RNS System LGS Feasibility Study

NCT05339126 | Active Not Recruiting Phase 2 DMC FDA Device

• 2 other identifiers: NP10015UH3NS109557
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 6

Brief Summary

To generate preliminary safety and effectiveness data for brain-responsive neurostimulation of thalamocortical networks as an adjunctive therapy in reducing the frequency of generalized seizures in individuals 12 years of age or older with Lennox Gastaut Syndrome (LGS) who are refractory to antiseizure medications. The intent is to determine the feasibility and the optimal design of a subsequent pivotal study in order to expand the indication for use for the RNS System as a treatment for patients with medically intractable LGS.

Conditions

Seizures, Generalized; Epilepsy; Lennox Gastaut Syndrome; Lennox-Gastaut Syndrome, Intractable; Seizures

Keywords

Medically refractory; Responsive neurostimulation; RNS System; Thalamocortical stimulation

Outcome Measures

Primary Outcomes (3)

• Safety: Annual device-related serious adverse event (SADE) rate

  The lower limit of the 95% confidence interval of the annual SADE rate at months 12 and 24 post-implant is less than 33.6% and 22.0%, respectively (twice the SADE rate of 16.8% and 11.0%, respectively, at the same time points in the RNS System pivotal study)

  12 months post-implant

• Safety: Annual device-related serious adverse event (SADE) rate

  The lower limit of the 95% confidence interval of the annual SADE rate at months 12 and 24 post-implant is less than 33.6% and 22.0%, respectively (twice the SADE rate of 16.8% and 11.0%, respectively, at the same time points in the RNS System pivotal study)

  24 months post-implant

• Effectiveness: Blinded evaluation period (BEP) responder rate

  The responder rate during one or both of the stimulation conditions (A or B) is ≥ 30%. The responder rate is the proportion of participants that are responders. A responder in this study is defined as a participant who has a ≥ 35% reduction in the frequency of drop seizures compared to that participant's pre-implant baseline.

  12 months post-implant

Secondary Outcomes (1)

• Safety: Post-op SAE rate

  4 weeks post-implant

Other Outcomes (10)

• Rate of SAEs of particular relevance

  Every 12 months post-implant

• Affective status

  Implant through 4 years post-implant

• Cognitive function

  Implant through 2 years post-implant

Study Arms (2)

Condition A

ACTIVE COMPARATOR

high-frequency short bursts (HFSB: 100 Hz, 160 µs pulse width, 200 msec burst)

Device: RNS System

Condition B

ACTIVE COMPARATOR

low-frequency long bursts (LFLB: 5 Hz, 160 µs pulse width, 5 sec burst)

Device: RNS System

Interventions

RNS System DEVICE

The RNS System provides closed loop responsive brain stimulation. The Neurostimulator monitors the electrical activity of the brain to detect abnormal activity that could lead to a seizure. If abnormal activity is detected, the neurostimulator delivers electrical stimulation to the brain through the leads to help prevent the seizure before it occurs.

Condition A; Condition B

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant is 15 years of age or older for first cohort; 12 years of age or older for second cohort. Note that age requirements for eligibility differ by cohort, as follows: the age limit for Cohort 1 is 15 years of age and above and the age limit for Cohort 2 may decrease to 12 years, pending a DSMB letter of recommendation, based on review of interim data analysis and concurrence with NINDS.
• Participant has medically intractable epilepsy defined as failure to achieve acceptable seizure control without unacceptable medication related side effects despite trials of 2 or more antiseizure medications.
• Participant had an average of ≥ 5 drop seizures per month in the 2 months preceding enrollment. A drop seizure is defined as an epileptic seizure (atonic, tonic, tonic-clonic, or myoclonic) involving the entire body, trunk, or head that leads or could lead to a fall, injury, or slumping in a chair.
• Participant's seizures are non-localized.
• Participant's scalp recorded EEG has features of LGS, such as multifocal spike, slow spike and wave discharges, and paroxysmal fast activity.
• Participant must (a) have a stable antiseizure medication (ASM) regimen for the 2 months preceding enrollment and (b) be willing to remain on the stable regimen, as medically able, through the Blinded Evaluation Period; rescue medication for acute seizure clusters are permitted. A stable ASM regimen is defined as no introduction or discontinuation of an ASM, and no change in an ASM dose of more than 25%.
• Participant is not on a therapeutic diet for epilepsy, or if participant is on a therapeutic diet for epilepsy must (a) have a stable diet for the 2 months preceding enrollment and (b) be willing to remain on the stable diet, as medically able, through the Blinded Evaluation Period.
• Participant does not have a vagus nerve stimulator (VNS), or if participant does have a VNS must (a) have had the VNS off for the 2 months preceding enrollment and (b) be willing to remain with the VNS off through the Blinded Evaluation Period.
• Participant is a male, or is a female of childbearing potential who is surgically sterile, 2 years postmenopausal, or practices a reliable method of contraception (hormonal, barrier method or abstention).
• Participant is willing to give informed consent (or assent, if a minor); if the participant assents or is not able to give informed consent, parent/legal guardian is willing to give informed consent.
• Participant is able to maintain a seizure log alone or with the assistance of a competent individual.
• Participant is able to attend study appointments in accordance with the study schedule.

You may not qualify if:

• Participant is participating in a therapeutic investigational drug or device study (including other RNS System studies).
• Participant is currently implanted with an electronic medical device that delivers electrical energy to the brain.
• Participant is currently implanted with an RNS Neurostimulator or NeuroPace Leads.
• Participant requires procedures that are contraindicated based on current RNS System labeling.
• Participant is pregnant.
• Participant has a diagnosed unstable psychiatric disorder or any attempt or expressed intent of suicide over the preceding 6 months.
• In the opinion of the investigator, the participant has a clinically significant or unstable medical condition \[including alcohol, opioid, recreational cannabis (not for therapeutic purposes) or other drug use disorder\] or a progressive central nervous system disease.
• Participant is taking any anticoagulants.
• In the opinion of the investigator, participant is an unsuitable candidate for this procedure.
• Participant has been diagnosed with psychogenic or non-epileptic seizures in the preceding year.
• Participant has experienced unprovoked status epilepticus in the preceding year.
• Participant has had therapeutic surgery to treat epilepsy in the preceding 3 months. Participants who have had epilepsy surgery more than 3 months prior to enrollment are eligible.
• Note: For contraindications, refer to current physician labeling (manuals) for the RNS System available at the NeuroPace website (www.neuropace.com).

Sponsors & Collaborators

• NeuroPace: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• University of Florida: collaborator

Study Sites (6)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

NYU Langone Medical Center

New York, New York, 10016, United States

Location

Mount Sinai Hospital

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Epilepsy; Lennox Gastaut Syndrome; Seizures

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Martha Morrell, MD

  NeuroPace, Inc.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2022
• First Posted: April 21, 2022
• Study Start: October 4, 2022
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 12, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: The dataset and any supporting documentation (including but not limited to the study protocol, statistical analysis plan, and data dictionary) required for the analysis of the data will be made available within one year of the primary publication or within 18 months of the last study visit of the last subject, whichever occurs first.
• Access Criteria: Requestors will provide a CV, a description of their resources \& facilities, along with a description of their planned analyses. Requests will be evaluated by a Research Review Committee at NeuroPace in accordance with NeuroPace data sharing policies. Approved requests will require execution of a data access agreement based on NeuroPace's existing template.

Locations

US (6)