An Open, Dose-escalating Early Clinical Trial to Evaluate the Tolerability, Safety, and Efficacy of VGN-R09b by Intra Striatum Injection in Patients With Aromatic L-amino Acid Decarboxylase (AADC) Deficiency.
试验速览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Number of Adverse Events (AEs), Serious Adverse Events (SAEs)
研究概览
简要总结
This early Phase trial is to prove the safety and efficacy of VGN-R09b 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. VGN-R09b is a kind of Gene therapy with adeno-associated virus (AAV) serotype 9 (AAV9) driven human AADC (hAADC) being injected directly into striatum.
This is a single-center, open, dose-climbing investigator-sponsored early-stage clinical study that included a dose-climbing phase and a dose-expanding phase.
This study is to give preliminary evidence for the safety and efficacy of VGN-R09b 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 7 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The child patient has to be ≥2 years old and < 8 years old, or a head circumference big enough for surgery.
- •Historical diagnosis of AADC deficiency with clinical symptoms consistency, AND confirmed by one of the lab tests: (1) CSF neurotransmitter profile demonstrating reduced HVA and 5-HIAA, and elevated L-Dopa concentrations; (2) Plasma AADC activity less than or equal to 5 pmol/min/mL, AND with Molecular genetic confirmation of homozygous or compound heterozygous mutation of IVS6+4A>T in DDC.
- •Motor development at baseline ≤3 months, and Failed to benefit from standard medical therapy (dopamine agonists, monoamine oxidase inhibitor or related form of Vitamin B6) at discretion of investigators.
- •Stable medication regimen for treatment of AADC deficiency: (i.e. no new medications introduced for at least 6 months, and no existing medication dose changes for at least 3 months prior to Baseline).
- •Parent(s)/legal guardian(s) with custody of subject must give their consent for subject to enroll in the study
- •Parent(s)/legal guardian(s) of the subject must agree to comply with the requirements of the study, including providing disease information and support disease assessment of symptoms.
排除标准
- •Intracranial neoplasm or any structural brain abnormality or lesion (e.g., severe brain atrophy, white matter degenerative changes), which, in the opinion of the study investigators, would confer excessive risk and/or inadequate potential for benefit.
- •Presence of other significant medical or neurological conditions that would create an unacceptable operative or anesthetic risk (including congenital heart disease, respiratory disease with home oxygen requirement, history of serious anesthesia complications during previous elective procedures, history of cardiorespiratory arrest), liver or renal failure, malignancy, or HIV positive.
- •Severe coagulopathy, or need for ongoing anticoagulant therapy.
- •clinically active infection or with severe infection within 12 weeks before screening (e.g. adenovirus or herpes virus, pneumonia, sepsis, central nervous system infection).
- •Previous stereotactic neurosurgery, or any gene/cell therapy.
- •Received live vaccination within 4 weeks.
- •Patients with anti-AAV9 neutralizing antibody titer over 1,200 folds.
- •Contraindication to sedation during surgery or imaging studies (PET or MRI).
研究组 & 干预措施
Aromatic L-amino acid decarboxylase (AADC) deficiency
This early Phase trial is to prove the safety and efficacy of VGN-R09b to treat patients with AADC deficiency.
干预措施: VGN-R09b (Drug)
结局指标
主要结局
Number of Adverse Events (AEs), Serious Adverse Events (SAEs)
时间窗: Week 52
Number of Adverse Events (AEs), Serious Adverse Events (SAEs)
Achievement Ratio of the four motor development milestones (Head control, Sit independently, Stand/stepping with support and Walk with minimal assistant)
时间窗: Week 52
Achievement Ratio of the four motor development milestones (Head control, Sit independently, Stand/stepping with support and Walk with minimal assistant) according to PDMS-II score.
次要结局
未报告次要终点