A Research Study Investigating Semaglutide in People With Early Alzheimer's Disease (EVOKE Plus)

Phase 3Active Not RecruitingNCT04777409

Novo Nordisk A/S1,840 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

1,840

Conditions

Early Alzheimer´s Disease

Interventions

Eligibility

Sex: ALLMin age: 55 YearsMax age: 85 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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 study unless medically necessary. Exclusion Criteria: * Brain Magnetic resonance imaging (MRI) (or Computed Tomography (CT)) scan suggestive of clinically significant structural CNS (central nervous system) disease confirmed by central read (e.g. cerebral large-vessel disease \[large vessel (cortical) infarcts greater than (\>) 10 milimeter (mm) in diameter\], prior macro-haemorrhage \[greater than 1 cubic centimetre (cm\^3)\], cerebral vascular malformations, cortical hemosiderosis, intracranial aneurism(s), intracranial tumours, changes suggestive of normal pressure hydrocephalus). * 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 mild cognitive impairment (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, human immunodeficiency virus (HIV), 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 participant 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 study per investigator's judgement.

Locations (491)

Banner Alzheimer's Institute

Phoenix, Arizona, United States

Imaging Endpoints

Scottsdale, Arizona, United States

Banner Sun Health Research Institute

Sun City, Arizona, United States

Tucson Neuroscience Research

Tucson, Arizona, United States

Advanced Research Center, Inc.

Anaheim, California, United States

Outcomes

Primary Outcomes

Change in the Clinical Dementia Rating - Sum of Boxes (CDR-SB) score

Score on scale (0 to 18) Measures the impact of cognitive decline on daily function using the following six domains commonly affected in Alzheimer's disease: * Cognitive domains: memory, orientation, and judgement and problem solving * Function domains: community affairs, home and hobbies, and personal care Based on clinical information obtained from the subject and informant, an individual box score ranging from 0 to 3 is determined that represents "none" to "severe" impairment for each of the six domains. The CDR-Sum of Boxes (CDR-SB) score will be derived by adding the individual scores of the six domains at a given time point. The total CDR-SB score ranges from 0 to 18 with higher scores representing greater impairment.

Time frame: From baseline (week 0) to week 104

Secondary Outcomes

Main Phase: Change in the 24-item Alzheimer's Disease Cooperative Study Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-ADL-MCI) score

Score on scale (0 to 53). An interview-based assessment of information provided by the study partner (informant). The total scores based on 18 items on the scale range from 0 to 53 with lower scores representing greater impairment.

Time frame: From baseline (week 0) to week 104

Extension phase: Change in the ADCS-ADL-MCI score

Score on scale (0 to 53) An interview-based assessment of information provided by the study partner (informant). The total scores based on 18 items on the scale range from 0 to 53 with lower scores representing greater impairment.