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
- Conditions
- Diseases of the musculo-skeletal system and connective tissue
- Registration Number
- KCT0005683
- Lead Sponsor
- Pfizer Pharmacueticals Korea
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Male
- Target Recruitment
- 99
1. Male participants who are =4 and <8 years of age at Screening (Visit 1).
2. 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).
3. 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
4. A NSAA total score >16 and <30 at Screening (Visit 1).
5. Ambulatory, defined as being able to walk 10 meters unassisted, at Screening (Visit 1).
6. 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.
7. 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.
8. 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).
1. Prior treatment with gene therapy, defined as any therapy introducing exogenous DNA or intended to permanently alter the endogenous DNA. Gene therapy (other than IP) will be prohibited for the duration of the study.
2. 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). These treatments will also be prohibited during the period
between Screening (Visit 1) and Day 1 (Visit 3) and for the first 2 years of the study.
3. 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 (Visit 1). These treatments will also be prohibited during the period between Screening (Visit 1) and Day 1 (Visit 3) and for the first 2 years of the study.
4. Known cognitive impairment or behavioral issues that would impede the ability to follow instructions, in the judgment of the Investigator, at Screening (Visit 1).
5. Any nonhealed injury at Screening (Visit 1) 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 (Visit 1).
6. Positive test for NAb to AAV9, based on the threshold determined by the Central Laboratory, from a sample taken at Screening (Visit 1).
7. Receipt of a live attenuated vaccination within 90 days prior to Screening (Visit 1). Receipt of a live attenuated vaccination will also be prohibited during the period between Screening (Visit 1) and Day 1 (Visit 3), for 90 days prior to Year 2 IP
administration, and for the first 2 months after each IP administration.
8. Receipt of an influenza vaccination, systemic antiviral and/or interferon therapy within 30 days prior to Screening (Visit 1). Receipt of an influenza vaccination, systemic antiviral and/or interferon therapy will also be prohibited during the period
between Screening (Visit 1) and Day 1 (Visit 3), for 30 days prior to Year 2 IP administration, and for the first 2 months after each IP administration.
9. Receipt of any systemic immunosuppressant agents other than glucocorticoids within 30 days prior to Screening (Visit 1). Receipt of any systemic immunosuppressant agents other than glucocorticoids will also be prohibited during the period between Screening (Visit 1) and Day 1 (Visit 3) and during the first 2 years of the study, unless administered in response to immunologic reaction.
10. Abnormality in hematology or chemistry profiles at Screening (Visit 1). A single repeat for value(s) outside allowable limits is permitted to re-assess eligibility:
a. Absolute neutrophil count <1000 cells/mm3;
b. Cystatin C >1.0 mg/L;
c. Positive hepatitis A virus (anti-HAV) immunoglobulin M, hepatitis B surface antigen (HBsAg), and/or
hepatitis C antibody (HCVAb);
d. 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.
11. Other acute or chronic medical or psychiatric condition at Screening (Visit 1), including recent
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Change from Baseline at Week 52 in the NSAA total score.
- Secondary Outcome Measures
Name Time Method Change from Baseline in percent normal mini-dystrophin expression level in biceps brachii muscle biopsies at Day 60 (or 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 60 (or 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(Pedatric Parent)