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

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ClinicalTrials.gov Identifier: NCT03375164
Recruitment Status : Completed
First Posted : December 15, 2017
Results First Posted : May 23, 2024
Last Update Posted : May 23, 2024
Sponsor:
Information provided by (Responsible Party):
Sarepta Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE December 4, 2017
First Posted Date  ICMJE December 15, 2017
Results First Submitted Date  ICMJE April 24, 2024
Results First Posted Date  ICMJE May 23, 2024
Last Update Posted Date May 23, 2024
Actual Study Start Date  ICMJE January 4, 2018
Actual Primary Completion Date April 25, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 24, 2024)
Number of Participants With Adverse Events (AEs) [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: December 14, 2017)
Safety based on number of participants with adverse events. [ Time Frame: 3 years ]
AEs will be monitored and scored for severity and relatedness to the study article.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 24, 2024)
  • Change From Baseline at Day 90 in Delandistrogene Moxeparvovec Dystrophin Expression as Measured by Western Blot [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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.
  • Change From Baseline at Year 5 in the 100 Meter Timed Test [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 14, 2017)
  • Gross Motor Subtest Scaled (Bayley-III) score [ Time Frame: Screening, Day 30-3 Years ]
    Gross Motor Scaled Score measures motor development. The Bayley-III Gross Motor Subtest will be scored for Cohort A on every follow up visit starting at Day 30 through 3 years. Any subject that is 43-47 months of age, inclusive, at time of screening will have the scaled score calculated compared to normative data for 42 month old children. The Bayley-III provides normative data for children 1-42 months of age.
  • Physical Therapy Assessments The 100 Meter Timed Test (100m) [ Time Frame: Screening, Day 30-3 Years ]
    The 100m will be the primary motor outcome for Cohort B. The 100 Meter Timed Test will be an exploratory outcome initiated for Cohort A as soon as the child is 3 years of age.
  • Physical Therapy Assessments North Star Ambulatory Assessment (NSAA) [ Time Frame: Screening, Day 30-3 Years ]
    The North Star Ambulatory Assessment (NSAA) will be an exploratory outcome initiated for Cohort A as soon as the child is four years of age and for cohort B. The NSAA measures the quality of ambulation in young boys with Duchenne Muscular Dystrophy.
  • Physical Therapy Assessments Timed Up and Go modified for children (TUG) [ Time Frame: Screening, Day 30-3 Years ]
    Exploratory outcomes for Cohort B will include the Timed Up and Go modified for children (TUG).
  • Physical Therapy Assessments Ascend and Descend of 4 steps [ Time Frame: Screening, Day 30-3 Years ]
    Exploratory outcomes for Cohort B will include ascend and descend of 4 steps.
  • Physical Therapy Assessments Hand Held Dynamometry (HHD) [ Time Frame: Screening, Day 30-3 Years ]
    Exploratory outcomes for Cohort B will include and hand held dynamometry (HHD) for knee extensors and knee flexors, and elbow flexors and elbow extensors.
  • Micro-dystrophin gene expression quantification by immunofluorescence [ Time Frame: Screening and Day 90 ]
    Micro-dystrophin gene expression levels will be quantified by immunofluorescence and compared in pre and post muscle biopsies.
  • Micro-dystrophin gene expression quantification by western blot [ Time Frame: Screening and Day 90 ]
    Micro-dystrophin gene expression levels will be quantified by western blot analysis and compared in pre and post muscle biopsies.
  • A decrease in CK following gene therapy [ Time Frame: 3 years ]
    Decrease in CK levels in circulating blood
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Gene Transfer Therapy Study to Evaluate the Safety of Delandistrogene Moxeparvovec (SRP-9001) in Participants With Duchenne Muscular Dystrophy (DMD)
Official Title  ICMJE Systemic Gene Delivery Phase I/IIa Clinical Trial for Duchenne Muscular Dystrophy Using rAAVrh74.MHCK7.Micro-dystrophin (microDys-IV-001)
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Duchenne Muscular Dystrophy
Intervention  ICMJE Genetic: delandistrogene moxeparvovec
Single IV infusion of delandistrogene moxeparvovec.
Other Names:
  • SRP-9001
  • delandistrogene moxeparvovec-rokl
  • ELEVIDYS
Study Arms  ICMJE
  • Experimental: Cohort A: Delandistrogene Moxeparvovec
    Participants will receive a Single IV infusion of delandistrogene moxeparvovec on Day 1.
    Intervention: Genetic: delandistrogene moxeparvovec
  • Experimental: Cohort B: Delandistrogene Moxeparvovec
    Participants will receive a Single IV infusion of delandistrogene moxeparvovec on Day 1.
    Intervention: Genetic: delandistrogene moxeparvovec
Publications * Mendell JR, Sahenk Z, Lehman K, Nease C, Lowes LP, Miller NF, Iammarino MA, Alfano LN, Nicholl A, Al-Zaidy S, Lewis S, Church K, Shell R, Cripe LH, Potter RA, Griffin DA, Pozsgai E, Dugar A, Hogan M, Rodino-Klapac LR. Assessment of Systemic Delivery of rAAVrh74.MHCK7.micro-dystrophin in Children With Duchenne Muscular Dystrophy: A Nonrandomized Controlled Trial. JAMA Neurol. 2020 Sep 1;77(9):1122-1131. doi: 10.1001/jamaneurol.2020.1484.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 6, 2019)
4
Original Estimated Enrollment  ICMJE
 (submitted: December 14, 2017)
12
Actual Study Completion Date  ICMJE April 25, 2023
Actual Primary Completion Date April 25, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 exclusion criteria could apply.

Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 3 Months to 7 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03375164
Other Study ID Numbers  ICMJE SRP-9001-101
2021-000077-83 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Sarepta Therapeutics, Inc.
Original Responsible Party Jerry R. Mendell, Nationwide Children's Hospital, Principal Investigator
Current Study Sponsor  ICMJE Sarepta Therapeutics, Inc.
Original Study Sponsor  ICMJE Nationwide Children's Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Sarepta Therapeutics, Inc.
PRS Account Sarepta Therapeutics, Inc.
Verification Date April 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP