A clinical study in 3 parts with a microdystrophin (called GNT0004), a new gene therapy in boys with Duchenne disease who can still walk. The study will start with finding the proper treatment dose (part 1). After that, a comparative study versus placebo will start to assess the safety and the effectiveness of the proper dose of this therapy (part 2). In the end, a follow up period will continue to investigate the treatment safety and efficacy over longer time (part 3).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Genethon

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

1 Mar 2021 → ongoing

Decision date (initial)

2026-03-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Genethon

External identifiers

EU CT number

2023-505187-11-00

EudraCT number

2020-002093-27

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Pharmacodynamic, Safety, Pharmacokinetic, Therapy, Efficacy

A phase I/II/III study consisting of 3 parts:
- Part 1: To determine the dose of IMP: a safe and tolerable dose with acceptable gene expression, to carry over to part 2.
- Part 2: To demonstrate clinical efficacy of IMP vs placebo at 1 year after inclusion. To assess the safety and tolerability of IMP vs placebo at 1 year after inclusion.
- Part 3. To assess the safety and tolerability of IMP

Secondary objectives 4

1. Part 2: To assess the biodistribution of IMP
2. Part 2:To demonstrate the pharmacodynamic activity of IMP
3. Part 2: To assess the immunogenicity of IMP
4. Part 2:To compare the efficacy on the disease course after 2 years after inclusion, between patients treated with active IMP at first and patients treated after a delay of one year

Conditions and MedDRA coding

Duchenne Muscular Dystrophy

Regulatory references

Scientific advice from competent authorities

National Agency For The Safety Of Medicine And Health Products, European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Ambulant Male
2. Being included in the GNT-014-MDYF study
3. 6 to 10 years (inclusive)
4. For participants enrolled in Part 1: BMI scale ≤75th percentile (validated chart in force in country site) For participants enrolled in Part 2: Body weight ≤95th percentile of the BMI or body weight scale (validated chart in force in country site)
5. Positive gene testing with detailed genotyping confirmation of Duchenne Muscular Dystrophy (DMD), i.e. DMD mutations expected to abolish the production of dystrophin

Exclusion criteria 5

1. DMD patients with any mutations affecting: - exons 1 through 17, (and any mutations affecting other exons as per a country’s requirement which will be applicable to this specific country) for Part 1 participants - affecting exons 8 and/or 9 (and any mutations affecting other exons as per a country’s requirement which will be applicable to this specific country) for Part 2 participants
2. Presence of neutralizing antibodies against AAV8
3. Cardiomyopathy based on physical/cardiological examination and echocardiography (or cardiac MRI if available) with Left Ventricular Ejection Fraction (LVEF) below 55% and fractional shortening (SF) below 28%
4. Any respiratory assistance needed including non-invasive daytime or nocturnal ventilation
5. Inability to perform the planned respiratory functions tests

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. NSAA: change from baseline at week 52

Secondary endpoints 3

1. - Safety and tolerability, measured by the incidence of adverse event (AE) or serious adverse event (SAE) evaluated by changes in laboratory parameters, vital signs and in the physical examination
2. PK/PD endpoints including vector shedding quantification in blood, urine, saliva, feces
3. Clinical efficacy endpoints including NSAA, Time to 10 Meters Walk/Run Test (10MWRT), Time to Rise From Floor (RFF), 6-Minutes Walk Test (6MWT)

Investigational products

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

Test 1

Placebo 2

Auxiliary 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Genethon

Sponsor organisation

Genethon

Address

1 Rue De L Internationale

City

Evry-Courcouronnes

Postcode

91000

Country

France

Scientific contact point

Organisation

Genethon

Contact name

Clinical Development Department

Public contact point

Organisation

Genethon

Contact name

Clinical Development Department

Third parties 12

Locations

3 EU/EEA countries · 10 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

Urgent safety measures 1 · Art. 54 CTR

Unexpected events 1 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Application history

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