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

Pompe Disease (Late-onset) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06391736
• Other study ID #: JLJY-GC301-LOPD-001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: April 19, 2024
• Est. completion date: December 2026

Study information

• Verified date: April 2024
• Source: GeneCradle Inc
• Contact: GeneCradle, Inc China
• Phone: 86-13501380583
• Email: ind[@]bj-genecradle.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 33
• Est. completion date: December 2026
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years and older

Eligibility

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);

Related Conditions & MeSH terms

• Glycogen Storage Disease Type II
• Pompe Disease (Late-onset)

Intervention

Genetic:
• GC301
GC301, is an adeno-associated virus 9 (AAV9) vector delivering a functional copy of the human GAA gene

Locations

Country	Name	City	State
China	Chinese PLA General Hospital	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
GeneCradle Inc

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	GAA enzymatic activity	Change from baseline in GAA enzymatic activity in muscle biopsies	52 weeks
Other	GAA enzymatic activity	Change from baseline in GAA enzymatic activity in blood	52 weeks
Other	Glycogen content in muscle	Change from baseline in glycogen content in muscle biopsies	52 weeks
Primary	Number of Participants With Adverse Events	Number of Participants with Adverse Events as a Measure of Safety and Tolerability	52 weeks
Primary	Dose-limiting toxicity (DLT) rate based on protocol-specific adverse events (Phase 1)		within 30 days after treatment
Primary	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	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
Secondary	Maximum Inspiratory Pressure (MIP)	Change from baseline in MIP measured by pulmonary function testing	52 weeks
Secondary	Maximum Expiratory Pressure (MEP)	Change from baseline in MEP measured by pulmonary function testing	52 weeks
Secondary	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
Secondary	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
Secondary	Time needed for non-invasive ventilatory support	Change from baseline in time duration that needed for non-invasive ventilatory support	52 weeks
Secondary	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
Secondary	Occurrence of immune response against AAV capsid annd GAA transgene		52 weeks