## Protocol Section
### Identification Module
**NCT ID:** NCT06422923

**Brief Title:** Effect of NRTX-1001, a Cellular Therapy Product, for the Treatment of Refractory Bilateral TLE

**Official Title:** A Study of Inhibitory Interneurons (NRTX-1001) for the Treatment of Drug-resistant Bilateral Temporal Lobe Focal Seizures

#### Organization Study ID Info
**ID:** NTE002
#### Organization
**Class:** INDUSTRY
**Full Name:** Neurona Therapeutics
### Status Module
#### Completion Date
**Date:** 2040-07-15

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-31

**Type:** ESTIMATED

**Last Update Submit Date:** 2024-05-29

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-07-15

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-07-15

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-21
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-15
**Study First Submit QC Date:** 2024-05-15
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Neurona Therapeutics

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** This study is designed to obtain open-label feasibility, safety, and seizure frequency data in patients with drug-resistant bilateral mesial temporal lobe epilepsy (MTLE) administered NRTX-1001.

**Detailed Description:** This is an open-label study of the bilateral intrahippocampal administration of NRTX1001, with the primary endpoint to evaluate safety and a secondary endpoint to evaluate seizure metrics.

### Conditions Module

**Conditions:**

- Epilepsy, Temporal Lobe

**Keywords:**

- Bilateral Temporal Lobe Epilepsy

- Bilateral MTLE

- Refractory Bilateral MTLE

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 10

**Type:** ESTIMATED

**Phases:**

- PHASE1

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** This is an open-label study of the bilateral intrahippocampal administration of NRTX-1001 in a single dose cohort of up to 10 subjects. Subjects will be temporarily immunosuppressed after surgery.

**Intervention Names:**

- Biological: NRTX-1001

**Label:** Treatment Arm

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Treatment Arm

**Description:** Cellular therapy consisting of GABAergic Inhibitory Interneurons

**Name:** NRTX-1001

**Type:** BIOLOGICAL

### Outcomes Module

#### Primary Outcomes

**Description:** Safety

**Measure:** Incidence of Serious Adverse Events at end of month 12

**Time Frame:** 12 months after treatment

#### Secondary Outcomes

**Description:** Seizure frequency change during months 7-12, compared to frequency of clinical seizures in the 6-month baseline period.

**Measure:** Change in frequency of clinical seizures

**Time Frame:** 12 months after treatment

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. Male or female, age 18-75 years.
2. Subjects of childbearing potential will use highly effective contraception (defined as documented failure rate ≤1%) while taking immunosuppressants. For females using enzyme-inducing anti-seizure medications (EI-ASM), hormonal contraception will not be considered as effective (EI-ASM determined from US Prescribing Information).
3. Proven history of focal seizures of hippocampal origin with bilateral seizure foci confirmed by scalp or intracranial ictal EEG (including confirmation by recordings from responsive neurostimulation \[RNS\] electrodes when applicable).
4. Either

   1. bilateral hippocampal sclerosis on MRI (evidenced by increased FLAIR signal intensity in both hippocampi or by visual assessment showing reduced volume compared to normal) or
   2. bilateral temporal hypometabolism on 18-Flourodeoxyglucose Positron Emission Tomography (FDG PET) (assessed by visual assessment, comparing temporal regions to frontal/parietal lobe neocortex). In this case, ictal EEG recordings must also include intracranial confirmation.

      or
   3. a combination of unilateral instances of the evidence described in a. and b. (e.g., one side can be evidenced by criterion a. and the other side by criterion b.) MRI or PET scans used for assessment must have been acquired within 3 years of screening.
5. For subjects with unilateral RNS, the contralateral side must meet one of the descriptions listed in inclusion criterion 4.
6. For subjects with RNS, the electrodes are in (or near) hippocampi and have been in place for ≥12 months prior to screening.
7. For subjects with RNS, the RNS device is MRI-conditional (RNS Neurostimulator model 320). Subjects with RNS® Neurostimulator, model RNS-300 devices are not eligible. Patients with other RNS model devices may be eligible depending on confirmation of MRI compatibility.
8. For subjects with RNS, RNS system batteries are not expected to need replacement during year 1 of this trial.
9. For subjects with RNS, settings for ES detection and stimulation have not changed in the past 6 months and should be held constant over the first 2 years after NRTX-1001 administration.
10. Subject has maintained a diary (written or electronic) recording clinical seizure frequency for at least 1 month prior to surgery.
11. Subject has had at least four clinical focal seizures, including at least two clinical focal seizures with objective manifestations, on average, per month for the 6 months prior to screening.
12. Subject has previously had adequate (in opinion of investigator) therapeutic trials of at least two Anti-Seizure Medicines (ASMs).
13. Current ASM regimen, and doses of other drugs known to affect seizure frequency (e.g., antidepressants), have been stable for at least three months prior to enrollment.
14. Subject has received Shingrix vaccine (first dose by at least 7 days prior to start of immunosuppression).
15. Subject can converse and read in English or Spanish. Able to participate in required study procedures and provide signed informed consent.
16. Subject has either 10th grade education or equivalent or full-scale intelligence quotient (IQ) ≥70, assessed either within 1 year of screening, or during the screening period.
17. Subject can comply with study visits \& procedures (may have caregiver assist).

Exclusion Criteria:

1. Evidence of seizure focus outside hippocampus (either by seizure semiology or EEG findings).
2. MRI indicating potential malignant lesion (low-grade glioma of any type is excluded) in any location or non-malignant potentially epileptogenic lesion outside the hippocampus. Small (\<2 cm) non invasive meningioma, remote from the affected temporal lobe, is not exclusionary.
3. Seizures of non-focal origin.
4. History of status epilepticus in the year prior to screening, as guided by ILAE criteria (Trinka 2015) in the judgement of the PI. A history of cluster seizures is permitted.
5. Clinical diagnosis of autoimmune epilepsy, supported by the presence of serum antibodies detected on a standard test panel (Labcorp Autoimmune Epilepsy Evaluation Profile test 505490, or Mayo Clinic Laboratories Epilepsy, Autoimmune/Paraneoplastic Evaluation test EPS2, or similar with approval from Sponsor), either within 3 years of screening or during the baseline period.
6. Psychogenic Non-Epileptic Seizures (PNES) within the past 3 years.
7. Severe psychiatric disorders.
8. Primary or secondary immunodeficiency.
9. Evidence of active cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection (symptomatic or asymptomatic as demonstrated by positive plasma polymerase chain reaction \[PCR\] or plasma Nucleic Acid Amplification Test \[NAAT\] and immunoglobulin M \[IgM\] tests). Subjects may re-screen after infection is resolved.
10. Substance use disorder (including alcohol) per the Diagnostic and Statistical Manual of Mental Illnesses (DSM-5) criteria.
11. Planned surgery within one year of enrollment.
12. Current pregnancy, or lactation.
13. Prior exposure to NRTX-1001 product, or other cell or gene therapy treatments (of any kind).
14. Participation in another investigational trial within past 30 days, excepting non-interventional studies.
15. Detection of clinically relevant donor-specific allo-HLA reactive antibodies.

**Maximum Age:** 75 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** holly@neuronatx.com

**Name:** Holly Finefrock, BSHS

**Phone:** 650-436-3045

**Role:** CONTACT

**Contact 2:**

**Email:** sheri@neuronatx.com

**Name:** Sheri Madrid, BS, BA

**Phone:** 949-500-0027

**Role:** CONTACT

#### Overall Officials

**Official 1:**

**Affiliation:** Neurona Therapeutics

**Name:** John Hixson, MD

**Role:** STUDY_DIRECTOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000001927

- Term: Brain Diseases

- ID: D000002493

- Term: Central Nervous System Diseases

- ID: D000009422

- Term: Nervous System Diseases

- ID: D000004828

- Term: Epilepsies, Partial

- ID: D000073376

- Term: Epileptic Syndromes

### Condition Browse Module - Browse Branches

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

### Condition Browse Module - Browse Leaves

- ID: M7983

- Name: Epilepsy

- Relevance: HIGH

- As Found: Epilepsy

- ID: M7989

- Name: Epilepsy, Temporal Lobe

- Relevance: HIGH

- As Found: Epilepsy, Temporal Lobe

- ID: M15452

- Name: Seizures

- Relevance: LOW

- As Found: Unknown

- ID: M5204

- Name: Brain Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5742

- Name: Central Nervous System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M7984

- Name: Epilepsies, Partial

- Relevance: LOW

- As Found: Unknown

- ID: M16355

- Name: Syndrome

- Relevance: LOW

- As Found: Unknown

- ID: M1165

- Name: Epileptic Syndromes

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000004827

- Term: Epilepsy

- ID: D000004833

- Term: Epilepsy, Temporal Lobe

### Misc Info Module

- Version Holder: 2024-05-31
