FIH Study of NRTX-1001 Neural Cell Therapy in Drug-Resistant Unilateral Mesial Temporal Lobe Epilepsy

Study Overview
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Brief Summary
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This clinical trial is designed to test whether a single stereotactic intracerebral administration of inhibitory nerve cells into subjects with drug-resistant mesial temporal lobe epilepsy is safe (frequency of adverse events) and effective (seizure frequency).

Detailed Description
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Subjects will undergo a single stereotactic intracerebral administration of neural cells, called interneurons, that secrete the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Subjects will then take medicines to partially suppress their immune system (aimed to prevent the body from rejecting the cells) for 1 year. Safety, tolerability, evidence of neural cell viability and local inflammation (using MRI scans of the brain), and effects on epilepsy disease symptoms will be assessed for 2 years post-transplant. Subjects will be followed for an additional 13 years with quarterly phone contact and annual visits.

Official Title
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A First-In-Human (FIH) Study of Inhibitory Interneurons (NRTX- 1001) in Drug-Resistant Unilateral Mesial Temporal Lobe Epilepsy (MTLE)

Conditions
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Mesial Temporal Lobe Epilepsy With Hippocampal Sclerosis

Intervention / Treatment
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* Biological: NRTX-1001
* Procedure: Sham Comparator


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male or Female, age ≥18 to 65 Focal seizures, clinically defined as TLE 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) of approved ASDs Single seizure focus confirmed as within one temporal lobe For subjects entering Stage 1, the seizure focus is either a) in the non-dominant hemisphere, or b) in the dominant hemisphere and the subject has a Rey Auditory Verbal Learning Test (RAVLT) assessed within one year of screening, or at the screening visit, that is at least 1.5 standard deviations below the population mean. Seizure frequency averages ≥2 per 28-day period over the 6 months prior to screening. Key Exclusion Criteria: Epilepsy due to other and/or progressive neurologic disease Significant other medical condition which would impair safe participation Primary or secondary immunodeficiency Suicide attempt in the past year Severe psychiatric disorders Chronic indwelling intracranial device MRI indicating potential malignant lesion Pregnancy, or currently breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a two-stage study. Stage 1 is an open-label, single arm, sequential dose escalation. Stage 2 is a parallel, randomized, 2-arm, sham controlled study.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NRTX-1001 (Stage 1)<br>Up to 10 subjects. | Biological: NRTX-1001<br>* Biological: NRTX-1001 is an experimental neural cell therapy product candidate derived from an allogeneic human embryonic stem cell line. The stem cells were converted into inhibitory nerve cells that produce GABA.<br>* Other names: GABA-secreting interneurons;|
| Experimental: NRTX-1001 (Stage 2)<br>Up to 20 subjects. | Biological: NRTX-1001<br>* Biological: NRTX-1001 is an experimental neural cell therapy product candidate derived from an allogeneic human embryonic stem cell line. The stem cells were converted into inhibitory nerve cells that produce GABA.<br>* Other names: GABA-secreting interneurons;|
| Sham Comparator: Sham Comparator (Stage 2)<br>Up to 10 subjects. | Procedure: Sham Comparator<br>* Sham Comparator.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of serious or severe AEs | The primary endpoint of the study is the frequency of serious or severe AEs over the period of 1 year after administration, comparing all subjects treated with NRTX-1001 (Stage 1 + Stage 2) with all subjects who receive sham treatment. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in seizure frequency | The difference in the median percentage change from baseline in seizure frequency (seizures per 28 days) between subjects that receive NRTX-1001 and those who receive sham treatment, assessed in Stage 2. | 1 year | 
| Responder rate | The difference in the 75% responder rate, e.g., the difference between the fraction of subjects who receive NRTX-1001 and those that receive sham treatment who experience at least a 75% reduction from baseline in seizure frequency, assessed in Stage 2. | 1 year |