A randomised double-blind placebo-controlled clinical trial investigating the effect and safety of oral semaglutide in subjects with early Alzheimer´s disease (EVOKE)

Study ID: 46439
Short Title: 4730 EVOKE -Semaglutide in people with early Alzheimer's disease
Organisation: Southern Health NHS Foundation Trust
Location: Marc
Condition: Dementia
Main Specialty: Dementias
Expected End Date: 17/05/2022
Postcode: SO40 2RZ
Contact Name: R&D department
Contact Email: research@southernhealth.nhs.uk
Active: Yes

Inclusion criteria, exclusion criteria and study summary

- Male or female, aged 55-85 years (both inclusive) at the time of signing informed consent. - MCI or mild dementia of the Alzheimer’s type according to the National Institute of Aging-Alzheimer’s Association (NIA-AA) 2018 criteria. - Clinical Dementia Rating (CDR) 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. - Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) delayed memory index score of less than or equal to 85. - Mini-Mental State Examination (MMSE) greater than or equal to 22. - Amyloid positivity established with either amyloid positron emission tomography (PET) or cerebrospinal fluid (CSF) Aβ1-42. - If receiving an approved Alzheimer's disease treatment (such as acetylcholinesterase inhibitors or memantine) 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. - Have a competent study partner who is a caregiver/partner/informant with a close relationship to the subject and willing to consent to attend clinic visits (that require informant input for scales) with the subject and to participate throughout the duration of the trial. The study partner needs to spend time with the subject at least 4 times a week (totalling a minimum of 10 hours per week), in order to be able to provide adequate information needed for the trial.

- Brain magnetic resonance imaging (MRI) (or computerised tomography (CT)) scan suggestive of clinically significant structural central nervous system (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 (or CT) scan suggestive of significant small vessel pathology confirmed by central read and defined as greater than 1 lacunar infarct and/or age-related white matter changes (ARWMC) greater than 2, (white matter (WM) greater than 20 mm). - 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 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.

The Evoke study is a randomised, double-blind, placebo-controlled trial to evaluate how effective and safe oral semaglutide is in patients with early Alzheimer’s disease. Alzheimer’s disease is a progressive disorder characterised by gradual cognitive and functional decline that ultimately leads to bodily dysfunction and death. Currently available treatments only provide symptomatic relief and there is a significant unmet need for treatments that can lower the rate of disease progression. Oral semaglutide is a Glucagon like peptide 1 receptor agonist (GLP1-RA), which is already approved for the treatment of Type 2 diabetes in many countries including the UK. This study is being conducted to assess at the potential benefits for patients with Alzheimer’s disease. Eligible patients will be randomised 1:1 to receive either semaglutide or placebo, both are to be administered orally once daily and added to standard patient care. Participants will require a study partner to attend some visits to share information about the participant and themselves. The study duration is approximately 173 weeks; consisting of a 12-week screening period, followed by a 156-week randomised treatment period and a 5-week follow-up period. The study consists of at least 17 clinic visits (screening assessments may require more than 1 visit) and 1 phone call. The study plans to include 1840 participants across 37 countries. In the UK, the planned number of participants is 32 across 15 sites which will include both NHS and non-NHS sites. Qualitative interviews will be performed in approximately 45 trial participants(15 subjects and 30 study partners)across 3 countries including the UK to understand participants experience with the disease and prior treatments and to explore their expectations for this treatment and this trial.

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