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

A Multi-centered, Single Arm, Open Labeled, Study to Evaluate the Safety, Tolerability, and Efficacy of an Adeno-associated Virus Vector Expressing the Human Acid Alpha-glucosidase (GAA) Transgene Intravenous Injection in Patients With Late-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 late-onset Pompe disease （LOPD） who are ≥ 6 years old will be studied.

Study Overview

• Status: Recruiting
• Conditions: Pompe Disease (Late-onset)
• Intervention / Treatment: Genetic: GC301

• Study Type: Interventional
• Enrollment (Estimated): 33
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: GeneCradle, Inc China; Phone Number: 86-13501380583; Email: ind@bj-genecradle.com

Study Locations

• China
  • Beijing, China, 100853
    • Recruiting
    • Chinese PLA General Hospital
    • Principal Investigator: Guang Yang
    • Contact: Xinting Liu; Phone Number: 16601558283; Email: lxting0531@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 6 years, males or females;
• Patient has a diagnosis of LOPD;
• Patient has upright FVC ≥ 30% of predicted normal value;
• A 6MWT ≥ 40 meters, assistive device allowed;
• 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:

• Patient who has any history or concurrent clinical organic disease, including cardiovascular and liver diseases, respiratory system, nervous system disease, or any other condition that, in the opinion of the investigator, makes the subject unsuitable for participation in the study.
• Patient who requires invasive mechanical ventilation, or rely on noninvasive non-non-invasive assisted ventilation when sitting upright;
• Patient who is positive for human immunodeficiency (HIV) antibody, hepatitis B surface antigen, hepatitis C antibody, or treponema pallidum antibody;
• Patient with a history of glucocorticoid allergy;
• Patient who has a contraindication to study drug or to corticosteroids, or has demonstrated hypersensitivity to any of the components of the study drug;
• Patient who has AAV9 neutralizing antibody titer ≥ 1:100；
• Patient who has participated in a previous gene therapy research trial;
• Pregnant or lactating female participants;
• Patients who have fertility plans within 6 months from screening to the end of the study and are unwilling to take effective physical contraceptive measures (such as a condom, intrauterine device, contraceptive ring, ligation, abstinence, etc.) for contraception (including the subject's partner);

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low dosage group; Single intravenous administration of GC301 at a dose of 3.0 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: High dosage group; Single intravenous administration of GC301 at a dose of 6.0 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events	Number of Participants with Adverse Events as a Measure of Safety and Tolerability	52 weeks
Dose-limiting toxicity (DLT) rate based on protocol-specific adverse events (Phase 1)		within 30 days after treatment
Percent Predicted Upright Forced Vital Capacity (FVC)(Phase 2)	Change from baseline in percentage of predicted FVC measured by pulmonary function testing	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6-Minute Walk Test	Change from baseline in the distance walked in the 6 minute walk test (6MWT), which is a standardized assessment of how far an individual can walk on a hard, flat surface in a period of 6 minutes	52 weeks
Maximum Inspiratory Pressure (MIP)	Change from baseline in MIP measured by pulmonary function testing	52 weeks
Maximum Expiratory Pressure (MEP)	Change from baseline in MEP measured by pulmonary function testing	52 weeks
Muscle Status Testing - Quick Motor Function Test (QMFT) Measure	Measurement of functional motor abilities using the Quick Motor Function Test (QMFT) will be performed and the results compared with baseline.	52 weeks
Quality of life evaluation: 12-item short form health survey (SF-12) for LOPD participants	SF-12, a 12 item-questionnaire, used to assess health-related quality of life in participants aged >=18 years at screening/baseline. SF-12 consisted of 12 items, which were categorized into eight domains (subscales) of functioning and well-being: physical functioning, role-physical, role emotional, mental health, bodily pain, general health, vitality and social functioning, with each domain score ranged from 0 (poor health) to 100 (better health), higher scores indicated good health condition. These eight domains were further summarized into 2 summary scores, physical component summary (PCS) and mental component summary (MCS). The score range for each of these 2 summary scores was from 0 (poor health) to 100 (better health), higher scores indicated a better health-related quality of life.	52 weeks
Time needed for non-invasive ventilatory support	Change from baseline in time duration that needed for non-invasive ventilatory support	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.	52 weeks
Occurrence of immune response against AAV capsid annd GAA transgene		52 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
GAA enzymatic activity	Change from baseline in GAA enzymatic activity in muscle biopsies	52 weeks
GAA enzymatic activity	Change from baseline in GAA enzymatic activity in blood	52 weeks
Glycogen content in muscle	Change from baseline in glycogen content in muscle biopsies	52 weeks

Collaborators and Investigators

• Sponsor: GeneCradle Inc
• Investigators: Study Chair: Guang Yang, Chinese PLA General Hospital; Principal Investigator: Guang Yang, Chinese PLA General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: April 25, 2024
• First Submitted That Met QC Criteria: April 25, 2024
• First Posted (Actual): April 30, 2024

Study Record Updates

• Last Update Posted (Actual): April 30, 2024
• Last Update Submitted That Met QC Criteria: April 25, 2024
• Last Verified: April 1, 2024

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-LOPD-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