Semaglutide for Early Alzheimer's Disease

(EVOKE Trial)

Recruiting at 705 trial locations

Overseen By Novo Nordisk

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novo Nordisk A/S

Must be taking: Alzheimer's treatments

Disqualifiers: Parkinson's, Schizophrenia, Bipolar, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 17

Duration: 173 weeks

1840 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

If you are taking an approved Alzheimer's treatment, you can continue as long as your dose has been stable for at least 3 months before the trial and doesn't change during the trial unless necessary.

How does the drug semaglutide differ from other treatments for Alzheimer's disease?

Semaglutide is unique because it is primarily used for diabetes and weight management, but it is being explored for Alzheimer's due to its potential effects on brain health. Unlike traditional Alzheimer's treatments that focus on symptoms, semaglutide may offer a novel approach by potentially modifying disease progression. ^{1 2 3 4 5}

What is the purpose of this trial?

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.

Research Team

Clinical Transparency (Dept. 2834)

Principal Investigator

Novo Nordisk A/S

Eligibility Criteria

The EVOKE trial is for people aged 55-85 with early Alzheimer's, having an MMSE score of ≥22 and specific memory index scores. They must have stable Alzheimer's medication for 3 months if applicable, and show amyloid presence via PET or CSF tests. A study partner is required. Pregnant women or those planning pregnancy are excluded.

Inclusion Criteria

My tests show amyloid buildup in my brain.

You scored 22 or higher on the Mini-Mental State Examination.

My Alzheimer's medication dose has been stable for 3 months.

Exclusion Criteria

A brain scan shows signs of specific types of strokes confirmed by a specialist.

I have a neurological disorder that is not mild cognitive impairment or mild Alzheimer's.

You have a serious mental health condition that is not stable.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either semaglutide or placebo for up to 173 weeks

173 weeks

17 clinic visits, 1 phone call

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension Phase

Participants continue to be monitored for changes in cognitive and functional scores

52 weeks

Treatment Details

Interventions

• Placebo (semaglutide)
• Semaglutide

Trial Overview Semaglutide's effect on early Alzheimer’s disease is being tested against a placebo over approximately 3 years with clinic visits and one phone call. Participants will undergo various tests, scans, and blood samples to assess the medicine's impact.

Participant Groups

Group I: Oral Semaglutide Experimental Treatment 1 Intervention

Participants are given oral semaglutide once daily

Group II: Placebo (semagludtide) Placebo Group 1 Intervention

Participants are given oral placebo once daily

Who Is Running the Clinical Trial?

Novo Nordisk A/S

Lead Sponsor

Trials

1,578

Recruited

3,813,000+

Lars Fruergaard Jørgensen

Novo Nordisk A/S

Chief Executive Officer since 2017

MSc in Finance and Business Administration, Aarhus School of Business, Aarhus University, Denmark

Martin Holst Lange

Novo Nordisk A/S

Chief Medical Officer since 2021

MD from University of Copenhagen

Findings from Research

Memantine, a drug that blocks NMDA receptors, showed a small but significant benefit in patients with moderate-to-severe Alzheimer's disease after 28 weeks, with a mean difference of 0.3 in the global score compared to placebo.

Patients taking memantine experienced less deterioration in daily living activities, with a score change of 2.1 compared to 3.4 in the placebo group, highlighting its potential as a valuable treatment option in a field with limited effective medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is memantine a breakthrough in the treatment of moderate-to-severe Alzheimer's disease? Doggrell, S.[2019]

Current Alzheimer's disease treatments mainly focus on improving symptoms rather than halting disease progression, with only selegiline and vitamin E showing any delay in important clinical endpoints.

Research is ongoing for new treatments aimed at slowing progression or preventing onset, including antioxidants, anti-inflammatory agents, and drugs targeting amyloid deposition, with trials also focusing on preventing Alzheimer's in individuals with mild cognitive impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trials to slow progression and prevent disease onset. Thal, LJ.[2019]

Selegiline showed a statistically significant but clinically unimportant improvement in cognitive performance and activities of daily living in Alzheimer's patients during the short term (4-17 weeks), based on data from 821 patients across 14 trials.

No long-term benefits were observed, and there were no significant differences in emotional state or overall global response between selegiline and placebo, indicating limited efficacy for this treatment in Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of selegiline in the treatment of people with Alzheimer's disease: a meta-analysis of published trials. Wilcock, GK., Birks, J., Whitehead, A., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Short-term administration of selegiline for mild-to-moderate dementia of the Alzheimer's type. [2017]

2. England pubmed.ncbi.nlm.nih.gov

Is memantine a breakthrough in the treatment of moderate-to-severe Alzheimer's disease? [2019]

3. Austria pubmed.ncbi.nlm.nih.gov

Trials to slow progression and prevent disease onset. [2019]

4. England pubmed.ncbi.nlm.nih.gov

The effect of selegiline in the treatment of people with Alzheimer's disease: a meta-analysis of published trials. [2019]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Immunotherapy against amyloid pathology in Alzheimer's disease. [2013]