First-in-Human Study of TSHA-101 Gene Therapy for Treatment of Infantile Onset GM2 Gangliosidosis
- Conditions
- Infantile GM2 Gangliosidosis (Disorder)
- Interventions
- Biological: TSHA-101
- Registration Number
- NCT04798235
- Lead Sponsor
- Dr. Anupam Sehgal
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 3
- male or female with age less than or equal to 15 months
- diagnosis of GM2 gangliosidosis with genetic and enzymatic documentation of infantile disease
Key
- a second neurodevelopmental disorder independent of the HEXA or HEXB
- inability to tolerate sedation or intrathecal administration
- invasive ventilatory support
- concomitant illness, allergies or known hypersensitivity to the required immunosuppression regimen
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description TSHA-101 TSHA-101 Subjects who will receive one-time intrathecal TSHA-101, brain volume based sliding scale for dosage
- Primary Outcome Measures
Name Time Method Safety and Tolerability: Number of participants with abnormal Laboratory assessments 1 year Number of participants with Changes from Baseline in laboratory assessments
Safety and tolerability: Treatment-emergent Adverse Events (TEAEs) 1 year Incidence, severity, and relatedness of TEAEs
Safety and Tolerability: Electrocardiogram (ECG) 1 year Changes from Baseline in 12-lead ECG findings in QT interval
- Secondary Outcome Measures
Name Time Method Assessment of Immunogenicity: Biomarkers in serum 1 year Summary of total antibodies (TAbs) titers for AAV9 and Hex A
Assessment of Immunogenicity: Biomarkers in peripheral blood mononuclear cells (PBMCs 5 years Summary of PBMCs for enzyme-linked immune absorbent spot (ELISpot) assays for cytokine secretion against AAV9 and Hex A
Safety and tolerability: Viral shedding analysis 1 year Positive presence of viral DNA from biological fluids (whole blood, urine, saliva, and stool)
Overall Survival treatment to death from any cause, up to 5 years Estimated using the Kaplan-Meier method
Hex A Enzyme Activity: Cerebrospinal fluid (CSF) and serum 1 year Change from baseline
Head Control: Number of events for abnormal head control 1 year change from Baseline
Change from Baseline in motor function: Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) 1 year 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.
Change from Baseline in Motor Function: Modified Ashworth Scale 1 year 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.
Clinical Efficacy Assessment: Progression of Hypotonia 1 year Assessed through neurological examinations as present or absent. Baseline to each post-Baseline visit
Clinical Efficacy Assessment: Dysphagia From onset up to 3 years, if present Assessment of the dysphagia events- assessed as present or absent.
Trial Locations
- Locations (1)
Queen's University/Kingston Health Sciences Centre
🇨🇦Kingston, Ontario, Canada