Clinical Exploration of Adeno-associated Virus (AAV) Expressing Human Acid Alpha- Glucosidase (GAA) Gene Therapy for Patients With Infantile-onset Pompe Disease

Single Arm, Multicenter, Open and Dose-escalation Clinical Study on Safety, Tolerance, and Efficacy of GC301, an AAV-Delivered Gene Transfer Therapy in Patients With Infantile-onset Pompe Disease

This study is being conducted to evaluate the safety and effectiveness of GC301 adeno-associated virus vector expressing codon-optimized human acid alpha-glucosidase (GAA) as potential gene therapy for Pompe disease. Patients diagnosed with infantile-onset Pompe disease who are younger than 6 months old will be studied.

Inclusion Criteria:

• The patient's legal guardian(s) must be able to understand the purpose and risks of the study and voluntarily provide signed and dated informed consent prior to any study-related procedures being performed;
• The patient must be no older than 6 months;
• The patient must be diagnosed with infantile-onset Pompe disease.

Exclusion Criteria:

• Class IV patient based on Modified Ross Heart Failure Classification for Children;
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) > 3x upper limit of normal (ULN), alkaline phosphatase (ALP) > 2x ULN (with the exception of liver abnormalities related to Pompe disease);
• Patient has severe organ dysfunction, such as liver and kidney failure (Liver failure: patients may have liver failure syndrome, including fatigue, severe gastrointestinal symptoms; clinical examination found prolonged prothrombin time, prothrombin activity less than 40%; Neuropsychiatric symptoms, such as restlessness, changes in personality and behavior, lethargy, coma, etc.; Toxic tympanic bowel, ascites, multiple organ dysfunction, etc.; hyperalbuminemia exceeding 171 μmol/L, hypoalbuminemia. Renal failure: creatinine exceeding 110 μmol/L, or glomerular filtration rate less than 100 mL/min), congenital/acquired encephalopathy, etc.;
• Patient with congenital organ absence;
• Patient with primary immunodeficiency;
• Patient who is positive for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen, hepatitis C antibody, or treponema pallidum antibody;
• Patient with a history of glucocorticoid allergy；
• Patient who has participated in a previous gene therapy research trial;
• Patient who has any concurrent clinically significant major disease or any other condition that, in the opinion of the Investigator, makes the subject unsuitable for participation in the study.