Trial Outcomes & Findings for Efficacy and Safety of Losmapimod in Subjects With Facioscapulohumeral Muscular Dystrophy (FSHD) (NCT NCT04003974)

Last Updated: 2024-07-10

Results Overview

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 \[average delta Ct across the 6 genes at baseline\].

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

80 participants

Primary outcome timeframe

Baseline and Week 16 to Week 36

Results posted on

2024-07-10

Participant Flow

This study was a randomized, double-blind placebo-controlled treatment period for 48 weeks which evaluated the efficacy and safety of losmapimod.

Participant milestones

Participant milestones
Measure	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	Placebo Participants were randomized to receive matching placebo tablets PO BID for 48 weeks.
Overall Study STARTED	40	40
Overall Study COMPLETED	39	38
Overall Study NOT COMPLETED	1	2

Reasons for withdrawal

Reasons for withdrawal
Measure	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	Placebo Participants were randomized to receive matching placebo tablets PO BID for 48 weeks.
Overall Study Missing	1	0
Overall Study Withdrawal by Subject	0	2

Baseline Characteristics

Efficacy and Safety of Losmapimod in Subjects With Facioscapulohumeral Muscular Dystrophy (FSHD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Losmapimod 15 Milligrams (mg) Twice Daily (BID) n=40 Participants Participants were randomized to receive losmapimod tablets 15 mg (2×7.5 mg tablets/dose BID) orally (PO) for 48 weeks	Placebo n=40 Participants Participants were randomized to receive matching placebo tablets PO BID for 48 weeks.	Total n=80 Participants Total of all reporting groups
Age, Continuous	45.7 Years STANDARD_DEVIATION 12.44 • n=5 Participants	45.7 Years STANDARD_DEVIATION 12.69 • n=7 Participants	45.7 Years STANDARD_DEVIATION 12.49 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	14 Participants n=7 Participants	26 Participants n=5 Participants
Sex: Female, Male Male	28 Participants n=5 Participants	26 Participants n=7 Participants	54 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	37 Participants n=5 Participants	36 Participants n=7 Participants	73 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	31 Participants n=5 Participants	39 Participants n=7 Participants	70 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 16 to Week 36

Population: Full Analysis Set. Only those participants with data available at the specified data points were analyzed.

Outcome measures

Outcome measures
Measure	Losmapimod 15 Milligrams (mg) Twice Daily (BID) n=39 Participants Participants were randomized to receive losmapimod tablets 15 mg (2×7.5 mg tablets/dose BID) orally (PO) for 48 weeks	Placebo n=38 Participants Participants were randomized to receive matching placebo tablets PO BID for 48 weeks.
Change From Baseline in Double Homeobox 4 (DUX4) Activity in Affected Skeletal Muscle	0.8292 Delta threshold cycle (Ct) Standard Error 0.6138	0.4008 Delta threshold cycle (Ct) Standard Error 0.6491

SECONDARY outcome

Timeframe: Up to Week 48

Population: Safety Analysis Set: included all participants who received any study drug.

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.

Outcome measures

Outcome measures
Measure	Losmapimod 15 Milligrams (mg) Twice Daily (BID) n=40 Participants Participants were randomized to receive losmapimod tablets 15 mg (2×7.5 mg tablets/dose BID) orally (PO) for 48 weeks	Placebo n=40 Participants Participants were randomized to receive matching placebo tablets PO BID for 48 weeks.
Number of Participants With Type of Adverse Events (AEs) to Losmapimod Type: SAEs	2 Participants	0 Participants
Number of Participants With Type of Adverse Events (AEs) to Losmapimod Type: TEAEs	29 Participants	23 Participants

SECONDARY outcome

Timeframe: Up to Week 48

Population: Safety Analysis Set

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.

Outcome measures

Outcome measures
Measure	Losmapimod 15 Milligrams (mg) Twice Daily (BID) n=40 Participants Participants were randomized to receive losmapimod tablets 15 mg (2×7.5 mg tablets/dose BID) orally (PO) for 48 weeks	Placebo n=40 Participants Participants were randomized to receive matching placebo tablets PO BID for 48 weeks.
Number of Participants With Severity of AEs to Losmapimod Severity: Severe	2 Participants	0 Participants
Number of Participants With Severity of AEs to Losmapimod Severity: Mild	18 Participants	15 Participants
Number of Participants With Severity of AEs to Losmapimod Severity: Moderate	9 Participants	8 Participants

SECONDARY outcome

Timeframe: Up to Week 48

Population: Safety Analysis Set

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)

Outcome measures

Outcome measures
Measure	Losmapimod 15 Milligrams (mg) Twice Daily (BID) n=40 Participants Participants were randomized to receive losmapimod tablets 15 mg (2×7.5 mg tablets/dose BID) orally (PO) for 48 weeks	Placebo n=40 Participants Participants were randomized to receive matching placebo tablets PO BID for 48 weeks.
Number of Participants With Relationship of AEs to Losmapimod Relationship: Unlikely related	4 Participants	7 Participants
Number of Participants With Relationship of AEs to Losmapimod Relationship: Not related	16 Participants	14 Participants
Number of Participants With Relationship of AEs to Losmapimod Relationship: Possibly related	9 Participants	1 Participants
Number of Participants With Relationship of AEs to Losmapimod Relationship: Probably related	0 Participants	1 Participants
Number of Participants With Relationship of AEs to Losmapimod Relationship: Definitely related	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Week 48

Population: Safety Analysis Set

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.

Outcome measures

Outcome measures
Measure	Losmapimod 15 Milligrams (mg) Twice Daily (BID) n=40 Participants Participants were randomized to receive losmapimod tablets 15 mg (2×7.5 mg tablets/dose BID) orally (PO) for 48 weeks	Placebo n=40 Participants Participants were randomized to receive matching placebo tablets PO BID for 48 weeks.
Number of Participants With Adverse Events of Special Interest (AESIs)	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Week 48

Population: Safety Analysis Set

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.

Outcome measures

Outcome measures
Measure	Losmapimod 15 Milligrams (mg) Twice Daily (BID) n=40 Participants Participants were randomized to receive losmapimod tablets 15 mg (2×7.5 mg tablets/dose BID) orally (PO) for 48 weeks	Placebo n=40 Participants Participants were randomized to receive matching placebo tablets PO BID for 48 weeks.
Number of Participants Who Prematurely Discontinued Study Drug Due to a Treatment Emergent Adverse Event (TEAE)	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Losmapimod 15 Milligrams (mg) Twice Daily (BID) n=30 Participants Participants were randomized to receive losmapimod tablets 15 mg (2×7.5 mg tablets/dose BID) orally (PO) for 48 weeks	Placebo n=29 Participants Participants were randomized to receive matching placebo tablets PO BID for 48 weeks.
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	0.52 Percentage point Standard Deviation 1.783
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	0.99 Percentage point Standard Deviation 1.723
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	1.67 Percentage point Standard Deviation 2.011

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Losmapimod 15 Milligrams (mg) Twice Daily (BID) n=30 Participants Participants were randomized to receive losmapimod tablets 15 mg (2×7.5 mg tablets/dose BID) orally (PO) for 48 weeks	Placebo n=29 Participants Participants were randomized to receive matching placebo tablets PO BID for 48 weeks.
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	-0.04 Liter Standard Deviation 0.045
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	-0.10 Liter Standard Deviation 0.114
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	-0.01 Liter Standard Deviation 0.067

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Losmapimod 15 Milligrams (mg) Twice Daily (BID) n=30 Participants Participants were randomized to receive losmapimod tablets 15 mg (2×7.5 mg tablets/dose BID) orally (PO) for 48 weeks	Placebo n=29 Participants Participants were randomized to receive matching placebo tablets PO BID for 48 weeks.
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	0.47 Percentage point Standard Deviation 0.655
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	0.24 Percentage point Standard Deviation 0.547
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	0.49 Percentage point Standard Deviation 0.921

SECONDARY outcome

Timeframe: 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.

Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of losmapimod.

Outcome measures

Outcome measures
Measure	Losmapimod 15 Milligrams (mg) Twice Daily (BID) n=40 Participants Participants were randomized to receive losmapimod tablets 15 mg (2×7.5 mg tablets/dose BID) orally (PO) for 48 weeks	Placebo Participants were randomized to receive matching placebo tablets PO BID for 48 weeks.
Plasma Concentration After Administration of Losmapimod Pre dose	NA Nanogram per milliliter NA indicates that Median and full range could not be calculated as the values were Below the level of quantification (BLQ)	—
Plasma Concentration After Administration of Losmapimod 4 hours post dose	61.200 Nanogram per milliliter Interval 6.56 to 147.0	—
Plasma Concentration After Administration of Losmapimod Week 4 pre dose	27.000 Nanogram per milliliter Interval 3.54 to 120.0	—
Plasma Concentration After Administration of Losmapimod Week 4: 4 hours post dose	87.600 Nanogram per milliliter Interval 46.4 to 165.0	—
Plasma Concentration After Administration of Losmapimod Week 12	58.300 Nanogram per milliliter Interval 15.4 to 232.0	—
Plasma Concentration After Administration of Losmapimod Week 16 pre dose	31.900 Nanogram per milliliter Interval 0.1 to 110.0	—
Plasma Concentration After Administration of Losmapimod Week 16: 4 hours post dose	82.450 Nanogram per milliliter Interval 21.3 to 145.0	—
Plasma Concentration After Administration of Losmapimod Week 24	62.150 Nanogram per milliliter Interval 0.1 to 239.0	—
Plasma Concentration After Administration of Losmapimod Week 36 pre dose	25.100 Nanogram per milliliter Interval 0.1 to 77.1	—
Plasma Concentration After Administration of Losmapimod Week 36: 4 hours post dose	68.200 Nanogram per milliliter Interval 37.6 to 182.0	—
Plasma Concentration After Administration of Losmapimod Week 48	73.400 Nanogram per milliliter Interval 0.51 to 163.0	—

SECONDARY outcome

Timeframe: Baseline, Week 16 and Week 36

Population: Pharmacokinetics Analysis Set. Only those participants with data available at the specified data points were analyzed.

Skeletal muscle biopsy samples were collected at indicated time points for the assessment of concentration of losmapimod.

Outcome measures

Outcome measures
Measure	Losmapimod 15 Milligrams (mg) Twice Daily (BID) n=16 Participants Participants were randomized to receive losmapimod tablets 15 mg (2×7.5 mg tablets/dose BID) orally (PO) for 48 weeks	Placebo Participants were randomized to receive matching placebo tablets PO BID for 48 weeks.
Concentration of Losmapimod in Skeletal Muscle Biopsy Baseline	0.301 Nanogram per gram Interval 0.13 to 68.4	—
Concentration of Losmapimod in Skeletal Muscle Biopsy Week 16	56.450 Nanogram per gram Interval 14.1 to 117.0	—
Concentration of Losmapimod in Skeletal Muscle Biopsy Week 36	93.800 Nanogram per gram Interval 37.3 to 144.0	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Losmapimod 15 Milligrams (mg) Twice Daily (BID) n=35 Participants Participants were randomized to receive losmapimod tablets 15 mg (2×7.5 mg tablets/dose BID) orally (PO) for 48 weeks	Placebo n=35 Participants Participants were randomized to receive matching placebo tablets PO BID for 48 weeks.
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	10.968 Percent change Standard Deviation 41.3115
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	39.497 Percent change Standard Deviation 92.6947
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	34.176 Percent change Standard Deviation 83.1994
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	20.445 Percent change Standard Deviation 203.8013
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	-8.908 Percent change Standard Deviation 74.6476

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Losmapimod 15 Milligrams (mg) Twice Daily (BID) n=37 Participants Participants were randomized to receive losmapimod tablets 15 mg (2×7.5 mg tablets/dose BID) orally (PO) for 48 weeks	Placebo n=39 Participants Participants were randomized to receive matching placebo tablets PO BID for 48 weeks.
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	-0.0022 Unitless Standard Deviation 0.06615
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	-0.0069 Unitless Standard Deviation 0.09547
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	-0.0094 Unitless Standard Deviation 0.10672
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	-0.0371 Unitless Standard Deviation 0.12235
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	-0.0267 Unitless Standard Deviation 0.08972
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	0.0189 Unitless Standard Deviation 0.07697
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	0.0084 Unitless Standard Deviation 0.08577
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 0.06960	0.0114 Unitless Standard Deviation 0.09087
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	-0.0069 Unitless Standard Deviation 0.09770
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 0.09090	-0.0129 Unitless Standard Deviation 0.09841

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	Losmapimod 15 Milligrams (mg) Twice Daily (BID) n=39 Participants Participants were randomized to receive losmapimod tablets 15 mg (2×7.5 mg tablets/dose BID) orally (PO) for 48 weeks	Placebo n=39 Participants Participants were randomized to receive matching placebo tablets PO BID for 48 weeks.
Change From Baseline in Classic Timed Up and Go (TUG) Average Completion Time Week 4	2.011 Seconds Standard Deviation 16.8603	0.297 Seconds Standard Deviation 2.0577
Change From Baseline in Classic Timed Up and Go (TUG) Average Completion Time Week 12	-0.340 Seconds Standard Deviation 2.5908	0.183 Seconds Standard Deviation 1.7839
Change From Baseline in Classic Timed Up and Go (TUG) Average Completion Time Week 24	0.960 Seconds Standard Deviation 2.8012	0.384 Seconds Standard Deviation 1.9678
Change From Baseline in Classic Timed Up and Go (TUG) Average Completion Time Week 36	0.252 Seconds Standard Deviation 2.8725	0.709 Seconds Standard Deviation 1.6041
Change From Baseline in Classic Timed Up and Go (TUG) Average Completion Time Week 48	-0.340 Seconds Standard Deviation 2.1289	0.789 Seconds Standard Deviation 1.7059

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Losmapimod 15 Milligrams (mg) Twice Daily (BID) n=36 Participants Participants were randomized to receive losmapimod tablets 15 mg (2×7.5 mg tablets/dose BID) orally (PO) for 48 weeks	Placebo n=38 Participants Participants were randomized to receive matching placebo tablets PO BID for 48 weeks.
Change From Baseline in Facioscapulohumeral Muscular Dystrophy (FSDH) TUG Average Completion Time Week 4	-0.993 Seconds Standard Deviation 3.4234	0.750 Seconds Standard Deviation 2.1824
Change From Baseline in Facioscapulohumeral Muscular Dystrophy (FSDH) TUG Average Completion Time Week 12	-0.380 Seconds Standard Deviation 2.7827	0.058 Seconds Standard Deviation 1.7805
Change From Baseline in Facioscapulohumeral Muscular Dystrophy (FSDH) TUG Average Completion Time Week 24	0.549 Seconds Standard Deviation 2.9794	0.304 Seconds Standard Deviation 1.8555
Change From Baseline in Facioscapulohumeral Muscular Dystrophy (FSDH) TUG Average Completion Time Week 36	-0.653 Seconds Standard Deviation 4.1121	0.389 Seconds Standard Deviation 1.7394
Change From Baseline in Facioscapulohumeral Muscular Dystrophy (FSDH) TUG Average Completion Time Week 48	0.342 Seconds Standard Deviation 3.7028	0.334 Seconds Standard Deviation 2.0296

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Losmapimod 15 Milligrams (mg) Twice Daily (BID) n=38 Participants Participants were randomized to receive losmapimod tablets 15 mg (2×7.5 mg tablets/dose BID) orally (PO) for 48 weeks	Placebo n=39 Participants Participants were randomized to receive matching placebo tablets PO BID for 48 weeks.
Change From Baseline in All Muscles Total Average Strength as Assessed by Hand-held Dynamometry Week 12	1.439 Kilograms Standard Deviation 11.5791	-0.230 Kilograms Standard Deviation 9.5417
Change From Baseline in All Muscles Total Average Strength as Assessed by Hand-held Dynamometry Week 24	-1.551 Kilograms Standard Deviation 22.8920	-9.477 Kilograms Standard Deviation 15.6318
Change From Baseline in All Muscles Total Average Strength as Assessed by Hand-held Dynamometry Week 36	-3.608 Kilograms Standard Deviation 33.1467	-11.772 Kilograms Standard Deviation 22.7106
Change From Baseline in All Muscles Total Average Strength as Assessed by Hand-held Dynamometry Week 48	-5.358 Kilograms Standard Deviation 22.0734	-15.021 Kilograms Standard Deviation 28.3042
Change From Baseline in All Muscles Total Average Strength as Assessed by Hand-held Dynamometry Week 4	5.064 Kilograms Standard Deviation 15.3103	-1.386 Kilograms Standard Deviation 9.2043

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and at Week 48

Population: Full Analysis Set. Only those participants with data available at the specified data points were analyzed.

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.

Outcome measures

Outcome measures
Measure	Losmapimod 15 Milligrams (mg) Twice Daily (BID) n=25 Participants Participants were randomized to receive losmapimod tablets 15 mg (2×7.5 mg tablets/dose BID) orally (PO) for 48 weeks	Placebo n=30 Participants Participants were randomized to receive matching placebo tablets PO BID for 48 weeks.
Change From Baseline in Motor Function Measure (MFM) Domain 1 Score	2.76 Scores on a scale Standard Deviation 9.079	2.00 Scores on a scale Standard Deviation 8.780

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and at Week 48

Population: Full Analysis Set. Only those participants with data available at the specified data points were analyzed.

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.

Outcome measures

Outcome measures
Measure	Losmapimod 15 Milligrams (mg) Twice Daily (BID) n=28 Participants Participants were randomized to receive losmapimod tablets 15 mg (2×7.5 mg tablets/dose BID) orally (PO) for 48 weeks	Placebo n=30 Participants Participants were randomized to receive matching placebo tablets PO BID for 48 weeks.
Change From Baseline in FSHD Health Index (HI)	1.17 Scores on a scale Standard Deviation 13.499	-0.64 Scores on a scale Standard Deviation 8.024

OTHER_PRE_SPECIFIED outcome

Timeframe: At Week 48

Population: Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Losmapimod 15 Milligrams (mg) Twice Daily (BID) n=40 Participants Participants were randomized to receive losmapimod tablets 15 mg (2×7.5 mg tablets/dose BID) orally (PO) for 48 weeks	Placebo n=40 Participants Participants were randomized to receive matching placebo tablets PO BID for 48 weeks.
Number of Participants With Improved and Not Improved Response to Patients' Global Impression of Change (PGIC) Improved: Week 48	8 Participants	2 Participants
Number of Participants With Improved and Not Improved Response to Patients' Global Impression of Change (PGIC) Not Improved: Week 48	21 Participants	29 Participants

Adverse Events

Losmapimod 15 Milligrams (mg) Twice Daily (BID)

Serious events: 2 serious events

Other events: 29 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Losmapimod 15 Milligrams (mg) Twice Daily (BID) n=40 participants at risk Participants were randomized to receive losmapimod tablets 15 mg (2×7.5 mg tablets/dose BID) orally (PO) for 48 weeks	Placebo n=40 participants at risk Participants were randomized to receive matching placebo tablets PO BID for 48 weeks.
Infections and infestations Postoperative wound infection	2.5% 1/40 • Up to Week 48 Safety population which included all participants who received any study drug.	0.00% 0/40 • Up to Week 48 Safety population which included all participants who received any study drug.
Injury, poisoning and procedural complications Alcohol poisoning	2.5% 1/40 • Up to Week 48 Safety population which included all participants who received any study drug.	0.00% 0/40 • Up to Week 48 Safety population which included all participants who received any study drug.
Psychiatric disorders Suicide attempt	2.5% 1/40 • Up to Week 48 Safety population which included all participants who received any study drug.	0.00% 0/40 • Up to Week 48 Safety population which included all participants who received any study drug.

Other adverse events

Additional Information

Call Center

Fulcrum Therapeutics

Phone: 617-651-8853

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER