E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Down Syndrome |
Sindrome de Down |
|
E.1.1.1 | Medical condition in easily understood language |
Down Syndrome |
Sindrome de Down |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10044688 |
E.1.2 | Term | Trisomy 21 |
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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is as follows: ? To evaluate the efficacy of 26 weeks of treatment with RO5186582 on a composite endpoint derived from clinically meaningful responses in working memory and on the level of independent functioning/adaptive behavior or global improvement as compared to placebo. |
Evaluar la eficacia de 26 semanas de tratamiento con RO5186582 sobre un criterio de valoración compuesto derivado de respuestas clínicamente significativas en la memoria de trabajo y el nivel de funcionamiento independiente/conducta adaptativa o mejora global en comparación con el placebo. |
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E.2.2 | Secondary objectives of the trial |
Safety Objective: ? Evaluate the tolerability and safety of 26 weeks treatment of RO5186582 and 4?6 weeks after the end of the treatment period Efficacy Objectives: ? Evaluate the effect of 26 weeks treatment of RO5186582 compared to placebo on working memory ? Evaluate the effect of 26 weeks treatment of RO5186582 compared to placebo on the level of independent functioning and adaptive behavior ? Assess the effect of 26 weeks treatment of RO5186582 compared to placebo on global clinical condition ? Evaluate the effect of 26 weeks treatment of RO518652 compared to placebo on executive function ? Evaluate the effect of 26 weeks treatment of RO518652 compared to placebo on language function ? Evaluate the effect of 26 weeks treatment of RO518652 compared to placebo on everyday memory function ? Evaluate the effect of 26 weeks treatment of RO518652 compared to placebo on subject?s cognition and health-related quality of life as reported by the parents |
Seguridad · Evaluar la tolerancia y seguridad de 26 semanas de tratamiento con RO5186582 y 4-6 semanas después de finalizar el tratamiento Eficacia · Evaluar el efecto de 26 semanas de tratamiento con RO5186582 en comparación con el placebo sobre la memoria de trabajo · Evaluar el efecto de 26 semanas de tratamiento con RO5186582 en comparación con el placebo sobre el nivel de funcionamiento independiente y conducta adaptativa · Valorar el efecto de 26 semanas de tratamiento con RO5186582 comparado con el placebo en condiciones clínicas globales |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Individuals aged 12?30 years of age inclusive.
2. Clinical diagnosis of Down syndrome (trisomy 21) confirmed by chromosomal analysis (karyotyping). Subjects may have standard trisomy 21, Robertsonian translocation, isochromosome 21 (so called 21q21q Robertsonian) translocation), Down syndrome with reciprocal translocation or mosaicism.
3. Males, or nonpregnant, nonlactating females. For females of childbearing potential, strict contraceptive prevention is required: continuation of hormonal contraception, or intra uterine device. True abstinence is acceptable provided that participants are under the supervision of a caregiver attesting that participants are not sexually active and the results of pregnancy tests are negative before onset of treatment.
4. Body-mass Index (BMI) 18?42 and 15?30 kg/m2 inclusive for adults and adolescents respectively
5. Ability to complete the Clinical Evaluation of Language Fundamentals (CELF)?preschool 2 word classes task (i.e., ? 7 in the expressive raw score). |
1. Individuos de 12-30 años, ambas edades incluidas. 2. Diagnóstico clínico del síndrome de Down (trisomía 21) confirmado por análisis cromosómico (cariotipado). Los sujetos deben tener una trisomía 21 estándar, translocación Robertsoniana, isocromosoma 21, síndrome de Down con translocación recíproca o en mosaico. 3. Hombres o mujeres no embarazadas ni lactantes. En el caso de mujeres en edad fértil, se requiere una prevención contraceptiva estricta: contracepción hormonal continua o mediante dispositivo intrauterino. La abstinencia real es aceptable siempre y cuando los participantes estén bajo la supervisión de un cuidador que asegure que los participantes no son sexualmente activos y el resultado de las pruebas de embarazo sea negativo antes de iniciar el tratamiento. 4. Índice de Masa Corporal (IMC) 18-42 y 15-30 kg/m2 incluidos para adultos y adolescentes respectivamente 5. Capacidad para completar la versión preescolar de la Evaluación Clínica de los Fundamentos del Lenguaje (CELF) utilizando clases de dos palabras (p. ej. ³7 en la nota de expresión). |
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E.4 | Principal exclusion criteria |
1. Subjects with a current Diagnostic and Statistical Manual of Mental Disorders (DSM 5) diagnosis of any primary psychiatric diagnosis (including autism spectrum disorder or major depressive disorder). Diagnoses that are secondary, such as intellectual disability, attention deficit hyperactivity disorder, depression and conduct disorder are allowed as long as they are considered to not interfere with study conduct and the subject is on stable treatment for 3 months preceding enrollment.
2. Subjects with a history of infantile spasms, of West syndrome, Lennox-Gastaut syndrome, Early Infantile Epileptic Encephalopathy or any treatment-refractory epilepsy associated with cognitive or developmental regression, of severe head trauma or CNS infections (e.g. meningitis).
3. Subjects with a known or suspected clinical seizure event of any type within 24 months prior to screening. |
1. Sujetos con un diagnóstico principal de algún trastorno psiquiátrico en la actualidad (incluido trastorno de espectro autista o trastorno depresivo mayor) de acuerdo con el Manual Diagnóstico y Estadístico de los Trastornos Mentales (DSM 5). Los diagnósticos secundarios, como discapacidad intelectual, trastorno por déficit de atención con hiperactividad, depresión y trastorno de conducta están permitidos siempre y cuando no se considere que interfieran en el estudio y el sujeto esté bajo tratamiento estable durante 3 meses antes de su inclusión en el estudio. 2. Sujetos con un historial de espasmos infantiles, síndrome de West, síndrome de Lennox-Gastaut, encefalopatía epiléptica infantil temprana o epilepsia refractaria al tratamiento asociada a regresión cognitiva o de desarrollo, traumatismo craneal o infecciones del sistema nervioso central (p. ej. meningitis). 3. Sujetos con una crisis epiléptica conocida o sospecha de cualquier tipo en los 24 meses previos a la selección. |
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E.5 End points |
E.5.1 | Primary end point(s) |
?Cognition as assessed by the Repeatable Battery for the Assessment of ?Neuropsychological Status (RBANS) sub-tests ?Clinical global impression as assessed by Clinician Rated Global Improvement (CGI-I) scale |
Cognición según las sub-pruebas de la Batería Repetible para la Evaluación del Estado Neuropsicológico (RBANS) Conducta adaptativa según las puntuaciones estándar de las Escalas de Conducta Adaptativa de Vineland II (VABSII) Impresión clínica global según la Mejoría Global de la Escala de Impresión Clínica Global (CGI-I) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
? Base Line (except for CGI-I) 12 weeks and 26 Weeks (see protocol for details) |
Linea de base (excepto para CGI-I) de 12 semanas y 26 semanas (ver protocolo para más detalle) |
|
E.5.2 | Secondary end point(s) |
? Everyday working memory as assessed by the Rivermead Behavioral Memory Test for Children (RBMT-C) sub-tests ? Executive function as assessed by the Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P) ? Daily functional memory as assessed by the Observer Memory Questionnaire-Parent Form (OMQ-PF) ? Language function as assessed by the Clinical Evaluation of Language Fundamentals (CELF-4) ? Health-related quality of life as assessed by the Pediatric Quality of Life (PedsQL) Generic Core Module v4.0 ? Cognition as assessed by the PedsQL Cognitive Functioning Scale |
-Memoria cotidiana según las sub-pruebas del Test Conductual de Memoria Rivermead para Niños (RBMT-C). -Función ejecutiva según el Inventario de Evaluación Conductual de la Función Ejecutiva para Preescolares (BRIEF-P). -Memoria diaria funcional según el Cuestionario de Memoria del Observador - Formulario para Padres (OMQ-PF). -Función del lenguaje según la Evaluación Clínica de Fundamentos del Lenguaje (CELF-4) -Calidad de vida relacionada con la salud según el cuestionario de Calidad de Vida Pediátrica (PedsQL), módulo general, versión 4.0 - Cognición según la Escala de Funcionamiento Cognitivo PedsQL |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
? 12 weeks and 26 Weeks |
12 semanas y 26 semanas |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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 |
France |
Italy |
New Zealand |
Argentina |
Germany |
Spain |
Mexico |
Singapore |
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
|
LVLS |
Ultima visita del ultimo paciente |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |