Evaluation of the Safety and Efficacy of BBM-D101 to Treat Patients with Duchenne Muscular Dystrophy

This is a single-arm, open-label study to evaluate the safety, tolerability, efficacy, pharmacokinetic, pharmacodynamic, and immune response of BBM-D101 within 52 weeks after a single intravenous infusion in DMD boys, as well as the long-term safety and efficacy of BBM-D101 for up to 5 years post infusion.

BBM-D101 is gene addition therapy based on engineered AAV delivery therapeutic protein gene cassette into muscle for treating DMD. Therapeutic protein could mediate the dystrophin-associated protein complex to prevent muscular dystrophy and to rescue the function of muscle.

Inclusion criteria

• The legal guardian of the subject fully understands the purpose, nature, methods, and possible risks of the study, and signs a written informed consent form;
• The study includes ambulatory male subjects who are at least 4 years old and less than 8 years old (4 years old ≤ age < 8 years old) ;
• Genetically confirmed diagnosis of DMD;
• Have at least 1 of the following typical clinical signs or laboratory abnormalities of DMD: proximal muscle weakness, waddling gait, pseudo gastrocnemius hypertrophy, Gower's sign, pterygoid scapula;
• Ability to cooperate with motor assessment testing, magnetic resonance imaging (MRI) and muscle biopsy according to the requirements of the study.

Exclusion criteria

• Hepatitis B surface antigen (HBsAg) positive, hepatitis B virus deoxyribonucleic acid (HBV-DNA) ≥1000U/mL, hepatitis C virus ribonucleic acid (HCV-RNA) positive or human immunodeficiency virus (HIV) positive;
• Receiving antiviral therapy for hepatitis B, hepatitis C, HIV, etc.;
• Left ventricular ejection fraction (LVEF) <50% or ≥ class III cardiac function defined by New York Heart Association (NYHA);
• With severe or persistent arrhythmias and congenital heart disease.
• The subject's preventive treatment/cardiomyopathy treatment changes within 1 month before the start of the study treatment;
• With underlying liver disease, such as previous diagnosis of portal hypertension, splenomegaly, hepatic encephalopathy, or hepatic fibrosis ≥ stage 3; or nodules, cysts found by B-ultrasound in the past, or elevated alpha-fetoprotein in laboratory tests during the screening period, etc., and these abnormalities are judged by the investigator to be clinically significant;