GM2 gangliosidoses are a group of autosomal recessive neurodegenerative diseases characterized by a deficiency of the Hex A enzyme to catabolize GM2, thereby causing GM2 accumulation within cellular lysosomes.Hex A is composed of 2 subunits, α- and β-, coded by the HEXA and HEXB genes, respectively. The primary purpose of the current study is to assess the safety and tolerability of TSHA101 administered via IT injection.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
3
AAV9 viral vector containing HEXA and HEXB genes to be administered via Intrathecal injection
Queen's University/Kingston Health Sciences Centre
Kingston, Ontario, Canada
Safety and tolerability: Treatment-emergent Adverse Events (TEAEs)
Incidence, severity, and relatedness of TEAEs
Time frame: 1 year
Safety and Tolerability: Number of participants with abnormal Laboratory assessments
Number of participants with Changes from Baseline in laboratory assessments
Time frame: 1 year
Safety and Tolerability: Electrocardiogram (ECG)
Changes from Baseline in 12-lead ECG findings in QT interval
Time frame: 1 year
Safety and tolerability: Viral shedding analysis
Positive presence of viral DNA from biological fluids (whole blood, urine, saliva, and stool)
Time frame: 1 year
Assessment of Immunogenicity: Biomarkers in serum
Summary of neutralizing antibodies (NAbs) titers for adeno-associated virus, serotype 9 (AAV9) and Hex A
Time frame: 1 year
Assessment of Immunogenicity: Biomarkers in serum
Summary of total antibodies (TAbs) titers for AAV9 and Hex A
Time frame: 1 year
Assessment of Immunogenicity: Biomarkers in peripheral blood mononuclear cells (PBMCs
Summary of PBMCs for enzyme-linked immune absorbent spot (ELISpot) assays for cytokine secretion against AAV9 and Hex A
Time frame: 5 years
Overall Survival
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Estimated using the Kaplan-Meier method
Time frame: treatment to death from any cause, up to 5 years
Hex A Enzyme Activity: Cerebrospinal fluid (CSF) and serum
Change from baseline
Time frame: 1 year
Head Control: Number of events for abnormal head control
change from Baseline
Time frame: 1 year
Change from Baseline in motor function: Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND)
The test consists of 16 items (body parts), where each item is tested for both sides of the body, left and right. The best score is taken for each item (with a maximum score of 4), and the scores are summed over all 16 items with a possible total CHOP-INTEND score of 64.
Time frame: 1 year
Change from Baseline in Motor Function: Modified Ashworth Scale
change from Baseline. Increase or decrease of muscle tone will be measured by the Modified Ashworth Scale. Frequency counts and percentages will be presented by score (0, 1, 1+, 2, 3, and 4), muscle, side, and visit for the safety population. Flexion and extension of the knee and elbow will be measured on both sides, along with hip adduction and abduction on both sides of the body.
Time frame: 1 year
Clinical Efficacy Assessment: Progression of Hypotonia
Assessed through neurological examinations as present or absent. Baseline to each post-Baseline visit
Time frame: 1 year
Clinical Efficacy Assessment: Dysphagia
Assessment of the dysphagia events- assessed as present or absent.
Time frame: From onset up to 3 years, if present