Responsive Neurostimulation for Generalized Epilepsy

(NAUTILUS Trial)

Recruiting at 25 trial locations

Overseen By Cairn Seale

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: NeuroPace

Must be taking: Antiseizure medications

Must not be taking: Anticoagulants

Disqualifiers: Pregnancy, Active psychosis, Major depression, others

Stay on Your Current Meds You can continue your current medications while participating

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

100 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 idiopathic generalized epilepsy who continue to experience seizures despite trying at least two different medications. The treatment uses the RNS System, a device that reduces primary generalized seizures by delivering electrical stimulation to specific brain areas. Participants will be randomly assigned to have the device either turned on or off to determine the effectiveness of the active treatment. This trial suits those who have recently experienced two or more generalized tonic-clonic seizures and can maintain a simple electronic diary. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial requires that you stay on a stable antiseizure medication regimen during the study, if medically possible. However, rescue benzodiazepine medications for acute seizure clusters are allowed.

What prior data suggests that the RNS System for thalamic stimulation is safe for individuals with drug-resistant idiopathic generalized epilepsy?

Research has shown that the RNS System is safe and well-tolerated for people with epilepsy. One study observed patients for nine years and found that the treatment significantly reduced seizures without major safety issues. It is safe for both older and younger adults. The RNS System has already received approval for treating focal epilepsy, further supporting its safety.

Overall, evidence suggests that the RNS System is a safe option for managing seizures in individuals whose epilepsy does not respond to medication. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the RNS System for treating generalized epilepsy because it offers a personalized approach by delivering responsive neurostimulation directly to the brain. Unlike traditional treatments like antiepileptic drugs, which affect the entire brain, the RNS System targets specific brain regions involved in seizures, potentially reducing side effects and improving seizure control. Additionally, the system continuously monitors brain activity and provides stimulation only when abnormal patterns are detected, making it a highly tailored and dynamic treatment option. This innovative mechanism could offer hope to patients who have not found relief with current therapies.

What evidence suggests that the RNS System is effective for reducing seizures in drug-resistant idiopathic generalized epilepsy?

Research has shown that the RNS System, which participants in this trial may receive, can significantly reduce seizures in individuals whose epilepsy does not respond to medication. In earlier studies, patients using the RNS System experienced 62% fewer seizures in the first six months. Over time, the system proved even more effective, with a 67% reduction in seizures after one year and up to 75% after two years. Another study found an 82% overall reduction in seizures, with some patients becoming completely seizure-free. These results suggest that the RNS System could be a promising treatment for epilepsy, particularly for those who have not found relief with medication. Participants in this trial will be in either the active group, receiving responsive stimulation, or the sham group, where the stimulation is off. ^{5 6 7 8 9}

Who Is on the Research Team?

Martha Morrell, MD

Principal Investigator

NeuroPace, Inc.

Are You a Good Fit for This Trial?

This trial is for individuals aged 12 or older with drug-resistant idiopathic generalized epilepsy who haven't had a neurostimulator implanted. They must have experienced at least two tonic-clonic seizures recently, be on stable seizure medication, and able to attend clinic visits. Women of childbearing age should use reliable contraception.

Inclusion Criteria

Participant does not have a vagus nerve stimulator (VNS, LivaNova) or Participant's VNS is OFF during the two month retrospective baseline and participant is willing to keep the VNS off during the study

I am 12 years old or older.

I have been diagnosed with a type of epilepsy that causes different seizure types.

Exclusion Criteria

You have a device in your brain that uses electricity to work.

I have been diagnosed with severe mental health issues like psychosis or major depression in the last year.

Participant is participating in a therapeutic investigational drug or other device study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline

Two-month retrospective and one-month prospective baseline period

3 months

Implantation

Participants are implanted with the RNS System and detection is enabled

1 month

Randomization and Blinded Treatment

Participants are randomized to Active or Sham stimulation and are blinded to their group

9 months

Unblinding and Open-label Treatment

Participants are unblinded and those in the Sham group have responsive stimulation enabled

Up to 2 years post-implant

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years post-implant

What Are the Treatments Tested in This Trial?

Interventions

• RNS System
• Sham stimulation

Trial Overview The RNS System NAUTILUS Study tests the safety and effectiveness of responsive thalamic stimulation as an additional treatment for reducing primary generalized seizures compared to sham (fake) stimulation in participants with drug-resistant epilepsy.

How Is the Trial Designed?

Group I: Active Group (responsive stimulation ON) Active Control 1 Intervention

Participants are implanted with the RNS System and are receiving treatment with responsive stimulation.

Group II: Sham Group (responsive stimulation OFF) Placebo Group 1 Intervention

Participants are implanted with the RNS System and are not receiving treatment with responsive stimulation.

Who Is Running the Clinical Trial?

NeuroPace

Lead Sponsor

Trials

11

Recruited

1,500+

Published Research Related to This Trial

The NeuroPace RNS System can provide symptomatic relief for patients with drug-resistant partial seizures, but it carries significant risks of implant site infection and bone flap osteomyelitis, as seen in 3 reported cases.

In this study, 10% of patients developed infections related to the RNS device, particularly after multiple battery replacements, highlighting the need for improved techniques to minimize these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implant Site Infection and Bone Flap Osteomyelitis Associated with the NeuroPace Responsive Neurostimulation System. Wei, Z., Gordon, CR., Bergey, GK., et al.[2019]

The responsive neurostimulator (RNS) has been clinically used since 2013 to treat patients with medically refractory partial epilepsy, showing significant seizure reduction compared to sham stimulation in a randomized clinical trial.

Long-term use of the RNS has provided valuable data on epilepsy dynamics, including insights into seizure onset patterns and the potential for early detection of treatment benefits, although optimal patient selection and lead placement remain areas for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Responsive neurostimulation: Review of clinical trials and insights into focal epilepsy. Geller, EB.[2019]

In patients with the RNS System for epilepsy, a significant reduction in 'long episodes' of electrographic seizures within the first week of starting new antiseizure drugs (ASDs) was highly predictive of the medication's efficacy.

In a larger multicenter study, a decrease in 'episode starts' by 50% or more within the first 1-2 weeks was 90% specific for effective medications, suggesting that early neurophysiological data can guide quicker medication adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early detection rate changes from a brain-responsive neurostimulation system predict efficacy of newly added antiseizure drugs. Quraishi, IH., Mercier, MR., Skarpaas, TL., et al.[2021]

The NeuroPace® RNS® System is a safe and effective neuromodulation device for patients with epilepsy who do not respond to traditional antiseizure medications, providing a nondestructive alternative to surgical resection.

Clinical trials have shown that the RNS System can detect and respond to epileptiform activity by delivering targeted electrical stimulation, which may lead to improved seizure control and could be adapted for other neurological disorders using advanced machine learning techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The RNS System: brain-responsive neurostimulation for the treatment of epilepsy. Jarosiewicz, B., Morrell, M.[2021]

The study involved 12 patients who underwent robotic-assisted placement of depth electrodes for the RNS® system, showing a mean seizure reduction of approximately 40% over two years, which aligns with results from previous pivotal trials.

Robotic-assisted stereotactic techniques provided a safe and accurate method for electrode placement, with a mean operative time of 121 minutes and minimal deviation from the intended target, although two patients experienced wound infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Robot-Assisted Responsive Neurostimulator System Placement in Medically Intractable Epilepsy: Instrumentation and Technique. McGovern, RA., Alomar, S., Bingaman, WE., et al.[2020]

In a study involving 16 patients with medically refractory focal epilepsy, robotic-assisted implantation of the responsive neurostimulation system (RNS) led to an impressive average seizure reduction of 82% at 6 months and 90% at 1 year, demonstrating its efficacy as a treatment.

The use of the ROSA robot for targeting ictal-onset zones resulted in a highly accurate lead placement, with only a 0.165-mm discrepancy between the expected and actual lead locations, indicating a precise method for improving seizure control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel Robotic-Assisted Technique to Implant the Responsive Neurostimulation System. Tran, DK., Paff, M., Mnatsakanyan, L., et al.[2021]

Citations

1. neuropace.com neuropace.com/blog/epilepsy-treatment-rns-system-epilepsy-research-post-approval-study/

Epilepsy Treatment Results with the RNS System New study shows the RNS System helps reduce seizures by 62% within the first 6 months in adults with drug-resistant focal epilepsy.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4233950/

Final results of the RNS System Pivotal trial - PMC Responsive stimulation to the seizure focus reduced the frequency of partial-onset seizures acutely, showed improving seizure reduction over time, was well ...

3. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2023.1240380/full

Clinical outcomes following responsive neurostimulation ... Subsequent real-world experience with RNS has demonstrated median seizure frequency reduction of 67% at 1 year and 75% at 2 years. Responder ...

4. neurology.org neurology.org/doi/10.1212/WNL.0000000000212230

Multicenter Post-approval Study of the RNS System in ... Data from 255 participants were included in the primary effectiveness endpoint. The reduction in seizures overall was 82% (1st quartile 100%; 3 ...

5. neuropace.com neuropace.com/press-release/neuropace-rns-system-seizure-reduction-new-data/

New Published Data Show NeuroPace's RNS® System ... Real-world data from a multicenter clinical study of the RNS System were published in Epilepsia, demonstrating seizure reductions not seen with ...

6. neuropace.com neuropace.com/providers/rns-system-safety-data/

RNS System | Proven Safety Profile Responsive neurostimulation was well tolerated and safe over time. Conclusions from 9 years of data in the largest prospective neuromodulation study in the ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8633477/

The Efficacy, Safety, and Outcomes of Brain‐responsive ... Our study suggests that older adults treated with the RNS System achieve seizure outcomes comparable to younger adults.

8. neuropace.com neuropace.com/patients/neuropace-rns-system/

NeuroPace RNS System | Focal Epilepsy Treatment Device The RNS System is a treatment for adults with drug-resistant focal epilepsy. Your doctor personalizes it to respond to your brain activity.

9. neurology.org neurology.org/doi/10.1212/WNL.0000000000010154

Nine-year prospective efficacy and safety of brain- ... This study provides Class IV evidence that brain-responsive neurostimulation significantly reduces focal seizures with acceptable safety over 9 years.