A Placebo-Controlled, Double-Blind, Parallel-Group, Randomized, Proof-of-Concept, Dose-Finding Study To Evaluate Safety, Tolerability, and Efficacy of E2609 in Subjects With Mild Cognitive Impairment Due to Alzheimer's Disease (Prodromal Alzheimer's Disease) and Mild to Moderate Dementia Due to Alzheimer's Disease
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Eisai Inc.
- 入组人数
- 70
- 主要终点
- Core Phase: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
研究概览
简要总结
This is a Phase 2 study to evaluate safety and efficacy in participants with Mild Cognitive Impairment due to Alzheimer's Disease/Prodromal Alzheimer's Disease (referred to as MCI/Prodromal) and mild to moderate dementia due to Alzheimer's Disease (referred to as mild to moderate AD). This study will have a Core Phase and an Extension Phase.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 50 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
MCI/Prodromal Cohort: Low Dose
A low dose of E2609 will be assessed.
干预措施: E2609 (Drug)
MCI/Prodromal Cohort: Middle Dose
A middle dose of E2609 will be assessed.
干预措施: E2609 (Drug)
MCI/Prodromal Cohort: High Dose
A high dose of E2609 will be assessed.
干预措施: E2609 (Drug)
MCI/Prodromal Cohort: Placebo
干预措施: Placebo (Drug)
Mild to Moderate AD Cohort: Low Dose
A low dose of E2609 will be assessed.
干预措施: E2609 (Drug)
Mild to Moderate AD Cohort: High Dose
A high dose of E2609 will be assessed.
干预措施: E2609 (Drug)
Mild to Moderate AD Cohort: Placebo
干预措施: Placebo (Drug)
Mild to Moderate AD cohort: Middle Dose
A middle dose of E2609 will be assessed.
干预措施: E2609 (Drug)
结局指标
主要结局
Core Phase: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
时间窗: Up to 21 months
A TEAE is defined as an adverse event that emerges during treatment, having been absent at pre-treatment (Baseline) or re-emerges during treatment, having been present at pre-treatment (Baseline) but stopped before treatment, or worsens in severity during treatment relative to the pre-treatment state, when the adverse event is continuous.
Extension Phase: Number of Participants With TEAEs and SAEs
时间窗: Up to 34 months
TEAE: adverse event that emerges during treatment, having been absent at pre-treatment or reemerges during treatment, having been present at pre-treatment but stopped before treatment, or worsens in severity during treatment relative to pre-treatment state. Number of participants with TEAEs were reported based on safety assessments of laboratory tests, physical examination, regular measurement of vital signs, magnetic resonance imaging and electrocardiogram parameter values. SAE: any untoward medical occurrence that at any dose: results in death; is life-threatening (immediate risk of death from adverse event, this does not include event that, had it occurred in more severe form or is allowed to continue, might have caused death); requires inpatient or prolongation of existing hospitalization; results in persistent/significant disability/incapacity; is congenital anomaly/birth defect (in child of participant exposed to drug). Number of participants with TEAEs and SAEs were reported.
Extension Phase: Number of Participants With Markedly Abnormal ECG Findings
时间窗: Up to 34 months
QTcF interval means QTc interval calculated using Fridericia's formula.
Extension Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values
时间窗: Up to 34 months
Extension Phase: Number of Participants With Markedly Abnormal Vital Sign Values
时间窗: Up to 34 months
Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values
时间窗: Month 0(Baseline,Week 2,Week 3,Week 4);Month 1(Week 5,Week 7);Month 2(Week 9,Week 11);Month 3(Week 13);Month 4(Week 17);Month 5(Week 21);Month 6(Week 27);Month 9(Week 40);Month 12(Week 53);Month 15(Week 66);Month 18(Week 79) and Follow-up at Month 1 and 3
Participants having no markedly abnormal vital sign values (no markedly abnormal high or no markedly abnormal low) in all core phase arms were not included in the data reported.
Extension Phase: Number of Participants With Abnormal Magnetic Resonance Imaging (MRI) Findings
时间窗: Up to 34 months
Brain MRIs are collected to assess for potential drug-related changes that might have constituted a safety concern. Safety brain MRI is assessed using a standardized procedure that included fluid-attenuated inversion recovery (FLAIR), gradient-echo, T1, and diffusion-weighted sequences to determine the presence of focal lesions including, but not limited to, evidence for ischemic and hemorrhagic stroke, subdural hematoma, neoplasm, arteriovenous malformation, micro and macrohemorrhages, superficial siderosis, lacunar infarcts, white matter abnormalities, and vasogenic edema. Participants with abnormal values related to safety brain MRI were reported.
Core Phase: Number of Participants With Serious Adverse Events (SAEs)
时间窗: Up to 21 months
A SAE is any untoward medical occurrence that at any dose: results in death; is life-threatening (that is, the participant is at immediate risk of death from the adverse event as it occurs, this does not include an event that, has it occurred in a more severe form or is allowed to continue, might have cause death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect (in the child of a participant who is exposed to the study drug).
Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values
时间窗: Up to 21 months
Core Phase: Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Findings
时间窗: Up to 21 months
QTcF interval means corrected QT interval (QTc) calculated using Fridericia's formula.
次要结局
- Extension Phase: Percent Change From Extension Phase Baseline in Plasma Amyloid (A) Beta(1-x) Measurements at Months 12 and 24(Month 12 and Month 24)
- Extension Phase: Percent Change From Extension Phase Baseline in Total Ventricular Volume at Month 24(Month 24)
- Core Phase: Mean Concentration of Elenbecestat in CSF(Month 1 (Week 5) and Month 18 (Week 79))
- Core Phase: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid (A) Beta(1-x) and Abeta(1-42) After 1 Month and 18 Months of Treatment(Month 1 (Week 5) and Month 18 (Week 79))
- Extension Phase: Change From Extension Phase Baseline in the Functional Assessment Questionnaire (FAQ) Score(Baseline, at Month 3, at Month 6, at Month 9, at Month 12, at Month 15, at Month 18, at Month 21, at Month 24, at Month 28 and at Month 32)
- Extension Phase: Percent Change From Extension Phase Baseline in Total Hippocampal Volume at Month 24(Month 24)
- Core Phase: Mean Concentration of Elenbecestat in Plasma(Month 0 (Week 3), Month 3 (Week 13), Month 6 (Week 27), Month 12 (Week 53): Pre-dose, 1 to 6 hours Post-dose; Month 1 (Week 5), Month 18 (Week 79): Pre-dose, 4 to 8 hours Post-dose)
- Extension Phase: Change From Extension Phase Baseline in the Mini-Mental State Examination (MMSE) Scores(Baseline, at Month 3, at Month 6, at Month 9, at Month 12, at Month 15, at Month 18, at Month 21, at Month 24, at Month 28 and at Month 32)
- Extension Phase: Percent Change From Extension Phase Baseline in Left and Right Hippocampal Volume at Month 24(Month 24)
- Extension Phase: Percent Change From Extension Phase Baseline in Whole Brain Volume at Month 24(Month 24)