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

Sarepta Therapeutics, Inc.126 enrolled

Overview

The study will evaluate the safety and efficacy of gene transfer therapy in boys with DMD. It is a randomized, double-blind, placebo-controlled study. The participants who are randomized to the placebo arm will have an opportunity for treatment with gene transfer therapy at the beginning of the second year.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

126

Conditions

Duchenne Muscular Dystrophy

Interventions

delandistrogene moxeparvovecGENETIC

Single IV infusion of delandistrogene moxeparvovec.

placeboGENETIC

Single IV infusion of matching placebo.

Eligibility

Sex: MALEMin age: 4 YearsMax age: 7 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Is ambulatory and from 4 to under 8 years of age at time of randomization. * Definitive diagnosis of DMD based on documented clinical findings and prior genetic testing. * Ability to cooperate with motor assessment testing. * Stable daily dose of oral corticosteroids for at least 12 weeks prior to Screening, and the dose is expected to remain constant throughout the study (except for modifications to accommodate changes in weight). * rAAVrh74 antibody titers are not elevated as per protocol-specified requirements. * A pathogenic frameshift mutation or premature stop codon contained between exons 18 and 79 (inclusive), with the exception of mutation fully contained within exon 45. 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 exclusion criteria could apply.

Locations (42)

Outcomes

Primary Outcomes

Part 1: Change From Baseline in North Star Ambulatory Assessment (NSAA) Total Score at Week 52

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)

Secondary Outcomes

Part 1: Quantity of Delandistrogene Moxeparvovec Dystrophin Protein Expression at Week 12 as Measured by Western Blot Adjusted by Muscle Content

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

Part 1: Change From Baseline in Time to Rise From the Floor at Week 52

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.

Data from ClinicalTrials.gov

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Arkansas Children's

Little Rock, Arkansas, United States

UC San Diego Altman Clinical and Translational Research Institute

La Jolla, California, United States

UCLA Medical Center

Los Angeles, California, United States

Lucile Packard Children's Hospital at Stanford

Palo Alto, California, United States

University of California, Davis

Sacramento, California, United States

Children's Hospital Colorado

Aurora, Colorado, United States

University of Florida

Gainesville, Florida, United States

Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

University of Iowa Stead Family Children's Hospital

Iowa City, Iowa, United States

The Johns Hopkins Hospital

Baltimore, Maryland, United States

...and 32 more locations

Time frame: Baseline, Week 52 (Part 1)

Part 1: Change From Baseline in Time to Complete 10 Meter Walk/Run (10MWR) at Week 52

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)

Part 1: Change From Baseline in Time to Complete 100 Meter Walk/Run (100MWR) at Week 52

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)

Part 1: Change From Baseline in the Timed Stair Ascend 4 Steps Test at Week 52

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)

Part 1: Change From Baseline in Stride Velocity 95th Centile (SV95C) at Week 52

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)

Part 1: Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Score in Mobility to Week 52

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)

Part 1: Change From Baseline in PROMIS Score in Upper Extremity Function to Week 52

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)

Part 1: Number of Skills Gained or Improved at Week 52 as Measured by the NSAA

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)

Parts 1 and 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

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

Parts 1 and 2: Number of Participants With Adverse Events of Special Interest (AESI)

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