E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Mild Alzheimer's Disease |
Malattia di Alzheimer di grado lieve |
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E.1.1.1 | Medical condition in easily understood language |
Mild Alzheimer's Disease |
Malattia di Alzheimer di grado lieve |
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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 | 14.1 |
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 test the hypothesis that solanezumabwill slow the cognitive and functional decline of AD as compared with placebo in patients with mild AD. |
Obiettivo principale: valutazione dell'ipotesi che solanezumab rallenti il declino delle capacità cognitive e funzionali della malattia di Alzheimer rispetto al placebo in pazienti affetti da malattia di Alzheimer lieve |
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E.2.2 | Secondary objectives of the trial |
• To assess the relationship between treatment effect and time.
• To test the hypothesis that solanezumab will slow the rate of cognitive and functional decline associated with ADassessed using a slope analysis from a repeated-measures model.
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•Valutare la correlazione tra effetto del trattamento e tempo.
•Valutare, mediante un'analisi della pendenza di un modello a misure ripetute, l'ipotesi che solanezumab rallenti la velocità del declino delle capacità cognitive e funzionali associato alla malattia di Alzheimer
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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 |
H8A-MC-LZAX Addendum – Lumbar Punctures
Lumbar punctures will be used to collect cerebrospinal fluid (CSF) for assays of several CSF measures
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H8A-MC-LZAX Addendum –Punture Lombari
Sarà raccolto il liquido cerebrospinale (CSF) tramite Punture Lombari per il saggio di diversi parametri collegati al CSF.
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E.3 | Principal inclusion criteria |
[1] Meets National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer’s Disease and Related Disorders Association (NINCDS/ADRDA) criteria for probable AD.
[2] Has a Modified Hachinski Ischemia Scale score of less than or equal to 4.
[3] Has an MMSE score of 20 through 26 at Visit 1 (Screening visit).
[4] Has a Geriatric Depression Scale score of less than or equal to 6 (on the staff-administered short form).
[5] Has had an MRI or computerized tomography (CT) scan performed within the past 2 years that has confirmed no findings inconsistent with a diagnosis of AD.
[6] Male or female patients ages 55 to 90 years old.
[7] Has a florbetapir PET scan or CSF result consistent with the presence of amyloid pathology at screening. |
[1] Soddisfano i criteri di malattia di Alzheimer probabile del NINCD/ADRDA secondo quanto determinato da un neurologo, geriatra, psichiatra o medico approvato dallo Sponsor o da un suo incaricato.
[2] Presentano un punteggio MHIS (Modified Hachinski Ischemia Scale) ≤4
[3] Presentano un punteggio MMSE compreso tra 20 e 26 inclusi alla Visita 1
[4] Presentano un punteggio GDS (Geriatric Depression Scale) ≤6 (forma breve somministrata dal personale).
[5] Sono stati sottoposti negli ultimi 2 anni a risonanza magnetica (RM) o a tomografia computerizzata (TAC) che non ha confermato referti incompatibili con una diagnosi di malattia di Alzheimer.
[6] Pazienti di entrambi i sessi, di età compresa tra 55 e 90 anni.
[7] Se trattati in concomitanza con un AChEI e/o memantina, devono essere stati trattati con il farmaco per almeno 4 mesi e a una dose stabile per almeno 2 mesi prima della Visita 2. Il dosaggio deve rimanere stabile per l'intera durata dello studio.
[8] Devono presentare risultati di una PET con florbetapir o dell'esame sul liquido cerebrospinale che siano compatibili con la presenza di patologia amiloide allo screening.
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E.4 | Principal exclusion criteria |
[1] Does not have a reliable caregiver who is in frequent contact with the patient (defined as at least 10 hours per week), will accompany the patient to the office and/or be available by telephone at designated times, and will monitor administration of prescribed medications.
[2] Meets National Institute of Neurological Disorders and Stroke/Association Internationale pour la Recherche et l’Enseignement en Neurosciences (NINDS/AIREN) criteria for vascular dementia.
[3] Has current serious or unstable illnesses including cardiovascular, hepatic, renal, gastroenterologic, respiratory, endocrinologic, neurologic (other than AD), psychiatric, immunologic, or hematologic disease and other conditions that, in the investigator’s opinion, could interfere with the analyses of safety and efficacy in this study; or has a life expectancy of <2 years.
