Pharmacokinetics, Safety and Tolerability of Zavesca (Miglustat) in Patients With Infantile Onset GM2 Gangliosidosis: Single and Steady State Oral Doses
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Biomarkers (level of GM2 ganglioside, chitotriosidase activity, anti-GM2 antibodies) in plasma, serum and CSF will be measured at initial visit (run-in period), Week 13, and Week 25.
研究概览
简要总结
We want to see if Zavesca (or miglustat) is safe and can be tolerated by patients with acute infantile onset GM2 gangliosidosis - classical Tay-Sachs and infantile onset Sandhoff disease. We know that miglustat inhibits the formation of GM2 ganglioside, the compound that is stored in the brains of children with Tay-Sachs and Sandhoff disease. Since it inhibits the synthesis of ganglioside, miglustat may be able to reduce or delay the onset of clinical symptoms.
详细描述
Specific Aims
The primary objective of the study is to investigate the pharmacokinetics of ZAVESCA® (miglustat, OGT918), when given as a single dose and at steady state, in infantile patients with GM2 gangliosidosis. The secondary objectives are to evaluate the tolerability and safety of single and multiple doses of miglustat and to monitor disease progression using physical and developmental assessments and disease-specific biomarkers.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Months 至 5 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of GM2 gangliosidosis, confirmed by demonstration of profound deficiency of -hexosaminidase A or A & B in peripheral blood leukocytes or in cultured skin fibroblasts, within the previous 1 year in non-bone marrow transplant recipients who are < 2 years of age, or prior to stem cell transplant in stably engrafted transplant patients who are < 5 years of age.
- •Onset of characteristic clinical symptoms of the disease before the age of 9 months.
- •Normal renal and hepatic function.
- •Written informed consent from parent or legal guardian.
排除标准
- •Patients who are unable to comply with the study procedures of this protocol, including the refusal to swallow the food used to mask the taste of the study drug and whose parents are unwilling to administer the drug through a nasogastric or gastrostomy tube.
- •Patients receiving other investigational agents within 3 months of study initiation.
- •Patients who are anemic (hemoglobin < 11 g/dl, and/or hematocrit < 34%)
- •Patients who have a history of significant gastrointestinal disorders, including clinically significant diarrhea (>3 liquid stools per day for > 7 days), without definable cause within 3 months of baseline visit.
- •Patients with a high probability of dying during the 6-month assessment period of the study.
- •Patients who in the opinion of the investigator (for whatever reason) are thought to be unsuitable for the study.
结局指标
主要结局
Biomarkers (level of GM2 ganglioside, chitotriosidase activity, anti-GM2 antibodies) in plasma, serum and CSF will be measured at initial visit (run-in period), Week 13, and Week 25.
次要结局
- Neurophysiologic Assessment - EEG and BEAR tests will be done at initial visit (run-in period), Week 13, and Week 25.
- Ophthalmology Assessment - comparision of the "cherry-red" macula changes will be made at initial visit (run-in period) and Week 25.