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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Pompe Disease Infantile-Onset
• Intervention / Treatment: Genetic: GC301

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100005
    • Peking Union Medical College
  • Beijing, China
    • 301 Chinese PLA General Hospital
  • Changsha, China
    • Central South University, Xiangya Hospital
  • Hangzhou, China
    • Zhejiang University, School of Medicine, The Children's Hospital
  • Zhengzhou, China
    • The First Affiliated Hospital of Zhengzhou University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 6 months (Child)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Single intravenous administration of GC301 at a dose of 8.0 x 10^13 vector genomes per kilogram body weight	Genetic: GC301; GC301, is an adeno-associated virus 9 (AAV9) vector delivering a functional copy of the human GAA gene
Experimental: Cohort 2; Single intravenous administration of GC301 at a dose of 1.2 x 10^14 vector genomes per kilogram body weight	Genetic: GC301; GC301, is an adeno-associated virus 9 (AAV9) vector delivering a functional copy of the human GAA gene
Experimental: Cohort 3; Single intravenous administration of GC301 at a dose of 1.8 x 10^14 vector genomes per kilogram body weight	Genetic: GC301; GC301, is an adeno-associated virus 9 (AAV9) vector delivering a functional copy of the human GAA gene

What is the study measuring?

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	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline glycogen content in muscle tissue		26 and 52 weeks
Change from baseline acid alpha-glucosidase (GAA) enzyme in muscle and blood		26 and 52 weeks
The viral load of adeno-associated virus (AAV) vector	To assess the change of AAV vector copy numbers within 52 weeks after administration.	At multiple time points from pre-dose through up to 1 years post-dose
Change in patient's motor function	To evaluate the changes in patient's mobility and physical ability using Hammersmith Infant Neurological Examination (HINE) scores	52 weeks

Collaborators and Investigators

• Sponsor: GeneCradle Inc

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2023
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: March 20, 2023
• First Submitted That Met QC Criteria: March 20, 2023
• First Posted (Actual): March 31, 2023

Study Record Updates

• Last Update Posted (Actual): July 3, 2025
• Last Update Submitted That Met QC Criteria: July 1, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Carbohydrate Metabolism, Inborn Errors; Lysosomal Storage Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Lysosomal Storage Diseases, Nervous System; Glycogen Storage Disease; Glycogen Storage Disease Type II
• Other Study ID Numbers: JLJY-GC301-IOPD-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No