Infantile-onset Pompe Disease
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 infantile-onset Pompe disease who are younger than 6 months old will be studied.
Interventions
BIOLOGICALGenetic: GC301
GC301, is an adeno-associated virus 9 (AAV9) vector delivering a functional copy of the human GAA gene
Sponsors
GeneCradle Therapeutics, Inc
Seventh Medical Center of PLA General Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 6 Months
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability over time | Infusion to the end of study, average 1 year | Frequency of adverse events (AEs), serious adverse events (SAEs), and changes from baseline in relevant clinical laboratory tests |
Secondary
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | 52 weeks | To evaluate the changes in patient's mobility and physical ability using Hammersmith Infant Neurological Examination (HINE) scores |
| The viral load of adeno-associated virus (AAV) vector | At multiple time points from pre-dose through up to 1 years post-dose | To assess the change of AAV vector copy numbers within 52 weeks after administration. |
Countries
China
Contacts
Primary ContactZhichun Feng
Outcome results
None listed