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 chronic neurodegenerative disease that destroys memory and other important mental functions. |
EA es una enfermedad neurodegenerativa que destruye la memoria y otras funciones mentales importantes |
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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 | 100000004852 |
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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 long-term safety and tolerability of continued treatment with subcutaneous (SC) gantenerumab at target dose in participants with AD who received gantenerumab in open-label extension (OLEs) of Studies WN25203 or WN28745 |
Evaluar la seguridad y la tolerancia a largo plazo del tratamiento continuado con gantenerumab SC utilizando la dosis establecida, en participantes con EA que han recibido gantenerumab en las partes OLE de los estudios WN25203 o WN28745 |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- All participants who completed the OLEs of Studies WN25203 or WN28745 (i.e., latest version of protocol in their countries, and did not discontinue study drug early) are eligible to participate in this study - For women of childbearing potential: agreement to remain abstinent or use contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 16 weeks after the last dose of study drug |
- Todos los participantes que hayan completado la parte de extensión abierta de los estudios WN25203 o WN28745 (es decir, de acuerdo con la última versión del protocolo aplicable a sus respectivos países y que no hayan terminado prematuramente el tratamiento con el fármaco del estudio) son elegibles para participar en este estudio. - Las mujeres potencialmente fértiles deben comprometerse a practicar la abstinencia sexual o a usar métodos anticonceptivos con una tasa de fallos anual de <1%, durante el período de tratamiento y como mínimo hasta 16 semanas después de la administración de la última dosis del fármaco del estudio. |
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E.4 | Principal exclusion criteria |
- Prematurely discontinued from the OLEs of Studies WN25203 or WN28745 or from study drug for any reason - Any medical condition that the investigator or Sponsor determines may jeopardize the participant’s safety if he or she continues to receive study treatment - If the participant is unlikely to benefit from gantenerumab therapy, based on disease progression or other factors, or if study participation is otherwise not in the participant’s best interest, by determination of the investigator or Sponsor - Any investigational treatment other than gantenerumab during or since completion of the OLEs of Studies WN25203 or WN28745 - Pregnancy - Evidence of disseminated leptomeningeal hemosiderosis - Evidence of intracerebral macrohemorrhage |
- Retirada prematura de la parte de extensión abierta de los estudios WN25203 o WN28745 o del fármaco del estudio por cualquier motivo - Cualquier afección que, de acuerdo con el criterio del investigador o del promotor, pueda comprometer la seguridad del participante si continúa recibiendo el tratamiento del estudio - El investigador o el promotor consideran que hay pocas probabilidades de que el participante se beneficie del tratamiento con gantenerumab, basándose en la progresión de la enfermedad u otros factores, o si por otros motivos la participación en el estudio no es lo más apropiado para el paciente - Administración de cualquier tratamiento en investigación distinto de gantenerumab durante la parte de extensión abierta de los estudios WN25203 o WN28745 o desde su terminación - Embarazo - Evidencia de hemosiderosis leptomeníngea diseminada - Evidencia de macrohemorragia intracerebral |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Incidence, nature, severity, and timing of adverse events and serious adverse events 2. Changes from baseline in vital signs, blood tests 3. Changes from baseline in electrocardiogram 4. Changes from baseline in the Columbia-Suicide Severity Rating Scale (C SSRS) 5. Incidence, nature, severity, and timing of magnetic resonance imaging (MRI) safety findings: amyloid-related imaging abnormality–edema/effusion (ARIA E) and amyloid-related imaging abnormality–hemosiderin depositions (ARIA H) 6. Incidence, nature, severity, and timing of injection-site reaction (ISRs) 7. Number and proportion of anti-drug antibody (ADA)-positive and ADA-negative participants during both the treatment and follow-up periods 8. Incidence of treatment discontinuations for adverse events 9. Incidence of adverse events of special interest |
1.Incidencia, tipo, gravedad y momento de aparición de los acontecimientos adversos 2.Cambios producidos respecto a la situación basal en las constantes vitales, resultados de los análisis de sangre 3.Cambios producidos respecto a la situación basal en electrocardiograma 4.Cambios producidos respecto a la situación basal en Columbia-Suicide Severity Rating Scale (C-SSRS) 5.Incidencia, tipo, gravedad y momento de aparición de los hallazgos de seguridad en la resonancia magnética (RM): anomalías en la imagen relacionadas con amiloide- edema/derrame (ARIA-E) y anomalías en la imagen relacionadas con amiloide-depósitos de hemosiderina (ARIA-H) 6.Incidencia, tipo, gravedad y momento de aparición de las reacciones en el lugar de la inyección (RLI) 7.Número y porcentaje de participantes con anticuerpos antifármaco (ADA) positivo y ADA negativo durante los períodos de tratamiento y seguimiento 8.Incidencia de casos que requieren la suspensión del tratamiento debido a acontecimientos adversos 9.Incidencia de acontecimientos adversos de especial interés |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Up to 4 weeks after the last dose of the study drug 2. Baseline (Day 1) to 4 weeks after the last dose of the study drug 3. At baseline and unscheduled visit (UV) 4-5. Baseline, Week 24, Week 52, Week 76, Week 104, follow-up (FU)/ early termination (ET) visit, UV 6. Up to 4 weeks after the last dose of the study drug 7. Day 1, Week 52, Week 104, FU/ET visit 8-9. Up to 4 weeks after the last dose of the study drug |
1.Hasta 4 semanas después de la última dosis del fármaco del estudio. 2.Desde la visita basal (día 1) hasta 4 semanas después de la última dosis del fármaco del estudio 3.En la visita basal y no programada (UV) 4-5.Basal, Semana 24, Semana 52, Semana 76, Semana 104, visita de seguimiento (FU) / terminación temprana (ET), UV 6.Hasta 4 semanas después de la última dosis del fármaco del estudio. 7.Día 1, Semana 52, Semana 104, visita de segumiento / visita de terminación temprana 8-9.Hasta 4 semanas después de la última dosis del fármaco del estudio. |
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E.5.2 | Secondary end point(s) |
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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 | 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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 32 |
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 |
Australia |
Belgium |
Canada |
Chile |
Denmark |
Italy |
Japan |
Korea, Republic of |
Mexico |
Netherlands |
Poland |
Russian Federation |
Spain |
Switzerland |
Turkey |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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 study is defined as the date when the last participant last visit (LPLV) occurs or the date on which the last data point required for safety follow-up is received from the participant in the study. |
La terminación del estudio se define como la fecha en la que tiene lugar la última visita del último participante (UVUP) o en la que se reciben los últimos datos del último participante en el estudio, requeridos para el seguimiento de la seguridad. |
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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 | |
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 | 10 |