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-ES

Lead Sponsor: eurocrine Biosciences, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

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 described by the following criteria:
•Male and female pediatric subjects aged between 4 and 12 years (inclusive) at screening
•Genetic, structural, or unknown origin of EECSWS
•SWI >50% during the first hour of overnight NREM sleep based on centralized reading
•Focal, multifocal, or generalized spike-and-wave complexes with sleep activation based on investigator assessment and confirmed by central EEG reader
•Cognitive stagnation or regression associated with continuous spike-and-wave during sleep (CSWS) as assessed by clinical evaluation
3. Have diagnosis of EECWS confirmed by the DCP
4. Subjects of childbearing potential must agree to use highly effective birth control methods consistently while participating in the study until 90 days after the last dose of the study treatment. A female subject of childbearing potential is defined as a subject who has had her first menstrual cycle (ie, menarche). A male subject of childbearing potential is defined as a subject who has reached spermarche. Acceptable methods of birth control are:
· Combined (estrogen and progestogen containing) hormonal contraception
· Progestogen-only hormonal contraception
· Intrauterine device (IUD)
· Intrauterine hormone-releasing system (IUS)
· Bilateral tubal occlusion
· Vasectomized partner
· Total abstinence from sexual intercourse (periodic abstinence is not acceptable)
Female subjects of childbearing potential must have a negative serum ß-human chorionic gonadotropin (ß-hCG) pregnancy test result at screening and a negative urine pregnancy test at Day 1.
5. Stable dosage and stable time of intake of at least 1 and up to 2 AEDs excluding systemic corticosteroids, 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 AEDs.
6. Treatment other than AEDs (excluding systemic corticosteroids) must be at a stable dosage from 2 weeks prior to screening and anticipated to be stable from screening until EOS.
7. The subject, if using a VNS, must have had the VNS placed at least 3 months prior to screening with stable settings for =1 month; settings must remain stable throughout the duration of the study
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. Females who are pregnant or currently breastfeeding.
2. Lennox-Gastaut syndrome, Doose syndrome (epilepsy with myoclonic-atonic seizures), or Dravet syndrome.
3. Have a history of neurodegenerative disorders.
4. Have a history of autistic spectrum disorders.
5. Presence of a relevant psychiatric disease interfering with cognitive functioning (eg, depression, schizophrenia) as assessed by the investigator.
6. 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.
7. Life expectancy <12 months due to any concomitant disease.
8. Body weight <10 kg at randomization.
9. Had a medically significant illness within 30 days before Day 1.
10. Have a medically significant abnormality, physical or neurological examination finding, or any other measurements observed during screening or Day 1.
11. Clinically relevant findings in systolic blood pressure (SBP), diastolic blood pressure (DBP), or pulse rate at screening or Day 1.
12. Have an average triplicate ECG corrected QT interval using Fridericia’s formula (QTcF) >450 msec or presence of any significant cardiac abnormality at screening.
13. Clinically relevant findings in clinical laboratory tests (hematology, clinical chemistry, and urinalysis) at screening.
14. Have aspartate aminotransferase (AST), alanine aminotransferase (ALT), or gamma-glutamyl transferase (GGT) levels >2 × the upper limit of normal (ULN) at screening.
15. Have mild to severe renal impairment.
16. Have a history of tonic seizures during sleep.
17. Significant eye disease in the opinion of the ophthalmologist or findings that would preclude ophthalmic safety examinations.
18. Have received any prohibited medication within 30 days before screening (Section 9.7.1).
19. Have taken cannabinoids within 30 days of screening.
20. Systemic corticosteroids are prohibited for at least 8 weeks prior to screening.
21. Have ingested grapefruit or Seville orange (including grapefruit/Seville orange products or juice) from 7 days prior to screening.
22. Have a known or suspected diagnosis of Acquired Immune Deficiency Syndrome (AIDS), or have tested seropositive for human immunodeficiency virus antibody (HIV-Ab) or antigen at screening.
23. Tested positive at screening for hepatitis B surface antigen (HBsAg) or hepatitis C virus antibody (HCV-Ab) with confirmatory positive polymerase chain reaction (PCR) reflex test.
24. Planned surgical intervention related to structural abnormalities of the brain from screening through the duration of the study.
25. Have a significant risk of suicidal or violent behavior. Subjects will be excluded if they have:
•Any lifetime history of suicidal behavior or
•Any lifetime history of suicidal ideation of type 4 (active suicidal ideation with some intent to act, without specific plan) or type 5 (active suicidal ideation with specific plan and intent) based on the Columbia-Suicide Severity Rating Scale (C-SSRS), or based on clinical impression for younger subjects.
26. Known intolerance or hypersensitivity to NBI-827104, selective T-type calcium channel blockers, or to any of the excipients of the minitablet.
27. 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 tre

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 SWI at the end of Week 6 to baseline during the first hour (60 minutes) of NREM sleep based on centralized video-EEG reading, where baseline is defined as the last value measured prior to intake of study treatment on Day 1.;Timepoint(s) of evaluation of this end point: week 6 and week 12

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): •Ratio of SWI at the end of Week 12 to baseline during the first hour (60 minutes) of NREM sleep, based on centralized evaluation. <br>•Caregiver GI-C and CGI-C scores at the end of Weeks 6 and 12. <br>•Change from baseline to the end of Weeks 6 and 12 in CGI-S scores.;Timepoint(s) of evaluation of this end point: week 6 and week 12

Related Trials