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Efficacy and Safety of Losmapimod in Subjects With Facioscapulohumeral Muscular Dystrophy (FSHD) (FSHD)

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ClinicalTrials.gov Identifier: NCT04003974
Recruitment Status : Recruiting
First Posted : July 1, 2019
Last Update Posted : August 15, 2019
Sponsor:
Information provided by (Responsible Party):
Fulcrum Therapeutics

Brief Summary:
This is a study to evaluate the safety and efficacy of Losmapimod in treating patients with Facioscapulohumeral Muscular Dystrophy (FSHD) over 24 weeks.

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

Detailed Description:

This study is a Phase 2, randomized, double-blind, placebo-controlled, parallel-group, multicenter study designed to evaluate the efficacy and safety of losmapimod in treating patients with Facioscapulohumeral Muscular Dystrophy (FSHD) over 24 weeks. Patients will participate in this study for approximately 29 weeks. This will include a 4-week screening period, a 24-week, placebo-controlled treatment period and a 7 day safety follow-up period. Patients must have a confirmed diagnosis of FSHD1 and genetic confirmation must be obtained prior to the screening MRI and baseline muscle biopsy. Patients will be randomized to receive 15 mg of losmapimod or placebo twice daily given as two 7.5 mg tablets per dose by mouth; for a total of 4 pills or 30 mg daily for 24 weeks. All patients will be asked to attend the study clinic for each scheduled visit.

The primary endpoint of the study is to evaluate the efficacy of losmapimod in inhibiting or reducing expression of DUX4, as measured by a subset of DUX4-regulated gene transcripts in skeletal muscle biopsies of FSHD patients. Secondary endpoints include evaluation of the safety and tolerability of losmapimod, the plasma concentrations of losmapimod, levels of losmapimod in skeletal muscle and losmapimod target engagement in blood and skeletal muscle in FSHD patients.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 66 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This study is a randomized, double-blind, placebo-controlled, 24-week parallel-group study.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: This study will be performed in a double-blind fashion. The investigator, study staff, subjects, sponsor and monitor will remain blinded to the treatment until study closure.
Primary Purpose: Treatment
Official Title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, 24-Week, Parallel-Group Study of the Efficacy and Safety of Losmapimod in Treating Subjects With Facioscapulohumeral Muscular Dystrophy (FSHD)
Actual Study Start Date : August 9, 2019
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : August 2020


Arm Intervention/treatment
Experimental: Treatment
FSHD1 patients with genetic confirmation will receive Losmapimod 15 mg twice daily given as two 7.5 mg tablets per dose by mouth; for a total of 4 pills or 30 mg daily for 24 weeks.
Drug: Losmapimod
This study includes a 24 week treatment period. Patients will receive Losmapimod 15 mg twice daily given as two 7.5 mg tablets per dose by mouth; for a total of 4 pills or 30 mg daily. The study drug should be taken with food and the date and time of each dose taken recorded in the subject diary.

Placebo Comparator: Placebo
FSHD1 patients with genetic confirmation will receive a Placebo twice daily given as two 7.5 mg tablets per dose by mouth; for a total of 4 pills or 30 mg daily for 24 weeks.
Drug: Placebo oral tablet
This study includes a 24 week treatment period. Patients will receive Placebo twice daily given as two 7.5 mg tablets per dose by mouth; for a total of 4 pills or 30 mg daily. The placebo tablets are identical to the Losmapimod tablets. Placebo should be taken with food and the date and time of each dose taken recorded in the subject diary.
Other Name: Placebo




Primary Outcome Measures :
  1. DUX4 activity [ Time Frame: Week 16 ]
    Change from baseline in DUX4 activity will be measured by quantitative polymerase chain reaction (qPCR) of skeletal muscle using a subset of DUX4‑regulated gene transcripts.


Secondary Outcome Measures :
  1. Treatment-Emergent Adverse Events [ Time Frame: Week 25 ]
    Incidence of treatment-emergent adverse events assessed by clinically significant laboratory test results, ECGs, and vital signs.

  2. Plasma Concentrations of Losmapimod [ Time Frame: Week 24 ]
    Blood samples will be collected to measure the plasma concentration of losmapimod at specified timepoints.

  3. Concentration of Losmapimod in Skeletal Muscle [ Time Frame: Week 16 ]
    Muscle biopsies will be collected at two specified timepoints to measure the concentration of losmapimod in skeletal muscle.

  4. Target Engagement [ Time Frame: Week 16 ]
    Change from baseline in phospho-HSP27 and ratio of pHSP27/total HSP27 will be measured in peripheral whole blood and muscle.


Other Outcome Measures:
  1. Muscle Lean Tissue Volume [ Time Frame: Week 24 ]
    Change from baseline in skeletal muscle lean tissue volume as measured by whole body magnetic resonance imaging (MRI).

  2. Muscle Tissue Replacement by Fat [ Time Frame: Week 24 ]
    Change from baseline in skeletal muscle tissue replacement by fat as measured by whole body magnetic resonance imaging (MRI).

  3. Muscle Disease Transcripts [ Time Frame: Week 24 ]
    To evaluate the change from baseline in inflammatory, immune, apoptotic, and muscle disease transcripts in muscle biopsies by quantitative PCR analysis.

  4. Circulating Proteins [ Time Frame: Week 24 ]
    To evaluate the change from baseline in circulating proteins in plasma and serum by ELISA analysis.

  5. Reachable Work Space (RWS) [ Time Frame: Week 25 ]
    Subjects are seated in front of a 3D camera and asked to perform a standardized upper extremity movement protocol under the supervision of a study clinical evaluator with and without weights.

  6. Timed Up and Go (TUG). [ Time Frame: Week 25 ]
    Subjects are timed as they start from a seated or laying position, rise to a standing position, walk a total of 6 meters and then return to either a seated or laying position.

  7. Muscle Strength [ Time Frame: Week 25 ]
    Muscle strength will be assessed by Hand-Held Quantitative Dynamometry.

  8. Motor Function Measure (MFM) Domain 1. [ Time Frame: Week 25 ]
    The MFM domain 1 is a validated evaluator administered functional measure for neuromuscular disorders, with 13 items related to standing and transfers.

  9. FSHD Health Index (FSHD-HI). [ Time Frame: Week 25 ]
    The HI is a 15 domain questionnaire designed and based on patient interviews to measure total FSHD health-related quality-of-life, including both motor impairment and the social and emotional impact of FSHD. 116 questions are combined into a total score, the score is transformed onto a percentage scale, with 100 representing maximal disability, and lower scores representing decreasing disability.

  10. Patients' Global Impression of Change (PGIC). [ Time Frame: Week 25 ]
    The PGIC is a single question that assesses on a scale of 1-7 if there has been an improvement, decline or no change in clinical status.



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 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 willing 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): NCT04003974


Contacts
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Contact: Call Center 617-651-8853 clinicaltrials@fulcrumtx.com

Locations
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United States, California
University of California Irvine Not yet recruiting
Irvine, California, United States, 92868
Contact: Shannon Ung    714-509-2663    ungsa@uci.edu   
University of California Los Angeles (UCLA) Not yet recruiting
Los Angeles, California, United States, 90095
Contact: Dianne de Guzman    310-825-3264    DDeGuzman@mednet.ucla.edu   
United States, Florida
University of Florida Not yet recruiting
Gainesville, Florida, United States, 32610
Contact: Victoria Hope    352-733-2436    Victoria.Hope@neurology.ufl.edu   
United States, Kansas
University of Kansas Medical Center Recruiting
Kansas City, Kansas, United States, 66160
Contact: Katie Roath, MS    913-945-9928    kroath@kumc.edu   
United States, Maryland
Kennedy Krieger Institute Recruiting
Baltimore, Maryland, United States, 21205
Contact: Genila Bibat, MD    443-923-2967    bibat@kennedykrieger.org   
United States, Missouri
Washington University School of Medicine Not yet recruiting
Saint Louis, Missouri, United States, 63110
Contact: June Smith    314-362-6986    smith.june@wustl.edu   
United States, New York
University of Rochester Medical Center Not yet recruiting
Rochester, New York, United States, 14642
Contact: Elizabeth Luebbe    585-275-7867    Elizabeth_Luebbe@URMC.Rochester.edu   
United States, Utah
University of Utah Not yet recruiting
Salt Lake City, Utah, United States, 84132
Contact: Summer Gibson, MD    801-581-4474    summer.gibson@hsc.utah.edu   
United States, Virginia
Virginia Commonwealth University Not yet recruiting
Richmond, Virginia, United States, 23298
Contact: Nicholas Johnson, MD    804-828-9350    nicholas.johnson@vcuhealth.org   
United States, Washington
University of Washinton Medical Center Not yet recruiting
Seattle, Washington, United States, 98195
Contact: Kate Aladjieva    206-598-7688    neustudy@uw.edu   
Canada, Ontario
Ottawa Hospital Research Institute Not yet recruiting
Ottawa, Ontario, Canada, K1Y 4E9
Contact: Sergio Guber, CRC    613-798-5555 ext 19627    sguber@toh.ca   
Canada, Quebec
Montreal Neurological Institute and Hospital Not yet recruiting
Montréal, Quebec, Canada, H3A 2B4
Contact: Xin Di Dong    514-398-5262    xin.dong@mcgill.ca   
France
CHU de NICE- CHU pasteur2 Not yet recruiting
Nice, France, 06001
Contact: Sabrini Sacconi    +33 0492035753    sacconi.s@chu-nice.fr   
Institut de Myologie Groupe Hospitalier Pitié-Salpêtrière Not yet recruiting
Paris, France, 75651
Contact: Kubéraka Mariampillai, PhD    01 42 17 80 86    kuberaka.mariampillai-ext@aphp.fr   
Contact: Teresinha Evangelista, MD    06 14 48 11 52    t.evangelista@institut-myologie.org   
Germany
University Hospital Bonn Not yet recruiting
Bonn, Germany, 53105
Contact: Iliana Johannes    +49 (0) 228 287 31383    iliana.johannes@ukbonn.de   
Friedrich-Baur Institute, Ludwig-Maximilian University - Munich Not yet recruiting
Munich, Germany, 80336
Contact: Benedikt Schoser, MD    0049089440057400    fbi@lmu.med.de   
Spain
Hospital de la Sta Creu i St Pau Not yet recruiting
Barcelona, Spain, 08041
Contact: Núria Vidal Fernandez, RN, MSc    +34.93.553.71.15    mvidalf@santpau.cat   
Hospital UiP La Fe Not yet recruiting
Valencia, Spain, 46026
Contact: Juan Vilchez, MD    961244153    unidadneuromuscularlafe@gmail.com   
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: NCT04003974     History of Changes
Other Study ID Numbers: FIS-002-2019
First Posted: July 1, 2019    Key Record Dates
Last Update Posted: August 15, 2019
Last Verified: August 2019
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 Dystrophies
Muscular Dystrophy
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