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

Nationwide Children's Hospital

Status and phase: Completed; Phase 1

Conditions: Duchenne Muscular Dystrophy

Treatments: Biological: rAAV2.5-CMV-minidystrophin (d3990)

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00428935

CCRI IRB05-00118

Details and patient eligibility

About

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).

Full 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.

Enrollment: 6 patients

Sex: Male

Ages: 5 to 15 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: Quadruple Blind

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6 participants in 2 patient groups

Low Dose

Experimental group

Description:

Low dose cohort - 2.0E10 vg/kg

Treatment:

Biological: rAAV2.5-CMV-minidystrophin (d3990)

High Dose

Experimental group

Description:

High Dose - 1.0E11 vg/kg

Treatment:

Biological: rAAV2.5-CMV-minidystrophin (d3990)