Evaluation of Safety, Tolerability, and Changes in Biomarker and Clinical Outcome Assessments of Losmapimod for FSHD1 (FSHD)
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|ClinicalTrials.gov Identifier: NCT04004000|
Recruitment Status : Recruiting
First Posted : July 1, 2019
Last Update Posted : August 28, 2019
|Condition or disease||Intervention/treatment||Phase|
|Facioscapulohumeral Muscular Dystrophy 1||Drug: Losmapimod||Phase 2|
This study is a Phase 2, single-centre, open-label pilot study that will investigate the safety, tolerability, pharmacokinetics (PK), and target engagement during long-term dosing with losmapimod tablets in adult subjects with Facioscapulohumeral Muscular Dystrophy 1 (FSHD1). Patients will participate in this for approximately 68 weeks. The total treatment duration will be approximately 52 weeks. Subjects will be evaluated during an 8-week pre-treatment period (Visits 1 through 3) to establish pre-treatment baseline assessments. Subjects will then be treated with losmapimod for approximately 52 weeks (Visits 4 through 9) and assessed at relatively regular intervals for change from pre-treatment in various assessments. 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 receive 15 mg of losmapimod twice daily given as two 7.5 mg tablets per dose by mouth; for a total of 4 pills or 30 mg daily for 52 weeks. All patients will be asked to visit the study clinic for each scheduled visit.
The primary endpoint of the study is to evaluate the safety and tolerability of long-term dosing of losmapimod tablets in subjects with FSHD1. Secondary endpoints include assessment of target engagement of losmapimod in blood and skeletal muscle and repeated dose pharmacokinetics in subjects with FSHD1 over long-term dosing.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||16 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||This is a single-centre, open-label pilot study.|
|Masking:||None (Open Label)|
|Official Title:||An Open-Label Pilot Study of Losmapimod to Evaluate the Safety, Tolerability, and Changes in Biomarker and Clinical Outcome Assessments in Subjects With Facioscapulohumeral Muscular Dystrophy 1 (FSHD1)|
|Actual Study Start Date :||August 23, 2019|
|Estimated Primary Completion Date :||December 2020|
|Estimated Study Completion Date :||January 2021|
FSHD1 patients with genetic confirmation with receive 15 mg of losmapimod twice daily given as two 7.5 mg tablets per dose by mouth; for a total of 4 pills or 30 mg daily for for up to approximately 52 weeks.
This study includes up to a 52 week treatment period. Patients will receive 15 mg of losmapimod 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.
- Treatment-Emergent Adverse Events [ Time Frame: Week 56 ]Incidence of treatment-emergent adverse events assessed by clinically significant laboratory test results, ECGs, and vital signs.
- Target Engagement in Blood [ Time Frame: Week 52 ]Change from baseline in phospho-HSP27 and ratio of pHSP27/total HSP27 will be measured in peripheral whole blood.
- Target Engagement in Skeletal Muscle [ Time Frame: Week 40 ]Change from baseline in phospho-HSP27 and ratio of pHSP27/total HSP27 will be measured in muscle.
- Plasma Concentration of Losmapimod [ Time Frame: Week 52 ]Blood samples will be collected to measure the plasma concentration of losmapimod at specified timepoints.
- Muscle Disease Transcripts [ Time Frame: Week 40 ]To evaluate the change from baseline in inflammatory, immune, apoptotic, and muscle disease transcripts in muscle biopsy and circulating proteins in plasma and serum.
- DUX4 Activity [ Time Frame: Week 40 ]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.
- Muscle Lean Tissue Volume [ Time Frame: Week 52 ]Change from baseline in skeletal muscle lean tissue volume as measured by whole body magnetic resonance imaging (MRI).
- Muscle Tissue Replacement by Fat [ Time Frame: Week 52 ]Change from baseline in skeletal muscle tissue replacement by fat as measured by whole body magnetic resonance imaging (MRI).
- Muscle Ultrasound [ Time Frame: Week 52 ]Ultrasound will be used to evaluate the echogenicity of specified muscles.
- Reachable Work Space (RWS) [ Time Frame: Week 52 ]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.
- Timed Up and Go (TUG) [ Time Frame: Week 52 ]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.
- Motor Function Measure (MFM) Domain 1 [ Time Frame: Week 52 ]The MFM domain 1 is a validated evaluator administered functional measure for neuromuscular disorders, with 13 items related to standing and transfers.
- Muscle Strength [ Time Frame: Week 52 ]Muscle strength will be assessed by Hand-Held Quantitative Dynamometry.
- FSHD Rasch-built Overall Disability Scale (RODS) [ Time Frame: Week 52 ]The FSHD-RODS is a patient-reported, linearly weighted scale that precisely measures activities of daily living (ADLs) and participation in subjects with FSHD using 50 items based on the Rasch model.
- FSHD Health Index (FSHD-HI) [ Time Frame: Week 52 ]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.
- Patients' Global Impression of Change (PGIC) [ Time Frame: Week 52 ]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.
- Real World Mobility Assessments [ Time Frame: Week 52 ]Each subject's activity will be monitored in the outpatient setting intermittently from the signing of the informed consent form (ICF) to the end of the study. Wearable activity monitoring devices will be provided to each subject at the start of the study. One device is placed on 1 arm, and 1 device goes on 1 leg.
- Respiratory Function [ Time Frame: Week 52 ]Forced vital capacity and forced expiratory volume in 1 second using bedside spirometry.
- Quantitative Dynamometry [ Time Frame: Week 52 ]Force will be measured on digital myometer, in KG-force.
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): NCT04004000
|Contact: Call Centerfirstname.lastname@example.org|
|Radboud University Medical Center||Recruiting|
|Nijmegen, Netherlands, 9101|
|Contact: Baziel Van Engelen, MD 024-361-34-59 email@example.com|
|Study Director:||Michelle Mellion, MD||Fulcrum Therapeutics|