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Muscular Dystrophy, DuchennePhase 1/2NCT03769116

A Randomized, Double-blind, Placebo-controlled Study of Delandistrogene Moxeparvovec (SRP-9001) for Duchenne Muscular Dystrophy (DMD)

A Phase 1/2 study testing delandistrogene moxeparvovec in people with Muscular Dystrophy, Duchenne, run by Sarepta Therapeutics, Inc. at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to evaluate the safety and efficacy of exogenous gene transfer in DMD participants by measuring biological and clinical endpoints in three parts: two 48-week randomized, double-blinded, placebo-controlled periods (Part 1 and Part 2), and an open-label follow-up period (Part 3). Read more about this study

Who is it for?
Ages 4 to 7 years, men only
Conditions the study is for
Muscular Dystrophy, Duchenne
What is being tested?
delandistrogene moxeparvovec
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
41 participants
Where
2 sitesUnited States
Study dates
5 Dec 2018to 16 Aug 2023
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 4 to 7 years
  • Men only
  • No healthy volunteers
  • Child

Who may be able to join

  • Established clinical diagnosis of DMD and documented dystrophin gene mutation of DMD phenotype.
  • Indication of symptomatic muscular dystrophy by protocol-specified criteria.
  • Ability to cooperate with motor assessment testing.
  • Stable dose equivalent of oral corticosteroids for at least 12 weeks.
  • A frameshift mutation contained between exons 18 and 58 (inclusive).

Who cannot join

  • Impaired cardiovascular function on echocardiogram.
  • Prior or ongoing medical condition on physical examination, electrocardiogram, or laboratory findings that could adversely affect participant safety, compromise completion of follow-up, or impair assessment of study results.
  • Exposure to another investigational drug or exon skipping medication within 6 months of screening.
  • Exposure to an investigational or commercial gene therapy product.
  • Abnormal liver or renal function by protocol-specified criteria.
  • Other inclusion/exclusion criteria apply.

Trial locations and contacts

2 sites in 1 country.

United States2 sites
  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

  • David Geffen School of Medicine at UCLA

    Los Angeles, California, 90095

Other trials in United States

About this study

Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial for Duchenne Muscular Dystrophy Using SRP-9001

The purpose of this study is to evaluate the safety and efficacy of exogenous gene transfer in DMD participants by measuring biological and clinical endpoints in three parts: two 48-week randomized, double-blinded, placebo-controlled periods (Part 1 and Part 2), and an open-label follow-up period (Part 3). Participants who are randomized to placebo in Part 1 will have the opportunity for treatment with delandistrogene moxeparvovec in Part 2.

In order to provide a uniform approach to monitoring long-term safety and efficacy in participants who received SRP-9001 in a clinical trial, the Sponsor has amended Study Completion for this study to occur at Week 130. Therefore, participants have transitioned and will complete the remainder of the Part 3 follow up visits in a long-term extension study, SRP-9001-305 (NCT05967351).

Being tested
delandistrogene moxeparvovec, placebo
Keywords
Duchenne Muscular Dystrophy, Gene-Delivery, DMD, Ambulatory, Pediatric, North Star Ambulatory Assessment (NSAA), Percent Dystrophin Positive Fibers (PDPF)
Medical subject headings
Muscular Dystrophy, Duchenne

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • delandistrogene moxeparvovecGenetic

    Also called SRP-9001, delandistrogene moxeparvovec-rokl, ELEVIDYS

    Single IV infusion of delandistrogene moxeparvovec

  • placeboGenetic

    Single IV infusion of matching placebo

Study groups in NCT03769116
Study groupRoleWhat they receive
Delandistrogene Moxeparvovec in Part 1 Followed by Placebo in Part 2ExperimentalParticipant will receive delandistrogene moxeparvovec at Part 1 followed by matching placebo at Part 2 followed by an open-label extension at Part 3.
Receives: Genetic: delandistrogene moxeparvovec; Genetic: placebo
Placebo in Part 1 Followed by Delandistrogene Moxeparvovec in Part 2ExperimentalParticipant will receive matching placebo at Part 1 followed by delandistrogene moxeparvovec at Part 2 followed by an open-label extension at Part 3.
Receives: Genetic: delandistrogene moxeparvovec; Genetic: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change From Baseline at Week 12 in Quantity of Delandistrogene Moxeparvovec Dystrophin Protein Expression as Measured by Western Blot Adjusted by Muscle Content

    Baseline muscle biopsies with ultrasound guidance were performed pre-treatment and post-treatment (Week 12) on all participants. The change from baseline in delandistrogene moxeparvovec dystrophin expression in these muscle biopsy samples was determined by Western Blot. 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.

    Measured: Baseline, Week 12 (Part 1)

  2. Change From Baseline at Week 48 in NSAA Total Score

    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.

    Measured: Baseline, Week 48 (Part 1)

Secondary outcomes (7)
  1. Change From Baseline at Week 48 in Time to Rise From the Floor

    This functional assessment was performed as a part of the NSAA and measures the time taken to rise from supine to standing. All functional assessments were administered by a clinical evaluator. A decrease in time indicates an improvement in motor function.

    Measured: Baseline, Week 48 (Part 1)

  2. Change From Baseline at Week 48 in Time to Ascend 4 Steps

    This functional assessment measures the time taken to climb 4 steps. All functional assessments were administered by a clinical evaluator. A decrease in time indicates an improvement in motor function.

    Measured: Baseline, Week 48 (Part 1)

  3. Change From Baseline at Week 48 in Time of 10-meter Timed Test

    This functional assessment measures the time needed to move 10 meters. All functional assessments were administered by a clinical evaluator. A decrease in time indicates an improvement in motor function.

    Measured: Baseline, Week 48 (Part 1)

  4. Change From Baseline at Week 48 in Time of 100-meter Timed Test

    This functional assessment measures the time needed to move 100 meters. All functional assessments were administered by a clinical evaluator. A decrease in time indicates an improvement in motor function.

    Measured: Baseline, Week 48 (Part 1)

  5. Change From Baseline at Week 12 in Quantity of Delandistrogene Moxeparvovec Dystrophin Protein Expression Measured by Immunofluorescence (IF) Fiber Intensity

    Baseline muscle biopsies were performed pre-treatment and post-treatment (Week 12) on all participants. The change from baseline in delandistrogene moxeparvovec dystrophin expression in these muscle biopsy samples was determined using IF fiber intensity. Automated software was used to quantify the intensity of dystrophin expression post-treatment compared to pre-treatment and reviewed by trained evaluators. An increase in IF fiber intensity (percent control) indicates increased delandistrogene moxeparvovec dystrophin expression, relative to non-dystrophic muscle (the control).

    Measured: Baseline, Week 12 (Part 1)

  6. Change From Baseline at Week 12 in Quantity of Delandistrogene Moxeparvovec Dystrophin Protein Expression Measured by IF Percent Dystrophin Positive Fibers (PDPF)

    Baseline muscle biopsies were performed pre-treatment and post-treatment (Week 12) 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. The number of muscle fibers expressing dystrophin was quantified by independent trained evaluators. An increase in IF PDPF indicates the number of muscle fibers with increased delandistrogene moxeparvovec dystrophin expression.

    Measured: Baseline, Week 12 (Part 1)

  7. Participants Experiencing Adverse Events (AEs) Since Treatment With Delandistrogene Moxeparvovec

    Participants experiencing AEs are reported based upon the time to AE onset after delandistrogene moxeparvovec infusion. Each analysis set includes data from both arms and is based upon the Delandistrogene Moxeparvovec-treated Population: all participants who were treated with delandistrogene moxeparvovec in Part 1 or Part 2.

    'Delandistrogene Moxeparvovec switched over to Placebo' participants received delandistrogene moxeparvovec in Part 1, followed by placebo in Part 2. AEs experienced by participants during Parts 1, 2, and 3 of the study are reported.

    'Placebo switched over to Delandistrogene Moxeparvovec' participants received placebo in Part 1, followed by delandistrogene moxeparvovec in Part 2. AEs experienced by participants during Parts 2 and 3 of the study are reported.

    No intervention was administered during Part 3. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module.

    Measured: Day 1 through final study visit (approximately 4.6 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Dec 2018
  2. Study start5 Dec 2018
  3. Primary completion8 Dec 2020
  4. Study completion16 Aug 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Parallel up to the measurement of the primary outcome at Week 48. At the beginning of Part 2, participants who were originally assigned to placebo will have the opportunity to receive delandistrogene moxeparvovec. All participants will be followed for 5 years following treatment with delandistrogene moxeparvovec.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03769116
Sponsor's protocol ID
SRP-9001-102
Other IDs
2021-000078-27
Status last verified
Nov 2024
First submitted
6 Dec 2018
Last updated
14 Nov 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • P Lowes L, Alfano LN, Iammarino MA, Reash NF, Giblin K, Hu L, Yu L, Wang S, Salazar R, Mendell JR. Validity of remote live stream video evaluation of the North Star Ambulatory Assessment in patients with Duchenne muscular dystrophy. PLoS One. 2024 May 16;19(5):e0300700. doi: 10.1371/journal.pone.0300700. eCollection 2024.

    PubMed 38753764
  • Zaidman CM, Proud CM, McDonald CM, Lehman KJ, Goedeker NL, Mason S, Murphy AP, Guridi M, Wang S, Reid C, Darton E, Wandel C, Lewis S, Malhotra J, Griffin DA, Potter RA, Rodino-Klapac LR, Mendell JR. Delandistrogene Moxeparvovec Gene Therapy in Ambulatory Patients (Aged >/=4 to <8 Years) with Duchenne Muscular Dystrophy: 1-Year Interim Results from Study SRP-9001-103 (ENDEAVOR). Ann Neurol. 2023 Nov;94(5):955-968. doi: 10.1002/ana.26755. Epub 2023 Sep 7.

    PubMed 37539981

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing delandistrogene moxeparvovec in people with Muscular Dystrophy, Duchenne, run by Sarepta Therapeutics, Inc. at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline at Week 12 in Quantity of Delandistrogene Moxeparvovec Dystrophin Protein Expression as Measured by Western Blot Adjusted by Muscle Content (time frame: Baseline, Week 12 (Part 1)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03769116, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2024.

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