Phase 3 study to evaluate the safety and efficacy of PF-06939926 for the treatment of Duchenne muscular dystrophy.
- Conditions
- Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]DUCHENNE MUSCULAR DYSTROPHY (DMD)MedDRA version: 20.0Level: PTClassification code 10013801Term: Duchenne muscular dystrophySystem Organ Class: 10010331 - Congenital, familial and genetic disorders
- Registration Number
- EUCTR2019-002921-31-BE
- Lead Sponsor
- Pfizer Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Male
- Target Recruitment
- 99
- 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
- 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, su
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To demonstrate superior efficacy of treatment with fordadistrogene<br>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<br>movaparvovec.<br>- To characterize the distribution of mini-dystrophin expression in the muscle of participants treated with fordadistrogene<br>movaparvovec.<br>- To characterize the change in serum creatine kinase (CK) concentration in participants treated with fordadistrogene<br>movaparvovec as compared to placebo.;Primary end point(s): Change from Baseline at Week 52 in the NSAA total score.;Timepoint(s) of evaluation of this end point: Week 52
- Secondary Outcome Measures
Name Time Method