A Gene Transfer Therapy Study to Evaluate the Safety and Efficacy of Delandistrogene Moxeparvovec (SRP-9001) in Participants With Duchenne Muscular Dystrophy (DMD)

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 52 (Part 1)

Population: Measured in the Modified Intent-to-Treat (mITT) Population, which included all randomized participants who received study treatment, with treatment group designated according to randomization. Here, Number of Participants Analyzed= number of participants evaluable for this outcome measure.

PROMIS is a family of instruments developed and validated to assess health-related quality of life, including mobility. Mobility function scores ranged from 1 (worst mobility function) to 5 (best mobility function), where higher scores indicate a better clinical outcome.

Time frame: Baseline, Week 52 (Part 1)

Population: Measured in the mITT Population, which included all randomized participants who received study treatment, with treatment group designated according to randomization. Here, Number of Participants Analyzed= number of participants evaluable for this outcome measure.

PROMIS is a family of instruments developed and validated to assess health-related quality of life, including upper extremity function. Upper extremity function scores ranged from 1 (not able to do so \[worst upper extremity function\]) to 5 (no trouble \[best upper extremity function\]), where higher scores indicate a better clinical outcome.

Time frame: Baseline, Week 52 (Part 1)

Population: Measured in the mITT Population, which included all randomized participants who received study treatment, with treatment group designated according to randomization. Here, Number of Participants Analyzed= number of participants evaluable for this outcome measure.

Each participant was provided with wearable devices to collect data on stride velocity. Participants wore a device on each ankle. SV95C data was derived based on stride velocity. Data are presented for change from baseline to Week 52 in SV95C.

Time frame: Baseline, Week 52 (Part 1)

Population: Measured in the mITT Population, which included all randomized participants who received study treatment, with treatment group designated according to randomization. Here, Number of Participants Analyzed= number of participants evaluable for this outcome measure.

The timed stair ascend 4 steps test quantifies the time required for the participant to ascend 4 standard steps (each step was 6 inches in height). Data presented is the change from baseline to Week 52 in the time (in seconds) to ascend 4 steps.

Time frame: Baseline, Week 52 (Part 1)

Population: Measured in the mITT Population, which included all randomized participants who received study treatment, with treatment group designated according to randomization. Here, Number of Participants Analyzed= number of participants evaluable for this outcome measure.

The timed 100MWR quantifies the time required for the participant to run or walk 100 meters (on a straight walkway) from a standing position. Data are presented for change from baseline to Week 52 in the time (in seconds) taken to complete the 100MWR.

Time frame: Baseline, Week 52 (Part 1)

Population: Measured in the mITT Population, which included all randomized participants who received study treatment, with treatment group designated according to randomization. Here, Number of Participants Analyzed= number of participants evaluable for this outcome measure.

The timed 10MWR quantifies the time required for the participant to run or walk 10 meters (on a straight walkway) from a standing position. Data are presented for change from baseline to Week 52 in the time (in seconds) taken to complete the 10MWR.

Time frame: Baseline, Week 52 (Part 1)

Population: Measured in the mITT Population, which included all randomized participants who received study treatment, with treatment group designated according to randomization. Here, Number of Participants Analyzed= number of participants evaluable for this outcome measure.

The time to rise from the floor test quantifies the time required for the participant to stand in an upright position with arms by sides, starting from the supine position with arms by sides. Data are presented for the change from baseline to Week 52 in the time taken (in seconds) to rise from the floor.

Time frame: Baseline, Week 52 (Part 1)

Population: Measured in the mITT Population, which included all randomized participants who received study treatment, with treatment group designated according to randomization. Here, Number of Participants Analyzed= number of participants evaluable for this outcome measure.

The NSAA is a clinician-administered scale that rates performance on various functional activities. As measured by the NSAA, data was collected for the number of skills gained (the average item score was 0 at Baseline and \> 0 at Part 1 Week 52) or improved (the average item score at Baseline was \> 0 but less than the average item score at Part 1 Week 52). As pre-specified, data are presented for the combined number of skills gained or improved at Week 52.

Time frame: Week 52 (Part 1)

Population: Measured in the mITT Population, which included all randomized participants who received study treatment, with treatment group designated according to randomization. Here, Number of Participants Analyzed= number of participants evaluable for this outcome measure.

Quantity of delandistrogene moxeparvovec dystrophin protein levels (in muscle biopsy samples) were determined by Western blot at Part 1, Week 12. For this endpoint, 2 blocks of tissues were analyzed by Western blot, each with 2 technical replicates to determine the delandistrogene moxeparvovec dystrophin protein level (percent control). The block average value from 2 technical replicates was computed. The overall average was calculated as the mean of the block average values. The overall average values were used for the analysis. 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: Week 12

Population: Measured in the mITT Population, which included all randomized participants who received study treatment, with treatment group designated according to randomization. Here, Number of Participants Analyzed= number of participants evaluable for this outcome measure.

AESIs were defined as adverse events (AEs) of special interest, based on pre-specified criteria and pertain to categories labeled hepatotoxicity, immune-mediated myositis, thrombotic microangiopathy (TMA), hypersensitivity, thrombocytopenia, rhabdomyolysis, and troponin I elevations. The data represent the number of participants who experienced an event within the specified AESI category as observed by the principal investigator (PI), after adjudication. Per prespecified analysis, AESI data were only collected based on the specified AESI categories. A Summary of all SAEs and nonserious AEs (Other), regardless of causality and regardless of the AESI category, is located in the Reported Adverse Events section.

Time frame: Up to 104 weeks

Population: Measured in the Safety Population in Part 1, which included all participants who received study treatment, with treatment group designated according to the treatment they received. Measured in the SRP-treated population in Part 2, which included all participants who received investigational study treatment (delandistrogene moxeparvovec) in the study.

TEAEs were defined as an adverse event (AE) that emerged during treatment, having been absent pre-treatment, or worsened relative to the pretreatment state. SAEs were defined as any adverse event that resulted in death, was life threatening, required or prolonged inpatient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or was an important medical event. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.

Time frame: Up to 104 weeks

Population: Measured in the Safety Population in Part 1, which included all participants who received study treatment, with treatment group designated according to the treatment they received. Measured in the SRP-treated population in Part 2, which included all participants who received investigational study treatment (delandistrogene moxeparvovec) in the study.