Safety Study of Mini-dystrophin Gene to Treat Duchenne Muscular Dystrophy

Phase 1

Completed

• Conditions: Duchenne Muscular Dystrophy
• Interventions: Biological: rAAV2.5-CMV-minidystrophin (d3990)

• Registration Number: NCT00428935
• Lead Sponsor: Nationwide Children's Hospital

Brief Summary

The purpose of this study is to determine the safety of a miniature dystrophin gene in the treatment of progressive muscle weakness due to Duchenne Muscular Dystrophy (DMD).

Detailed Description

This phase I randomized double blind dose escalation study investigates the safety and efficacy of the mini-dystrophin gene transferred to the biceps muscle for Duchenne muscular dystrophy patients, ages 5 to 12 years of age, using a recombinant adeno-associated virus. Eligible participants must have a known dystrophin gene mutation and may be concurrently treated with corticoid steroids. The mini-dystrophin gene or a placebo agent (normal saline or empty viral capsids) are injected directly into both biceps muscles while under conscious sedation. Following the gene transfer, patients are admitted to the hospital for 48 hours of observation followed by weekly outpatient visits at the Columbus Children's Hospital Neuromuscular Clinic. A bilateral muscle biopsy is preformed following 6 weeks with long term follow up will consisting of bi-annual visits for the next 2 years.

Study Timeline

• Study Start: 2006-03
• Study First Submitted: 2007-01-26
• Study First Submitted QC: 2007-01-26
• Study First Posted: 2007-01-30
• Primary Completion: 2009-03
• Study Completion: 2010-07
• Status Verified: 2013-02
• Last Update Submitted: 2013-02-04
• Last Update Posted: 2013-02-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 6

Inclusion Criteria

• Known null mutation of the Dystrophin gene
• Male age of 5 years or older
• If taking corticosteroids, must have dose unchanged for the past 3 months
• Serum creatine kinase elevation greater than 10x normal value (established by Children's Hospital)
• Progressive, symmetrical proximal muscle weakness of arms and legs

Exclusion Criteria

• Unable to cooperate for muscle strength testing
• Joint contractures that prohibit muscle strength testing
• Concomitant illness
• Individuals predisposed to excessive vagal responses (bradyarrhythmia or hypotension)
• Controlled substance abuse

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Low Dose	rAAV2.5-CMV-minidystrophin (d3990)	Low dose cohort - 2.0E10 vg/kg
High Dose	rAAV2.5-CMV-minidystrophin (d3990)	High Dose - 1.0E11 vg/kg

Primary Outcome Measures

Name	Time	Method
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	followed for 2 years post injection	Physical Exams assessing major organ systems and safety labs (GGT, Bilirubin, Glucose, Amylase, CBC/Diff, AFP, Platelets, PT/PTT, Creatinine, Electrolytes, Total protein, Alkaline phosphatase, and Urinalysis)

Secondary Outcome Measures

Name	Time	Method
mini-dystrophin gene expression at the site of gene transfer	90 days post injection
Maximal Volume Isometric Contraction Testing as a measure of muscle strength	out to 2 years post injection

Trial Locations

Locations (1)

Columbus Children's Hospital; 🇺🇸 Columbus, Ohio, United States