Clinical trial NCT05567627: Clinical Exploration of Adeno-associated Virus (AAV) Expressing Human Acid Alpha- Glucosidase (GAA) Gene Therapy for Patients With Infantile-onset Pompe Disease
Official title: Single Arm, Multicenter, Open and Dose-escalation Clinical Study on Safety, Tolerance, and Efficacy of GC301, an AAV-Delivered Gene Transfer Therapy in Patients With Infantile-onset Pompe Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Infantile-onset Pompe Disease
Lead sponsor: Seventh Medical Center of PLA General Hospital
Sponsor class: OTHER
Collaborators: name: GeneCradle Therapeutics, Inc
First posted: 2022-10-05
Enrollment: 6
Sex: ALL
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
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 infantile-onset Pompe disease who are younger than 6 months old will be studied.


Eligibility criteria: 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.

Primary outcomes:
measure: Safety and tolerability over time
timeFrame: Infusion to the end of study, average 1 year
Secondary outcomes:
measure: Proportion of patients treated w/ GC301 who were alive and free of ventilator support at 12 months of age;
timeFrame: 52 weeks
measure: Changes from baseline Left Ventricular Mass (LVM)
timeFrame: 26 and 52 weeks
measure: Changes from baseline creatine kinase (CK)
timeFrame: 26 and 52 weeks
Other outcomes:
measure: Change from baseline glycogen content in muscle tissue
timeFrame: 26 and 52 weeks
measure: Change from baseline acid alpha-glucosidase (GAA) enzyme in muscle and blood
timeFrame: 26 and 52 weeks
measure: Improvement in patient's motor function
timeFrame: 52 weeks
measure: The viral load of adeno-associated virus (AAV) vector
timeFrame: At multiple time points from pre-dose through up to 1 years post-dose
Locations:
city: Beijing
country: China
facility: Bayi Children's Hospital, Seventh Medical Center, PLA general hospital
state: Beijing
Study officials:
References: