A research study looking at the effect of semaglutide on the immune system and other biological processes in people with Alzheimer's disease

Start 25 Jul 2023 · End 8 Sep 2025 · Status Ended · 2 EU/EEA countries · 2 sites · Protocol NN6535-7519

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)

Status Ended

Participants planned 23

Countries 2

Sites 2

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

To investigate the effect of semaglutide s.c. 1.0 mg once-weekly versus placebo on central and peripheral inflammation in participants with Alzheimer’s disease

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: 25 Jul 2023 → 8 Sep 2025
Decision date (initial): 2023-11-17
Transition trial: Yes
Low-intervention: No
Rare-disease indication: No
Vulnerable population: No
Funding sources: Novo Nordisk A/S

External identifiers

EU CT number: 2023-506825-13-00
EudraCT number: 2022-003384-24
WHO UTN: U1111-1283-8743

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To investigate the effect of semaglutide s.c. 1.0 mg once-weekly versus placebo on central and peripheral inflammation in participants with Alzheimer’s disease

Secondary objectives 3

To compare the effects of semaglutide s.c. 1.0 mg once-weekly versus placebo on safety and tolerability in participants with Alzheimer’s disease
To evaluate the effects of semaglutide s.c. 1.0 mg once-weekly on safety and tolerability in participants with Alzheimer’s disease
To evaluate the steady state pharmacokinetics of semaglutide s.c. 1.0 mg once-weekly in participants with Alzheimer’s disease

Conditions and MedDRA coding

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

Version	Level	Code	Term	System organ class
20.0	LLT	10001896	Alzheimer's disease	10029205

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

Male or female, aged 55-75 years (both inclusive) at the time of signing the informed consent
MCI or mild dementia of the Alzheimer’s type according to the NIA-AA 2018 criteria
Clinical dementia rating (CDR) global score of 0.5 or 1 at screening (visit 1)
Amyloid positivity established with either historical amyloid positron emission tomography (PET) or historical cerebrospinal fluid (CSF) Aβ1-42 or historical CSF Aβ1-42/Aβ1-40 (historical data within the last 5 years) or blood sample for amyloid biomarker (Aβ42/Aβ40 ratio and p-tau217/np-tau217 ratio) at screening (visit 1)
Treated with acetylcholinesterase inhibitors (approved for the treatment of Alzheimer’s disease) and on stable dose for > 90 days before screening (visit 1)

Exclusion criteria 5

Brain magnetic resonance imaging (MRI) scan suggestive of clinically significant structural central nervous system (CNS) disease confirmed by local read (e.g., cerebral large-vessel disease [large vessel (cortical) infarcts >10 mm in diameter], prior macro-haemorrhage [>1 cm3 ], cerebral vascular malformations, cortical hemosiderosis, intracranial aneurism(s), intracranial tumours, changes suggestive of normal pressure hydrocephalus)
Brain MRI scan suggestive of significant small vessel pathology confirmed by local read and defined as >1 lacunar infarct and/or white matter hyperintensity (WMH) Fazekas scale >2, (WM >20 mm) in the deep white matter and periventricular regions
History or evidence of autoimmune diseases such as inflammatory bowel disease, rheumatoid arthritis, lupus, glomerulonephritis, psoriasis (but not limited to): Any other medical condition that would require use of systemic corticosteroids or immunosuppressants or immunostimulants in the 12 months prior to screening (visit 1)
Received a vaccine product (including booster) 4 weeks prior to screening (visit 1) or expected to receive a vaccine product (including booster) before visit 5
Use of any systemic immunomodulating drugs (small molecules and/or biologics) in the last 12 months prior to screening (visit 1) or anticipated use of such drugs during study intervention period 1 (i.e., during the first 12 weeks of treatment until visit 5), such as corticosteroids for systemic use, immunostimulants and immunosuppressants

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

Change in gene expression assessed by single-cell ribonucleic acid sequencing (scRNAseq) (cells in CSF) from baseline (week 0) to visit 5 (week 12)
Change in gene expression assessed by scRNAseq (cells in blood) from baseline (week 0) to visit 5 (week 12)

Secondary endpoints 3

Number of treatment emergent adverse events (TEAEs) from baseline (week 0) to visit 5 (week 12)
Number of treatment emergent adverse events (TEAEs) from baseline (week 0) to end of treatment (week 64)
Weekly average semaglutide concentration (C avg) based on population pharmacokinetics (PK) analysis from visit 3 (week 4) to end of treatment (week 64)

Investigational products

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

Test 3

Ozempic 1 mg solution for injection in pre-filled pen

PRD6392564 · Product

Active substance: Semaglutide
Pharmaceutical form: SOLUTION FOR INJECTION
Route of administration: SUBCUTANEOUS
Max daily dose: 00 mg milligram(s)
Max total dose: 00 mg milligram(s)
Max treatment duration: 65 Week(s)
Authorisation status: Authorised
ATC code: A10BJ06 — -
Marketing authorisation: EU/1/17/1251/005
MA holder: NOVO NORDISK A/S
MA country: EU
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: Yes
Modification description: The clinical study product is assembled in a clinical variant of the PDS290 pen-injector. Clinical batches are produced in a smaller batch size than the marketed product

Ozempic 0.5 mg solution for injection in pre-filled pen

PRD6392562 · Product

Active substance: Semaglutide
Pharmaceutical form: SOLUTION FOR INJECTION
Route of administration: SUBCUTANEOUS
Max daily dose: 00 mg milligram(s)
Max total dose: 00 mg milligram(s)
Max treatment duration: 65 Week(s)
Authorisation status: Authorised
ATC code: A10BJ06 — -
Marketing authorisation: EU/1/17/1251/003
MA holder: NOVO NORDISK A/S
MA country: EU
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: Yes
Modification description: The clinical study product is assembled in a clinical variant of the PDS290 pen-injector. Clinical batches are produced in a smaller batch size than the marketed product

Ozempic 0.25 mg solution for injection in pre-filled pen

PRD6392561 · Product

Active substance: Semaglutide
Pharmaceutical form: SOLUTION FOR INJECTION
Route of administration: SUBCUTANEOUS
Max daily dose: 00 mg milligram(s)
Max total dose: 00 mg milligram(s)
Max treatment duration: 65 Week(s)
Authorisation status: Authorised
ATC code: A10BJ06 — -
Marketing authorisation: EU/1/17/1251/002
MA holder: NOVO NORDISK A/S
MA country: EU
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: Yes
Modification description: The clinical study product is assembled in a clinical variant of the PDS290 pen-injector. Clinical batches are produced in a smaller batch size than the marketed product

Placebo 1

Semaglutide Placebo

N/A · Product

Other product name: N/A
Pharmaceutical form: N/A
ATC code: N/A — N/A
Marketing authorisation: N/A
MA holder: N/A
MA country: Iceland
Paediatric formulation: No

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

Organisation	City, country	Duties
Signant Health Management Limited ORG-100040504	Reading, United Kingdom	Other
C2n Diagnostics LLC ORG-100049457	Saint Louis, United States	Other
Pharma Bio-Research Group ORG-100012586	Groningen, Netherlands	Other
4G Clinical B.V. ORG-100044721	Amsterdam, Netherlands	Code 14
Q Squared Solutions Limited ORG-100042527	Reading, United Kingdom	Laboratory analysis
F. Hoffmann-La Roche AG ORG-100001445	Basel, Switzerland	Other
Sahlgrenska University Hospital-Vastra Gotalandsregionen ORG-100006518	Molndal, Sweden	Other
Oxford Centre for Neuroinflammation, Nuffield Department of Clinical Neurosciences ORL-000002861	Oxford, United Kingdom	Other
Oracle Danmark ApS ORG-100044663	Hellerup, Denmark	Other
Olink Proteomics AB ORG-100045757	Uppsala, Sweden	Other
Celerion Switzerland AG ORG-100013062	Fehraltorf, Switzerland	Other

Locations

2 EU/EEA countries · 2 investigational sites

By country

Country	MS status	Planned subjects	Sites
Denmark	Ended	7	1
Sweden	Ended	6	1
Rest of world Canada, Switzerland, United States	—	10	—

Investigational sites

Denmark

1 site · Ended

Rigshospitalet

N/A, Inge Lehmanns Vej 7, 2100, Copenhagen Oe

Sweden