E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Dravet syndrome or Lennox-Gastaut syndrome |
Syndrome de Dravet ou syndrome de Lennox-Gastaut |
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E.1.1.1 | Medical condition in easily understood language |
Dravet syndrome or Lennox-Gastaut syndrome |
Syndrome de Dravet ou syndrome de Lennox-Gastaut |
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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 | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10048816 |
E.1.2 | Term | Lennox-Gastaut syndrome |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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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 | 10073682 |
E.1.2 | Term | Dravet syndrome |
E.1.2 | System Organ Class | 100000004850 |
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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 long-term safety and tolerability of ZX008 |
Évaluer la sécurité d’emploi et la tolérance à long terme du ZX008 |
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E.2.2 | Secondary objectives of the trial |
To assess the effect of ZX008 on the following effectiveness measures: − Investigator assessment of convulsive seizure response (<25%, ≥25%, ≥50%, ≥75%, or 100% [ie, seizure-free] improvement) − Clinical Global Impression – Improvement (CGI-I) rating, as assessed by the investigator − CGI-I rating, as assessed by the parent/caregiver − Symptomatic CGI-I for cognition, behavior, motor abilities, as assessed by the investigator − Symptomatic CGI-I for cognition, behavior, motor abilities, as assessed by the parent/caregiver |
Évaluer l’effet du ZX008 sur les mesures d’efficacité suivantes : - Évaluation par l’investigateur de la réponse aux crises convulsives (amélioration de < 25 %, ≥ 25 %, ≥ 50 %, ≥ 75 %, ou 100 % [c.-à-d. absence de crises]) - Score à l’échelle d’impression clinique globale – Amélioration (Clinical Global Impression - Improvement, CGI-I), évalué par l’investigateur - Score CGI-I, évalué par le parent/l’aidant - Score CGI-I symptomatique pour la cognition, le comportement, les capacités motrices, évalué par l’investigateur - Score CGI-I symptomatique pour la cognition, le comportement, les capacités motrices, évalué par le parent/l’aidant
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male or nonpregnant, nonlactating female • Satisfactory completion of a core study • Has a rare seizure disorder, such as epileptic encephalopathy and has successfully completed another Zogenix-sponsored clinical trials with ZX008 • Subject's caregiver is willing and able to be compliant with study procedures, visit schedule and study drug accountability |
• Homme ou femme non enceinte, non allaitante • Ayant terminé avec succès l’étude principale • Atteint d’un trouble convulsif rare, comme l’encéphalopathie épileptique, et ayant terminé avec succès un autre essai clinique commandité par Zogenix sur le ZX008 • L’aidant du sujet est disposé et capable de se conformer aux procédures de l’étude, au calendrier des visites et à la comptabilisation du médicament à l’étude |
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E.4 | Principal exclusion criteria |
• Current cardiac valvulopathy or pulmonary hypertension that is clinically significant • Moderate or severe hepatic impairment • Receiving monoamine oxidase inhibitors, serotonin agonists, serotonin antagonists, and serotonin reuptake inhibitors within 14 days of receiving ZX008 |
• Présence d'une valvulopathie cardiaque ou une hypertension pulmonaire cliniquement significative • Présence d’une insuffisance hépatique modérée ou sévère • Administration d’inhibiteurs de la monoamine oxydase, d’agonistes de la sérotonine, d’antagonistes de la sérotonine et d’inhibiteurs du recaptage de la sérotonine dans les 14 jours précédant le traitement par ZX008. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The safety endpoints of the study are: • AEs • Laboratory safety (hematology, chemistry) • Vital signs (blood pressure, heart rate, temperature, and respiratory rate) • Physical examination • Neurological examination • Electrocardiogram (ECGs) • Doppler echocardiogram (ECHOs) • Body weight/height • Chest x-ray (subjects in France and Netherlands only) • Electroencephalogram (EEG) (in Italy only) |
Les critères de sécurité d’emploi de l'étude sont : • événements indésirables (EI) • paramètres biologiques de sécurité (hématologie, chimie) • signes vitaux (tension artérielle, fréquence cardiaque, température et fréquence respiratoire) • examen clinique • examen neurologique, • électrocardiogramme (ECG) • ECHO Doppler • taille/poids corporel • radiographies pulmonaires (en France et aux Pays-Bas uniquement) • électroencéphalogramme (EEG) (en Italie uniquement) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to 36 months |
Jusqu'à 36 mois |
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E.5.2 | Secondary end point(s) |
The effectiveness endpoints of the study are: • CGI-I as assessed by parent/caregiver • CGI-I as assessed by investigator (or designee) • Symptomatic CGI-I for cognition, behavior, motor abilities, as assessed by the investigator (or designee) • Symptomatic CGI-I for cognition, behavior, motor abilities, as assessed by parent/caregiver • Percent improvement in seizure burden as assessed by the investigator (or designee) |
Les critères d'efficacité de l'étude sont : • CGI-I évaluée par le parent/aidant • CGI-I évaluée par l’investigateur (ou son représentant) • CGI-I symptomatique pour la cognition, le comportement, les capacités motrices, évaluée par l’investigateur (ou son représentant) • CGI-I symptomatique pour la cognition, le comportement et les capacités motrices, évaluée par le parent/l’aidant • Pourcentage d’amélioration du fardeau des crises convulsives évalué par l’investigateur (ou son représentant)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Up to 36 months |
Jusqu'à 36 mois |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 43 |
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 |
Australia |
Belgium |
Canada |
Denmark |
France |
Germany |
Italy |
Japan |
Mexico |
Netherlands |
Poland |
Spain |
Sweden |
United Kingdom |
United States |
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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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LVLS |
Dernière visite du dernier patient |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 22 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 22 |