E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Early Alzheimer's Disease (mild cognitive impairment due to AD (ie, prodromal AD) and mild dementia of the Alzheimer's type) |
Enfermedad de Alzheimer en fase temprana (deterioro cognitivo leve debido a la EA (DCL-EA) o demencia leve de tipo Alzheimer |
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E.1.1.1 | Medical condition in easily understood language |
Early Alzheimer's Disease |
Enfermedad de Alzheimer en fase temprana |
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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 | 10012271 |
E.1.2 | Term | Dementia Alzheimer's type |
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 disease modification as outlined in Liu-Seifert (2015). This will be accomplished by testing the three delayed-start hypotheses in both doses of LY3314814 across Study AZES and up to Week 26 (Visit 7) of Study AZFD. |
Evaluar la modificación de la enfermedad, según describen Liu-Seifert (2015). Esto se llevará a cabo contrastando las tres hipótesis de inicio diferido en ambas dosis de LY3314814, a lo largo del estudio AZES y hasta la semana 26 (visita 7) del estudio AZFD |
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E.2.2 | Secondary objectives of the trial |
1. To evaluate the disease modification of both doses of LY3314814 on functional and cognitive outcomes across Study AZES and up to Week 26 (Visit 7) of Study AZFD using the primary analysis methodology. 2. The delayed start analyses as outlined above will also be examined at Week 52 (Visit 11) for cognitive and functional outcomes. 3. Collect information in order to further characterize the safety and tolerability of LY3314814 in patients with early AD dementia (at the time of entry into Study AZES) |
1. Evaluar la modificación de la enfermedad de ambas dosis de LY3314814, desde el punto de vista de los resultados cognitivos y funcionales, a lo largo del estudio AZES y hasta la semana 26 (visita 7) del estudio AZFD, utilizando la metodología del análisis principal 2. Los análisis del inicio diferido descritos anteriormente también se llevarán a cabo en la semana 52 (visita 11) para los resultados cognitivos y funcionales. 3. Recoger información para continuar caracterizando la seguridad y la tolerabilidad de LY3314814 en pacientes con EA en fase temprana (en el momento de inclusión en el estudio AZES). |
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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 |
- To evaluate the effect of LY3314814 on brain amyloid burden using positron emission tomography (PET) in the longitudinal PET sub-study (included in the main protocol). - Protocol Addendum I8D-MC-AZFD(1) - FDG PET Imaging biomarker, v 16 Nov 2016. The objectives are to evaluate the effect of LY3314814 on brain metabolic rates using FDG PET and to evaluate change from baseline (in Study AZES) in brain metabolism as measured by FDG PET. - Protocol Addendum I8D-MC-AZFD (2) - Flortaucipir F 18 (18F-AV-1451) Tau PET Imaging Biomarker, v 16 Nov 2016. The objective is to evaluate change from baseline (in Study AZES) in tau as measured by flortaucipir F 18 PET. -Protocol Addendum I8D-MC-AZFD(3) Genetics v 16 Nov 2016: being conducted to collect and store whole blood deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) samples for future investigation of variable response to LY3314814 and genetic variants thought to play a role in Alzheimer’s disease (AD) and neurodegeneration. |
-Evaluar el efecto de LY3314814 sobre la placa amiloide cerebral, usando Tomografía por Emisión de Positrones (PET) en el subestudio longitudinal PET (incluido en el protocolo principal). -Adenda al protocolo I8D-MC-AZFD (1)- FDG PET biomarcadores de imagen, V 16 nov 2016. Los objetivos son evaluar el efecto de LY3314814 en el metabolismo cerebral usando FDG PET y evaluar el cambio desde el momento basal (en el estudio AZES) en el metabolismo cerebral medido a través de FDG PET -Adenda al protocolo I8D-MC-AZFD (2)- Flortaupicir F18 (18F-AV-1451) Tau PET biomarcador de imagen, v 16 Nov 2016. El objetivo es evaluar el cambio desde el momento basal (en el estudio AZES) en tau medido a través de Flortaupicir F18 PET. -Adenda al protocolo I8D-MC-AZFD (3)-Genética, v 16 Nov 2016: Llevada a cabo para recoger y almacenar muestras de ácido desoxirribonucleico (ADN) y ácido ribonucleico (ARN) en sangre entera para futura investigación sobre la variable de respuesta a LY3314814 y variantes genéticas que se piensa que pueden jugar un papel en la Enfermedad de Alzheimer (EA) y neurodegeneración. |
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E.3 | Principal inclusion criteria |
Participants previously enrolled in AMARANTH (NCT02245737) who meet eligibility criteria for delayed start I8D-MC-AZFD |
Participantes previamente reclutados en AMARANTH (NCT02245737) que cumplen con los criterios de elegibilidad para inicio diferido I8D-MC-AZFD. |
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E.4 | Principal exclusion criteria |
Participants who participate in AMARANTH (NCT02245737) who develop new conditions precluding them from enrolling into I8D-MC-AZFD. |
Participantes que participan en AMARANTH (NCT02245737) que desarrollen nuevas alteraciones que sean excluyentes para su reclutamiento en I8D-MC-AZFD. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Delayed start analysis on the ADAS-Cog13 |
1. Análisis de inicio diferido en ADAS-Cog13 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. V. 5, 7, 11, and at early discontinuation |
1. V. 5, 7, 11, y en finalización prematura |
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E.5.2 | Secondary end point(s) |
1. Delayed start analysis on the ADCS-iADL 2. Delayed start analysis on the FAQ 3. Delayed start analysis on the iADRS 4. Delayed start analysis on the MMSE 5. Delayed start analysis on the ADAS-Cog13 Standard safety assessments: 6. Spontaneously reported AEs 7. Clinical laboratory tests 8. Vital signs 9. Body weight 10. 12-lead ECGs 11. Physical examinations including neurological examinations Additional safety assessments: 12. Eye examinations 13. Skin examinations 14. Serial MRI 15. Columbia-Suicide Severity Rating Scale (C-SSRS) |
1. Análisis de inicio diferido en ADCS-iADL 2. Análisis de inicio diferido en FAQ 3. Análisis de inicio diferido en iADRS 4. Análisis de inicio diferido en MMSE 5. Análisis de inicio diferido en ADAS-Cog13
Evaluaciones de seguridad estandar: 6. Notificación Acontecimienos adversos espontáneos 7. Analisis clinicos 8. Constantes vitales 9. Peso 10. ECGs de 12 derivaciones 11. Examen físico incluyendo examen neurológico
Evaluaciones de seguridad adicionales: 12. Examen ocular 13. Examen dermatológico 14. Serial MRI 15. Columbia-Suicide Severity Rating Scale (C-SSRS) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. V. 7, 11 & early discontinuation 2. V. 7, 11 & early discontinuation 3. V. 7, 11 & early discontinuation 4. V. 5, 7, 11 & early discontinuation 5. V. 5, 7, 11 & early discontinuation 6, As observed 7. V. 3, 4, 5, 7, 9, 11 & early discontinuation 8. V. 2, 3, 4, 5, 6, 7, 9, 10, 11 & early discontinuation 9 V. 5, 7, 11 & early discontinuation 10. V. 2, 3, 5, 7, 9, 11 & early discontinuation 11. V. 3, 5, 7, 9, 11 & early discontinuation 12. V. 11 & early discontinuation 13. V. 5, 11 & early discontinuation 14. V. 11 & early discontinuation 15. V. 2, 3, 4, 5, 6, 7, 9, 10, 11 & early discontinuation |
1. V. 7, 11 y finalización prematura 2. V. 7, 11 y finalización prematura 3. V. 7, 11 y finalización prematura 4. V. 5, 7, 11 y finalización prematura 5. V. 5, 7, 11 y finalización prematura 6, Según observado 7. V. 3, 4, 5, 7, 9, 11 y finalización prematura 8. V. 2, 3, 4, 5, 6, 7, 9, 10, 11 y finalización prematura 9 V. 5, 7, 11 y finalización prematura 10. V. 2, 3, 5, 7, 9, 11 y finalización prematura 11. V. 3, 5, 7, 9, 11 y finalización prematura 12. V. 11 y finalización prematura 13. V. 5, 11 y finalización prematura 14. V. 11 y finalización prematura 15. V. 2, 3, 4, 5, 6, 7, 9, 10, 11 y finalización prematura |
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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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
LY3314814, bien 20 mg o bien 50 mg |
LY3314814 either 20 mg or 50 mg |
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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 | Yes |
E.8.2.3.1 | Comparator description |
LY3314814, bien 20 mg o bien 50 mg |
LY3314814 either 20 mg or 50 mg |
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E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 19 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 113 |
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 |
Belgium |
Canada |
France |
Germany |
Hungary |
Italy |
Japan |
Korea, Republic of |
Poland |
Romania |
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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LVLS |
Ultima visita 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 | 3 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |