Multicenter, Single-blind, Randomized, Placebo-controlled Study of a Single Intravenous Infusion of a Gene Therapy Product GNR-097 in Pediatric Patients With Duchenne Muscular Dystrophy
The study will evaluate the tolerability, safety and efficacy of gene therapy product in boys with Duchenne muscular dystrophy (DMD). In Phase I the participants will be included in two sequential dose cohorts with increasing doses of the investigational product. Based on the results of Phase I, the dose of the investigational product for use in Phase II will be determined. Phase II is a randomized, single-blind, placebo-controlled study. The participants who are randomized to the placebo arm will have an opportunity for treatment with gene therapy at the beginning of the second year.
• 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.