A Randomized, Double-blind, Placebo-controlled Study of Delandistrogene Moxeparvovec (SRP-9001) for Duchenne Muscular Dystrophy (DMD)

Baseline muscle biopsies with ultrasound guidance were performed pre-treatment and post-treatment (Week 12) on all participants. The change from baseline in delandistrogene moxeparvovec dystrophin expression in these muscle biopsy samples was determined by Western Blot. Dystrophin protein was measured and then adjusted based on the percentage of muscle content in the biopsy sample. An increase in protein expression indicates production of the delandistrogene moxeparvovec dystrophin protein.

Time frame: Baseline, Week 12 (Part 1)

Population: ITT Population: all randomized participants who received study treatment during Part 1.

The NSAA is a healthcare provider administered scale that rates performance of various motor abilities in ambulant children with Duchenne Muscular Dystrophy and is used to monitor disease progression and treatment effects. During assessment, participants are asked to perform 17 different functional activities that are graded as: 2 - Normal - no obvious modification of activity; 1 - Modified method but achieves goal independent of assistance; 0 - Unable to achieve independently. The NSAA total score is defined as the sum of all 17 items, ranging from 0 (worst) to 34 (best). The response vector consists of the change from baseline in NSAA total score at the post-baseline visit. The model includes the covariates of treatment group, visit, treatment group by visit interaction, age group, baseline NSAA total score, and baseline NSAA total score by visit interaction. All covariates are fixed effects in this analysis. An increase in score indicates an improvement in motor function.

Time frame: Baseline, Week 48 (Part 1)

Population: ITT Population: all randomized participants who received study treatment during Part 1 and who were evaluable for this outcome measure. Here, overall number of participants analyzed = the number of participants with evaluable data for the outcome measure.

Baseline muscle biopsies were performed pre-treatment and post-treatment (Week 12) 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. The number of muscle fibers expressing dystrophin was quantified by independent trained evaluators. An increase in IF PDPF indicates the number of muscle fibers with increased delandistrogene moxeparvovec dystrophin expression.

Time frame: Baseline, Week 12 (Part 1)

Population: ITT Population: all randomized participants who received study treatment during Part 1.

Baseline muscle biopsies were performed pre-treatment and post-treatment (Week 12) on all participants. The change from baseline in delandistrogene moxeparvovec dystrophin expression in these muscle biopsy samples was determined using IF fiber intensity. Automated software was used to quantify the intensity of dystrophin expression post-treatment compared to pre-treatment and reviewed by trained evaluators. An increase in IF fiber intensity (percent control) indicates increased delandistrogene moxeparvovec dystrophin expression, relative to non-dystrophic muscle (the control).

Time frame: Baseline, Week 12 (Part 1)

Population: ITT Population: all randomized participants who received study treatment during Part 1.

This functional assessment measures the time needed to move 100 meters. All functional assessments were administered by a clinical evaluator. A decrease in time indicates an improvement in motor function.

Time frame: Baseline, Week 48 (Part 1)

Population: ITT Population: all randomized participants who received study treatment during Part 1 and who were evaluable for this outcome measure. Here, overall number of participants analyzed = the number of participants with evaluable data for the outcome measure.

This functional assessment measures the time needed to move 10 meters. All functional assessments were administered by a clinical evaluator. A decrease in time indicates an improvement in motor function.

Time frame: Baseline, Week 48 (Part 1)

Population: ITT Population: all randomized participants who received study treatment during Part 1 and who were evaluable for this outcome measure. Here, overall number of participants analyzed = the number of participants with evaluable data for the outcome measure.

This functional assessment measures the time taken to climb 4 steps. All functional assessments were administered by a clinical evaluator. A decrease in time indicates an improvement in motor function.

Time frame: Baseline, Week 48 (Part 1)

Population: ITT Population: all randomized participants who received study treatment during Part 1 and who were evaluable for this outcome measure. Here, overall number of participants analyzed = the number of participants with evaluable data for the outcome measure.

This functional assessment was performed as a part of the NSAA and measures the time taken to rise from supine to standing. All functional assessments were administered by a clinical evaluator. A decrease in time indicates an improvement in motor function.

Time frame: Baseline, Week 48 (Part 1)

Population: ITT Population: all randomized participants who received study treatment during Part 1 and who were evaluable for this outcome measure. Here, overall number of participants analyzed = the number of participants with evaluable data for the outcome measure.

Participants experiencing AEs are reported based upon the time to AE onset after delandistrogene moxeparvovec infusion. Each analysis set includes data from both arms and is based upon the Delandistrogene Moxeparvovec-treated Population: all participants who were treated with delandistrogene moxeparvovec in Part 1 or Part 2. 'Delandistrogene Moxeparvovec switched over to Placebo' participants received delandistrogene moxeparvovec in Part 1, followed by placebo in Part 2. AEs experienced by participants during Parts 1, 2, and 3 of the study are reported. 'Placebo switched over to Delandistrogene Moxeparvovec' participants received placebo in Part 1, followed by delandistrogene moxeparvovec in Part 2. AEs experienced by participants during Parts 2 and 3 of the study are reported. No intervention was administered during Part 3. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module.

Time frame: Day 1 through final study visit (approximately 4.6 years)

Population: Delandistrogene Moxeparvovec-treated Population: all participants who were treated with delandistrogene moxeparvovec in Part 1 or Part 2 and who were evaluable for this outcome measure. Here, overall number of participants analyzed = the number of participants with evaluable data for the outcome measure.

The NSAA is a healthcare provider administered scale that rates performance of various motor abilities in ambulant children with Duchenne Muscular Dystrophy and is used to monitor disease progression and treatment effects. During assessment, participants are asked to perform 17 different functional activities that are graded as: 2 - Normal - no obvious modification of activity; 1 - Modified method but achieves goal independent of assistance; 0 - Unable to achieve independently. The NSAA total score is defined as the sum of all 17 items, ranging from 0 (worst) to 34 (best). This outcome measure presents only the baseline NSAA total score of the ITT population by the following age groups: 4-5 years old; 6-7 years old.

Time frame: Baseline

Population: ITT Population: all randomized participants who received study treatment during Part 1.

The NSAA is a healthcare provider administered scale that rates performance of various motor abilities in ambulant children with Duchenne Muscular Dystrophy and is used to monitor disease progression and treatment effects. During assessment, participants are asked to perform 17 different functional activities that are graded as: 2 - Normal - no obvious modification of activity; 1 - Modified method but achieves goal independent of assistance; 0 - Unable to achieve independently. The NSAA total score is defined as the sum of all 17 items, ranging from 0 (worst) to 34 (best). The response vector consists of the change from baseline in NSAA total score at the post-baseline visit. The model includes the covariates of treatment group, visit, treatment group by visit interaction, age group, baseline NSAA total score, and baseline NSAA total score by visit interaction. All covariates are fixed effects in this analysis. An increase in score indicates an improvement in motor function.

Time frame: Baseline, Week 48 (Part 1)

Population: ITT Population: all randomized participants who received study treatment during Part 1 and who were evaluable for this outcome measure. Here, overall number of participants analyzed = the number of participants with evaluable data for the outcome measure, and number analyzed = those who were evaluable for the specific category.