Clinical Trial Results:
Systemic Gene Delivery Phase I/IIa Clinical Trial for Duchenne Muscular Dystrophy Using rAAVrh74.MHCK7.micro-dystrophin (microDys-IV-001)
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Summary
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EudraCT number |
2021-000077-83 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
25 Apr 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
14 Dec 2023
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First version publication date |
14 Dec 2023
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
SRP-9001-101
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03375164 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Sarepta Therapeutics, Inc.
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Sponsor organisation address |
215 First Street, Cambridge, MA, United States, 02142
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Public contact |
Medical Director, Sarepta Therapeutics, Inc., 1 888-727-3782, SareptAlly@sarepta.com
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Scientific contact |
Medical Director, Sarepta Therapeutics, Inc., 1 888-727-3782, SareptAlly@sarepta.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-002677-PIP01-19 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
25 Apr 2023
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
25 Apr 2023
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The main objective of this study is the assessment of the safety of intravenous (IV) administration of delandistrogene moxeparvovec (SRP-9001/microDys-IV-001) for DMD participants via peripheral limb vein.
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Protection of trial subjects |
Written informed consent from each subject or subjects parent(s) or legal guardian(s), if applicable, and written assent from each subject, if applicable, were obtained before any study-specific screening or baseline period evaluations were performed. The anonymity of participating subject will be maintained to the extent required by applicable laws and in accordance with current HIPAA standards. This study was designed and monitored in accordance with Sponsor procedures, which complied with the ethical principles of Good Clinical Practice (GCP) as required by the major regulatory authorities, and in accordance with the Declaration of Helsinki.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
04 Jan 2018
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 4
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Worldwide total number of subjects |
4
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
4
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||
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Pre-assignment
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Screening details |
In total, 4 participants were screened for the study. There were no screen failures. | ||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||
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Arms
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Arm title
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Delandistrogene Moxeparvovec | ||||||||
Arm description |
Participants received a single IV infusion of delandistrogene moxeparvovec on Day 1. | ||||||||
Arm type |
Experimental | ||||||||
Investigational medicinal product name |
delandistrogene moxeparvovec
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Investigational medicinal product code |
SRP-9001
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Other name |
SRP-9001, delandistrogene moxeparvovec-rokl, ELEVIDYS, rAAVrh74.MHCK7.micro-dystrophin, microDys-IV-001
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Single IV infusion
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Baseline characteristics reporting groups
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Reporting group title |
Delandistrogene Moxeparvovec
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Reporting group description |
Participants received a single IV infusion of delandistrogene moxeparvovec on Day 1. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Full Analysis Set
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
all participants who received study treatment.
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End points reporting groups
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Reporting group title |
Delandistrogene Moxeparvovec
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Reporting group description |
Participants received a single IV infusion of delandistrogene moxeparvovec on Day 1. | ||
Subject analysis set title |
Full Analysis Set
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
all participants who received study treatment.
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End point title |
Number of Participants with Adverse Events (AEs) [1] | ||||||
End point description |
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.
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End point type |
Primary
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End point timeframe |
Up to 5 years
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No pre-specified statistical analysis was carried out for this end point. |
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| Notes [2] - Full Analysis Set |
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| No statistical analyses for this end point | |||||||
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End point title |
Change From Baseline at Day 90 in Delandistrogene Moxeparvovec Dystrophin Expression as Measured by Western Blot | ||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Baseline, Day 90
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| Notes [3] - Full Analysis Set |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline at Year 5 in the 100 Meter Timed Test | ||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Baseline, Year 5
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| Notes [4] - Full Analysis Set |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline at Day 90 in Delandistrogene Moxeparvovec Dystrophin Expression as Measured by IF Percent Dystrophin Positive Fibers (PDPF) | ||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Baseline, Day 90
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| Notes [5] - Full Analysis Set |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline at Day 90 in Delandistrogene Moxeparvovec Dystrophin Expression as Measured by Immunofluorescence (IF) Fiber Intensity | ||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Baseline, Day 90
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| Notes [6] - Full Analysis Set |
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Up to 5 years
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.1
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Reporting groups
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Reporting group title |
Delandistrogene Moxeparvovec
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Reporting group description |
Participants received a single IV infusion of delandistrogene moxeparvovec on Day 1. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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04 Dec 2017 |
Protocol Version 2.0 developed in Nationwide Children’s Hospital without summary of changes and redline versions. |
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14 Dec 2017 |
Protocol Version 3.0 developed in Nationwide Children’s Hospital without summary of changes and redline versions. |
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14 Feb 2018 |
Protocol Version 4.0 developed in Nationwide Children’s Hospital without summary of changes and redline versions. |
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12 Apr 2018 |
Protocol Version 5.0 developed in Nationwide Children’s Hospital without summary of changes and redline versions. |
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08 May 2018 |
Protocol Version 6.0 developed in Nationwide Children’s Hospital without summary of changes and redline versions. |
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01 Aug 2018 |
Protocol Version 7.0 developed in Nationwide Children’s Hospital without summary of changes and redline versions. |
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26 Jun 2019 |
- The protocol was transferred from the Nationwide Children’s Hospital template to the Sarepta template.
- The protocol was updated to reflect the change in responsibilities from investigator to sponsor. |
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25 Aug 2020 |
Study duration extended to 5 years in order to fulfill regulatory requirements to follow participants in a clinical trial setting for 5 years following therapeutic infusion. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/32539076 http://www.ncbi.nlm.nih.gov/pubmed/37577753 |
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