DelfaGLP-1 Atlas

← Trials/Trial dossier/NCT04777409

EVOKE Plus

CompletedPhase 3

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

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

Lead sponsor

Novo Nordisk A/S

Asset

Semaglutide

Oral · GLP-1 agonist

Listed sites

495

Recruiting sites

—

Enrollment

1,840

actual

Study population

Alzheimer's / cognition

Key I/E criterion

—

Primary endpoint

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

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

NCT IDNCT04777409
Org study IDNN6535-4725
Secondary ID2023-506918-45European Medical Agency (EMA)
Secondary IDU1111-1259-2920World Health Organization (WHO)

Timeline

Milestones

Study first posted2021-03-02actual
Study start2021-05-18actual
Primary completion2025-09-15actual
Study completion2026-01-30actual
Last update posted2026-03-27actual

Assets

Investigational agents

Semaglutide

Study populations

Who this study enrolls

Alzheimer's / cognition

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 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.

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

Other clinical outcomes
19
Cardiovascular outcomes
4
Patient-reported / QoL
3
Cardiometabolic biomarkers
2
Safety / tolerability / PK
2

Cardiovascular outcomes

4 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 allcause death

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

Expanded / custom MACE composite

time to event, event

componentsNon-fatal MI, Non-fatal stroke, All-cause death

Secondary/protocol endpoint

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

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

Expanded / custom MACE composite

time to event, event

componentsNon-fatal MI, Non-fatal stroke, All-cause death

Secondary/protocol endpoint

Main Phase: Time to first occurrence of stroke

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

Stroke (any)

time to event, event

SNOMED 230690007

Secondary/protocol endpoint

Extension Phase: Time to first occurrence of stroke

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

Stroke (any)

time to event, event

SNOMED 230690007

Cardiometabolic biomarkers

2 endpoints
Secondary/protocol endpoint

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

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

hs-CRP, change

ratio, improvement

LOINC 30522-7

Secondary/protocol endpoint

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

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

hs-CRP, change

ratio, improvement

LOINC 30522-7

Patient-reported / QoL

3 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

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

EQ-5D index

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

EQ-5D index

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

Treatment-emergent AEs (any)

event count, event

Secondary/protocol endpoint

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

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

Treatment-emergent AEs (any)

event count, event

Other clinical outcomes

19 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

change from baseline, improvement

Secondary/protocol endpoint

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

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

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

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

change from baseline, improvement

Secondary/protocol endpoint/low confidence

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

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

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

change from baseline, improvement

Secondary/protocol endpoint/low confidence

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

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

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

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

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

change from baseline, improvement

Secondary/protocol endpoint

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

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

time to event, event

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

change from baseline, improvement

componentsCDR-SB, ADCS-ADL-MCI, ADAS-Cog-13

Secondary/protocol endpoint/low confidence

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

change from baseline, improvement

componentscdr sb, adcs adl mci, adas cog 13

Secondary/protocol endpoint

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

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

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

change from baseline, improvement

Secondary/protocol endpoint

Extension phase: Change in the CDR-SB score

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

change from baseline, improvement

Publications (32)

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 1, 2026
Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)
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 1, 2026 snapshot.