A Gene Transfer Therapy Study to Evaluate the Safety and Efficacy of Delandistrogene Moxeparvovec (SRP-9001) in Participants With Duchenne Muscular Dystrophy (DMD)
- Conditions
- Duchenne Muscular Dystrophy
- Interventions
- Genetic: delandistrogene moxeparvovecGenetic: placebo
- Registration Number
- NCT05096221
- Lead Sponsor
- Sarepta Therapeutics, Inc.
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 126
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Delandistrogene Moxeparvovec followed by Placebo placebo Participants will receive single intravenous (IV) infusion of delandistrogene moxeparvovec on Day 1. Then, participants will receive a single IV infusion of matching placebo at Year 2. Delandistrogene Moxeparvovec followed by Placebo delandistrogene moxeparvovec Participants will receive single intravenous (IV) infusion of delandistrogene moxeparvovec on Day 1. Then, participants will receive a single IV infusion of matching placebo at Year 2. Placebo followed by Delandistrogene Moxeparvovec delandistrogene moxeparvovec Participants will receive matching placebo IV infusion on Day 1. Then, participants will have the opportunity to receive a single IV infusion of delandistrogene moxeparvovec at Year 2. Placebo followed by Delandistrogene Moxeparvovec placebo Participants will receive matching placebo IV infusion on Day 1. Then, participants will have the opportunity to receive a single IV infusion of delandistrogene moxeparvovec at Year 2.
- Primary Outcome Measures
Name Time Method Part 1: Change From Baseline in North Star Ambulatory Assessment (NSAA) Total Score at Week 52 Baseline, Week 52 (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.
- Secondary Outcome Measures
Name Time Method Part 1: Change From Baseline in Time to Rise From the Floor at Week 52 Baseline, Week 52 (Part 1) 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 is presented for the change from baseline to Week 52 in the time taken (in seconds) to rise from the floor.
Part 1: Change From Baseline in Time to Complete 10 Meter Walk/Run (10MWR) at Week 52 Baseline, Week 52 (Part 1) 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 is presented for change from baseline to Week 52 in the time (in seconds) taken to complete the 10MWR.
Part 1: Change From Baseline in Time to Complete 100 Meter Walk/Run (100MWR) at Week 52 Baseline, Week 52 (Part 1) 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 is presented for change from baseline to Week 52 in the time (in seconds) taken to complete the 100MWR.
Part 1: Change From Baseline in the Timed Stair Ascend 4 Steps Test at Week 52 Baseline, Week 52 (Part 1) 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.
Part 1: Change From Baseline in Stride Velocity 95th Centile (SV95C) at Week 52 Baseline, Week 52 (Part 1) 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 is presented for change from baseline to Week 52 in SV95C.
Part 1: Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Score in Mobility to Week 52 Baseline, Week 52 (Part 1) 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.
Part 1: Change From Baseline in PROMIS Score in Upper Extremity Function to Week 52 Baseline, Week 52 (Part 1) 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.
Part 1: Number of Skills Gained or Improved at Week 52 as Measured by the NSAA Week 52 (Part 1) 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.
Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Up to 52 weeks (Part 1) 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.
Part 1: Number of Participants With Adverse Events of Special Interest (AESI) Up to 52 weeks (Part 1) 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 elevations. The data represent the number of participants who experienced an event within the specified AESI category as observed by the 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.
Part 1: Quantity of Delandistrogene Moxeparvovec Dystrophin Protein Expression at Week 12 as Measured by Western Blot Adjusted by Muscle Content Week 12 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.
Trial Locations
- Locations (42)
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
UC San Diego Altman Clinical and Translational Research Institute
🇺🇸La Jolla, California, United States
Arkansas Children's
🇺🇸Little Rock, Arkansas, United States
Lucile Packard Children's Hospital at Stanford
🇺🇸Palo Alto, California, United States
UCLA Medical Center
🇺🇸Los Angeles, California, 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
Columbia University/NYPH
🇺🇸New York, New York, United States
Washington University of St. Louis
🇺🇸Saint Louis, Missouri, United States
The Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
University of Texas Southwestern
🇺🇸Dallas, Texas, United States
Children's Hospital of the King's Daughters
🇺🇸Norfolk, Virginia, United States
LMU - Klinikum der Universitaet Muenchen - Kinderklinik und
🇩🇪Bayern, Germany
Universitätsklinikum Essen - Klinik für Kinderheilkunde I
🇩🇪Essen, Germany
University Hospital Hamburg- Eppendorf
🇩🇪Hamburg, Germany
Hong Kong Children's Hospital
🇭🇰Kowloon, Hong Kong
IRCCS Istituto G.Gaslini, U.O.
🇮🇹Genoa, Italy
UOC Neurologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
🇮🇹Milano, Italy
Kobe University Hospital
🇯🇵Kobe, Japan
National Center for Child Health and Development
🇯🇵Tokyo, Japan
Hospital Sant Joan de Déu
🇪🇸Barcelona, Spain
Hospital Universitari i Politécnico La Fe
🇪🇸Valencia, Comunidad Valencia, Spain
Tokyo Women's Medical University Hospital - Pediatrics
🇯🇵Tokyo, Japan
National Center of Neurology and Psychiatry
🇯🇵Tokyo, Japan
Kaohsiung Medical University Chung-Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Oxford University Hospitals NHS Foundation Trust
🇬🇧Headington, Oxford, United Kingdom
The Newcastle Upon Tyne NHS Hospital NHS Foundation Trust, Royal Victoria Infirmary
🇬🇧Newcastle Upon Tyne, United Kingdom
University of Rochester
🇺🇸Rochester, New York, United States
University Hospital Ghent
🇧🇪Ghent, Belgium
Duke University Medical Center, Lenox Baker Children's Hospital
🇺🇸Durham, North Carolina, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
University of Utah Hospital
🇺🇸Salt Lake City, Utah, United States
UOC Neuropsichiatria Infantile, Area Salute del Bambino, Fondazione Policlinico Universitario A. Gamelli IRCCS
🇮🇹Roma, Italy
Great Ormond Street Hospital for Children NHS Foundation Trust
🇬🇧London, United Kingdom
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
Children's Wisconsin
🇺🇸Milwaukee, Wisconsin, 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