Duchenne Muscular Dystrophy
Conditions
Keywords
Duchenne, Muscle, Muscular Dystrophy, Gene Therapy, Dystrophin, Adeno-Associated Virus, AAV
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.
Interventions
BIOLOGICALrAAV2.5-CMV-minidystrophin (d3990)
Recombinant adeno-associated virus (AAV) carrying a truncated human dystrophin gene (mini-dystrophin) expressed from a cytomegalovirus (CMV) promoter.
Sponsors
AskBio Inc
Nationwide Children's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
5 Years to 15 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 |
Countries
United States
Outcome results
None listed