RNS™ System Pivotal Clinical Investigation

The RNS™ System Pivotal Clinical Investigation is designed to assess the safety and to demonstrate that the RNS™ System is effective as an add-on (adjunctive) therapy in reducing the frequency of seizures in individuals 18 years of age or older with partial onset seizures that are refractory (resistant or hard to treat) to two or more antiepileptic medications. Candidates will continue to receive their epilepsy medications while participating in the trial.

NeuroPace, Inc is sponsoring an investigational device study of the RNS™ System, the company's responsive brain stimulation therapy for refractory epilepsy. The RNS™ System Pivotal Investigation is a randomized, double-blinded, sham stimulation controlled investigation being conducted at approximately 28 sites throughout the United States. The investigation is designed to assess the safety and effectiveness of the RNS™ System in reducing the frequency of medically uncontrolled and disabling partial onset seizures (those that start from one area of the brain).

The neurostimulator and leads are implanted in the head. The RNS™ System neurostimulator (a pacemaker-like device) has a small battery for power and a microprocessor that detects (senses) and stores electrical activity from the brain. When the RNS™ System neurostimulator detects a seizure, it responds by sending electrical stimulation through leads (tiny wires with electrodes) to a small part of the patient's brain to stop the seizure. This type of treatment is called responsive stimulation, but it is not yet known if it will work for the treatment of epilepsy. Direct brain stimulation therapy has already received approval in the United States, Europe, Canada, and Australia for the treatment of Essential Tremor and Parkinson's disease. Direct brain stimulation is not approved for the treatment of epilepsy.

Study participation is expected to last approximately 2 to 3 years. All patients in the trial will be implanted with the RNS device. During the double-blind portion of the trial, half of the patients will have responsive stimulation turned ON and half will have responsive stimulation turned OFF. Patients will not know whether stimulation is being delivered or not. Five months after the RNS™ System has been implanted, when the double-blinded portion of the trial is completed, all patients will be able to have stimulation turned ON. Seizure frequency and severity, as well as physical and emotional health will be followed throughout the study.

• Active Comparator: 1
  Subjects will have responsive stimulation turned ON after implant with the RNS(TM) System.
  Intervention: Device: Responsive Neurostimulator System
• Sham Comparator: 2
  Subjects will have responsive stimulation turned OFF after implant with the RNS(TM) System. After completion of the Blinded Evaluation Period (week 20 post-implant), all subjects will have responsive stimulation enabled.
  Intervention: Device: Responsive Neurostimulator System

1. Disabling motor simple partial seizures, complex partial seizures, and/or secondarily generalized seizures. Disabling refers to seizures that are severe enough to cause injuries, or significantly impair areas of function such as employment, psychological or social wellbeing, or mobility.
2. Failed treatment with a minimum of two anti-seizure medications
3. An average of three or more seizures every 28 days for three consecutive 28-day periods
4. Between the ages of 18 and 70 years.
5. No more than two epileptogenic regions in the brain.

Note: Patients with vagus nerve stimulators may be eligible for this clinical trial if the device has been turned off for a specified period of time and the patient agrees to have the generator explanted (excluding leads) prior to or at the time of the RNS implant.