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

• ClinicalTrials.gov Identifier: NCT04386304
• Recruitment Status: Completed
• First Posted: May 13, 2020
• Last Update Posted: March 23, 2022
• Sponsor: Epirium Bio Inc.
• Information provided by (Responsible Party): Epirium Bio Inc.

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Becker Muscular Dystrophy	Drug: (+)-Epicatechin	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 22 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: July 13, 2020
• Actual Primary Completion Date: March 1, 2022
• Actual Study Completion Date: March 1, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Number of participants with treatment-emergent adverse events (TEAEs) [ Time Frame: 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 :

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, California

UCLA Dept of Human Genetics

Los Angeles, California, United States, 90095

University of California - Davis Department of Physical Medicine and Rehabilitation

Sacramento, California, United States, 95817

United States, Missouri

Washington University School of Medicine

Saint Louis, Missouri, United States, 63110

Sponsors and Collaborators

Epirium Bio Inc.

Investigators

• Study Director: Chief Medical Officer; Epirium Bio Inc.

More Information

• Responsible Party: Epirium Bio Inc.
• ClinicalTrials.gov Identifier: NCT04386304
• Other Study ID Numbers: EPM-01-101
• First Posted: May 13, 2020
• Last Update Posted: March 23, 2022
• Last Verified: March 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Muscular Dystrophies; Muscular Dystrophy, Duchenne; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked