NRTX-1001 for Temporal Lobe Epilepsy

Recruiting at 15 trial locations

Overseen By Ngoc Minh Le, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called NRTX-1001, which uses special nerve cells to help manage seizures in people with a specific type of epilepsy that doesn't respond to medication. The focus is on drug-resistant epilepsy affecting both sides of the brain's temporal lobes, leading to frequent, difficult-to-control seizures. Ideal participants are those who have struggled with these seizures despite trying multiple anti-seizure medications and have a confirmed seizure origin from the hippocampus, a part of the brain involved in memory and navigation. As a Phase 1 trial, this research aims to understand how NRTX-1001 works in people, offering participants the opportunity to be among the first to receive this innovative treatment.

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.

Is there any evidence suggesting that NRTX-1001 is likely to be safe for humans?

Research has shown that NRTX-1001 is safe in clinical studies. In earlier research, ten patients with drug-resistant temporal lobe epilepsy received this treatment, and they tolerated it well. Additionally, new data indicates that both high and low doses of NRTX-1001 have not caused any unexpected negative side effects.

Initial findings suggest that the treatment does not lead to major surgical problems. This is encouraging for those considering joining the trial, as it suggests that NRTX-1001 could be a safe option for managing epilepsy symptoms. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for temporal lobe epilepsy, which often involve anti-seizure medications or surgery, NRTX-1001 is unique because it uses a novel approach involving the bilateral intrahippocampal administration of a potential therapeutic agent. This treatment directly targets the hippocampus, a key brain area involved in seizures, which could offer more precise control over seizure activity. Researchers are excited because this innovative delivery method might provide a new option for patients with drug-resistant epilepsy, potentially reducing seizures more effectively than current methods.

What evidence suggests that NRTX-1001 might be an effective treatment for temporal lobe epilepsy?

Research has shown that NRTX-1001, a treatment using special nerve cells, can greatly reduce seizures in people with drug-resistant temporal lobe epilepsy. In earlier studies, patients experienced a median 92% drop in severe seizures within 7 to 12 months after receiving the treatment. Additionally, 80% of the patients demonstrated clear improvements. This treatment uses specific nerve cells called interneurons to help control seizures. So far, NRTX-1001 has been well-tolerated and has shown promising results in reducing the number of seizures. ^{1 3 4 6 7}

Who Is on the Research Team?

Ngoc Minh Le, MD

Principal Investigator

Neurona Therapeutics

Are You a Good Fit for This Trial?

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 meet one of the required conditions.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. neuronatherapeutics.com neuronatherapeutics.com/news/press-releases/040825/

Phase 1/2 - clinical trial of - NRTX-1001 EFFICACY: 92% median reduction in disabling seizures during 7-12-month efficacy endpoint period, and 80% (4/5) of patients responding with ...

2. neurology.org neurology.org/doi/10.1212/WNL.0000000000210525

First-in-Human Trial of NRTX-1001 GABAergic Interneuron ... NRTX-1001 administration has been well-tolerated in ten patients with drug-resistant TLE, with preliminary data suggesting significant reductions in seizure ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05135091

NCT05135091 | FIH Study of NRTX-1001 Neural Cell ... NRTX-1001 is intended to suppress the onset and spread of seizures. Safety, tolerability, and effects on reducing seizure frequency and epilepsy disease ...

4. neuronatherapeutics.com neuronatherapeutics.com/news/press-releases/100725/

Neurona Expands Investigation of NRTX-1001 Cell ... Neurona Expands Investigation of NRTX-1001 Cell Therapy into Mesial Temporal Lobe Epilepsy (MTLE) without Mesial Temporal Sclerosis (MTS).

5. innovation.ucsf.edu innovation.ucsf.edu/sites/venture.ucsf.edu/files/wysiwyg/Neurona%20-%20EMBARGOED%20FPD%20Bilateral%20Study%20PR.pdf

Neurona Doses First Patient in Phase 1/2 Trial of NRTX- ... Neurona's lead product candidate, NRTX-1001, comprising GABAergic interneurons, is currently being studied for safety and efficacy in two ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06422923

NCT06422923 | A Phase 1/2 Study of NRTX-1001 ... This is a multicenter, single arm, open-label study of NRTX-1001 in subjects with drug-resistant bilateral MTLE, with the objective of evaluating safety and ...

7. neuronatherapeutics.com neuronatherapeutics.com/news/press-releases/120624/

New Data from NRTX-1001 Cell Therapy Trial in Drug ... SAFETY: NRTX-1001 has been well-tolerated to date at both high and low doses. No adverse events have been attributed to the cell therapy.