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

Ongoing corticosteroid therapy with prednisolone (or prednisone) according to standard of care (participants receiving deflazacort or vamorolone daily dose can switch to prednisolone (or prednisone) 4 weeks before screening)

• Ambulant male.
• 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.
• 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).

• 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.
• 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.