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

Phase 1

Completed

• Conditions: Becker Muscular Dystrophy
• Interventions: Drug: (+)-Epicatechin

• Registration Number: NCT04386304
• Lead Sponsor: Epirium Bio Inc.

Brief Summary

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

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 Timeline

• Study First Submitted: 2020-05-01
• Study First Submitted QC: 2020-05-08
• Study First Posted: 2020-05-13
• Study Start: 2020-07-13
• Status Verified: 2022-03
• Primary Completion: 2022-03-01
• Study Completion: 2022-03-01
• Last Update Submitted: 2022-03-22
• Last Update Posted: 2022-03-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 22

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose escalation of (+)-epicatechin	(+)-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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (3)

University of California - Davis Department of Physical Medicine and Rehabilitation; 🇺🇸 Sacramento, California, United States

UCLA Dept of Human Genetics; 🇺🇸 Los Angeles, California, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States