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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Duchenne Muscular Dystrophy
• Intervention / Treatment: Genetic: PF-06939926; Other: Placebo; Other: Placebo; Genetic: PF-06939926

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 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.

• Study Type: Interventional
• Enrollment (Estimated): 99
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • The Children's Hospital at Westmead
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • The Royal Children's Hospital Melbourne
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Perth Children's Hospital
• Belgium
  • Gent, Belgium, 9000
    • UZ Gent
  • Leuven, Belgium, 3000
    • UZ Leuven
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3B 6A8
      • Alberta Children's Hospital
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • Children's Hospital - London Health Sciences Centre
    • London, Ontario, Canada, N6A 4G5
      • Children's Hospital - London Health Sciences Centre
    • Ottawa, Ontario, Canada, K1H8L1
      • Childrens Hospital of Eastern Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children
• France
  • Nantes, France, 44093
    • CHU de Nantes- Hotel Dieu
  • Paris, France, 75015
    • Hôpital Necker
• Germany
  • Berlin, Germany, 13353
    • Charité - Universitätsmedizin Berlin
  • Berlin, Germany, 13353
    • Charite Universitaetsmedizin Berlin
  • Essen, Germany, 45147
    • Universitatsklinikum Essen
  • Essen, Germany, 45147
    • Universitaetsklinikum Essen
  • North Rhine-westphalia
    • Essen, North Rhine-westphalia, Germany, 45147
      • Universitaetsklinikum Essen
• Israel
  • Jerusalem, Israel, 91120
    • Hadassah University Medical Center, Ein Kerem
  • Petach Tikvah, Israel, 4920235
    • Schneider Children's Medical Center of Israel
• Italy
  • Roma, Italy, 00168
    • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
  • Rome, Italy, 00165
    • IRCCS Ospedale Pediatrico Bambino Gesu
• Japan
  • Tokyo, Japan, 187-8551
    • National Center of Neurology and Psychiatry
  • Aichi
    • Nagoya, Aichi, Japan, 467-8602
      • Nagoya City University Hospital
  • Hyogo
    • Nishinomiya, Hyogo, Japan, 663-8501
      • Hyogo College of Medicine College Hospital
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Gyeongsangnam-do
    • Yangsan-si, Gyeongsangnam-do, Korea, Republic of, 50612
      • Pusan National University Yangsan Hospital
• Russian Federation
  • Saint Petersburg, Russian Federation, 194100
    • Saint Petersburg State Paediatric Medical University
  • Yekaterinburg, Russian Federation, 620134
    • State Autonomous Healthcare Institution of Sverdlovsk Region Children's City Clinical Hospital No 9
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebrón
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe de Valencia
  • Barcelona
    • Esplugues de Llobregat, Barcelona, Spain, 08950
      • Hospital Sant Joan De Deu
• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital, University Children's Hospital Berne
  • Zurich, Switzerland, 8032
    • Universitaets-Kinderspital Zuerich
• Taiwan
  • Kaohsiung, Taiwan, 807
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
• United Kingdom
  • London, United Kingdom, WCIN 1EH
    • Great Ormond Street Institute of Child Health
  • England
    • Newcastle upon Tyne, England, United Kingdom, NE1 4LP
      • The Newcastle upon Tyne Hospitals NHS Foundation Trust, Royal Victoria Infirmary
  • Merseyside
    • Liverpool, Merseyside, United Kingdom, L12 2AP
      • Alder Hey Children's NHS Foundation Trust
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Hospital
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Medical Center
    • Los Angeles, California, United States, 90095
      • UCLA Mattel Children's Hospital
    • Los Angeles, California, United States, 90095
      • MRI Research Center
    • Los Angeles, California, United States, 90095
      • Reed Neurological Research Center
    • Los Angeles, California, United States, 90095
      • Ronald Reagan UCLA Medical Center (Investigational Drug Section)
    • Los Angeles, California, United States, 90095
      • UCLA (David Geffen School of Medicine)
    • Los Angeles, California, United States, 90095
      • UCLA Outpatient Surgery Center
    • Los Angeles, California, United States, 90095
      • Ronald Reagan UCLA Medical Center - Drug Information Center
    • Los Angeles, California, United States, 90095
      • UCLA Children's Heart Center
    • Los Angeles, California, United States, 90095
      • UCLA Clinical Lab Services
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Kansas
    • Fairway, Kansas, United States, 66205
      • KU Clinical Research Center - Clinical and Translational Science Unit (CTSU) - Fairway
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
    • Kansas City, Kansas, United States, 66160
      • KU Clinical Research Center - Clinical and Translational Science Unit (CTSU) - Rainbow
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Hospital - Investigational Pharmacy
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Hospital - Pediatric and Pediatric ICU - Operating Room
    • Prairie Village, Kansas, United States, 66208
      • Pediatric Cardiology
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15224
      • UPMC Children's Hospital of Pittsburgh
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • Primary Children's Hospital
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Hospital
    • Salt Lake City, Utah, United States, 84108
      • University of Utah Imaging and Neurosciences Center
    • Salt Lake City, Utah, United States, 84112
      • University of Utah Hospital & Clinics Investigational Drug Services
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Clinical Neurosciences Center
    • Salt Lake City, Utah, United States, 84108
      • University of Utah Center for Clinical & Tranlational Science
  • Virginia
    • Norfolk, Virginia, United States, 23510
      • Children's Specialty Group, PLLC Division of Child & Adolescent Neurology
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 7 years (Child)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2020
• Primary Completion (Estimated): May 31, 2024
• Study Completion (Estimated): April 18, 2029

Study Registration Dates

• First Submitted: February 11, 2020
• First Submitted That Met QC Criteria: February 20, 2020
• First Posted (Actual): February 24, 2020

Study Record Updates

• Last Update Posted (Actual): April 4, 2024
• Last Update Submitted That Met QC Criteria: April 3, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Clinical trial; Gene therapy; Duchenne muscular dystrophy; fordadistrogene movaparvovec
• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: C3391003; 2019-002921-31 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No