E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Encephalopathy with electrical status epilepticus in sleep, also called ESES syndrome |
Encefalopathie met elektrische status epilepticus in slaap, ook ESES syndroom genoemd |
|
E.1.1.1 | Medical condition in easily understood language |
Sleep epilepsy |
Epilepsie in slaap |
|
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 | LLT |
E.1.2 | Classification code | 10032061 |
E.1.2 | Term | Other forms of epilepsy |
E.1.2 | System Organ Class | 100000004852 |
|
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 compare the effects on cognition of treatment with either corticosteroids or clobazam in children with ESES syndrome |
Het vergelijken van de effecten op cognitie van behandeling met corticosteroiden of clobazam in kinderen met ESES syndroom. |
|
E.2.2 | Secondary objectives of the trial |
- To compare the effects of treatment with corticosteroids or clobazam on sleep induced spike-wave index in children with ESES syndrome.
- To compare the effects of treatment with corticosteroids or clobazam on the frequency of seizures in children with ESES syndrome.
- To compare the side-effects and tolerability of treatment with corticosteroids or clobazam in children with ESES syndrome.
- To compare the effects of treatment with corticosteroids or clobazam in children with ESES syndrome as measured with a VAS score.
- To assess demographic and disease-related predictive factors, including immunological factors, of succes of treatment with corticosteroids or clobazam in children with ESES syndrome.
- To identify a biomarker for disease activity and treatment response. |
- Het vergelijken van de effecten van behandeling met corticosteroiden of clobazam op de piekgolf index in slaap bij kinderen met ESES syndroom, beoordeeld met een EEG.
- Het vergelijken van de effecten van behandeling met corticosteroiden of clobazam op de aanvalsfrequentie bij kinderen met ESES syndroom
- Het vergelijken van de bijwerkingen van en verdraagzaamheid van behandeling met corticosteroiden of clobazam bij kinderen met ESES syndroom
- Het vergelijken van de effecten van behandeling met corticosteroiden of clobazam bij kinderen met het ESES syndroom, gemeten met een VAS score.
- Het bepalen van demografische en ziekte-gerelateerde predictoren, zoals immunologische factoren, voor het succes van behandeling met corticosteroiden of clobazam bij kinderen met ESES syndroom.
- Het bepalen van een biomarker voor ziekteactiviteit en reactie op therapie. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Age 2 to 12 years
•A diagnosis within six months prior to study inclusion (preferentially as soon as possible) of either typical or atypical ESES syndrome (as defined in study protocol)
•No previous treatment with either clobazam or steroids
•No current treatment with carbamazepine, oxcarbazepine, vigabatrin, tiagabine, gabapentin and pregabalin and no treatment with any of these drugs in the previous three months;
•Written informed consent by parents/tutors or legal representatives |
•Leeftijd 2-12 jaar
• Diagnose typisch of atypisch ESES syndroom, zoals beschreven in protocol minder dan 6 maanden voor inclusie (liefst zo recent mogelijk)
•Geen eerdere behandeling met clobazam of steroiden
•Geen huidige behandeling met carbamazepine, oxcarbazepine, vigabatrin, tiagabine, gabapentin en pregabalin en geen behandeling met deze middelen in de voorgaande 3 maanden.
•Geschreven toestemmingsverklaring van ouders of voogd |
|
E.4 | Principal exclusion criteria |
•Patients with a spike wave index during wakefulness of > 50%
•Any condition that, in the investigator’s judgement, contraindicates the use of clobazam or steroids. |
•Patienten met een piekgolf index in waak van meer dan 50%
•Iedere omstandigheid die, naar beoordeling van de onderzoeker, een contra-indicatie vormt voor het gebruik van clobazam of steroiden. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
- Intelligence quotient, or developmental quotient
- Cognitive sumscore
Improvement is defined as significant when improved by at least 75% of the standard deviation. |
- Intelligentie quotient of ontwikkelingsquotient
- Cognitieve somscore
Verbetering is gedefinieerd als significant wanneer toename van tenminste 75% van de standaarddeviatie. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
after six months |
na zes maanden |
|
E.5.2 | Secondary end point(s) |
- Individual absolute test results, and IQ scores;
- Spike wave index during non-REM sleep. Improvement is defined as a rdecrease to less than
25%;
- Seizure frequency. Improvement is defined as a reduction of 50% or more as compared with
baseline;
- Global improvement of functioning assessed with a VAS score (-5 to 5)
- Safety and tolerability, as assessed by the occurrence of serious
adverse events;
- Differences in pro-inflammatory cytokine levels in patients with ESES
who respond to either treatment strategies compared to nonresponders. |
- Individuele absolute testresultaten en IQ-scores.
- Piekgolf index tijdens non-REM slaap. Verbetering is gedefinieerd als daling tot
minder dan 25%
- Aanvalsfrequentie. Verbetering is gedefinieerd als vermindering van 50% of meer ten
opzichte van de uitgangssituatie
- Globale verbetering van functioneren beoordeeld met een VAS score (-5 tot 5)
- Veiligheid en tolerantie, beoordeeld in de vorm van optreden van
ernstige complicaties
- Verschil in pro-inflammatoire cytokine waarden in patienten die wel op
behandeling reageren ten opzichte van patienten die niet op behandeling
reageren. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
after six and 18 months |
Na zes en 18 maanden |
|
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 | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Geblindeerde bepaling van uitkomsten door klinisch neurofysioloog en neuropsycholoog |
Blinded outcome assessment by clinical neurophysiologist and neuropsychologist |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |