A Randomised Double-blind Placebo-controlled Clinical Trial Investigating the Effect and Safety of Oral Semaglutide in Subjects With Early Alzheimer´s Disease (EVOKE Plus)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,840
- 试验地点
- 980
- 主要终点
- Change in the Clinical Dementia Rating - Sum of Boxes (CDR-SB) score
研究概览
简要总结
This study is done to find out whether the medicine, semaglutide, has a positive effect on early Alzheimer's disease.
Participants will either get semaglutide or placebo (a "dummy" medicine which does not contain any study medicine) - which treatment participants get is decided by an equal chance.
The study will last for up to 173 weeks (about 3 years and 4 months). Participants will have 17 clinic visits and 1 phone call with the study doctor. The study includes various tests and scans. At 10 of the clinic visits participants will have blood samples taken.
Participants must have a study partner, who is willing to take part in the study.
Women cannot take part if pregnant, breastfeeding or plan to become pregnant during the study period.
A cerebrospinal fluid (CSF) sub-study will be performed as a part of the study. The sub-study will be performed on a selection of sites based on their experience with CSF sampling and willingness to participate in this sub-study. The endpoints related to this sub-study are exploratory only.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Sponsor staff involved in the clinical trial is masked according to company standard procedures.
入排标准
- 年龄范围
- 55 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, aged 55-85 years (both inclusive) at the time of signing informed consent.
- •MCI (mild cognitive impairment) or mild dementia of the Alzheimer's type according to the NIA-AA (National Institute of Aging-Alzheimer's Association) 2018 criteria.
- •CDR (Clinical Dementia Rating) 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
- •RBANS (Repeatable Battery for the Assessment of Neuropsychological Status) delayed memory index score of below or equal to (≤) 85
- •MMSE (Mini-Mental State Examination) greater than or equal to (≥) 22
- •Amyloid positivity established with either amyloid PET (positron emission tomography), CSF (cerebrospinal fluid) Aβ1-42 or CSF Aβ1-42/Aβ1-
- •If receiving an approved Alzheimer's disease treatment (such as acetylcholinesterase inhibitors, memantine or aducanumab) the dose must have been stable for at least 3 months prior to screening and should not be changed during the study unless medically necessary.
排除标准
- •Brain Magnetic resonance imaging (MRI) (or Computed Tomography (CT)) scan suggestive of clinically significant structural CNS (central nervous system) disease confirmed by central read (e.g. cerebral large-vessel disease [large vessel (cortical) infarcts greater than (>) 10 milimeter (mm) in diameter], prior macro-haemorrhage [greater than 1 cubic centimetre (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 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 participant 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 study per investigator's judgement.
研究组 & 干预措施
Placebo (semaglutide)
Participants are given oral placebo once daily
干预措施: Placebo (semaglutide) (Drug)
Oral semaglutide
Participants are given oral semaglutide once daily
干预措施: Semaglutide (Drug)
结局指标
主要结局
Change in the Clinical Dementia Rating - Sum of Boxes (CDR-SB) score
时间窗: From baseline (week 0) to week 104
Score on scale (0 to 18) Measures the impact of cognitive decline on daily function using the following six domains commonly affected in Alzheimer's disease: * Cognitive domains: memory, orientation, and judgement and problem solving * Function domains: community affairs, home and hobbies, and personal care Based on clinical information obtained from the subject and informant, an individual box score ranging from 0 to 3 is determined that represents "none" to "severe" impairment for each of the six domains. The CDR-Sum of Boxes (CDR-SB) score will be derived by adding the individual scores of the six domains at a given time point. The total CDR-SB score ranges from 0 to 18 with higher scores representing greater impairment.
次要结局
- Main Phase: Change in the 24-item Alzheimer's Disease Cooperative Study Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-ADL-MCI) score(From baseline (week 0) to week 104)
- Extension phase: Change in the ADCS-ADL-MCI score(From baseline (week 0) to week 156)
- Main Phase: Time to progression to Clinical Dementia Rating (CDR) global score greater than or equal to (≥)1.0 among patients with CDR global score equal to (=) 0.5 at baseline(From baseline (week 0) up to week 156)
- Extension Phase: Time to progression to Clinical Dementia Rating (CDR) global score greater than or equal to (≥)1.0 among patients with CDR global score equal to (=) 0.5 at baseline(From baseline (week 0) to week 156)
- Main Phase: Change in the 13-item Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog-13) score(From baseline (week 0) to week 104)
- Extension Phase: Change in the 13-item Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog-13) score(From baseline (week 0) to week 156)
- Main Phase: Change in the Montreal Cognitive Assessment (MoCA) score(From baseline (week 0) to week 104)
- Extension Phase: Change in the Montreal Cognitive Assessment (MoCA) score(From baseline (week 0) to week 156)
- Main Phase: Change in the Alzheimer's Disease Composite Score (ADCOMS)(From baseline (week 0) to week 104)
- Extension Phase: Change in the Alzheimer's Disease Composite Score (ADCOMS)(From baseline (week 0) to week 156)
- Main Phase: Change in the Mini-Mental State Examination (MMSE) score(From baseline (week 0) to week 104)
- Extension Phase: Change in the Mini-Mental State Examination (MMSE) score(From baseline (week 0) to week 156)
- Main Phase: Time to progression in disease stage based on CDR global score(From baseline (week 0) up to week 156)
- Extension Phase: Time to progression in disease stage based on CDR global score(From baseline (week 0) to week 156)
- Main Phase: Change in the composite Z-score based on the three outcome measures CDR-SB, ADCS-ADL-MCI, and ADAS-Cog-13(From baseline (week 0) to week 104)
- Extension Phase: Change in the composite Z-score based on the three outcome measures CDR-SB, ADCS-ADL-MCI, and ADAS-Cog-13(From baseline (week 0) to week 156)
- Main Phase: Change in the 10-item Neuropsychiatric Inventory (NPI) score(From baseline (week 0) to week 104)
- Extension Phase: Change in the 10-item Neuropsychiatric Inventory (NPI) score(From baseline (week 0) to week 156)
- Main Phase: Change in high sensitivity C-reactive protein level(From baseline (week 0) to week 104)
- Extension Phase: Change in high sensitivity C-reactive protein level(From baseline (week 0) to week 156)
- Main Phase: Number of treatment emergent adverse events (TEAEs)(From baseline (week 0) up to week 156)
- Extension Phase: Number of treatment emergent adverse events (TEAEs)(From baseline (week 0) to week 156)
- Main Phase: 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)
- Extension Phase: 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 156)
- Main Phase: Time to first occurrence of stroke(From baseline (week 0) to week 104)
- Extension Phase: Time to first occurrence of stroke(From baseline (week 0) to week 156)
- Main Phase: Change in the EQ-5D-5L (proxy version) index score(From baseline (week 0) to week 104)
- Extension Phase: Change in the EQ-5D-5L (proxy version) index score(From baseline (week 0) to week 156)
- Extension phase: Change in the CDR-SB score(From baseline (week 0) to week 156)