E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Alzheimer’s Disease (AD) |
Enfermedad de Alzheimer (EA) |
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E.1.1.1 | Medical condition in easily understood language |
AD is a progressive disorder that causes problems with memory, thinking and behavior. Symptoms usually develop slowly and get worse over time, becoming severe enough to interfere with daily tasks |
La EA es un desorden que causa problemas de memoria, pensamiento y comportamiento. Los síntomas se desarrollan despacio y empeoran convirtiéndose en severos e interfiriendo en las tareas diarias |
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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 | HLT |
E.1.2 | Classification code | 10001897 |
E.1.2 | Term | Alzheimer's disease (incl subtypes) |
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 | PT |
E.1.2 | Classification code | 10074616 |
E.1.2 | Term | Prodromal Alzheimer's disease |
E.1.2 | System Organ Class | 10029205 - Nervous system 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 |
• To evaluate the efficacy of gantenerumab administered by subcutaneous injection compared with placebo on global outcome |
• Evaluar la eficacia de gantenerumab administrado mediante inyección subcutánea en comparación con placebo en el resultado global |
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E.2.2 | Secondary objectives of the trial |
•To evaluate the efficacy of gantenerumab versus placebo on cognition and function •To evaluate the safety of gantenerumab compared with placebo •To characterize the pharmacokinetic profile of gantenerumab |
•Evaluar la eficacia de gantenerumab en comparación con placebo sobre la cognición y la función •Evaluar la seguridad de gantenerumab en comparación con placebo •Determinar el perfil farmacocinético de gantenerumab |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
The substudies associated with Study WN39658 will be described in separate protocols, and patients consenting to enroll in these substudies will be asked to sign the associated Informed Consent Forms. |
Los subestudios asociados con el ensayo WN39658 se describirán en protocolos separados, y a los pacientes que consientan a participar en esos subestudios se les pedirá que firmen los consentimientos informados asociados |
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E.3 | Principal inclusion criteria |
-Age 50-90 years -Meets National Institute on Aging/Alzheimer's Association (NIAAA) core clinical criteria for probable AD dementia or prodromal AD (consistent with the NIAAA diagnostic criteria and guidelines for mild cognitive impairment) -Evidence of AD pathological process, as confirmed by cerebrospinal fluid or amyloid positron emission tomography scan -Demonstrate abnormal memory function MMSE score between 22-30 (inclusive) -Clinical Dementia Rating Global Score of 0.5 or 1.0 -Availability of a reliable study partner who accepts to participate in study procedure throughout the study duration -If receiving symptomatic AD medication the dosing regimen must have been stable for 3 months prior to screening |
-Edad de 50-90 años -Demencia por EA probable (compatible con los criterios clínicos del NIA/AA de demencia por EA probable) o EA prodrómica (compatible con los criterios diagnósticos y las directrices sobre deterioro cognitivo leve debido a EA del NIA/AA). -Datos del proceso patológico de EA, confirmados en LCR o una PET -Función anormal de la memoria demostrada -Puntuación MMSE entre 22 y 30 (inclusive) -Clinical Dementia Rating Global Score de 0,5 o 1,0. -Disponibilidad de una persona de confianza que acceda a participar en los procedimientos del estudio a lo largo de todo el ensayo -Si el paciente está recibiendo medicación sintomática para la EA, pauta posológica estable durante al menos tres meses antes del screening |
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E.4 | Principal exclusion criteria |
-Any evidence of a condition other than AD that may affect cognition -History or presence of clinically evident systemic vascular disease that in the opinion of the investigator has the potential to affect cognitive function -History of schizophrenia, schizoaffective disorder, major depression, or bipolar disorder -Unstable or clinically significant cardiovascular, kidney or liver disease -At risk of suicide in the opinion of the investigator -Alcohol or substance abuse in past 2 years -Relevant brain hemorrhage, bleeding disorder and cerebrovascular abnormalities -Any contraindications to brain magnetic resonance imaging -Uncontrolled hypertension |
-Cualquier signo de un trastorno distinto de la EA que pueda afectar a la cognición -Antecedentes o presencia de una enfermedad vascular sistémica clínicamente evidente que, en opinión del investigador, pueda afectar a la función cognitiva -Antecedentes de esquizofrenia, trastorno esquizoafectivo, depresión mayor o trastorno bipolar. -Enfermedad cardiovascular, renal o hepatica clínicamente significativa o inestable -Riesgo de suicidio, en opinión del investigador. -Abuso o dependencia de alcohol en los últimos 2 años -Hemorragia cerebral relevante, desorden hemorragico y anormalidades cerebrovasculares -Cualquier contraindicación a las resonancias magneticas cerebrales -Hipertension no controlada |
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E.5 End points |
E.5.1 | Primary end point(s) |
1.The change from baseline (Day 1) to Week 104 in global outcome, as measured by the Clinical Dementia Rating-Sum of Boxes |
1. El cambio desde basal (dia 1) a la semana 104 en el resultado global, medido por el Clinical Dementia Rating-Sum of Boxes |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Baseline (Day 1) to Week 104 |
1. Basal (dia 1) a semana 104 |
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E.5.2 | Secondary end point(s) |
1. The change from baseline to Week 104 in cognition, as measured by MMSE total score, Alzheimer's Disease Assessment Scale-Cognition, Subscale 11 and 13, Verbal Fluency Task and Coding 2. The change from baseline to Week 104 in function, as measured by Functional Activities Questionnaire and Alzheimer’s Disease Cooperative Study Group-Activities of Daily Living total score and instrumental score 3. Nature, frequency, severity, and timing of adverse events and serious adverse events 4. Physical examinations, vital signs, blood tests, ECGs, and Columbia-Suicide Severity Rating Scale 5. Nature, frequency, severity, and timing of MRI findings: ARIA-E and amyloid-related imaging abnormality-hemosiderin deposition 6. Nature, frequency, severity, and timing of injection-site reactions 7. Presence of anti-drug antibody (ADAs) during the study relative to the presence of ADAs at baseline 8. Plasma concentration of gantenerumab at specified timepoints 9. Change from baseline in brain amyloid load, as measured by amyloid PET scan in a subset of patients 10. Change from baseline in brain tau load, as measured by tau PET scan in a subset of patients 11. Change from baseline in cerebral spinal fluid markers of disease in a subset of patients, including, but not limited to, A beta1−42, total tau, and phosphorylated tau 12. MRI-derived measurements over time, such as volumetric changes in whole brain, ventricles, hippocampus, or other structures, in all patients |
1. El cambio desde la visita basal hasta la semana 104 en la cognición medido mediante Puntuación total MMSE, ADAS-Cog11, ADAS-Cog13, Prueba de fluidez verbal y Codificación. 2. Cambio con respecto al valor basal en la semana 104 en función, medido por Escala del Alzheimer Disease Cooperative Study Group-Puntuacion de actividades de vida cotidianas diarias y puntuación instrumental. 3. Naturaleza, frecuencia, intensidad y cronología de los acontecimientos adversos y acontecimientos adversos graves 4. Exploraciones físicas, constantes vitales, análisis de sangre, ECG y C-SSRS 5. Naturaleza, frecuencia, intensidad y cronología de los hallazgos de RM: ARIA-E y ARIA-H 6. Naturaleza, frecuencia, intensidad y cronología de las reacciones en el lugar de la inyección 7. Presencia de anticuerpos contra el fármaco (ACF) durante el estudio con respecto a su presencia en la visita basal 8. Concentración plasmática de gantenerumab en momentos especificados 9. Cambio con respecto al valor basal en la carga de amiloide cerebral, determinada mediante PET para amiloide en un subgrupo de pacientes 10. Cambio con respecto al valor basal en la carga de proteína tau cerebral, determinada mediante PET para tau en un subgrupo de pacientes 11. Cambio con respecto al valor basal de marcadores de enfermedad en líquido cefalorraquídeo en un subgrupo de pacientes, entre otros, Aβ1−42, tau total y tau fosforilada 12. Mediciones derivadas de la RM a lo largo del tiempo en todos los pacientes, como variaciones volumétricas de todo el cerebro, los ventrículos, el hipocampo u otras estructuras |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-2. Baseline to Week 104 3-7. Baseline up to end of study (week 152) 8. Baseline, Week 2, 24, 41, 52, 76, 103, 116, 152 and at early termination and unscheduled visit 9-12. Baseline up to week 104 |
1-2. Basal a semana 104 3-7. Basal hasta como máximo el fin de ensayo (semana 152) 8. Basal, semanas 2, 24, 41, 52, 76, 103, 116, 152 y en las visitas de terminación temprana y no programadas 9-12. Basal hasta como maximo la semana 104 |
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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 | Yes |
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 |
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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 | 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 | 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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 18 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 62 |
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 |
Argentina |
Belgium |
Chile |
Croatia |
Denmark |
Finland |
Japan |
Korea, Republic of |
Mexico |
Netherlands |
Poland |
Portugal |
Singapore |
Spain |
Sweden |
Turkey |
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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The end of the study is defined as the date when the last patient, last visit (LPLV) occurs or the date at which the last data point required for safety analyses or safety follow-up is received for the last patient, whichever occurs later. |
El final del estudio se define como la fecha en la que se produzca la última visita del último paciente (UVUP) o la fecha en la que se reciban los últimos datos necesarios para los análisis de la seguridad o el seguimiento de la seguridad del último paciente, lo que ocurra más tarde |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |