Trial · Interventional

CompletedPhase 3Results postedRegistry data

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

NCTNCT05891496Other idNN6535-7519Other idU1111-1283-8743Other id2022-003384-24Other id2023-506825-13

Open at ClinicalTrials.govAsk about this trial

Overview

Status: Completed
Phase: Phase 3
Enrollment: 23 participants (actual)
Sponsor: Novo Nordisk A/S · Industry
Design: Randomized · Quadruple masking
Countries: 6 countries
United States, Canada, Denmark, Italy, Sweden, Switzerland
Start: 20 Jun 2023
Primary completion: 19 Aug 2024
Completion: 8 Sept 2025
First posted: 7 Jun 2023
Last update posted: 18 Aug 2026
Conditions: Alzheimers Disease

Timeline

1 trial · 1 completed · 1 with posted results

Completed
Ongoing
Not yet recruiting
Stopped
Estimated dates (est.)
Results posted

2023202420252026

Ph 3
A Research Study Looking at the Effect of Semaglutide on the Immune System and Other Biological Processes in People With Alzheimer's Disease
NCT05891496
20 Jun 2023 to 8 Sept 2025

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

SemaglutideDrug
PlaceboDrug

Arms2

Experimental
Study intervention period 1
Participants will receive either semaglutide or placebo matched to semaglutide once-weekly subcutaneous (s.c.) injections for 12 weeks as an add on therapy to standard of care. Participants initially received 0.25 milligram (mg) once weekly and the dose was then escalated once in 4 weeks until the maintenance dose (1.0 mg) was reached: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12).
Placebo comparator
Study intervention period 2
All participants will receive 1.0 mg semaglutide s.c. injections once weekly for 52 weeks during study intervention period 2 as an add-on therapy to standard of care. Participants randomised to semaglutide s.c. 1.0 mg during study intervention period 1 remained on 1.0 mg target maintenance dose for 52 weeks from weeks 12-64. Participants initially randomised to placebo during study intervention period 1 will receive semaglutide s.c. in dose escalation fashion for 8 weeks (0.25 mg from weeks 12-16 and 0.5 mg from weeks 16-20) followed by a maintenance period from weeks 20-64 at dose 1.0 mg.

Primary outcomes2

Outcomes the sponsor listed as primary.

Change in Gene Expression Assessed by Single-cell Ribonucleic Acid Sequencing (scRNAseq) (Cells in Cerebrospinal Fluid [CSF])
Time frame · Baseline (week 0), week 12
Registry description
Change in gene expression assessed by scRNAseq (cells in CSF) from baseline (week 0) to week 12 is presented. Change in gene expression is presented as the mean number of differentially expressed genes (DEG).
Change in Gene Expression Assessed by scRNAseq (Cells in Blood)
Time frame · Baseline (week 0), week 12
Registry description
Change in gene expression assessed by scRNAseq (cells in blood) from baseline (week 0) to week 12 is presented. Change in gene expression is presented as the mean number of differentially expressed genes.

Secondary outcomes(3)

Number of Treatment Emergent Adverse Events (TEAEs)
Time frame · From baseline (week 0) to week 12
Registry description
An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant that is temporally associated with the use of investigational medicinal product (IMP), whether or not considered related to the IMP. All AEs mentioned here are treatment emergent adverse events (TEAE) defined as an event with onset during the on-treatment period.
Number of TEAEs
Time frame · From baseline (week 0) to week 64
Weekly Average Semaglutide Concentration [Average Concentration (Cavg)] Based on Population Pharmacokinetics (PK) Analysis
Time frame · From week 4 to week 64

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· Baseline (week 0), week 12

Change in Gene Expression Assessed by Single-cell Ribonucleic Acid Sequencing (scRNAseq) (Cells in Cerebrospinal Fluid [CSF])

Group	Value (Differentially expressed genes)	Spread
Semaglutide	41.25	29.68
Placebo	21.00	25.70

Primary outcomeMean· Baseline (week 0), week 12

Change in Gene Expression Assessed by scRNAseq (Cells in Blood)

Group	Value (Differentially expressed genes)	Spread
Semaglutide	10.00	5.97
Placebo	16.50	15.86

Secondary and other outcome results(3)

Secondary outcomeNumber· From baseline (week 0) to week 12

Number of Treatment Emergent Adverse Events (TEAEs)

Group	Value (Events)
Semaglutide	31
Placebo	8

Secondary outcome· From baseline (week 0) to week 64

Number of TEAEs

Group	Value

Secondary outcome· From week 4 to week 64

Weekly Average Semaglutide Concentration [Average Concentration (Cavg)] Based on Population Pharmacokinetics (PK) Analysis

Group	Value

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
Group	Deaths	Serious events	Other events
Semaglutide Period 1Participants received once-weekly subcutaneous (s.c.) injections of semaglutide for 12 weeks as an add on therapy to standard of care. Participants initially received once weekly semaglutide and the dose was then escalated once in 4 weeks until the maintenance dose was reached.	0 / 11	0 / 11	9 / 11
PlaceboParticipants received once-weekly s.c. injections of placebo matched to semaglutide for 12 weeks.	0 / 12	0 / 12	5 / 12
Semaglutide Period 2Participants from semaglutide period 1 arm received once weekly s.c. injection of maintenance dose semaglutide and participants from placebo arm received s.c. administration of semaglutide in dose escalation manner until the maintenance dose was reached up to 64 weeks.	1 / 22	1 / 22	15 / 22

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex: All
Age: from 55 Years up to 75 Years
Healthy volunteers: Not accepted

Inclusion and exclusion criteria, as posted

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

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