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


About this study

The purposes of this research are to assess the effect of NBI-827104, compared with placebo (no active drug), on the overnight epileptiform electroencephalogram (EEG) activity in pediatric participants with epileptic encephalopathy with continuous spike-and-wave during sleep (EECSWS), to evaluate the safety and tolerability of multiple doses of NBI-827104 in pediatric participants with EECSWS, and to evaluate the effect of NBI-827104 on sleep and on cognition in pediatric participants with EECSWS.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Signed informed consent by the parent(s) or legal representative(s) and, if applicable, assent from developmentally capable pediatric subjects. Consent/assent may be done remotely, if allowed per the site’s institutional policy and remote consenting procedures are in place.
  • 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. Determination of potential genetic origin of EECSWS should be based on prior genetic testing results, if available; however, no genetic testing is required for the determination of study eligibility;
    • 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. Subjects with Landau Kleffner Syndrome are eligible to participate in the study if they meet the above specified diagnostic criteria.
  • Have diagnosis of EECSWS confirmed by the DCP.
  • 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 (i.e., menarche). A male subject of childbearing potential is defined as a subject who has reached spermarche. Acceptable methods of birth control for female subjects of childbearing potential are:
    • Combined (estrogen and progestogen containing) hormonal contraception or progestogen-only hormonal contraception associated with the inhibition of ovulation used with an effective nonhormonal methed of contraception (e.g., barrier contraception used with spermicide);
    • Intrauterine hormone-releasing system (IUS) used with an effective nonhormonal method of contraception (e.g., barrier contraception used with spermicide)
    • Intrauterine device (IUD);
    • Bilateral tubal occlusion;
    • Vasectomized partner;
    • True abstinence from sexual intercourse (as the preferred and usual lifestyle.  Note that periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
  • Female subjects of childbearing potential must have a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test result at screening and a negative urine pregnancy test at Day 1. 
  • The acceptable method of contraception for male subjects of childbearing potential is condom with spermicide (cream, spray, foam, gel, suppository, or polymer film).
  • 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 (VNS) and ketogenic diet are not counted as ASMs.
  • Treatment other than ASMs (excluding pulse therapies such as 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.
  • 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.

Exclusion Criteria:

  • Are females who are pregnant or currently breastfeeding.
  • Lennox-Gastaut syndrome, Doose syndrome (epilepsy with myoclonic-atonic seizures), or Dravet syndrome.
  • Have a history of neurodegenerative disorders.
  • Presence of a relevant psychiatric disease interfering with cognitive or behavioral functioning (e.g., depression, schizophrenia, autism spectrum disorders) 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.
  • Life expectancy 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 gammaglutamyl transferase (GGT) levels > 2 × the upper limit of normal (ULN) at screening.
  • Have mild to severe renal impairment as determined by the investigator.
  • Have a history of tonic seizures during sleep.
  • Significant eye disease at screening, which in the opinion of the investigator would affect the subject's ability to safely participate in the study, or findings that would preclude ophthalmic safety examinations.
  • Have received any prohibited medication within 30 days before screening.
  • 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.
  • Have ingested grapefruit or Seville orange (including grapefruit/Seville orange products or juice) from 7 days prior to screening.
  • 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.
  • Tested positive at screening for hepatitis B surface antigen (HBsAg) or hepatitis C virus antibody (HCV-Ab) with confirmatory positive nucleic acid amplification reflex test.
  • Planned surgical intervention related to structural abnormalities of the brain from screening through the duration of the study.
  • 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.
  • Known intolerance or hypersensitivity to NBI-827104, selective T-type calcium channel blockers, or to any of the excipients of the minitablet.
  • 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 participation in the study or compliance with the protocol.

Eligibility last updated 1/26/22. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Anthony Fine, M.D.

Open for enrollment

Contact information:

Vanessa Morrow

(507) 538-0266


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