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

Duchenne Muscular Dystrophy Clinical Trial

Official title:

Phase 1 Clinical Trial of rAAV2.5-CMV-mini-Dystrophin Gene Vector in Duchenne Muscular Dystrophy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00428935
• Other study ID #: CCRI IRB05-00118
• Status: Completed
• Phase: Phase 1
• First received: January 26, 2007
• Last updated: February 4, 2013
• Start date: March 2006
• Est. completion date: July 2010

Study information

• Verified date: February 2013
• Source: Nationwide Children's Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: July 2010
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 5 Years to 15 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Duchenne Muscular Dystrophy
• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

Intervention

Biological:
• rAAV2.5-CMV-minidystrophin (d3990)
Recombinant adeno-associated virus (AAV) carrying a truncated human dystrophin gene (mini-dystrophin) expressed from a cytomegalovirus (CMV) promoter.

Locations

Country	Name	City	State
United States	Columbus Children's Hospital	Columbus	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Nationwide Children's Hospital	Asklepios Biopharmaceutical, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (4)

Bowles DE, McPhee SW, Li C, Gray SJ, Samulski JJ, Camp AS, Li J, Wang B, Monahan PE, Rabinowitz JE, Grieger JC, Govindasamy L, Agbandje-McKenna M, Xiao X, Samulski RJ. Phase 1 gene therapy for Duchenne muscular dystrophy using a translational optimized AA — View Citation

Mendell JR, Campbell K, Rodino-Klapac L, Sahenk Z, Shilling C, Lewis S, Bowles D, Gray S, Li C, Galloway G, Malik V, Coley B, Clark KR, Li J, Xiao X, Samulski J, McPhee SW, Samulski RJ, Walker CM. Dystrophin immunity in Duchenne's muscular dystrophy. N En — View Citation

Wang B, Li J, Xiao X. Adeno-associated virus vector carrying human minidystrophin genes effectively ameliorates muscular dystrophy in mdx mouse model. Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13714-9. — View Citation

Watchko J, O'Day T, Wang B, Zhou L, Tang Y, Li J, Xiao X. Adeno-associated virus vector-mediated minidystrophin gene therapy improves dystrophic muscle contractile function in mdx mice. Hum Gene Ther. 2002 Aug 10;13(12):1451-60. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Adverse Events as a Measure of Safety and Tolerability	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)	followed for 2 years post injection	Yes
Secondary	mini-dystrophin gene expression at the site of gene transfer		90 days post injection	No
Secondary	Maximal Volume Isometric Contraction Testing as a measure of muscle strength		out to 2 years post injection	No

External Links

•   Asklepios BioPharmaceutical Inc.
•   Columbus Children's Research Institute
•   Muscular Dystrophy Association