Efficacy and Safety of Losmapimod in Treating Participants With Facioscapulohumeral Muscular Dystrophy (FSHD) (REACH)

A Phase 3 Global, Randomized, Double-Blind, Placebo-Controlled, 48-Week, Parallel-Group Study of the Efficacy and Safety of Losmapimod in Treating Patients With Facioscapulohumeral Muscular Dystrophy (FSHD) (REACH)

Status

Terminated

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05397470

Enrollment

260

Registered

2022-05-31

Start date

2022-06-16

Completion date

2024-11-19

Last updated

2025-11-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Facioscapulohumeral Muscular Dystrophy (FSHD)

Keywords

Facioscapulohumeral muscular dystrophy (FSHD), Facioscapulohumeral muscular dystrophy type 1 (FSHD 1), Facioscapulohumeral muscular dystrophy type 2 (FSHD 2), Muscular Dystrophy, Facioscapulohumeral Muscular Disorders, Musculoskeletal Diseases, Neuromuscular Diseases, REACH

Brief summary

This is a study to evaluate the safety and efficacy of losmapimod in treating participants with Facioscapulohumeral Muscular Dystrophy (FSHD). Participants diagnosed with Facioscapulohumeral muscular dystrophy type 1 (FSHD1) or Facioscapulohumeral muscular dystrophy type 2 (FSHD2) will participate in Part A (Placebo-controlled treatment period) and will be randomized in a 1:1 ratio to receive losmapimod 15 milligrams (mg) or placebo orally twice daily (BID). Upon completion of Part A, participants will have the option to rollover into Part B (open-label extension) to evaluate the long-term safety, tolerability, and efficacy of losmapimod and will receive losmapimod 15 mg orally BID.

Interventions

DRUGLosmapimod

Losmapimod 15 mg will be administered BID by mouth along with food.

DRUGPlacebo oral tablet

Placebo will be administered BID by mouth along with food.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Masking description

Part B of the study will be performed in an open-label fashion.

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Inclusion criteria

Key Inclusion Criteria: * Participants must be between 18 and 65 years of age, inclusive. * Genetically confirmed diagnosis of FSHD 1 or FSHD 2. * Clinical severity score of 2 to 4 (Ricci Score; Range 0-5), at screening. Participants who are wheelchair-dependent or dependent on walker or wheelchair for activities are not permitted to enroll in the study. * Screening total RSA (Q1-Q4) without weight in the dominant UE assessed by RWS ≥ 0.2 and ≤ 0.7. * No contraindications to MRI. Key

Exclusion criteria

* Previously diagnosed cancer that has not been in complete remission for at least 5 years. Localized carcinomas of the skin and carcinoma in situ of the cervix that have been resected or ablated for cure are not exclusionary. * Participants who are on drug(s) or supplements that may affect muscle function, as determined by the Investigator: participants 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. * Known active opportunistic or life-threatening infections including Human Immunodeficiency virus (HIV) and hepatitis B or C. * Known active or inactive tuberculosis infection. * Acute or chronic history of liver disease. * Known severe renal impairment. * History of cardiac dysrhythmias requiring anti-arrhythmia treatment(s); or history or evidence of abnormal ECGs. * Use of another investigational product within 30 days or 5 half-lives (whichever is longer) or currently participating in a study of an investigational device. * Current or anticipated participation in a natural history study. Previous participation is allowed but participants cannot continue after enrollment in Study 1821-FSH-301. * Known hypersensitivity to losmapimod or any of its excipients. * Previous participation in a Fulcrum-sponsored FSHD losmapimod study (FIS-001-2019 or FIS-002-2019). Note that all other inclusion and

Design outcomes

Primary

Measure	Time frame	Description
Part A: Change From Baseline in Total Relative Surface Area (RSA) Quadrants 1 to 5 (Q1-Q5) With 500 Grams (g) Wrist Weight Averaged Over Both Arms as Assessed by Reachable Workspace (RWS) at Week 48	Baseline (Day 1) and at Week 48	Participants are instructed to complete a simple set of standardized movements of each arm centered around the shoulder joint. These arm movements are captured and quantitated with the use of a video camera. The RWS is a clinical outcome measure that measures the relative surface area that a participant may reach with an outstretched arm. Responses are rated on a scale of 0 (no reachable workspace) to 1.25 (maximal reachable workspace). Higher scores indicate better outcomes. Baseline is the last non-missing evaluation prior to first dose of study drug. Change from Baseline was calculated as the post-treatment value minus the value at Baseline.
Part B: Number of Participants Reporting Serious Treatment Emergent Adverse Events (Serious TEAEs) and Non-serious TEAEs > 5%	Week 48 to Week 127	Treatment-emergent adverse event is an AE that begins on or after the first dose of study drug and on or before the stop of study drug + 35 days or begins before the first dose of study drug and worsens on or after the first dose of study drug and on or before the stop of study drug + 35 days. A SAE is defined as an AE that results in any of the following outcomes: death; life-threatening adverse event; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; congenital anomaly/birth defect.
Part B: Number of Participants With Clinically Significant Changes in Chemistry Parameters	Week 48 to Week 127	Blood samples were collected for the analysis of chemistry parameters: Glucose, sodium, potassium, calcium, inorganic phosphate, total protein, albumin, blood urea nitrogen, creatinine, total bilirubin, direct bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase and creatine phosphokinase.
Part B: Number of Participants With Clinically Significant Changes in Hematology Parameters	Week 48 to Week 127	Blood samples were collected for the analysis of hematology parameters: hemoglobin (including mean corpuscular volume), mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, hematocrit, red blood cell count, total white blood cell count, platelet count. Differential blood counts, including basophils, eosinophils, neutrophils, lymphocytes, and monocytes
Part B: Number of Participants With Clinically Significant Changes in Urinalysis	Week 48 to Week 127	Urine samples were collected for the analysis of urinalysis parameters: Leucocytes, blood, nitrite, protein, urobilinogen, bilirubin, potential of Hydrogen (pH), specific gravity, ketones, glucose.
Part B: Number of Participants With Clinically Significant Changes in Vital Parameters	Week 48 to Week 127	Vital parameters including pulse rate, respiration rate, blood pressure, and temperature were measured in seated or recumbent for at least 5 minutes. Data for number of participants with abnormal clinically significant changes for vital signs have been presented.
Part B: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters	Week 48 to Week 127	Twelve-lead ECGs were performed after participants has been recumbent for at least 5 minutes.
Part B: Number of Participants With Clinically Significant Changes in Physical Examinations	Week 48 to Week 127	Physical examinations included an evaluation of body systems, including but not limited to the following: skin; head, eyes, ears, nose, and throat; respiratory system; cardiovascular system; abdomen (liver, spleen); lymph nodes; neurological system; and musculoskeletal system.

Secondary

Measure	Time frame	Description
Part A: Number of Participants With Clinically Significant Changes in Vital Parameters	Up to Week 48	Vital parameters including pulse rate, respiration rate, blood pressure, and temperature were measured in seated or recumbent for at least 5 minutes. Data for number of participants with abnormal clinically significant changes for vital signs have been presented.
Part A: Change From Baseline in Quality of Life in Neurologic Disorders Upper Extremity (Neuro-QoL UE) Scale at Week 48	Baseline (Day 1) and at Week 48	The Neuro-QoL Upper Extremity (UE) scale is a patient-reported outcome measure designed to assess upper limb function in individuals with neurologic conditions. It evaluates a participant's self-reported difficulty in performing activities for daily living (ADLs) involving digital, manual, and reach-related function and self-care. Responses are divided into 5 ordinal levels (1 = unable to do, 2 = with much difficulty, 3 = with some difficulty, 4 = with a little difficulty, 5 = without any difficulty). Lower scores indicate worse symptoms. Change from Baseline was calculated as the post-treatment value minus the value at Baseline.
Part A: Number of Participants With Clinically Significant Changes in Physical Examinations	Up to Week 48	Physical examinations included an evaluation of body systems, including but not limited to the following: skin; head, eyes, ears, nose, and throat; respiratory system; cardiovascular system; abdomen (liver, spleen); lymph nodes; neurological system; and musculoskeletal system.
Part A: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters	Up to Week 48	Twelve-lead ECGs was performed after participants has been recumbent for at least 5 minutes.
Part A: Number of Participants With Response to Patient's Global Impression of Change (PGIC) at Week 48	At Week 48	The Patient Global Impression of Change (PGIC) is a standard participant-report outcome that measures the participant's self-reported change in health status compared to the start of the study. The PGIC uses a single question and 7-point patient self-reporting scale of overall improvement during treatment ranging from 1 (very much improved) to 7 (very much worse). Higher scores indicate worse symptoms.
Part A: Change From Baseline in Whole Body (WB) Longitudinal Composite Muscle Fat Infiltration (MFI) of B Muscles at Week 48	Baseline (Day 1) and at Week 48	The whole-body longitudinal composite muscle fat infiltration (MFI) of predefined B muscles is measured by musculoskeletal (MSK) magnetic resonance imaging (MRI). MFI quantifies the extent of fat replacement in muscle tissue, which is a key marker of disease progression in facioscapulohumeral muscular dystrophy (FSHD). The B muscles are a prespecified subset of muscles that are most relevant to FSHD progression. A decrease or smaller increase in MFI indicates slower disease progression or a potential treatment benefit. Change from Baseline was calculated as the post-treatment value minus the value at Baseline.
Part A: Relative Change From Baseline in Average Shoulder Abductor Strength by Hand-held Quantitative Dynamometry at Week 48	Baseline (Day 1) and at Week 48	Average shoulder abductor strength was assessed using hand-held dynamometry (HHD). Bilateral strength measurements were acquired from both upper limbs, with the average calculated for each participant. The relative change from baseline was expressed as a percentage. This evaluated the effect of losmapimod, relative to placebo, on muscle strength in individuals diagnosed with facioscapulohumeral muscular dystrophy (FSHD). Standardized procedures and equipment were employed across all study sites for strength testing, and trained personnel conducted all measurements to ensure consistency. Baseline is the last non-missing evaluation prior to first dose of study drug. Relative change from Baseline = 100 x (Post-baseline value - Baseline value) / (Baseline value).
Part A: Number of Participants Serious TEAEs and TEAEs	Up to Week 48	Treatment-emergent adverse event is an AE that begins on or after the first dose of study drug and on or before the stop of study drug + 35 days or begins before the first dose of study drug and worsens on or after the first dose of study drug and on or before the stop of study drug + 35 days. A SAE is defined as an AE that results in any of the following outcomes: death; life-threatening adverse event; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; congenital anomaly/birth defect.
Part A: Number of Participants With Clinically Significant Changes in Clinical Chemistry Parameters	Up to Week 48	Blood samples were collected for the analysis of clinical chemistry parameters including Glucose, sodium, potassium, calcium, inorganic phosphate, total protein, albumin, blood urea nitrogen, creatinine, total bilirubin, direct bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase and creatine phosphokinase
Part A: Number of Participants With Clinically Significant Changes in Hematology Parameters	Up to Week 48	Blood samples were collected for the analysis of hematology parameters: hemoglobin (including mean corpuscular volume), mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, hematocrit, red blood cell count, total white blood cell count, platelet count. Differential blood counts, including basophils, eosinophils, neutrophils, lymphocytes, and monocytes
Part A: Number of Participants With Clinically Significant Changes in Urinalysis	Up to Week 48	Urine samples were collected for the analysis of urinalysis parameters: Leucocytes, blood, nitrite, protein, urobilinogen, bilirubin, potential of Hydrogen (pH), specific gravity, ketones, glucose.

Countries

Canada, Denmark, France, Germany, Italy, Netherlands, Spain, United Kingdom, United States

Participant flow

Recruitment details

This was a two-part study. Part A was a global, randomized, double-blind, placebo-controlled, parallel-group, multicenter study that enrolled up to 260 participants. Part B was an open-label extension phase in which approximately 249 participants from Part A rolled over to receive Losmapimod treatment.

Pre-assignment details

Participants who completed 48 Weeks treatment period in Part A were enrolled in Part B. Part A of the study was completed as planned; however, Part B was terminated prematurely due to a Sponsor decision.

Participants by arm

Arm	Count
Losmapimod 15 mg Participants received Losmapimod 15 mg orally twice daily (BID) with food for 48 weeks.	130
Matching Placebo Participants received matching placebo orally twice daily (BID) with food for 48 weeks.	130
Total	260

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Part A: PCT Period (Up to 48 Weeks)	Adverse Event	0	1	0
Part A: PCT Period (Up to 48 Weeks)	Other	0	1	0
Part A: PCT Period (Up to 48 Weeks)	Protocol Violation	1	1	0
Part A: PCT Period (Up to 48 Weeks)	Withdrawal by Subject	2	1	0
Part B: OLE Period (Up to Week 127)	Lost to Follow-up	0	0	1
Part B: OLE Period (Up to Week 127)	Study closed/terminated	0	0	244
Part B: OLE Period (Up to Week 127)	Withdrawal by Subject	0	0	4

Baseline characteristics

Characteristic	Matching Placebo	Total	Losmapimod 15 mg
Age, Continuous	44.3 Years STANDARD_DEVIATION 12	43.9 Years STANDARD_DEVIATION 12.2	43.4 Years STANDARD_DEVIATION 12.3
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants	14 Participants	8 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	112 Participants	225 Participants	113 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	12 Participants	21 Participants	9 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	3 Participants	6 Participants	3 Participants
Race (NIH/OMB) Black or African American	0 Participants	3 Participants	3 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	11 Participants	20 Participants	9 Participants
Race (NIH/OMB) White	116 Participants	231 Participants	115 Participants
Sex: Female, Male Female	59 Participants	115 Participants	56 Participants
Sex: Female, Male Male	71 Participants	145 Participants	74 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 130	1 / 130	0 / 249
other Total, other adverse events	122 / 130	112 / 130	94 / 249
serious Total, serious adverse events	5 / 130	8 / 130	7 / 249

Outcome results

Primary

Part A: Change From Baseline in Total Relative Surface Area (RSA) Quadrants 1 to 5 (Q1-Q5) With 500 Grams (g) Wrist Weight Averaged Over Both Arms as Assessed by Reachable Workspace (RWS) at Week 48

Participants are instructed to complete a simple set of standardized movements of each arm centered around the shoulder joint. These arm movements are captured and quantitated with the use of a video camera. The RWS is a clinical outcome measure that measures the relative surface area that a participant may reach with an outstretched arm. Responses are rated on a scale of 0 (no reachable workspace) to 1.25 (maximal reachable workspace). Higher scores indicate better outcomes. Baseline is the last non-missing evaluation prior to first dose of study drug. Change from Baseline was calculated as the post-treatment value minus the value at Baseline.

Time frame: Baseline (Day 1) and at Week 48

Population: Full Analysis Set comprised of all participants with FSHD1 or FSHD2 who are randomized and receive at least 1 dose of study drug in the placebo-controlled treatment period. Only those participants with data available at specified timepoints has been presented.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Part A: Losmapimod 15 Milligrams (mg)	Part A: Change From Baseline in Total Relative Surface Area (RSA) Quadrants 1 to 5 (Q1-Q5) With 500 Grams (g) Wrist Weight Averaged Over Both Arms as Assessed by Reachable Workspace (RWS) at Week 48	0.013 Scores on a scale	Standard Error 0.007
Part A: Placebo	Part A: Change From Baseline in Total Relative Surface Area (RSA) Quadrants 1 to 5 (Q1-Q5) With 500 Grams (g) Wrist Weight Averaged Over Both Arms as Assessed by Reachable Workspace (RWS) at Week 48	0.010 Scores on a scale	Standard Error 0.007

p-value: 0.750195% CI: [-0.014, 0.02]Mixed Model Repeated Measures

Primary

Part B: Number of Participants Reporting Serious Treatment Emergent Adverse Events (Serious TEAEs) and Non-serious TEAEs > 5%

Treatment-emergent adverse event is an AE that begins on or after the first dose of study drug and on or before the stop of study drug + 35 days or begins before the first dose of study drug and worsens on or after the first dose of study drug and on or before the stop of study drug + 35 days. A SAE is defined as an AE that results in any of the following outcomes: death; life-threatening adverse event; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; congenital anomaly/birth defect.