Gene Transfer Clinical Trial for Duchenne Muscular Dystrophy Using rAAVrh74.MCK.GALGT2

Phase I Gene Transfer Clinical Trial for Duchenne Muscular Dystrophy Using rAAVrh74.MCK.GALGT2

The proposed clinical trial study of rAAVrh74.MCK.GALGT2 for duchenne muscular dystrophy (DMD) patients that will involve direct intramuscular injection to the extensor digitorum brevis muscle (EDB).

This is a phase I safety and tolerability study. Three DMD subjects will receive bilateral injections into the EDB muscle, with one EDB receiving the GALGT2 vector (rAAVrh74.MCK.GALGT2) and the other side receiving saline alone (assigned in a randomized fashion). Three subjects will receive a single gene transfer dose of 1E12 vector genomes, and patients and investigators will be blinded as to which muscle is injected with vector. Muscle biopsies will be performed at three months (12 weeks) in two subjects and at 1.5 months (6 weeks) in one subject and evaluated blindly for the expression of the GALGT2 transgene.

Inclusion Criteria:

• Nonambulant subjects, age 9 or older
• Confirmed mutation in the DMD gene using a clinically accepted technique that completely defines the mutation
• A magnetic resonance image of the EDB showing preservation of sufficient muscle mass to permit transfection
• Males of any ethnic group will be eligible
• Ability to cooperate with all study procedures
• Willingness of sexually active subjects with reproductive capacity to practice reliable method of contraception (If appropriate).
• Stable dose of corticosteroid therapy (including either prednisone or deflazacort and their generic forms) for 12 weeks prior to gene transfer

Exclusion Criteria:

• Active viral infection based on clinical observations.
• The presence of a DMD mutation without weakness or loss of function
• Symptoms or signs of cardiomyopathy, including:
• Dyspnea on exertion, pedal edema, shortness of breath upon lying flat, or rales at the base of the lungs
• Echocardiogram with ejection fraction below 40%
• Serological evidence of HIV infection, or Hepatitis A, B or C infection
• Diagnosis of (or ongoing treatment for) an autoimmune disease
• Persistent leukopenia or leukocytosis (WBC ≤ 3.5 K/µL or ≥ 20.0 K/µL) or an absolute neutrophil count < 1.5K/µL
• Concomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer
• Subjects with rAAVrh74 binding antibody titers ≥ 1:400 as determined by ELISA immunoassay
• Presence of circulating anti-Sda antibodies as determined by study approved laboratory.
• Abnormal laboratory values in the clinically significant range, based upon normal values in the Nationwide Children's Hospital Laboratory