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Duchene Muscular DystrophyPhase 2/3NCT07856329

A Clinical Study to Assess Safety, Efficacy and Pharmacodynamic Profile of GNT0004 in Duchenne Muscular Dystrophy

A Phase 2/3 study testing GNT0004 (1x10e13 vg/kg) and GNT0004 (3x10e13 vg/kg) in people with Duchene Muscular Dystrophy, run by Genethon at 14 sites in 4 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

GNT0004 is a recombinant adeno-associated viral (AAV) vector gene therapy composed of an AAV8 serotype capsid containing a sequence-optimized gene for a human microdystrophin. Duchenne muscular dystrophy (DMD) is a neuromuscular disorder caused by dystrophin gene mutations leading to absence of functional dystrophin… Read more about this study

Who is it for?
Ages 6 to 10 years, men only
Conditions the study is for
Duchene Muscular Dystrophy
What is being tested?
GNT0004 (1x10e13 vg/kg) and GNT0004 (3x10e13 vg/kg)
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
77 participants
Where
14 sitesin 4 countries
Study dates
1 Mar 2021to 1 Oct 2028
Phase
Phase 2/3
Are there results?
Not yet: the study is under way

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 6 to 10 years
  • Men only
  • No healthy volunteers
  • Child

Who may be able to join

  • Ambulant male.
  • Being included in the GNT-014-MDYF study.
  • 6 to 10 years (inclusive).
  • For participants enrolled in Part 1: BMI scale ≤ 75th percentile. For participants enrolled in Part 2: Body weight ≤ 95th percentile of the BMI or body weight scale.
  • Positive genetic testing with detailed genotyping confirmation of DMD.
  • Able to achieve a score in the North Star Ambulatory Assessment (NSAA) scale ≥ 18 at the screening visit.
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  • Stable or descending evolution in the NSAA total score during the last assessment periods recorded in study GNT-014-MDYF.
  • Gowers test (Time to Rise From Floor) ≤ 7 sec.
  • Ongoing corticosteroid therapy according to standard of care: for at least 6 months before the screening.
  • Up to date vaccination record.
  • Willing and able to comply with all protocol requirements and procedures.
  • Signed informed consents and assent as required by local law.
  • Affiliated/beneficiary of an insurance health care scheme or National Health service (if required by local law).

Who cannot join

  • DMD patients with any mutations affecting: exons 1 through 17, for Part 1 participants; affecting exons 8 and/or 9 for Part 2 participants.
  • Presence of neutralizing antibodies against AAV8.
  • Cardiomyopathy based on physical/cardiological examination and echocardiography (or cardiac MRI if available).
  • Any respiratory assistance needed including non-invasive daytime or nocturnal ventilation.
  • Inability to perform the planned respiratory functions tests.
  • Any co-morbidity (ies) and/or previous or planned surgical event(s), which may interfere with DMD evolution /or evaluation of patient's safety or Investigational Medicinal Product (IMP)'s tolerability.
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  • Acute infection that is not expected to be fully resolved for a sufficient time before gene therapy administration.
  • Clinically significant laboratory abnormality values as per protocol.
  • Inability to cooperate with muscle strength and functional assessments.
  • Nuclear Magnetic Resonance Imaging (MRI) contraindications: metal implants, or other contraindication for MRI such as severe phobia.
  • Unwilling and/or unable to comply with all the study protocol requirements and/or procedures.
  • Chronic hepatitis B or C, i.e., positive hepatitis B surface antigen or hepatitis C RNA viral load positive.
  • Previous inclusion to another clinical trial with any non-gene therapy related.
  • Previously treated with any drugs that may interfere with either natural diasease course and/or IMP evaluation (except for corticosteroid therapy), the last dose administration less than protocol defined washout period.
  • Received any of the treatment designed to increase dystrophin expression (e.g., exon skipping or stop codon read-through agents for DMD) within protocol defined period prior to screening.
  • Previous gene therapy for DMD.

Trial locations and contacts

14 sites in 4 countries. Contact the study team or a site near you to ask about taking part.

