Clinical Trials in Spain / NCT07856329
Recruiting
Phase 2/3
A Clinical Study to Assess Safety, Efficacy and Pharmacodynamic Profile of GNT0004 in Duchenne Muscular Dystrophy
NCT07856329 · tracked via the Priya Life Science Spain tracker
Condition(s) studied
Duchene Muscular Dystrophy
Investigational drug(s) / intervention(s)
GNT0004 (1x10e13 vg/kg)GNT0004 (3x10e13 vg/kg)Placebo
GNT0004 (1x10e13 vg/kg): Single intravenous administration of GNT0004
GNT0004 (3x10e13 vg/kg): Single intravenous administration of GNT0004
Placebo: Single intravenous administration of GNT0004 placebo (IMP placebo)
Study 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, 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.
Eligibility
Inclusion Criteria:
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. For participants enrolled in Part 2: Body weight ≤ 95th percentile of the BMI or body weight scale.
5. Positive genetic testing with detailed genotyping confirmation of DMD.
6. Able to achieve a score in the North Star Ambulatory Assessment (NSAA) scale ≥ 18 at the screening visit.
7. Stable or descending evolution in the NSAA total score during the last assessment periods recorded in study GNT-014-MDYF.
8. Gowers test (Time to Rise From Floor) ≤ 7 sec.
9. Ongoing corticosteroid therapy according to standard of care: for at least 6 months before the screening.
10. Up to date vaccination record.
11. Willing and able to comply with all protocol requirements and procedures.
12. Signed informed consents and assent as required by local law.
13. Affiliated/beneficiary of an insurance health care scheme or National Health service (if required by local law).
Exclusion Criteria:
1. DMD patients with any mutations affecting: exons 1 through 17, for Part 1 participants; affecting exons 8 and/or 9 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).
4. Any respiratory assistance needed including non-invasive daytime or nocturnal ventilation.
5. Inability to perform the planned respiratory functions tests.
6. 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.
7. Acute infection that is not expected to be fully resolved for a sufficient time before gene therapy administration.
8. Clinically significant laboratory abnormality values as per protocol.
9. Inability to cooperate with muscle strength and functional assessments.
10. Nuclear Magnetic Resonance Imaging (MRI) contraindications: metal implants, or other contraindication for MRI such as severe phobia.
11. Unwilling and/or unable to comply with all the study protocol requirements and/or procedures.
12. Chronic hepatitis B or C, i.e., positive hepatitis B surface antigen or hepatitis C RNA viral load positive.
13. Previous inclusion to another clinical trial with any non-gene therapy related.
14. 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.
15. 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.
16. Previous gene therapy for DMD.
Primary outcome measure(s)
- 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 — From the Screening Visit through the end of Part 1 (Week 12)
- PART 1 - Immunogenicity Outcomes: Antibodies to AAV8, antibodies to recombinant dystrophin (hMD1) and of cellular immune biomarkers (ELISPOT tests) — From the Screening Visit through the end of Part 1 (Week 12)
- PART 1: Vector shedding quantification in blood, urine, saliva, feces (DNA level) — Once a week through Week 12
- PART 1: Percentage change from baseline on Creatine kinase (CK) in blood over time — From the Screening Visit through the end of Part 1 (Week 12)
- PART 1: Quantification of Microdystrophin positive myofibers level from muscle biopsy at Week 8 — Week 8
- PART 1: Quantification of Microdystrophin protein expression from muscle biopsy at Week 8 — Week 8
- PART 1: Quantification of vector copy number (VCN) over time — From the Screening Visit through the end of Part 1 (Week 12)
- PART 2: Change from baseline in the North Star Ambulatory Assessment (NSAA) total score at Month 18 — From the Screening Visit to Month 18 (Week 78)
- 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 — From the end of Part 1 or Part 2 to 5 years post-treatment administration
Trial sites (14)
| Facility | City | Region | Status |
|---|---|---|---|
| Hôpital Universitaire des Enfants Reine Fabiola | Brussels | Belgium | Recruiting |
| UZ Leuven | Leuven | Belgium | Recruiting |
| Hôpital de la Citadelle | Liège | Belgium | Not Yet Recruiting |
| University Hospital of Bordeaux | Bordeaux | France | Recruiting |
| Brest University Hospital Centre | Brest | France | Recruiting |
| Hôpital Femme Mère Enfant | Bron | France | Recruiting |
| CHU Lille | Lille | France | Recruiting |
| Centre Hospitalier Universitaire De Montpellier | Montpellier | France | Not Yet Recruiting |
| Institut I-Motion, Hôpital Armand Trousseau | Paris | France | Recruiting |
| Hôpitaux Universitaires de Strasbourg | Strasbourg | France | Recruiting |
| Hospital Sant Joan de Déu Barcelona | Esplugues de Llobregat | Spain | Recruiting |
| Hospital Universitario y Politécnico La Fe | Valencia | Spain | Not Yet Recruiting |
| Great Ormond Street Hospital for Children | London | United Kingdom | Recruiting |
| The Newcastle upon Tyne Hospitals NHS Foundation Trust | Newcastle upon Tyne | United Kingdom | Not Yet Recruiting |
More Genethon trials in Spain
Official registry record
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
View NCT07856329 on ClinicalTrials.gov ↗ ← All trials in Spain