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

Prior treatment

• Subject is amenable to or is currently being treated with eteplirsen
• 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 ≥ 1:50 as determined by ELISA immunoassay

Other illness

• Active viral infection based on clinical observations
• Serological evidence of HIV infection, or Hepatitis B or C infection
• Diagnosis of (or ongoing treatment for) an autoimmune disease

Lab values

• 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%
• Persistent leukopenia or leukocytosis (WBC ≤ 3.5 K/µL or ≥ 20.0 K/µL) or an absolute neutrophil count \< 1.5K/µL
• 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

Other

• The presence of a DMD mutation without weakness or loss of function

• Ambulant patients age 4 years or older
• Confirmed mutations in the DMD gene using a clinical accepted technique that completely defines the mutation 1,2
• • Measurably impaired muscle function (defined as less than 80% of the predicted value for 100 MWT), but with sufficient muscle preservation to ensure assessment of muscle transfection based on clinical evaluation by the PI and expert colleagues. This degree of preservation will include:
  • Ability to extend the knee fully against gravity
  • Preserved ambulation with ability to walk ≥ 350 meters during the 6MWT
  • A magnetic resonance image of the quadriceps showing preservation of sufficient muscle mass to permit transfection
• Males of any ethnic group will be eligible
• Ability to cooperate with muscle testing
• Stable daily dose of corticosteroid therapy (including either prednisone, prednisolone, deflazacort or their generic forms) for 12 weeks prior to gene transfer