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

Phase 2
Active, not recruiting
Conditions
Focal Onset Seizures
Interventions
Registration Number
NCT06377930
Lead Sponsor
Rapport Therapeutics Inc.
Brief Summary

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.

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.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
30
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
RAP-219RAP-219Participants 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.
Primary Outcome Measures
NameTimeMethod
Change in long episode frequency during the treatment period compared to pre-treatment baseline: Responder proportion, Percent Change Percent changeScreening until 5 months after enrollment

Change in long episode frequency per 28-day period during the treatment period compared to baseline

Secondary Outcome Measures
NameTimeMethod
Change in focal clinical seizure frequency during the treatment period compared to pre-treatment baseline: Percent Change, Responder proportionScreening until 5 months after enrollment

Change in focal clinical seizure frequency per 28-day period during the treatment period compared to baseline

Change in frequency of estimated electrographic seizures based on RNS® system data during the treatment period compared to pre-treatment baselineScreening until 5 months after enrollment

Change in the frequency per 28-day period of estimated electrographic seizures based on RNS data during the treatment period compared to baseline

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 countScreening until 5 months after enrollment

Change in long episode-free days during the treatment period compared to pre-treatment baseline

Change in focal clinical seizure-free days during the treatment period compared to pre-treatment baseline: Count, Longest continuous interval, Time until pre-treatment countScreening until 5 months after enrollment

Change in focal clinical seizure-free days 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 baselineDosing until 5 months after dosing

Change in RNS® system electrographic biomarkers other than long episodes during the treatment period compared to pre-treatment baseline

Change in the Seizure Severity Response Questionnaire (SSRQ) during the treatment period compared to pre-treatment baselineScreening until 5 months after enrollment

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.

Count and proportion of responders on the clinical global impression of change (CGIC) scale during the treatment period compared to pre-treatment baselineScreening until 5 months after enrollment

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.

Plasma concentrations of RAP-219Dosing until 5 months after dosing

Analysis of plasma concentrations of RAP-219

Incidence of treatment-emergent adverse events (TEAEs)Dosing until 5 months after enrollment

Analysis of AEs during the treatment and pre-treatment baseline periods

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-219Screening until 5 months after enrollment

Analysis of vital signs, ECGs, CBC, serum chemistries and liver function tests during the treatment and pre-treatment baseline periods

Incidence of participants expressing suicidal ideation assessed with the Columbia-Suicide Severity Rating Scale (C-SSRS)Screening until 5 months after enrollment

Analysis of C-SSRS entries during the treatment and pre-treatment baseline periods

Cognitive function as measured using the Cogstate Digital BatteryScreening until 5 months after enrollment

Analysis of the Cogstate Digital Battery during the treatment and pre-treatment baseline periods

Trial Locations

Locations (12)

Yale University

🇺🇸

New Haven, Connecticut, United States

Consultants in Epilepsy and Neurology, PLLC

🇺🇸

Boise, Idaho, United States

IU Health Neuroscience Center, Goodman Hall

🇺🇸

Indianapolis, Indiana, United States

The University of Kansas Medical Center Epilepsy Clinic

🇺🇸

Kansas City, Kansas, United States

Mayo Clinic

🇺🇸

Rochester, Minnesota, United States

NYU Langone Comprehensive Epilepsy Center

🇺🇸

New York, New York, United States

Cleveland Clinic Foundation

🇺🇸

Cleveland, Ohio, United States

University of Pennsylvania - Department of Neurology

🇺🇸

Philadelphia, Pennsylvania, United States

Thomas Jefferson University

🇺🇸

Philadelphia, Pennsylvania, United States

Vanderbilt University Medical Center

🇺🇸

Nashville, Tennessee, United States

Scroll for more (2 remaining)
Yale University
🇺🇸New Haven, Connecticut, United States

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