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

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.

Study Overview

• Status: Recruiting
• Conditions: Duchenne Muscular Dystrophy
• Intervention / Treatment: Genetic: GNR-097; Genetic: Placebo followed by GNR-097

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Elena I. Zagoruyko, M.D.; Phone Number: +7 (926) 344 84 48; Email: eizagoruiko@generium.ru
• Study Contact Backup: Name: Oksana A. Markova, M.D.; Phone Number: +7 (985) 441 89 59; Email: oamarkova@generium.ru

Study Locations

• Belarus
  • Minsk, Belarus, 220053
    • Recruiting
    • Republican Scientific and Practical Center Mother and Child
    • Principal Investigator: Irina V. Zhevneronok, Ph.D.
• Russia
  • Moscow, Russia, 117513
    • Recruiting
    • Russian Children's Clinical Hospital
    • Principal Investigator: Svetlana V. Mikhailova, Dr. Med. Sci.
  • Moscow, Russia, 119991
    • Recruiting
    • National Medical Research Center for Children
    • Principal Investigator: Lyudmila M. Kuzenkova, Dr. Med. Sci., professor
  • Moscow, Russia, 125412
    • Recruiting
    • Veltischev Research and Clinical Institute for Pediatrics and Pediatric Surgery of the Pirogov Russian National Research Medical University
    • Principal Investigator: Dmitry V. Vlodavets, Dr. Med. Sci.
  • Saint Petersburg, Russia, 194100
    • Recruiting
    • Saint Petersburg State Pediatric Medical University
    • Principal Investigator: Vasily M. Suslov, Ph.D.
  • Yekaterinburg, Russia, 620149
    • Recruiting
    • Regional Children's Clinical Hospital
    • Principal Investigator: Olga A. Lvova, Dr. Med. Sci.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Written informed consent for participation in the trial.
2. Ambulatory boys aged 4-9 years with a documented diagnosis of DMD and clinical manifestations of the disease.
3. A frameshift mutation or nonsense mutation in the DMD gene.
4. Сreatine phosphokinase level >5000 U/L.
5. Binding antibody titer to AAV9 ≤1:50 [method: ELISA].
6. The patient is able to interact with the study physician and perform tests to assess functional activity.

7. 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.
8. 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.
9. 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.
10. 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.

Exclusion Criteria:

1. Hypersensitivity to any component of GNR-097 or placebo.
2. 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.
3. 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.
4. Clinical signs of cardiomyopathy, including left ventricular ejection fraction (Simpson) <40% based on echocardiography performed during screening.
5. Contraindications to magnetic resonance imaging.
6. History of any autoimmune disease, with the exception of drug-compensated autoimmune thyroiditis.
7. History of tuberculosis; positive or indeterminate result of Diaskintest® TigraTest® or T-SPOT.TB screening.
8. Positive results of tests for hepatitis B, hepatitis C, or HIV screening.
9. Acute infectious diseases that resolved less than 4 weeks before administration of GNR-097/placebo.
10. 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.

11. 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.
12. History of taking antisense oligonucleotides, ataluren, gene therapy using vector constructs, or cell therapy.
13. Use of immunosuppressive drugs other than glucocorticosteroids less than 12 weeks prior to signing the Informed Consent Form.
14. Participation in clinical trials less than 6 months prior to signing the Informed Consent Form.
15. Unwillingness or inability of the patient and/or their parent/legal guardian to comply with the protocol requirements and/or the trial procedures.
16. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GNR-097; Participants will receive single intravenous (IV) infusion of GNR-097 on Day 1.	Genetic: GNR-097; Single IV infusion of GNR-097 (recombinant adeno-associated virus, serotype 9 (AAV9) carrying a truncated human dystrophin gene (micro-dystrophin)).
Placebo Comparator: Placebo followed by GNR-097; In Phase II participants will receive matching placebo IV infusion on Day 1. Then, they will have the opportunity to receive a single IV infusion of GNR-097 at the beginning of the second year.	Genetic: Placebo followed by GNR-097; Single IV infusion of matching placebo followed by single IV infusion of GNR-097 at the beginning of the second year.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and percentage of participants with treatment-emergent adverse events (AEs), AEs of special interest and serious adverse events (SAEs)	AEs of special interest include immune-mediated myositis, myocarditis, thrombotic microangiopathy and hemolytic uremic syndrome	Baseline to End of Study (Week 104)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antibodies to AAV9 and microdystrophin	Presence and titer of binding and neutralizing antibodies to AAV9 and total antibodies to microdystrophin as measured by ELISA	Baseline to End of Study (Week 104)
Quantity of dystrophin and microdystrophin in biopsied muscle	Measured by Western blot	Baseline, Week 12
Percentage of dystrophin-positive muscle fibers in biopsied muscle	Measured by immunohistochemistry (IHC)	Baseline, Week 12
Intensity of immunofluorescence of muscle fibers in biopsied muscle when they are stained for dystrophin	Measured by IHC	Baseline, Week 12
North Star Ambulatory Assessment (NSAA) score	Confirmed by independent assessor	Baseline to End of Study (Week 104)
Time to rise from the floor from a supine position	Time to rise from the floor from a supine position	Baseline to End of Study (Week 104)
Six minute walk test (6MWT) distance	Confirmed by independent assessor	Baseline to End of Study (Week 104)

Collaborators and Investigators

• Sponsor: AO GENERIUM
• Investigators: Study Chair: Oksana A. Markova, M.D., AO GENERIUM

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2025
• Primary Completion (Estimated): August 2, 2029
• Study Completion (Estimated): August 2, 2029

Study Registration Dates

• First Submitted: June 23, 2026
• First Submitted That Met QC Criteria: June 23, 2026
• First Posted (Actual): June 29, 2026

Study Record Updates

• Last Update Posted (Actual): June 29, 2026
• Last Update Submitted That Met QC Criteria: June 23, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Gene Therapy; Duchenne Muscular Dystrophy; DMD; AAV; Ambulatory; AAV9; Micro-dystrophin
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Muscular Disorders, Atrophic; Muscular Dystrophies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: GNR097-DMD01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No