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.

Study Overview

• Status: Recruiting
• Conditions: Infantile-onset Pompe Disease
• Intervention / Treatment: Biological: Genetic: GC301

• Study Type: Interventional
• Enrollment (Estimated): 6
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Zhichun Feng; Phone Number: +86(10) 66721786; Email: zhichunfeng81@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100700
      • Recruiting
      • Bayi Children's Hospital, Seventh Medical Center, PLA general hospital
      • Contact: Xiaodong Wang, PhD; Phone Number: +86 17801060980; Email: donnawang@bj-genecradle.com
      • Contact: Zhichun Feng, Prof; Phone Number: +86(10) 66721786; Email: zhichunfeng81@163.com

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Initial dose cohort; 1.2x10^14 vg/kg of GC301 administered via intravenous infusion	Biological: 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	Infusion to the end of study, average 1 year

Secondary Outcome Measures

Outcome Measure	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

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
Improvement 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
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

Collaborators and Investigators

• Sponsor: Seventh Medical Center of PLA General Hospital
• Collaborators: GeneCradle Therapeutics, Inc

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2022
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: September 25, 2022
• First Submitted That Met QC Criteria: September 30, 2022
• First Posted (Actual): October 5, 2022

Study Record Updates

• Last Update Posted (Actual): November 1, 2023
• Last Update Submitted That Met QC Criteria: October 30, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Lysosomal Storage Diseases, Nervous System; Glycogen Storage Disease; Glycogen Storage Disease Type II
• Other Study ID Numbers: JLJY-GC301-IOPD-003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No