RENAISSANCE 2: SPN-817 Phase 2, Double-Blind, Placebo-Controlled Study in Adults with Focal Onset Seizures

Phase 2

Recruiting

• Conditions: Focal Onset Seizures
• Interventions: Drug: SPN-817; Drug: Placebo

• Registration Number: NCT06798896
• Lead Sponsor: Supernus Pharmaceuticals, Inc.

Brief Summary

This is a Phase 2 double-blind, randomized, placebo-controlled, multicenter, parallel-group study to evaluate the efficacy, safety, and tolerability of SPN-817 in adults with focal onset seizures.

Detailed Description

This is a Phase 2 double-blind, randomized, placebo-controlled, multicenter, parallel-group study to evaluate the efficacy, safety, and tolerability of SPN-817 administered as an adjunctive treatment in adults with focal onset seizures that have previously failed at least 2 anti-seizure medication (ASM) regimens. Participants will be taking 1 to 4 ASMs, with at least 4 seizures during the 6-week Screening Period. Following the Screening Period, eligible participants will be randomized 2:1 to SPN-817 (3.0-4.0 mg BID) or placebo and begin the Titration Period (8-10 weeks). In both treatment groups, open-label ondansetron (8 mg oral \[PO\]) will be taken prophylactically approximately 30 minutes before each SM dose (ie, BID) during the first 5 weeks of dose titration as an antiemetic; after the first 5 weeks, ondansetron may be taken as needed as either a preventative or therapeutic antiemetic. After the target dose of 3.0-4.0 mg BID is reached, participants will enter the Maintenance Period (14 weeks). Participants who complete the Maintenance Period will have the opportunity to enroll in a separate open-label study for continued treatment with SPN-817. Participants who do not enroll in the open-label study will undergo a Tapering Period (up to 4 weeks) and a follow-up safety phone call.

Study Timeline

• Study Start: 2024-12-30
• Study First Submitted: 2025-01-16
• Study First Submitted QC: 2025-01-27
• Study First Posted: 2025-01-29
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-03
• Last Update Posted: 2025-02-06
• Primary Completion: 2026-10
• Study Completion: 2026-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 258

Inclusion Criteria

1. Diagnosis of treatment-resistant focal epilepsy as adjudicated by the Epilepsy Study Consortium, Inc (ESCI);
2. Failed to achieve sustained seizure freedom after ≥2 tolerated, appropriately chosen, and adequately dosed ASM drug schedules;
3. Able to keep accurate Seizure eDiaries (with the aid of a caregiver as needed);
4. Has a body mass index (BMI) between 18.0 and 40.0 kg/m2;
5. Treatment with a stable dose of 1 to 4 current ASMs for ≥28 days prior to screening. If following a diet plan along with the ASM, the participant should have been on a stable diet plan for at least 1 month prior to Visit 1. The diet plan should be maintained throughout the duration of the study;
6. At least 4 clinically observable focal onset seizures accepted by the ESCI prior to the first dose of SM (during the days of baseline Seizure eDiary data collection) and no more than a consecutive 21-day period that was seizure free. To be eligible for the study, participants must comply with the eDiary on at least 90% of the days of baseline data collection;

Exclusion Criteria

1. Has taken huperzine A within the past 6 months;
2. Prior diagnosis of combined focal and generalized epilepsy syndrome as evidenced by severe developmental delay and multiple seizure types and confirmed by electroencephalography (EEG) (eg, Lennox-Gastaut syndrome). Participants should also be excluded in case of nondiagnostic information;
3. History of or current nonepileptic events that could be confused by the participant and/or study staff as epileptic seizures;
4. Only has seizures that are difficult to count; for example, seizures that are not clinically observable;
5. History of uncountable seizures, such as seizures that happen in a cluster that are too rapid to be counted individually;
6. History of status epilepticus within 6 months prior to screening;
7. Vagus nerve stimulation, deep brain stimulation, responsive neurostimulator system, or other neurostimulation for epilepsy device implanted or activated within 1 year prior to screening; or epilepsy surgery within 1 year prior to screening. Stimulation parameters for devices must have been stable for at least 3 months prior to Screening. Battery change for any epilepsy devices will be allowed; however, stimulation parameters must remain stable during the duration of the study;
8. Any suicidal behavior or suicidal ideation related to item 4 (active suicidal ideation with some intent to act, without specific plan) or item 5 (active suicidal ideation with specific plan and intent) based on the C-SSRS assessment in the 1 year before screening; a suicide attempt in the last 2 years before screening; or more than 1 lifetime suicide attempt;
9. Chronic concomitant therapy with non-ASMs that are cholinergic or anticholinergic.
10. History of >2 allergic reactions to an ASM or 1 serious hypersensitivity reaction to an ASM;
11. Any other reason which, in the opinion of the Investigator, would prevent the participant from taking part in the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SPN-817	SPN-817	SPN-817, bid
Placebo	Placebo	Placebo, bid

Primary Outcome Measures

Name	Time	Method
Percent change (PCH) from baseline in focal onset seizure frequency per 28 days over the Maintenance Period	Baseline and Maintenance Period (Maintenance Week 1-14)	Percent change in 28-day frequency of focal seizures during the 14 week Maintenance Period relative to baseline

Secondary Outcome Measures

Name	Time	Method
Proportion of subjects experiencing ≥50% reduction in focal seizure frequency per 28 days from baseline	Baseline through Titration Week 1 up to Week 10 and Maintenance Weeks 1-14	Greater than or equal to 50% reduction in 28-day frequency of focal seizures during the Treatment Period (Titration Period + Maintenance Period) relative to baseline.
PCH from baseline in focal onset seizure frequency per 28 days over the entire Treatment Period	Baseline through Titration Week 1 up to Week 10 and Maintenance Weeks 1-14	Percent change in 28-day frequency of focal seizures during the entire Treatment Period (Titration Period + Maintenance Period) relative to baseline
Longest seizure-free interval over the entire Treatment Period	Baseline through Titration Week 1 up to Week 10 and Maintenance Weeks 1-14	The longest intervals in days between two seizures during the entire Treatment Period.
Incidence of adverse events (AEs)	Baseline through Titration Week 1 up to Week 10, Maintenance Weeks 1-14, and Tapering Period up to Week 4	The percent of subjects who took at least one dose of SPN-817 and reported at least one adverse event during SPN-817 treatment.

Trial Locations

Locations (1)

Medsol Clinical Research Center; 🇺🇸 Port Charlotte, Florida, United States