Clinical trial NCT04281485: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Duchenne Muscular Dystrophy
Keywords: Clinical trial
Gene therapy
Duchenne muscular dystrophy
fordadistrogene movaparvovec
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2020-02-24
Enrollment: 114
Sex: MALE
Minimum age (years): 4
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change From Baseline in North Star Ambulatory Assessment (NSAA) Total Score at Week 52
timeFrame: Baseline, Week 52
Secondary outcomes:
measure: 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
timeFrame: Baseline, Week 52
measure: Change From Baseline in Percent of Muscle Fibers Expressing Mini-Dystrophin in Muscle Biopsies by Immunofluorescence at Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in Serum Creatine Kinase (CK) Concentration at Week 52
timeFrame: Baseline, Week 52
measure: Least Square Mean of Proportion of Skills Gained Based on the Individual Items of the NSAA at Week 52
timeFrame: Baseline, Week 52
measure: Least Square Mean of Proportion of Skills Either Improved or Maintained Based on the Individual Items of the NSAA at Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in 10 Meter Run/Walk Velocity at Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in Rise From Floor Velocity at Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in Modified Pediatric Outcome Data Collection Instrument (PODCI)- Transfer and Basic Mobility Core Scale at Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in Modified PODCI- Sports and Physical Functioning Core Scale at Week 52
timeFrame: Baseline, Week 52
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Little Rock
country: United States
facility: Arkansas Children's
state: Arkansas
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Fairway
country: United States
facility: KU Clinical Research Center - Clinical and Translational Science Unit (CTSU) - Fairway
state: Kansas
city: Kansas City
country: United States
facility: KU Clinical Research Center - Clinical and Translational Science Unit (CTSU) - Rainbow
state: Kansas
city: Kansas City
country: United States
facility: University of Kansas Hospital - Investigational Pharmacy
state: Kansas
city: Kansas City
country: United States
facility: University of Kansas Hospital - Pediatric and Pediatric ICU - Operating Room
state: Kansas
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Prairie Village
country: United States
facility: Pediatric Cardiology
state: Kansas
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Salt Lake City
country: United States
facility: University of Utah Clinical Neurosciences Center
state: Utah
city: Seattle
country: United States
facility: Seattle Children's
state: Washington
city: Westmead
country: Australia
facility: The Children's Hospital at Westmead
state: New South Wales
city: Parkville
country: Australia
facility: The Royal Children's Hospital Melbourne
state: Victoria
city: Nedlands
country: Australia
facility: Perth Children's Hospital
state: Western Australia
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: UZ leuven
city: Calgary
country: Canada
facility: Alberta Children's Hospital
state: Alberta
city: London
country: Canada
facility: Children's Hospital - London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: Childrens Hospital of Eastern Ontario
state: Ontario
city: Toronto
country: Canada
facility: The Hospital For Sick Children
state: Ontario
city: Nantes
country: France
facility: CHU de Nantes- Hotel Dieu
city: Paris
country: France
facility: Hopital Necker
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Essen
country: Germany
facility: Universitatsklinikum Essen
city: Jerusalem
country: Israel
facility: Hadassah University Medical Center, Ein Kerem
city: Petach Tikvah
country: Israel
facility: Schneider Children's Medical Center of Israel
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
city: Rome
country: Italy
facility: IRCCS Ospedale Pediatrico Bambino Gesù
city: Nagoya
country: Japan
facility: Nagoya City University Hospital
state: Aichi
city: Nishinomiya
country: Japan
facility: Hyogo College of Medicine College Hospital
state: Hyogo
city: Tokyo
country: Japan
facility: National Center of Neurology and Psychiatry
city: Yangsan-si
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
state: Gyeongsangnam-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Saint Petersburg
country: Russian Federation
facility: Saint Petersburg State Paediatric Medical University
city: Yekaterinburg
country: Russian Federation
facility: State Autonomous Healthcare Institution of Sverdlovsk Region Children's City Clinical Hospital No 9
city: Esplugues de Llobregat
country: Spain
facility: Hospital Sant Joan de Déu
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
city: Bern
country: Switzerland
facility: Inselspital, University Children's Hospital Berne
city: Zurich
country: Switzerland
facility: Universitaets-Kinderspital Zuerich
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Newcastle upon Tyne
country: United Kingdom
facility: The Newcastle upon Tyne Hospitals NHS Foundation Trust, Royal Victoria Infirmary
state: England
city: Liverpool
country: United Kingdom
facility: Alder Hey Children's NHS Foundation Trust
state: Merseyside
city: London
country: United Kingdom
facility: Great Ormond Street Institute of Child Health
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: