A Study to Evaluate the Tolerability, Safety and Efficacy of GNR-097 Gene Therapy in Pediatric Patients With Duchenne Muscular Dystrophy

Prior treatment

• Acute infectious diseases that resolved less than 4 weeks before administration of GNR-097/placebo.
• Immunization with a live attenuated vaccine less than 3 months before administration of GNR-097/placebo OR immunization with any inactivated vaccine less than 4 weeks before administration of GNR-097/placebo.
• Use of immunosuppressive drugs other than glucocorticosteroids less than 12 weeks prior to signing the Informed Consent Form.
• Participation in clinical trials less than 6 months prior to signing the Informed Consent Form.

Other illness

• Hypersensitivity to any component of GNR-097 or placebo.
• Patient with cognitive impairment or a sedentary lifestyle that, in the opinion of the investigator, may interfere with the development or manifestation of motor activity.
• History of any autoimmune disease, with the exception of drug-compensated autoimmune thyroiditis.
• History of tuberculosis; positive or indeterminate result of Diaskintest® TigraTest® or T-SPOT.TB screening.
• Positive results of tests for hepatitis B, hepatitis C, or HIV screening.
• History of taking antisense oligonucleotides, ataluren, gene therapy using vector constructs, or cell therapy.
• Other diseases or conditions not listed above that, in the opinion of the physician investigator and/or the Sponsor, prevent the patient from participating in the trial, including for safety reasons.

Lab values

• Clinical signs of cardiomyopathy, including left ventricular ejection fraction (Simpson) \<40% based on echocardiography performed during screening.
• Abnormal laboratory parameters:
  • GGT level is more than three upper limits of normal;
  • total bilirubin \>50.0 μmol/L (except for patients with a confirmed diagnosis of Gilbert's syndrome);
  • creatinine \>160.0 μmol/L;
  • hemoglobin \<80 or \>180 g/L;
  • white blood cell count \>18,500/μL;
  • platelet count below the lower limit of normal.

Other

• Mutations in exons 8 and/or 9 of the DMD gene; for patients planned for inclusion in Cohort A, additionally: mutations in exons 1-17 and/or 59-71 of the DMD gene.
• Contraindications to magnetic resonance imaging.
• Unwillingness or inability of the patient and/or their parent/legal guardian to comply with the protocol requirements and/or the trial procedures.

• Written informed consent for participation in the trial.
• Ambulatory boys aged 4-9 years with a documented diagnosis of DMD and clinical manifestations of the disease.
• A frameshift mutation or nonsense mutation in the DMD gene.
• Сreatine phosphokinase level \>5000 U/L.
• Binding antibody titer to AAV9 ≤1:50 \[method: ELISA\].
• The patient is able to interact with the study physician and perform tests to assess functional activity.
• Results of functional activity assessment tests at screening (at least in one of the two attempts performed on different days):
  • NSAA ≥22;
  • time to rise from a supine position without using surrounding objects or furniture \<5 sec;
  • 6MWT distance ≥350 m.
• The patient received oral glucocorticosteroids at a stable dose for ≥12 weeks prior to signing the Informed Consent Form, and it is planned that glucocorticosteroids will be continued during the screening stage and after the patient's inclusion in the study.
• For patients receiving deflazacort at study entry: switching the patient from deflazacort to prednisolone, in the opinion of the investigator, will not result in a significant deterioration in the patient's health.
• The patient has been immunized with a vaccine against meningococcal serotypes A, C, Y, W135 (and B, if available) no later than 4 weeks prior to administration of GNR-097/placebo, and the immunization period expires no more than three months after the expected date of administration of GNR-097/placebo.