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

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

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).

Study Overview

• Status: Completed
• Conditions: Becker Muscular Dystrophy
• Intervention / Treatment: Drug: (+)-Epicatechin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Dept of Human Genetics
    • Sacramento, California, United States, 95817
      • University of California - Davis Department of Physical Medicine and Rehabilitation
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 59 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

INCLUSION CRITERIA:

1. Participant must be ≥16 to <60 years of age.
2. Genotype confirmation showing a mutation of the dystrophin gene.
3. Ambulation - participants must show a history of ambulation past the age of 16 years, with continued ambulation thereafter.
4. 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:

1. A diagnosis of other neurological diseases or presence of relevant somatic disorders that are not related to Becker muscular dystrophy.
2. Participants with a history of migraine headaches requiring medical attention and active treatment within the past 6 months.
3. Participants with allergies to chocolate or cocoa.
4. 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.
5. Presence of a concomitant neurologic disease (e.g., Parkinson's disease) that could negatively impact mobility or balance.
6. Symptomatic heart failure (New York Heart Association Class III or IV) or known left ventricular ejection fraction <40% by echocardiogram.
7. Presence of documented intrinsic lung disease (e.g., chronic obstructive pulmonary disease, pulmonary fibrosis).
8. Evidence of current liver disease or impairment.
9. Inadequate renal function.
10. Platelet count, WBC count, and hemoglobin at Screening <Lower Limit of Normal (LLN).
11. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose escalation of (+)-epicatechin; 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; (+)-Epicatechin is a synthetic flavanol; Other Names: EB 002; EPM-01

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Epirium Bio Inc.
• Investigators: Study Director: Chief Medical Officer, Epirium Bio Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 13, 2020
• Primary Completion (Actual): March 1, 2022
• Study Completion (Actual): March 1, 2022

Study Registration Dates

• First Submitted: May 1, 2020
• First Submitted That Met QC Criteria: May 8, 2020
• First Posted (Actual): May 13, 2020

Study Record Updates

• Last Update Posted (Actual): March 23, 2022
• Last Update Submitted That Met QC Criteria: March 22, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: EPM-01-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No