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

• ClinicalTrials.gov Identifier: NCT03375164
• Recruitment Status: Completed
• First Posted: December 15, 2017
• Last Update Posted: August 1, 2023
• Sponsor: Sarepta Therapeutics, Inc.
• Information provided by (Responsible Party): Sarepta Therapeutics, Inc.

Tracking Information

• First Submitted Date: December 4, 2017
• First Posted Date: December 15, 2017
• Last Update Posted Date: August 1, 2023
• Actual Study Start Date: January 4, 2018
• Actual Primary Completion Date: April 25, 2023 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: February 8, 2022): Cohorts A and B: Number of Participants with Adverse Events (AEs) [ Time Frame: Up to 5 Years ]

Original Primary Outcome Measures (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.

Current Secondary Outcome Measures (submitted: July 28, 2023)

• Cohort A: Gross Motor Subtest Scaled (Bayley-III) Score [ Time Frame: Day 30 up to 3 Years ]
• Cohorts A and B: The 100 Meter Timed Test (100m) Physical Therapy Assessment [ Time Frame: Up to 5 Years ]
• Cohorts A and B: Change From Baseline of Delandistrogene Moxeparvovec Dystrophin Expression Quantification by Immunofluorescence [ Time Frame: Baseline, Day 90 ]
• Cohorts A and B: Change From Baseline of Delandistrogene Moxeparvovec Dystrophin Expression Quantification by Western Blot [ Time Frame: Baseline, Day 90 ]

Original Secondary Outcome Measures (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: A Gene Transfer Therapy Study to Evaluate the Safety of Delandistrogene Moxeparvovec (SRP-9001) in Participants With Duchenne Muscular Dystrophy (DMD)
• Official Title: Systemic Gene Delivery Phase I/IIa Clinical Trial for Duchenne Muscular Dystrophy Using rAAVrh74.MHCK7.Micro-dystrophin (microDys-IV-001)
• Brief Summary: This is an open-label single-dose gene transfer therapy study evaluating the safety of delandistrogene moxeparvovec intravenous (IV) administration in boys with DMD. This study will consist of 2 Cohorts. Cohort A will include participants ages 3 months to 3 years, and Cohort B will include participants ages 4 to 7 years old. All participants in the study will receive IV delandistrogene moxeparvovec.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Duchenne Muscular Dystrophy

Intervention

Genetic: delandistrogene moxeparvovec

Single IV infusion of delandistrogene moxeparvovec.

Other Names:

• SRP-9001
• delandistrogene moxeparvovec-rokl
• ELEVIDYS

Study Arms

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 6, 2019): 4
• Original Estimated Enrollment (submitted: December 14, 2017): 12
• Actual Study Completion Date: April 25, 2023
• Actual Primary Completion Date: April 25, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

• Sexes Eligible for Study: Male

• Ages: 3 Months to 7 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03375164
• Other Study ID Numbers: 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: Not Provided
• Current Responsible Party: Sarepta Therapeutics, Inc.
• Original Responsible Party: Jerry R. Mendell, Nationwide Children's Hospital, Principal Investigator
• Current Study Sponsor: Sarepta Therapeutics, Inc.
• Original Study Sponsor: Nationwide Children's Hospital
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Sarepta Therapeutics, Inc.

• PRS Account: Sarepta Therapeutics, Inc.
• Verification Date: July 2023