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) |
Encefalopatía epiléptica de puntas-ondas continuas durante el sueño (EEPOCS) |
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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. |
La EEPOCS es un síndrome caracterizado por puntas y ondas continuas durante el sueño, convulsiones y disminución de las capacidades de aprendizaje, el lenguaje y dominios cognitivos. |
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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 evaluate the long-term safety and tolerability of NBI-827104 in pediatric subjects with epileptic encephalopathy with continuous spike-and-wave during sleep (EECSWS) when administered for up to 106 weeks |
Evaluar la seguridad y tolerabilidad a largo plazo del NBI-827104 en sujetos pediátricos con encefalopatía epiléptica con puntas-ondas continuas durante el sueño (EEPOCS) cuando se administra durante un máximo de 106 semanas. |
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E.2.2 | Secondary objectives of the trial |
• To investigate the effect of NBI-827104 on the overnight epileptiform video-electroencephalogram (video-EEG) activity in pediatric subjects with EECSWS. • To investigate the long-term effect of NBI-827104 on the symptoms of EECSWS, including sleep and cognition, in pediatric subjects. |
● Investigar el efecto de NBI-827104 en la actividad del videoelectroencefalograma epileptiforme nocturno (vídeo-EEG) en sujetos pediátricos con EEPOCS. ● Investigar el efecto a largo plazo de NBI-827104 sobre los síntomas de EEPOCS, incluyendo el sueño y las facultades cognitivas, en sujetos pediátricos. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written or oral pediatric assent from the subject deemed capable of providing assent and written informed consent from the subject’s parent(s) or legal guardian(s) in accordance with the governing Institutional Review Board (IRB) or Independent Ethics Committee (IEC) and according to local laws and regulations. Informed consent/assent may be done remotely, if allowed per site and remote consenting procedures are in place. 2. Completed 12 weeks of treatment (3 weeks titration and 9 weeks maintenance) in Study NBI-827104-CSWS2010. 3. 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 (ie, menarche). A male subject of childbearing potential is defined as a subject who has reached spermarche. 4. Willing to comply with all study procedures and restrictions. |
1. El asentimiento pediátrico por escrito u oral del sujeto que se considere capaz de proporcionar el asentimiento y el consentimiento informado por escrito del/de los progenitor(es) o tutor(es) legal(es) del sujeto de acuerdo con el Comité de Ética de la Investigación con medicamentos (CEIm) y de acuerdo con las leyes y normativas locales. El consentimiento/asentimiento informado se puede realizar de forma remota, si lo permite el centro y si se dispone de procedimientos de consentimiento remotos. 2. Haber completado el tratamiento durante 12 semanas (3 semanas de ajuste posológico y 9 semanas de mantenimiento) en el estudio NBI-827104-CSWS2010. 3. Los sujetos en edad fértil deben aceptar el uso de métodos anticonceptivos altamente eficaces de forma sistemática mientras participen en el estudio hasta 90 días después de la última dosis del tratamiento del estudio. Se define como mujer en edad fértil a una paciente que ha tenido su primer ciclo menstrual (es decir, menarquia). Se define como sujeto varón en edad fértil a un paciente que ha alcanzado la espermarquia. 4. Estar dispuesto a cumplir con todos los procedimientos y restricciones del estudio. |
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E.4 | Principal exclusion criteria |
1. Pregnant or breastfeeding. 2. Planned surgical intervention related to structural abnormalities of the brain from screening through the Week 6 Visit. 3. Used any active investigational drug other than NBI-827104 in the context of a clinical study within 30 days or 5 half-lives (whichever is longer) before Day 1 or plans to use such an investigational drug (other than NBI-827104) during the study. 4. It is anticipated that the subject will require treatment with at least 1 of the prohibited concomitant medications or other restrictions during the specified study time frame. 5. Have developed any other disorder for which the treatment takes priority over treatment of EECSWS or is likely to interfere with study treatment or impair treatment compliance. 6. The subject or the subject’s parent(s)/caregiver(s) are, in the investigator’s opinion, unlikely to comply with the protocol, including the requirement to travel to the study sites for study visits, or is unsuitable for any reason. |
1. Estar embarazada o en período de lactancia. 2. Intervención quirúrgica prevista relacionada con anomalías estructurales del cerebro desde la selección hasta la visita de la Semana 6. 3. Uso de cualquier medicamento activo en investigación distinto de NBI-827104 en el contexto de un ensayo clínico en los 30 días o 5 vidas medias (lo que sea más largo) anteriores al Día 1, o previsión de utilizar un medicamento en investigación (distinto al NBI-827104) durante el estudio. 4. Previsión de que el paciente requerirá tratamiento con al menos 1 de los medicamentos concomitantes prohibidos u otras restricciones durante el período de tiempo especificado para el estudio. 5. Haber desarrollado cualquier otro trastorno para el cual el tratamiento tenga prioridad sobre el tratamiento de la EEPOCS o que pueda interferir con el tratamiento del estudio o perjudique el cumplimiento del tratamiento. 6. El sujeto o el/los progenitor(es)/cuidador(es) tiene(n) pocas probabilidades, en opinión del investigador, de cumplir con el protocolo, incluido el requisito de desplazarse a los centros del estudio para las visitas del estudio, o no son adecuados por cualquier motivo. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The occurrence of serious Treatment-emergent adverse event (TEAEs), TEAEs leading to discontinuation of study treatment, and fatal TEAEs |
La aparición de acontecimientos adversos graves surgidos durante el tratamiento (AAST), AAST que conducen a la interrupción del tratamiento del estudio y AAST mortales. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
110 Weeks for subjects who enrol directly and 114 Weeks for subjects who do not enrol directly. |
110 semanas para sujetos que se inscriben directamente y 114 semanas para sujetos que no se inscriben directamente. |
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E.5.2 | Secondary end point(s) |
• Ratio of SWI at Week 26 compared to baseline during the first hour of NREM sleep, based on centralized video-EEG reading. • Change from baseline in CGI-S score at Week 26 • CGI-C and Caregiver GI-C scores at Week 26. |
● Cociente del índice de punta onda en la Semana 26 en comparación con el valor inicial durante la primera hora de sueño NREM basado en la lectura centralizada de vídeo-EEG. ● Cambio con respecto al inicio en la puntuación de la Impresión Global del médico sobre la Gravedad (CGI-S) en la Semana 26. ● Puntuaciones de Impresión global del médico sobre el cambio (CGI-C) e Impresión global del cuidador sobre el cambio (GI-C) en la Semana 26 |
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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 | No |
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) | 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 | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
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 |
Denmark |
France |
Germany |
Spain |
Switzerland |
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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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 | 4 |
E.8.9.1 | In the Member State concerned days | 8 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |