Alzheimers Disease
Conditions
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.
Interventions
DRUGSemaglutide
Semagllutide will be administered once weekly subcutaneously.
DRUGPlacebo
Placebo matched to semaglutide will be administered once weekly subcutaneously.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
55 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Gene Expression Assessed by Single-cell Ribonucleic Acid Sequencing (scRNAseq) (Cells in Cerebrospinal Fluid [CSF]) | Baseline (week 0), week 12 | 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) | Baseline (week 0), week 12 | 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
| Measure | Time frame | Description |
|---|---|---|
| Number of Treatment Emergent Adverse Events (TEAEs) | From baseline (week 0) to week 12 | 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 | From baseline (week 0) to week 64 | — |
| Weekly Average Semaglutide Concentration [Average Concentration (Cavg)] Based on Population Pharmacokinetics (PK) Analysis | From week 4 to week 64 | — |
Countries
Canada, Denmark, Italy, Sweden, Switzerland, United States
Contacts
STUDY_DIRECTORClinical Transparency (dept. 2834)
Novo Nordisk A/S
Participant flow
Recruitment details
The trial was conducted at 7 sites in 5 countries (Canada, Denmark, Sweden, Switzerland and the United States).
Pre-assignment details
Participants with mild cognitive impairment (MCI) or mild dementia, both of the Alzheimer's type were randomised in 1:1 ratio to receive subcutaneous (s.c.) injection of once weekly semaglutide or placebo matched to semaglutide. The final data for outcome measures 1,2 and 3 are reported with no further updates. Adverse events are presented for period 1 + period 2.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 65.8 Years STANDARD_DEVIATION 5.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 23 Participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 12 | 1 / 22 |
| other Total, other adverse events | 9 / 11 | 5 / 12 | 15 / 22 |
| serious Total, serious adverse events | 0 / 11 | 0 / 12 | 1 / 22 |
Outcome results
None listed