Study to assess the safety and expression of RO7494222 (SRP-9001) in participants under the age of 4 with Duchenne muscular dystrophy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

26 Oct 2023 → ongoing

Decision date (initial)

2024-08-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche Ltd

External identifiers

EU CT number

2023-509901-57-00

EudraCT number

2022-000691-19

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacodynamic, Efficacy, Others

To evaluate the safety of delandistrogene moxeparvovec

Secondary objectives 1

1. To evaluate SRP-9001-dystrophin expression from delandistrogene moxeparvovec at 12 weeks as measured by Western blot of biopsied muscle tissue

Conditions and MedDRA coding

Duchenne Muscular Dystrophy

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002677-PIP01-19

Plan to share IPD

Yes

IPD plan description

Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/innovation/process/clinical-trials/data-sharing/).

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Signed Informed Consent Form
2. Signed Assent Form when appropriate, as determined by patient's age and individual site and country standards
3. Male at birth
4. Meets the following age requirements at the time of study drug infusion: – For Cohort A: 3 years of age – For Cohort B: 2 years of age Note: To ensure that cohort-specific age criteria are met at the time of dosing, at the time of signing the Informed Consent Form participants should be approximately 1 month younger than the maximum age to qualify for a cohort that is actively enrolling.
5. Has a definitive diagnosis of DMD prior to screening based on documentation of clinical findings and prior confirmatory genetic testing using a clinical diagnostic genetic test. Genetic report must describe a frameshift deletion, frameshift duplication, premature stop ("nonsense"), canonical splice site mutation, or other pathogenic variant in the DMD gene fully contained between exons 18 to 79 (inclusive) that is expected to lead to absence of dystrophin protein – Mutations between or including exons 1-17 are not eligible. – In-frame deletions, in-frame duplications, and variants of uncertain significance (“VUS”) are not eligible.
6. Able to cooperate with age-appropriate motor assessment testing in the opinion of the investigator.
7. Has (a) parent(s) or legal guardian(s) who is (are) able to understand and comply with the study visit schedule and all protocol requirements.

Exclusion criteria 18

1. Has elevated anti rAAVrh74 antibody titers as determined by an investigational Elecsys anti-rAAVrh74 antibody assay obtained within 31 days of the infusion day
2. Family does not want to disclose participant's study participation with general practitioner or primary care physician and other medical providers.
3. Poor peripheral venous access, which, in the opinion of the investigator, will lead to difficulty in venipuncture for the purposes of protocol-mandated procedures.
4. Receiving regular oral corticosteroids as a treatment for DMD or planning to receive oral corticosteroids as a treatment for DMD within 1 year of baseline.
5. Major surgery within 3 months prior to Day 1 or planned surgery during Part 1 of the study.
6. 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 creates unnecessary risks to participate in the study in the opinion of the investigator.
7. Known hypersensitivity to delandistrogene moxeparvovec or any excipients of the formulation.
8. 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 well-being or safety, or clinical interpretability.
9. Left ventricular ejection fraction <50% on the screening echocardiogram (ECHO) or clinical signs and/or symptoms of cardiomyopathy
10. Known contact with acute or active hepatitis within 12 weeks or known contact with an infected person (e.g., suspected Epstein-Barr virus [EBV], Varicella zoster virus [VZV], parvovirus B19, human herpes virus 6, and cytomegalovirus [CMV]) within 6 weeks prior to Day 1
11. Symptomatic infection (e.g., upper respiratory tract infection, pneumonia, pyelonephritis, meningitis) within 4 weeks prior to Day 1.
12. Positive serology testing for HIV 1 and/or 2, hepatitis C, or hepatitis B
13. Demonstrates cognitive delay or impairment that could confound motor development in the opinion of the investigator.
14. Treatment with any of the following therapies during the specified time periods: – Any time: o Gene therapy o Cell-based therapy (e.g., stem cell transplantation) o CRISPR/Cas9, or any other form of gene editing – Within 12 weeks of Day 1 and any time during the study: o Use of human growth factor – Within 6 months of Day 1 and any time during the study: o Any investigational medication o Any treatment designed to increase dystrophin expression (e.g., Translarna™, EXONDYS 51™, VILTEPSO™)
15. Has received a live virus vaccine or mRNA vaccine within 4 weeks or inactive vaccine within 2 weeks of the Day 1 visit, or expects to receive a vaccination that cannot be reasonably delayed to accommodate concomitant corticosteroid administration during the first 3 months after Day 1.
16. Has abnormal laboratory values considered clinically significant including but not limited to: – GGT >2 x upper limit of normal (ULN) – GLDH > ULN – Total bilirubin >ULN. o Elevations in total bilirubin confirmed to be due to Gilbert's syndrome are not exclusionary. – White blood cell count >18,500 per µl – Platelets ≤ 150,000 per µl
17. In the opinion of the investigator, the participant is not likely to be compliant with the study protocol.
18. Positive COVID-19 test (antigen or PCR) on Day 1 prior to infusion

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. Incidence of treatment-emergent adverse events
2. Incidence of serious adverse events
3. Incidence of adverse events of special interest
4. Clinically significant changes in vital signs and physical examination findings
5. Clinically significant changes in safety laboratory assessments, ECGs, and ECHOs

Secondary endpoints 1

1. Change in quantity of SRP-9001-dystrophin protein expression from baseline to Week 12 as measured by Western blot

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

Sponsor organisation

F. Hoffmann-La Roche AG

Address

Grenzacherstrasse 124

City

Basel

Postcode

4058

Country

Switzerland

Scientific contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Third parties 1

Locations

5 EU/EEA countries · 5 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

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

Temporary halts 5 · Art. 38 CTR

Results and documents

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

Documents 169 files

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

Application history

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