E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Alzheimer's Disease |
Malattia di Alzheimer |
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E.1.1.1 | Medical condition in easily understood language |
Alzheimer's Disease |
Malattia di Alzheimer |
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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 | LLT |
E.1.2 | Classification code | 10001896 |
E.1.2 | Term | Alzheimer's disease |
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 assess the efficacy of ABBV-8E12 in slowing disease progression (cognitive and functional impairment) in subjects with Early Alzheimer's Disease (AD) as measured by the Clinical Dementia Rating – Sum of Boxes (CDR-SB). • To assess the long term safety of ABBV-8E12 for up to 96 weeks in subjects with Early AD.
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• Valutare l’efficacia di ABBV-8E12 nel rallentare la progressione della malattia (compromissione cognitiva e funzionale) in soggetti affetti da malattia di Alzheimer (AD) in fase precoce misurata mediante il questionario CDR-SB (Clinical Dementia Rating – Sum of Boxes). • Valutare la sicurezza a lungo termine di ABBV-8E12 per un periodo massimo di 96 settimane in soggetti affetti da AD in fase precoce. |
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E.2.2 | Secondary objectives of the trial |
• To assess the pharmacokinetics of ABBV-8E12 in subjects with Early AD. • To assess the efficacy of ABBV-8E12 in slowing cognitive and functional impairment in subjects with Early AD as measured by the Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale (14-Item) Cognition Portion (ADAS-Cog-14), Repeatable Battery for Assessment of Neuropsychological Status (RBANS), 24-Item Alzheimer's Disease Cooperative Study/Activities of Daily Living Scale Adapted for Patients with Mild Cognitive Impairment (ADCS-MCI-ADL-24), Functional Activities Questionnaire (FAQ) and University of California's Performance Based Skills Assessment, Brief Version (UPSA-Brief). • To assess the global impact of ABBV-8E12 on cognition, function and behavior as measured by Alzheimer's Disease Cooperative Study Clinical Global Impression of Change for Mild Cognitive Impairment (ADCS-CGIC-MCI).
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• Valutare la farmacocinetica di ABBV-8E12 in soggetti affetti da AD in fase precoce. • Valutare l’efficacia di ABBV-8E12 nel rallentare la compromissione cognitiva e funzionale in soggetti affetti da AD in fase precoce misurata mediante le scale di valutazione MMSE (Mini-Mental State Examination), ADAS-Cog-14 (Alzheimer's Disease Assessment Scale (14-Item) Cognition Portion), RBANS (Repeatable Battery for Assessment of Neuropsychological Status), ADCS-MCI-ADL-24 (24-Item Alzheimer's Disease Cooperative Study/Activities of Daily Living Scale Adapted for Patients with Mild Cognitive Impairment), FAQ (Functional Activities Questionnaire) e UPSA-Brief (University of California's Performance Based Skills Assessment, Brief Version). • Valutare l’impatto globale di ABBV-8E12 sulle funzioni cognitive, esecutive e comportamentamentali, misurato mediante il questionaro ADCS-CGIC-MCI (Alzheimer's Disease Cooperative Study Clinical Global Impression of Change for Mild Cognitive Impairment). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Subject who meets the National Institute on Aging and the Alzheimer's Association (NIA-AA) clinical criteria for mild cognitive impairment or probable AD, and have: - Clinical Dementia Rating (CDR)-Global Score of 0.5 - Mini-Mental State Examination (MMSE) score of 22 to 30, inclusive - Repeatable Battery for the Assessment of Neuropsychological Status-Delayed Memory Index (RBANS –DMI) score of 85 or lower - Subject has a positive amyloid Positron Emission Tomography (PET) scan. - Subject has a Modified Hachinski Ischemic Scale (MHIS) score of 4. - The subject has an identified, reliable, study partner (e.g., family member). - If using medications to treat symptoms related to AD, doses must be stable for at least 12 weeks prior to randomization. |
- Soggetti che soddisfino i criteri clinici NIA-AA (National Institute on Aging and the Alzheimer's Association) per la compromissione cognitiva lieve o probabile AD, e che presentino: - Punteggio di CDR (Clinical Dementia Rating)-Global pari a 0,5; - Punteggio MMSE (Mini-Mental State Examination) compreso fra 22 e 30, inclusi; - Punteggio RBANS – DMI (Repeatable Battery for the Assessment of Neuropsychological Status-Delayed Memory Index) pari o inferiore a 85 - Soggetto con positività alla scansione PET (tomografia a emissione di positroni) per amiloide - Soggetto con punteggio MHIS (Modified Hachinski Ischemic Scale) = 4 - Disponibilità per il soggetto di un partner identificato e affidabile per la sperimentazione (ad esempio un familiare), che abbia frequenti contatti con il soggetto e sia in grado di fornire informazioni relative alle capacità cognitive e funzionali del soggetto. - Qualora vengano usati medicinali per il trattamento dei sintomi correlati ad AD, le dosi devono essere stabili da almeno 12 settimane prima della randomizzazione. |
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E.4 | Principal exclusion criteria |
- Subject has any contraindications or inability to tolerate to brain magnetic resonance imaging (MRI), PET scans or lumbar puncture. - Subject has evidence of any other clinically significant neurological disorder other than Early AD. - In the opinion of the investigator, the subject has any clinically significant or uncontrolled medical or psychiatric illness, or has had an infection requiring medical intervention in the past 30 days. - Subject has had a myocardial infarction, unstable angina, stroke, transient ischemic attack or required intervention for any of these conditions within 6 months of Screening. |
- Soggetto con qualsiasi controindicazione o impossibilità a tollerare l’esecuzione di risonanza magnetica (RM) cerebrale, scansione PET cerebrale oppure puntura lombare. - Soggetto con evidenza di altri disturbi neurologici clinicamente significativi diversi da AD in fase precoce. - Soggetto che, a giudizio dello sperimentatore, presenta qualsiasi patologia medica o psichiatrica clinicamente significativa o non controllata oppure che ha avuto un’infezione che ha richiesto un intervento medico negli ultimi 30 giorni. - Soggetto che ha avuto un infarto miocardico, angina instabile, ictus, attacco ischemico transitorio o che ha richiesto interventi per una qualsiasi di queste condizioni entro 6 mesi dalla Visita 1 di Screening. |
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E.5 End points |
E.5.1 | Primary end point(s) |
CDR-SB |
CDR-SB (Clinical Dementia Rating sum of boxes) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
PK, MMSE, ADAS-Cog-14, RBANS, ADCS-MCI-ADL-24, FAQ, UPSA-B, ADCS-CGIC-MCI |
- PK; - MMSE (Mini Mental State Examination) - ADAS-Cog-14 (Alzheimer's Disease Assessment Scale); - RBANS (Repeatable Battery for Assessment of Neuropsychological Status); - Scala ADCS-MCI-ADL-24 (24-item Alzheimer's Disease Cooperative Study/Activities of Daily Living) adattata per i pazienti con compromissione cognitiva lieve; - FAQ (Functional Activities Questionnaire); - UPSA-Brief (University of California's Performance Based Skills Assessment, Brief Version); - ADCS-CGIC-MCI (Alzheimer's Disease Cooperative Study Clinician's Global Impression of Change for Mild Cognitive Impairment). |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
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) | 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 | 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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
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 | Information not present in EudraCT |
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 |
New Zealand |
United States |
European Union |
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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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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |