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

• ClinicalTrials.gov Identifier: NCT05397470
• Recruitment Status: Active, not recruiting
• First Posted: May 31, 2022
• Last Update Posted: September 28, 2023
• Sponsor: Fulcrum Therapeutics
• Information provided by (Responsible Party): Fulcrum Therapeutics

Tracking Information

• First Submitted Date: May 4, 2022
• First Posted Date: May 31, 2022
• Last Update Posted Date: September 28, 2023
• Actual Study Start Date: June 16, 2022
• Estimated Primary Completion Date: October 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 16, 2023)

• Part A: Change from Baseline in total Relative surface area (RSA) Quadrants 1 to 5 (Q1-Q5) with 500 grams (g) wrist weight in dominant arm as assessed by Reachable workspace (RWS) at Week 48 [ Time Frame: Baseline and at Week 48 ]
  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.
• Part B: Number of participants reporting Adverse events (AEs) [ Time Frame: Up to Week 192 ]
• Part B: Number of participants with clinically significant changes in clinical laboratory parameters, Electrocardiogram (ECG), vital signs and physical examinations [ Time Frame: Up to Week 192 ]

Original Primary Outcome Measures (submitted: May 25, 2022)

Reachable Workspace (RWS) [ Time Frame: Screening, Baseline and Weeks 4, 12, 24, 36, and 48 ]

The Reachable Workspace will be used to measure change(s) from baseline in the participants upper extremity function. The Reachable Workspace is a clinical outcome measure that measures the relative surface area that an individual may reach with an outstretched arm. Responses are rated on a scale of 0 (no reachable workspace) to 1.25 (maximal reachable workspace).

Current Secondary Outcome Measures (submitted: May 16, 2023)

• Part A: Change from Baseline in Quality of Life in Neurologic Disorders upper extremity (Neuro-QoL UE) Scale at Week 48 [ Time Frame: Baseline and at Week 48 ]
  The Neuro-QoL UE will be used to measure change(s) from Baseline in the participants upper extremity function. The Neuro-QoL UE is a questionnaire that measures the participants self-reported upper extremity function including activities of daily living (ADLs) involving digital, manual, and reach-related function and self-care. Responses are rated from 1 (unable to do) to 5 (without any difficulty). Lower scores indicate worse symptoms.
• Part A: Patient's Global Impression of Change (PGIC) at Week 48 [ Time Frame: At Week 48 ]
  The Patient Global Impression of Change (PGIC) is a standard and validated 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 [ Time Frame: Baseline and at Week 48 ]
  Change from Baseline in skeletal muscle tissue replacement by fat will be measured by WB musculoskeletal (MSK) magnetic resonance imaging (MRI).
• Part A: Number of participants reporting Adverse events (AEs) [ Time Frame: Up to Week 48 ]
• Part A: Number of participants with clinically significant changes in clinical laboratory parameters, ECG, vital signs and physical examinations [ Time Frame: Up to Week 48 ]

Original Secondary Outcome Measures (submitted: May 25, 2022)

• Neuro-QoL Upper Extremity (UE) Scale [ Time Frame: Screening, Baseline and Weeks 4, 12, 24, 36, and 48 ]
  The Neuro-QoL UE will be used to measure change(s) from baseline in the participants upper extremity function. The Neuro-QoL UE is a questionnaire that measures the participants self-reported upper extremity function including activities of daily living (ADLs) involving digital, manual, and reach-related function and self-care. Responses are rated from 1 (unable to do) to 5 (without any difficulty).
• Patient's Global Impression of Change (PGIC) [ Time Frame: Weeks 4, 12, 24, 36, and 48 ]
  The Patient Global Impression of Change (PGIC) is a standard and validated patient-report outcome that measures the patient'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).
• Muscle Fat Infiltration [ Time Frame: Week 48 ]
  Change from baseline in skeletal muscle tissue replacement by fat will be measured by whole body (WB) musculoskeletal (MSK) magnetic resonance imaging (MRI).
• Treatment-Emergent Adverse Events [ Time Frame: Screening, Baseline and Weeks 4, 12, 24, 36, 48 and 7 days after the last dose of study drug ]
  Incidence of treatment-emergent adverse events (TEAEs) will be monitored continuously from screening to the end of safety follow-up visit. A treatment-emergent adverse event is defined as any event that was not present before exposure to the study drug or any event already present that worsens in either intensity or frequency after exposure to the study drug.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy and Safety of Losmapimod in Treating Participants With Facioscapulohumeral Muscular Dystrophy (FSHD) (REACH)
• Official Title: 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)
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Part A of this study will be performed in a double-blind fashion. Part B of the study will be performed in an open-label fashion. The investigator, study staff, subjects, sponsor, and monitor will remain blinded to the treatment in Part A until study closure (i.e., until closure of Part B).

Primary Purpose: Treatment

• Condition: Facioscapulohumeral Muscular Dystrophy (FSHD)

Intervention

• Drug: Losmapimod
  Losmapimod 15 mg will be administered BID by mouth along with food.
• Drug: Placebo oral tablet
  Placebo will be administered BID by mouth along with food.

Study Arms

• Experimental: Part A: Placebo-controlled treatment period: Losmapimod
  Participants will be randomized to receive losmapimod.
  Intervention: Drug: Losmapimod
• Placebo Comparator: Part A: Placebo-controlled treatment period: Placebo
  Participants will be randomized to receive placebo
  Intervention: Drug: Placebo oral tablet
• Experimental: Part B: Open-label extension
  Participants will receive losmapimod, upon completion of all assessments for Part A.
  Intervention: Drug: Losmapimod

Publications *

• Barbour AM, Sarov-Blat L, Cai G, Fossler MJ, Sprecher DL, Graggaber J, McGeoch AT, Maison J, Cheriyan J. Safety, tolerability, pharmacokinetics and pharmacodynamics of losmapimod following a single intravenous or oral dose in healthy volunteers. Br J Clin Pharmacol. 2013 Jul;76(1):99-106. doi: 10.1111/bcp.12063.
• Han JJ, Kurillo G, Abresch RT, de Bie E, Nicorici A, Bajcsy R. Reachable workspace in facioscapulohumeral muscular dystrophy (FSHD) by Kinect. Muscle Nerve. 2015 Feb;51(2):168-75. doi: 10.1002/mus.24287. Epub 2014 Nov 19.
• Mellion ML, Ronco L, Berends CL, Pagan L, Brooks S, van Esdonk MJ, van Brummelen EMJ, Odueyungbo A, Thompson LA, Hage M, Badrising UA, Raines S, Tracewell WG, van Engelen B, Cadavid D, Groeneveld GJ. Phase 1 clinical trial of losmapimod in facioscapulohumeral dystrophy: Safety, tolerability, pharmacokinetics, and target engagement. Br J Clin Pharmacol. 2021 Dec;87(12):4658-4669. doi: 10.1111/bcp.14884. Epub 2021 May 14.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: September 27, 2023): 260
• Original Estimated Enrollment (submitted: May 25, 2022): 230
• Estimated Study Completion Date: January 2026
• Estimated Primary Completion Date: October 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

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.
• Orally administered cytochrome P450 (CYP3A4) substrates and multidrug and toxin extrusion (MATE) and organic anion transporter (OAT)3 substrates are not permitted as concomitant therapy during the administration of losmapimod (defined as Baseline visit through end of study treatment).
• 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 exclusion criteria are listed in the protocol and only key are presented.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Denmark, France, Germany, Italy, Netherlands, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT05397470
• Other Study ID Numbers: 1821-FSH-301
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Fulcrum Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: Fulcrum Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Fulcrum Therapeutics
• Verification Date: September 2023