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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
70
Each participant will receive 2 tablets, which when combined will make up the required doses of E2609 or placebo, to be administered orally once per day (QD) with food.
Each participant will receive 2 tablets, which when combined will make up the required doses of E2609 or placebo, to be administered orally once per day (QD) with food.
Unnamed facility
Bellflower, California, United States
Unnamed facility
Costa Mesa, California, United States
Unnamed facility
Glendale, California, United States
Unnamed facility
Irvine, California, United States
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Aventura, Florida, United States
Unnamed facility
Boca Raton, Florida, United States
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Brooksville, Florida, United States
Unnamed facility
Lake Worth, Florida, United States
Unnamed facility
Orlando, Florida, United States
Unnamed facility
Port Charlotte, Florida, United States
...and 11 more locations
Core Phase: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
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.
Time frame: Up to 21 months
Core Phase: Number of Participants With Serious Adverse Events (SAEs)
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).
Time frame: Up to 21 months
Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values
Time frame: Up to 21 months
Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values
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.
Time frame: 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
Core Phase: Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Findings
QTcF interval means corrected QT interval (QTc) calculated using Fridericia's formula.
Time frame: Up to 21 months
Extension Phase: Number of Participants With TEAEs and SAEs
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.
Time frame: Up to 34 months
Extension Phase: Number of Participants With Markedly Abnormal Vital Sign Values
Time frame: Up to 34 months
Extension Phase: Number of Participants With Markedly Abnormal ECG Findings
QTcF interval means QTc interval calculated using Fridericia's formula.
Time frame: Up to 34 months
Extension Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values
Time frame: Up to 34 months
Extension Phase: Number of Participants With Abnormal Magnetic Resonance Imaging (MRI) Findings
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.
Time frame: Up to 34 months
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
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.
Time frame: Month 1 (Week 5) and Month 18 (Week 79)
Core Phase: Mean Concentration of Elenbecestat in CSF
Time frame: Month 1 (Week 5) and Month 18 (Week 79)
Core Phase: Mean Concentration of Elenbecestat in Plasma
Time frame: 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
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.
Time frame: 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: Change From Extension Phase Baseline in the Functional Assessment Questionnaire (FAQ) Score
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.
Time frame: 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 Plasma Amyloid (A) Beta(1-x) Measurements at Months 12 and 24
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
The measurement of the amyloid protein Abeta(1-x), in plasma has been shown to be an important biomarker for alzheimer's disease.
Time frame: Month 12 and Month 24
Extension Phase: Percent Change From Extension Phase Baseline in Total Hippocampal Volume at 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.
Time frame: Month 24
Extension Phase: Percent Change From Extension Phase Baseline in Left and Right Hippocampal Volume at 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.
Time frame: Month 24
Extension Phase: Percent Change From Extension Phase Baseline in Whole Brain Volume at 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.
Time frame: Month 24
Extension Phase: Percent Change From Extension Phase Baseline in Total Ventricular Volume at 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.
Time frame: Month 24