A 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

Phase 1

Conditions: Epileptic Encephalopathy with Continuous Spike-and-Wave During Sleep (EECSWS)
MedDRA version: 20.0Level: PTClassification code 10077380Term: Epileptic encephalopathySystem Organ Class: 10029205 - Nervous system disorders
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Registration Number: EUCTR2020-003141-11-DE

Lead Sponsor: eurocrine Biosciences, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: A

Sex: All

Target Recruitment: 24

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 EECWS confirmed by the Diagnosis Confirmation Panel (DCP).
4. Stable dosage and stable time of intake of at least 1 and up to 3 ASMs, excluding pulse therapies such as 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 or (VNS) and ketogenic diet are not counted as ASMs
5. Treatment other than ASMs (excluding pulse therapies such as systemic corticosteroids and IVG) must be at a stable dosage from 2 weeks prior to screening and anticipated to be stable from screening until EOS.
Are the trial subjects under 18? yes
Number of subjects for this age range: 24
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Lennox-Gastaut syndrome, Doose syndrome (epilepsy with myoclonicatonic seizures), or Dravet syndrome.
2.Presence of a relevant psychiatric disease interfering with cognitive or behavioral functioning (eg, depression, schizophrenia, autism spectrum disorders) 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 participation in the study or compliance with the protocol.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the effect of NBI-827104 on the overnight epileptiform video-electroencephalogram (video-EEG) activity in pediatric subjects with epileptic encephalopathy with continuous spike-and-wave during sleep (EECSWS);Secondary Objective: To evaluate the safety and tolerability of multiple doses of NBI-827104 in pediatric subjects with EECSWS ;Primary end point(s): Ratio of spike-wave index (SWI) during first hour of nonrapid eye movement (NREM) sleep based on centralized video-EEG reading.;Timepoint(s) of evaluation of this end point: Baseline to week 6

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): •Ratio of SWI during the first hour of NREM sleep, based on centralized evaluation. [Time Frame: Baseline to Week 12]<br>•Caregiver Global Impression of Change (GI-C) and Clinical Global Impression of Change (CGI-C) scores. [Time Frame: Week 6 and Week 12]<br>•Clinical Global Impression of Severity (CGI-S) scores. [Time Frame: Baseline to the end of Week 6 and Week 12]<br>;Timepoint(s) of evaluation of this end point: week 6 and week 12

Related Trials