Phase 1/2, Open-Label Clinical Study to Evaluate the Safety and Efficacy of Intrathecal TSHA-101 Gene Therapy for Treatment of Infantile Onset GM2 Gangliosidosis
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 3
- 试验地点
- 2
- 主要终点
- Safety and tolerability: Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 15 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •male or female with age less than or equal to 15 months
- •diagnosis of GM2 gangliosidosis with genetic and enzymatic documentation of infantile disease
排除标准
- •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
结局指标
主要结局
Safety and tolerability: Treatment-emergent Adverse Events (TEAEs)
时间窗: 1 year
Incidence, severity, and relatedness of TEAEs
Safety and Tolerability: Electrocardiogram (ECG)
时间窗: 1 year
Changes from Baseline in 12-lead ECG findings in QT interval
Safety and Tolerability: Number of participants with abnormal Laboratory assessments
时间窗: 1 year
Number of participants with Changes from Baseline in laboratory assessments
次要结局
- Assessment of Immunogenicity: Biomarkers in peripheral blood mononuclear cells (PBMCs(5 years)
- Safety and tolerability: Viral shedding analysis(1 year)
- Overall Survival(treatment to death from any cause, up to 5 years)
- Hex A Enzyme Activity: Cerebrospinal fluid (CSF) and serum(1 year)
- Head Control: Number of events for abnormal head control(1 year)
- Change from Baseline in motor function: Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND)(1 year)
- Change from Baseline in Motor Function: Modified Ashworth Scale(1 year)
- Clinical Efficacy Assessment: Progression of Hypotonia(1 year)
- Clinical Efficacy Assessment: Dysphagia(From onset up to 3 years, if present)
- Assessment of Immunogenicity: Biomarkers in serum(1 year)
研究者
Dr. Anupam Sehgal
Primary Investigator
Queen's University