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

Prior treatment

• Presence of neutralizing antibodies against AAV8.
• 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.
• Nuclear Magnetic Resonance Imaging (MRI) contraindications: metal implants, or other contraindication for MRI such as severe phobia.
• 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.

Other illness

• Cardiomyopathy based on physical/cardiological examination and echocardiography (or cardiac MRI if available).
• Acute infection that is not expected to be fully resolved for a sufficient time before gene therapy administration.
• Chronic hepatitis B or C, i.e., positive hepatitis B surface antigen or hepatitis C RNA viral load positive.

Lab values

• Clinically significant laboratory abnormality values as per protocol.

Other

• DMD patients with any mutations affecting: exons 1 through 17, for Part 1 participants; affecting exons 8 and/or 9 for Part 2 participants.
• Any respiratory assistance needed including non-invasive daytime or nocturnal ventilation.
• Inability to perform the planned respiratory functions tests.
• Inability to cooperate with muscle strength and functional assessments.
• Unwilling and/or unable to comply with all the study protocol requirements and/or procedures.

• 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.
• 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).