Mild cognitive impairment (MCI) or mild dementia, both of the Alzheimer’s type MedDRA version: 20.0 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 100000004852
Conditions
Sponsors
Novo Nordisk A/S
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Male or female, aged 55-85 years (both inclusive) at the time of signing informed consent. - MCI or mild dementia of the Alzheimer’s type according to the National Institute of Aging-Alzheimer’s Association (NIA-AA) 2018 criteria. - Clinical Dementia Rating (CDR) global score of 0.5 and CDR of 0.5 or more in at least one of the three instrumental activities of daily living categories (personal care, home & hobbies, community affairs) Or CDR global score of 1.0 - Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) delayed memory index score of less than or equal to 85 - Mini-Mental State Examination (MMSE) greater than or equal to 22. - Amyloid positivity established with either amyloid positron emission tomography (PET) or cerebrospinal fluid (CSF) Aß1-42. - If receiving an approved Alzheimer's disease treatment (such as acetylcholinesterase inhibitors or memantine) the dose must have been stable for at least 3 months prior to screening and should not be changed during the trial unless medically necessary Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 276 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 1564
Exclusion criteria
Exclusion criteria: - Brain magnetic resonance imaging (MRI) (or computerised tomography (CT)) scan suggestive of clinically significant structural central nervous system (CNS) disease confirmed by central read (e.g. cerebral large-vessel disease [large vessel (cortical) infarcts greater than 10 mm in diameter], prior macro-haemorrhage [ greater than 1 cm^3], cerebral vascular malformations, cortical hemosiderosis, intracranial aneurism(s), intracranial tumours, changes suggestive of normal pressure hydrocephalus). - Brain MRI (or CT) scan suggestive of significant small vessel pathology confirmed by central read and defined as greater than 1 lacunar infarct and/or age-related white matter changes (ARWMC) greater than 2, (white matter (WM) greater than 20 mm). - Brain MRI (or CT) scan suggestive of strategic infarcts defined as bilateral thalamic lacunar infarcts and singular paramedian thalamic infarcts confirmed by central read. - Evidence of a relevant neurological disorder other than mild cognitive impairment (MCI) or mild dementia of the Alzheimer’s type at screening, including but not limited to Parkinson’s disease, Lewy body disease, frontotemporal dementia of any type, Huntington’s disease, amyotrophic lateral sclerosis, multiple sclerosis, systemic lupus erythematosus, progressive supranuclear palsy, neurosyphilis, human immunodeficiency virus (HIV), learning disability, intellectual disability, hypoxic cerebral damage, or significant head trauma with loss of consciousness that led to persistent cognitive deficits. - Evidence of a clinically relevant or unstable psychiatric disorder, based on Diagnostic and Statistical Manual of Mental Disorders (DSM–5) criteria, including schizophrenia or other psychotic disorder, or bipolar disorder. A subject with a history of major depression who has not had an episode in the last 24 months before the day of screening and is considered in remission or whose depression is controlled with treatment can be included in the trial per investigator’s judgement.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To confirm the superiority of oral semaglutide versus placebo on the change in cognition and function in subjects with MCI or mild dementia, both of the Alzheimer’s type.;Secondary Objective: To compare the effects of oral semaglutide versus placebo in subjects with MCI or mild dementia, both of the Alzheimer’s type, on: - progression to dementia among subjects with MCI at baseline - neuropsychiatric symptoms - safety and tolerability - quality of life;Primary end point(s): Change in the Clinical Dementia Rating – Sum of Boxes (CDR-SB) score;Timepoint(s) of evaluation of this end point: From baseline (week 0) to week 104 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Change in the Alzheimer’s Disease Cooperative Study Activities of Daily Living Scale for mild cognitive impairment (MCI) (ADCS-ADL-MCI) score 2. Time to progression to dementia (CDR global greater than or equal to 1.0) among subjects with MCI (CDR global equal to 0.5) at baseline 3. Change in the 13-item Alzheimer’s Disease Assessment Scale – Cognitive Subscale (ADAS-Cog-13) score 4. Change in the Montreal Cognitive Assessment (MoCA) score 5. Change in the Alzheimer’s Disease Composite Score (ADCOMS) 6. Change in the Mini-Mental State Examination (MMSE) score 7. Change in the 10-item Neuropsychiatric Inventory (NPI) score 8. Time to progression in disease stage based on global CDR score 9. Number of treatment emergent adverse events (TEAEs) 10. Change in high sensitivity C-reactive protein level 11. Time to first occurrence of major adverse cardiovascular event (MACE) comprising non-fatal myocardial infarction, non-fatal stroke and all-cause death 12. Time to first occurrence of stroke 13. Change in the EQ-5D-5L proxy score Extension phase 14. Change in the CDR-SB score 15. Change in the ADCS-ADL-MCI total score 16. Time to progression to dementia (CDR global greater than or equal to 1.0) among subjects with MCI (CDR global equal to 0.5) at baseline;Timepoint(s) of evaluation of this end point: 1.-13 From baseline (week 0) to week 104 14.-16. From baseline (week 0) to week 156 | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Czech Republic, Denmark, European Union, Finland, France, Germany, Greece, Ireland, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Norway, Poland, Portugal, Russian Federation, Serbia, Slovakia, Slovenia, South Africa, Spain, Sweden, Switzerland, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Transparency (1452)
Novo Nordisk A/S
Outcome results
None listed