An Open-label Phase 1/2/3 Study Consisting of a Phase 1/2 Safety and Dose-escalation and Phase 3 Dose-expansion Study to Evaluate Safety and Efficacy of a Single Intrathecal Administration of TSHA-102, an AAV9-Delivered Gene Therapy in Females With Rett Syndrome
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 17
- 试验地点
- 13
- 主要终点
- Part A: Safety and Tolerability of TSHA-102
研究概览
简要总结
The primary objectives of this study are to evaluate the safety of a single intrathecal (IT) dose of TSHA-102 in females with typical Rett syndrome, to select the TSHA-102 dose with the best benefit/risk profile based on the totality of safety and efficacy data and to evaluate the efficacy and safety of TSHA-102 at the selected dose.
详细描述
REVEAL Part A (Phase 1/2) is an open-label safety and dose-finding study designed to evaluate the safety and preliminary efficacy of two dose levels of TSHA-102 to establish initial safety of TSHA-102 and select a safe and efficacious dose for further evaluation. Enrollment of 6 participants in Part A is complete.
REVEAL Part B (Phase 3) will evaluate the efficacy and safety of TSHA-102 at the dose level 2 determined in Part A in 15 females ages 6 to <22 years with typical Rett syndrome. TSHA-102 is designed to target the genetic root cause of Rett syndrome by regulating the expression of MECP2 in cells.
Each participant will be followed for the observation period of 5 years after TSHA-102 administration in Part A and B.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
Central raters assessing the gain or regain of a developmental milestone from videos are blinded to the timing of each video.
入排标准
- 年龄范围
- 6 Years 至 21 Years（Child, Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Females between the ages of 12 and <22 in Part A (closed) and females between the ages of 6 and <22 in Part B (pivotal cohort).
- •Participant has a clinical diagnosis of classic/typical Rett syndrome with a documented pathogenic mutation of the methyl-CpG-binding protein 2 (MECP2) gene that results in loss of gene function.
- •Participants must be willing to receive blood or blood products for the treatment of an AE if medically needed.
- •Participants and parent/caregiver must agree to reside within easy access to the study site prior to the baseline visit and at least 3 months after TSHA-102 treatment
排除标准
- •Participant has another neurodevelopmental disorder independent of the MECP2 loss-of-function mutation, or any other genetic syndrome with a progressive course.
- •Participant has a history of brain injury that causes neurological problems or had grossly abnormal psychomotor development in the first 6 months of life.
- •Participant has a diagnosis of atypical Rett syndrome or a MECP2 gene mutation that does not cause Rett syndrome.
- •Participant requires invasive ventilatory support.
- •Note: Other protocol defined inclusion/exclusion criteria may apply
研究组 & 干预措施
Part A Cohort 2
TSHA-102 Dose Level 2: 1.0×10¹⁵ total vector genomes (vg)
Participants receive a single intrathecal (IT) administration of TSHA-102 at Dose Level 2 (fully enrolled, 4 participants).
干预措施: TSHA-102 (Genetic)
Part A Cohort 1
TSHA-102 Dose Level 1: 5.7×10¹⁴ total vector genomes (vg). Participants receive a single intrathecal (IT) administration of TSHA-102 at Dose Level 1 (fully enrolled, 2 participants).
干预措施: TSHA-102 (Genetic)
Part B Pivotal Cohort
TSHA-102 at Selected Dose (Dose Level 2): 1.0 × 10¹⁵ total vector genomes (vg)
Participants receive a single intrathecal (IT) administration of TSHA-102 at Dose Level 2 (1.0 × 10¹⁵) (fully enrolled, 17 participants).
干预措施: TSHA-102 (Genetic)
结局指标
主要结局
Part A: Safety and Tolerability of TSHA-102
时间窗: Baseline through Week 52
Proportions of participants experiencing any treatment-emergent adverse events (AEs) and serious adverse events (SAEs)
Part B: Efficacy of TSHA-102
时间窗: Baseline through Week 52
Change from baseline in percentage of participants who gain or regain any one or more of the 28 items from the Developmental Milestones Assessment (DMA), which are video recorded and scored by independent, blinded central raters.
次要结局
未报告次要终点