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

February 4, 2013 updated by: Jerry R. Mendell, Nationwide Children's Hospital

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

6

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Columbus, Ohio, United States, 43205
        • Columbus Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 years to 13 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Low Dose
Low dose cohort - 2.0E10 vg/kg
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.
Experimental: High Dose
High Dose - 1.0E11 vg/kg
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Time Frame: 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)
followed for 2 years post injection

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nationwide Children's Hospital

Collaborators

Asklepios Biopharmaceutical, Inc.

Investigators

  • Principal Investigator: Jerry R. Mendell, MD, Nationwide Children's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2006

Primary Completion (Actual)

March 1, 2009

Study Completion (Actual)

July 1, 2010

Study Registration Dates

First Submitted

January 26, 2007

First Submitted That Met QC Criteria

January 26, 2007

First Posted (Estimate)

January 30, 2007

Study Record Updates

Last Update Posted (Estimate)

February 5, 2013

Last Update Submitted That Met QC Criteria

February 4, 2013

Last Verified

February 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CCRI IRB05-00118

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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