NRTX-1001 Neural Cell Therapy for Epilepsy

(EPIC Trial)

Recruiting at 32 trial locations

Overseen By Eduardo Dunayevich, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Neurona Therapeutics

Must be taking: ASDs

Disqualifiers: Neurologic disease, Immunodeficiency, Psychiatric disorders, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 1 year

88 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for individuals with unilateral mesial temporal lobe epilepsy (MTLE) that does not respond to medication. The treatment, NRTX-1001 neural cell therapy, involves placing special nerve cells into the brain to determine if they can safely reduce seizures. Participants must experience frequent seizures that persist despite trying at least two different anti-seizure drugs. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that participants must be on stable doses of approved anti-seizure drugs for at least one month before joining.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that NRTX-1001 has been safe for patients so far. Studies have found that both high and low doses of this treatment have not caused any unwanted side effects. The treatment introduces special nerve cells that release a chemical called GABA, which helps calm brain activity. Based on current data, this approach appears safe, as no major issues have been reported in patients treated with NRTX-1001. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

NRTX-1001 is unique because it uses neural cell therapy to address epilepsy, a condition typically managed with medications like antiepileptic drugs, or in some cases, surgery. Unlike these standard treatments, NRTX-1001 involves the transplantation of specially engineered neural cells into the brain, which could potentially restore normal brain function and offer longer-lasting relief. Researchers are excited about this treatment because it targets the root of epileptic activity rather than just managing symptoms, offering hope for a transformative approach to epilepsy care.

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

Studies have shown that NRTX-1001, which participants in this trial may receive, can greatly reduce seizures in people with medication-resistant epilepsy. Research indicates a 92% average drop in severe seizures after treatment. Additionally, 80% of patients experienced a reduction in seizure frequency by more than 75%. The treatment uses special nerve cells that release GABA, a chemical that helps calm the brain. Early findings suggest this method is safe and highly effective in reducing seizures. ^{1 2 3 5 6}

Who Is on the Research Team?

Eduardo Dunayevich, MD

Principal Investigator

Neurona Therapeutics

Are You a Good Fit for This Trial?

This trial is for adults aged 18 to 65 with drug-resistant mesial temporal lobe epilepsy. Participants must have a history of focal seizures, be on stable epilepsy medication doses, and have confirmed seizure focus in one temporal lobe. They should not have attempted suicide in the past year, severe psychiatric disorders, pregnancy or breastfeeding status, progressive neurological diseases other than epilepsy, significant medical conditions that impair participation, immunodeficiency or chronic intracranial devices.

Inclusion Criteria

I have been on a stable dose of my seizure medication for at least a month.

I have had an average of 2 or more seizures every month for the last 6 months.

I still have seizures despite trying at least 2 different seizure medications.

Exclusion Criteria

Your MRI shows a possible cancerous growth.

My epilepsy is caused by a progressive neurological condition.

You have another medical condition that would make it unsafe for you to take part in the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single stereotactic intracerebral administration of inhibitory nerve cells (NRTX-1001) and take immunosuppressive medicines for 1 year

1 year

Follow-up

Participants are monitored for safety, tolerability, neural cell viability, local inflammation, and effects on epilepsy symptoms

2 years

Regular MRI scans and assessments

Long-term follow-up

Participants are followed for an additional 13 years with quarterly phone contact and annual visits

13 years

Quarterly phone contact, annual visits

What Are the Treatments Tested in This Trial?

Interventions

• NRTX-1001
• Sham Comparator

Trial Overview

The study tests NRTX-1001 neural cell therapy's safety and effectiveness against placebo (sham comparator) in reducing seizure frequency. It involves a single stereotactic injection of inhibitory nerve cells directly into the brain of subjects with unilateral mesial temporal lobe epilepsy who haven't responded to at least two anti-seizure drugs.

How Is the Trial Designed?

Group I: NRTX-1001 (Phase 3) Experimental Treatment 1 Intervention

Approximately 40 subjects

Group II: NRTX-1001 (Phase 1/2) Experimental Treatment 1 Intervention

Up to 28 subjects

Group III: Sham Comparator (Phase 3) Placebo Group 1 Intervention

Approximately 20 subjects

Who Is Running the Clinical Trial?

Neurona Therapeutics

Lead Sponsor

Trials

2

Recruited

50+

California Institute for Regenerative Medicine (CIRM)

Collaborator

Trials

70

Recruited

3,300+

Published Research Related to This Trial

In a Phase I clinical trial involving patients with drug-resistant epilepsy, the use of autologous mesenchymal stem cells (MSC) was well tolerated and did not lead to severe adverse effects, indicating a good safety profile for this therapy.

The MSC therapy showed promising efficacy, with 30% of patients achieving seizure remission and 50% becoming responders to anti-epileptic drugs, compared to only 17% in the control group, highlighting the potential of MSC as a treatment option for epilepsy resistant to conventional medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of refractory epilepsy patients with autologous mesenchymal stem cells reduces seizure frequency: An open label study. Hlebokazov, F., Dakukina, T., Ihnatsenko, S., et al.[2018]

Hematopoietic Stem Cell (HSC) therapy shows potential as a novel treatment for epilepsy, particularly in cases where traditional pharmacotherapy is ineffective, as seen in refractory epilepsy.

While pre-clinical studies indicate promising results for HSC therapy in promoting neuroprotection and neuronal regeneration, clinical effects remain marginal, highlighting the need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review on Hematopoietic Stem Cell Treatment for Epilepsy. Ghanta, MK., Merchant, N., Bhaskar, LVKS.[2022]

Transplanting embryonic GABAergic interneurons into the epileptic brain shows promise in stopping seizures by enhancing inhibition in affected areas, making it a potential treatment for difficult-to-treat epilepsy.

Recent research focuses on isolating and transplanting these cortical interneuron precursors from both mouse and human sources, although several challenges remain before this therapy can be widely used in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interneuron Transplantation as a Treatment for Epilepsy. Hunt, RF., Baraban, SC.[2018]

The study successfully induced differentiation of embryonic stem cell-derived neural stem/progenitor cells into GABAergic neurons, which were then transplanted into epileptic mice, showing significant recovery from seizures compared to the control group.

Transplanted GABAergic neurons led to substantial re-innervation in the hippocampus and reduced seizure activity, indicating that these cells could be a promising therapy for treating difficult-to-manage epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Seizure suppression in amygdala-kindled mice by transplantation of neural stem/progenitor cells derived from mouse embryonic stem cells. Shindo, A., Nakamura, T., Matsumoto, Y., et al.[2019]

The 2018 NINDS workshop emphasized the urgent need for therapies that can prevent epilepsy (antiepileptogenesis) and modify the disease, highlighting the complexities in trial design, such as timing of intervention and appropriate dosing.

Recent trials, like those using vigabatrin for children with tuberous sclerosis, illustrate the challenges and potential strategies for developing effective treatments, while also addressing regulatory hurdles that impact the progress of these therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiepileptogenesis and disease modification: Clinical and regulatory issues. French, JA., Bebin, M., Dichter, MA., et al.[2022]

Out of 101 registered trials for pediatric drug-resistant epilepsy, 32% focus on neurotechnological interventions, with 46% of those specifically investigating methods like vagus nerve stimulation and deep brain stimulation.

The study highlights a gap between the current clinical research on neurotechnology for pediatric epilepsy and its practical application, emphasizing the need for timely evidence to support the adoption of these interventions in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Clinical Research Landscape of Pediatric Drug-Resistant Epilepsy. Kaal, KJ., Aguiar, M., Harrison, M., et al.[2021]

Neural stem cells and progenitors (NSC/NPs) show great potential for treating epilepsy due to their ability to integrate into brain circuitry and restore lost functions, as highlighted by various studies in animal models.

While there are promising results regarding the use of NSC/NPs for neuro-restorative therapy, significant challenges remain that must be overcome before these therapies can be applied in clinical settings for epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stem cells as a potential therapy for epilepsy. Roper, SN., Steindler, DA.[2022]

Approximately 30% of epilepsy patients do not respond to existing antiepileptic drugs, highlighting the need for new treatment strategies.

Cell-based therapies show promise as a novel approach to treat epilepsy by either producing natural anticonvulsants or repairing damaged neuronal circuits, potentially offering new hope for patients with drug-resistant epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Commentary: the prospect of cell-based therapy for epilepsy. Kriegstein, AR., Pitkänen, A.[2021]

Citations

1.

neuronatherapeutics.com

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

Phase 1/2 - clinical trial of - NRTX-1001

92% median reduction in disabling seizures during 7-12-month efficacy endpoint period, and 80% (4/5) of patients responding with >75% seizure reduction in ...

2.

aesnet.org

aesnet.org/abstractslisting/first-in-human-trial-of-nrtx-1001-gabaergic-interneuron-cell-therapy-for-drug-resistant-focal-epilepsy-updated-results

first-in-human trial of nrtx-1001 gabaergic interneuron cell ...

The five subjects in the low dose cohort are all at least six months post-administration. Median monthly seizure reduction from baseline was 75% ...

3.

neuronatherapeutics.com

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

New Data from NRTX-1001 Cell Therapy Trial in Drug ...

Results: · 92% median seizure reduction from baseline · 80% of subjects with >50% seizure reduction · 80% of subjects with >75% seizure reduction ...

4.

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 ...

5.

neuronatherapeutics.com

neuronatherapeutics.com/news/press-releases/022025/

Neurona Unveils Phase 3 EPIC Study for NRTX-1001 Cell ...

The low-dose cohort demonstrated a 92% median reduction in disabling seizures from baseline, with 80% of subjects reporting >80% seizure ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05135091

NCT05135091 | FIH Study of NRTX-1001 Neural Cell ...

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 ...