A Multi-center, Phase 1/2a, First-in-human (FIH) Study Investigating the Safety, Tolerability, and Efficacy of AMT-260 in Adults With Unilateral Refractory Mesial Temporal Lobe Epilepsy (MTLE) Administered Via Magnetic Resonance Imaging (MRI)-Guided Convection-enhanced Delivery (CED)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 12
- 试验地点
- 30
- 主要终点
- To evaluate the safety and tolerability of AMT-260 in adults with unilateral refractory MTLE.
研究概览
简要总结
The main goals of this clinical study are to learn if AMT-260 is safe and tolerable and works to reduce the frequency of seizures in adults with unilateral mesial temporal lobe epilepsy (MTLE).
详细描述
In this first clinical study of AMT-260, two dose levels will be studied to find the best dose of AMT-260. All eligible participants will receive AMT-260 at one of the two dose levels (i.e., there is no placebo in this study).
AMT-260 is intended for a one-time administration, without the need to remove or destroy any part of the brain. Participation in this study would not prevent later pursuit of other treatment options.
Participants will be monitored through study site visits, telephone calls, blood tests, and questionnaires about how their seizures affect daily life. Participants will record seizures using an electronic seizure diary.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of unilateral refractory MTLE
- •History of seizures with an average of ≥ 2 documented focal impaired awareness seizures or focal to bilateral tonic-clonic seizures per 30-day period over the 3 month Retrospective Period.
- •On a stable type and dose regimen of up to a maximum of 4 approved Anti Seizure Drugs for at least 1 month prior to the Retrospective Period.
- •Confirmed unilateral hippocampal pathology and concordant unilateral seizure focus
- •No evidence of focal neurocognitive dysfunction, inconsistent with disease pathology- related MRI and/or (18F)FDG-PET findings.
- •Women of childbearing potential (WOCBP) and fertile male subjects must be willing and able to use highly effective methods of birth control consistently and correctly throughout the study.
- •For WOCBP only: Negative pregnancy test.
排除标准
- •Implanted devices that would contraindicate MRI; MRI-compatible devices must be implanted ≥3 months prior to Screening (vagus nerve stimulation devices will be up to discretion of the Investigator).
- •Any other contraindications to general anesthesia, surgery, or intra-operative magnetic resonance imaging (MRI).
- •Medications that could confound clinical (e.g., antipsychotic medication and anti-viral therapy) and laboratory evaluations or could affect a participant's safety or their ability to undergo the neurosurgical procedure or comply with the procedures and study visit schedule.
- •Bilateral or multifocal epilepsy; or inability to confidently lateralize seizure onset.
- •Dementia or other progressive neurological disorders and progressive brain lesions.
- •Previous major disease-unrelated neurosurgical intervention due to intracranial tumor, trauma, or bleeding and/or history of previous intracranial surgery for treatment of epileptic seizures, not including diagnostic stereo-EEG.
- •MRI evidence of epileptogenic, extra-temporal lesions, or dual temporal lobe pathology.
- •Status epilepticus within the year prior to Screening.
研究组 & 干预措施
AMT-260
Cohort 1: AMT-260 starting dose (1.0x 10E12 gc/mL). Cohort 2: AMT-260 adapted dose (6.0x 10E11 gc/mL or 3.0x 10E12 gc/mL).
干预措施: AAV9-hSyn1-miGRIK2 (Genetic)
结局指标
主要结局
To evaluate the safety and tolerability of AMT-260 in adults with unilateral refractory MTLE.
时间窗: 1 year
Occurrence of Adverse Events during the period of 1 year after AMT-260 administration, including seriousness, severity, and causal relationship to AMT-260.
次要结局
- To evaluate first signs of efficacy of AMT-260.(1 year)
- To evaluate the biodistribution properties of AMT-260.(1 year)