Study to Evaluate the Safety and Efficacy of PF-06939926 for the Treatment of Duchenne Muscular Dystrophy
- Conditions
- Duchenne Muscular Dystrophy
- Interventions
- Other: PlaceboGenetic: PF-06939926
- Registration Number
- NCT04281485
- Lead Sponsor
- Pfizer
- Brief 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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Male
- Target Recruitment
- 122
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 2 Placebo Approximately one third of participants will be randomized to Cohort 2. Cohort 1 PF-06939926 Approximately two thirds of participants will be randomized to Cohort 1. Cohort 2 PF-06939926 Approximately one third of participants will be randomized to Cohort 2. Cohort 1 Placebo Approximately two thirds of participants will be randomized to Cohort 1.
- Primary Outcome Measures
Name Time Method Change from Baseline in North Star Ambulatory Assessment (NSAA) Week 52 The NSAA is a 17-item test that measures gross motor function in children with Duchenne.
- Secondary Outcome Measures
Name Time Method Change from Baseline in the Modified Pediatric Outcomes Data Collection Instrument (PODCI): Transfer and Basic Mobility Core Scale Week 52 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.
Change from Baseline in the 10-meter run/walk test velocity Week 52 Velocity is calculated based on the time that it takes to complete the 10-meter run/walk test.
Change from Baseline in mini-dystrophin expression level in muscle Week 52 Mini-dystrophin expression level from a muscle biopsy will be assessed by liquid chromatography mass spectrometry (LC-MS).
Number of skills gained based on the individual items of the NSAA. Week 52 To count the skills that each child gained, based on the individual items of the NSAA.
Number of skills improved or maintained based on the individual items of the NSAA Week 52 To count the skills that each child improved or maintained, based on the individual items of the NSAA.
Change from Baseline in distribution of mini-dystrophin expression in the muscle Week 52 Mini-dystrophin distribution from a muscle biopsy will be assessed by immunofluorescence.
Change from Baseline in serum creatine kinase (CK) Week 52 Changes in the circulating levels of CK.
Change from Baseline in the rise from floor velocity Week 52 Velocity is calculated based on the time that it takes to the rise from floor.
Change from Baseline in the Modified Pediatric Outcomes Data Collection Instrucment (PODCI): Sports and Physical Functioning Core Scale Week 52 The PODCI contains a list of questions to assess how each caregiver/child evaluates the child´s ability to perform recreational activities.
Trial Locations
- Locations (49)
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 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
Pediatric Cardiology
🇺🇸Prairie Village, Kansas, United States
The Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
University of Utah Clinical Neurosciences Center
🇺🇸Salt Lake City, Utah, United States
Seattle Children's
🇺🇸Seattle, Washington, United States
The Children's Hospital at Westmead
🇦🇺Westmead, New South Wales, Australia
The Royal Children's Hospital Melbourne
🇦🇺Parkville, Victoria, Australia
Perth Children's Hospital
🇦🇺Nedlands, Western Australia, Australia
UZ Gent
🇧🇪Gent, Belgium
UZ leuven
🇧🇪Leuven, Belgium
Alberta Children's Hospital
🇨🇦Calgary, Alberta, Canada
Children's Hospital - London Health Sciences Centre
🇨🇦London, Ontario, Canada
Childrens Hospital of Eastern Ontario
🇨🇦Ottawa, Ontario, Canada
The Hospital For Sick Children
🇨🇦Toronto, Ontario, Canada
CHU de Nantes- Hotel Dieu
🇫🇷Nantes, France
Hopital Necker
🇫🇷Paris, France
Charité - Universitätsmedizin Berlin
🇩🇪Berlin, Germany
Universitatsklinikum Essen
🇩🇪Essen, Germany
Hadassah University Medical Center, Ein Kerem
🇮🇱Jerusalem, Israel
Schneider Children's Medical Center of Israel
🇮🇱Petach Tikvah, Israel
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
🇮🇹Roma, Italy
IRCCS Ospedale Pediatrico Bambino Gesù
🇮🇹Rome, Italy
Nagoya City University Hospital
🇯🇵Nagoya, Aichi, Japan
Hyogo College of Medicine College Hospital
🇯🇵Nishinomiya, Hyogo, Japan
National Center of Neurology and Psychiatry
🇯🇵Tokyo, Japan
Pusan National University Yangsan Hospital
🇰🇷Yangsan-si, Gyeongsangnam-do, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Saint Petersburg State Paediatric Medical University
🇷🇺Saint Petersburg, Russian Federation
State Autonomous Healthcare Institution of Sverdlovsk Region Children's City Clinical Hospital No 9
🇷🇺Yekaterinburg, Russian Federation
Hospital Sant Joan de Déu
🇪🇸Esplugues de Llobregat, Barcelona, Spain
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Universitari i Politecnic La Fe de Valencia
🇪🇸Valencia, Spain
Inselspital, University Children's Hospital Berne
🇨🇭Bern, Switzerland
Universitaets-Kinderspital Zuerich
🇨🇭Zurich, Switzerland
Kaohsiung Medical University Chung-Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
The Newcastle upon Tyne Hospitals NHS Foundation Trust, Royal Victoria Infirmary
🇬🇧Newcastle upon Tyne, England, United Kingdom
Alder Hey Children's NHS Foundation Trust
🇬🇧Liverpool, Merseyside, United Kingdom
Great Ormond Street Institute of Child Health
🇬🇧London, United Kingdom