[4] Has had a history within the last 5 years of a serious infectious disease affecting the brain or head trauma resulting in protracted loss of consciousness.
[5] Has a history within the last 5 years of a primary or recurrent malignant disease with the exception of resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or in situ prostate cancer with a normal prostate-specific antigen posttreatment.
[6] Has a known history of human immunodeficiency virus (HIV), clinically significant multiple or severe drug allergies, or severe posttreatment hypersensitivity reactions
[7] Has received AChEIs, memantine and/or other AD therapy for less than 4 months or has less than 2 months of stable therapy on these treatments
[8] Has received medications that affect the central nervous system (CNS), except treatments for AD for less than 4 weeks. |
[1] Non dispongono di una persona che presta le cure affidabile e che sia in contatto frequente con loro (almeno 10 ore alla settimana), che li accompagni all'ambulatorio e/o sia disponibile al telefono a orari prefissati e che controlli la somministrazione dei farmaci prescritti.
[2] Soddisfano i criteri di demenza vascolare del NINDS/AIREN (National Institute of Neurological Disorders and Stroke/Association Internationale pour la Recherche et l'Enseignement en Neurosciences)
[3] Soffrono attualmente di malattie gravi o instabili comprese malattie cardiovascolari (tra cui malattia cardiovascolare ischemica instabile), epatiche, renali, gastroenterologiche, respiratorie, endocrine, neurologiche (diverse dalla malattia di Alzheimer), psichiatriche, immunologiche o ematologiche e altre condizioni che, secondo il parere dello sperimentatore, potrebbero interferire con le analisi della sicurezza e dell'efficacia in questo studio oppure hanno un'aspettativa di vita inferiore a 2 anni.
[4] Hanno sofferto negli ultimi 5 anni di una malattia infettiva grave a carico del cervello (comprese neurosifilide, meningite o encefalite) oppure hanno subito un traumatismo cranico che ha determinato una perdita di coscienza prolungata.
[5] Hanno sofferto negli ultimi 5 anni di una malattia maligna primitiva o ricorrente fatta eccezione per le forme sottoposte a resezione di carcinoma cutaneo squamocellulare in situ, carcinoma basocellulare, carcinoma in situ della cervice o carcinoma prostatico in situ con antigene prostatico specifico nella norma dopo il trattamento.
[6] Presentano un'anamnesi nota di infezione da virus dell'immunodeficienza umana (HIV), allergie da farmaci molteplici o gravi clinicamente significative oppure reazioni da ipersensibilità gravi dopo il trattamento
[7] Sono stati trattati con AChEI, memantina e/o altra terapia per la malattia di Alzheimer per meno di 4 mesi o al momento della Visita 2 erano stati trattati per meno di 2 mesi con una dose stabile di questi trattamenti
[8] Sono stati trattati con farmaci che influiscono sul sistema nervoso centrale (SNC), fatta eccezione per trattamenti per la malattia di Alzheimer per meno di 4 settimane.
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E.5 End points |
E.5.1 | Primary end point(s) |
ADAS-Cog14 and ADCS-iADL |
ADAS-Cog14 e ADCS-iADL |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Week 0, 12, 28, 40, 52, 64, 80 and Early Discontinuation Visits |
Settimane 0, 12, 28, 40, 52, 64, 80 e Visite di Interruzione Anticipata |
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E.5.2 | Secondary end point(s) |
ADAS-Cog11, MMSE, ADCS-ADL, FAQ, CDR-SB, NPI, RUD-Lite, QoL-AD, and EQ-5D Proxy. |
ADAS-Cog11, MMSE, ADCS-ADL, FAQ, CDR-SB, NPI, RUD-Lite, QoL-AD, e EQ-5D Proxy. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 0, 28, 52, 80 and Early Discontinuation Visits |
Settimane 0, 28, 52, 80 e Visite di Interruzione Anticipata |
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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 | Yes |
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 | 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 | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 53 |
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 |
France |
Germany |
Italy |
Poland |
Spain |
Sweden |
United Kingdom |
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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 | 3 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |