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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Infantile-onset Pompe Disease

Intervention / Treatment
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* Biological: Genetic: GC301


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Maximum Age: 6 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Initial dose cohort<br>1.2x10^14 vg/kg of GC301 administered via intravenous infusion | Biological: Genetic: GC301<br>* GC301, is an adeno-associated virus 9 (AAV9) vector delivering a functional copy of the human GAA gene<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability over time | Frequency of adverse events (AEs), serious adverse events (SAEs), and changes from baseline in relevant clinical laboratory tests | Infusion to the end of study, average 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients treated w/ GC301 who were alive and free of ventilator support at 12 months of age; |  | 52 weeks | 
| Changes from baseline Left Ventricular Mass (LVM) |  | 26 and 52 weeks | 
| Changes from baseline creatine kinase (CK) |  | 26 and 52 weeks |