Clinical trial NCT06798896: RENAISSANCE 2: SPN-817 Phase 2, Double-Blind, Placebo-Controlled Study in Adults with Focal Onset Seizures
Official title: RENAISSANCE 2: a 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Focal Onset Seizures
Keywords: focal seizures
focal epilepsy
Phase 2
anti-seizure medication
Lead sponsor: Supernus Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2025-01-29
Enrollment: 258
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percent change (PCH) from baseline in focal onset seizure frequency per 28 days over the Maintenance Period
timeFrame: Baseline and Maintenance Period (Maintenance Week 1-14)
Secondary outcomes:
measure: Proportion of subjects experiencing ≥50% reduction in focal seizure frequency per 28 days from baseline
timeFrame: Baseline and Maintenance Period (Maintenance Week 1-14)
measure: PCH from baseline in focal onset seizure frequency per 28 days over the entire Treatment Period
timeFrame: Baseline through Titration Week 1 up to Week 10 and Maintenance Weeks 1-14
measure: Proportion of subjects experiencing ≥50% reduction in focal seizure frequency per 28 days from baseline
timeFrame: Baseline through Titration Week 1 up to Week 10 and Maintenance Weeks 1-14
measure: Longest seizure-free interval over the entire Treatment Period
timeFrame: Baseline through Titration Week 1 up to Week 10 and Maintenance Weeks 1-14
measure: Incidence of adverse events (AEs)
timeFrame: Baseline through Titration Week 1 up to Week 10, Maintenance Weeks 1-14, and Tapering Period up to Week 4
Other outcomes:
Locations:
city: Port Charlotte
country: United States
facility: Medsol Clinical Research Center
state: Florida
Study officials:
affiliation: Supernus Pharmaceuticals, Inc.
name: Himanshu Upadhyaya, MBBS, MS, MBA
role: STUDY_DIRECTOR
References: