Facioscapulohumeral Muscular Dystrophy (FSHD)
Conditions
Keywords
FSHD, FSHD1, Muscular Dystrophies, Muscular Dystrophy, Facioscapulohumeral Muscular Disorders, Musculoskeletal Diseases, Neuromuscular Diseases
Brief summary
This is a study to evaluate the safety and efficacy of Losmapimod in treating patients with Facioscapulohumeral Muscular Dystrophy (FSHD) over 48 weeks.
Detailed description
This study is a Phase 2, randomized, double-blind, placebo-controlled, parallel-group, multicenter study designed to evaluate the efficacy and safety of losmapimod in treating patients with Facioscapulohumeral Muscular Dystrophy (FSHD) over 48 weeks. Patients will participate in this study for approximately 53 weeks. This will include a 4-week screening period, a 48-week, placebo-controlled treatment period and a 7 day safety follow-up period. Patients must have a confirmed diagnosis of FSHD1 and genetic confirmation must be obtained prior to the screening MRI and baseline muscle biopsy. Patients will be randomized to receive 15 mg of losmapimod or placebo twice daily given as two 7.5 mg tablets per dose by mouth; for a total of 4 pills or 30 mg daily for 48 weeks. All patients will be asked to attend the study clinic for each scheduled visit. The primary endpoint of the study is to evaluate the efficacy of losmapimod in inhibiting or reducing expression of DUX4, as measured by a subset of DUX4-regulated gene transcripts in skeletal muscle biopsies of FSHD patients. Secondary endpoints include evaluation of the safety and tolerability of losmapimod, the plasma concentrations of losmapimod, levels of losmapimod in skeletal muscle and losmapimod target engagement in blood and skeletal muscle in FSHD patients. This study was conducted during the Coronavirus Disease-2019 (COVID-19) Pandemic. The pandemic restrictions limited some assessments in the FSHD1 population in the clinic, including collection of some data for Week 24.
Interventions
Losmapimod will be administered with food when possible.
DRUGPlacebo oral tablet
Placebo will be administered with food when possible
Sponsors
Fulcrum Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
This study will be performed in a double-blind fashion. The investigator, study staff, subjects, sponsor and monitor will remain blinded to the treatment until study closure.
Intervention model description
This study is a randomized, double-blind, placebo-controlled, 48-week parallel-group study.
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 IRB-approved informed consent form that conforms to federal and institutional guidelines. * Male or female subjects * 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. * Clinical severity score of 2 to 4 (RICCI Score; Range 0-5), inclusive at screening * Must have a MRI-eligible muscle for biopsy * 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. * 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. * Known severe renal impairment (defined as a glomerular filtration rate of \<30 mL/min/1.73m2). * Positive screen for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or antibodies against human immunodeficiency virus (HIV)-1 and -2. * 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. * Use of another investigational product within 30 days or 5 half-lives (whichever is longer), or according to local regulations, or currently participating in a study with an investigational product. Note: concurrent participation in other non-drug studies may be acceptable if confirmed in writing by the sponsor.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Double Homeobox 4 (DUX4) Activity in Affected Skeletal Muscle | Baseline and Week 16 to Week 36 | Skeletal muscle biopsies were collected at Baseline and post-Baseline. DUX4 activity in skeletal muscle biopsies was assessed by measuring expression levels of a panel of 6 genes known to be regulated by DUX4. Expression levels of genes were measured using a validated quantitative RT-PCR assay and expressed as Ct (PCR cycles). Raw Ct for each of the 6 genes was normalized to the specified reference genes to generate a normalized Ct. The DUX4 activity is the average of the normalized Cts of each of the identified 6 genes, where the Ct for each of the 6 genes is first normalized to reference genes before the average is generated. Change in Baseline is calculated as \[average delta Ct across the 6 genes post-baseline\] minus \[average delta Ct across the 6 genes at baseline\]. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Relationship of AEs to Losmapimod | Up to Week 48 | An AE is any untoward medical occurrence in a clinical study participant,temporally associated with use of a study intervention, whether or not considered related to study intervention. An 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. Number of participants with relationship of AEs to losmapimod has been presented:Unlikely related(most likely produced by other factors and temporal relationship of AE to drug makes a causal relationship unlikely),not related (no association between drug and AE), possibly related (treatment with drug caused/contributed to AE),probably related (reasonable temporal sequence of event with drug exists) and definitely related (definite causal relationship exists between drug and AE) |
| Number of Participants Who Prematurely Discontinued Study Drug Due to a Treatment Emergent Adverse Event (TEAE) | Up to Week 48 | TEAE was an AE that began 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 worsened in severity on or after the first dose of study drug and before the stop of study drug + 7 days. An AE with completely missing onset and end dates were considered as treatment-emergent AE. Number of participants who prematurely discontinued study drug due to a TEAE has been presented. |
| Change From Baseline in Muscle Fat Fraction (MFF) at Week 12, Week 24 and Week 48 | Baseline and at Week 12, Week 24 and Week 48 | Measurement of the extent of skeletal muscle tissue replacement by fat in FSHD participants were done through automatic skeletal muscle segmentation for the 3D muscle volumes and fat fraction analysis via robust algorithms using Dixon imaging. Composite variables, incorporating pre-selected muscles, were derived for longitudinal analysis of MFF. Baseline was defined as the last non-missing evaluation on or before the day of first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. |
| Change From Baseline in Lean Muscle Volume (LMV) at Week 12, Week 24 and Week 48 | Baseline and at Week 12, Week 24 and Week 48 | Measurement of the extent of skeletal muscle tissue replacement by fat in FSHD participants were done through automatic skeletal muscle segmentation for the 3D muscle volumes and fat fraction analysis via robust algorithms using Dixon imaging. Composite variables, incorporating pre-selected muscles, were derived for longitudinal analysis of LMV. Baseline was defined as the last non-missing evaluation on or before the day of first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. |
| Change From Baseline in Muscle Fat Infiltration (MFI) at Week 12, Week 24 and Week 48 | Baseline and at Week 12, Week 24 and Week 48 | Measurement of the extent of skeletal muscle tissue replacement by fat in FSHD participants were done through automatic skeletal muscle segmentation for the 3D muscle volumes and fat fraction analysis via robust algorithms using Dixon imaging. Composite variables, incorporating pre-selected muscles, were derived for longitudinal analysis of MFI. Baseline was defined as the last non-missing evaluation on or before the day of first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. |
| Plasma Concentration After Administration of Losmapimod | Pre dose, 4 hours post dose, Week 4 pre dose, Week 4: 4 hours post dose, Week 12, Week 16 pre dose, Week 16: 4 hours post dose, Week 24, Week 36 pre dose, Week 36: 4 hours post dose, Week 48 | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of losmapimod. |
| Concentration of Losmapimod in Skeletal Muscle Biopsy | Baseline, Week 16 and Week 36 | Skeletal muscle biopsy samples were collected at indicated time points for the assessment of concentration of losmapimod. |
| Percent Change From Baseline in Phosphorylated Heat Shock Protein 27 (pHSP27)/Total Heat Shock Protein 27 (tHSP27) | Baseline and at Day 1: 4 hours post dose, Week 16: pre dose, Week 16: 4 hours post dose, Week 36 pre dose, Week 36: 4 hours post dose | Blood samples were collected for Pharmacodynamic (PD) analysis of pHSP27/tHSP27. Baseline was defined as the last non-missing evaluation on or before the day of first dose of study drug. Percent change from Baseline was defined as value of post Baseline minus Baseline value divided by Baseline value and multiplied by 100. |
| Number of Participants With Type of Adverse Events (AEs) to Losmapimod | Up to Week 48 | 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 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. A treatment emergent adverse events (TEAE) is defined as any event that was not present before exposure to study drug or any event that was already present but worsens in either intensity or frequency after exposure to study drug. Number of participants with type of AEs to losmapimod has been presented which included: TEAEs and SAEs. |
| Number of Participants With Severity of AEs to Losmapimod | Up to Week 48 | 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. An 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. Number of participants with severity grading of AEs to losmapimod has been presented: Mild (An event that is usually transient in nature and generally does not interfere with normal activities), Moderate (An AE that is sufficiently discomforting to interfere with normal activities) and Severe (An AE that is incapacitating and prevents normal activities). The higher the grade, the more severe the symptoms. |
| Number of Participants With Adverse Events of Special Interest (AESIs) | Up to Week 48 | An AESI (serious or non-serious) is one of scientific and medical concern for which ongoing monitoring and rapid communication by the investigator to the sponsor can be appropriate. Adverse events of special interest for this study included liver tests that met the criteria for potential drug-induced liver injury (DILI), in accordance with the Unites States (US) Food and Drug Administration (FDA) Guidance for Industry-Drug-Induced Liver Injury: Premarketing Clinical Evaluation. Number of participants with AESIs has been presented. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Facioscapulohumeral Muscular Dystrophy (FSDH) TUG Average Completion Time | Baseline and at Week 4, Week 12, Week 24, Week 36 and Week 48 | The TUG test was a simple test that was used to assess a person's mobility and required both static and dynamic balance. It measured the time that a person takes to rise from a chair, walk 3 meters, turn around, walk back to the chair, and sit down. The optimized TUG test was the classic TUG but added the component of getting up from a laying position on a bed-like table in the clinic at the start of the test and laying back down on his or her back at the end of the test. Participants were timed as they started from a seated or laying position, rise to a standing position, walked a total of 6 meters and then returned to either a seated or laying position. Baseline was defined as the last non-missing evaluation on or before the day of first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value |
| Change From Baseline in All Muscles Total Average Strength as Assessed by Hand-held Dynamometry | Baseline and at Week 4, Week 12, Week 24, Week 36 and Week 48 | Quantitative isometric dynamometry (hand-held dynamometer) was used to assess the skeletal muscles strength of study participants in both the upper and lower limbs bilaterally. The MicroFET2 hand-held dynamometer was used to measure strength in the bilateral shoulders, elbow flexors and extensors, and ankle dorsiflexors. The Jamar Plus Digital Hand Dynamometer was used to measure bilateral grip strengths. Baseline was defined as the last non-missing evaluation on or before the day of first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. |
| Change From Baseline in Motor Function Measure (MFM) Domain 1 Score | Baseline and at Week 48 | The MFM scale assessed the severity of the motor deficit as determined by an experienced physical therapist. The MFM domain 1 was a validated evaluator administered functional measure for neuromuscular disorders, with 13 items related to standing and transfers. Generic Values for each domain were: 0 = cannot perform the task, 1 = initiated the task, 2 - performs the movement incompletely, or completely but imperfectly, 3 = performs the task fully and 'normally'. Total score was the sum of all the domains for D1 divided by the maximum score possible and multiplied by 100. Min=0, Max = 100. Lower numbers on the scale represented a worse outcome. Baseline was defined as the last non-missing evaluation on or before the day of first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. |
| Change From Baseline in FSHD Health Index (HI) | Baseline and at Week 48 | The FSHD-HI was a 15-domain questionnaire designed and based on participant interviews to measure total FSHD health-related quality-of-life, including both motor impairment and the social and emotional impact of FSHD. 116 questions were combined into a total score, the score is transformed onto a percentage scale, with score ranging from 0 (no disability) to 100 (maximal disability); lower scores represented decreasing disability. Baseline was defined as last non-missing evaluation on or before the day of first dose of study drug. Change from Baseline was calculated as Baseline minus post-dose value. |
| Number of Participants With Improved and Not Improved Response to Patients' Global Impression of Change (PGIC) | At Week 48 | The PGI-C was a one-time assessment to measure the participant's impression of the how their illness had changed over time. It is a single question that assessed on a scale of 1-7 if there has been an improvement, decline or no change in clinical status. The score ranged from: Responses of 1= Very much improved, 2= Much improved, and 3= Minimally improved which were considered as improved and responses of 4 = No change, 5 = Minimally worse, 6= Much worse, and 7=Very much worse were considered as not improved. Higher scores indicated worse symptoms. |
| Change From Baseline in Reachable Work Space (RWS) Dominant and Non-dominant Total Relative Surface Area (RSA) With Weight Quintant (Q)1 to Q5 | Baseline and Week 4, Week 12, Week 24, Week 36 and Week 48 | The RWS was a 3-dimensional sensor-based system (using a single depth-ranging sensor) that could unobtrusively detect an individual's RWS and reflect an individual global upper extremity function, including shoulder and proximal arm. Participants were seated in front of a 3D camera and asked to perform a standardized upper extremity movement protocol under the supervision of a study clinical evaluator with and without weights and on both the right and left arms at indicated time points. The absolute total RWS surface envelope area as well as areas for each of the quadrants was calculated and provided in a blinded fashion, with no access to treatment assignment information. The RWS RSA represented the portion of the unit hemisphere that was covered by an individual's hand movement. Baseline was defined as the last non-missing evaluation on or before the day of first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. |
| Change From Baseline in Classic Timed Up and Go (TUG) Average Completion Time | Baseline and at Week 4, Week 12, Week 24, Week 36 and Week 48 | The TUG test was a simple test that was used to assess a person's mobility and required both static and dynamic balance. It measured the time that a person takes to rise from a chair, walk 3 meters, turn around, walk back to the chair, and sit down. The optimized TUG test was the classic TUG but added the component of getting up from a laying position on a bed-like table in the clinic at the start of the test and laying back down on his or her back at the end of the test. Participants were timed as they started from a seated or laying position, rise to a standing position, walked a total of 6 meters and then returned to either a seated or laying position. Baseline was defined as the last non-missing evaluation on or before the day of first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value |
Countries
Canada, France, Spain, United States
Participant flow
Pre-assignment details
This study was a randomized, double-blind placebo-controlled treatment period for 48 weeks which evaluated the efficacy and safety of losmapimod.
Participants by arm
| Arm | Count |
|---|---|
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) Participants were randomized to receive losmapimod tablets 15 mg (2×7.5 mg tablets/dose BID) orally (PO) for 48 weeks | 40 |
| Placebo Participants were randomized to receive matching placebo tablets PO BID for 48 weeks. | 40 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Missing | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Placebo | Total | Losmapimod 15 Milligrams (mg) Twice Daily (BID) |
|---|---|---|---|
| Age, Continuous | 45.7 Years STANDARD_DEVIATION 12.69 | 45.7 Years STANDARD_DEVIATION 12.49 | 45.7 Years STANDARD_DEVIATION 12.44 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 3 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 36 Participants | 73 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 5 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) White | 39 Participants | 70 Participants | 31 Participants |
| Sex: Female, Male Female | 14 Participants | 26 Participants | 12 Participants |
| Sex: Female, Male Male | 26 Participants | 54 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 40 |
| other Total, other adverse events | 29 / 40 | 23 / 40 |
| serious Total, serious adverse events | 2 / 40 | 0 / 40 |
Outcome results
Primary
Change From Baseline in Double Homeobox 4 (DUX4) Activity in Affected Skeletal Muscle
Skeletal muscle biopsies were collected at Baseline and post-Baseline. DUX4 activity in skeletal muscle biopsies was assessed by measuring expression levels of a panel of 6 genes known to be regulated by DUX4. Expression levels of genes were measured using a validated quantitative RT-PCR assay and expressed as Ct (PCR cycles). Raw Ct for each of the 6 genes was normalized to the specified reference genes to generate a normalized Ct. The DUX4 activity is the average of the normalized Cts of each of the identified 6 genes, where the Ct for each of the 6 genes is first normalized to reference genes before the average is generated. Change in Baseline is calculated as \[average delta Ct across the 6 genes post-baseline\] minus \[average delta Ct across the 6 genes at baseline\].
Time frame: Baseline and Week 16 to Week 36
Population: Full Analysis Set. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Change From Baseline in Double Homeobox 4 (DUX4) Activity in Affected Skeletal Muscle | 0.8292 Delta threshold cycle (Ct) | Standard Error 0.6138 |
| Placebo | Change From Baseline in Double Homeobox 4 (DUX4) Activity in Affected Skeletal Muscle | 0.4008 Delta threshold cycle (Ct) | Standard Error 0.6491 |
p-value: 0.562195% CI: [-1.0376, 1.8945]ANCOVA
Secondary
Change From Baseline in Lean Muscle Volume (LMV) at Week 12, Week 24 and Week 48
Measurement of the extent of skeletal muscle tissue replacement by fat in FSHD participants were done through automatic skeletal muscle segmentation for the 3D muscle volumes and fat fraction analysis via robust algorithms using Dixon imaging. Composite variables, incorporating pre-selected muscles, were derived for longitudinal analysis of LMV. Baseline was defined as the last non-missing evaluation on or before the day of first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline and at Week 12, Week 24 and Week 48
Population: Full Analysis Set. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Change From Baseline in Lean Muscle Volume (LMV) at Week 12, Week 24 and Week 48 | Week 12 | -0.02 Liter | Standard Deviation 0.069 |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Change From Baseline in Lean Muscle Volume (LMV) at Week 12, Week 24 and Week 48 | Week 48 | -0.10 Liter | Standard Deviation 0.093 |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Change From Baseline in Lean Muscle Volume (LMV) at Week 12, Week 24 and Week 48 | Week 24 | 0.00 Liter | Standard Deviation 0.032 |
| Placebo | Change From Baseline in Lean Muscle Volume (LMV) at Week 12, Week 24 and Week 48 | Week 24 | -0.04 Liter | Standard Deviation 0.045 |
| Placebo | Change From Baseline in Lean Muscle Volume (LMV) at Week 12, Week 24 and Week 48 | Week 48 | -0.10 Liter | Standard Deviation 0.114 |
| Placebo | Change From Baseline in Lean Muscle Volume (LMV) at Week 12, Week 24 and Week 48 | Week 12 | -0.01 Liter | Standard Deviation 0.067 |
Secondary
Change From Baseline in Muscle Fat Fraction (MFF) at Week 12, Week 24 and Week 48
Measurement of the extent of skeletal muscle tissue replacement by fat in FSHD participants were done through automatic skeletal muscle segmentation for the 3D muscle volumes and fat fraction analysis via robust algorithms using Dixon imaging. Composite variables, incorporating pre-selected muscles, were derived for longitudinal analysis of MFF. Baseline was defined as the last non-missing evaluation on or before the day of first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline and at Week 12, Week 24 and Week 48
Population: Full Analysis Set. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Change From Baseline in Muscle Fat Fraction (MFF) at Week 12, Week 24 and Week 48 | Week 12 | 0.53 Percentage point | Standard Deviation 1.433 |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Change From Baseline in Muscle Fat Fraction (MFF) at Week 12, Week 24 and Week 48 | Week 24 | 0.45 Percentage point | Standard Deviation 1.053 |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Change From Baseline in Muscle Fat Fraction (MFF) at Week 12, Week 24 and Week 48 | Week 48 | 1.22 Percentage point | Standard Deviation 2.269 |
| Placebo | Change From Baseline in Muscle Fat Fraction (MFF) at Week 12, Week 24 and Week 48 | Week 24 | 0.99 Percentage point | Standard Deviation 1.723 |
| Placebo | Change From Baseline in Muscle Fat Fraction (MFF) at Week 12, Week 24 and Week 48 | Week 48 | 1.67 Percentage point | Standard Deviation 2.011 |
| Placebo | Change From Baseline in Muscle Fat Fraction (MFF) at Week 12, Week 24 and Week 48 | Week 12 | 0.52 Percentage point | Standard Deviation 1.783 |
Secondary
Change From Baseline in Muscle Fat Infiltration (MFI) at Week 12, Week 24 and Week 48
Measurement of the extent of skeletal muscle tissue replacement by fat in FSHD participants were done through automatic skeletal muscle segmentation for the 3D muscle volumes and fat fraction analysis via robust algorithms using Dixon imaging. Composite variables, incorporating pre-selected muscles, were derived for longitudinal analysis of MFI. Baseline was defined as the last non-missing evaluation on or before the day of first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline and at Week 12, Week 24 and Week 48
Population: Full Analysis Set. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Change From Baseline in Muscle Fat Infiltration (MFI) at Week 12, Week 24 and Week 48 | Week 12 | -0.02 Percentage point | Standard Deviation 0.842 |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Change From Baseline in Muscle Fat Infiltration (MFI) at Week 12, Week 24 and Week 48 | Week 24 | -0.16 Percentage point | Standard Deviation 0.438 |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Change From Baseline in Muscle Fat Infiltration (MFI) at Week 12, Week 24 and Week 48 | Week 48 | 0.07 Percentage point | Standard Deviation 0.796 |
| Placebo | Change From Baseline in Muscle Fat Infiltration (MFI) at Week 12, Week 24 and Week 48 | Week 12 | 0.24 Percentage point | Standard Deviation 0.547 |
| Placebo | Change From Baseline in Muscle Fat Infiltration (MFI) at Week 12, Week 24 and Week 48 | Week 24 | 0.49 Percentage point | Standard Deviation 0.921 |
| Placebo | Change From Baseline in Muscle Fat Infiltration (MFI) at Week 12, Week 24 and Week 48 | Week 48 | 0.47 Percentage point | Standard Deviation 0.655 |
Secondary
Concentration of Losmapimod in Skeletal Muscle Biopsy
Skeletal muscle biopsy samples were collected at indicated time points for the assessment of concentration of losmapimod.
Time frame: Baseline, Week 16 and Week 36
Population: Pharmacokinetics Analysis Set. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Concentration of Losmapimod in Skeletal Muscle Biopsy | Baseline | 0.301 Nanogram per gram |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Concentration of Losmapimod in Skeletal Muscle Biopsy | Week 16 | 56.450 Nanogram per gram |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Concentration of Losmapimod in Skeletal Muscle Biopsy | Week 36 | 93.800 Nanogram per gram |
Secondary
Number of Participants Who Prematurely Discontinued Study Drug Due to a Treatment Emergent Adverse Event (TEAE)
TEAE was an AE that began 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 worsened in severity on or after the first dose of study drug and before the stop of study drug + 7 days. An AE with completely missing onset and end dates were considered as treatment-emergent AE. Number of participants who prematurely discontinued study drug due to a TEAE has been presented.
Time frame: Up to Week 48
Population: Safety Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Number of Participants Who Prematurely Discontinued Study Drug Due to a Treatment Emergent Adverse Event (TEAE) | 0 Participants |
| Placebo | Number of Participants Who Prematurely Discontinued Study Drug Due to a Treatment Emergent Adverse Event (TEAE) | 0 Participants |
Secondary
Number of Participants With Adverse Events of Special Interest (AESIs)
An AESI (serious or non-serious) is one of scientific and medical concern for which ongoing monitoring and rapid communication by the investigator to the sponsor can be appropriate. Adverse events of special interest for this study included liver tests that met the criteria for potential drug-induced liver injury (DILI), in accordance with the Unites States (US) Food and Drug Administration (FDA) Guidance for Industry-Drug-Induced Liver Injury: Premarketing Clinical Evaluation. Number of participants with AESIs has been presented.
Time frame: Up to Week 48
Population: Safety Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Number of Participants With Adverse Events of Special Interest (AESIs) | 0 Participants |
| Placebo | Number of Participants With Adverse Events of Special Interest (AESIs) | 0 Participants |
Secondary
Number of Participants With Relationship of AEs to Losmapimod
An AE is any untoward medical occurrence in a clinical study participant,temporally associated with use of a study intervention, whether or not considered related to study intervention. An 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. Number of participants with relationship of AEs to losmapimod has been presented:Unlikely related(most likely produced by other factors and temporal relationship of AE to drug makes a causal relationship unlikely),not related (no association between drug and AE), possibly related (treatment with drug caused/contributed to AE),probably related (reasonable temporal sequence of event with drug exists) and definitely related (definite causal relationship exists between drug and AE)
Time frame: Up to Week 48
Population: Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Number of Participants With Relationship of AEs to Losmapimod | Relationship: Unlikely related | 4 Participants |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Number of Participants With Relationship of AEs to Losmapimod | Relationship: Not related | 16 Participants |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Number of Participants With Relationship of AEs to Losmapimod | Relationship: Possibly related | 9 Participants |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Number of Participants With Relationship of AEs to Losmapimod | Relationship: Probably related | 0 Participants |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Number of Participants With Relationship of AEs to Losmapimod | Relationship: Definitely related | 0 Participants |
| Placebo | Number of Participants With Relationship of AEs to Losmapimod | Relationship: Definitely related | 0 Participants |
| Placebo | Number of Participants With Relationship of AEs to Losmapimod | Relationship: Probably related | 1 Participants |
| Placebo | Number of Participants With Relationship of AEs to Losmapimod | Relationship: Not related | 14 Participants |
| Placebo | Number of Participants With Relationship of AEs to Losmapimod | Relationship: Unlikely related | 7 Participants |
| Placebo | Number of Participants With Relationship of AEs to Losmapimod | Relationship: Possibly related | 1 Participants |
Secondary
Number of Participants With Severity of AEs to Losmapimod
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. An 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. Number of participants with severity grading of AEs to losmapimod has been presented: Mild (An event that is usually transient in nature and generally does not interfere with normal activities), Moderate (An AE that is sufficiently discomforting to interfere with normal activities) and Severe (An AE that is incapacitating and prevents normal activities). The higher the grade, the more severe the symptoms.
Time frame: Up to Week 48
Population: Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Number of Participants With Severity of AEs to Losmapimod | Severity: Mild | 18 Participants |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Number of Participants With Severity of AEs to Losmapimod | Severity: Moderate | 9 Participants |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Number of Participants With Severity of AEs to Losmapimod | Severity: Severe | 2 Participants |
| Placebo | Number of Participants With Severity of AEs to Losmapimod | Severity: Mild | 15 Participants |
| Placebo | Number of Participants With Severity of AEs to Losmapimod | Severity: Moderate | 8 Participants |
| Placebo | Number of Participants With Severity of AEs to Losmapimod | Severity: Severe | 0 Participants |
Secondary
Number of Participants With Type of Adverse Events (AEs) to Losmapimod
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 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. A treatment emergent adverse events (TEAE) is defined as any event that was not present before exposure to study drug or any event that was already present but worsens in either intensity or frequency after exposure to study drug. Number of participants with type of AEs to losmapimod has been presented which included: TEAEs and SAEs.
Time frame: Up to Week 48
Population: Safety Analysis Set: included all participants who received any study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Number of Participants With Type of Adverse Events (AEs) to Losmapimod | Type: TEAEs | 29 Participants |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Number of Participants With Type of Adverse Events (AEs) to Losmapimod | Type: SAEs | 2 Participants |
| Placebo | Number of Participants With Type of Adverse Events (AEs) to Losmapimod | Type: TEAEs | 23 Participants |
| Placebo | Number of Participants With Type of Adverse Events (AEs) to Losmapimod | Type: SAEs | 0 Participants |
Secondary
Percent Change From Baseline in Phosphorylated Heat Shock Protein 27 (pHSP27)/Total Heat Shock Protein 27 (tHSP27)
Blood samples were collected for Pharmacodynamic (PD) analysis of pHSP27/tHSP27. Baseline was defined as the last non-missing evaluation on or before the day of first dose of study drug. Percent change from Baseline was defined as value of post Baseline minus Baseline value divided by Baseline value and multiplied by 100.
Time frame: Baseline and at Day 1: 4 hours post dose, Week 16: pre dose, Week 16: 4 hours post dose, Week 36 pre dose, Week 36: 4 hours post dose
Population: Pharmacodynamics Analysis Set: included all participants who received at least 1 dose of losmapimod and have evaluable PD data for losmapimod. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Percent Change From Baseline in Phosphorylated Heat Shock Protein 27 (pHSP27)/Total Heat Shock Protein 27 (tHSP27) | Day 1: 4 hours post dose | -34.228 Percent change | Standard Deviation 21.3731 |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Percent Change From Baseline in Phosphorylated Heat Shock Protein 27 (pHSP27)/Total Heat Shock Protein 27 (tHSP27) | Week 16: pre dose | 16.392 Percent change | Standard Deviation 102.7915 |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Percent Change From Baseline in Phosphorylated Heat Shock Protein 27 (pHSP27)/Total Heat Shock Protein 27 (tHSP27) | Week 36 pre dose | -46.203 Percent change | Standard Deviation 28.4928 |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Percent Change From Baseline in Phosphorylated Heat Shock Protein 27 (pHSP27)/Total Heat Shock Protein 27 (tHSP27) | Week 36: 4 hours post dose | -62.250 Percent change | Standard Deviation 18.6709 |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Percent Change From Baseline in Phosphorylated Heat Shock Protein 27 (pHSP27)/Total Heat Shock Protein 27 (tHSP27) | Week 16: 4 hours post dose | -18.888 Percent change | Standard Deviation 59.0971 |
| Placebo | Percent Change From Baseline in Phosphorylated Heat Shock Protein 27 (pHSP27)/Total Heat Shock Protein 27 (tHSP27) | Week 36 pre dose | 20.445 Percent change | Standard Deviation 203.8013 |
| Placebo | Percent Change From Baseline in Phosphorylated Heat Shock Protein 27 (pHSP27)/Total Heat Shock Protein 27 (tHSP27) | Day 1: 4 hours post dose | 10.968 Percent change | Standard Deviation 41.3115 |
| Placebo | Percent Change From Baseline in Phosphorylated Heat Shock Protein 27 (pHSP27)/Total Heat Shock Protein 27 (tHSP27) | Week 16: pre dose | 39.497 Percent change | Standard Deviation 92.6947 |
| Placebo | Percent Change From Baseline in Phosphorylated Heat Shock Protein 27 (pHSP27)/Total Heat Shock Protein 27 (tHSP27) | Week 16: 4 hours post dose | 34.176 Percent change | Standard Deviation 83.1994 |
| Placebo | Percent Change From Baseline in Phosphorylated Heat Shock Protein 27 (pHSP27)/Total Heat Shock Protein 27 (tHSP27) | Week 36: 4 hours post dose | -8.908 Percent change | Standard Deviation 74.6476 |
Secondary
Plasma Concentration After Administration of Losmapimod
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of losmapimod.
Time frame: Pre dose, 4 hours post dose, Week 4 pre dose, Week 4: 4 hours post dose, Week 12, Week 16 pre dose, Week 16: 4 hours post dose, Week 24, Week 36 pre dose, Week 36: 4 hours post dose, Week 48
Population: Pharmacokinetics Analysis Set: included all participants who received at least 1 dose of losmapimod and had an evaluable PK data for losmapimod. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Plasma Concentration After Administration of Losmapimod | Week 16: 4 hours post dose | 82.450 Nanogram per milliliter |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Plasma Concentration After Administration of Losmapimod | Week 24 | 62.150 Nanogram per milliliter |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Plasma Concentration After Administration of Losmapimod | Week 36 pre dose | 25.100 Nanogram per milliliter |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Plasma Concentration After Administration of Losmapimod | Week 36: 4 hours post dose | 68.200 Nanogram per milliliter |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Plasma Concentration After Administration of Losmapimod | Week 48 | 73.400 Nanogram per milliliter |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Plasma Concentration After Administration of Losmapimod | Pre dose | NA Nanogram per milliliter |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Plasma Concentration After Administration of Losmapimod | 4 hours post dose | 61.200 Nanogram per milliliter |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Plasma Concentration After Administration of Losmapimod | Week 4 pre dose | 27.000 Nanogram per milliliter |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Plasma Concentration After Administration of Losmapimod | Week 4: 4 hours post dose | 87.600 Nanogram per milliliter |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Plasma Concentration After Administration of Losmapimod | Week 12 | 58.300 Nanogram per milliliter |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Plasma Concentration After Administration of Losmapimod | Week 16 pre dose | 31.900 Nanogram per milliliter |
Other Pre-specified
Change From Baseline in All Muscles Total Average Strength as Assessed by Hand-held Dynamometry
Quantitative isometric dynamometry (hand-held dynamometer) was used to assess the skeletal muscles strength of study participants in both the upper and lower limbs bilaterally. The MicroFET2 hand-held dynamometer was used to measure strength in the bilateral shoulders, elbow flexors and extensors, and ankle dorsiflexors. The Jamar Plus Digital Hand Dynamometer was used to measure bilateral grip strengths. Baseline was defined as the last non-missing evaluation on or before the day of first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline and at Week 4, Week 12, Week 24, Week 36 and Week 48
Population: Full Analysis Set. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Change From Baseline in All Muscles Total Average Strength as Assessed by Hand-held Dynamometry | Week 4 | 5.064 Kilograms | Standard Deviation 15.3103 |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Change From Baseline in All Muscles Total Average Strength as Assessed by Hand-held Dynamometry | Week 36 | -3.608 Kilograms | Standard Deviation 33.1467 |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Change From Baseline in All Muscles Total Average Strength as Assessed by Hand-held Dynamometry | Week 48 | -5.358 Kilograms | Standard Deviation 22.0734 |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Change From Baseline in All Muscles Total Average Strength as Assessed by Hand-held Dynamometry | Week 12 | 1.439 Kilograms | Standard Deviation 11.5791 |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Change From Baseline in All Muscles Total Average Strength as Assessed by Hand-held Dynamometry | Week 24 | -1.551 Kilograms | Standard Deviation 22.892 |
| Placebo | Change From Baseline in All Muscles Total Average Strength as Assessed by Hand-held Dynamometry | Week 36 | -11.772 Kilograms | Standard Deviation 22.7106 |
| Placebo | Change From Baseline in All Muscles Total Average Strength as Assessed by Hand-held Dynamometry | Week 4 | -1.386 Kilograms | Standard Deviation 9.2043 |
| Placebo | Change From Baseline in All Muscles Total Average Strength as Assessed by Hand-held Dynamometry | Week 12 | -0.230 Kilograms | Standard Deviation 9.5417 |
| Placebo | Change From Baseline in All Muscles Total Average Strength as Assessed by Hand-held Dynamometry | Week 24 | -9.477 Kilograms | Standard Deviation 15.6318 |
| Placebo | Change From Baseline in All Muscles Total Average Strength as Assessed by Hand-held Dynamometry | Week 48 | -15.021 Kilograms | Standard Deviation 28.3042 |
Other Pre-specified
Change From Baseline in Classic Timed Up and Go (TUG) Average Completion Time
The TUG test was a simple test that was used to assess a person's mobility and required both static and dynamic balance. It measured the time that a person takes to rise from a chair, walk 3 meters, turn around, walk back to the chair, and sit down. The optimized TUG test was the classic TUG but added the component of getting up from a laying position on a bed-like table in the clinic at the start of the test and laying back down on his or her back at the end of the test. Participants were timed as they started from a seated or laying position, rise to a standing position, walked a total of 6 meters and then returned to either a seated or laying position. Baseline was defined as the last non-missing evaluation on or before the day of first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value
Time frame: Baseline and at Week 4, Week 12, Week 24, Week 36 and Week 48
Population: Full Analysis Set. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Change From Baseline in Classic Timed Up and Go (TUG) Average Completion Time | Week 12 | -0.340 Seconds | Standard Deviation 2.5908 |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Change From Baseline in Classic Timed Up and Go (TUG) Average Completion Time | Week 24 | 0.960 Seconds | Standard Deviation 2.8012 |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Change From Baseline in Classic Timed Up and Go (TUG) Average Completion Time | Week 48 | -0.340 Seconds | Standard Deviation 2.1289 |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Change From Baseline in Classic Timed Up and Go (TUG) Average Completion Time | Week 36 | 0.252 Seconds | Standard Deviation 2.8725 |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Change From Baseline in Classic Timed Up and Go (TUG) Average Completion Time | Week 4 | 2.011 Seconds | Standard Deviation 16.8603 |
| Placebo | Change From Baseline in Classic Timed Up and Go (TUG) Average Completion Time | Week 48 | 0.789 Seconds | Standard Deviation 1.7059 |
| Placebo | Change From Baseline in Classic Timed Up and Go (TUG) Average Completion Time | Week 4 | 0.297 Seconds | Standard Deviation 2.0577 |
| Placebo | Change From Baseline in Classic Timed Up and Go (TUG) Average Completion Time | Week 12 | 0.183 Seconds | Standard Deviation 1.7839 |
| Placebo | Change From Baseline in Classic Timed Up and Go (TUG) Average Completion Time | Week 24 | 0.384 Seconds | Standard Deviation 1.9678 |
| Placebo | Change From Baseline in Classic Timed Up and Go (TUG) Average Completion Time | Week 36 | 0.709 Seconds | Standard Deviation 1.6041 |
Other Pre-specified
Change From Baseline in Facioscapulohumeral Muscular Dystrophy (FSDH) TUG Average Completion Time
The TUG test was a simple test that was used to assess a person's mobility and required both static and dynamic balance. It measured the time that a person takes to rise from a chair, walk 3 meters, turn around, walk back to the chair, and sit down. The optimized TUG test was the classic TUG but added the component of getting up from a laying position on a bed-like table in the clinic at the start of the test and laying back down on his or her back at the end of the test. Participants were timed as they started from a seated or laying position, rise to a standing position, walked a total of 6 meters and then returned to either a seated or laying position. Baseline was defined as the last non-missing evaluation on or before the day of first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value
Time frame: Baseline and at Week 4, Week 12, Week 24, Week 36 and Week 48
Population: Full Analysis Set. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Change From Baseline in Facioscapulohumeral Muscular Dystrophy (FSDH) TUG Average Completion Time | Week 12 | -0.380 Seconds | Standard Deviation 2.7827 |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Change From Baseline in Facioscapulohumeral Muscular Dystrophy (FSDH) TUG Average Completion Time | Week 36 | -0.653 Seconds | Standard Deviation 4.1121 |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Change From Baseline in Facioscapulohumeral Muscular Dystrophy (FSDH) TUG Average Completion Time | Week 24 | 0.549 Seconds | Standard Deviation 2.9794 |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Change From Baseline in Facioscapulohumeral Muscular Dystrophy (FSDH) TUG Average Completion Time | Week 48 | 0.342 Seconds | Standard Deviation 3.7028 |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Change From Baseline in Facioscapulohumeral Muscular Dystrophy (FSDH) TUG Average Completion Time | Week 4 | -0.993 Seconds | Standard Deviation 3.4234 |
| Placebo | Change From Baseline in Facioscapulohumeral Muscular Dystrophy (FSDH) TUG Average Completion Time | Week 48 | 0.334 Seconds | Standard Deviation 2.0296 |
| Placebo | Change From Baseline in Facioscapulohumeral Muscular Dystrophy (FSDH) TUG Average Completion Time | Week 4 | 0.750 Seconds | Standard Deviation 2.1824 |
| Placebo | Change From Baseline in Facioscapulohumeral Muscular Dystrophy (FSDH) TUG Average Completion Time | Week 12 | 0.058 Seconds | Standard Deviation 1.7805 |
| Placebo | Change From Baseline in Facioscapulohumeral Muscular Dystrophy (FSDH) TUG Average Completion Time | Week 24 | 0.304 Seconds | Standard Deviation 1.8555 |
| Placebo | Change From Baseline in Facioscapulohumeral Muscular Dystrophy (FSDH) TUG Average Completion Time | Week 36 | 0.389 Seconds | Standard Deviation 1.7394 |
Other Pre-specified
Change From Baseline in FSHD Health Index (HI)
The FSHD-HI was a 15-domain questionnaire designed and based on participant interviews to measure total FSHD health-related quality-of-life, including both motor impairment and the social and emotional impact of FSHD. 116 questions were combined into a total score, the score is transformed onto a percentage scale, with score ranging from 0 (no disability) to 100 (maximal disability); lower scores represented decreasing disability. Baseline was defined as last non-missing evaluation on or before the day of first dose of study drug. Change from Baseline was calculated as Baseline minus post-dose value.
Time frame: Baseline and at Week 48
Population: Full Analysis Set. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Change From Baseline in FSHD Health Index (HI) | 1.17 Scores on a scale | Standard Deviation 13.499 |
| Placebo | Change From Baseline in FSHD Health Index (HI) | -0.64 Scores on a scale | Standard Deviation 8.024 |
Other Pre-specified
Change From Baseline in Motor Function Measure (MFM) Domain 1 Score
The MFM scale assessed the severity of the motor deficit as determined by an experienced physical therapist. The MFM domain 1 was a validated evaluator administered functional measure for neuromuscular disorders, with 13 items related to standing and transfers. Generic Values for each domain were: 0 = cannot perform the task, 1 = initiated the task, 2 - performs the movement incompletely, or completely but imperfectly, 3 = performs the task fully and 'normally'. Total score was the sum of all the domains for D1 divided by the maximum score possible and multiplied by 100. Min=0, Max = 100. Lower numbers on the scale represented a worse outcome. Baseline was defined as the last non-missing evaluation on or before the day of first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline and at Week 48
Population: Full Analysis Set. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Change From Baseline in Motor Function Measure (MFM) Domain 1 Score | 2.76 Scores on a scale | Standard Deviation 9.079 |
| Placebo | Change From Baseline in Motor Function Measure (MFM) Domain 1 Score | 2.00 Scores on a scale | Standard Deviation 8.78 |
Other Pre-specified
Change From Baseline in Reachable Work Space (RWS) Dominant and Non-dominant Total Relative Surface Area (RSA) With Weight Quintant (Q)1 to Q5
The RWS was a 3-dimensional sensor-based system (using a single depth-ranging sensor) that could unobtrusively detect an individual's RWS and reflect an individual global upper extremity function, including shoulder and proximal arm. Participants were seated in front of a 3D camera and asked to perform a standardized upper extremity movement protocol under the supervision of a study clinical evaluator with and without weights and on both the right and left arms at indicated time points. The absolute total RWS surface envelope area as well as areas for each of the quadrants was calculated and provided in a blinded fashion, with no access to treatment assignment information. The RWS RSA represented the portion of the unit hemisphere that was covered by an individual's hand movement. Baseline was defined as the last non-missing evaluation on or before the day of first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline and Week 4, Week 12, Week 24, Week 36 and Week 48
Population: Full Analysis Set. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Change From Baseline in Reachable Work Space (RWS) Dominant and Non-dominant Total Relative Surface Area (RSA) With Weight Quintant (Q)1 to Q5 | Week 4: Dominant Total RSA Weighted Q1 to Q5 | -0.0009 Unitless | Standard Deviation 0.07652 |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Change From Baseline in Reachable Work Space (RWS) Dominant and Non-dominant Total Relative Surface Area (RSA) With Weight Quintant (Q)1 to Q5 | Week 24: Dominant Total RSA Weighted Q1 to Q5 | -0.0066 Unitless | Standard Deviation 0.10246 |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Change From Baseline in Reachable Work Space (RWS) Dominant and Non-dominant Total Relative Surface Area (RSA) With Weight Quintant (Q)1 to Q5 | Week 36: Dominant Total RSA Weighted Q1 to Q5 | -0.0169 Unitless | Standard Deviation 0.09346 |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Change From Baseline in Reachable Work Space (RWS) Dominant and Non-dominant Total Relative Surface Area (RSA) With Weight Quintant (Q)1 to Q5 | Week 48: Dominant Total RSA Weighted Q1 to Q5 | 0.0103 Unitless | Standard Deviation 0.07273 |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Change From Baseline in Reachable Work Space (RWS) Dominant and Non-dominant Total Relative Surface Area (RSA) With Weight Quintant (Q)1 to Q5 | Week 4: Non-Dominant Total RSA Weighted Q1 to Q5 | 0.0077 Unitless | Standard Deviation 0.07212 |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Change From Baseline in Reachable Work Space (RWS) Dominant and Non-dominant Total Relative Surface Area (RSA) With Weight Quintant (Q)1 to Q5 | Week 12: Non-Dominant Total RSA Weighted Q1 to Q5 | 0.0156 Unitless | Standard Deviation 0.07221 |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Change From Baseline in Reachable Work Space (RWS) Dominant and Non-dominant Total Relative Surface Area (RSA) With Weight Quintant (Q)1 to Q5 | Week 24: Non-Dominant Total RSA Weighted Q1 to Q5 | 0.0259 Unitless | Standard Deviation 0.0696 |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Change From Baseline in Reachable Work Space (RWS) Dominant and Non-dominant Total Relative Surface Area (RSA) With Weight Quintant (Q)1 to Q5 | Week 12: Dominant Total RSA Weighted Q1 to Q5 | 0.0109 Unitless | Standard Deviation 0.09214 |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Change From Baseline in Reachable Work Space (RWS) Dominant and Non-dominant Total Relative Surface Area (RSA) With Weight Quintant (Q)1 to Q5 | Week 36: Non-Dominant Total RSA Weighted Q1 to Q5 | 0.0287 Unitless | Standard Deviation 0.09934 |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Change From Baseline in Reachable Work Space (RWS) Dominant and Non-dominant Total Relative Surface Area (RSA) With Weight Quintant (Q)1 to Q5 | Week 48: Non-Dominant Total RSA Weighted Q1 to Q5 | 0.0169 Unitless | Standard Deviation 0.0909 |
| Placebo | Change From Baseline in Reachable Work Space (RWS) Dominant and Non-dominant Total Relative Surface Area (RSA) With Weight Quintant (Q)1 to Q5 | Week 12: Non-Dominant Total RSA Weighted Q1 to Q5 | 0.0084 Unitless | Standard Deviation 0.08577 |
| Placebo | Change From Baseline in Reachable Work Space (RWS) Dominant and Non-dominant Total Relative Surface Area (RSA) With Weight Quintant (Q)1 to Q5 | Week 12: Dominant Total RSA Weighted Q1 to Q5 | -0.0069 Unitless | Standard Deviation 0.09547 |
| Placebo | Change From Baseline in Reachable Work Space (RWS) Dominant and Non-dominant Total Relative Surface Area (RSA) With Weight Quintant (Q)1 to Q5 | Week 24: Dominant Total RSA Weighted Q1 to Q5 | -0.0094 Unitless | Standard Deviation 0.10672 |
| Placebo | Change From Baseline in Reachable Work Space (RWS) Dominant and Non-dominant Total Relative Surface Area (RSA) With Weight Quintant (Q)1 to Q5 | Week 24: Non-Dominant Total RSA Weighted Q1 to Q5 | 0.0114 Unitless | Standard Deviation 0.09087 |
| Placebo | Change From Baseline in Reachable Work Space (RWS) Dominant and Non-dominant Total Relative Surface Area (RSA) With Weight Quintant (Q)1 to Q5 | Week 36: Dominant Total RSA Weighted Q1 to Q5 | -0.0371 Unitless | Standard Deviation 0.12235 |
| Placebo | Change From Baseline in Reachable Work Space (RWS) Dominant and Non-dominant Total Relative Surface Area (RSA) With Weight Quintant (Q)1 to Q5 | Week 48: Non-Dominant Total RSA Weighted Q1 to Q5 | -0.0129 Unitless | Standard Deviation 0.09841 |
| Placebo | Change From Baseline in Reachable Work Space (RWS) Dominant and Non-dominant Total Relative Surface Area (RSA) With Weight Quintant (Q)1 to Q5 | Week 48: Dominant Total RSA Weighted Q1 to Q5 | -0.0267 Unitless | Standard Deviation 0.08972 |
| Placebo | Change From Baseline in Reachable Work Space (RWS) Dominant and Non-dominant Total Relative Surface Area (RSA) With Weight Quintant (Q)1 to Q5 | Week 4: Dominant Total RSA Weighted Q1 to Q5 | -0.0022 Unitless | Standard Deviation 0.06615 |
| Placebo | Change From Baseline in Reachable Work Space (RWS) Dominant and Non-dominant Total Relative Surface Area (RSA) With Weight Quintant (Q)1 to Q5 | Week 4: Non-Dominant Total RSA Weighted Q1 to Q5 | 0.0189 Unitless | Standard Deviation 0.07697 |
| Placebo | Change From Baseline in Reachable Work Space (RWS) Dominant and Non-dominant Total Relative Surface Area (RSA) With Weight Quintant (Q)1 to Q5 | Week 36: Non-Dominant Total RSA Weighted Q1 to Q5 | -0.0069 Unitless | Standard Deviation 0.0977 |
Other Pre-specified
Number of Participants With Improved and Not Improved Response to Patients' Global Impression of Change (PGIC)
The PGI-C was a one-time assessment to measure the participant's impression of the how their illness had changed over time. It is a single question that assessed on a scale of 1-7 if there has been an improvement, decline or no change in clinical status. The score ranged from: Responses of 1= Very much improved, 2= Much improved, and 3= Minimally improved which were considered as improved and responses of 4 = No change, 5 = Minimally worse, 6= Much worse, and 7=Very much worse were considered as not improved. Higher scores indicated worse symptoms.
Time frame: At Week 48
Population: Full Analysis Set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Number of Participants With Improved and Not Improved Response to Patients' Global Impression of Change (PGIC) | Improved: Week 48 | 8 Participants |
| Losmapimod 15 Milligrams (mg) Twice Daily (BID) | Number of Participants With Improved and Not Improved Response to Patients' Global Impression of Change (PGIC) | Not Improved: Week 48 | 21 Participants |
| Placebo | Number of Participants With Improved and Not Improved Response to Patients' Global Impression of Change (PGIC) | Improved: Week 48 | 2 Participants |
| Placebo | Number of Participants With Improved and Not Improved Response to Patients' Global Impression of Change (PGIC) | Not Improved: Week 48 | 29 Participants |