| Eligibility |
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.
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