Clinical trial NCT05891496: A Research Study Looking at the Effect of Semaglutide on the Immune System and Other Biological Processes in People With Alzheimer's Disease
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Alzheimers Disease
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2023-06-07
Enrollment: 24
Sex: ALL
Minimum age (years): 55
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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) 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 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

Primary outcomes:
measure: Change in gene expression assessed by single-cell ribonucleic acid sequencing (scRNAseq) (cells in cerebrospinal fluid [CSF])
timeFrame: From baseline (week 0) to visit 5 (week 12)
measure: Change in gene expression assessed by scRNAseq (cells in blood)
timeFrame: From baseline (week 0) to visit 5 (week 12)
Secondary outcomes:
measure: Number of treatment emergent adverse events (TEAEs)
timeFrame: From baseline (week 0) to visit 5 (week 12)
measure: Number of treatment emergent adverse events (TEAEs)
timeFrame: From baseline (week 0) to end of treatment (week 64)
measure: Weekly average semaglutide concentration (Cavg) based on population pharmacokinetic (PK) analysis
timeFrame: From visit 3 (week 4) to end of treatment (week 64)
Other outcomes:
Locations:
city: Sun City
country: United States
facility: Banner Sun Health Research Institute
state: Arizona
city: Delray Beach
country: United States
facility: Brain Matters Research
state: Florida
city: Ottawa
country: Canada
facility: Ottawa Memory Clinic
state: Ontario
city: Toronto
country: Canada
facility: Memory Program
state: Ontario
city: København Ø
country: Denmark
facility: Rigshospitalet - afsnit 8015
city: Brescia
country: Italy
facility: Azienda Ospedaliera Spedali Civili di Brescia
city: Perugia
country: Italy
facility: Azienda Ospedaliera di Perugia;Ospedale S. Maria della Miser
city: Roma
country: Italy
facility: Fondazione Santa Lucia IRCCS
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset, Huddinge
city: Genève
country: Switzerland
facility: Centre de la Mémoire
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Transparency (dept. 2834)
role: STUDY_DIRECTOR
References: