A Study of Inhibitory Interneurons (NRTX-1001) in Drug-Resistant Unilateral Mesial Temporal Lobe Epilepsy (MTLE)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 88
- 试验地点
- 62
- 主要终点
- Frequency of serious or severe AEs (Phase 1/2)
研究概览
简要总结
This clinical trial is designed to test whether a single image-guided intracerebral administration of inhibitory nerve cells, called interneurons (NRTX-1001), into subjects with drug-resistant unilateral mesial temporal lobe epilepsy (MTLE), with or without mesial temporal sclerosis (MTS), is safe (frequency of adverse events) and effective (seizure frequency). NRTX-1001 comprises human interneurons that secrete a neurotransmitter, gamma-aminobutyric acid (GABA).
详细描述
Subjects will undergo a single CT or MRI-guided intracerebral administration of human interneurons that secrete the inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), into the temporal lobe region of the brain where the seizures are thought to arise. NRTX-1001 is intended to suppress the onset and spread of seizures. Safety, efficacy, tolerability, and effects on reducing seizure frequency and epilepsy disease symptoms will be assessed at regular intervals for 2 years after the administration of NRTX-1001. After the two-year period, subjects will be followed with quarterly phone calls and annual visits in years 3 through 5, and then annual visits in years 6 through 15. Subjects will be placed on an immunosuppressant medication regimen for a duration of one year to partially suppress the subjects' immune system to promote the intended long-term persistence of NRTX-1001. This immunosuppressant medication is intended to be discontinued after the first year; however, the NRTX-1001 cells are intended to persist long-term.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
This is a two-phase study. Phase 1/2 is open-label and unmasked. Phase 3 is blinded with participant, part of investigator team, and outcomes assessor masked to treatment assignment.
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
- •Male or Female, age ≥18 to ≤75
- •Focal seizures, clinically defined as unilateral MTLE
- •Has failed to achieve seizure control despite adequate trials of at least 2 ASDs at appropriate doses
- •Currently on stable doses (at least 1 month prior to Screening) of approved ASDs
- •Single seizure focus confirmed within one hippocampus
- •Seizure frequency averages ≥4 per 28-day period, including at least 2 clinical focal seizures per 28-day period with objective manifestations or more severe types, over the 6 months prior to the Screening Visit. (Phase 1/2 only)
- •Disabling seizure frequency of ≥2 per 28-day period averaged over 3 months prior to the Screening visit and over a prospective 10-week baseline period prior to Randomization (Phase 3 Only)
排除标准
- •Epilepsy due to other medical conditions and/or progressive neurologic disease
- •Evidence of seizure focus outside of the hippocampus or evidence of seizures of non- focal origin.
- •Significant other medical conditions which would impair safe participation
- •History of status epilepticus in the 3 years prior to screening.
- •Primary or secondary immunodeficiency
- •Suicide attempts in the past year 3 years
- •Severe psychiatric disorders
- •Prior lobectomy or LITT procedure
- •MRI indicating potential malignant lesion
- •Pregnancy, or currently breastfeeding.
研究组 & 干预措施
NRTX-1001 (Phase 1/2)
Up to 28 subjects
干预措施: NRTX-1001 (Biological)
NRTX-1001 (Phase 3)
Approximately 40 subjects
干预措施: NRTX-1001 (Biological)
Sham Comparator (Phase 3)
Approximately 20 subjects
干预措施: Sham Comparator (Procedure)
结局指标
主要结局
Frequency of serious or severe AEs (Phase 1/2)
时间窗: 1 year
The primary endpoint of the study is the frequency of serious or severe AEs over the period of 1 year after administration.
Change in disabling seizure frequency (Phase 3)
时间窗: 4-6 months after surgery
The difference in median percent change from baseline in diary-reported disabling seizure frequency (seizures per 28 days) between subjects that receive NRTX-1001 and those who receive sham treatment.
Frequency of serious or severe AEs (Phase 1/2)
时间窗: 1 year
The primary endpoint of the study is the frequency of serious or severe AEs over the period of 1 year after administration.
Change in disabling seizure frequency (Phase 3)
时间窗: 4-6 months after surgery
The difference in median percent change from baseline in diary-reported disabling seizure frequency (seizures per 28 days) between subjects that receive NRTX-1001 and those who receive sham treatment.
次要结局
- Responder rate (Phase 3)(4-6 months after surgery)