This study has been transitioned to CTIS with ID 2023-506919-18-00 check the CTIS register for the current data. Primary objectiveTo confirm the superiority of oral semaglutide versus placebo on the change in cognition and function in subjects with…
ID
Source
Brief title
Condition
- Dementia and amnestic conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Change in the Clinical Dementia Rating - Sum of Boxes (CDR-SB) score From
baseline (week 0) to week 104
Secondary outcome
Secondary confirmatory endpoints
-Change in the Alzheimer*s Disease Cooperative Study Activities of Daily Living
Scale for MCI (ADCS-ADLMCI) score from baseline (week 0) to week 104
-Time to progression to dementia (CDR global >=1.0) among subjects with MCI (CDR
global = 0.5) at baseline From baseline (week 0) to week 104
Supportive secondary endpoints
-Change in the 13-item Alzheimer*s Disease Assessment Scale - Cognitive
Subscale (ADAS-Cog-13) score From baseline (week 0) to week 104
-Change in the Montreal Cognitive Assessment (MoCA) score from baseline (week
0) to week 104
-Change in the Alzheimer*s Disease Composite Score (ADCOMS) From baseline (week
0) to week 104
-Change in the Mini-Mental State Examination (MMSE) score from baseline (week
0) to week 104
-Change in the 10-item Neuropsychiatric Inventory (NPI) score from baseline
(week 0) to week 104
-Time to progression in disease stage based on global CDR score from baseline
(week 0) to week 104
-Number of treatment emergent adverse events (TEAEs) From baseline (week 0) to
week 104
-Change in high sensitivity C-reactive protein level from baseline (week 0) to
week 104
-Time to first occurrence of major adverse cardiovascular event (MACE)
comprising non-fatal myocardial infarction, non-fatal stroke and allcause death
from baseline (week 0) to week 104
-Time to first occurrence of stroke from baseline (week 0) to week 104
-Change in the EQ-5D-5L proxy score from baseline (week 0) to week 104
Extension phase
-Change in the CDR-SB score from baseline (week 0) to week 156
-Change in the ADCS-ADL-MCI score from baseline (week 0) to week 156
-Time to progression to dementia (CDR global >=1.0) among subjects with MCI (CDR
global = 0.5) at baseline From baseline (week 0) to week 156
Background summary
Dementia is a rapidly growing public health concern causing a significant
global socioeconomic impact. Clinically, the continuum of disease progression
from mild cognitive impairment (MCI) to mild, moderate and severe dementia is
accompanied by gradual loss of cognitive function and increasing difficulties
in performing activities of daily living. Therefore, therapeutic interventions
targeting the early stages of cognitive impairment could have substantial
clinical and economic consequences for patients, their caregivers and society.
Currently there are no treatments available
for the treatment of MCI and only symptomatic treatments are available for
dementia of the Alzheimer*s type. Semaglutide and liraglutide are structurally
similar glucagon-like peptide-1 receptor agonists (GLP-1 RAs) modified via
fatty acid acylation, while semaglutide was further optimised to provide the
convenience of oral administration. The potential effects of semaglutide and
liraglutide on cognition and related mechanisms have been investigated in
relevant preclinical models of Alzheimer*s disease, atherosclerosis and
inflammation.
Study objective
This study has been transitioned to CTIS with ID 2023-506919-18-00 check the CTIS register for the current data.
Primary 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 objectives
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
Study design
This is a randomised (1:1), double-blind, placebo-controlled, multicentre,
multinational trial comparing oral semaglutide 14 mg OD versus placebo, both
added to standard of care in subjects with MCI or mild dementia of the
Alzheimer*s type.
Intervention
Oral semaglutide 3mg, 7mg, 14mg tablets or placebo tablets
Study burden and risks
The safety and tolerability of oral semaglutide is well established in a
comprehensive clinical development programme for T2DM. Based on this extensive
clinical experience, all necessary precautions are implemented in the trial
design and planned conduct of the trial to minimise risks
associated with the treatment as well as participation in the trial. Taking
into account the measures taken to minimise risk to subjects participating in
this trial, the potential risks identified in association with oral semaglutide
are justified by the anticipated benefits that may be afforded to subjects with
MCI or mild dementia of the Alzheimer*s type.
Flemingweg 8
Alphen aan den Rijn 2408AV
NL
Flemingweg 8
Alphen aan den Rijn 2408AV
NL
Listed location countries
Age
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) Aβ1-42.
-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
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
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-506919-18-00 |
| EudraCT | EUCTR2020-004848-29-NL |
| CCMO | NL76795.056.21 |
| Other | UTN: U1111-1259-2929 |