EVOKE

CompletedPhase 3

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

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

Lead sponsor

Novo Nordisk A/S

Asset

Semaglutide

Listed sites

447

Recruiting sites

Enrollment

1,840

actual

Study population

Alzheimer’s disease

Key I/E criterion

•CDR global 0.5

Primary endpoint

•Clinical Dementia Rating-Sum of Boxes (CDR-SB)

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Secondary ID2023-506919-18European Medical Agency (EMA)

NCT IDNCT04777396

Org study IDNN6535-4730

Secondary IDU1111-1259-2929World Health Organization (WHO)

Timeline

Milestones

Study first posted2021-03-02actual

Study start2021-05-18actual

Primary completion2025-09-16actual

Study completion2026-01-30actual

Last update posted2026-07-07actual

Assets

Drug assets

Semaglutide

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age55 Years

Maximum age85 Years

SexAll

Healthy volunteersNot accepted

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 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.

Endpoints (30)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Global cognition

Other (unclassified)

Behavior / neuropsychiatric

Function / daily living

Safety / tolerability / PK

Other clinical outcomes

Global cognition

14 endpoints

Primary/protocol endpoint

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

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

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Secondary/protocol endpoint

Main Phase: Time to progression to Clinical Dementia Rating (CDR) global score greater than or equal to (≥) 1.0 among patients with CDR global score equal to (=) 0.5 at baseline

Time frame:From baseline (week 0) up to week 156

time to event, event

Secondary/protocol endpoint

Extension Phase: Time to progression to Clinical Dementia Rating (CDR) global score greater than or equal to (≥) 1.0 among patients with CDR global score equal to (=) 0.5 at baseline

Time frame:From baseline (week 0) to week 156

time to event, event

Secondary/protocol endpoint

Main Phase: Change in the 13-item Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog-13) score

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

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint

Extension Phase: Change in the 13-item Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog-13) score

Time frame:From baseline (week 0) to week 156

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint

Main Phase: Change in the Montreal Cognitive Assessment (MoCA) score

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

Montreal Cognitive Assessment (MoCA)

change from baseline, improvement

Secondary/protocol endpoint

Extension Phase: Change in the Montreal Cognitive Assessment (MoCA) score

Time frame:From baseline (week 0) to week 156

Montreal Cognitive Assessment (MoCA)

change from baseline, improvement

Secondary/protocol endpoint

Main Phase: Change in the Alzheimer's Disease Composite Score (ADCOMS)

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

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint

Extension Phase: Change in the Alzheimer's Disease Composite Score (ADCOMS)

Time frame:From baseline (week 0) to week 156

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint

Main Phase: Change in the Mini-Mental State Examination (MMSE) score

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

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Secondary/protocol endpoint

Extension Phase: Change in the Mini-Mental State Examination (MMSE) score

Time frame:From baseline (week 0) to week 156

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Secondary/protocol endpoint

Main Phase: Change in the composite Z-score based on the three outcome measures CDR-SB, ADCS-ADL-MCI, and ADAS-Cog-13

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

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint

Extension Phase: Change in the composite Z-score based on the three outcome measures CDR-SB, ADCS-ADL-MCI, and ADAS-Cog-13

Time frame:From baseline (week 0) to week 156

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint

Extension phase: Change in the CDR-SB score

Time frame:From baseline (week 0) to week 156

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Function / daily living

2 endpoints

Secondary/protocol endpoint

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

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

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Secondary/protocol endpoint

Extension Phase:Change in the ADCS-ADL-MCI (Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory-Mild Cognitive Impairment ) score

Time frame:From baseline (week 0) to week 156

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Behavior / neuropsychiatric

4 endpoints

Secondary/protocol endpoint

Main Phase: Change in the 10-item Neuropsychiatric Inventory (NPI) score

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

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/protocol endpoint

Extension Phase: Change in the 10-item Neuropsychiatric Inventory (NPI) score

Time frame:From baseline (week 0) to week 156

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/protocol endpoint

Main Phase: Change in the EQ-5D-5L (proxy version) index score

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

change from baseline, improvement

Secondary/protocol endpoint

Extension Phase: Change in the EQ-5D-5L (proxy version) index score

Time frame:From baseline (week 0) to week 156

change from baseline, improvement

Safety / tolerability / PK

2 endpoints

Secondary/protocol endpoint

Main Phase: Number of treatment emergent adverse events (TEAEs)

Time frame:From baseline (week 0) up to week 156

event count, event

Secondary/protocol endpoint

Extension Phase: Number of treatment emergent adverse events (TEAEs)

Time frame:From baseline (week 0) up to week 156

event count, event

Other clinical outcomes

2 endpoints

Secondary/protocol endpoint

Main Phase: Time to first occurrence of major adverse cardiovascular event (MACE) comprising non-fatal myocardial infarction, non-fatal stroke and all-cause death

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

time to event, event

Secondary/protocol endpoint

Extension Phase: Time to first occurrence of major adverse cardiovascular event (MACE) comprising non-fatal myocardial infarction, non-fatal stroke and all-cause death

Time frame:From baseline (week 0) to week 156

time to event, event

Other (unclassified)

6 endpoints

Secondary/protocol endpoint/low confidence

Main Phase: Time to progression in disease stage based on global CDR score

Time frame:From baseline (week 0) up to week 156

time to event, event

Secondary/protocol endpoint/low confidence

Extension Phase: Time to progression in disease stage based on global CDR score

Time frame:From baseline (week 0) up to week 156

time to event, event

Secondary/protocol endpoint/low confidence

Main Phase: Change in high sensitivity C-reactive protein level

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

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Extension Phase: Change in high sensitivity C-reactive protein level

Time frame:From baseline (week 0) to week 156

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Main Phase: Time to first occurrence of stroke

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

time to event, event

Secondary/protocol endpoint/low confidence

Extension Phase: Time to first occurrence of stroke

Time frame:From baseline (week 0) to week 156

time to event, event

Publications (3)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.