E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Epileptic Encephalopathy with Continuous Spike-and-Wave During Sleep (EECSWS) |
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E.1.1.1 | Medical condition in easily understood language |
EECSWS is a syndrome characterized by continuous spike-and-wave during sleep, seizures, and decline in learning abilities, language and cognitive domains. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10077380 |
E.1.2 | Term | Epileptic encephalopathy |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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) |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of multiple doses of NBI-827104 in pediatric subjects with EECSWS |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. |
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E.4 | Principal 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.
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E.5 End points |
E.5.1 | 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. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
•Ratio of SWI during the first hour of NREM sleep, based on centralized evaluation. [Time Frame: Baseline to Week 12] •Caregiver Global Impression of Change (GI-C) and Clinical Global Impression of Change (CGI-C) scores. [Time Frame: Week 6 and Week 12] •Clinical Global Impression of Severity (CGI-S) scores. [Time Frame: Baseline to the end of Week 6 and Week 12]
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
United States |
Denmark |
France |
Germany |
Italy |
Spain |
Switzerland |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 9 |