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

Novo Nordisk

Status and phase: Active, not recruiting; Phase 3

Conditions: Early Alzheimer´s Disease

Treatments: Drug: Placebo (semaglutide); Drug: Semaglutide

Study type: Interventional

Funder types: Industry

Identifiers

NCT04777409

2020-004864-25 (Registry Identifier)

U1111-1259-2920 (Other Identifier)

NN6535-4725

Details and patient eligibility

About

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.

Enrollment: 1,840 estimated patients

Sex: All

Ages: 55 to 85 years old

Volunteers: No Healthy Volunteers

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 trial unless medically necessary.

Exclusion criteria

• Brain MRI (or 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 than10 mm in diameter], prior macro-haemorrhage [greater than1 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 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,840 participants in 2 patient groups, including a placebo group

Oral semaglutide 14 mg

Experimental group

Description:

Participants are given oral semaglutide once daily

Treatment:

Drug: Semaglutide

Placebo (semaglutide)

Placebo Comparator group

Description:

Participants are given oral placebo once daily

Treatment:

Drug: Placebo (semaglutide)