NRTX-1001 for Temporal Lobe Epilepsy

Recruiting at 9 trial locations

Overseen By Manher Joshi, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Neurona Therapeutics

Must be taking: Anti-seizure medicines

Disqualifiers: Progressive neurologic disease, Severe psychiatric disorders, Immunodeficiency, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 22

Duration: 1 day

10 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a multicenter, single arm, open label clinical trial that is designed to test the safety and preliminary efficacy of single administration inhibitory nerve cells called interneurons (NRTX-1001), into both temporal lobes of subjects with drug-resistant bilateral mesial temporal lobe epilepsy.

Will I have to stop taking my current medications?

The trial requires that your current anti-seizure medication and any other drugs affecting seizure frequency have been stable for at least three months before joining. This suggests you should not stop taking your current medications.

What data supports the effectiveness of the treatment NRTX-1001 for Temporal Lobe Epilepsy?

The research on responsive neurostimulation (RNS) for temporal lobe epilepsy shows that it is effective, with a 76.9% responder rate, suggesting that targeting specific brain areas can help manage seizures. This indicates that treatments like NRTX-1001, which may involve similar targeting strategies, could also be effective. ^{1 2 3 4 5}

Research Team

John Hixson, MD

Principal Investigator

Neurona Therapeutics

Eligibility Criteria

Adults aged 18-75 with drug-resistant bilateral mesial temporal lobe epilepsy, confirmed by EEG and MRI or PET scans within the last 3 years. Participants must have a history of focal seizures originating in the hippocampus. Those with certain neurostimulator models or expecting battery replacement within a year are ineligible. Women of childbearing potential must use effective non-hormonal contraception.

Inclusion Criteria

My RNS system battery won't need replacing in the first year of the trial.

My RNS device electrodes are near my hippocampi and have been in place for over a year.

I will use highly effective birth control while on immunosuppressants.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Single stereotactic CT or MRI-guided intracerebral administration of NRTX-1001 into both temporal lobes

1 day

1 visit (in-person)

Follow-up

Safety, tolerability, and effects on epilepsy disease symptoms assessed quarterly for 2 years

24 months

8 visits (in-person)

Long-term follow-up

Quarterly phone calls and annual visits in years 3 through 15 to monitor long-term effects

13 years

13 visits (in-person), quarterly phone calls

Treatment Details

Interventions

• NRTX-1001

Trial Overview The trial is testing NRTX-1001, an interneuron cell therapy administered once into both temporal lobes to assess safety and initial effectiveness for controlling seizures in individuals whose epilepsy doesn't respond to drugs.

Participant Groups

Group I: Treatment Arm Experimental Treatment 1 Intervention

This is an open-label study of the bilateral intrahippocampal administration of NRTX-1001 in a single dose cohort of up to 10 subjects with drug-resistant bilateral MTLE.

Who Is Running the Clinical Trial?

Neurona Therapeutics

Lead Sponsor

Trials

2

Recruited

50+

Findings from Research

In a study of 26 patients undergoing surgery for temporal lobe epilepsy, significant atrophy (12%) of the contralateral hippocampus was observed, particularly in the hippocampal body, which showed a 27% reduction post-surgery.

Atrophy began as early as the first post-operative day and progressed significantly during the first week, with ongoing seizures correlating with greater atrophy, suggesting that early imaging could help predict surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progressive contralateral hippocampal atrophy following surgery for medically refractory temporal lobe epilepsy. Elliott, CA., Gross, DW., Wheatley, BM., et al.[2018]

In a study of 14 patients with temporal lobe low-grade epilepsy-associated tumors, MRI-guided laser interstitial thermal therapy (MRgLITT) demonstrated comparable effectiveness to open resection, with 57% of MRgLITT patients achieving seizure freedom at 12 months, similar to 50% for open resection.

MRgLITT was associated with a shorter hospital stay and fewer minor adverse events compared to open resection, suggesting it may be a safer option for patients undergoing treatment for these tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open surgery or laser interstitial thermal therapy for low-grade epilepsy-associated tumors of the temporal lobe: A single-institution consecutive series. Hedaya, AA., Hewitt, KC., Hu, R., et al.[2023]

In a systematic review and meta-analysis of 20 studies involving 2,734 patients, surgery for drug-resistant temporal lobe epilepsy resulted in 44% of patients becoming seizure-free, compared to only 12% in non-operated controls, indicating a significant benefit from surgical intervention.

The analysis showed that patients who underwent surgery were 4 times more likely to achieve freedom from seizures compared to those who only received medical treatment, highlighting the efficacy of surgery in appropriately selected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term seizure outcome of surgery versus no surgery for drug-resistant partial epilepsy: a review of controlled studies. Schmidt, D., Stavem, K.[2022]

Patients who underwent anterior temporal lobectomy (ATL) for refractory epilepsy reported significantly improved health-related quality of life (HRQOL) and reduced concerns about living with epilepsy compared to those awaiting surgery, based on assessments from 125 postoperative patients and 71 preoperative patients.

Factors such as mood status, employment, driving ability, and the cessation of antiepileptic drugs (AEDs) were found to be important predictors of better HRQOL after surgery, rather than just being seizure-free.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-oriented outcome assessment after temporal lobectomy for refractory epilepsy. Gilliam, F., Kuzniecky, R., Meador, K., et al.[2019]

A study of 13 patients with refractory temporal lobe epilepsy showed that using an orthogonal approach for placing responsive neurostimulation (RNS) leads targeting the entorhinal cortex resulted in a 76.9% responder rate over an average follow-up of 57.3 months.

The findings suggest that this novel lead placement strategy is both safe and effective, potentially offering better modulation of the limbic network, but further research with larger patient groups is necessary to confirm these results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Strategic targeting of the temporal lobe with orthogonal placement of responsive neurostimulation leads. Ho, VM., Dewar, S., Salamon, N., et al.[2022]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Progressive contralateral hippocampal atrophy following surgery for medically refractory temporal lobe epilepsy. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Open surgery or laser interstitial thermal therapy for low-grade epilepsy-associated tumors of the temporal lobe: A single-institution consecutive series. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Long-term seizure outcome of surgery versus no surgery for drug-resistant partial epilepsy: a review of controlled studies. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Patient-oriented outcome assessment after temporal lobectomy for refractory epilepsy. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Strategic targeting of the temporal lobe with orthogonal placement of responsive neurostimulation leads. [2022]