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Trial · Interventional

CompletedPhase 3Registry data

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

Short name EVOKE Plus

NCTNCT04777409 (opens ClinicalTrials.gov in a new tab)Other idNN6535-4725Other idU1111-1259-2920Other id2023-506918-45Other id2023
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase 3
Enrollment
1,840 participants (actual)
Sponsor
Novo Nordisk A/S · Industry
Design
Randomized · Quadruple masking
Countries
30 countries

United States, Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, China, Croatia, Czechia, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Japan, Netherlands, Poland, Portugal, Romania, Russia, Serbia, Slovakia, Slovenia, South Africa

Start
18 May 2021
Primary completion
15 Sept 2025
Completion
30 Jan 2026
First posted
2 Mar 2021
Last update posted
26 Jun 2026
Conditions
Early Alzheimer´s Disease

Timeline

1 trial · 1 completed

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2021202220232024202520262027
  1. Ph 3

    EVOKE Plus

    NCT04777409

    18 May 2021 to 30 Jan 2026

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

  • SemaglutideDrug
  • Placebo (semaglutide)Drug

Arms2

  • Experimental

    Oral semaglutide

    Participants are given oral semaglutide once daily

  • Placebo comparator

    Placebo (semaglutide)

    Participants are given oral placebo once daily

Primary outcomes1

Outcomes the sponsor listed as primary.

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

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

    Registry description

    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.

Secondary outcomes(20)

  1. 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

    Registry description

    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.

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

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

    Registry description

    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.

  3. 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

    Registry description

    Week(s)

  4. 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

    Registry description

    Week(s)

  5. 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

    Registry description

    Score on scale (0 to 85) Measures the severity of cognitive impairment in various domains including memory, language, orientation, praxis and executive function. The total scores on the scale range from 0 to 85 with higher scores representing greater impairment.

  6. 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

    Registry description

    Score on scale (0 to 85) Measures the severity of cognitive impairment in various domains including memory, language, orientation, praxis and executive function. The total scores on the scale range from 0 to 85 with higher scores representing greater impairment.

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

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

    Registry description

    Score on scale (0 to 30) The assessment includes 8 domains of cognitive function with total scores ranging from 0 to 30 and lower scores indicating greater impairment.

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

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

    Registry description

    Score on scale (0 to 30) The assessment includes 8 domains of cognitive function with total scores ranging from 0 to 30 and lower scores indicating greater impairment.

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

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

    Registry description

    Score on scale (0 to 1.97) The ADCOMS is a composite clinical outcome comprising 4 items from the ADAS-Cog-13, 2 items from the MMSE and all 6 items from the CDR-SB.32 The total scores on the scale range from 0 to 1.97 with higher scores indicating greater impairment.

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

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

    Registry description

    Score on scale (0 to 1.97) The ADCOMS is a composite clinical outcome comprising 4 items from the ADAS-Cog-13, 2 items from the MMSE and all 6 items from the CDR-SB.32 The total scores on the scale range from 0 to 1.97 with higher scores indicating greater impairment.

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

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

    Registry description

    Score on scale (0 to 30) The MMSE measures orientation, attention, memory, language and visuo-spatial function. The total scores on the scale range from 0 to 30 with lower scores indicating greater impairment.

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

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

    Registry description

    Score on scale (0 to 30) The MMSE measures orientation, attention, memory, language and visuo-spatial function. The total scores on the scale range from 0 to 30 with lower scores indicating greater impairment.

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

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

    Registry description

    Week(s)

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

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

    Registry description

    Week(s)

  15. 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

    Registry description

    Score

  16. 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

    Registry description

    Score

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

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

    Registry description

    104 Score on scale (0 to 120) The 10-item scale assesses symptoms including delusions, hallucinations, agitation/aggression, dysphoria, anxiety, euphoria, apathy, disinhibition, irritability/lability and aberrant motor activity. For each domain the frequency (4-point scale) and severity (3-point scale) of symptoms is reported. The score for each domain is calculated by multiplying the frequency and severity score. The total 10-item NPI score is 0 to 120 with higher scores indicating a greater symptomatology.

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

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

    Registry description

    104 Score on scale (0 to 120) The 10-item scale assesses symptoms including delusions, hallucinations, agitation/aggression, dysphoria, anxiety, euphoria, apathy, disinhibition, irritability/lability and aberrant motor activity. For each domain the frequency (4-point scale) and severity (3-point scale) of symptoms is reported. The score for each domain is calculated by multiplying the frequency and severity score. The total 10-item NPI score is 0 to 120 with higher scores indicating a greater symptomatology.

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

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

    Registry description

    Ratio to baseline

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

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

    Registry description

    Ratio to baseline

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

No results are posted for this trial.

Completed trials do not always post results.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies3

Studies that cite this trial.

Studies with results

1 study on this page

Indexing hint: Randomized controlled trial · 2026

4 results

Efficacy and safety of oral semaglutide 14 mg (flexible dose) in early-stage symptomatic Alzheimer's disease (evoke and evoke+): two phase 3, randomised, placebo-controlled trials.

Cummings et al. 2026Lancet (London, England)cited by 52

PMID 41865758DOI 10.1016/s0140-6736(26)00459-9PUB-41865758

Full text at the publisher4 results
Publisher pageSee results (4)

Indexing hint: Randomized controlled trial · 2025

evoke and evoke+: design of two large-scale, double-blind, placebo-controlled, phase 3 studies evaluating efficacy, safety, and tolerability of semaglutide in early-stage symptomatic Alzheimer's disease.

Cummings et al. 2025Alzheimer's research & therapycited by 146

PMID 39780249PMC11708093DOI 10.1186/s13195-024-01666-7PUB-39780249

Free to read · publisher termsCC BY-NC-ND
Read at source

More studies

1 study on this page

PubMed tag: none · 2026

Baseline characteristics from evoke and evoke+: Two phase 3 randomized placebo-controlled trials of semaglutide in participants with early-stage symptomatic Alzheimer's disease.

Scheltens et al. 2026Alzheimer's & dementia (New York, N. Y.)cited by 12

PMID 41522368PMC12789876DOI 10.1002/trc2.70200PUB-41522368

Free to read · publisher termsCC BY-NC-ND
Read at source

Other registry references

References listed at the registry that are not in PepBank. They link to PubMed.

  • Derivedvan Sloten TT, Luchsinger JA, Launer LJ, Strachan M, Cukierman-Yaffe T, Gerstein HC, Sattar N, Biessels GJ. Call for effective therapies for preventing dementia in people with type 2 diabetes. Lancet Diabetes Endocrinol. 2024 Aug;12(8):510-513. doi: 10.1016/S2213-8587(24)00158-X. Epub 2024 Jun 17. No abstract available. PMID 38901446

Eligibility

Who could join, as posted.

Sex
All
Age
from 55 Years up to 85 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
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.

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