A Study to Evaluate the Safety and Tolerability of PF-06939926 Gene Therapy in Duchenne Muscular Dystrophy

This is a first-in-human/first-in-patient, multi-center, open-label, non-randomized, ascending dose, safety and tolerability study of a single intravenous infusion of PF-06939926 in ambulatory subjects with Duchenne muscular dystrophy (DMD). Other objectives include measurement of dystrophin expression and distribution, and assessments of muscle strength, quality, and function.

Two dose cohorts are planned with up to 6 subjects for each. In order to mitigate unanticipated risks to subject safety, enrollment will be staggered within and between the two cohorts and will include a formal review by an external data monitoring committee (E-DMC) prior to dose progression.

Inclusion Criteria:

• Diagnosis of Duchenne muscular dystrophy confirmed by medical history and genetic testing
• Body weight between 15 and 50 kg
• Receipt of glucocorticoids for 6 months and a stable daily dose for at least 3 months prior to study entry
• Ability to rise from floor within seven (7) seconds and ability to walk
• Ability to tolerate magnetic resonance imaging (MRI) without sedation and with no contraindications to these procedures
• Ability to tolerate muscle biopsies under anesthesia with no contraindications to these procedures

Exclusion Criteria:

• Receipt of live attenuated vaccination within 3 months prior or exposure to a systemic antiviral and/or interferon therapy within 30 days prior to receipt of PF-06939926
• Prior exposure to any gene therapy agent, including exon-skipping and missense agents
• Exposure to other investigational drugs within 30 days or 5 half-lives, whichever is longer
• Neutralizing antibodies (NAb) against adeno-associated virus, serotype 9 (AAV9) or pre-existing anti-dystrophin T-cell response
• Compromised cardiac function as indicated by a left ventricular ejection fraction of less than 55% on cardiac MRI
• Inadequate hepatic or renal function or risk factors for autoimmune disease on screening laboratory assessments.