Safety and Biomarker Response to (+)-Epicatechin in Becker Muscular Dystrophy

Study Overview
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Brief Summary
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This is a Phase 1, open-label, dose escalation study aimed at evaluating the safety, early efficacy and potential biomarkers of (+)-epicatechin in patients with Becker or Becker-like Muscular Dystrophy (BMD).

Detailed Description
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The safety and tolerability of three escalating doses of (+)-epicatechin will be assessed and early effectiveness measured by changes in plasma biomarkers, tissue biomarkers from muscle biopsies, cardiac imaging, and on clinical function assessments of participants' muscle strength. All patients will receive oral (+)-epicatechin for a total duration of approximately 52 weeks. Three doses of (+)-epicatechin will be tested in sequential 2 month periods with total daily doses of 75, 150, and 225 mg/day (+)-epicatechin. Doses will be escalated every 2 months, if tolerated, for the first 6 months of the study. Participants will then continue to receive the highest does they tolerated for an additional 6 months.

Official Title
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A Phase 1, Open-label, Dose Escalation Study to Evaluate the Safety and Preliminary Efficacy of Orally Administered (+)-Epicatechin in Patients With Becker or Becker-like Muscular Dystrophy With Continued Ambulation Past 16 Years of Age

Conditions
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Becker Muscular Dystrophy

Intervention / Treatment
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* Drug: (+)-Epicatechin


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Participant must be ≥16 to <60 years of age. Genotype confirmation showing a mutation of the dystrophin gene. Ambulation - participants must show a history of ambulation past the age of 16 years, with continued ambulation thereafter. If on glucocorticoid treatment in the last 12 months, participants must be on a stable dose at screening. Participants cannot start steroids during the study. EXCLUSION CRITERIA: A diagnosis of other neurological diseases or presence of relevant somatic disorders that are not related to Becker muscular dystrophy. Participants with a history of migraine headaches requiring medical attention and active treatment within the past 6 months. Participants with allergies to chocolate or cocoa. Surgery or orthopedic injury that might affect muscle strength or function within 3 months before study entry or planned surgery at any time during the study. Presence of a concomitant neurologic disease (e.g., Parkinson's disease) that could negatively impact mobility or balance. Symptomatic heart failure (New York Heart Association Class III or IV) or known left ventricular ejection fraction <40% by echocardiogram. Presence of documented intrinsic lung disease (e.g., chronic obstructive pulmonary disease, pulmonary fibrosis). Evidence of current liver disease or impairment. Inadequate renal function. Platelet count, WBC count, and hemoglobin at Screening <Lower Limit of Normal (LLN). Surgery or orthopedic injury that might affect muscle strength or function within 3 months before study entry or planned surgery at any time during the study

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 59 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose escalation of (+)-epicatechin<br>Subjects will receive escalating doses of (+)-epicatechin starting at 75 mg/day and progressing to 150 mg/day and 225 mg/day with 2 months treatment duration for each dose. Subjects will continue treatment on the individual's maximum tolerated dose for another 6 months. | Drug: (+)-Epicatechin<br>* (+)-Epicatechin is a synthetic flavanol<br>* Other names: EPM-01;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-emergent adverse events (TEAEs) | The TEAEs will be graded using the adult National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0). | Through study completion, up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cardiac function as assessed by cardiac magnetic resonance imaging (MRI) |  | Through study completion, up to 1 year | 
| Change in cardiac function as assessed by plasma biomarkers [e.g. pro-B-type natriuretic peptide (pro-BNP), nitrates]. |  | Through study completion, up to 1 year | 
| Change in muscle function as assessed by 6-minute walk test (6MWT) |  | Through study completion, up to 1 year | 
| Change in muscle function as assessed by Time to Run/Walk 10-meter Test (TTRW10) |  | Through study completion, up to 1 year | 
| Change in muscle function as assessed by Time to 4-stair Climb Test (TT4SC) |  | Through study completion, up to 1 year | 
| Change in muscle function as assessed by Time to Run/Walk 100-meter Test (TTRW100) |  | Through study completion, up to 1 year | 
| Change in muscle structure and function as assessed by Western blot analysis of biopsy specimens (e.g. dystrophin expression) |  | Through study completion, up to 1 year | 
| Change in muscle biomarkers of regeneration in biopsy specimens (e.g. follistatin) |  | Through study completion, up to 1 year | 
| Change in plasma biomarkers of muscle regeneration (e.g. follistatin, myostatin) |  | Through study completion, up to 1 year |