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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novo Nordisk A/S

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

17 May 2021 → 30 Jan 2026

Decision date (initial)

2024-03-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Novo Nordisk A/S

External identifiers

EU CT number

2023-506918-45-00

EudraCT number

2020-004864-25

WHO UTN

U1111-1259-2920

ClinicalTrials.gov

NCT04777409

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Others

To confirm the superiority of oral semaglutide once daily versus placebo when added to standard of care with respect to the change in cognition and function as measured by the Clinical Dementia Rating – Sum of Boxes (CDR-SB) score from baseline to week 104 in patients with MCI or mild dementia, both of the Alzheimer’s type.

Secondary objectives 4

1. To confirm the superiority of oral semaglutide once daily versus placebo when added to standard of care with respect to the change in function (activities of daily living) as measured by the Alzheimer’s Disease Cooperative Study Activities of Daily Living Scale for MCI (ADCS-ADL-MCI) score from baseline to week 104 in patients with MCI or mild dementia, both of the Alzheimer’s type.
2. To confirm the superiority of oral semaglutide once daily versus placebo when added to standard of care with respect to the time to progression to CDR global score ≥1.0 among patients with CDR global score = 0.5 at baseline, as measured by the Clinical Dementia Rating (CDR) scale, from baseline up to week 156 in patients with MCI or mild dementia, both of the Alzheimer's type.
3. To compare the efficacy with respect to changes in cognition and function as measured by CDR-SB score and ADCS-ADL-MCI score, from baseline to week 156, of oral semaglutide once daily versus placebo when added to standard of care in patients with MCI or mild dementia, both of the Alzheimer’s type.
4. To compare the effects of oral semaglutide versus placebo in subjects with MCI or mild dementia, both of the Alzheimer’s type, on quality of life

Conditions and MedDRA coding

Mild cognitive impairment (MCI) or mild dementia, both of the Alzheimer’s type

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration, Pharmaceuticals And Medical Devices Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Male or female, aged 55-85 years (both inclusive) at the time of signing informed consent
2. MCI or mild dementia of the Alzheimer’s type according to the NIA-AA 2018 criteria
3. CDR 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
4. RBANS delayed memory index score of below or equal to 85
5. MMSE greater than or equal to 22
6. Amyloid positivity established with either amyloid PET or CSF A beta 1-42 or CSF A beta 1-42/A beta 1-40
7. 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 4

1. 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 more than 10 mm in diameter], prior macro-haemorrhage [more than 1 cm3], cerebral vascular malformations, cortical hemosiderosis, intracranial aneurism(s), intracranial tumours, changes suggestive of normal pressure hydrocephalus)
2. Brain MRI (or CT) scan suggestive of strategic infarcts defined as bilateral thalamic lacunar infarcts and singular paramedian thalamic infarcts confirmed by central read
3. 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, learning disability, intellectual disability, hypoxic cerebral damage, or significant head trauma with loss of consciousness that led to persistent cognitive deficits
4. 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 who´s depression is controlled with treatment can be included in the trial per investigator’s judgement

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in the Clinical Dementia Rating – Sum of Boxes (CDR-SB) Score. From baseline (week 0) to week 104. Score on scale (0 to 18).

Secondary endpoints 2

1. Change in the 24-item Alzheimer’s Disease Cooperative Study Activities of Daily Living Scale for MCI (ADCS-ADL-MCI) score. From baseline (week 0) to week 104. Score on scale (0 to 53).
2. Time to progression to CDR global score ≥1.0 among patients with CDR global score = 0.5 at baseline. From baseline (week 0) up to week 156.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novo Nordisk A/S

Sponsor organisation

Novo Nordisk A/S

Address

Novo Alle 1

City

Bagsvaerd

Postcode

2880

Country

Denmark

Scientific contact point

Organisation

Novo Nordisk A/S

Contact name

EU Submission Hub

Public contact point

Organisation

Novo Nordisk A/S

Contact name

EU Submission Hub

Third parties 11

Locations

21 EU/EEA countries · 111 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 1 · Art. 52 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 216 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

11 submissions — initial application plus substantial / non-substantial modifications