Muscular Dystrophy, Duchenne
Conditions
Keywords
Early Stage Duchenne Muscular Dystrophy, DMD, gene therapy, fordadistrogene movaparvovec
Brief summary
The study will evaluate the safety and dystrophin expression following gene therapy in boys with Duchenne Muscular Dystrophy (DMD). It is a single-arm, non-randomized, open-label study
Detailed description
The study will assess the safety and tolerability of fordadistrogene movaparvovec gene therapy. Approximately 10 participants will be enrolled in the study and receive a single IV infusion of PF-06939926; there is no placebo arm. The study includes boys who are at least 2 years old and less than 4 years old (including 3 year olds up until their 4th birthday). 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 The primary analysis will occur when all participants have completed visits through Week 52 (or withdrawn from the study prior to Week 52). All participants will be followed in the study for 5 years after treatment with gene therapy.
Interventions
GENETICPF-06939926
All participants will receive a single dose of PF-06939926 on Day 1.
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
2 Years to 3 Years
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of DMD by prior genetic testing.
Exclusion criteria
* Any of the following genetic abnormalities in the dystrophin gene: a. Any mutation (exon deletion, exon duplication, insertion, or point mutation) affecting any exon between exon 9 and exon 13, inclusive; OR b. A deletion that affects both exon 29 and exon 30; OR c. A deletion that affects any exons between 56-71, inclusive. * Positive test performed by Pfizer for neutralizing antibodies to AAV9. * Any prior treatment with gene therapy. * Any treatment designed to increase dystrophin expression within 6 months prior to screening (including, but not limited to, exon-skipping and nonsense read through). * Previous or current treatment with oral glucocorticoids or other immunosuppressive agents for the indication of DMD. * Abnormality in specified laboratory tests, including blood counts, liver and kidney function.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of Treatment-Emergent Adverse Events and Serious Adverse Events | Through Week 52 | — |
| Number of participants with abnormal hematology test results | Through Week 52 | Blood samples will be collected from subjects for the analysis of hematology |
| Number of participants with abnormal biochemistry test results | Through Week 52 | Blood samples will be collected from subjects for the analysis of biochemistry |
| Number of participants with abnormal urine analysis | Through Week 52 | Urine samples will be collected from subjects for the analysis of urine |
| Number of participants with abnormal and clinically relevant changes in neurological examinations | Through Week 52 | — |
| Number of participants with abnormal and clinically relevant changes in body weight | Through Week 52 | — |
| Number of participants with abnormal and clinically relevant changes in vital signs | Through Week 52 | — |
| Number of participants with abnormal and clinically relevant changes on cardiac troponin I | Through Week 52 | — |
| Number of participants with abnormal and clinically relevant changes on electrocardiogram (ECG) | Through Week 52 | — |
| Number of participants with abnormal and clinically relevant changes on echocardiogram | Through Week 52 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with abnormal and clinically relevant changes on electrocardiogram (ECG) | Through 5 years | — |
| Distribution of mini-dystrophin expression in muscle | At Week 9, Week 52 and Year 5 (if available) | Mini-dystrophin distribution from a muscle biopsy will be assessed by immunofluorescence |
| Number of participants with abnormal and clinically relevant changes on echocardiogram | Through 5 years | — |
| Level of mini-dystrophin expression in muscle | At Week 9, Week 52 and Year 5 (if available) | Mini-dystrophin expression level from a muscle biopsy will be assessed by liquid chromatography mass spectrometry |
| Incidence and severity of Treatment-Emergent Adverse Events and Serious Adverse Events | Through 5 years | — |
| Number of participants with abnormal hematology test results | Through 5 years | Blood samples will be collected from subjects for the analysis of hematology |
| Number of participants with abnormal biochemistry test results | Through 5 years | Blood samples will be collected from subjects for the analysis of biochemistry |
| Number of participants with abnormal urine analysis | Through 5 years | Urine samples will be collected from subjects for the analysis of urine |
| Number of participants with abnormal and clinically relevant changes in neurological examinations | Through 5 years | — |
| Number of participants with abnormal and clinically relevant changes in body weight | Through 5 years | — |
| Number of participants with abnormal and clinically relevant changes in vital signs | Through 5 years | — |
| Number of participants with abnormal and clinically relevant changes on cardiac troponin I | Through 5 years | — |
Countries
Australia, United States
Outcome results
None listed