Evaluation of the NaviFUS System in Drug Resistant Epilepsy

Prior treatment

• History of multiple strokes, or a stroke within the six (6) months prior to Screening.
• Presence of central nervous system (CNS) disease(s) other than epilepsy including but not limited to infections of the CNS (e.g., syphilis, Lyme disease, borreliosis, viral or bacterial meningitis/encephalitis, human immunodeficiency virus \[HIV\] encephalopathy), cerebral vascular disease, Parkinson's disease, traumatic brain injury, alcoholic encephalopathy within three (3) years prior to Screening.
• Patients with concurrent major psychiatric disorder, such as schizophrenia or bipolar disorder, severe depression, active suicidal ideation, active psychosis (excluding time-limited postictal psychosis) or psychiatric hospitalization within one (1) year before Screening.
• Prior diagnosis of cancer within the past two (2) years and evidence of continued malignancy within the past two (2) years (except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or in situ prostate cancer with normal prostate-specific antigens post resection).
• Patients who had major surgery six (6) weeks before study enrollment or who are not fully recovered from a surgical procedure or with planned surgery during study period or within fourteen (14) days thereafter.
• Patients who have received radiofrequency thermocoagulation (RFTC) within two (2) months of Screening.

Other illness

• Patients who have primary generalized epilepsy or non-epileptic seizures in the last two (2) years.
• More than two (2) seizure onset zones (foci) (except bitemporal foci) or unknown likely site of seizure onset, as determined by usual clinical, electroencephalography (EEG) and imaging practice.
• Presence of devices including but not limited to cardiac pacemaker, implantable cardioverter-defibrillator (ICD), permanent medication pumps, cochlear implants, responsive neurostimulator (RNS) or deep brain stimulation (DBS). Vagus nerve stimulators (VNS) do not represent an exclusion criterion, but settings should be stable throughout the trial.
• Patients with more than thirty percent (30%) of the skull area traversed by the sonication pathway covered by scars, scalp disorders (e.g., eczema), or atrophy of the scalp at Screening.
• History of intracranial hemorrhage.
• Inability to tolerate MRI procedures or contraindication to MRI (e.g. claustrophobia, too large for MRI scanner), including, but not limited to, presence of pacemakers (with the exception of MRI-safe pacemakers), aneurysm clips, artificial heart valves, ear implants, or foreign metal objects in the eyes, skin, or other areas of the body that would contraindicate an MRI scan.

Lab values

• Patients who have a medical or surgical history of severe systemic disease(s), such as (but not limited to) coronary artery disease, myocardial infarct, progressive heart failure, uncontrolled hypertension or abnormal ECG, severe pulmonary hypertension (pulmonary artery pressure \> 90 mmHg), chronic obstructive pulmonary disease (COPD), adult respiratory distress syndrome, hepatic and renal insufficiency (ALT or AST 3 times above normal range; serum creatinine \> 1.3 mg/dL), diabetic patients with poor control of blood sugar (HbA1c \> 8.5 %) at Screening.

Other

• Patients who have experienced tonic-clonic status epilepticus in the three (3) months leading up to enrollment in the study.
• Patients with clips or other metallic implanted objects in the FUS exposure path, except shunts.
• Patients with intracranial aneurysms requiring treatment or arterial venous malformations (AVMs) requiring treatment at any time.
• Patients who are not able or willing to tolerate the required prolonged stationary semi-supine position during treatment.

• Diagnosis of drug resistant temporal lobe epilepsy (TLE)
• Patients must experience at least four (4) observable seizures over the 60-day baseline, each on a separate day.
• Patients have focal-onset seizures with or without secondary generalization.
• Patients have had at least 24 hours video-electroencephalography (EEG) monitoring and comprehensive epilepsy evaluation confirming TLE.
• Seizure medication treatment is anticipated to remain stable during the trial, except for rescue medicines or occasional extra doses of ongoing medicines, as required.
• Patients should be capable of and willing to completing assessments and neuropsychological testing in English either alone or with the help of the study partner (where appropriate), per local guidelines. A study partner is a carer or family member of the patient.
• Patients and study partner (if applicable) who in the Investigator's opinion are reliable and able to use the seizure diary to record seizure throughout the study and are willing to comply with study procedures and visits.