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

• ClinicalTrials.gov Identifier: NCT04281485
• Recruitment Status: Active, not recruiting
• First Posted: February 24, 2020
• Last Update Posted: April 4, 2024
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: February 11, 2020
• First Posted Date: February 24, 2020
• Last Update Posted Date: April 4, 2024
• Actual Study Start Date: November 5, 2020
• Estimated Primary Completion Date: May 31, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 20, 2020)

Change from Baseline in North Star Ambulatory Assessment (NSAA) [ Time Frame: Week 52 ]

The NSAA is a 17-item test that measures gross motor function in children with Duchenne.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 20, 2020)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Evaluate the Safety and Efficacy of PF-06939926 for the Treatment of Duchenne Muscular Dystrophy
• Official Title: 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
• 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 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
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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 (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

The study will be quadruple blind.

Primary Purpose: Treatment

• Condition: Duchenne Muscular Dystrophy

Intervention

• 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

Study Arms

• Cohort 1
  Approximately two thirds of participants will be randomized to Cohort 1.
  Interventions:

  • Genetic: PF-06939926
  • Other: Placebo
• Cohort 2
  Approximately one third of participants will be randomized to Cohort 2.
  Interventions:

  • Other: Placebo
  • Genetic: PF-06939926

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: February 20, 2020): 99
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 18, 2029
• Estimated Primary Completion Date: May 31, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Male

• Ages: 4 Years to 7 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, Canada, France, Germany, Israel, Italy, Japan, Korea, Republic of, Russian Federation, Spain, Switzerland, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT04281485
• Other Study ID Numbers: C3391003; 2019-002921-31 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Current Responsible Party: Pfizer
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: April 2024