Dose-Finding Study To Evaluate Safety, Tolerability, and Efficacy of E2609 in Participants With Mild Cognitive Impairment Due to Alzheimer's Disease (Prodromal Alzheimer's Disease) and Mild to Moderate Dementia Due to Alzheimer's Disease
- Conditions
- Alzheimer DiseaseDementia, Alzheimer Type
- Interventions
- Drug: Placebo
- Registration Number
- NCT02322021
- Lead Sponsor
- Eisai Inc.
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 70
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description MCI/Prodromal Cohort: Placebo Placebo - MCI/Prodromal Cohort: Middle Dose E2609 A middle dose of E2609 will be assessed. Mild to Moderate AD Cohort: High Dose E2609 A high dose of E2609 will be assessed. Mild to Moderate AD Cohort: Placebo Placebo - Mild to Moderate AD Cohort: Low Dose E2609 A low dose of E2609 will be assessed. MCI/Prodromal Cohort: High Dose E2609 A high dose of E2609 will be assessed. Mild to Moderate AD cohort: Middle Dose E2609 A middle dose of E2609 will be assessed. MCI/Prodromal Cohort: Low Dose E2609 A low dose of E2609 will be assessed.
- Primary Outcome Measures
Name Time Method Core Phase: Number of Participants With Treatment Emergent Adverse Events (TEAEs) 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 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 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 Up to 34 months Extension Phase: Number of Participants With Markedly Abnormal Vital Sign Values Up to 34 months Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values 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 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) 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 Up to 21 months Core Phase: Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Findings Up to 21 months QTcF interval means corrected QT interval (QTc) calculated using Fridericia's formula.
- Secondary Outcome Measures
Name Time Method 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 The measurement of the amyloid protein Abeta(1-x), in plasma has been shown to be an important biomarker for alzheimer's disease.
Extension Phase: Percent Change From Extension Phase Baseline in Total Ventricular Volume at Month 24 Month 24 Total Ventricular Volume is measured by vMRI. Volumetric imaging is a 3D technique where all the MRI signals are collected from the entire tissue sample and imaged as a whole entity, therefore providing a high signal to noise ratio. Total ventricular volume represents a summary measure of total including right and left lateral ventricles, third ventricle and fourth ventricle of brain.
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) The measurement of the amyloid proteins Abeta(1-x) and Abeta(1-42), in CSF have been shown to be important biomarkers for alzheimer's disease.
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 The FAQ has 10 items concerned with performing daily tasks necessary for independent living. The caregiver or informant provides performance ratings on 10 complex activities of daily living performed within the preceding 4 weeks. Score ranges from 0 (independent) to 30 (dependent). Lower score indicates that participant can live independently. Higher score indicates that participant cannot live independently.
Extension Phase: Percent Change From Extension Phase Baseline in Total Hippocampal Volume at Month 24 Month 24 Total hippocampal volume is measured by volumetric magnetic resonance imaging (vMRI). Volumetric imaging is a 3D technique where all the MRI signals are collected from the entire tissue sample and imaged as a whole entity, therefore providing a high signal to noise ratio. Total hippocampal volume is calculated by summing up right and left hippocampal volumes.
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 MMSE is a 30-point scale that measures orientation to time and place, registration, immediate and delayed recall, attention, language, and drawing. Scores ranges from 0 (most impaired) to 30 (no impairment). Lower score indicates more impairment.
Extension Phase: Percent Change From Extension Phase Baseline in Left and Right Hippocampal Volume at Month 24 Month 24 Left and right hippocampal volume is measured by vMRI. Volumetric imaging is a 3D technique where all the MRI signals are collected from the entire tissue sample and imaged as a whole entity, therefore providing a high signal to noise ratio. Left and right hippocampal volumes represent a summary measure in the left and right hippocampal regions.
Extension Phase: Percent Change From Extension Phase Baseline in Whole Brain Volume at Month 24 Month 24 Whole brain volume is measured by vMRI. Volumetric imaging is a 3D technique where all the MRI signals are collected from the entire tissue sample and imaged as a whole entity, therefore providing a high signal to noise ratio. Whole brain volume represents a summary measure of total brain parenchyma which includes the cerebrum, basal ganglia, diencephalon, and cerebellum.