A Study to Investigate How Effective, Safe and Tolerable the Drug NBI-921352 is When Used With Anti-seizure Medications in Adults With Focal Onset Seizures

Study Overview
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Brief Summary
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This study will evaluate the safety, pharmacokinetics, and efficacy of three different doses of NBI-921352 versus placebo in adults with focal onset seizures

Official Title
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A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Study to Investigate Safety, Tolerability, Pharmacokinetics, and Efficacy of NBI-921352 as Adjunctive Therapy in Adult Subjects With Focal Onset Seizures (FOS)

Conditions
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Focal Onset Seizure, Focal Onset Epilepsy

Intervention / Treatment
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* Drug: NBI-921352
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Capable of providing consent and has completed the written informed consent. Male or female, 18 to 65 years of age, inclusive, with a body mass index (BMI) < 40 kg/m^2. Diagnosis of focal onset epilepsy according to the International League Against Epilepsy (ILAE) Classification of Epilepsy (2017) at least 18 months before screening. History of uncontrolled seizures despite adequate treatment with at least 1 anti-seizure medication (ASM) for at least 18 months prior to screening. Treatment with at least 1 but not more than 4 ASMs for at least 1 month before screening, during the baseline seizure diary data collection, and throughout the duration of the study. Be able to keep accurate seizure diaries. Documented seizure frequency in the baseline seizure diary of ≥8 countable focal seizures during the 8-week seizure baseline period. Key Exclusion Criteria: History of epilepsy with only nonmotor seizures without an observable component, psychogenic nonepileptic seizures, or primary generalized seizures. Presence or previous history of developmental and/or epileptic encephalopathy. Presence of seizure types other than FOS. History of repetitive seizures within the 12-month period preceding study entry where the individual seizures cannot be counted. Status epilepticus within the last 12 months before enrollment. Any suicidal behavior or suicidal ideation of type 4 (active suicidal ideation with some intent to act, without specific plan) or type 5 (active suicidal ideation with specific plan and intent) based on the C-SSRS in the 2 years before screening, a history of suicide attempt in the last 2 years, or more than 1 lifetime suicide attempt. History or presence of any significant medical or surgical condition, lab value, or concomitant medication that would place the subject at increased risk. A known history of clinically concerning cardiac arrhythmia (including long QT syndrome) or prolongation of screening (pre-treatment) QT interval corrected for heart rate. Require use of rescue medication more than once per week. Multiple drug allergies or a severe drug reaction to an ASM(s), including dermatological (eg, Stevens-Johnson syndrome), hematological, or organ toxicity reactions. An implanted responsive neurostimulator system (RNS).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo schedule<br>Participant follows Placebo schedule (13 weeks) | Drug: Placebo<br>* Matching placebo tablets for oral administration<br>|
| Experimental: Dose schedule A<br>Participant follows Dose schedule A (13 weeks) | Drug: NBI-921352<br>* Tablets for oral administration<br>|
| Experimental: Dose schedule B<br>Participant follows Dose schedule B (13 weeks) | Drug: NBI-921352<br>* Tablets for oral administration<br>|
| Experimental: Dose schedule C<br>Participant follows Dose schedule C (13 weeks) | Drug: NBI-921352<br>* Tablets for oral administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Serious Treatment-emergent Adverse Events (TEAEs), TEAEs Leading to Discontinuation of Study Treatment, and Fatal TEAEs |  | Through Week 15 | 
| NBI-921352 exposure-efficacy response relationship, defined as the slope of the relationship between reduction in monthly focal onset seizure frequency and plasma concentration at steady state |  | Baseline to Week 11 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change from Baseline in Monthly Focal Onset Seizure Frequency During the Treatment Period |  | Baseline and Weeks 1 to 11 | 
| Percent Change from Baseline in Monthly Focal Onset Seizure Frequency During the Maintenance period |  | Baseline and Weeks 4 to 11 | 
| Clinical Global Impression of Change (CGIC) Scores at Week 11 |  | Week 11 | 
| Percentage of Participants with a ≥ 50% reduction in monthly (28 days) focal onset seizure frequency during the treatment period |  | Baseline and Weeks 1 to 11 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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partial onset epilepsy, Epilepsy, focal seizure, sodium channel, voltage-gated, alpha subunit, Nav1.6 inhibitor, Antiseizure medication, ASM, Antiepileptic drug, AED, partial seizure