term safety, tolerability, and efficacy of losmapimod treatment in subjects with FSHD
- Conditions
- Facioscapulohumeral Muscular Dystrophy 1 (FSHD1)MedDRA version: 20.0Level: PTClassification code: 10064087Term: Facioscapulohumeral muscular dystrophy Class: 100000004850Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]
- Registration Number
- CTIS2024-512732-30-00
- Lead Sponsor
- Fulcrum Therapeutics Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 80
1. Capable of understanding the written informed consent, and providing signed, dated, and witnessed written informed consent. 2. Male or female subjects between the ages of 18 and 65 years, inclusive. 3. Confirmed diagnosis of FSHD1 with 1 to 9 repeats via assessment of the size of the D4Z4 array on chromosome 4. Randomization will be stratified to ensure that treatment allocation is balanced across FSHD repeat number categories (ie, 1 to 3 repeats versus 4 to 9 repeats). Genetic confirmation must be obtained before the subject is randomized and before the baseline muscle biopsy is performed; genetic confirmation can come from previous testing if verified with appropriate documentation from an accredited laboratory. Due to stable transmission of repeat sizes within families, subjects with a clinical diagnosis of FSHD who have a first-degree relative with a genetically confirmed diagnosis of FSHD1 may be entered into the study for screening assessments, including MRI. During screening, a confirmatory genetic diagnosis is conducted. If genetic testing during screening is necessary, the 4-week screening window will not start until the results are obtained and verified by the principal investigator. 4. Clinical severity score of 2 to 4 (RICCI score; range 0-5), inclusive, at screening. Subjects who use a wheelchair or walker for any activity are not permitted to enroll in the study. 5. Has an MRI-eligible muscle for biopsy, as determined by a central reader. 6. Willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures. 7. Willing to practice an approved method of birth control: - A female subject is eligible to participate if she is of non-child-bearing potential, defined as premenopausal females with permanent sterilization (includes hysterectomy, bilateral oophorectomy, or bilateral salpingectomy in a female subject of any age); or postmenopausal, defined as 12 months of spontaneous amenorrhea; or, if of child-bearing potential, if she is using a highly effective method for avoidance of pregnancy and will continue to use these methods for the duration of the study and until 90 days after the last dose of study drug. The decision to include or exclude women of child-bearing potential may be made at the discretion of the investigator and in accordance with local practice in relation to adequate contraception. - Male subjects must agree to use one of the contraception methods listed in the protocol. This criterion must be followed for the duration of the study and until 90 days after the last dose of study drug.
1. 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. 2. 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. 3. 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 Appendix 13.2: 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. 4. History of febrile illness within 5 days before randomization. Subjects who were healthy during screening but develop febrile illness in the 5 days before randomization need to have the baseline visit postponed until the febrile illness is fully resolved. Once the febrile illness is fully resolved, the subject’s baseline visit can be scheduled. The duration of the screening visit in such cases can be extended for up to 35 days. 5. Known active tuberculosis, active opportunistic, or life-threatening infections. 6. Acute or chronic history of liver disease or known to have current alanine aminotransferase =2 × upper limit of normal (ULN) or total bilirubin >1.5 × ULN, or known history of hepatitis B or C. 7. Known severe renal impairment (defined as a glomerular filtration rate of <30 mL/min/1.73m2). 8. Positive screen for hepatitis B surface antigen (HbsAg), hepatitis C virus (HCV) antibody, or antibodies against human immunodeficiency virus (HIV)-1 and -2. 9. Standard 12-lead ECG demonstrating QTcF >450 msec for male subjects or 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. 10. 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. 11. Blood donation (of approximately 1 pint [500 mL] or more) or any significant loss of blood within 90 days before the first dose of study drug, as determined by the investigator. 12. Vaccination with a live attenuated vaccine within 6 weeks of randomization and throughout the study. 13. Use of any anticoagulants for at least 1 month and antiplatelet agents for at least 1 week before the baseline biopsy, as they increase the risk of hematomas following skeletal muscle biopsy. 14. Male subjects with a female partner who is planning to become pregnant during the study or within 90 days after the last dose of study drug. 15. Positive pregnancy test or
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the safety and tolerability of long-term dosing of losmapimod in FSHD1 subjects;Secondary Objective: To evaluate the plasma concentrations of losmapimod in FSHD1 subjects;Primary end point(s): The primary endpoint of the OLE is the safety and tolerability of long-term treatment of losmapimod based on AEs, clinical laboratory tests, ECGs, vital signs, and physical examination.
- Secondary Outcome Measures
Name Time Method Secondary end point(s):The secondary endpoint of the OLE is the plasma concentrations of losmapimod after long-term dosing (at every-12-week time points).