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Trial record 1 of 3 for:    losmapimod | FSHD
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Efficacy and Safety of Losmapimod in Treating Subjects With Facioscapulohumeral Muscular Dystrophy (FSHD) With Open-Label Extension (OLE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04264442
Recruitment Status : Enrolling by invitation
First Posted : February 11, 2020
Last Update Posted : June 22, 2020
Sponsor:
Information provided by (Responsible Party):
Fulcrum Therapeutics

Tracking Information
First Submitted Date  ICMJE January 30, 2020
First Posted Date  ICMJE February 11, 2020
Last Update Posted Date June 22, 2020
Actual Study Start Date  ICMJE February 13, 2020
Estimated Primary Completion Date February 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 7, 2020)
Safety and Tolerability of Losmapimod [ Time Frame: Every 12 Weeks from the date of enrollment through study completion, up to 60 months ]
Safety and tolerability of losmapimod will be evaluated by the following: a. Type, frequency, severity and relationship of adverse events (AEs) to losmapimod
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 22, 2020)
  • Lean Muscle Volume [ Time Frame: Every 24 Weeks from the date of enrollment through study completion, up to 60 months ]
    Change from baseline in lean muscle volume (LMV) after long term dosing will be measured by whole body magnetic resonance imaging (MRI).
  • Muscle Fat Fraction [ Time Frame: Every 24 Weeks from the date of enrollment through study completion, up to 60 months ]
    Change from baseline in muscle fat fraction (MMF) after long term dosing will be measured by whole body magnetic resonance imaging (MRI).
  • Muscle Fat Infiltration [ Time Frame: Every 24 Weeks from the date of enrollment through study completion, up to 60 months ]
    Change from baseline in muscle fat infiltration (MFI) after long term dosing will be measured by whole body magnetic resonance imaging (MRI).
  • Plasma Concentrations of Losmapimod After Long Term Dosing of Losmapimod [ Time Frame: Every 12 Weeks from the date of enrollment through study completion, up to 60 months ]
    Blood samples will be collected to measure the plasma concentration of losmapimod after long-term dosing.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 7, 2020)
  • Lean Muscle Volume [ Time Frame: Every 24 Weeks from the date of enrollment through study completion, up to 60 months ]
    Change from baseline in lean muscle volume after long term dosing will be measured by whole body magnetic resonance imaging (MRI).
  • Mean Fat Fraction [ Time Frame: Every 24 Weeks from the date of enrollment through study completion, up to 60 months ]
    Change from baseline in mean fat fraction after long term dosing will be measured by whole body magnetic resonance imaging (MRI).
  • Muscle Fat Infiltration [ Time Frame: Every 24 Weeks from the date of enrollment through study completion, up to 60 months ]
    Change from baseline in muscle fat infiltration after long term dosing will be measured by whole body magnetic resonance imaging (MRI).
  • DUX4 Activity in Patients Randomized to Losmapimod during the Placebo-Controlled Treatment Period [ Time Frame: Week 48 ]
    Change from baseline in DUX4 activity in affected skeletal muscle will be measured by quantitative reverse transcription polymerase chain reaction (QRT-PCR) in a panel of DUX4-regulated gene transcripts.
  • DUX4 Activity in Patients Randomized to Placebo during the Placebo-Controlled Treatment Period [ Time Frame: Week 48 ]
    Change from baseline in DUX4 activity in affected skeletal muscle will be measured by quantitative reverse transcription polymerase chain reaction (QRT-PCR) in a panel of DUX4-regulated gene transcripts.
  • Plasma Concentrations of Losmapimod After Long Term Dosing of Losmapimod [ Time Frame: Every 12 Weeks from the date of enrollment through study completion, up to 60 months ]
    Blood samples will be collected to measure the plasma concentration of losmapimod after long-term dosing.
  • Concentrations of Losmapimod in Skeletal Muscle Biopsy [ Time Frame: Week 48 ]
    Muscle biopsy will be collected to measure the concentrations of losmapimod in skeletal muscle.
  • Target Engagement Parameter in Blood and Skeletal Muscle Biopsy [ Time Frame: Week 48 ]
    Peripheral whole blood and skeletal muscle biopsy will be collected to measure the change from baseline in phospho-HSP27 and ratio of pHSP27/total HSP27.
Current Other Pre-specified Outcome Measures
 (submitted: February 7, 2020)
  • Reachable Work Space (RWS) - Clinical Outcome Assessment [ Time Frame: Every 12 Weeks from the date of enrollment through study completion, up to 60 months ]
    Changes from baseline in the Reachable Work Space clinical outcome assessment performed with and without weights will be evaluated after long-term dosing of losmapimod.
  • Timed Up and Go (TUG) - Clinical Outcome Assessment [ Time Frame: Every 12 Weeks from the date of enrollment through study completion, up to 60 months ]
    Changes from baseline in the Classic and FSHD TUG clinical outcome assessment will be evaluated after long-term dosing of losmapimod.
  • Muscle Strength - Clinical Outcome Assessment [ Time Frame: Every 12 Weeks from the date of enrollment through study completion, up to 60 months ]
    Changes from baseline in muscle strength assessed by Hand-Held Quantitative Dynamometry will be evaluated after long-term dosing of losmapimod.
  • Motor Function Measure (MFM) Domain 1 - Clinical Outcome Assessment [ Time Frame: Every 12 Weeks from the date of enrollment through study completion, up to 60 months ]
    Changes from baseline in the MFM domain 1 will be evaluated after long-term dosing of losmapimod.
  • FSHD Health Index (FSHD-HI) - Clinical Outcome Assessment [ Time Frame: Every 12 Weeks from the date of enrollment through study completion, up to 60 months ]
    Changes from baseline in the FSHD-HI will be evaluated after long-term dosing of losmapimod.
  • Patients' Global Impression of Change (PGIC) - Clinical Outcome Assessment [ Time Frame: Every 12 Weeks from the date of enrollment through study completion, up to 60 months ]
    Changes from baseline in the PGIC will be evaluated after long-term dosing of losmapimod.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of Losmapimod in Treating Subjects With Facioscapulohumeral Muscular Dystrophy (FSHD) With Open-Label Extension (OLE)
Official Title  ICMJE A Phase 2, Randomized, Double-Blind, Placebo-Controlled, 48-Week, Parallel-Group Study of the Efficacy and Safety of Losmapimod in Treating Subjects With Facioscapulohumeral Muscular Dystrophy (FSHD) With Open-Label Extension (OLE)
Brief Summary This study is an open-label extension to evaluate the safety and tolerability of long-term dosing of Losmapimod in patients with FSHD1 who participated in the ReDux4 study.
Detailed Description

