A Research Study Looking at the Effect of Semaglutide on the Immune System and Other Biological Processes in People With Alzheimer's Disease

Alzheimers Disease Clinical Trial

Official title:

A Randomised Double-blind Placebo-controlled Clinical Study Investigating the Effects of Semaglutide s.c. Once-weekly Versus Placebo on Central and Peripheral Inflammation in Participants With Alzheimer's Disease

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05891496
• Other study ID #: NN6535-7519
• Secondary ID: U1111-1283-87432
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 20, 2023
• Est. completion date: September 11, 2025

Study information

• Verified date: May 2024
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study is being conducted to understand how the medicine, semaglutide, affects the immune system and other biological processes in people with Alzheimer's disease. Semaglutide is a medicine that doctors can prescribe in some countries for the treatment of type 2 diabetes and excess body weight. This study will help us understand whether semaglutide can also be used for the treatment of Alzheimer's disease. The study will last for about 77 weeks. In the first 12 weeks of treatment, participants will either get semaglutide (active medicine) or placebo (inactive dummy medicine). Which treatment participants get is decided by chance. In the following 52 weeks of treatment, all participants taking part in the study will get semaglutide. Participants must have a study partner, who is willing to take part in the study. Participants will get study medicine in a pen injector. The study partner will need to inject the study medicine into the skin of participant's stomach, thigh or upper arm once every week.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 24
• Est. completion date: September 11, 2025
• Est. primary completion date: May 16, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years to 75 Years

Eligibility

Inclusion Criteria:

• Male or female, aged 55-75 years (both inclusive) at the time of signing the informed consent
• Mild cognitive impairment (MCI) or mild dementia of the Alzheimer's type according to the National Institute on Aging- Alzheimer's Association (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) Aß1-42 or historical CSF Aß1-42/Aß1-40 (historical data within the last 5 years) or blood sample for amyloid biomarker (Aß42/Aß40 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 greater than 90 days before screening (visit 1)

Exclusion Criteria:

• Brain magnetic resonance imaging (MRI) scan suggestive of clinically significant structural central nervous system (CNS) disease confirmed by local read (example cerebral large-vessel disease [large vessel (cortical) infarcts greater than 10 millimeter (mm) in diameter], prior macro-haemorrhage [greater than 1centimeter cube (cm^3)], 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 greater than 1 lacunar infarct and/or white matter hyperintensity (WMH) Fazekas13 scale greater than 2, (white matter [WM] greater than 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

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimers Disease

Intervention

Drug:
• Semaglutide
Semagllutide will be administered once weekly subcutaneously.
• Placebo
Placebo matched to semaglutide will be administered once weekly subcutaneously.

Locations

Country	Name	City	State
Canada	Ottawa Memory Clinic	Ottawa	Ontario
Canada	Memory Program	Toronto	Ontario
Denmark	Rigshospitalet - afsnit 8015	København Ø
Italy	Azienda Ospedaliera Spedali Civili di Brescia	Brescia
Italy	Azienda Ospedaliera di Perugia;Ospedale S. Maria della Miser	Perugia
Italy	Fondazione Santa Lucia IRCCS	Roma
Sweden	Karolinska Universitetssjukhuset, Huddinge	Stockholm
Switzerland	Centre de la Mémoire	Genève
United States	Brain Matters Research	Delray Beach	Florida
United States	Banner Sun Health Research Institute	Sun City	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Canada,  Denmark,  Italy,  Sweden,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in gene expression assessed by single-cell ribonucleic acid sequencing (scRNAseq) (cells in cerebrospinal fluid [CSF])	Measured as number of differentially expressed genes.	From baseline (week 0) to visit 5 (week 12)
Primary	Change in gene expression assessed by scRNAseq (cells in blood)	Measured as number of differentially expressed genes.	From baseline (week 0) to visit 5 (week 12)
Secondary	Number of treatment emergent adverse events (TEAEs)	Measured as count of events. An adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. A TEAE is defined as an event for which the onset of the event occurs during the treatment period.	From baseline (week 0) to visit 5 (week 12)
Secondary	Number of treatment emergent adverse events (TEAEs)	Measured as count of events. An adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. A TEAE is defined as an event for which the onset of the event occurs during the treatment period.	From baseline (week 0) to end of treatment (week 64)
Secondary	Weekly average semaglutide concentration (Cavg) based on population pharmacokinetic (PK) analysis	Measured in nanomoles per liter (nmol/L).	From visit 3 (week 4) to end of treatment (week 64)