Clinical trial NCT05793307: Evaluation of the Safety and Efficacy of Infantile-onset Pompe Disease Gene Therapy Drug
Official title: A Multi-centered, Single Arm, Open Labeled, Study to Evaluate the Safety and Efficacy of an Adeno-associated Virus Vector Expressing the Human Acid Alpha-glucosidase (GAA) Transgene Intravenous Injection in Patients With Infantile-onset Pompe Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Pompe Disease Infantile-Onset
Lead sponsor: GeneCradle Inc
Sponsor class: INDUSTRY
First posted: 2023-03-31
Enrollment: 16
Sex: ALL
Maximum age (years): 6
Standard ages: CHILD
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 infantile-onset Pompe disease who are younger than 6 months old will be studied.


Eligibility criteria: Inclusion Criteria:

* Age \< 6 months
* Patient has diagnosis of infantile onset Pompe disease
* 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:

* Left ventricle ejection fraction (LVEF) \< 40%;
* Patient who has AAV9 neutralizing antibody titer ≥ 1:100；
* Patient who has received enzyme replacement therapy (ERT) more than twice;
* Patient who has respiratory dysfunction before enrollment, including the blood oxygen (O2) saturation level \< 90%, or the partial pressure of carbon dioxide (PCO2) in venous blood \> 55 mmHg, or PCO2 in arterial blood \> 40 mmHg;
* Patient who has laboratory abnormalities of: creatinine \> Upper Limit of Normal (ULN), hemoglobin \< 90 g/L;
* Patient with congenital organ absence;
* Patient with a history of glucocorticoid allergy;
* Patient who is positive for human immunodeficiency (HIV) antibody, hepatitis B surface antigen, hepatitis C antibody, or treponema pallidum antibody;
* 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: 52 weeks
measure: Proportion of patients treated with GC301 who are alive
timeFrame: 52 weeks
Secondary outcomes:
measure: Proportion of patients treated w/ GC301 who were alive and free of ventilator support
timeFrame: 52 weeks
measure: Changes from baseline Left Ventricular Mass (LVM) annd LVMI (LVM index)
timeFrame: 26 and 52 weeks
measure: Changes from baseline creatine kinase (CK), CK-MB, Troponin I, B-Type Natriuretic Peptide (BNP)
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: Change 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: Peking Union Medical College
city: Beijing
country: China
facility: 301 Chinese PLA General Hospital
city: Changsha
country: China
facility: Central South University, Xiangya Hospital
city: Hangzhou
country: China
facility: Zhejiang University, School of Medicine, The Children's Hospital
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
Study officials:
References: