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

Epileptic Encephalopathy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04625101
• Other study ID #: NBI-827104-CSWS2010
• Secondary ID: 2020-003141-11
• Status: Completed
• Phase: Phase 2
• Start date: April 26, 2021
• Est. completion date: October 11, 2022

Study information

• Verified date: August 2023
• Source: Neurocrine Biosciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: October 11, 2022
• Est. primary completion date: August 8, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years to 12 Years

Eligibility

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.

Related Conditions & MeSH terms

• Brain Diseases
• Continuous Spike and Wave During Sleep
• Epilepsy
• Epileptic Encephalopathy

Intervention

Drug:
• NBI-827104
Triple T-type calcium channel blocker.
• Placebo
Non-active dosage form.

Locations

Country	Name	City	State
Canada	Neurocrine Clinical Site	Calgary	Alberta
Denmark	Neurocrine Clinical Site	Dianalund
Spain	Neurocrine Clinical Site	Barcelona
Spain	Neurocrine Clinical Site	Madrid
Switzerland	Neurocrine Clinical Site	Basel
Switzerland	Neurocrine Clinical Site	Zürich
United Kingdom	Neurocrine Clinical Site	London
United States	Neurocrine Clinical Site	Aurora	Colorado
United States	Neurocrine Clinical Site	Cleveland	Ohio
United States	Neurocrine Clinical Site	Durham	North Carolina
United States	Neurocrine Clinical Site	Miami	Florida
United States	Neurocrine Clinical Site	Orange	California
United States	Neurocrine Clinical Site	Philadelphia	Pennsylvania
United States	Neurocrine Clinical Site	Rochester	Minnesota
United States	Neurocrine Clinical Site	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Neurocrine Biosciences

Countries where clinical trial is conducted

United States,  Canada,  Denmark,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Ratio of SWI during first hour of NREM sleep, based on centralized evaluation.		Baseline to Week 12
Secondary	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
Secondary	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

External Links

•   Study Website - Stillwater Study