RNS® System Epilepsy PAS

Study Overview
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Brief Summary
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The purpose of the study is to follow patients with partial onset seizures prospectively over 5 years in the real-world environment to gather data on the long-term safety and effectiveness of the RNS System at qualified CECs by qualified neurologists, epileptologists, and neurosurgeons trained on the RNS System.

Detailed Description
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NeuroPace, Inc. is sponsoring a post-approval study (PAS) of the RNS System device. The RNS System is the first FDA-approved closed loop responsive neurostimulator designed to reduce the frequency of seizures in individuals with partial onset seizures. The RNS System Epilepsy PAS is a 5 year, non-randomized, open-label, multi-center prospective observational study. Data regarding safety and efficacy are collected at enrollment and periodically throughout the 5-year study. The study is designed to assess the long-term safety and effectiveness of the RNS System as an adjunctive therapy in reducing the frequency of seizures in individuals 18 years of age or older with partial onset seizures who have undergone diagnostic testing that localized no more than 2 epileptogenic foci, are refractory to two or more antiepileptic medications, and currently have frequent and disabling seizures (motor partial seizures, complex partial seizures and/or secondarily generalized seizures). Data from the RNS System Epilepsy PAS will be used to calculate long-term SAE rates, median percent change in seizure frequency (from pre-implant retrospective data), as well as other safety and effectiveness endpoints.

Official Title
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RNS® System Post-Approval Study in Epilepsy

Conditions
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Epilepsy

Intervention / Treatment
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* Device: RNS System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A clinical decision to treat the patient with the RNS System in accordance with its approved indication for use has been made prior to enrollment in the study. For approved indication for use and contraindications, refer to current physician labeling and instructions for use (manuals) for the RNS System available at the NeuroPace website (www.neuropace.com). This post-approval study also has the following additional study related inclusion criteria: Subject or legal guardian is able to provide appropriate consent to participate Subject is able to maintain a seizure diary alone or with the assistance of a competent individual Subject is able to attend clinic appointments in accordance with the study schedule Exclusion Criteria: Per clinician assessment, treatment with the RNS System is contraindicated based on current RNS System labeling. For approved indication for use and contraindications, refer to current physician labeling and instructions for use (manuals) for the RNS System available at the NeuroPace website (www.neuropace.com). This post-approval study has the following additional study related exclusion criteria: Subject is participating in a therapeutic investigational drug or device study Subject was treated with a VNS within the last three months (90 days) Subject is pregnant

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Evaluation<br>A group of subjects with the RNS System implanted who elect to continue to receive RNS System responsive stimulation for the long term. | Device: RNS System<br>* The RNS System provides closed loop responsive brain stimulation. In response to detection of previously identified electrocorticographic activity, the neurostimulator delivers stimulation to the seizure foci by way of the leads to interrupt the activity before the patient experiences clinical seizures. The typical patient is treated with a cumulative total of 5 minutes of stimulation a day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SAE rate | Calculate annual SAE rates over time in the entire subject population as well as within subpopulations. | Implant through 5 years post-implant | 
| Neurosurgeon experience | Demonstrate there is no difference in safety in 6-week perioperative period based on the experience of NeuroPace qualified and trained implanting physicians. | Implant through 41 days post-implant | 
| Physician experience | Demonstrate there is no difference in safety 1 year post-implant based on experience of NeuroPace qualified and trained treating physicians and Comprehensive Epilepsy Centers. | Implant through 1 year post-implant | 
| Product use - surgical procedures | Present the incidence and number of AEs related to surgical procedures associated with implant, explant, reimplantation, and revision of the neurostimulator and lead(s). |  | 
| Autopsy | Present data from autopsies obtained from any patient implanted with neurostimulator/leads. |  | 
| Median percentage reduction in disabling seizure | Demonstrate that the median percentage reduction in disabling seizures over time in the entire subject population is comparable to the median percentage reduction in disabling seizures over time in the LTT study. Characterize the median percentage reduction in disabling seizures over time within subpopulations. | Pre-implant (retrospective data) compared to 30 to 36 months post-implant | 
| Neurostimulator programming | Demonstrate that stimulation programming classes have similar effects on the overall seizure frequency. | Through 5 years post-implant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seizure worsening | Demonstrate that there is not a worsening in disabling seizures over time in the entire subject population. Assess the sustained effect on disabling seizure frequency over time within subpopulations. | 6 months post-implant through 36 months post-implant | 
| Neurostimulator programming | Characterize the effects of stimulation programming classes on the overall 5-year rate of SAEs and device-related non-serious AEs. | Implant through 5 years post-implant |