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

Duchenne Muscular Dystrophy Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04281485
• Other study ID #: C3391003
• Secondary ID: 2019-002921-31
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: November 5, 2020
• Est. completion date: April 19, 2029

Study information

• Verified date: June 2024
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 122
• Est. completion date: April 19, 2029
• Est. primary completion date: May 15, 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 4 Years to 7 Years

Eligibility

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.

Related Conditions & MeSH terms

• Duchenne Muscular Dystrophy
• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

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.
• 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

Locations

Country	Name	City	State
Australia	Perth Children's Hospital	Nedlands	Western Australia
Australia	The Royal Children's Hospital Melbourne	Parkville	Victoria
Australia	The Children's Hospital at Westmead	Westmead	New South Wales
Belgium	UZ Gent	Gent
Belgium	UZ leuven	Leuven
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	Children's Hospital - London Health Sciences Centre	London	Ontario
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
France	CHU de Nantes- Hotel Dieu	Nantes
France	Hopital Necker	Paris
Germany	Charité - Universitätsmedizin Berlin	Berlin
Germany	Charité Universitaetsmedizin Berlin	Berlin
Germany	Universitaetsklinikum Essen	Essen
Germany	Universitaetsklinikum Essen	Essen	North Rhine-westphalia
Germany	Universitatsklinikum Essen	Essen
Israel	Hadassah University Medical Center, Ein Kerem	Jerusalem
Israel	Schneider Children's Medical Center of Israel	Petach Tikvah
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Roma
Italy	IRCCS Ospedale Pediatrico Bambino Gesù	Rome
Japan	Nagoya City University Hospital	Nagoya	Aichi
Japan	Hyogo College of Medicine College Hospital	Nishinomiya	Hyogo
Japan	National Center of Neurology and Psychiatry	Tokyo
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Pusan National University Yangsan Hospital	Yangsan-si	Gyeongsangnam-do
Russian Federation	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
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Hospital Sant Joan de Déu	Esplugues de Llobregat	Barcelona
Spain	Hospital Universitari i Politecnic La Fe de Valencia	Valencia
Switzerland	Inselspital, University Children's Hospital Berne	Bern
Switzerland	Universitaets-Kinderspital Zuerich	Zurich
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
United Kingdom	Alder Hey Children's NHS Foundation Trust	Liverpool	Merseyside
United Kingdom	Great Ormond Street Institute of Child Health	London
United Kingdom	The Newcastle upon Tyne Hospitals NHS Foundation Trust, Royal Victoria Infirmary	Newcastle upon Tyne	England
United States	KU Clinical Research Center - Clinical and Translational Science Unit (CTSU) - Fairway	Fairway	Kansas
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
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	Arkansas Children's	Little Rock	Arkansas
United States	Arkansas Children's Hospital	Little Rock	Arkansas
United States	MRI Research Center	Los Angeles	California
United States	Reed Neurological Research Center	Los Angeles	California
United States	Ronald Reagan UCLA Medical Center (Investigational Drug Section)	Los Angeles	California
United States	Ronald Reagan UCLA Medical Center - Drug Information Center	Los Angeles	California
United States	UCLA (David Geffen School of Medicine)	Los Angeles	California
United States	UCLA Children's Heart Center	Los Angeles	California
United States	UCLA Clinical Lab Services	Los Angeles	California
United States	UCLA Mattel Children's Hospital	Los Angeles	California
United States	UCLA Medical Center	Los Angeles	California
United States	UCLA Outpatient Surgery Center	Los Angeles	California
United States	Children's Specialty Group, PLLC Division of Child & Adolescent Neurology	Norfolk	Virginia
United States	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	UPMC Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Pediatric Cardiology	Prairie Village	Kansas
United States	Primary Children's Hospital	Salt Lake City	Utah
United States	University of Utah Center for Clinical & Tranlational Science	Salt Lake City	Utah
United States	University of Utah Clinical Neurosciences Center	Salt Lake City	Utah
United States	University of Utah Hospital	Salt Lake City	Utah
United States	University of Utah Hospital & Clinics Investigational Drug Services	Salt Lake City	Utah
United States	University of Utah Imaging and Neurosciences Center	Salt Lake City	Utah
United States	Seattle Children's	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Germany,  Israel,  Italy,  Japan,  Korea, Republic of,  Russian Federation,  Spain,  Switzerland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Change from Baseline in serum creatine kinase (CK)	Changes in the circulating levels of CK.	Week 52
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

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