Clinical trial NCT04625101: Efficacy, Safety, Tolerability, and Pharmacokinetics of NBI-827104 in Pediatric Subjects With Epileptic Encephalopathy With Continuous Spike-and-Wave During Sleep
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Epileptic Encephalopathy
Continuous Spike and Wave During Sleep
Lead sponsor: Neurocrine Biosciences
Sponsor class: INDUSTRY
First posted: 2020-11-12
Enrollment: 24
Sex: ALL
Minimum age (years): 4
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

1. Signed informed consent by the parent(s) or legal representative(s) and, if applicable, assent from developmentally capable pediatric subjects.
2. Diagnosis of EECSWS.
3. Have diagnosis of EECSWS confirmed by the Diagnosis Confirmation Panel (DCP).
4. 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.
5. 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:

1. Lennox-Gastaut syndrome, Doose syndrome (epilepsy with myoclonic-atonic seizures), or Dravet syndrome.
2. 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.
3. 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.
4. Body weight \<10 kg at randomization.
5. 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.
6. Have an average triplicate ECG corrected QT interval using Fridericia's formula (QTcF) \>450 msec or presence of any significant cardiac abnormality at screening.
7. Clinically relevant findings in clinical laboratory tests (hematology, clinical chemistry including thyroid function parameters, and urinalysis) at screening as determined by the investigator.
8. Have aspartate aminotransferase (AST), alanine aminotransferase (ALT), or gamma-glutamyl transferase (GGT) levels \>2 × the upper limit of normal (ULN) at screening.
9. Have mild to severe renal impairment as determined by the investigator.
10. Have taken cannabinoids, excluding Epidiolex®/Epidyolex®, within 30 days of screening.
11. Pulse therapy such as systemic corticosteroids and IVIG are prohibited for at least 8 weeks prior to screening.
12. Planned surgical intervention related to structural abnormalities of the brain from screening through the duration of the study.
13. 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.
14. Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.

Primary outcomes:
measure: Ratio of spike-wave index (SWI) during first hour of nonrapid eye movement (NREM) sleep based on centralized video-EEG reading.
timeFrame: Baseline to Week 6
Secondary outcomes:
measure: Ratio of SWI during first hour of NREM sleep, based on centralized evaluation.
timeFrame: Baseline to Week 12
measure: Caregiver Global Impression of Change (GI-C) and Clinical Global Impression of Change (CGI-C) scores.
timeFrame: Week 6 and Week 12
measure: Clinical Global Impression of Severity (CGI-S) scores.
timeFrame: Baseline to the end of Week 6 and Week 12
Other outcomes:
Locations:
city: Orange
country: United States
facility: Neurocrine Clinical Site
state: California
city: Aurora
country: United States
facility: Neurocrine Clinical Site
state: Colorado
city: Washington
country: United States
facility: Neurocrine Clinical Site
state: District of Columbia
city: Miami
country: United States
facility: Neurocrine Clinical Site
state: Florida
city: Rochester
country: United States
facility: Neurocrine Clinical Site
state: Minnesota
city: Durham
country: United States
facility: Neurocrine Clinical Site
state: North Carolina
city: Cleveland
country: United States
facility: Neurocrine Clinical Site
state: Ohio
city: Philadelphia
country: United States
facility: Neurocrine Clinical Site
state: Pennsylvania
city: Calgary
country: Canada
facility: Neurocrine Clinical Site
state: Alberta
city: Dianalund
country: Denmark
facility: Neurocrine Clinical Site
city: Barcelona
country: Spain
facility: Neurocrine Clinical Site
city: Madrid
country: Spain
facility: Neurocrine Clinical Site
city: Basel
country: Switzerland
facility: Neurocrine Clinical Site
city: Zürich
country: Switzerland
facility: Neurocrine Clinical Site
city: London
country: United Kingdom
facility: Neurocrine Clinical Site
Study officials:
affiliation: Neurocrine Biosciences
name: Clinical Development Lead
role: STUDY_DIRECTOR
References: