Efficacy, Safety, Tolerability, and Pharmacokinetics of NBI-827104 in Pediatric Subjects With Epileptic Encephalopathy With Continuous Spike-and-Wave During Sleep

Study Overview
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Brief Summary
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This is a phase 2, double-blind study to assess the efficacy, safety, tolerability, and pharmacokinetics of NBI-827104 when administered once daily for 13 weeks in pediatric subjects with Epileptic Encephalopathy with Continuous Spike-and-Wave During Sleep (EECSWS).

Official Title
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Phase 2 Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of NBI-827104 in Pediatric Subjects With Epileptic Encephalopathy With Continuous Spike-and-Wave During Sleep

Conditions
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Epileptic Encephalopathy, Continuous Spike and Wave During Sleep

Intervention / Treatment
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* Drug: NBI-827104
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent by the parent(s) or legal representative(s) and, if applicable, assent from developmentally capable pediatric subjects. Diagnosis of EECSWS. Have diagnosis of EECSWS confirmed by the Diagnosis Confirmation Panel (DCP). Stable dosage and stable time of intake of at least 1 and up to 3 antiseizure medications (ASMs) excluding systemic corticosteroids and intravenous immunoglobulin (IVIG), from 4 weeks prior to screening and anticipated to be stable from screening until end of study (EOS). Vagal nerve stimulator (VNS) and ketogenic diet are not counted as ASMs. Treatment other than ASMs (excluding systemic corticosteroids and IVIG) must be at a stable dosage from 2 weeks prior to screening and anticipated to be stable from screening until EOS. Exclusion Criteria: Lennox-Gastaut syndrome, Doose syndrome (epilepsy with myoclonic-atonic seizures), or Dravet syndrome. Presence of a relevant psychiatric disease interfering with cognitive or behavioral functioning (eg, depression, schizophrenia, autism spectrum disorder) unless associated with the EECSWS diagnosis as assessed by the investigator. Presence of relevant neurological disorders other than EECSWS and its underlying conditions as judged by the investigator. Symptomatic conditions underlying EECSWS (eg, neonatal strokes) have to be stable for at least 1 year prior to screening. Body weight <10 kg at randomization. Clinically relevant findings in systolic blood pressure (SBP), diastolic blood pressure (DBP), or pulse rate at screening or Day 1 as determined by the investigator. Have an average triplicate ECG corrected QT interval using Fridericia's formula (QTcF) >450 msec or presence of any significant cardiac abnormality at screening. Clinically relevant findings in clinical laboratory tests (hematology, clinical chemistry including thyroid function parameters, and urinalysis) at screening as determined by the investigator. Have aspartate aminotransferase (AST), alanine aminotransferase (ALT), or gamma-glutamyl transferase (GGT) levels >2 × the upper limit of normal (ULN) at screening. Have mild to severe renal impairment as determined by the investigator. Have taken cannabinoids, excluding Epidiolex®/Epidyolex®, within 30 days of screening. Pulse therapy such as systemic corticosteroids and IVIG are prohibited for at least 8 weeks prior to screening. Planned surgical intervention related to structural abnormalities of the brain from screening through the duration of the study. Have received any other investigational drug within 30 days or 5 half-lives (if known), whichever is longer, of Day 1 or plan to use an investigational drug (other than the study treatment) during the study. Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 12 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 |
| --- | --- |
| Experimental: NBI-827104<br>NBI-827104 administered orally for 13 weeks. | Drug: NBI-827104<br>* Triple T-type calcium channel blocker.<br>|
| Placebo Comparator: Placebo<br>Placebo administered orally for 13 weeks. | Drug: Placebo<br>* Non-active dosage form.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ratio of spike-wave index (SWI) during first hour of nonrapid eye movement (NREM) sleep based on centralized video-EEG reading. |  | Baseline to Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ratio of SWI during first hour of NREM sleep, based on centralized evaluation. |  | Baseline to Week 12 | 
| Caregiver Global Impression of Change (GI-C) and Clinical Global Impression of Change (CGI-C) scores. | The Caregiver GI-C is a 7-point scale that rates the overall global improvement since the initiation of study drug dosing, ranging from 1 (very much improved) to 7 (very much worse), as assessed by the caregiver. The CGI-C is a 7-point scale that rates the overall global improvement since the initiation of study drug dosing, ranging from 1 (very much improved) to 7 (very much worse), as assessed by the clinician. | Week 6 and Week 12 | 
| Clinical Global Impression of Severity (CGI-S) scores. | The CGI-S rates overall symptom severity on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill patients), as assessed by the investigator. | Baseline to the end of Week 6 and Week 12 |