Facioscapulohumeral Muscular Dystrophy MedDRA version: 20.0 Level: PT Classification code 10064087 Term: Facioscapulohumeral muscular dystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: Losmapimod
Product Code: FTX-1821
Pharmaceutical Form: Tablet
INN or Proposed INN: Losmapimod
CAS Number: 585543-15-3
Current Sponsor code: FTX-1821
Concentration unit: mg milligram(s)
C
Sponsors
Fulcrum Therapeutics
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patient will sign and date an informed consent form (ICF). 2. Patients will have a diagnosis of FSHD1 or FSHD2 verified by genetic testing - Randomization will be stratified for FSHD1 to ensure that treatment allocation is balanced across FSHD repeat number categories (ie, 1 to 3 repeats versus 4 to 9 repeats). - Randomization will be stratified for FSHD2 to ensure that an equal number of patients will be allocated to treatment and placebo. 3. Patients will have a Clinical Severity Score of 2 to 4 (Ricci score; range 0 to 5) at screening. Patients who are wheelchair-dependent or dependent on walker or wheelchair for activities are not permitted to enroll in the study. 4. Patients with baseline total RSA (Q1-Q4) without weight in the dominant UE assessed by RWS = 0.2 and = 0.7. 5. At least one short tau inversion recovery (STIR)-positive muscle in the lower extremities. 6. Willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures. 7. No contraindications to MRI. 8. Patients (male and female) will be between the ages of 18 and 65 years, inclusive. - A female patient is eligible to participate if she is of non-child bearing potential, defined as pre-menopausal females with a documented tubal ligation or hysterectomy; if she is postmenopausal, defined as 12 months of spontaneous amenorrhea; OR - if of child-bearing potential, she is using a highly effective method for avoidance of pregnancy for the duration of dosing and until 2 weeks after the last dose. The decision to include or exclude women of childbearing potential may be made at the discretion of the Investigator and in accordance with local practice in relation to adequate contraception. - Male patients must agree to use one of the contraception methods. This criterion must be followed from the time of the first dose of study medication and until 90 days after the last dose of study drug. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 230 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. 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 patient. 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. 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 patients who are on drug(s) or supplements that may affect muscle function, as determined by the Investigator, or that are included in the list of drugs presented in Appendix 2 of the Protocol: patients 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 the first study drug dose. Patients 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 (fever-free without the use of antipyretic agents for 24 hours). Once the febrile illness is fully resolved, the patient’s baseline visit can be scheduled. The duration of the screening period in such cases can be extended to up to 35 days. 5. Known active opportunistic or life-threatening infections including HIV and hepatitis B or C. 6. Acute or chronic history of liver disease or known to have current ALT =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 450 msec for male patients and QTcF >470 msec for female patients 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 patient’s eligibility. 9. 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 patient’s participation in the study. 10. Male patients with a female partner who is planning to become pregnant during the study or within 90 days after the last study drug dose. 11. Concomitant use of cytotoxic chemotherapy for cancer or known ongoing or anticipated use of chronic severe immunosuppressive agents. 12. Positive pregnancy test or known to be pregnant or lactating. 13. Any current mental condition (psychiatric disorder, senility or dementia) that may affect study compliance or prevent understanding of the aims, investigational procedures, or possible consequences of the study. 14. Patient has any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy, or other gastrointestinal tract surgery, except appendectomy). 15. History of alcohol, analgesic/opioid, and/or illicit drug abuse, as defined
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of losmapimod for the treatment of FSHD by demonstrating slowing of disease progression assessed by RWS quantification of RSA Q1-Q5 with 500 g wrist weight in the dominant arm.;Secondary Objective: 1. To evaluate the change in Neuro-QoL UE relative to placebo 2. To evaluate Patient Global Impression of Change (PGIC) relative to placebo 3. To evaluate efficacy of losmapimod to slow accumulation of fat in muscle by MFI with WB MSK MRI relative to placebo 4. To assess safety and tolerability of losmapimod in patients with FSHD;Primary end point(s): Change from baseline compared to placebo in total RSA Q1-Q5 with 500 g wrist weight in dominant arm at Week 48;Timepoint(s) of evaluation of this end point: RSA Q1-Q5 with 500 g wrist weight in dominant arm at Week 48 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Change from baseline compared to placebo in Neuro-QoL UE at Week 48 2. Change from baseline compared to placebo in PGIC at Week 48 3. Change from baseline compared to placebo in WB longitudinal composite MFI at Week 48 4. Safety and tolerability, based on the assessment of AEs, SAEs, clinically significant laboratory test abnormalities, ECGs, and vital signs;Timepoint(s) of evaluation of this end point: At Week 48 and throughout the study | — |
Countries
Canada, Denmark, France, Germany, Italy, Netherlands, Spain, United Kingdom, United States
Contacts
Public ContactChristopher Morabito
Fulcrum Therapeutics, Inc.
Outcome results
None listed