Study to Evaluate NBI-921352 as Adjunctive Therapy in Subjects With SCN8A Developmental and Epileptic Encephalopathy Syndrome (SCN8A-DEE)

Study Overview
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Brief Summary
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The objective of this study is to assess the efficacy, safety, and pharmacokinetics of NBI-921352 as adjunctive therapy for seizures in subjects with SCN8A Developmental and Epileptic Encephalopathy Syndrome (SCN8A-DEE).

Official Title
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A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of NBI-921352 as Adjunctive Therapy in Subjects With SCN8A Developmental and Epileptic Encephalopathy Syndrome (SCN8A-DEE)

Conditions
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SCN8A Developmental and Epileptic Encephalopathy Syndrome

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female 2 to 21 years of age, inclusive. Have a diagnosis of SCN8A-DEE supported by both clinical and genetic findings Have on average at least 1 countable motor seizure per week and not be seizure-free for more than 20 consecutive days Being treated with at least 1 other antiseizure medication (ASM), but no more than 4 ASMs Have failed to achieve seizure freedom with at least 2 ASMs Must be using a nocturnal alerting system or practice consistent with standards of care at the time of screening and continue to use this for the duration of the study Must have an adequate rescue medication regimen per the investigator's judgment in place at the time of screening and for the duration of the study Have a body weight of at least 10 kg The subject's parent/caregiver is able to accurately identify seizure types, especially countable motor seizures (defined as GTCS, tonic, atonic or FOS with noticeable motor component) and is able to complete seizure diary Exclusion Criteria: Have previously been enrolled in this study and received blinded treatment Have participated in an interventional clinical trial < 30 days prior to screening Have symptoms that would be more consistent with another epilepsy disorder such as Dravet syndrome (eg, fever-induced episodes of status epilepticus, frequent myoclonic seizures, worsening on sodium channel blockers, absence seizures with generalized spike-and-wave EEG as the sole seizure type) Are currently receiving cannabinoids or medical marijuana except Epidiolex/Epidyolex, unless approved by the Sponsor Are currently taking systemic steroids (excluding inhaled medication for asthma treatments and intranasal steroids for allergies). If subject has received these medications in the past, must be off these medications for at least 3 months prior to the screening visit and these drugs may not be initiated during the duration of the study. Intermittent steroids to treat nonepilepsy related diseases (such as allergies or dermatological conditions) are not exclusionary Have a history of moderate or severe head trauma or other neurological disorders or systemic medical diseases that are, in the investigator's opinion, likely to affect nervous system functioning Have a clinically significant medical condition or chronic disease, that in the opinion of the investigator would preclude the subject from participating in and completing the study or that could confound interpretation of study outcome Have clinically significant abnormal vital signs at the screening visit as determined by the investigator Have one or more clinical laboratory test values outside the reference range, based on blood samples taken at the screening visit, that are of potential risk to the subject's safety as determined by the investigator Have, at the screening visit, an electrocardiogram (ECG) finding of a corrected QT interval using Fridericia's formula (QTcF) > 450 msec or presence of any significant cardiac abnormality.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 21 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<br>Participants will receive matching placebo for up to 18 weeks. | Drug: Placebo<br>* Administered orally<br>|
| Experimental: NBI-921352<br>In the first 6 weeks participants will receive increasing doses of NBI-921352 (Titration Period) based on weight, followed by 10 weeks of treatment at their final tolerated dose (Maintenance Period) and 2 weeks of treatment with decreasing doses (Taper Period). | Drug: NBI-921352<br>* Administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change from Baseline in 28-day Seizure Frequency for Countable Motor Seizures During the Treatment Period |  | Baseline, Treatment Period: Day 1 to Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with a ≥ 50% Treatment Response for Countable Motor Seizures During the Treatment Period |  | Baseline, Treatment Period: Day 1 to Week 16 | 
| Percentage Change from Baseline in 28-day Seizure Frequency for Countable Motor Seizures During the Maintenance Period |  | Baseline, Maintenance Period: Week 6 to Week 16 | 
| Percentage of Participants with a ≥ 25%, ≥ 75%, or 100% Treatment Response During the Treatment Period |  | Baseline, Treatment Period: Day 1 to Week 16 | 
| Percentage of Participants with a ≥ 25%, ≥ 50%, ≥ 75%, or 100% Treatment Response During the Maintenance Period |  | Baseline, Maintenance Period: Week 6 to Week 16 | 
| Clinical Global Impression of Change (CGIC) |  | Treatment Period: Up to Week 16 | 
| Parent/Caregiver Global Impression of Change (GIC) |  | Treatment Period: Up to Week 16 | 
| Change from Baseline in Clinical Global Impression of Severity (CGIS) |  | Baseline, Treatment Period: Up to Week 16 | 
| Change from Baseline in Parent/Caregiver Global Impression of Severity (GIS) |  | Baseline, Treatment Period: Up to Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epilepsy, Sodium channel, voltage-gated, type VIII, alpha subunit (SCN8A), NaV1.6 inhibitor