Medical Lead contact

+33 01 69 47 25 38

contact@genethon.fr

14 sites in 4 countries

France7 sites, 7 recruiting

  • University Hospital of Bordeaux

    Bordeaux, 33076

    Recruiting

  • Brest University Hospital Centre

    Brest, 29609

    Recruiting

  • Hôpital Femme Mère Enfant

    Bron, 69677

    Recruiting

  • CHU Lille

    Lille, 59037

    Recruiting

  • Centre Hospitalier Universitaire De Montpellier

    Montpellier, 34090

    Not yet recruiting

  • Institut I-Motion, Hôpital Armand Trousseau

    Paris, 75012

    Recruiting

  • Hôpitaux Universitaires de Strasbourg

    Strasbourg, 67098

    Recruiting

Other trials in France

Belgium3 sites, 3 recruiting

  • Hôpital Universitaire des Enfants Reine Fabiola

    Brussels, 1020

    Recruiting

  • UZ Leuven

    Leuven, 3000

    Recruiting

  • Hôpital de la Citadelle

    Liège, 4000

    Not yet recruiting

Other trials in Belgium

Spain2 sites, 2 recruiting

  • Hospital Sant Joan de Déu Barcelona

    Esplugues de Llobregat, 08950

    Recruiting

  • Hospital Universitario y Politécnico La Fe

    Valencia, 46026

    Not yet recruiting

Other trials in Spain

United Kingdom2 sites, 2 recruiting

  • Great Ormond Street Hospital for Children

    London, WC1N 3JH

    Recruiting

  • The Newcastle upon Tyne Hospitals NHS Foundation Trust

    Newcastle upon Tyne, NE7 7DN

    Not yet recruiting

Other trials in United Kingdom

About this study

Official title: Microdystrophin (GNT0004) Gene Therapy Clinical Trial in Duchenne Muscular Dystrophy: A Phase I/II/III Study With a Dose Determination Part Followed by an Efficacy and Safety Evaluation, Quadruple Blind Placebo-controlled Part and Then by a Long-term Safety Follow up Part, in Ambulant Boys

GNT0004 is a recombinant adeno-associated viral (AAV) vector gene therapy composed of an AAV8 serotype capsid containing a sequence-optimized gene for a human microdystrophin. Duchenne muscular dystrophy (DMD) is a neuromuscular disorder caused by dystrophin gene mutations leading to absence of functional dystrophin, a key protein that prevents muscle cell damage during physiological contractions. To address the underlying cause of the disease, GNT0004 delivers an optimized dystrophin gene that is capable to produce a shortened but functional dystrophin protein in target tissues (heart and skeletal muscles) in DMD subjects. It is expected to significantly delay or slow disease progression. GNT0004 will be given as a one-time intravenous (IV) infusion to help it reach muscles throughout the body.

Read the detailed description

The study includes 3 parts. Part 1: A dose-escalation part where two dose levels were studied in five DMD boys. Based on the review of the first 12 weeks of data, the higher dose (3×10¹³ vg/kg) was considered the most efficient dose of GNT0004 with an acceptable safety profile and was selected for Part 2. This part was completed. Part 2: A confirmatory part to evaluate the efficacy and side effects of GNT0004. Participants are randomly assigned to receive either GNT0004 or placebo in a blinded manner. This part lasts 18 months. After 18 months, participants initially receiving placebo will receive GNT0004, and those initially receiving GNT0004 will receive placebo. Part 3: A long-term follow-up part in which all participants who received GNT0004 in Parts 1 and 2 will be followed for a total of 5 years from dosing to monitor potential late-onset side effects and assess the duration of the treatment's beneficial effects. The five participants from Part 1 are currently being followed in Part 3.

Being tested
GNT0004 (1x10e13 vg/kg), GNT0004 (3x10e13 vg/kg), Placebo
Keywords
DMD, ambulant, gene therapy, AAV, microdystrophine

What participants receive

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

  • GNT0004 (1x10e13 vg/kg)Genetic

    Also called rAAV2/8-Spc5-12-hMD1

    Single intravenous administration of GNT0004

  • GNT0004 (3x10e13 vg/kg)Genetic

    Also called rAAV2/8-Spc5-12-hMD1

    Single intravenous administration of GNT0004

  • PlaceboGenetic

    Single intravenous administration of GNT0004 placebo (IMP placebo)

Study groups in NCT07856329
Study groupRoleWhat they receive
Part 1 - Cohort 1ExperimentalFirst cohort of the dose determination part (Part 1)
Receives: Genetic: GNT0004 (1x10e13 vg/kg)
Part 1 - Cohort 2ExperimentalSecond cohort of the dose determination part (Part 1)
Receives: Genetic: GNT0004 (3x10e13 vg/kg)
GNT0004 in Part 2 followed by placebo in Part 3ExperimentalNot described
Receives: Genetic: GNT0004 (3x10e13 vg/kg); Genetic: Placebo
Placebo in Part 2 followed by GNT0004 in Part 3ExperimentalNot described
Receives: Genetic: GNT0004 (3x10e13 vg/kg); Genetic: Placebo

What is being measured

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

  1. PART 1 - Safety Outcomes: Incidence of adverse events (AEs), serious adverse events (SAEs), adverse events of special interest (AESIs), adverse drug reactions (ADRs) and clinically significant laboratory and clinical examination findings

    Measured: From the Screening Visit through the end of Part 1 (Week 12)

  2. PART 1 - Immunogenicity Outcomes: Antibodies to AAV8, antibodies to recombinant dystrophin (hMD1) and of cellular immune biomarkers (ELISPOT tests)

    Measured: From the Screening Visit through the end of Part 1 (Week 12)

  3. PART 1: Vector shedding quantification in blood, urine, saliva, feces (DNA level)

    Measured: Once a week through Week 12

  4. PART 1: Percentage change from baseline on Creatine kinase (CK) in blood over time

    Measured: From the Screening Visit through the end of Part 1 (Week 12)

  5. PART 1: Quantification of Microdystrophin positive myofibers level from muscle biopsy at Week 8

    Measured: Week 8

  6. PART 1: Quantification of Microdystrophin protein expression from muscle biopsy at Week 8

    Measured: Week 8

  7. PART 1: Quantification of vector copy number (VCN) over time

    Measured: From the Screening Visit through the end of Part 1 (Week 12)

  8. PART 2: Change from baseline in the North Star Ambulatory Assessment (NSAA) total score at Month 18

    The NSAA is a validated unidimensional functional scale for ambulant male patients with DMD. An age-appropriate modified NSAA validated for young ambulant male patients from the age of 3 years with DMD is used in this study.

    This scale consists of 17 functional assessments, ranging from standing to running and includes several items assessing abilities that are necessary to remain functionally ambulant in the context of DMD. Each item can be scored on a 3 point-scale from 2 ("achieves goal without any assistance") to 0 ("unable to achieve independently"). A total score (maximum "34", minimum "0") is obtained by summing all the individual items, with higher scores reflecting better functional performance.

    Measured: From the Screening Visit to Month 18 (Week 78)

  9. PART 3 - Safety Outcomes: Incidence of adverse events (AEs), serious adverse events (SAEs), adverse events of special interest (AESIs), adverse drug reactions (ADRs) and clinically significant laboratory and clinical examination findings

    Measured: From the end of Part 1 or Part 2 to 5 years post-treatment administration

Secondary outcomes (20)

  1. PART 2 - Safety Outcomes: Incidence of adverse events (AEs), serious adverse events (SAEs), adverse events of special interest (AESIs), adverse drug reactions (ADRs) and clinically significant laboratory and clinical examination findings

    Measured: From the Screening Visit through the end of Part 2 (Month 18/Week 78)

  2. PART 2: Percentage change from baseline on Creatine kinase (CK) in blood over time

    Measured: From the Screening Visit through the end of Part 2 (Month 18/Week 78)

  3. PART 2: Quantification of Microdystrophin positive myofibers level from muscle biopsy at Week 8

    Measured: Week 8

  4. PART 2: Quantification of Microdystrophin protein expression from muscle biopsy at Week 8

    Measured: Week 8

  5. PART 2: Quantification of vector copy number (VCN)

    Measured: From the Screening Visit through the end of Part 2 (Month 18/Week 78)

  6. PART 2: Change from baseline on stride velocity 95th centile (SV95C) at Month 18

    Measured: Month 18 (Week 78)

  7. PART 2: Change from baseline on time to rise from floor (RFF) test at Month 18

    Measured: Month 18 (Week 78)

  8. PART 2: Change from baseline on Time to 10 Meters Walk/Run Test (10MW/RT) at Month 18

    Measured: Month 18 (Week 78)

  9. PART 2: Change from baseline on ACTIVLIM (patient reported outcome questionnaire) at Month 18

    Measured: Month 18 (Week 78)

  10. PART 2: Change from baseline on 4-Stair Climbing (4SC) time over 18 months

    Measured: From Day 0 visit through the end of Part 2 (Month 18/Week 78)

  11. PART 2: Change from baseline on MyoTools (Grip, Pinch) assessments over 18 months

    Measured: From the Screening Visit through the end of Part 2 (Month 18/Week 78)

  12. PART 2: Change from baseline of muscle-fat replacement (fat fraction, FF, in %) and progression in glutei and thigh muscle groups over 18 months assessed through muscle Magnetic Resonance Imaging (MRI)

    Measured: From the Screening Visit through the end of Part 2 (Month 18/Week 78)

  13. PART 2: Change from baseline of muscle volume in glutei and thigh muscle groups (contractile cross-sectional area cCSA, in mm2) over 18 months assessed through muscle Magnetic Resonance Imaging (MRI)

    Measured: From the Screening Visit through the end of Part 2 (Month 18/Week 78)

  14. PART 2: EQ-5D evolution over 18 months

    Measured: From Day 0 visit through the end of Part 2 (Month 18/Week 78)

  15. PART 2: PedsQL™ Duchenne Muscular Dystrophy Module evolution over 18 months

    Measured: From Day 0 visit through the end of Part 2 (Month 18/Week 78)

  16. PART 3: Percentage change from pre active IMP administration level on blood Creatine kinase (CK) over time

    Measured: From the Screening Visit through the end of Part 3 (5 years post-treatment administration)

  17. PART 3: Change from baseline in the North Star Ambulatory Assessment (NSAA) total score over time

    The NSAA is a validated unidimensional functional scale for ambulant male patients with DMD. An age-appropriate modified NSAA validated for young ambulant male patients from the age of 3 years with DMD is used in this study.

    This scale consists of 17 functional assessments, ranging from standing to running and includes several items assessing abilities that are necessary to remain functionally ambulant in the context of DMD. Each item can be scored on a 3 point-scale from 2 ("achieves goal without any assistance") to 0 ("unable to achieve independently"). A total score (maximum "34", minimum "0") is obtained by summing all the individual items, with higher scores reflecting better functional performance.

    Measured: Up to 5 years post GNT0004 infusion

  18. PART 3: Change from baseline on Forced Vital Capacity (FVC) over time

    Measured: Up to 5 years post GNT0004 infusion

  19. PART 3: Change from baseline on Forced Expiratory Volume in one second (FEV1) over time

    Measured: Up to 5 years post GNT0004 infusion

  20. PART 3: Change from baseline of muscle-fat replacement (fat fraction, FF, in %) and progression in glutei and thigh muscle groups over time assessed through muscle Magnetic Resonance Imaging (MRI)

    Measured: Up to 5 years post GNT0004 infusion

Timeline

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

  1. First posted2 Oct 2026
  2. Study start1 Mar 2021
  3. Primary completion1 Oct 2028 (estimated)
  4. Study completion1 Oct 2028 (estimated)

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 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Model description
This Phase I/II/III (All-in-one) study includes 3 parts. Part 1 (phase I/II): Dose escalation (cohorts C1 and C2), open-label, sequential enrollment. Part 2 (phase III): quadruple blind, placebo-controlled, randomized (ratio 1:1) to either GNT0004 or placebo group. Part 3: Crossover to the alternate treatment after the 18-month pivotal parallel evaluation period for Part 2 participants. Long term safety and efficacy follow-up for all participants enrolled in Parts 1 and 2.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
77 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07856329
Sponsor's protocol ID
GNT-016-MDYF
Other IDs
2023-505187-11-00, 2023
Status last verified
Jul 2026
First submitted
28 Sep 2026
Last updated
13 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing GNT0004 (1x10e13 vg/kg) and GNT0004 (3x10e13 vg/kg) in people with Duchene Muscular Dystrophy, run by Genethon at 14 sites in 4 countries.

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 13 inclusion and 16 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: looking for participants now, as of the sponsor's last update on 13 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in France, Belgium, Spain, United Kingdom. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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

Contact Medical Lead (+33 01 69 47 25 38, contact@genethon.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

PART 1 - Safety Outcomes: Incidence of adverse events (AEs), serious adverse events (SAEs), adverse events of special interest (AESIs), adverse drug reactions (ADRs) and clinically significant laboratory and clinical examination findings (time frame: From the Screening Visit through the end of Part 1 (Week 12)). The study lists 9 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 NCT07856329.

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 13 Oct 2026.

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