A Phase 3 Study to Evaluate the Safety and Efficacy of PF-06939926 for the Treatment of Duchenne Muscular Dystrophy

Sponsor

Pfizer (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04281485

Collaborator

(none)

Enrollment

Locations

Arms

98.8

Anticipated Duration (Months)

2.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Duchenne Muscular Dystrophy	Genetic: PF-06939926 Other: Placebo Other: Placebo Genetic: PF-06939926	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

99 participants

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.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

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

Actual Study Start Date :

Nov 5, 2020

Anticipated Primary Completion Date :

Jan 30, 2024

Anticipated Study Completion Date :

Jan 29, 2029

Arms and Interventions

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 2 for Cohort 1.
Other: Cohort 2 Approximately one third of participants will be randomized to Cohort 2.	Other: Placebo Placebo will be administered as a single IV infusion at Year 1 for Cohort 2. Genetic: PF-06939926 PF-06939926 will be administered as a single IV infusion at Year 2 for Cohort 2

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 2 for Cohort 1.

Other: Cohort 2

Approximately one third of participants will be randomized to Cohort 2.

Other: Placebo

Placebo will be administered as a single IV infusion at Year 1 for Cohort 2.

Genetic: PF-06939926

PF-06939926 will be administered as a single IV infusion at Year 2 for Cohort 2

Outcome Measures

Primary Outcome Measures

Change from Baseline in North Star Ambulatory Assessment (NSAA) [Week 52]
The NSAA is a 17-item test that measures gross motor function in children with Duchenne.

Secondary Outcome Measures

Change from Baseline in mini-dystrophin expression level in muscle [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 [Week 52]
Mini-dystrophin distribution from a muscle biopsy will be assessed by immunofluorescence.
Change from Baseline in serum creatine kinase (CK) [Week 52]
Changes in the circulating levels of CK.
Number of skills gained based on the individual items of the NSAA. [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 [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 [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 [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 [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 [Week 52]
The PODCI contains a list of questions to assess how each caregiver/child evaluates the child´s ability to perform recreational activities.

Eligibility Criteria

Criteria

Ages Eligible for Study:

4 Years to 7 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Key inclusion criteria:

Confirmed diagnosis of Duchenne muscular dystrophy by prior genetic testing
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
Ambulatory, as assessed by protocol-specified criteria

Key exclusion criteria:

Positive test performed by Pfizer for neutralizing antibodies to AAV9
Any treatment designed to increase dystrophin expression within 6 months prior to screening (e.g., Translarna™, EXONDYS 51™, VYONDYS 53™)
Any prior treatment with gene therapy
Any non-healed injury that may impact functional testing (eg NSAA)
Abnormality in specified laboratory tests, including blood counts, liver and kidney function
Any of the following genetic abnormalities in the dystrophin gene:
Any mutation (exon deletion, exon duplication, insertion, or point mutation) affecting any exon between exon 9 and exon 13, inclusive; OR
A deletion that affects both exon 29 and exon 30.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
2	KU Clinical Research Center - Clinical and Translational Science Unit (CTSU) - Fairway	Fairway	Kansas	United States	66205
3	University of Kansas Medical Center	Kansas City	Kansas	United States	66103
4	KU Clinical Research Center - Clinical and Translational Science Unit (CTSU) - Rainbow	Kansas City	Kansas	United States	66160
5	University of Kansas Hospital - Investigational Pharmacy	Kansas City	Kansas	United States	66160
6	University of Kansas Hospital - Pediatric and Pediatric ICU - Operating Room	Kansas City	Kansas	United States	66160
7	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
8	Pediatric Cardiology	Prairie Village	Kansas	United States	66208
9	Children's Specialty Group, PLLC Division of Child & Adolescent Neurology	Norfolk	Virginia	United States	23510
10	Seattle Children's	Seattle	Washington	United States	98105
11	UZ Gent	Gent		Belgium	9000
12	UZ Leuven	Leuven		Belgium	3000
13	CHR Citadelle	Liege		Belgium	4000
14	Alberta Children's Hospital	Calgary	Alberta	Canada	T3B 6A8
15	Children's and Women's Health Centre of British Columbia	Vancouver	British Columbia	Canada	V6H 3V4
16	Children's Hospital - London Health Sciences Centre	London	Ontario	Canada	N6A 5W9
17	Childrens Hospital of Eastern Ontario	Ottawa	Ontario	Canada	K1H8L1
18	The Hospital For Sick Children	Toronto	Ontario	Canada	M5G 1X8
19	CHU de Nantes- Hotel Dieu	Nantes		France	44093
20	Hopital Necker	Paris		France	75015
21	Hadassah University Medical Center, Ein Kerem	Jerusalem		Israel	91120
22	Schneider Children's Medical Center of Israel	Petach Tikvah		Israel	4920235
23	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Roma		Italy	00168
24	IRCCS Ospedale Pediatrico Bambino Gesù	Rome		Italy	00165
25	Nagoya City University Hospital	Nagoya	Aichi	Japan	467-8602
26	Hyogo College of Medicine College Hospital	Nishinomiya	Hyogo	Japan	663-8501
27	National Center of Neurology and Psychiatry	Tokyo		Japan	187-8551
28	Pusan National University Yangsan Hospital	Yangsan	Gyeongsangnam-do	Korea, Republic of	50612
29	Seoul National University Hospital	Seoul		Korea, Republic of	03080
30	Samsung Medical Center	Seoul		Korea, Republic of	06351
31	Saint Petersburg State Paediatric Medical University	Saint Petersburg		Russian Federation	194100
32	State Autonomous Healthcare Institution of Sverdlovsk Region Children's City Clinical Hospital No 9	Yekaterinburg		Russian Federation	620134
33	Hospital Sant Joan de Déu	Esplugues de Llobregat	Barcelona	Spain	08950
34	Hospital Universitario Vall d'Hebron	Barcelona		Spain	08035
35	Hospital Universitari i Politecnic La Fe de Valencia	Valencia		Spain	46026
36	Inselspital, University Children's Hospital Berne	Bern		Switzerland	3010
37	Universitaets-Kinderspital Zuerich	Zurich		Switzerland	8032
38	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung		Taiwan	807
39	National Taiwan University Hospital	Taipei		Taiwan	100
40	Taipei Veterans General Hospital	Taipei		Taiwan	11217
41	The Newcastle upon Tyne Hospitals NHS Foundation Trust, Royal Victoria Infirmary	Newcastle upon Tyne	England	United Kingdom	NE1 4LP
42	Alder Hey Children's NHS Foundation Trust	Liverpool	Merseyside	United Kingdom	L12 2AP
43	Great Ormond Street Institute of Child Health	London		United Kingdom	WCIN 1EH