A Gene Transfer Therapy Study to Evaluate the Safety and Efficacy of Delandistrogene Moxeparvovec (SRP-9001) Following Imlifidase Infusion in Participants With Duchenne Muscular Dystrophy (DMD) Determined to Have Pre-existing Antibodies to Recombinant Adeno-Associated Virus Serotype (rAAVrh74)

2024-512624-11-00 Protocol SRP-9001-104 Human pharmacology (Phase I) - Other Ended

Start 15 Dec 2023 · End 10 Oct 2025 · Status Ended · 1 EU/EEA countries · 1 sites · Protocol SRP-9001-104

Overview

Sponsor-declared trial summary

Phase Human pharmacology (Phase I) - Other
Status Ended
Participants planned 7
Countries 1
Sites 1

Duchenne muscular dystrophy (DMD)

• Change From Baseline in Quantity of Delandistrogene Moxeparvovec Dystrophin Protein Expression as Measured by Western Blot Adjusted by Muscle Content [Time Frame: Baseline, Week 12] • Change From Baseline in Quantity of Delandistrogene Moxeparvovec Dystrophin Expression in Biopsied Muscle as Measured by Immunofluores…

Key facts

Sponsor
Sarepta Therapeutics Inc.
Participant type
Pediatric, Patients
Age range
0-17 years
Gender
Male
Therapeutic area
Diseases [C] - Musculoskeletal Diseases [C05], Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
Trial duration
15 Dec 2023 → 10 Oct 2025
Decision date (initial)
2024-08-29
Transition trial
Yes
Low-intervention
No
Rare-disease indication
Yes
Vulnerable population
Yes
Funding sources
Sarepta Therapeutics, Inc

External identifiers

EU CT number
2024-512624-11-00
EudraCT number
2022-003407-15
ClinicalTrials.gov
NCT06241950

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Therapy, Efficacy, Pharmacogenetic, Pharmacodynamic

• Change From Baseline in Quantity of Delandistrogene Moxeparvovec Dystrophin Protein Expression as Measured by Western Blot Adjusted by Muscle Content [Time Frame: Baseline, Week 12]
• Change From Baseline in Quantity of Delandistrogene Moxeparvovec Dystrophin Expression in Biopsied Muscle as Measured by Immunofluorescence (IF) Fiber Intensity [Time Frame: Baseline, Week 12]
• Change From Baseline in Quantity of Delandistrogene Moxeparvovec Dystrophin Expression in Biopsied Muscle as Measured by IF Percent Dystrophin-positive Fibers (PDPF) [Time Frame: Baseline, Week 12]
• Mean Concentration of Vector Genome Copies Using Polymerase Chain Reaction in Muscle Tissue Biopsy, After Delandistrogene Moxeparvovec Administration [Time Frame: Week 12]

Secondary objectives 5

  1. Maximum Observed Plasma Concentration (Cmax) of Imlifidase [Time Frame: Up to Day 7]
  2. Total IgG in Serum After Imlifidase Administration [Time Frame: Up to Week 12]
  3. rAAVrh74 Antibody Titers After Imlifidase Administration [Time Frame: Up to Hour 120]
  4. Concentration of Vector Genome Copies Using Polymerase Chain Reaction in Serum, After Delandistrogene Moxeparvovec Administration [Time Frame: Up to Day 7]
  5. Number of Participants with a Treatment Emergent Adverse Event (TEAE), Adverse Event of Special Interest (AESI), and Serious Adverse Event (SAE) [Time Frame: Up to Week 104]

Conditions and MedDRA coding

Duchenne muscular dystrophy (DMD)

VersionLevelCodeTermSystem organ class
20.1 PT 10052655 Duchenne muscular dystrophy gene carrier 100000004850

