Resumen

This study is done to find out whether the medicine, semaglutide, has a positive effect on early Alzheimer's disease. Participants will either get semaglutide or placebo (a "dummy" medicine which does not contain any study medicine) - which treatment participants get is decided by an equal chance. The study will last for up to 173 weeks (about 3 years and 4 months). Participants will have 17 clinic visits and 1 phone call with the study doctor. The study includes various tests and scans. At 10 of the clinic visits participants will have blood samples taken. Participants must have a study partner, who is willing to take part in the study. Women cannot take part if pregnant, breastfeeding or plan to become pregnant during the study period. A cerebrospinal fluid (CSF) sub-study will be performed as a part of the study. The sub-study will be performed on a selection of sites based on their experience with CSF sampling and willingness to participate in this sub-study. The endpoints related to this sub-study are exploratory only.

Elegibilidad

Edad mínima: 55 YearsEdad máxima: 85 YearsSexo: ALL

Criterios de inclusión

Male or female, aged 55-85 years (both inclusive) at the time of signing informed consent.
MCI (mild cognitive impairment) or mild dementia of the Alzheimer's type according to the NIA-AA (National Institute of Aging-Alzheimer's Association) 2018 criteria.
CDR (Clinical Dementia Rating) global score of 0.5 and CDR of 0.5 or more in at least one of the three instrumental activities of daily living categories (personal care, home \& hobbies, community affairs) Or CDR global score of 1.0
RBANS (Repeatable Battery for the Assessment of Neuropsychological Status) delayed memory index score of below or equal to 85
MMSE (Mini-Mental State Examination) greater than or equal to 22
Amyloid positivity established with either amyloid PET (positron emission tomography), CSF (cerebrospinal fluid) Aβ1-42 or CSF Aβ1-42/Aβ1-40 .
If receiving an approved Alzheimer's disease treatment (such as acetylcholinesterase inhibitors, memantine or aducanumab) the dose must have been stable for at least 3 months prior to screening and should not be changed during the trial unless medically necessary.

Criterios de exclusión

Brain MRI (or CT) scan suggestive of clinically significant structural CNS disease confirmed by central read (e.g. cerebral large-vessel disease \[large vessel (cortical) infarcts greater than 10 mm in diameter\], prior macro-haemorrhage \[greater than 1 cm\^3\], cerebral vascular malformations, cortical hemosiderosis, intracranial aneurism(s), intracranial tumours, changes suggestive of normal pressure hydrocephalus).
Brain MRI (magnetic resonance imaging) (or CT) scan suggestive of significant small vessel pathology confirmed by central read and defined as greater than1 lacunar infarct and/or ARWMC (age-related white matter changes) greater than 2, (WM (white matter) greater than 20 mm) in the deep white matter and periventricular regions.
Brain MRI (or CT) scan suggestive of strategic infarcts defined as bilateral thalamic lacunar infarcts and singular paramedian thalamic infarcts confirmed by central read.
Evidence of a relevant neurological disorder other than MCI or mild dementia of the Alzheimer's type at screening, including but not limited to Parkinson's disease, Lewy body disease, frontotemporal dementia of any type, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, systemic lupus erythematosus, progressive supranuclear palsy, neurosyphilis, HIV (human immunodeficiency virus), learning disability, intellectual disability, hypoxic cerebral damage, or significant head trauma with loss of consciousness that led to persistent cognitive deficits
Evidence of a clinically relevant or unstable psychiatric disorder, based on Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, including schizophrenia or other psychotic disorder, or bipolar disorder. A subject with a history of major depression who has not had an episode in the last 24 months before the day of screening and is considered in remission or whose depression is controlled with treatment can be included in the trial per investigator's judgement.

Ubicaciones

Instituto Medico Especializado_Capital Federal

Ciudad de Buenos Aires, Buenos Aires, Argentina

Instituto de Investigaciones Metabolicas (IDIM)

Buenos Aires, Argentina

Hospital Italiano

Buenos Aires, Argentina

Clínica Nuestra Señora de las Nieves

CABA, Argentina

FLENI

CABA, Argentina

Instituto Privado Kremer

Córdoba, Argentina

Fundación Scherbovsky

Mendoza, Argentina

A Randomised Double-blind Placebo-controlled Clinical Trial Investigating the Effect and Safety of Oral Semaglutide in Subjects With Early Alzheimer´s Disease (EVOKE)