This study is an open-label extension study to evaluate the safety and tolerability of long-term dosing of Losmapimod in patients with FSHD1 who participated in the ReDux4 study.

This study is a multi-center clinical trial. It will be conducted in North America, Canada and Europe. Only patients who participated and competed all study procedures in the ReDUX4 Study treatment period will be eligible to participate in this open label extension study.

Patients who complete the randomized, placebo-controlled portion of the study will have the option to roll over into the open-label extension study.

Patients will receive 15 mg of losmapimod by mouth twice daily for a total of 30 mg by mouth daily. All patients will attend clinic visits approximately every 12 weeks and 7 days after the last dose of study drug for safety follow-up assessment.

Participation in this open-label extension study will continue until losmapimod becomes commercially available, the patient withdraws from the study, or the Sponsor decides to close the study.

The primary endpoint of the study is to evaluate the safety and tolerability of long-term dosing of losmapimod in patients with FSHD.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
This study is part two of NCT04003974 which was a randomized, double-blind placebo-controlled treatment period for 48 weeks. This study is an open-label extension with losmapimod in patients with FSHD1.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Facioscapulohumeral Muscular Dystrophy (FSHD)
Intervention  ICMJE Drug: Losmapimod
Patients will receive Losmapimod 15 mg by mouth twice daily for a total of 30 mg daily. The study drug should be taken with food and the date and time of each dose taken should be recorded in the subject diary.
Study Arms  ICMJE Experimental: Losmapimod
FSHD1 patients with genetic confirmation will receive Losmapimod 15 mg by mouth twice daily for a total of 30 mg daily until study drug approval or until the study is discontinued by the Sponsor.
Intervention: Drug: Losmapimod
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Enrolling by invitation
Estimated Enrollment  ICMJE
 (submitted: February 7, 2020)
76
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 2025
Estimated Primary Completion Date February 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • The patient must have consented to participate and must have provided signed, dated and witnessed an IRB-approved informed consent form that conforms to federal and institutional guidelines.
  • Male or female subjects
  • Patients must be between 18 and 65 years of age, inclusive
  • Confirmed diagnosis of FSHD1 with 1 to 9 repeats via assessment of the size of the D4Z4 array on chromosome 4. Genetic confirmation must be obtained prior to the screening MRI and baseline muscle biopsy.
  • Clinical severity score of 2 to 4 (RICCI Score; Range 0-5), inclusive at screening
  • Must have a MRI-eligible muscle for biopsy
  • Must be will and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines and other study procedures.
  • Will practice an approved method of birth control

Exclusion Criteria:

  • Has a history of any illness or any clinical condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject. This may include, but is not limited to, a history of relevant drug or food allergies; history of cardiovascular or central nervous system disease; neuromuscular diseases except FSHD (eg, myopathy, neuropathy, neuromuscular junction disorders); or clinically significant history of mental disease.
  • For subjects who are on drug(s) or supplements that may affect muscle function, as determined by the treating physician, or that are included in the list of drugs presented in the protocol, subjects must be on a stable dose of that drug(s) or supplement for at least 3 months prior to the first dose of study drug and remain on that stable dose for the duration of the study. Changes to the dose or treatment discontinuation during the study can only be done for strict medical reasons by the treating physician with clear documentation and notification to the sponsor.
  • Acute or chronic history of liver disease or known to have current alanine aminotransferase ≥2 × upper limit of normal (ULN) or total bilirubin >1.5 × ULN, or known history of hepatitis B or C.
  • Known severe renal impairment (defined as a glomerular filtration rate of <30 mL/min/1.73m2).
  • Positive screen for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or antibodies against human immunodeficiency virus (HIV)-1 and -2.
  • Male subjects with a female partner who is planning to become pregnant during the study or within 90 days after the last dose of study drug.
  • Use of another investigational product within 30 days or 5 half-lives (whichever is longer), or according to local regulations, or currently participating in a study with an investigational product. Note: Concurrent participation in other non-drug studies may be acceptable if confirmed in writing by the sponsor.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   France,   Spain,   United States
Removed Location Countries Germany
 
Administrative Information
NCT Number  ICMJE NCT04264442
Other Study ID Numbers  ICMJE FIS-002-2019 OLE
Has Data Monitoring Committee No
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  ICMJE
Plan to Share IPD: No
Responsible Party Fulcrum Therapeutics
Study Sponsor  ICMJE Fulcrum Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Michelle Mellion, MD Fulcrum Therapeutics
PRS Account Fulcrum Therapeutics
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP