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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
114
PF-06939926 will be administered as a single IV infusion at Year 1 for Cohort 1.
Placebo will be administered as a single IV infusion at Year 1 for Cohort 2.
Placebo will be administered as a single IV infusion at Year 2 for Cohort 1.
Change From Baseline in North Star Ambulatory Assessment (NSAA) Total Score at Week 52
The NSAA was a 17-item test that graded performance of various functional skills using the following scale: 0 (unable to achieve independently), 1 (modified method but achieves goal independent of physical assistance from another), and 2 ("normal"- no obvious modification of activity). Total score was calculated as the sum of all 17 individual item responses and ranged from 0 (worst) to 34 (fully independent function) with higher scores indicating better function. Baseline NSAA total score is defined as the last non-missing NSAA total score collected prior to Year 1 drug administration.
Time frame: Baseline, Week 52
Change From Baseline in Percent Normal Dystrophin Expression Level in Muscle Biopsies by Liquid Chromatography Mass Spectrometry (LC-MS) Based on LLQV Peptide at Week 52
The LC-MS assay measured the LLQVAVEDR (LLQV) peptide that detected full-length endogenous dystrophin as well as the mini-dystrophin transgene protein.
Time frame: Baseline, Week 52
Change From Baseline in Percent of Muscle Fibers Expressing Mini-Dystrophin in Muscle Biopsies by Immunofluorescence at Week 52
Muscle fibers expressing mini-dystrophin transgene protein were evaluated by immunofluorescent staining using the mini-dystrophin specific antibody which only recognized the mini-dystrophin transgene protein.
Time frame: Baseline, Week 52
Change From Baseline in Serum Creatine Kinase (CK) Concentration at Week 52
The CK results were analyzed by the central laboratory.
Time frame: Baseline, Week 52
Least Square Mean of Proportion of Skills Gained Based on the Individual Items of the NSAA at Week 52
Proportion of skills gained at Week 52 were expressed as a proportion of the number of skills at Baseline that could be gained (numerator was number of items on NSAA gained at Week 52, with response 1 or 2 and denominator was number of items on NSAA with score 0 at baseline). The NSAA was a 17-item test that graded performance of various functional skills using the following scale: 0 (unable to achieve independently), 1 (modified method but achieves goal independent of physical assistance from another), and 2 ("normal"- no obvious modification of activity). Total score was calculated as the sum of all 17 individual item responses and ranged from 0 (worst) to 34 (fully independent function) with higher scores indicating better function.
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PF-06939926 will be administered as a single IV infusion at Year 2 for Cohort 2
Arkansas Children's Hospital
Little Rock, Arkansas, United States
Arkansas Children's
Little Rock, Arkansas, United States
UCLA Medical Center
Los Angeles, California, United States
University of Florida
Gainesville, Florida, United States
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States
KU Clinical Research Center - Clinical and Translational Science Unit (CTSU) - Fairway
Fairway, Kansas, United States
KU Clinical Research Center - Clinical and Translational Science Unit (CTSU) - Rainbow
Kansas City, Kansas, United States
University of Kansas Hospital - Investigational Pharmacy
Kansas City, Kansas, United States
University of Kansas Hospital - Pediatric and Pediatric ICU - Operating Room
Kansas City, Kansas, United States
University of Kansas Medical Center
Kansas City, Kansas, United States
...and 43 more locations
Time frame: Baseline, Week 52
Least Square Mean of Proportion of Skills Either Improved or Maintained Based on the Individual Items of the NSAA at Week 52
Proportion of skills either improved or maintained at Week 52 was expressed as a proportion of the number of items at Baseline that could be improved or maintained (numerator was the number of items on NSAA improved or maintained at Week 52 and denominator is number of items on NSAA which is 17). The NSAA was a 17-item test that graded performance of various functional skills using the following scale: 0 (unable to achieve independently), 1 (modified method but achieves goal independent of physical assistance from another), and 2 ("normal"- no obvious modification of activity). Total score was calculated as the sum of all 17 individual item responses and ranged from 0 (worst) to 34 (fully independent function) with higher scores indicating better function.
Time frame: Baseline, Week 52
Change From Baseline in 10 Meter Run/Walk Velocity at Week 52
Velocity was calculated based on the time it took to complete the 10-meter run/walk test.
Time frame: Baseline, Week 52
Change From Baseline in Rise From Floor Velocity at Week 52
Velocity was calculated based on the time it took to rise from floor.
Time frame: Baseline, Week 52
Change From Baseline in Modified Pediatric Outcome Data Collection Instrument (PODCI)- Transfer and Basic Mobility Core Scale at Week 52
Modified PODCI- transfer and basic mobility core scale (parent of pediatric participant) consisted of 11 items that assessed how caregivers of participants evaluated a participant's ability to walk, stand, and perform activities of daily living. The scale produced an independent, standardized score ranging from 0-100, with lower scores representing lower levels of function.
Time frame: Baseline, Week 52
Change From Baseline in Modified PODCI- Sports and Physical Functioning Core Scale at Week 52
Modified PODCI- sports and physical functioning core scale (parent of pediatric participant) consisted of 21 items that assessed how caregivers of participants evaluated a participant's ability to perform recreational activities. The scale produced an independent, standardized score ranging from 0-100, with lower scores representing lower levels of function.
Time frame: Baseline, Week 52