Regulatory references

Scientific advice from competent authorities
European Medicines Agency, Federal Agency For Medicines And Health Products
Plan to share IPD
No
EU CT numberTitleSponsor
2022-000691-19 A two-part, open-label systemic gene delivery study to evaluate the safety and expression of RO7494222 (SRP-9001) in subjects under the age of four with Duchenne muscular dystrophy, Estudio abierto, de dos partes, de administración génica sistémica para evaluar la seguridad y la expresión de RO7494222 (SRP-9001) en sujetos menores de cuatro años con Distrofia Muscular de Duchenne, Uno studio in due parti, in aperto, sulla terapia genica sistemica per valutare la sicurezza e l’espressione di RO7494222 (SRP-9001) in soggetti di età inferiore a quattro anni affetti da distrofia muscolare di Duchenne, Etude en 2 parties, en ouvert, de transfert de gène par voir systémique, évaluant la sécurité et l'expression de RO7494222 (SRP-9001) chez l'enfant âgé de moins de quatre ans présentant une dystrophie musculaire de Duchenne
2020-002372-13 A Phase 3, Multinational, Randomized, Double-Blind, Placebo-Controlled Systemic Gene Transfer Therapy Study to Evaluate the Safety and Efficacy of SRP-9001 in Non-Ambulatory and Ambulatory Subjects With Duchenne Muscular Dystrophy (ENVISION) , Étude de phase 3, internationale, randomisée, en double aveugle, contrôlée contre placebo, de thérapie génique systémique, destinée à évaluer la sécurité d’emploi et l’efficacité du SRP9001 chez des patients non ambulatoires et ambulatoires atteints de dystrophie musculaire de Duchenne (ENVISION), Studio di fase 3, internazionale, randomizzato, in doppio cieco, controllato verso placebo, sulla terapia di trasferimento sistemico di geni, per valutare la sicurezza e l’efficacia di SRP-9001 in soggetti deambulanti e non deambulanti con distrofia muscolare di Duchenne (ENVISION), Estudio de fase 3, multinacional, aleatorizado, en doble ciego y controlado con placebo, del tratamiento mediante transferencia génica para evaluar la seguridad y la eficacia de SRP-9001 en sujetos, no ambulatorios y ambulatorios, con distrofia muscular de Duchenne (ENVISION)
2019-003374-91 A Phase 3 Multinational, Randomized, Double-Blind, Placebo-Controlled Systemic Gene Delivery Study to Evaluate the Safety and Efficacy of SRP-9001 in Subjects With Duchenne Muscular Dystrophy (EMBARK) , Étude de phase 3, multinationale, randomisée, en double aveugle, contrôlée par placebo, sur le transfert systémique de gènes, visant à évaluer la sécurité d’emploi et l’efficacité du SRP-9001 chez des sujets atteints de dystrophie musculaire de Duchenne (EMBARK), Estudio de fase III multinacional, aleatorizado, doble ciego, controlado con placebo, de liberación génica sistémica para evaluar la seguridad y la eficacia de SRP-9001 en sujetos con distrofia muscular de Duchenne (EMBARK), Studio di fase 3, internazionale, randomizzato, in doppio cieco, controllato verso placebo, sul rilascio sistemico di geni, per valutare la sicurezza e l’efficacia di SRP-9001 in soggetti con distrofia muscolare di Duchenne (EMBARK)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

  1. Ambulatory per protocol specified criteria.
  2. Has a definitive diagnosis of DMD prior to Screening based on documentation of clinical findings and confirmatory genetic testing.
  3. Ability to cooperate with motor assessment testing.
  4. Has elevated rAAVrh74 antibody titers per protocol-specified requirements.
  5. A pathogenic frameshift mutation, nonsense mutation or premature stop codon or pathogenic variant in the DMD gene that is expected to lead to absence of dystrophin protein.
  6. 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).

Exclusion criteria 4

  1. Previous treatment with imlifidase.
  2. Presence of any other clinically significant illness, including cardiac, pulmonary, hepatic, renal, hematologic, immunologic, or behavioral disease, or infection or malignancy or concomitant illness or requirement for chronic drug treatment that in the opinion of the Investigator creates unnecessary risks for receiving the study drugs or a medical condition or extenuating circumstance that, in the opinion of the Investigator, might compromise the participant's ability to comply with the protocol required testing or procedures or compromise the participant's wellbeing, safety, or clinical interpretability.
  3. Exposure to gene therapy, investigational medication, or other protocol-specified treatment within the protocol specified time limits.
  4. Abnormality in protocol-specified diagnostic evaluations or laboratory tests. Note: Other inclusion or exclusion criteria could apply.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

  1. Change From Baseline in Quantity of Delandistrogene Moxeparvovec Dystrophin Protein Expression as Measured by Western Blot Adjusted by Muscle Content [Time Frame: Baseline, Week 12]
  2. Change From Baseline in Quantity of Delandistrogene Moxeparvovec Dystrophin Expression in Biopsied Muscle as Measured by Immunofluorescence (IF) Fiber Intensity [Time Frame: Baseline, Week 12]
  3. Change From Baseline in Quantity of Delandistrogene Moxeparvovec Dystrophin Expression in Biopsied Muscle as Measured by IF Percent Dystrophin-positive Fibers (PDPF) [Time Frame: Baseline, Week 12]
  4. Mean Concentration of Vector Genome Copies Using Polymerase Chain Reaction in Muscle Tissue Biopsy, After Delandistrogene Moxeparvovec Administration [Time Frame: Week 12]

Secondary endpoints 5

  1. Maximum Observed Plasma Concentration (Cmax) of Imlifidase [Time Frame: Up to Day 7]
  2. Total IgG in Serum After Imlifidase Administration [Time Frame: Up to Week 12]
  3. rAAVrh74 Antibody Titers After Imlifidase Administration [Time Frame: Up to Hour 120]
  4. Concentration of Vector Genome Copies Using Polymerase Chain Reaction in Serum, After Delandistrogene Moxeparvovec Administration [Time Frame: Up to Day 7]
  5. Number of Participants with a Treatment Emergent Adverse Event (TEAE), Adverse Event of Special Interest (AESI), and Serious Adverse Event (SAE) [Time Frame: Up to Week 104]

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Delandistrogene moxeparvovec-rokl

PRD8656851 · Product

Active substance
Delandistrogene Moxeparvovec
Pharmaceutical form
SOLUTION FOR INJECTION/INFUSION
Route of administration
INTRAVENOUS USE
Authorisation status
Not Authorised
MA holder
SAREPTA THERAPEUTICS INC
Paediatric formulation
No
Orphan designation
Yes
Orphan designation number
EU/3/20/2250

Idefirix 11 mg powder for concentrate for solution for infusion

PRD8297747 · Product

Active substance
Imlifidase
Substance synonyms
IMMUNOGLOBULIN G DEGRADING ENZYME OF STREPTOCOCCUS PYOGENES, HMED-IDES, IDES
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS USE
Authorisation status
Authorised
ATC code
L04AA41 — -
Marketing authorisation
EU/1/20/1471/001
MA holder
HANSA BIOPHARMA AB
MA country
EU
Paediatric formulation
No
Orphan designation
Yes
Orphan designation number
EU/3/16/1826
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sarepta Therapeutics Inc.

9 Total trials 3 Recruiting 4 Ended
Commercial
Sponsor organisation
Sarepta Therapeutics Inc.
Address
215 1st Street
City
Cambridge
Postcode
02142-1213
Country
United States

Scientific contact point

Organisation
Sarepta Therapeutics Inc.
Contact name
Patient Recruitment

Public contact point

Organisation
Sarepta Therapeutics Inc.
Contact name
Patient Recruitment

Third parties 1

OrganisationCity, countryDuties
PPD Global Limited
ORG-100007533
 Cambridge, United Kingdom On site monitoring, Code 12, Code 5, Data management, E-data capture, Code 9

Locations

1 EU/EEA country · 1 investigational sites

By country

CountryMS statusPlanned subjectsSites
Spain Ended 7 1
Rest of world — 0 —

Investigational sites

Spain

1 site · Ended
Hospital Sant Joan De Deu Barcelona
Servicio de Neurología, Passeig De Sant Joan De Deu 2, 08950, Esplugues De Llobregat

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
Spain 2023-12-15 2024-01-17 2025-03-31

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Temporary halt TH-77165

Halt date
2025-03-31
Member states concerned
Spain
Publication date
2025-03-31
Reason
Safety related (clinical or pre-clinical results), Study management related
Explanation
In response to the post marketing Acute liver Failure (ALF) safety event communicated through a Dear Investigator Letter (DIL) enrollment and dosing is temporary halted at the request of EU regulators.
Follow-up measures
The Sponsor will continue patient safety monitoring for already enrolled patients and continue recording data.
Benefit-risk balance changed
Yes
Treatment stopped
Yes

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

TitleSubmission dateStatusType
Sarepta_SRP-9001-104_CT Summary Result_04Mar2026_Public
SUM-127507
 2026-04-07T09:53:56 Submitted Summary of Results

Layperson summary Annex V

TitleSubmission dateStatusType
Plain Language Summary 2026-04-07T09:54:05 Submitted Laypersons Summary of Results

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Laypersons summary of results (for publication) Sarepta_SRP-9001-104__Plain Language Summary_ESP_Public N/A
Laypersons summary of results (for publication) Sarepta_SRP-9001-104_Plain Language Summary_ENG_Public n/a
Protocol (for publication) D1_ Sarepta_SRP_9001-104_2024-512624-11-00_LOAC_Public 1
Protocol (for publication) D1_Sarepta_SRP_9001-104_2024-512624-11-00_Public 3.0
Summary of results (for publication) Sarepta_SRP-9001-104_CT Summary Result_Public N/A
Synopsis of the protocol (for publication) D1_Sarepta_SRP-9001-104 _Protocol Synopsis_2024-512624-11-00_ENG_Public 1
Synopsis of the protocol (for publication) D1_Sarepta_SRP-9001-104 _Protocol Synopsis_2024-512624-11-00_ESP_Public 1

Application history

3 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-08-23 Spain Acceptable with conditions
2024-08-29
 2024-08-29
2 SUBSTANTIAL MODIFICATION SM-1 2024-11-25 Spain Acceptable
2025-02-06
 2025-02-06
3 NON SUBSTANTIAL MODIFICATION NSM-1 2025-03-18 Spain Acceptable
2025-02-06
 2025-03-18

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