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

NCT04625101 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: NBI-827104-CSWS20102020-003141-11
• Study Type: interventional
• Target: 24
• Locations: 6 countries
• Sites: 15

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).

Conditions

Epileptic Encephalopathy; Continuous Spike and Wave During Sleep

Outcome Measures

Primary Outcomes (1)

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

  Baseline to Week 6

Secondary Outcomes (4)

• 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

Study Arms (2)

NBI-827104

EXPERIMENTAL

NBI-827104 administered orally for 13 weeks.

Drug: NBI-827104

Placebo

PLACEBO COMPARATOR

Placebo administered orally for 13 weeks.

Drug: Placebo

Interventions

NBI-827104 DRUG

Triple T-type calcium channel blocker.

NBI-827104

Placebo DRUG

Non-active dosage form.

Placebo

Eligibility Criteria

• Age: 4 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• Pulse therapy such as systemic corticosteroids and IVIG are prohibited for at least 8 weeks prior to screening.
• Planned surgical intervention related to structural abnormalities of the brain from screening through the duration of the study.
• 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.
• Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.

Sponsors & Collaborators

• Neurocrine Biosciences: lead

Study Sites (15)

Neurocrine Clinical Site

Orange, California, 92868, United States

Location

Neurocrine Clinical Site

Aurora, Colorado, 80045, United States

Location

Neurocrine Clinical Site

Washington D.C., District of Columbia, 20010, United States

Location

Neurocrine Clinical Site

Miami, Florida, 33155, United States

Location

Neurocrine Clinical Site

Rochester, Minnesota, 55905, United States

Location

Neurocrine Clinical Site

Durham, North Carolina, 27710, United States

Location

Neurocrine Clinical Site

Cleveland, Ohio, 44195, United States

Location

Neurocrine Clinical Site

Philadelphia, Pennsylvania, 19104, United States

Location

Neurocrine Clinical Site

Calgary, Alberta, T3B 6A8, Canada

Location

Neurocrine Clinical Site

Dianalund, 4293, Denmark

Location

Neurocrine Clinical Site

Barcelona, 08950, Spain

Location

Neurocrine Clinical Site

Madrid, 28034, Spain

Location

Neurocrine Clinical Site

Basel, 4031, Switzerland

Location

Neurocrine Clinical Site

Zurich, 8032, Switzerland

Location

Neurocrine Clinical Site

London, WC1N 3JH, United Kingdom

Location

Results Point of Contact

• Title: Neurocrine Medical Information
• Organization: Neurocrine Biosciences

medinfo@neurocrine.com

+1 877-641-3461

Study Officials

• Clinical Development Lead

  Neurocrine Biosciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2020
• First Posted: November 12, 2020
• Study Start: April 26, 2021
• Primary Completion: August 8, 2022
• Study Completion: October 11, 2022
• Last Updated: September 5, 2025
• Results First Posted: September 5, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (8); GB (1); DK (1); CA (1); ES (2); CH (2)