A Phase 1B, Open-label, Randomized, Controlled, Multicenter, Dose Escalation Study of the Safety, Tolerability, and Biological Effects of VY-HTT01 Administered Via Intraparenchymal Infusion of the Putamen and Thalamus in Adults With Huntington's Disease
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- Incidence and type of AEs
研究概览
简要总结
This is the first clinical study of VY-HTT01, a gene therapy for early-stage Huntington's Disease (HD) patients. The primary goal of this trial is to evaluate the safety and tolerability of VY-HTT01. This study is a first in human study, Phase 1b, open-label, randomized, multicenter, dose escalation study with a delayed treatment control arm.
详细描述
This dose escalation trial will evaluate the safety and tolerability of 4 single dose levels of VY-HTT01. The maximum duration that a subject randomized to treatment may be involved in the study is up to 15 months. Delayed treatment subjects will be followed for a minimum of 6 months as a control before moving up into the treatment arm in the next cohort. The maximum duration that a delayed treatment subject may be involved in the study is up to 24 months. Subjects who participate in this study will be asked to enroll in a long-term observation study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must be at least 18 years old.
- •Have CAGn repeat >
- •Have diagnostic confidence score of 4 based on motor, cognitive, or behavioral symptoms.
- •Have a TFC score of 13 to
- •Have stable dosing of neurological and psychiatric medications.
- •Capable of giving informed consent.
- •Able to comply with all procedures and study visits.
排除标准
- •Have any significant structural or degenerative neurologic disease other than HD.
- •Have any chronic disability, significant systemic illness and/or, unstable medical condition, or clinical findings noted.
- •Have primary or secondary immune-compromise due to infections or medical conditions or chronic therapies.
- •Have contraindications to lumbar puncture or increased risks of bleeding upon surgery.
- •Started or changed dose of a concomitant CNS medication within 30 days.
- •Had prior neurosurgical procedures that could complicate the study procedures.
- •Have used any investigational therapies within 30 days prior to Screening, oligonucleotide therapies within 9 months prior to Baseline, or any prior gene therapy.
- •Male or female with reproductive capacity and is unwilling to use highly effective contraception for 12 months after surgery.
- •Have contraindications to MRI such as claustrophobia, embedded metal in the body, or known allergy or intolerance to contrast agents.
研究组 & 干预措施
Cohort 1 Unilateral low dose
3.0 x 10^9 (vg/mL) rAAV1-miHHT
干预措施: Intraparenchymal rAAV1 - (mi)RNA HTT (Genetic)
Cohort 2 Bilateral low dose
3.0 x 10^9 (vg/mL) rAAV1-miHHT
干预措施: Intraparenchymal rAAV1 - (mi)RNA HTT (Genetic)
Cohort 3 Bilateral mid dose
1.7 x 10^10 (vg/mL) rAAV1-miHHT
干预措施: Intraparenchymal rAAV1 - (mi)RNA HTT (Genetic)
Cohort 4 Bilateral high dose
9.9 x 10^10 (vg/mL) rAAV1-miHHT
干预措施: Intraparenchymal rAAV1 - (mi)RNA HTT (Genetic)
结局指标
主要结局
Incidence and type of AEs
时间窗: Collected for duration of study, average of 1 year after treatment
Safety will be assessed by measuring the number and type of AE or SAEs.
次要结局
- Level of VY-HTT01 in blood(Collected for duration of study, average of 1 year after treatment)
- Unified Huntington Disease Rating Scale (UHDRS)(Collected for duration of study, average of 1 year after treatment)
- Clinical Global Impression (CGI) Measures(Collected for duration of study, average of 1 year after treatment)
- Huntington's Disease Quality of Life (HD-QOL) Measure(Collected for duration of study, average of 1 year after treatment)
- EuroQol 5 Dimension 5 Level (EQ-5D-5L) Measure(Collected for duration of study, average of 1 year after treatment)