Duchenne Muscular Dystrophy
Conditions
Keywords
Duchenne, Gene Therapy, DMD, Dystrophin, Pediatric, Gene-Delivery, Gene Transfer Therapy
Brief summary
This study was an open-label single-dose gene transfer therapy study evaluating the safety of delandistrogene moxeparvovec intravenous (IV) administration in boys with DMD. This study was originally designed to consist of 12 patients across 2 Cohorts. Cohort A would have included participants ages 3 months to 3 years, and Cohort B included participants ages 4 to 7 years old. No participants were enrolled in Cohort A.
Interventions
GENETICdelandistrogene moxeparvovec
Single IV infusion of delandistrogene moxeparvovec.
Sponsors
Sarepta Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
3 Months to 7 Years
Healthy volunteers
No
Inclusion criteria
* Cohort A participants: 3 months to 3 years of age, inclusive * Cohort B participants: 4 to 7 years of age, inclusive * Definitive diagnosis of DMD based on documented clinical findings and prior genetic testing. * Ability to cooperate with motor assessment testing. * Cohort A participants: No previous treatment with corticosteroids. * Cohort B participants: Stable dose equivalent of oral corticosteroids for at least 12 weeks prior to screening and the dose is expected to remain constant (except for potential modifications to accommodate changes in weight) throughout the first year of the study. * Cohorts A & B: A frameshift mutation contained between exons 18 and 58 (inclusive).
Exclusion criteria
* Exposure to gene therapy, investigational medication, or any treatment designed to increase dystrophin expression within protocol specified time limits. * Abnormality in protocol-specified diagnostic evaluations or laboratory tests. * Presence of any other clinically significant illness, medical condition, or requirement for chronic drug treatment that in the opinion of the Investigator creates unnecessary risk for gene transfer. Other inclusion or
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | Up to 5 years | An AE is any untoward medical occurrence in a clinical study participant that does not necessarily have a causal relationship with the study drug. An AE can, therefore, be any unfavorable and unintended symptom, sign, disease, condition, or test abnormality that occurs during or after administration of a study drug, whether or not considered related to the study drug. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline at Year 5 in the 100 Meter Timed Test | Baseline, Year 5 | This assessment measures the time needed to move 100 meters and served as the primary motor outcome measure for this study. A decrease in the time needed to move 100 meters indicates increased motor function. |
| Change From Baseline at Day 90 in Delandistrogene Moxeparvovec Dystrophin Expression as Measured by Western Blot | Baseline, Day 90 | Baseline muscle biopsies with ultrasound guidance were performed pre-treatment and post-treatment (Day 90) on all participants. The change from baseline in delandistrogene moxeparvovec dystrophin protein levels in these muscle biopsy samples was determined by Western blot. An increase in protein expression indicates production of the delandistrogene moxeparvovec dystrophin protein. |
| Change From Baseline at Day 90 in Delandistrogene Moxeparvovec Dystrophin Expression as Measured by Immunofluorescence (IF) Fiber Intensity | Baseline, Day 90 | Baseline muscle biopsies with ultrasound guidance were performed pre-treatment and post-treatment (Day 90) on all participants. The change from baseline in delandistrogene moxeparvovec dystrophin expression in these muscle biopsy samples was determined using IF. Automated software was used to quantify the intensity of dystrophin expression post-treatment compared to pre-treatment (Percent Normal). The number of muscle fibers expressing micro-dystrophin was quantified by independent trained evaluators. An increase in IF fiber intensity indicates increased delandistrogene moxeparvovec dystrophin expression. |
| Change From Baseline at Day 90 in Delandistrogene Moxeparvovec Dystrophin Expression as Measured by IF Percent Dystrophin Positive Fibers (PDPF) | Baseline, Day 90 | Baseline muscle biopsies with ultrasound guidance were performed pre-treatment and post-treatment (Day 90) on all participants. The change from baseline in delandistrogene moxeparvovec dystrophin expression in these muscle biopsy samples was determined by IF PDPF. Automated software was used to quantify the intensity of dystrophin expression post-treatment compared to pre-treatment (Percent Normal). The number of muscle fibers expressing micro-dystrophin was quantified by independent trained evaluators. An increase in IF PDPF indicates increased delandistrogene moxeparvovec dystrophin expression. |
Countries
United States
Participant flow
Pre-assignment details
In total, 4 participants were screened for the study. There were no screen failures.
Participants by arm
| Arm | Count |
|---|---|
| Delandistrogene Moxeparvovec Participants received a single IV infusion of delandistrogene moxeparvovec on Day 1. | 4 |
| Total | 4 |
Baseline characteristics
| Characteristic | Delandistrogene Moxeparvovec |
|---|---|
| Age, Continuous | 5.14 years STANDARD_DEVIATION 0.91 |
| Age, Customized 85 years and over | 0 Participants |
| Age, Customized Adolescents (12-17 years) | 0 Participants |
| Age, Customized Adults (18-64 years) | 0 Participants |
| Age, Customized Children (2-11 years) | 4 Participants |
| Age, Customized From 65-84 years | 0 Participants |
| Age, Customized Infants and toddlers (28 days-23 months) | 0 Participants |
| Age, Customized In utero | 0 Participants |
| Age, Customized Newborns (0-27 days) | 0 Participants |
| Age, Customized Preterm newborn infants (gestational age < 37 wks) | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 4 |
| other Total, other adverse events | 4 / 4 |
| serious Total, serious adverse events | 0 / 4 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs)
An AE is any untoward medical occurrence in a clinical study participant that does not necessarily have a causal relationship with the study drug. An AE can, therefore, be any unfavorable and unintended symptom, sign, disease, condition, or test abnormality that occurs during or after administration of a study drug, whether or not considered related to the study drug. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: Up to 5 years
Population: Full Analysis Set: all participants who received study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Delandistrogene Moxeparvovec | Number of Participants With Adverse Events (AEs) | 4 Participants |
Secondary
Change From Baseline at Day 90 in Delandistrogene Moxeparvovec Dystrophin Expression as Measured by IF Percent Dystrophin Positive Fibers (PDPF)
Baseline muscle biopsies with ultrasound guidance were performed pre-treatment and post-treatment (Day 90) on all participants. The change from baseline in delandistrogene moxeparvovec dystrophin expression in these muscle biopsy samples was determined by IF PDPF. Automated software was used to quantify the intensity of dystrophin expression post-treatment compared to pre-treatment (Percent Normal). The number of muscle fibers expressing micro-dystrophin was quantified by independent trained evaluators. An increase in IF PDPF indicates increased delandistrogene moxeparvovec dystrophin expression.
Time frame: Baseline, Day 90
Population: Full Analysis Set: all participants who received study treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Delandistrogene Moxeparvovec | Change From Baseline at Day 90 in Delandistrogene Moxeparvovec Dystrophin Expression as Measured by IF Percent Dystrophin Positive Fibers (PDPF) | 81.18 percent dystrophin positive fibers | Standard Deviation 10.19 |
Secondary
Change From Baseline at Day 90 in Delandistrogene Moxeparvovec Dystrophin Expression as Measured by Immunofluorescence (IF) Fiber Intensity
Baseline muscle biopsies with ultrasound guidance were performed pre-treatment and post-treatment (Day 90) on all participants. The change from baseline in delandistrogene moxeparvovec dystrophin expression in these muscle biopsy samples was determined using IF. Automated software was used to quantify the intensity of dystrophin expression post-treatment compared to pre-treatment (Percent Normal). The number of muscle fibers expressing micro-dystrophin was quantified by independent trained evaluators. An increase in IF fiber intensity indicates increased delandistrogene moxeparvovec dystrophin expression.
Time frame: Baseline, Day 90
Population: Full Analysis Set: all participants who received study treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Delandistrogene Moxeparvovec | Change From Baseline at Day 90 in Delandistrogene Moxeparvovec Dystrophin Expression as Measured by Immunofluorescence (IF) Fiber Intensity | 93.59 percent fluorescent expression | Standard Deviation 43.86 |
Secondary
Change From Baseline at Day 90 in Delandistrogene Moxeparvovec Dystrophin Expression as Measured by Western Blot
Baseline muscle biopsies with ultrasound guidance were performed pre-treatment and post-treatment (Day 90) on all participants. The change from baseline in delandistrogene moxeparvovec dystrophin protein levels in these muscle biopsy samples was determined by Western blot. An increase in protein expression indicates production of the delandistrogene moxeparvovec dystrophin protein.
Time frame: Baseline, Day 90
Population: Full Analysis Set: all participants who received study treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Delandistrogene Moxeparvovec | Change From Baseline at Day 90 in Delandistrogene Moxeparvovec Dystrophin Expression as Measured by Western Blot | 70.52 percent control | Standard Deviation 76.1 |
Secondary
Change From Baseline at Year 5 in the 100 Meter Timed Test
This assessment measures the time needed to move 100 meters and served as the primary motor outcome measure for this study. A decrease in the time needed to move 100 meters indicates increased motor function.
Time frame: Baseline, Year 5
Population: Full Analysis Set: all participants who received study treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Delandistrogene Moxeparvovec | Change From Baseline at Year 5 in the 100 Meter Timed Test | -4.02 second | Standard Deviation 4.64 |