Pompe Disease (Late-onset)
Conditions
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.
Interventions
GENETICGC301
GC301, is an adeno-associated virus 9 (AAV9) vector delivering a functional copy of the human GAA gene
Sponsors
GeneCradle Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
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);
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | 52 weeks | Change from baseline in percentage of predicted FVC measured by pulmonary function testing |
| Number of Participants With Adverse Events | 52 weeks | Number of Participants with Adverse Events as a Measure of Safety and Tolerability |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Expiratory Pressure (MEP) | 52 weeks | Change from baseline in MEP measured by pulmonary function testing |
| Muscle Status Testing - Quick Motor Function Test (QMFT) Measure | 52 weeks | Measurement of functional motor abilities using the Quick Motor Function Test (QMFT) will be performed and the results compared with baseline. |
| Time needed for non-invasive ventilatory support | 52 weeks | Change from baseline in time duration that needed for non-invasive ventilatory support |
| The viral load of adeno-associated virus (AAV) vector | 52 weeks | To assess the change of AAV vector copy numbers within 52 weeks after administration. |
| Occurrence of immune response against AAV capsid annd GAA transgene | 52 weeks | — |
| Quality of life evaluation: 12-item short form health survey (SF-12) for LOPD participants | 52 weeks | 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. |
| 6-Minute Walk Test | 52 weeks | 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 |
| Maximum Inspiratory Pressure (MIP) | 52 weeks | Change from baseline in MIP measured by pulmonary function testing |
Other
| Measure | Time frame | Description |
|---|---|---|
| GAA enzymatic activity | 52 weeks | Change from baseline in GAA enzymatic activity in muscle biopsies |
| Glycogen content in muscle | 52 weeks | Change from baseline in glycogen content in muscle biopsies |
Countries
China
Contacts
Primary ContactGeneCradle, Inc China
Outcome results
None listed