E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Fragile X Syndrome |
Síndrome X Frágil |
|
E.1.1.1 | Medical condition in easily understood language |
Fragile X Syndrome |
Síndrome X Frágil |
|
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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10017324 |
E.1.2 | Term | Fragile X syndrome |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
|
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 safety and tolerability of AFQ056 in adult patients with FXS as assessed by: -Incidence and severity of adverse events and serious adverse events -Changes in vital signs, laboratory assessments, and ECGs |
Evaluar la seguridad y tolerabilidad de AFQ056 en pacientes adultos con SXF según la evaluación de: -La incidencia y gravedad de los acontecimientos adversos y acontecimientos adversos graves. -Cambios en las constantes vitales, pruebas analíticas y ECG. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of AFQ056 treatment in both Fully Methylated and Partially Methylated patients with FXS as assessed by: -Change from baseline in the Aberrant Behavior Checklist ? Community edition (ABC-C) total score and subscale scores -Rating of global improvement of symptoms in Fragile X patients using the Clinical Global Impression - Improvement (CGI-I) scale. -Change from baseline in the Repetitive Behavior Symptom ? Research version (RBS) total score and subscale scores |
Evaluar la eficacia del tratamiento con AFQ056 en pacientes con el gen TM (totalmente metilado) y PM (parcialmente metilado) con SXF según la evaluación de: -Cambio respecto a la visita basal en la puntuación total y puntuaciones de las subescalas en la Lista de de Conductas Aberrantes ? Edición Comunidad (ABC-C). -Valoración de la mejoría global de los síntomas en pacientes con síndrome X frágil mediante la escala Impresión Clínica Global-Mejoría (ICG-M). -Cambio respecto a la visita basal en la puntuación total y puntuaciones de las subescalas de los Síntomas de Conductas Repetitivas - Versión Investigación (RBS). |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Must have been enrolled in Studies CAFQ056A2204 or CAFQ056A2212 - Has a caregiver who spends, on average, at least 6 hours per day with the patient , who is willing to and capable of supervising treatment, providing input into efficacy and safety assessments, and accompanying the patient to study visits. Other protocol-defined inclusion criteria may apply |
- Deben haber participado en el estudio CAFQ056A2212 o CAFQ056A2204.
- Tener un cuidador que pase, como media, al menos seis horas al día con el paciente, que desee y sea capaz de supervisar el tratamiento facilitando información en las evaluaciones de eficacia y seguridad y que acompañe al paciente a las visitas del estudio.
Ver criterios de inclusión página del protocolo número 19. |
|
E.4 | Principal exclusion criteria |
- Any advanced, severe or unstable disease - History of severe self-injurious behavior - History of uncontrolled seizure disorder or resistant to therapy within the past 2 years (Patients who are clinically stable under anti-convulsant therapy for the past 2 years are not excluded) - History of clinically significant allergies requiring hospitalization or non-inhaled corticosteroid therapy (asthma, anaphylaxis, etc.) - Any treatment regimen, including psychotropic and/or anticonvulsant therapy that has not been stable for ? 6 weeks prior to randomization - Current treatment with more than two psychoactive medications, excluding medication used specifically for seizure control - Using (or used within 6 weeks before randomization) concomitant medications that are potent inhibitors or inducers of CYP3A4 - Using glutamatergic agents (riluzole, memantine, etc.) or lithium within 6 weeks of randomization - Planning to initiate or change pharmacologic or non-pharmacologic interventions during the course of the study Other protocol-defined exclusion criteria may apply |
1. Cualquier enfermedad avanzada, severa o inestable que pueda interferir con las evaluaciones de las variables principales o secundarias del estudio o que pueda poner al paciente en un riesgo en particular. 2. Antecedentes patológicos de anomalías clínicamente significativas en el ECG o QTcF > 450 msec en los hombres y > 470 msec en las mujeres en la selección (grupo 2) o la basal (grupo 1). 3. Valores del laboratorio en la selección que incluyen AST, ALT, GGT, bilirrubina total o creatinina ? 1,5 X LSN (límite superior normal); se permiten niveles de bilirrubina total o no conjugada (indirecta) de hasta 3 X LSN del laboratorio central si el paciente tiene un diagnóstico de síndrome de Gilbert. 4. Antecedentes de intervención mayor o acontecimiento medico mayor que requiera hospitalización o intervención mayor durante los últimos 6 meses, salvo que el paciente esté totalmente recuperado o se considere clínicamente estable. 5. Antecedentes y/o presencia de esquizofrenia, enfermedad bipolar, psicosis, estados de confusión y/o alucinaciones repetidas según los criterios del Manual diagnóstico y estadístico de los trastornos mentales (DSM-IV). 6. Antecedentes de conducta suicida o considerada de un alto riesgo suicida. 7. Antecedentes de conducta autolesiva severa. 8. Antecedentes de trastorno convulsivo no controlado o resistente al tratamiento durante los 2 últimos años (los pacientes clínicamente estables con tratamiento anticonvulsivo durante los dos últimos años no están excluidos). 9. Antecedentes de alergias clínicamente significativas que precisen hospitalización o tratamiento con corticosteroides no inhalados (asma, anafilaxia, etc.).
Ver criterios de exclusión página del protocolo número 22. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Evaluation of the safety and tolerability of AFQ056 in adult patients with FXS as assessed by: Incidence and severity of adverse events and serious adverse events and change in vital signs, laboratory assessments, and ECGs. |
Evaluar la seguridad y tolerabilidad de AFQ056 en pacientes adultos con SXF según la evaluación de: -La incidencia y gravedad de los acontecimientos adversos y acontecimientos adversos graves. -Cambios en las constantes vitales, pruebas analíticas y ECG. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
At multiple visits: weekly during first month and monthly afterwards Time Frame: 9 months |
At multiple visits: weekly during first month and monthly afterwards
Periodo 9 meses En varias visitas: Semanales durante el primer mes, y mensuales después. |
|
E.5.2 | Secondary end point(s) |
- Aberrant Behavour Checklist - Community Edition (ABC-C): Total score and subscales - Clinical Global Impression - Improvement (CGI-I) scale - Repetitive Behaviour Symptom-Research version (RBS-R) - total score and subscale scores |
- Puntuación total de la ABC-C y en las subescalas - Mejora global de los síntomas del Síndrome X Frágil usando la escala ICG-M (Impresión clínica global - Mejoría) - Cambios en la puntuación total de la RBS-R y las puntuaciones de las subescalas. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
- ABC-C: Week 4, week 12, week 24, week 36 - CGI - I: Week 4, week 12, week 24, 36 week - RBS: Week 4, week 36 Time frame: 9 months for each |
- ABC-C: Semana 4, Semana 12, Semana 24, Semana 36 - CGI - I: Semana 4, Semana 12, Semana 24, Semana 36 - RBS: Semana 4, Semana 36
Periodo: 9 meses cada una |
|
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability |
Tolerabilidad |
|
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.8.2.4 | Number of treatment arms in the trial | 1 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 |
Denmark |
France |
Germany |
Italy |
Spain |
Switzerland |
United Kingdom |
United States |
|
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
|
last visit of last subject |
Última visita último paciente |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 14 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 14 |
E.8.9.2 | In all countries concerned by the trial days | 0 |