Clinical trial NCT06391736: Evaluation of the Safety and Efficacy of Late-onset Pompe Disease Gene Therapy Drug
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Pompe Disease (Late-onset)
Lead sponsor: GeneCradle Inc
Sponsor class: INDUSTRY
First posted: 2024-04-30
Enrollment: 33
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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);

Primary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: 52 weeks
measure: Dose-limiting toxicity (DLT) rate based on protocol-specific adverse events (Phase 1)
timeFrame: within 30 days after treatment
measure: Percent Predicted Upright Forced Vital Capacity (FVC)(Phase 2)
timeFrame: 52 weeks
Secondary outcomes:
measure: 6-Minute Walk Test
timeFrame: 52 weeks
measure: Maximum Inspiratory Pressure (MIP)
timeFrame: 52 weeks
measure: Maximum Expiratory Pressure (MEP)
timeFrame: 52 weeks
measure: Muscle Status Testing - Quick Motor Function Test (QMFT) Measure
timeFrame: 52 weeks
measure: Quality of life evaluation: 12-item short form health survey (SF-12) for LOPD participants
timeFrame: 52 weeks
measure: Time needed for non-invasive ventilatory support
timeFrame: 52 weeks
measure: The viral load of adeno-associated virus (AAV) vector
timeFrame: 52 weeks
measure: Occurrence of immune response against AAV capsid annd GAA transgene
timeFrame: 52 weeks
Other outcomes:
measure: GAA enzymatic activity
timeFrame: 52 weeks
measure: GAA enzymatic activity
timeFrame: 52 weeks
measure: Glycogen content in muscle
timeFrame: 52 weeks
Locations:
city: Beijing
country: China
facility: Chinese PLA General Hospital
Study officials:
affiliation: Chinese PLA General Hospital
name: Guang Yang
role: STUDY_CHAIR
affiliation: Chinese PLA General Hospital
name: Guang Yang
role: PRINCIPAL_INVESTIGATOR
References: