Inclusion Criteria

Part A:

• Diagnosis of refractory focal epilepsy

• Completed the Open-label Treatment Period of the parent study (RAP-219-FOS-201) with acceptable tolerability, per the Investigator’s assessment

• Stable RNS® system configuration settings (no setting changes, including changes to stimulation or detection) and ASM dosing regimen for 2 months prior to Visit 1, unless medically indicated per Investigator

• Able and willing to provide written informed consent to participate in the study in accordance with ICH-GCP guidelines, and willing and able to comply with all aspects of the protocol

• Women of childbearing potential must agree to use of a highly effective or acceptable method of contraception from the first dose of study drug to the last study visit.

• In the Investigator’s opinion, participant is and will likely continue to be able and willing to comply with all components of the study protocol, including dosing and e-diary adherence as well as evaluations for the entire duration of the study

Part B:

• Completed the Double-blind Treatment Period of the parent study (RAP-219-FOS-301 or -302) with acceptable tolerability, per the Investigator’s assessment

• Written informed consent signed by the participant or legally authorized representative(s) (LAR[s]) prior to entering the study, in accordance with ICH-GCP. If consent is provided by the LAR(s) because the participant is unable to do so, a written or verbal assent agreeing to participate in the study from the participant must also be obtained.

• Women of childbearing potential must agree to use of a highly effective or acceptable method of contraception from the first dose of study drug to the last study visit.

• In the Investigator’s opinion, participant is and will likely continue to be able and willing to comply with all components of the study protocol, including dosing and paper diary adherence as well as evaluations for the entire duration of the study.

Part C:

• Previously:

  • Has not participated in any previous clinical study of RAP-219; OR

  • Failed RAP-219-FOS-301 or -302 screening, discontinued RAP-219-FOS-301 or -302 treatment early, or otherwise did not continue treatment directly from RAP-219-FOS-301 or -302 into RAP-219-FOS-901 Part B, and have permission to enroll after review by the Investigator and study Medical Monitor

• Aged 18 to 80 years at Visit 1

• Written informed consent signed by the participant or LAR(s) prior to entering the study, in accordance with ICH-GCP. If consent is provided by the LAR(s) because the participant is unable to do so, a written or verbal assent agreeing to participate in the study from the participant must also be obtained.

• Diagnosis of focal epilepsy (for ≥12 months prior to Visit 1 [Day -56]) according to the ILAE classification of the epilepsies (Scheffer et al., 2017), and epileptic seizures (Beniczky et al., 2025) supported by:

  • at least 1 brain magnetic resonance imaging (MRI) or computed tomography (CT) scan and electroencephalogram (EEG) study, completed within 10 years prior to Visit 1 (Day -56), that may be normal but are compatible with focal epilepsy (ie, may be normal but do not suggest an alternative diagnosis to FS) Note: If a participant may otherwise be eligible but lacks an available neuroimaging report and/or EEG report from within 10 years before Visit 1, a CT scan and/or EEG may be performed at Visit 1 (Day -56), but only as required for enrollment eligibility

  • continued inadequate FS control despite failed trials of ≥2 ASMs due to lack of antiseizure efficacy (ie, not only due to intolerability)

• At least one FS in the Prospective Baseline Period as recorded in the paper seizure diary over the 8 weeks after Visit 1.

• Concomitant treatment with between 1 and 3 total ASM(s), inclusive, not including rescue or pro re nata (PRN) ASMs. Note: concomitant ASM dosing (dosage strength, frequency, and timing; formulation, and branded/generic drug product) must remain unchanged for 4 weeks prior to Visit 1 (Day -56)

• Women of childbearing potential must agree to use of a highly effective or acceptable method of contraception from the first dose of study drug to the last study visit.

• In the Investigator’s opinion, participant is and will likely continue to be able and willing to comply with all components of the study protocol, including dosing and paper diary adherence and evaluations for the entire duration of the study.

Exclusion Criteria

Part A:

• Known hypersensitivity to RAP-219 or any of its excipients

• Treatment with any of the following concomitant medications:

  • perampanel within 8 weeks prior to Visit 1 (Day -28)

  • felbamate, unless dose regimen (dosage, frequency, and timing) remains unchanged for ≥12 months prior to Visit 1 (Day -28), with documented medical history indicating that liver function tests and complete blood counts remained stable during that 12-month period.

  • vigabatrin, unless dose regimen (dosage, frequency, and timing) remains unchanged for ≥24 months prior to Visit 1 (Day -28), with documented medical history of normal visual fields for ≥12 months prior to Visit 1 (Day -28).

• Pregnant or breastfeeding, or intending to become pregnant during the course of the study

• Any finding on the C-SSRS during the parent study (RAP-219-FOS-201) or at Visit 1 of RAP-219-FOS-901, that, per Investigator, would place the participant at unacceptable risk by participating in the study

• Any clinically significant, ongoing or likely to recur, unstable or serious medical, neurologic (other than epilepsy), or psychiatric condition, or ongoing AE from RAP-219-FOS-301 or -302 as assessed by medical history or laboratory testing which, per Investigator, would make the participant less likely to experience benefit or place them at unacceptable risk by participating

• Family history of long QT syndrome or corrected QT interval by Fridericia’s formula >470 msec for females and >450 msec for males at Visit 1

• Participation in any other interventional studies (aside from the parent study RAP-219-FOS-201) involving a study drug or device at least 12 weeks or 5 terminal elimination half-lives prior to Visit 1, whichever is longer, or plans to participate for the duration of the study. Participation in observational studies is not exclusionary.

• 8. Employment by or relation to an employee of the Sponsor, a Sponsor representative, or study site.

Part B:

• Participation in any other interventional studies (aside from the parent study RAP-219-FOS-301 or -302) involving a study drug or device at least 12 weeks or 5 terminal elimination half-lives prior to Visit 1 (Day -1), whichever is longer, or plans to participate for the duration of the study. Participation in observational studies is not exclusionary

• Family history of long QT syndrome or a corrected QT interval by Fridericia’s formula >470 msec for women and >450 msec for men at Visit 1 (Day -1)

• Any finding on the C-SSRS during the parent study (RAP-219-FOS-301 or -302) or at Visit 1 of RAP-219-FOS-901, that, per Investigator, would place the participant at unacceptable risk by participating in the study

• Pregnant or breastfeeding, or intending to become pregnant during the course of the study

• Any clinically significant, ongoing or likely to recur, unstable or serious medical, neurologic (other than epilepsy), or psychiatric condition, or ongoing AE from RAP-219-FOS-301 or -302 as assessed by medical history or laboratory testing which, per Investigator, would make the participant less likely to experience benefit or place them at unacceptable risk by participating

• Known hypersensitivity to RAP-219 or any of its excipients

• Employment by or relation to an employee of the Sponsor, a Sponsor representative, or study site

Part C:

• For those participants with prior RAP-219 exposure, any Investigator concern that resumed RAP-219 dosing or study participation would place the participant at unacceptable risk, based on Investigator clinical assessment of this participant's prior RAP-219 exposure

• For participants who previously enrolled in RAP-219-FOS-301 or -302, a history of frequent or severe RAP-219 dosing or other study conduct nonadherence during RAP-219-FOS-301 or -302.

• Any clinically significant, ongoing or likely to recur, unstable or serious medical, neurologic (other than epilepsy), or psychiatric condition, or ongoing AE from RAP-219-FOS-301 or -302 as assessed by medical history or laboratory testing which, per Investigator, would make the participant less likely to experience benefit or place them at unacceptable risk by participating

• Epilepsy surgery within 3 months prior to Visit 1 (Day -56)

• Family history of long QT syndrome or a corrected QT interval by Fridericia’s formula >470 msec for women and >450 msec for men at Visit 1 (Day -56).

• Current diagnosis of hepatic or renal failure, per Investigator

• Any malignancy that has required active treatment within the past 24 months prior to Visit 1 (Day -56), as assessed by medical history. Skin basal carcinoma and indolent prostate cancer treated with hormone therapy are allowable provided that in the opinion of the Investigator it is stable and does not pose any risk to participant or to the study results.

• Suicidal ideation with intent (with or without a plan) within 24 months prior to Visit 1 (Day -56) (ie, answering “Yes” to questions 4 or 5 on the Suicidal Ideation section of the C-SSRS), or any suicidal behavior in the past 24 months, or lifetime history of >1 suicide attempt (per the Suicidal Behavior section of the C-SSRS)

• Medical history of any of the following:

  • functional/dissociative seizures, also known as psychogenic nonepileptic seizures, that are recent and frequent and/or difficult for the participant to distinguish from their epileptic FS, per Investigator; note that only epileptic seizures should be recorded in the paper seizure diary

  • developmental and epileptic encephalopathy, including but not limited to, Dravet or Lennox-Gastaut Syndrome

• Treatment with any of the following concomitant medications:

  • perampanel within 8 weeks prior to Visit 1 (Day -56)

  • felbamate, unless dose regimen (dosage, frequency, and timing) remains unchanged for ≥12 months prior to Visit 1 (Day -56), with documented medical history indicating that LFTs and complete blood counts remained stable during that 12-month period

  • vigabatrin, unless dose regimen (dosage, frequency, and timing) remains unchanged for ≥24 months prior to Visit 1 (Day -56), with documented medical history of normal visual fields for ≥12 months prior to Visit 1 (Day -56)

• Any of the following indicators of current or recent history of substance abuse:

  • drug or alcohol dependency or abuse, per Investigator assessment, within 12 months prior to Visit 1 (Day -56)

  • positive drug screen, other than for cannabinoids and/or due to prescribed concomitant medications, at Visit 1 (Day -56)

• Pregnant or breastfeeding, or intending to become pregnant during the course of the study

• Participation or plans to participate in any other clinical study involving an investigational product or device within 12 weeks or 5 half-lives of the study drug prior to Visit 1 (Day -56), whichever is longer. Observational studies are not exclusionary.

• Known hypersensitivity to RAP-219 or any of its excipients

• Employment by or relation to an employee of the Sponsor, a Sponsor representative, or study site

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

Eligibility last updated 09/02/2026. Questions regarding updates should be directed to the study team contact.