study to evaluate the safety and efficacy of pf-06939926 for the treatment of duchenne muscular dystrophy

Conditions: Duchenne Muscular Dystrophy

Summary: the study will evaluate the safety and efficacy of gene therapy in boys with dmd. it is a randomized, double-blind, placebo-controlled study with two thirds of participants assigned to gene therapy. the one third of participants who are randomized to the placebo arm will have an opportunity for treatment with gene therapy at the beginning of the second year.

the study will assess the efficacy of pf-06939926 gene therapy on ambulatory function while also monitoring its safety. approximately 99 boys with dmd will be enrolled and randomly assigned to one of two groups: approximately two thirds will be in cohort 1 and receive gene therapy at the start of the study; approximately one third will be in cohort 2 and receive placebo at the start of the study and receive gene therapy after one year, as long as it remains safe to do so. the treatment (pf-06939926 gene therapy or placebo) will be given as an intravenous infusion lasting up to 2 hours. the study includes boys who are at least 4 years old and less than 8 years old (including 7 year olds up until their 8th birthday). all boys will need to be on a daily dose of glucocorticoids (prednisone, prednisolone, or deflazacort) for at least 3 months prior to enrolling and to stay on daily glucocorticoids for the first 2 years of the study. all boys will need to be negative for neutralizing antibodies against aav9, as measured by the test done for the study as part of screening. the primary outcome of the study will be assessed at 52 weeks. all participants will be followed in the study for 15 years after treatment with gene therapy. participants who received fordadistrogene movaparvovec in pfizer studies c3391001 and c3391008 or are currently enrolled in pfizer study c3391011 will be allowed to roll over into the long-term safety follow-up period of this study and will be considered cohort 3. the study medication, all medical tests associated with the study, and the visits to the study sites are free of charge. participants will also be supported for travel costs associated with study visits.

Eligibility criteria:
key inclusion criteria: 1. confirmed diagnosis of duchenne muscular dystrophy by prior genetic testing 2. receiving a stable daily dose (at least 0.5 mg/kg/day prednisone or prednisolone, or at least 0.75 mg/kg/day deflazacort) for at least 3 months prior to screening 3. ambulatory, as assessed by protocol-specified criteria key exclusion criteria: 1. positive test performed by pfizer for neutralizing antibodies to aav9 2. any treatment designed to increase dystrophin expression within 6 months prior to screening (e.g., translarna™, exondys 51™, vyondys 53™) 3. any prior treatment with gene therapy 4. any non-healed injury that may impact functional testing (eg nsaa) 5. abnormality in specified laboratory tests, including blood counts, liver and kidney function 6. any of the following genetic abnormalities in the dystrophin gene: 1. any mutation (exon deletion, exon duplication, insertion, or point mutation) affecting any exon between exon 9 and exon 13, inclusive; or 2. a deletion that affects both exon 29 and exon 30;or 3. a deletion that affects any exons between 56-71, inclusive.

Keywords: clinical trial gene therapy duchenne muscular dystrophy fordadistrogene movaparvovec