Phase 3 study to evaluate the safety and efficacy of PF-06939926 for the treatment of Duchenne muscular dystrophy.

• Register: EUCTR
• Last refreshed on: 15 July 2024
• Main ID: EUCTR2019-002921-31-DE
• Date of registration: 28/07/2020
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc.
• Public title: Phase 3 study to evaluate the safety and efficacy of PF-06939926 for the treatment of Duchenne muscular dystrophy.
• Scientific 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
• Date of first enrolment: 10/10/2022
• Target sample size: 99
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-002921-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

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

Contacts

• Name: Clinical Trials.gov Call Centre
• Affiliation: Pfizer Inc.

• Name: Clinical Trials.gov Call Centre
• Affiliation: Pfizer Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
- Male participants who are =4 and <8 years of age at Screening (Visit 1).
- Confirmed diagnosis of DMD by prior genetic testing demonstrating the presence of a mutation in the dystrophin gene consistent with DMD at Screening (Visit 1). If the Investigator determines that the results are inconclusive, a repeat genetic testing will be allowed through the central laboratory at Screening (Visit 1).
- Receipt of a stable daily dose of glucocorticoids (=0.5 mg/kg/day prednisone, prednisolone, or =0.75 mg/kg/day deflazacort) for at least 3 months prior to Screening (Visit 1) and during the period between Screening (Visit 1) and Day 1 (Visit 3). In order to comply with protocol procedures, there should also be a reasonable expectation that this daily dose of glucocorticoids will remain stable for the first 2 years of the study. A stable dose is defined as one in which any change is =0.2 mg/kg
- A NSAA total score >16 and <30 at Screening (Visit 1).
- Ambulatory, defined as being able to walk 10 meters unassisted, at Screening (Visit 1).
- Participants/legally acceptable representatives who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures including, potentially, open and/or needle muscle biopsies under general anesthesia and cardiac MRI under general anesthesia.
- Participants/legally acceptable representatives who are capable of giving assent/signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the assent/informed consent document (ICD) and in this protocol.
- Participants/legally acceptable representatives who are willing to protect the integrity of the study data by not actively seeking sensitive clinical data (eg, CK, ALT, AST, NAb to AAV9) through independent laboratory tests and by not sharing trial experiences with other participants or publicly (eg, through social media).
Are the trial subjects under 18? yes
Number of subjects for this age range: 99
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
- Prior treatment with gene therapy, defined as any therapy introducing exogenous DNA or intended to permanently alter the endogenous DNA
- Exposure within 6 months prior to Screening (Visit 1) to any treatment designed to increase dystrophin expression (including, but not limited to exon-skipping and nonsense read-through)
- Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives (whichever is longer) at Screening. These treatments will also be prohibited during the period between Screening and Day 1 (Visit 3) and for the first 2 years of the study
- Known cognitive impairment or behavioral issues that would impede the ability to follow instructions, in the judgment of the Investigator, at Screening
- Any nonhealed injury at Screening which, in the opinion of the Investigator, may impact functional testing; additionally, lower limb fractures must have been healed for at least 3 months prior to Screening
-Positive test for NAb to AAV9, based on the threshold determined by the Central Laboratory, from a sample taken at Screening
-Receipt of a live attenuated vaccination within 30 days prior to Screening. Receipt of a live attenuated vaccination will also be prohibited for 90 days before Day 1 (Visit 3), for 90 days prior to Year 2 IP administration, and for the first 2 months after each IP administration
-Abnormality in hematology or chemistry profiles at Screening. A single repeat for value(s) outside allowable limits is permitted to re-assess eligibility:
a. Absolute neutrophil count <1000 cells/mm3
b. Platelets <150 x 103/µl
c. Cystatin C >1.2 x ULN
d. Positive hepatitis A virus (anti-HAV) immunoglobulin M, hepatitis B surface antigen (HBsAg), and/or hepatitis C antibody (HCVAb)
e. Markers of hepatic inflammation or overt or occult cirrhosis as evidenced by one or more of the following:
1. Prothrombin time (PT) > upper limit of normal (ULN); prolonged international normalized ratio (INR) >ULN
2. GLDH >2 x ULN
3. Total bilirubin >1.5 x ULN(unless the participant has a history of Gilbert disease) and direct bilirubin >0.5 mg/dL
4. Gamma-glutamyl transferase (GGT) >1.5 x ULN.
-Other acute or chronic medical or psychiatric condition at Screening, including recent (within the past year) or active suicidal ideation or behavior (using screening by the Child Behavior Check List (CBCL) and determined by the Investigator, as described in Section 8.2.11) or laboratory abnormality that may increase the risk associated with study participation or IP administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the participant inappropriate for entry into this study
-Acute infection at Screening or Baseline (Visit 2) that, in the judgement of the Investigator is not expected to be fully resolved at least 2 weeks before Day 1 (Visit 3). At Day 1 (Visit 3), participants must have been infection-free for at least 2 weeks prior to IP administration. Delay of IP administration for up to 14 days is permitted to enable infections to become fully resolved
-Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or Pfizer employees, including their family members, directly involved in the conduct of the study
- Known hypersensitivity to any of the components of the IP or solution for infusion, such as hypersensitiv

Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

DUCHENNE MUSCULAR DYSTROPHY (DMD)
MedDRA version: 20.0 Level: PT Classification code 10013801 Term: Duchenne muscular dystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Product Name: PF-06939926
Product Code: PF-06939926
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: fordadistrogene movaparvovec
Current Sponsor code: PF-06939926
Other descriptive name: Adeno-associated viral vector serotype 9 containing the human mini-dystrophin gene
Concentration unit: vector genomes (vg)/mL
Concentration type: equal
Concentration number: 1E+14 -
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 52

Main Objective: To demonstrate superior efficacy of treatment with fordadistrogene movaparvovec as compared to placebo based on change from Baseline in the North Star Ambulatory Assessment (NSAA).

Secondary Objective: - To quantify the mini-dystrophin expression level in the muscle of participants treated with fordadistrogene movaparvovec .
- To characterize the distribution of mini-dystrophin expression in the muscle of participants treated with fordadistrogene movaparvovec .
- To characterize the change in serum creatine kinase (CK) concentration in participants treated with fordadistrogene movaparvovec as compared to placebo.

Primary end point(s): Change from Baseline at Week 52 in the NSAA total score.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 52

Secondary end point(s): - Change from Baseline in percent normal mini-dystrophin expression level in biceps brachii muscle biopsies at Day 360 using an LC-MS assay.
- Change from Baseline in percent of muscle fibers expressing mini-dystrophin in biceps brachii muscle biopsies at Day 360 as assessed by immunofluorescence.
- Change from Baseline at Week 52 in serum CK concentration.
- Number of skills gained at Week 52 based on the individual items of the NSAA.
- Number of skills either improved or maintained at Week 52 based on the individual items of the NSAA.
-Change from Baseline at Week 52 in the 10 meter run/walk velocity.
-Change from Baseline at Week 52 in the rise from floor velocity.
-Change from Baseline at Week 52 in the Modified Pediatric Outcomes Data Collection Instrument (PODCI): Transfer and Basic Mobility Core Scale (Pediatric Parent).
- Change from Baseline at Week 52 in the Modified PODCI: Sports and Physical Functioning Core Scale (Pediatric Parent).

Secondary ID(s)

C3391003

2019-002921-31-GB

Source(s) of Monetary Support

Pfizer Inc., 66 Hudson Boulevard East, New York, NY 10001

Ethics review

Status: Approved
Approval date: 10/10/2022
Contact: