Facioscapulohumeral Muscular Dystrophy (FSHD)
Conditions
Keywords
FSHD, FSHD1, Muscular Dystrophy, Muscular Dystrophies, Facioscapulohumeral Muscular Disorders, Musculoskeletal Diseases, Neuromuscular Diseases
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.
Interventions
DRUGLosmapimod
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.
Sponsors
Fulcrum Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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 willing 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Reporting Serious Treatment Emergent Adverse Events (Serious TEAEs) and TEAEs | Up to 57 months | 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. |
| Number of Participants With Clinically Significant Changes in Chemistry Parameters | Up to 57 months | 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. |
| Number of Participants With Clinically Significant Changes in Hematology Parameters | Up to 57 months | 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 |
| Number of Participants With Clinically Significant Changes in Serum Coagulation Parameters | Up to 57 months | Blood samples were collected for the analysis of Serum coagulation parameters: International normalized ratio, prothrombin time, partial thromboplastin time. |
| Number of Participants With Clinically Significant Changes in Urinalysis | Up to 57 months | Urine samples were collected for the analysis of urinalysis parameters: Leucocytes, blood, nitrite, protein, urobilinogen, bilirubin, pH, specific gravity, ketones, glucose. |
| Number of Participants With Clinically Significant Changes in Vital Parameters | Up to 57 months | 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. |
| Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters | Up to 57 months | Twelve-lead ECGs was performed after participants has been recumbent for at least 5 minutes. |
| Number of Participants With Clinically Significant Changes in Physical Examinations | Up to 57 months | 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. |
Countries
Canada, France, Spain, United States
Participant flow
Recruitment details
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.
Pre-assignment details
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 by arm
| Arm | Count |
|---|---|
| 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). | 76 |
| Total | 76 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lack of Efficacy | 6 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Sponsor Decision | 23 |
| Overall Study | Study Termination | 5 |
| Overall Study | Withdrawal by Subject | 11 |
Baseline characteristics
| Characteristic | Losmapimod 15 Milligrams (mg) Twice Daily (BID) |
|---|---|
| Age, Continuous | 46.2 Years STANDARD_DEVIATION 12.43 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 69 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 66 Participants |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 76 |
| other Total, other adverse events | 71 / 76 |
| serious Total, serious adverse events | 7 / 76 |
Outcome results
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.
Time frame: Up to 57 months
Population: Open-Label Analysis Set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Number of Participants Reporting Serious Treatment Emergent Adverse Events (Serious TEAEs) and TEAEs | Any serious TEAE | 7 Participants |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Number of Participants Reporting Serious Treatment Emergent Adverse Events (Serious TEAEs) and TEAEs | Any TEAE | 71 Participants |
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.
Time frame: Up to 57 months
Population: Open-Label Analysis Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Number of Participants With Clinically Significant Changes in Chemistry Parameters | 0 Participants |
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.
Time frame: Up to 57 months
Population: Open-Label Analysis Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters | 0 Participants |
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
Time frame: Up to 57 months
Population: Open-Label Analysis Set:
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Number of Participants With Clinically Significant Changes in Hematology Parameters | 0 Participants |
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.
Time frame: Up to 57 months
Population: Open-Label Analysis Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Number of Participants With Clinically Significant Changes in Physical Examinations | 0 Participants |
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.
Time frame: Up to 57 months
Population: Open-Label Analysis Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Number of Participants With Clinically Significant Changes in Serum Coagulation Parameters | 0 Participants |
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.
Time frame: Up to 57 months
Population: Open-Label Analysis Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Number of Participants With Clinically Significant Changes in Urinalysis | 0 Participants |
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.
Time frame: Up to 57 months
Population: Open-Label Analysis Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Number of Participants With Clinically Significant Changes in Vital Parameters | 0 Participants |