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 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
• Enrollment (Actual): 114
• 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
  • Ghent, 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 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
  • Essen, Germany, 45147
    • Universitätsklinikum 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-ken
    • Nagoya, Aichi-ken, Japan, 467-8602
      • Nagoya City University Hospital
  • Hyōgo
    • Nishinomiya, Hyōgo, Japan, 663-8501
      • Hyogo College of Medicine College Hospital
• Russia
  • Saint Petersburg, Russia, 194100
    • Saint Petersburg State Paediatric Medical University
  • Yekaterinburg, Russia, 620134
    • State Autonomous Healthcare Institution of Sverdlovsk Region Children's City Clinical Hospital No 9
• South Korea
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 06351
    • Samsung Medical Center
  • Gyeongsangnam-do
    • Yangsan, Gyeongsangnam-do, South Korea, 50612
      • Pusan National University Yangsan Hospital
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe de Valencia
  • Barcelona
    • Esplugues de Llobregat, Barcelona, Spain, 08950
      • Hospital Sant Joan de Déu
• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital, University Children's Hospital Berne
  • Zurich, Switzerland, 8008
    • Universitaets-Kinderspital Zuerich
• Taiwan
  • Kaohsiung City, 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
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
  • 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
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Lenox Baker Children's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Hospital
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Clinical Neurosciences Center
    • Salt Lake City, Utah, United States, 84113
      • Primary Childrens Hospital
  • 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) 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.	Baseline, Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	Baseline, Week 52
Change From Baseline in Serum Creatine Kinase (CK) Concentration at Week 52	The CK results were analyzed by the central laboratory.	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.	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.	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.	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.	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.	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.	Baseline, Week 52

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Muntoni F, Nascimento A, Shin J, Guglieri M, Stettner GM, Veerapandiyan A, Gallo S, Shi H, Gundapaneni B, Neelakantan S, Lobello K, Shen Q, Levy DI, Mercuri E; CIFFREO Study Group. Safety and efficacy of fordadistrogene movaparvovec in ambulatory participants with Duchenne muscular dystrophy (CIFFREO): a phase 3, double-blind, randomised, placebo-controlled study. Lancet Neurol. 2026 Mar;25(3):245-255. doi: 10.1016/S1474-4422(26)00036-0.

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 (Actual): May 15, 2024
• Study Completion (Estimated): April 15, 2039

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): March 2, 2026
• Last Update Submitted That Met QC Criteria: February 16, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Clinical trial; Gene therapy; Duchenne muscular dystrophy; fordadistrogene movaparvovec
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Muscular Disorders, Atrophic; Muscular Dystrophies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Muscular Dystrophy, Duchenne; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: C3391003; 2023-508510-42-00 (Registry Identifier: CTIS (EU))

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