Evaluation of the Safety and Efficacy of Infantile-onset Pompe Disease Gene Therapy Drug

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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A Multi-centered, Single Arm, Open Labeled, Study to Evaluate the Safety and Efficacy of an Adeno-associated Virus Vector Expressing the Human Acid Alpha-glucosidase (GAA) Transgene Intravenous Injection in Patients With Infantile-onset Pompe Disease

Conditions
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Pompe Disease Infantile-Onset

Intervention / Treatment
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* Genetic: GC301


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age < 6 months Patient has diagnosis of infantile onset Pompe disease 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. Exclusion Criteria: Left ventricle ejection fraction (LVEF) < 40%; Patient who has AAV9 neutralizing antibody titer ≥ 1:100； Patient who has received enzyme replacement therapy (ERT) more than twice; Patient who has respiratory dysfunction before enrollment, including the blood oxygen (O2) saturation level < 90%, or the partial pressure of carbon dioxide (PCO2) in venous blood > 55 mmHg, or PCO2 in arterial blood > 40 mmHg; Patient who has laboratory abnormalities of: creatinine > Upper Limit of Normal (ULN), hemoglobin < 90 g/L; Patient with congenital organ absence; Patient with a history of glucocorticoid allergy; Patient who is positive for human immunodeficiency (HIV) antibody, hepatitis B surface antigen, hepatitis C antibody, or treponema pallidum antibody; 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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Single intravenous administration of GC301 at a dose of 8.0 x 10^13 vector genomes per kilogram body weight | Genetic: GC301<br>* GC301, is an adeno-associated virus 9 (AAV9) vector delivering a functional copy of the human GAA gene<br>|
| Experimental: Cohort 2<br>Single intravenous administration of GC301 at a dose of 1.2 x 10^14 vector genomes per kilogram body weight | Genetic: GC301<br>* GC301, is an adeno-associated virus 9 (AAV9) vector delivering a functional copy of the human GAA gene<br>|
| Experimental: Cohort 3<br>Single intravenous administration of GC301 at a dose of 1.8 x 10^14 vector genomes per kilogram body weight | 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 | 52 weeks | 
| Proportion of patients treated with GC301 who are alive |  | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients treated w/ GC301 who were alive and free of ventilator support |  | 52 weeks | 
| Changes from baseline Left Ventricular Mass (LVM) annd LVMI (LVM index) |  | 26 and 52 weeks | 
| Changes from baseline creatine kinase (CK), CK-MB, Troponin I, B-Type Natriuretic Peptide (BNP) |  | 26 and 52 weeks |