E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Childhood absence epilepsy and juvenile absence epilepsy |
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E.1.1.1 | Medical condition in easily understood language |
Absence seizures are a type of seizure that involves brief, sudden lapses in attention. Symptoms include staring into space for a few seconds, lip smacking, eyelid fluttering, and chewing motions.
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Investigate the efficacy of brivaracetam monotherapy in study participants 2 to 25 years of age inclusive, with childhood absence epilepsy (CAE) or juvenile absence epilepsy (JAE) |
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E.2.2 | Secondary objectives of the trial |
Evaluate the safety and tolerability of brivaracetam monotherapy in study participants 2 to 25 years of age inclusive, with CAE or JAE |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Study participant is 2 to 25 years of age inclusive, at the time of signing the informed consent. No study participants from 2 to <4 years of age will be included in Stage 1. -Study participant is diagnosed with either childhood absence epilepsy (CAE) or juvenile absence epilepsy (JAE) as defined by the International League Against Epilepsy (ILAE) criteria -Study participants 2 to <4 years of age and participants who had onset of absence seizures at an age younger than 4 years must have a negative glucose transporter type 1 deficiency syndrome (GLUT1DS) genetic test -Study participant is untreated with antiepileptic drugs (AEDs) or pretreated for absence seizures with a maximum of 2 historical AEDs, but without AED treatment for a period of at least 5 half-lives of the AED before randomization into this study. The UCB study physician should be consulted if in doubt -Study participant has electroencephalogram (EEG) evidence of bilateral synchronous, symmetric generalized paroxysmal spike waves (2.5-6 hertz) with normal background activity and with at least 1 electrographically recorded seizure lasting 3 seconds or more on a 1-hour EEG with hyperventilation (HV) while awake at Visit 1 (V1), or on a historical EEG up to 12 weeks before enrollment -Study participant has a history of clinically evident absence seizures occurring on at least 3 days per week in the 2 weeks prior to enrollment -Study participant is without treatment with psychoactive drugs or on a stable dose for at least 2 weeks prior to randomization -Study participant has normal neurological examination, head size, development and cognition -Body weight is ≥9 kg -Male and female a) A sexually active male study participant must agree to use contraception during the treatment period and for at least 2 days, corresponding to the time needed to eliminate study treatment, after the last dose of study treatment and refrain from donating sperm during this period b) A female study participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: The study participant is premenarchial OR A woman of childbearing potential (WOCBP) who agrees to follow the contraceptive guidance during the treatment period and for at least 2 days after the last dose of study treatment, corresponding to the time needed to eliminate study treatment - Study participant is capable of and provides consent/assent, and the study participant’s parent/legal representative/caregiver provides signed informed consent for minor study participants, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol |
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E.4 | Principal exclusion criteria |
-Study participant has a history of nonfebrile seizures other than absence seizures (eg, generalized tonic-clonic seizures or myoclonic seizures) -Study participant has a history of absence status epilepticus -Study participant has a history or presence of paroxysmal nonepileptic seizures -Study participant has a clinically relevant electrocardiogram (ECG) abnormality in the opinion of the Principal Investigator -Study participant has hepatic impairment (Child Pugh Score A, B, or C) based on the Investigator’s assessment -Study participant has a history of major psychiatric disease or any clinically significant medical condition that would preclude appropriate study participation -Study participant has active suicidal ideation prior to study entry as indicated by a positive response (“Yes”) to either Question 4 or Question 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS; for study participants 6 years or older) or clinical judgement (for study participants younger than 6 years). The study participant should be referred immediately to a Mental Healthcare Professional -Study participant has a lifetime history of suicide attempt (including an active attempt, interrupted attempt, or aborted attempt). The study participant should be immediately evaluated by a Mental Healthcare Professional to address safety concerns -Study participant with known fructose intolerance or hypersensitivity of any of the ingredients in brivaracetam oral solution -Study participant has end-stage kidney disease requiring dialysis -Concomitant use of rifampicin/rifampin; prior use must have been stopped at least 2 months before randomization -Concomitant use of strong CYP2C19 inhibitors like fluconazole, fluoxetine and fluvoxamine, prior use must have been stopped at least 1 week before randomization -Study participant has participated in another study of an investigational medicinal product (IMP; and/or an investigational device) within the previous 30 days prior to informed consent -Study participant has clinical or EEG findings not consistent with a diagnosis of childhood absence epilepsy (CAE) or juvenile absence epilepsy (JAE) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of participants who met the criteria for absence seizure freedom within 4 days prior to or during the 24-hour ambulatory electroencephalogram (EEG) at Day 14
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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) |
1. Percentage of participants who met the criteria for absence seizure freedom during the randomized withdrawal (RDW) period as determined by electroencephalogram (EEG) 2. Percent change from Baseline to Day 14 in number of absence seizures on 24-hour ambulatory electroencephalogram (EEG) 3. Percentage of participants who met the criteria for absence seizure freedom based on diary during the 4 days prior to the visit at Day 14 4. Percentage of participants who met the criteria for absence seizure freedom on 24-hour ambulatory electroencephalogram (EEG) at Week 12 5. Percentage of participants who met the criteria for absence seizure freedom based on diary during the 4 days prior to the visit at Week 12 6. Percentage of participants with treatment-emergent adverse events (TEAEs) during the study 7. Percentage of participants with treatment-emergent adverse events (TEAEs) leading to discontinuation of study treatment 8. Percentage of participants with serious adverse events (SAEs) during the study 9. Percentage of participants with drug-related treatment-emergent adverse events (TEAEs) during the study |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. From Week 13 to Week 17 2. From Baseline to Day 14 3. Day 14 4.; 5. Week 12 6.; 9.: From Day 1 until End of Safety Follow-Up (up to Week 23) 7. From Day 1 until End of Down Titration Period (up to Week 21) 8. From Screening Period (Day -14 to Day -2) until End of Safety Follow-Up (up to Week 23) |
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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 | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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) | Yes |
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 | 8 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
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 |
Ukraine |
Australia |
Georgia |
United States |
Belgium |
Italy |
Poland |
Romania |
Slovakia |
Spain |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 25 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 25 |