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Completed

NCT Number: NCT04777396

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

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.

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Key information

Conditions

Early Alzheimer's Disease Alzheimer Disease Brain Diseases Central Nervous System Diseases Dementia Mental Disorders Nervous System Diseases Neurocognitive Disorders Neurodegenerative Diseases Tauopathies

Age range

55 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Instituto Medico Especializado_Capital Federal, Ciudad de Buenos Aires, Buenos Aires, Argentina

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Semagludtide

Drug

Oral semaglutide once-daily, dose gradually increased to 14 mg. The study will last for up to 173 weeks

Placebo (semaglutide)

Drug

Oral placebo (semaglutide) once-daily, The study will last for up to 173 weeks

Primary outcomes

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

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

    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

  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

    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 (Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory-Mild Cognitive Impairment ) score

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

    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

    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

    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

    Score on scale (0 to 85) ADAS-Cog-13 measures the severity of cognitive impairment in various domains including memory, language, orientation, praxis and executive function. The ADAS-Cog-13 is composed of tasks in the original 11-item ADAS-Cog as well as delayed word recall and number cancellation items. 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

    Score on scale (0 to 85) ADAS-Cog-13 measures the severity of cognitive impairment in various domains including memory, language, orientation, praxis and executive function. The ADAS-Cog-13 is composed of tasks in the original 11-item ADAS-Cog as well as delayed word recall and number cancellation items. 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

    Score on scale (0 to 30) The MoCA is a brief assessment of cognitive abilities including orientation, short-term memory, clock-drawing test, executive function, language abilities, animal naming, attention and abstrac-tion. 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

    Score on scale (0 to 30) The MoCA is a brief assessment of cognitive abilities including orientation, short-term memory, clock-drawing test, executive function, language abilities, animal naming, attention and abstrac-tion. 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

    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

    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

    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

    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 global CDR score

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

    Week(s)

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

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

    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

    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

    Score

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

    Time frame: From baseline (week 0) to week 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

    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

    Ratio to baseline

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

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

    Ratio to baseline

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

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

    Number of events

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

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

    Number of events

  23. 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

    Week(s)

  24. 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

    Week(s)

  25. Main Phase: Time to first occurrence of stroke

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

    Week(s

  26. Extension Phase: Time to first occurrence of stroke

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

    Week(s

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

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

    Score The EQ-5D-5L descriptive system comprises mobility, self-care, usual activities, pain/discomfort and anxiety/depression with five response levels each (no problems, slight problems, moderate problems, severe problems, unable to /extreme problems). The EQ-5D-5L proxy version 1 (the study partner is asked to rate how he/she [the proxy] would rate the subject´s health) will be used in this trial.

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

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

    Score The EQ-5D-5L descriptive system comprises mobility, self-care, usual activities, pain/discomfort and anxiety/depression with five response levels each (no problems, slight problems, moderate problems, severe problems, unable to /extreme problems). The EQ-5D-5L proxy version 1 (the study partner is asked to rate how he/she [the proxy] would rate the subject´s health) will be used in this trial.

  29. Extension phase: Change in the CDR-SB score

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

    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.

Sponsors and collaborators

Lead sponsor

Novo Nordisk A/S

Industry

Registry information

Official study title

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

Acronym: EVOKE

Important dates

Study start
2021
Primary completion
2025
Study completion
2026
First posted
Mar 2, 2021
Registry last updated
Jul 7, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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