Study Evaluating the Efficacy and Safety of RAP-219 in Adult Participants With Focal Seizures (FOCUS 2)

A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of RAP-219 in Adult Participants With Focal Seizures

This is a clinical research study for an investigational drug called RAP-219 in adult participants with focal seizures. This study is being conducted to determine if RAP-219 is safe and effective in reducing focal seizure frequency.

Study Overview

• Status: Not yet recruiting
• Conditions: Epilepsy; Focal Epilepsy; Focal Seizure
• Intervention / Treatment: Drug: RAP-219; Drug: RAP-219; Other: Placebo

Detailed Description

Approximately 312 subjects will be randomized into one of two active treatment groups or placebo in a 1:1:1 randomization ratio (Medium Dosage, Low Dosage and Placebo). After completing the Double-blind Treatment Period, participants will either transition into the RAP-219-FOS-901 long-term safety (open-label extension) study or enter the 8-week post-treatment Follow-up Period of this study.

• Study Type: Interventional
• Enrollment (Estimated): 312
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Rapport Medical; Phone Number: 857 323 9048; Email: RAP-219-FOS@rapportrx.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age 18 - 75
2. BMI 18-45 kg/m2
3. Diagnosis of focal epilepsy for ≥24 months prior to Visit 1
4. Report from at least 1 brain MRI or CT scan and 1 EEG study, each completed within 10 years prior to Visit 1, consistent with focal epilepsy diagnosis
5. Concomitant use of between 1 and 3, inclusive, antiseizure medication(s) ASM(s) as maintenance, not including rescue or pro re nata (PRN) ASMs
6. Ability to keep accurate daily focal seizure records using an e-diary

Exclusion Criteria:

1. Known hypersensitivity or prior exposure to RAP-219.
2. Unstable or uncontrolled serious medical, neurologic (other than focal epilepsy), or psychiatric condition that is ongoing or considered likely to recur
3. Anticipated need for surgery during the study period

4. Medical history of any of the following:

   1. generalized epilepsy
   2. focal preserved consciousness without observable manifestations (also known as focal aware nonmotor) as the participant's only seizure type
   3. psychogenic nonepileptic seizure (PNES)
   4. status epilepticus or seizure clusters (when individual seizures cannot be counted) within 12 months prior to Visit 1 (Day -56).
   5. epilepsy surgery within 12 months prior to Visit 1 (Day -56).
5. Participation in another clinical study of an investigational product within 12 weeks or 5 half-lives of this other investigational product

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Inert comparator matching the active treatment	Other: Placebo; Matching placebo tablets administered orally
Experimental: Active Arm- Medium Dose; RAP-219 daily tablets administered orally	Drug: RAP-219; RAP-219 medium dose tablets administered orally daily; Drug: RAP-219; RAP-219 low dose tablets administered orally daily
Experimental: Active Arm-Low Dose; RAP-219 daily tablets administered orally	Drug: RAP-219; RAP-219 medium dose tablets administered orally daily; Drug: RAP-219; RAP-219 low dose tablets administered orally daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Percent Change in Seizure Frequency	Median percent change in seizure frequency and ≥ 50% seizure frequency reduction responder rates	End of double-blind treatment period (end of week 14) vs Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
≥50% seizure frequency reduction responder rates	Proportion of participants with at least 50% reduction from baseline in seizure frequency after treatment with RAP-219 compared with placebo	End of double-blind treatment period (end of week 14) vs Baseline.
Longest Seizure Free Interval	To evaluate the longest seizure-free interval after treatment with RAP-219 compared with placebo	Across the entire 14-week double-blind treatment period

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
RAP-219 safety and tolerability	incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and AEs leading to discontinuation	From Visit 1 through End of Study, on average Week 22.

Collaborators and Investigators

• Sponsor: Rapport Therapeutics Inc.
• Investigators: Principal Investigator: Vicente Villaneuva, M.D., PhD, Hospital Universitari i Politecnic La Fe, Spain

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): September 1, 2029

Study Registration Dates

• First Submitted: May 11, 2026
• First Submitted That Met QC Criteria: May 11, 2026
• First Posted (Actual): May 18, 2026

Study Record Updates

• Last Update Posted (Actual): May 18, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Focal Preserved Consciousness; Focal Impaired Consciousness
• 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-302

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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