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

This is an open-label, dose escalation trial where the vector will be delivered via the
femoral artery to the muscles of both legs of DMD subjects.

The primary objective of this study is the assessment of the safety of intravascular
administration of rAAVrh74.MCK.GALGT2 to DMD patients. Safety endpoints will be assessed by
changes in hematology, serum chemistry, urinalysis, immunologic response to rAAVrh74 and
GALGT2, and reported history and observations of symptoms. Efficacy measures will be used as
secondary outcome for this disorder including a combination of functional 6 minute walk test
(6MWT) and direct muscle testing for strength (MVICT) of lower limb muscles.

Subjects will be evaluated at baseline, infusion visit (days 0-2), and return for follow up
visits on days 7, 14, 30, 60, 90, and 180 and months 12, 18 and 24

Inclusion Criteria

- 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

Exclusion Criteria

- Active viral infection based on clinical observations

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

- Subject is amenable to or is currently being treated with eteplirsen

- 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 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 ≥ 1:50 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