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

Primary Purpose

Facioscapulohumeral Muscular Dystrophy (FSHD)

Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Losmapimod
Placebo oral tablet
Sponsored by
Fulcrum Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Facioscapulohumeral Muscular Dystrophy (FSHD) focused on measuring Facioscapulohumeral muscular dystrophy (FSHD), Facioscapulohumeral muscular dystrophy type 1 (FSHD 1), Facioscapulohumeral muscular dystrophy type 2 (FSHD 2), Muscular Dystrophies, Muscular Dystrophy, Facioscapulohumeral Muscular Disorders, Musculoskeletal Diseases, Neuromuscular Diseases, REACH

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients 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. Patients who are wheelchair-dependent or dependent on walker or wheelchair for activities are not permitted to enroll in the study.
  • Screening total relative surface area (RSA) (Q1-Q4) without weight in the dominant upper extremities (UE) assessed by reachable workspace (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.
  • Patients who are on drug(s) or supplements that may affect muscle function, as determined by the Investigator: patients 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 CYP3A4 substrates and MATE and OAT3 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 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 patients 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).

Sites / Locations

  • University of California Irvine
  • University of California Los Angeles (UCLA)
  • University of Colorado Anschutz Medical Campus
  • University of Florida
  • University of Kansas Medical Center
  • Kennedy Krieger Institute
  • University of Massachusetts Memorial Medical Center
  • Mayo Clinic
  • Washington University School of Medicine
  • University of Rochester Medical Center
  • Ohio State University Medical Center
  • University of Utah
  • Virginia Commonwealth University
  • University of Washington Medical Center
  • University of Calgary
  • The Ottawa Hospital Research Institute
  • Montreal Neurological Institute and Hospital
  • Aarhus Universitetshospital
  • Rigshospitalet
  • Nice University Hospital - CHU Nice
  • Institute de Myologie, Groupe Hospitalier Pitié-Salpêtrière
  • University Hospital Bonn
  • LMU Klinikum Ludwig-Maximilians-Universität München
  • Universitätsklinikum Ulm
  • Fondazione Serena Onlus- Centro Clinico NEMO
  • Fondazione IRCCS Istituto Neurologico Carlo Besta
  • Radboudumc
  • Leiden University Medical Centre
  • Hospital Universitario Donostia
  • Hospital Universitario Vall d'Hebron
  • Hospital Universitari i Politecnic La Fe
  • University College of London Hospitals
  • Newcastle upon Tyne NHS Foundation Trust

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Experimental

Arm Label

Part A: Placebo-controlled treatment period: Losmapimod

Part A: Placebo-controlled treatment period: Placebo

Part B: Open-label extension

Arm Description

Participants will be randomized to receive losmapimod.

Participants will be randomized to receive placebo

Participants will receive losmapimod, upon completion of all assessments for Part A.

Outcomes

Primary Outcome Measures

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
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)
Part B: Number of participants with clinically significant changes in clinical laboratory parameters, Electrocardiogram (ECG), vital signs and physical examinations

Secondary Outcome Measures

Part A: Change from Baseline in Quality of Life in Neurologic Disorders upper extremity (Neuro-QoL UE) Scale 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
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
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)
Part A: Number of participants with clinically significant changes in clinical laboratory parameters, ECG, vital signs and physical examinations

Full Information

First Posted
May 4, 2022
Last Updated
September 27, 2023
Sponsor
Fulcrum Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT05397470
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)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 16, 2022 (Actual)
Primary Completion Date
October 2024 (Anticipated)
Study Completion Date
January 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fulcrum Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Facioscapulohumeral Muscular Dystrophy (FSHD)
Keywords
Facioscapulohumeral muscular dystrophy (FSHD), Facioscapulohumeral muscular dystrophy type 1 (FSHD 1), Facioscapulohumeral muscular dystrophy type 2 (FSHD 2), Muscular Dystrophies, Muscular Dystrophy, Facioscapulohumeral Muscular Disorders, Musculoskeletal Diseases, Neuromuscular Diseases, REACH

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes 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).
Allocation
Randomized
Enrollment
260 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part A: Placebo-controlled treatment period: Losmapimod
Arm Type
Experimental
Arm Description
Participants will be randomized to receive losmapimod.
Arm Title
Part A: Placebo-controlled treatment period: Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will be randomized to receive placebo
Arm Title
Part B: Open-label extension
Arm Type
Experimental
Arm Description
Participants will receive losmapimod, upon completion of all assessments for Part A.
Intervention Type
Drug
Intervention Name(s)
Losmapimod
Intervention Description
Losmapimod 15 mg will be administered BID by mouth along with food.
Intervention Type
Drug
Intervention Name(s)
Placebo oral tablet
Intervention Description
Placebo will be administered BID by mouth along with food.
Primary Outcome Measure Information:
Title
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
Description
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.
Time Frame
Baseline and at Week 48
Title
Part B: Number of participants reporting Adverse events (AEs)
Time Frame
Up to Week 192
Title
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
Secondary Outcome Measure Information:
Title
Part A: Change from Baseline in Quality of Life in Neurologic Disorders upper extremity (Neuro-QoL UE) Scale at Week 48
Description
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.
Time Frame
Baseline and at Week 48
Title
Part A: Patient's Global Impression of Change (PGIC) at Week 48
Description
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.
Time Frame
At Week 48
Title
Part A: Change from Baseline in Whole body (WB) longitudinal composite Muscle Fat Infiltration (MFI) of B muscles at Week 48
Description
Change from Baseline in skeletal muscle tissue replacement by fat will be measured by WB musculoskeletal (MSK) magnetic resonance imaging (MRI).
Time Frame
Baseline and at Week 48
Title
Part A: Number of participants reporting Adverse events (AEs)
Time Frame
Up to Week 48
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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.
Facility Information:
Facility Name
University of California Irvine
City
Irvine
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
University of California Los Angeles (UCLA)
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
University of Colorado Anschutz Medical Campus
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Kennedy Krieger Institute
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
Facility Name
University of Massachusetts Memorial Medical Center
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01655
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
University of Rochester Medical Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Ohio State University Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
Virginia Commonwealth University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
University of Washington Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195
Country
United States
Facility Name
University of Calgary
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4Z6
Country
Canada
Facility Name
The Ottawa Hospital Research Institute
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1Y 4E9
Country
Canada
Facility Name
Montreal Neurological Institute and Hospital
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H3A 2B4
Country
Canada
Facility Name
Aarhus Universitetshospital
City
Aarhus
ZIP/Postal Code
8200
Country
Denmark
Facility Name
Rigshospitalet
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark
Facility Name
Nice University Hospital - CHU Nice
City
Nice
State/Province
Paca
ZIP/Postal Code
06001
Country
France
Facility Name
Institute de Myologie, Groupe Hospitalier Pitié-Salpêtrière
City
Paris
ZIP/Postal Code
75013
Country
France
Facility Name
University Hospital Bonn
City
Bonn
ZIP/Postal Code
53127
Country
Germany
Facility Name
LMU Klinikum Ludwig-Maximilians-Universität München
City
München
ZIP/Postal Code
80336
Country
Germany
Facility Name
Universitätsklinikum Ulm
City
Ulm
ZIP/Postal Code
89081
Country
Germany
Facility Name
Fondazione Serena Onlus- Centro Clinico NEMO
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20162
Country
Italy
Facility Name
Fondazione IRCCS Istituto Neurologico Carlo Besta
City
Milano
ZIP/Postal Code
20133
Country
Italy
Facility Name
Radboudumc
City
Nijmegen
State/Province
Gelderland
ZIP/Postal Code
9101
Country
Netherlands
Facility Name
Leiden University Medical Centre
City
Leiden
State/Province
Southern Holland
ZIP/Postal Code
2333 ZA
Country
Netherlands
Facility Name
Hospital Universitario Donostia
City
San Sebastián
State/Province
Guipuzkoa
ZIP/Postal Code
20014
Country
Spain
Facility Name
Hospital Universitario Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Universitari i Politecnic La Fe
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Facility Name
University College of London Hospitals
City
London
ZIP/Postal Code
WC1N 3BG
Country
United Kingdom
Facility Name
Newcastle upon Tyne NHS Foundation Trust
City
Newcastle upon Tyne
ZIP/Postal Code
NE1 3BZ
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
23215699
Citation
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.
Results Reference
background
PubMed Identifier
24828906
Citation
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.
Results Reference
background
PubMed Identifier
33931884
Citation
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.
Results Reference
background

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

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