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

Neurocrine Biosciences1 site in 1 country24 target enrollmentApril 26, 2021

ConditionsEpileptic Encephalopathy Continuous Spike and Wave During Sleep

InterventionsNBI-827104 Placebo

DrugsNBI-827104 Placebo

Overview

Phase: Phase 2
Intervention: NBI-827104
Conditions: Epileptic Encephalopathy
Sponsor: Neurocrine Biosciences
Enrollment: 24
Locations: 1
Primary Endpoint: Ratio of Spike-Wave Index (SWI) During First Hour of Nonrapid Eye Movement (NREM) Sleep at Week 6
Status: Completed
Last Updated: 7 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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).

Registry

clinicaltrials.gov

Start Date

April 26, 2021

End Date

October 11, 2022

Last Updated

7 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Neurocrine Biosciences

Responsible Party

Sponsor

Eligibility Criteria

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.

Arms & Interventions

NBI-827104

NBI-827104 administered orally for 13 weeks.

Intervention: NBI-827104

Placebo

Placebo administered orally for 13 weeks.

Intervention: Placebo

Outcomes

Primary Outcomes

Ratio of Spike-Wave Index (SWI) During First Hour of Nonrapid Eye Movement (NREM) Sleep at Week 6

Time Frame: Baseline to Week 6

The ratio of SWI at the end of Week 6 to baseline during the first hour (60 minutes) of NREM sleep based on centralized video-electroencephalograph (EEG) reading using a log base 10 scale. Baseline was defined as the last value measured prior to intake of study treatment on Day 1. SWI was defined as the percentage of seconds with ≥1 spike-wave complex(es) during defined periods of overnight NREM sleep.

Secondary Outcomes

Ratio of SWI During First Hour of NREM Sleep at Week 12(Baseline to Week 12)
Number of Participants Considered as Responders as Assessed by the Caregiver Global Impression of Change (CaGI-C) Score(Week 6 and Week 12)
Number of Participants Considered as Responders as Assessed by the Clinician Global Impression of Change (CGI-C) Score(Week 6 and Week 12)
Number of Participants Considered as Responders as Assessed by the Clinical Global Impression of Severity (CGI-S) Scores(Weeks 6 and 12)