Study Evaluating the Safety and Efficacy of RAP-219 in Adult Participants With Refractory Focal Epilepsy

A Phase 2A, Multicenter, Open-label Study Evaluating the Safety and Efficacy of RAP-219 in Adult Participants With Refractory Focal Epilepsy

This is a clinical research study for an investigational drug called RAP-219 in patients with Refractory Focal Epilepsy. This study is being conducted to determine if RAP-219 works and is safe in patients with Refractory Focal Epilepsy.

Study Overview

• Status: Completed
• Conditions: Focal Onset Seizures
• Intervention / Treatment: Drug: RAP-219

Detailed Description

This is a Phase 2A, proof-of-concept, multi-center, open-label study designed to evaluate the efficacy, safety, tolerability, and PK/PD relationship of RAP-219 in adult participants with refractory focal epilepsy. The activity of RAP-219 will be assessed in approximately 30 participants treated with the RNS® system.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale University
  • Idaho
    • Boise, Idaho, United States, 83702
      • Consultants in Epilepsy and Neurology, PLLC
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • IU Health Neuroscience Center, Goodman Hall
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • The University of Kansas Medical Center Epilepsy Clinic
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Comprehensive Epilepsy Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania - Department of Neurology
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center, Houston
    • Houston, Texas, United States, 770300
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Medically refractory focal epilepsy with an implanted responsive neurostimulator device placed correctly in a seizure onset zone that meet several device-related criteria and demonstrated history of compliance with interrogation of the RNS device and upload of data
• If currently treated with antiseizure medications, up to a maximum of 4 concomitant mediations are allowed
• At least 1 clinical seizure during the 8-week retrospective eligibility period
• Participants in otherwise good health as determined by the investigator
• Willing and able to adhere to all aspects of the protocol
• A demonstrated history of compliance with interrogation of the RNS device and upload of data before screening

Exclusion Criteria:

• Participants with generalized onset seizures in the past 10 years
• History of status epilepticus while on antiseizure medications within 2 years of screening
• Individuals of reproductive potential who do not agree to simultaneously use two effective birth-control methods
• Participants who have had epilepsy surgery within the last 12 months before screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RAP-219; Participants will receive 0.75 mg RAP-219 daily for 5 days followed by 1.25 mg RAP-219 daily for the remainder of the 8-week treatment period.	Drug: RAP-219; RAP-219 oral tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in long episode frequency during the treatment period compared to pre-treatment baseline: Responder proportion, Percent Change Percent change	Change in long episode frequency per 28-day period during the treatment period compared to baseline	Screening until 5 months after enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in focal clinical seizure frequency during the treatment period compared to pre-treatment baseline: Percent Change, Responder proportion	Change in focal clinical seizure frequency per 28-day period during the treatment period compared to baseline	Screening until 5 months after enrollment
Change in frequency of estimated electrographic seizures based on RNS® system data during the treatment period compared to pre-treatment baseline	Change in the frequency per 28-day period of estimated electrographic seizures based on RNS data during the treatment period compared to baseline	Screening until 5 months after enrollment
Change in RNS® system long episode-free days during the treatment period compared to pre-treatment baseline: Count, Longest continuous interval, Time until pre-treatment count	Change in long episode-free days during the treatment period compared to pre-treatment baseline	Screening until 5 months after enrollment
Change in focal clinical seizure-free days during the treatment period compared to pre-treatment baseline: Count, Longest continuous interval, Time until pre-treatment count	Change in focal clinical seizure-free days during the treatment period compared to pre-treatment baseline	Screening until 5 months after enrollment
Change in RNS® system electrographic biomarkers other than long episodes during the treatment period compared to pre-treatment baseline	Change in RNS® system electrographic biomarkers other than long episodes during the treatment period compared to pre-treatment baseline	Dosing until 5 months after dosing
Change in the Seizure Severity Response Questionnaire (SSRQ) during the treatment period compared to pre-treatment baseline	Measurement of seizure severity by participant rating scale of the Seizure Severity Scale. Seizure severity will be assessed by asking participants to respond to 4 questions using a 0-10 numerical rating scale and circling the number that best describes how their seizures have impacted them since their last study visit. Higher scores = higher impact.	Screening until 5 months after enrollment
Count and proportion of responders on the clinical global impression of change (CGIC) scale during the treatment period compared to pre-treatment baseline	Change in overall clinical status as measured by Clinical Global Impression of Change scores rated by investigator and participant. Both the participant (PGIC) and the clinician (CGIC) will rate their global impression of changes in the participant's condition throughout the study. The CGI scale measures the change in the participant's clinical status from a specific point in time, i.e., the Baseline Period and is rated on a 7-point Likert scale ranging from a score of 1 for very much improved to 7 for very much worse. Higher scores = worse outcome.	Screening until 5 months after enrollment
Plasma concentrations of RAP-219	Analysis of plasma concentrations of RAP-219	Dosing until 5 months after dosing
Incidence of treatment-emergent adverse events (TEAEs)	Analysis of AEs during the treatment and pre-treatment baseline periods	Dosing until 5 months after enrollment
Clinically meaningful changes, if any, from baseline in vital signs, electrocardiograms (ECGs), complete blood counts, serum chemistries, or liver function tests after treatment with RAP-219	Analysis of vital signs, ECGs, CBC, serum chemistries and liver function tests during the treatment and pre-treatment baseline periods	Screening until 5 months after enrollment
Incidence of participants expressing suicidal ideation assessed with the Columbia-Suicide Severity Rating Scale (C-SSRS)	Analysis of C-SSRS entries during the treatment and pre-treatment baseline periods	Screening until 5 months after enrollment
Cognitive function as measured using the Cogstate Digital Battery	Analysis of the Cogstate Digital Battery during the treatment and pre-treatment baseline periods	Screening until 5 months after enrollment

Collaborators and Investigators

• Sponsor: Rapport Therapeutics Inc.
• Investigators: Principal Investigator: Jaqueline A French, MD, NYU Langone Comprehensive Epilepsy Center

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2024
• Primary Completion (Actual): September 26, 2025
• Study Completion (Actual): September 26, 2025

Study Registration Dates

• First Submitted: April 17, 2024
• First Submitted That Met QC Criteria: April 17, 2024
• First Posted (Actual): April 22, 2024

Study Record Updates

• Last Update Posted (Actual): February 5, 2026
• Last Update Submitted That Met QC Criteria: February 4, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Epilepsy; FOS; RNS; long episode; Refractory focal epilepsy
• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Epilepsy; Seizures; Epilepsies, Partial
• Other Study ID Numbers: RAP-219-FOS-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No