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

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

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.

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

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

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.

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

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

Week(s)

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

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

Week(s)

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

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

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.

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

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

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.

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

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

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.

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

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

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.

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

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

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.

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

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

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.

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

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

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.

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

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

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.

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

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

Week(s)

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

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

Week(s)

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

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

Score

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

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

Score

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

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

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.

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

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

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.

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

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

Ratio to baseline

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

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

Ratio to baseline

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

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

Number of events

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

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

Number of events

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

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

Week(s)

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

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

Week(s)

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

Main Phase: Time to first occurrence of stroke

Week(s

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

Extension Phase: Time to first occurrence of stroke

Week(s

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

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

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.

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

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

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.

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

Extension phase: Change in the CDR-SB score

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.

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