Study to Evaluate the Safety and Efficacy of PF-06939926 for the Treatment of Duchenne Muscular Dystrophy

Study Overview
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Brief Summary
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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.

Detailed Description
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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 5 years after treatment with gene therapy. 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.

Official Title
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A PHASE 3, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO CONTROLLED STUDY TO EVALUATE THE SAFETY AND EFFICACY OF PF 06939926 FOR THE TREATMENT OF DUCHENNE MUSCULAR DYSTROPHY

Conditions
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Duchenne Muscular Dystrophy

Intervention / Treatment
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* Genetic: PF-06939926
* Other: Placebo
* Other: Placebo
* Genetic: PF-06939926


Participation Criteria
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Eligibility Criteria
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Key inclusion criteria: Confirmed diagnosis of Duchenne muscular dystrophy by prior genetic testing 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 Ambulatory, as assessed by protocol-specified criteria Key exclusion criteria: Positive test performed by Pfizer for neutralizing antibodies to AAV9 Any treatment designed to increase dystrophin expression within 6 months prior to screening (e.g., Translarna™, EXONDYS 51™, VYONDYS 53™) Any prior treatment with gene therapy Any non-healed injury that may impact functional testing (eg NSAA) Abnormality in specified laboratory tests, including blood counts, liver and kidney function Any of the following genetic abnormalities in the dystrophin gene: Any mutation (exon deletion, exon duplication, insertion, or point mutation) affecting any exon between exon 9 and exon 13, inclusive; OR A deletion that affects both exon 29 and exon 30;OR A deletion that affects any exons between 56-71, inclusive.

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 7 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel up to the measurement of the primary outcome at Week 52. At the beginning of study Year 2 participants who were originally assigned to placebo will have the opportunity to receive PF-06939926. All participants will be followed for 5 years following treatment with PF-06939926.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Cohort 1<br>Approximately two thirds of participants will be randomized to Cohort 1. | Genetic: PF-06939926<br>* PF-06939926 will be administered as a single IV infusion at Year 1 for Cohort 1.<br>Other: Placebo<br>* Placebo will be administered as a single IV infusion at Year 2 for Cohort 1.<br>|
| Other: Cohort 2<br>Approximately one third of participants will be randomized to Cohort 2. | Other: Placebo<br>* Placebo will be administered as a single IV infusion at Year 1 for Cohort 2.<br>Genetic: PF-06939926<br>* PF-06939926 will be administered as a single IV infusion at Year 2 for Cohort 2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in North Star Ambulatory Assessment (NSAA) | The NSAA is a 17-item test that measures gross motor function in children with Duchenne. | Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in mini-dystrophin expression level in muscle | Mini-dystrophin expression level from a muscle biopsy will be assessed by liquid chromatography mass spectrometry (LC-MS). | Week 52 | 
| Change from Baseline in distribution of mini-dystrophin expression in the muscle | Mini-dystrophin distribution from a muscle biopsy will be assessed by immunofluorescence. | Week 52 | 
| Change from Baseline in serum creatine kinase (CK) | Changes in the circulating levels of CK. | Week 52 | 
| Number of skills gained based on the individual items of the NSAA. | To count the skills that each child gained, based on the individual items of the NSAA. | Week 52 | 
| Number of skills improved or maintained based on the individual items of the NSAA | To count the skills that each child improved or maintained, based on the individual items of the NSAA. | Week 52 | 
| Change from Baseline in the 10-meter run/walk test velocity | Velocity is calculated based on the time that it takes to complete the 10-meter run/walk test. | Week 52 | 
| Change from Baseline in the rise from floor velocity | Velocity is calculated based on the time that it takes to the rise from floor. | Week 52 | 
| Change from Baseline in the Modified Pediatric Outcomes Data Collection Instrument (PODCI): Transfer and Basic Mobility Core Scale | The PODCI contains a list of questions to assess how each caregiver/child evaluates the child´s ability to to walk, stand, and perform activities of daily living. | Week 52 | 
| Change from Baseline in the Modified Pediatric Outcomes Data Collection Instrucment (PODCI): Sports and Physical Functioning Core Scale | The PODCI contains a list of questions to assess how each caregiver/child evaluates the child´s ability to perform recreational activities. | Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clinical trial, Gene therapy, Duchenne muscular dystrophy, fordadistrogene movaparvovec