E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Rett syndrome (RTT) [typical or atypical] |
Síndrome de Rett (RTT) (Típico o atípico) |
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E.1.1.1 | Medical condition in easily understood language |
Rett syndrome (RTT) [typical or atypical] |
Síndrome de Rett (RTT) (Típico o atípico) |
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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 | 10077709 |
E.1.2 | Term | Rett syndrome |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic 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 of GWP42003-P in patients with RTT |
Evaluar la seguridad a largo plazo GWP42003-P en pacientes con RTT |
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E.2.2 | Secondary objectives of the trial |
•To evaluate the effect of GWP42003-P in measures of disease severity o Rett Syndrome Behaviour Questionnaire (RSBQ) o Clinical Global Impressions - Improvement (CGI-I) o Clinical Global Impressions - Severity (CGI-S) o 9-items Motor Behavioral Assessment (MBA-9) o Children’s Sleep Habits Questionnaire (CSHQ)
Exploratory objectives: •To evaluate the effect of GWP42003-P on caregiver and patient quality of life (QoL) o 36-item Short Form [SF-36] and Child Health Questionnaire Parent Form 50 [CHQ-PF50], respectively • To evaluate the effect of GWP42003-P on health utilization o Hospital Services Use Questionnaire o Caregiver Assessment of Rett Symptoms |
•Evaluar el efecto de GWP42003-P en medidas de gravedad de la enfermedad oCuestionario de conducta en síndrome de Rett (RSBQ) oImpresiones globales clínicas: mejora (CGI-I) oImpresiones globales clínicas: gravedad (CGI-I) oEvaluación de conducta motora de 9 puntos (MBA-9) oCuestionario sobre los hábitos del sueño de los niños |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
For inclusion in the trial, patients must fulfil all of the following criteria: • Patient has completed all scheduled visits of the treatment phase of the RCT, GWND18064, and has transitioned to OLE by the point of RCT follow-up (Visit 11). • Patient (if possessing adequate understanding, in the investigator’s opinion) and/or her parent(s)/legal representative is willing and able to give informed consent/assent for participation in the trial. • Patient and her caregiver are willing and able (in the investigator’s opinion) to comply with all trial requirements (including the completion of all caregiver assessments by the same caregiver throughout the trial). • Patient must have the ability to swallow the investigational medicinal product (IMP) provided as a liquid solution or the ability for the IMP to be delivered via gastrostomy (G) or nasogastric (NG) feeding tube (only G- or NG-tubes made from polyurethane or silicon are allowed). • Patient and/or parent(s)/legal representative is willing to allow the responsible authorities to be notified of participation in the trial, if mandated by local law. • Patient and/or parent(s)/legal representative is willing to allow the patient’s primary care practitioner (if she has one) and consultant (if she has one) to be notified of participation in the trial if the primary care practitioner/consultant is different from the investigator. |
Para ser incluidos en este studio los pacientes Deben cumplir estos criterios •El paciente ha completado todas las visitas programadas de la fase de tratamiento del ensayo aleatorizado controlado, GWND18064 y ha pasado a OLE en el momento del seguimiento de ensayo aleatorizado controlado (Visita 11). •El paciente (si posee el entendimiento adecuado en opinión del investigador) y/o sus padres/ representante legal está dispuesto y puede dar el consentimiento/asentimiento informado para la participación en el ensayo. •El paciente y su cuidador están dispuestos y pueden (en opinión del investigador) cumplir todos los requisitos del ensayo (incluida la conclusión de todas las evaluaciones del cuidador por parte del mismo cuidador a lo largo del ensayo). •El paciente debe tener la capacidad de tragar el medicamento en fase de investigación proporcionado como solución líquida o la capacidad para que se le administre el medicamento en fase de investigación por sonda de alimentación de gastrostomía (G) o nasogástrica (NG) (solo están permitidos las sondas G o NG de poliuretano o silicona). •El paciente y/o padres/representante legal está dispuesto a permitir que se le notifique a las autoridades responsables la participación en el ensayo, si es obligatorio por la ley local. •El paciente y/o padres/representante local está dispuesto a permitir que se notifique al médico de familia del paciente (si tiene uno) y al especialista (si tiene uno) su participación en el ensayo si el médico de familia /especialista es distinto del investigador |
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E.4 | Principal exclusion criteria |
• Patient meets the withdrawal criteria (including clinically significant abnormal laboratory values), in the investigator’s opinion. • Patient met during the RCT the criteria for permanent IMP discontinuation (unless in case of an AE, if AE was not considered related with the IMP; patients that met alanine aminotransferase (ALT)/aspartate aminotransferase (AST) elevations discontinuation criteria must be excluded). • Patient is of childbearing potential, unless willing to ensure that they or their partner use a highly effective method of birth control (e.g., combined [estrogen and progestogen containing] hormonal contraceptiona associated with inhibition of ovulation [oral, intravaginal or transdermal], progestogen-only hormonal contraceptiona associated with inhibition of ovulation [oral, injectable or implantableb] intrauterine devices/hormone-releasing systemsc, bilateral tubal occlusiona, vasectomized partnera, a, sexual abstinenceb during the trial and for 3 months thereafter. • Patient has been previously enrolled and dosed in this trial. • Patient is unwilling to abstain from donation of blood during the trial. |
•El paciente cumple los criterios de retirada (incluidos valores anómalos de laboratorio clínicamente significativos) en opinión del investigador. •El paciente cumple durante el ensayo aleatorizado controlado el criterio para interrupción permanente del medicamento en fase de investigación ( a menos en el caso de AA, si el AA no se consideraba relacionado con el medicamento en fase de investigación; los pacientes que cumplen los criterios de interrupción por elevaciones de alanina aminotransferasa (ALT)/Aspartato aminotransferasa (AST) deben ser excluidos). •La paciente en edad fértil, a menos que esté dispuesta a garantizar que ellas o sus parejas utilizan un método anticonceptivo sumamente eficaz (p. ej. un anticonceptivo hormonal [con estrógenos y progesterona] relacionado con la inhibición de la ovulación [oral, intravaginal o dérmico], anticonceptivo hormonal solo progesterona relacionada con la inhibición de la ovulación [oral, inyectable o implantable ] dispositivos intrauterinos/sistemas liberadoras de hormonas oclusión tubárica bilateral , pareja vasectomizadac, abstinencia sexual durante el ensayo y los 3 meses posteriores al mismo. •El paciente se ha inscrito y se le ha administrado el medicamento previamente en este ensayo. El paciente no está dispuesto a abstenerse de donar sangre durante el ensayo. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety: The long-term safety profile of GWP42003-P will be assessed by evaluating changes in the following, relative to the prerandomization baseline of the RCT: • AEs • Clinical laboratory parameters • Vital signs • Physical examination procedures • 12-lead ECG • Effects on menstruation cycles • Suicidality • Change in growth and development by measurement of height, weight, IGF-1 levels, and Tanner Staging (for patients aged ≥ 7 years or earlier, if clinically indicated by the onset of menarche or other signs of precocious puberty) |
Seguridad: El perfil de seguridad a largo plazo de GWP42003-P será valorado evaluando los cambios en lo siguiente, en relación a la referencia inicial previa a la aleatorización del ensayo aleatorizado controlado: •AA •Parámetros de laboratorio clínico •Constantes vitales •Procedimientos de exploración física •Electrocardiograma (ECG) de 12 derivaciones •Efectos en la menstruación •Tendencias suicidas •Cambio en crecimiento y desarrollo midiendo la altura, peso, niveles del factor 1 de crecimiento parecido a la insulina en suero (IGF-1), y escala de Tanner (para pacientes con edades ≥ 7 años o anteriores, si está indicado clínicamente por la aparición de la menarquía u otros signos de pubertad precoz) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
at all visits |
En todas las visitas |
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E.5.2 | Secondary end point(s) |
The following will be assessed by evaluating changes relative to the prerandomization baseline of the RCT: • RSBQ • CGI-I • CGI-S • MBA-9 • CSHQ |
The following will be assessed by evaluating changes relative to the prerandomization baseline of the RCT: • RSBQ • CGI-I • CGI-S • MBA-9 • CSHQ |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Please refer to Protocol schedule of events table for detailed information |
Por favor consulte la table de eventos del protocol para una información más detallada |
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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 | 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) | 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) | 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.8.2.4 | 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 | 4 |
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 |
Australia |
Canada |
Italy |
Spain |
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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |