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

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.

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.