1840 Participants Needed

Semaglutide for Early Alzheimer's Disease

(EVOKE Plus Trial)

Recruiting at 790 trial locations
NN
Overseen ByNovo Nordisk
Age: 18+
Sex: Any
Trial Phase: Phase 3
Sponsor: Novo Nordisk A/S
Must be taking: Alzheimer's treatments
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 4 JurisdictionsThis treatment is already approved in other countries

What You Need to Know Before You Apply

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.

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 study and doesn't change during the study unless necessary.

Is semaglutide safe for humans?

Semaglutide, used for type 2 diabetes under names like Rybelsus, Ozempic, and Wegovy, has been shown to be generally safe in humans. It has a tolerability profile similar to other drugs in its class and has been tested in thousands of patients, showing no major safety concerns.12345

How is the drug Semaglutide unique for treating early Alzheimer's disease?

Semaglutide is unique because it is a glucagon-like peptide-1 (GLP-1) analogue that may protect against Alzheimer's disease by enhancing autophagy (the body's way of cleaning out damaged cells) and inhibiting apoptosis (cell death). It is also notable for its once-weekly administration, which is different from many other treatments.15678

Who Is on the Research Team?

CT

Clinical Transparency (dept. 2834)

Principal Investigator

Novo Nordisk A/S

Are You a Good Fit for This Trial?

This trial is for people aged 55-85 with early Alzheimer's, confirmed by specific tests. They must have certain cognitive scores and stable treatment if they're already on Alzheimer's medication. Participants need a study partner and can't join if pregnant or planning pregnancy during the trial.

Inclusion Criteria

I am between 55 and 85 years old.
My Alzheimer's medication dose has been stable for 3 months.
I have mild dementia, with some difficulty in daily activities.
See 8 more

Exclusion Criteria

You have specific signs of stroke in a brain scan.
I do not have an active severe mental health condition.
I do not have a major neurological disorder besides mild Alzheimer's or MCI.
See 1 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either semaglutide or placebo for the duration of the study

104 weeks
17 clinic visits, 1 phone call

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Participants continue to be monitored for changes in cognitive scores and adverse events

52 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • Placebo (semaglutide)
  • Semaglutide
Trial Overview The EVOKE Plus study is testing Semaglutide against a placebo to see if it helps with early Alzheimer's disease symptoms. Over roughly 3 years, participants will visit clinics for tests and scans, including blood samples at some visits.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Oral semaglutideExperimental Treatment1 Intervention
Participants are given oral semaglutide once daily
Group II: Placebo (semaglutide)Placebo Group1 Intervention
Participants are given oral placebo once daily

Semaglutide is already approved in European Union, United States, Canada, Japan for the following indications:

🇪🇺
Approved in European Union as Ozempic for:
  • Type 2 diabetes
  • Cardiovascular disease
  • Obesity
🇺🇸
Approved in United States as Ozempic for:
  • Type 2 diabetes
  • Cardiovascular disease
  • Obesity
🇨🇦
Approved in Canada as Ozempic for:
  • Type 2 diabetes
  • Cardiovascular disease
  • Obesity
🇯🇵
Approved in Japan as Ozempic for:
  • Type 2 diabetes
  • Cardiovascular disease
  • Obesity
🇺🇸
Approved in United States as Wegovy for:
  • Obesity
🇺🇸
Approved in United States as Rybelsus for:
  • Type 2 diabetes

Find a Clinic Near You

Who Is Running the Clinical Trial?

Novo Nordisk A/S

Lead Sponsor

Trials
1,578
Recruited
3,813,000+
Lars Fruergaard Jørgensen profile image

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 profile image

Martin Holst Lange

Novo Nordisk A/S

Chief Medical Officer since 2021

MD from University of Copenhagen

Published Research Related to This Trial

Semaglutide has shown potential protective effects against Alzheimer's disease by enhancing autophagy and inhibiting apoptosis in SH-SY5Y cells treated with Aβ25-35, a model for Alzheimer's.
The study found that semaglutide increased levels of autophagy-related proteins (like LC3II and Beclin-1) and decreased apoptosis-related proteins (like Bax), suggesting a mechanism through which it may help protect against neurodegeneration.
Semaglutide-mediated protection against Aβ correlated with enhancement of autophagy and inhibition of apotosis.Chang, YF., Zhang, D., Hu, WM., et al.[2021]
Oral semaglutide (Rybelsus®) has been shown to provide better glycaemic control and promote weight loss in patients with type 2 diabetes (T2DM) compared to standard oral glucose-lowering medications, based on data from the PIONEER clinical trial program involving 9543 patients.
The safety profile of oral semaglutide is similar to other GLP-1 receptor agonists, and it demonstrated cardiovascular safety comparable to placebo in high-risk patients, making it a viable option for T2DM management.
[Oral semaglutide, first oral GLP-1 receptor agonist (Rybelsus®)].Paquot, N.[2022]
In a study of 20 patients with type 2 diabetes in Slovenia, oral semaglutide significantly reduced HbA1c levels and fasting plasma glucose, indicating its efficacy in improving glycaemic control.
Patients reported high satisfaction with the treatment, and while some experienced mild gastrointestinal side effects, the overall safety profile was considered good, suggesting that oral semaglutide is a promising option for diabetes management.
Efficacy, safety, and patient satisfaction with oral semaglutide: first single-centre clinical experience.Janić, M., Jovanović, M., Janež, A., et al.[2023]

Citations

Semaglutide-mediated protection against Aβ correlated with enhancement of autophagy and inhibition of apotosis. [2021]
[Oral semaglutide, first oral GLP-1 receptor agonist (Rybelsus®)]. [2022]
Efficacy, safety, and patient satisfaction with oral semaglutide: first single-centre clinical experience. [2023]
Semaglutide as a therapeutic option for elderly patients with type 2 diabetes: Pooled analysis of the SUSTAIN 1-5 trials. [2022]
[New drug for type 2 diabetes: introduction of oral Semaglutide (Rybelsus® tablets), an oral GLP-1 receptor agonist]. [2022]
[Semaglutide, once weekly GLP-1 receptor agonist (Ozempic®)]. [2019]
[An orally administered glucagon-like peptide 1 (GLP1) analogue: A landmark in the treatment of type 2 diabetes]. [2022]
Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as an add-on to metformin, thiazolidinediones, or both, in patients with type 2 diabetes (SUSTAIN 2): a 56-week, double-blind, phase 3a, randomised trial. [2022]
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