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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)

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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

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.

Condition or disease Intervention/treatment Phase
Facioscapulohumeral Muscular Dystrophy (FSHD) Drug: Losmapimod Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 76 participants
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
Official Title: 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)
Actual Study Start Date : February 13, 2020
Estimated Primary Completion Date : February 2024
Estimated Study Completion Date : February 2025


Arm Intervention/treatment
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.
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.




Primary Outcome Measures :
  1. 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



Secondary Outcome Measures :
  1. 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).

  2. 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).

  3. 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).

  4. 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.


Other Outcome Measures:
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04264442


Locations
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Sponsors and Collaborators
Fulcrum Therapeutics
Investigators
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Study Director: Michelle Mellion, MD Fulcrum Therapeutics
Publications:

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Responsible Party: Fulcrum Therapeutics
ClinicalTrials.gov Identifier: NCT04264442    
Other Study ID Numbers: FIS-002-2019 OLE
First Posted: February 11, 2020    Key Record Dates
Last Update Posted: June 22, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Fulcrum Therapeutics:
FSHD, FSHD1
Muscular Dystrophy
Muscular Dystrophies
Facioscapulohumeral Muscular Disorders
Musculoskeletal Diseases
Neuromuscular Diseases
Additional relevant MeSH terms:
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Muscular Dystrophies
Muscular Dystrophy, Facioscapulohumeral
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn