A Phase I/II Clinical Trial for Treatment of Aromatic L-amino Acid Decarboxylase (AADC) Deficiency Using AAV2-hAADC
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Evaluation of therapeutic effect
研究概览
简要总结
This Phase I/II trial is to prove the efficacy and safety of AAV2-hAADC to treat patients with AADC deficiency.
详细描述
Aromatic L-amino acid decarboxylase (AADC) is an enzyme responsible for the final step in the synthesis of neurotransmitters dopamine and serotonin. AADC deficiency is a rare genetic disorder. Taiwanese carry a high prevalence of AADC deficiency due to the founder mutation IVS6+4 A>T, and patients usually die before the age 5-6 years due to severe motor dysfunction.
Gene therapy with adeno-associated virus (AAV) serotype 2 (AAV2) driven human AADC (hAADC) has been tested in both animal models and Phase I clinical trials of Parkinson disease. We have done a compassionate treatment of 8 patients with AADC deficiency by AAV2-hAADC and demonstrated a result that among the treated patients, 4 could stand with support, 3 could sit with support, and there was no virus-associated toxicity. The longest follow up has exceeded 4 years.
This study is to prove the safety and efficacy of AAV2-hAADC treatment for patients with Aromatic L-amino acid decarboxylase (AADC) deficiency.
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
- 24 Months 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •With a confirmed diagnosis of AADC, including cerebrospinal fluid analysis to show reduced levels of neurotransmitter metabolites, HVA and 5-HIAA, and higher L-Dopa, together with more than one mutation within AADC gene.
- •Classical clinical characteristics of AADC deficiency, such as oculogyric crises, hypotonia and developmental retardation.
- •The sick child has to be over 2 years old or a head circumference big enough for surgery.
- •Participating patients must cooperate completely for all evaluations and examinations before, during and after the whole trial.
- •Parents or guardians must sign to agree on this informed consent.
- •Exclusion criteria
- •Significant brain structure abnormality
- •Patients with any health or neurological doubts that may increase the risk of surgery cannot join this trial. PI has the right to evaluate the feasibility of subjects for this trial based on his/her health condition.
- •Since high-level neutralizing antibodies may disturb the therapeutic effect of gene therapy, patients with anti-AAV2 neutralizing antibody titer over 1,200 folds or an ELISA OD over 1 cannot be enrolled into this trial.
- •Subjects enrolled in this clinical trial cannot take any medications that may affect this trial.
排除标准
- 未提供
研究组 & 干预措施
Gene therapy
Intracerebral infusion of AAV2-hAADC viral vector will be performed
干预措施: gene therapy (Drug)
结局指标
主要结局
Evaluation of therapeutic effect
时间窗: 12 months
1. At one year post-surgery, neurotransmitter metabolites (HVA or HIAA) is detectable in CSF (higher than that at pre-surgery) 2. At one year post-surgery, PDMS-II score is higher than that at pre-surgery, with an improvement over 10 points
次要结局
- Evaluation of safety and other therapeutic effects Evaluation for the treatment safety(12 months)
- Evaluation of secondary therapeutic effects(5 years)
- Exploratory endpoint(5 years)