Clinical Trials

Inclusion Criteria:

• Medically refractory focal epilepsy.
• An implanted responsive neurostimulator device with at least one RNS detecting/stimulating electrode placed correctly in a seizure onset zone within the mesial temporal lobe that meets the following criteria as determined by the RNS Patient Data Management System (PDMS)
  • RNS implanted at least 15 months before screening .
  • Stable device configuration settings, stimulation and detection settings (including long episode duration) for at least 8 weeks before screening.
  • No anticipated need for device setting changes during the study period.
  • Available retrospective long episode count data for at least 8 weeks before screening.
  • A demonstrated history of compliance with interrogation of the RNS device and upload of data to the RNS PDMS in the last 8 weeks before screening analysis is performed.
  • At least an average of 8 long episodes per 4-week interval in the 8-week retrospective eligibility period.
  • At least 16 long episode iEEG tracing records since the last RNS configuration change for review and determination of concordance.
  • At least 50% concordance of electrographic seizures among recorded long episodes during the retrospective eligibility evaluation period based on consensus review by the Principal Investigator (PI) and one central epileptologist reviewer of available long episode iEEG traces from the retrospective eligibility period (review for concordance determination should include review of at least 16 iEEG traces, and may include review of consecutive traces prior to the 8-week retrospective eligibility review period as long as they are from a period of time since the last configuration change; if there are more than 50 iEEG traces from the 8-week retrospective baseline period, PIs and eligibility reviewers can stop their review after 50 iEEG traces); exceptions may be made for participants with more than 20 long episodes per 4-week interval during the retrospective baseline period, where a threshold of at least 25% concordance will be required for eligibility, with approval from the Sponsor .
  • Bursts must not exceed 1,000 ms (2,000 ms within a therapy) in the RNS programming during the eligibility period.
• If currently treated with ASMs, up to a maximum of 4 concomitant ASMs are allowed provided that doses have remained stable for at least 8 weeks before screening and that the doses of concomitant ASMs are not expected to require changes or titrations during the study. Vagus nerve stimulators (VNS) are allowed in the study provided that they were implanted > 18 months prior to the beginning of the retrospective eligibility review period and settings have been stable for at least 3 months at the time of enrollment and are not expected to change during the study. VNS does not contribute to the count of ASMs (See Exclusion Criterion 12 and 13 and Section 8.3 for ASMs that are exclusionary).
• At least 1 clinical seizure (of a seizure type with known electrographic correlates historically) during the 8-week retrospective eligibility review period by participant report.
• Rescue benzodiazepines have only been necessary at most two times per 4-week interval during the 8-week retrospective eligibility review period.
• Participants in otherwise good health (with the exception of epilepsy), as determined by the PI via the medical history, and physical examination.
• Participants aged 18-65 years.
• Weight ≥ 45 kg by chart review at screening Visit 1 (to be confirmed at Visit 2) and a body mass index (BMI) between 18 to 45 kg/m2.
• Able and willing to provide written informed consent to participate in the study in accordance with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH)-Good Clinical Practice GCP guidelines.
• Willing and able to comply with all aspects of the protocol.

Central Eligibility Review

• Medically refractory focal epilepsy with one or two known seizure onset zones or seizure foci:
  • Central eligibility committee agrees that at least one RNS detecting/stimulating electrode has been placed correctly in a seizure onset zone within the mesial temporal lobe.
  • Central eligibility committee confirms upon review of RNS device data report that they meet device-related eligibility criteria

Visit 3, participants should continue to meet criteria from Visit 1 and meet the following criteria:

• At least 8 long episodes in the 4-week prospective baseline period.
• Rescue benzodiazepines have only been necessary at most two times during the 4-week prospective baseline period.

Exclusion Criteria:

Visit 1:

• Participants with clinical events considered psychogenic non-epileptic events are excluded unless non-epileptic events can clearly and consistently be differentiated from seizure types that have historically had an electrographic correlate, and enrollment is approved by the Medical Monitor, Sponsor, and Epilepsy Study Consortium member.
• Participants with generalized onset seizures in the past 10 years.
• History of status epilepticus while on antiepileptic medication(s) within 2 years of screening.
• Females who are pregnant or lactating.
• Individuals of reproductive potential (all individuals assigned female at birth will be considered of childbearing potential unless they are postmenopausal or have been sterilized surgically) who do not agree to simultaneously use two effective birth-control methods during the study period and for 6 weeks following their last dose of study drug. If male participants or male partners of female participants are not vasectomized, one of the methods must be a highly-effective barrier method (condoms). No sperm donation is allowed during the study period and for 6 weeks after the last dose of study drug.
• Any clinically significant history of cardiac arrhythmia or cardiac structural change which, in the opinion of the Investigator, should exclude the participant from the study.
• An active central nervous system (CNS) infection, demyelinating disease, degenerative neurological disease, CNS malignancy, or any CNS disease deemed to be progressive during the course of the study that may confound the interpretation of the study results.
• Any clinically significant psychiatric diagnosis, psychological or behavioral problems which, in the opinion of the Investigator, would interfere with the participant’s ability to participate in the study.
• Participants who are currently enrolled in or have participated in any other clinical trials involving an investigational product or device within 12 weeks or 5 half-lives of the study drug of screening or longer as required by local regulations, except the investigational study of non-invasive seizure monitoring tools or wearables.
• Participants receiving more than 4 concomitant ASMs for their epilepsy.
• Participants who have had epilepsy surgery within the last 12 months before screening.
• Use of perampanel within 12 weeks before screening.
• If participants are on felbamate, they must have been on a stable dose for > 12 months and have normal liver function tests. If participants are on vigabatrin, they must have been on a stable dose for > 24 months and have documentation of normal visual fields within the last 3 months.
• On a ketogenic diet with any regimen changes within the last 12 weeks before screening. Stable ketogenic or modified Atkins diets are allowed.
• History of drug or alcohol dependency or abuse within the 24 months before screening, or those participants who have a positive drug test at baseline.
• History of or ongoing multiple drug allergies or severe drug reaction to ASM(s), including dermatological (e.g., DRESS, or Stevens-Johnson syndrome), hematological, or organ toxicity reactions.
• Any psychotic disorder(s) or unstable recurrent affective or mood disorder(s) evident by use of antipsychotics or prior suicide attempt(s) within approximately the last 5 years.

At Visit 2 and Visit 3, participants should continue to meet criteria from Visit 1 and additionally, the following exclusion criteria will be evaluated:

• Any clinically significant laboratory abnormality which, in the opinion of the Investigator, should exclude the participant from the study.
• Participants with corrected QT interval by Fridericia’s formula (QTcF) > 470 msec are excluded from the study.
• Participants who are suffering from clinically significant active liver disease indicated by abnormal liver function tests greater than 3 times the upper limit of normal (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]).
• Any suicidal ideation with intent with or without a plan within 2 years before screening or during screening (i.e., answering “Yes” to questions 4 or 5 on the Suicidal Ideation section of the C-SSRS).
• Any lifetime suicidal behavior (per the Suicidal Behavior section of the C-SSRS).

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 4/16/2024. Questions regarding updates should be directed to the study team contact.