Alzheimer DiseasePhase 2NCT02322021
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
A Phase 2 study testing E2609 in people with Alzheimer Disease and Dementia, Alzheimer Type, run by Eisai Inc. at 21 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 50 to 85 years
- Conditions the study is for
- Alzheimer Disease, Dementia, Alzheimer Type
- What is being tested?
- E2609
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 21 sitesUnited States
- Study dates
- 26 Nov 2014to 20 Dec 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must meet all of the following criteria to be included in this study:
- Meets the core clinical research criteria of the National Institute on Aging-Alzheimer's Association (NIA-AA) for MCI due to AD (which is consistent with Prodromal AD) or AD dementia and is 'staged' or classified as either MCI or mild to moderate dementia.
- Amyloid positive Positron Emission Tomography (PET) image based on centralized PET scan reading.
- Male or female, age 50 to 85 years, inclusive at time of consent.
- Must have an identified caregiver or informant who is willing and able to provide follow-up information on the participant throughout the course of the study.
- If receiving an Acetylcholinesterase Inhibitor (AChEI) or memantine, must have been on a stable dose for at least 12 weeks before the Baseline cognitive assessments, with no plans for dose adjustment in the foreseeable future. Treatment-naive participants can be entered into the study but there should be no plans to initiate treatment with AChEIs or memantine at the time of entry into the study.
- Must have been on stable doses of all other permitted chronically used concomitant medications (that is, not related to their cognitive decline) for at least 4 weeks before randomization.
Who cannot join
- Participants who meet any of the following criteria will be excluded from this study:
- Any neurological condition that may be contributing to cognitive impairment above and beyond that caused by the participant's AD pathology, including any co-morbidities such as cerebrovascular disease, detected by medical history, neurological examination, or magnetic resonance imaging (MRI).
- History of transient ischemic attacks or stroke within 12 months of Screening.
- History of epilepsy.
- Evidence of depression on a rating scale at Screening or any psychiatric diagnosis or symptoms, (example, hallucinations, major depression, etc.) that could confound the diagnosis or could interfere with study assessments or procedures. This includes suicidal ideation or suicidal behavior within 6 months prior to Screening, or hospitalization or treatment for suicidal behavior in the past 5 years.
- Abnormally low serum vitamin B12.
Show all 31Show fewer
- Thyroid stimulating hormone above the normal range. This applies to all participants regardless of whether or not they are taking thyroid supplements.
- Participants with liver disease (hepatic impairment), at Screening or Baseline. Participant with Gilbert's syndrome need not be excluded.
- Not able to have a MRI, PET scanning, or cerebrospinal fluid (CSF) collection by Lumbar Puncture (LP).
- Severe visual or hearing impairment that would prevent the participant from performing psychometric tests accurately.
- History of immunodeficiency disorders.
- Participants with chronic viral hepatitis.
- History of Tuberculosis (TB). Participants with no history of TB will be tested for previous TB exposure and a positive test will be exclusionary.
- History of ophthalmic shingles or ocular Herpes Simplex Virus (HSV) infection.
- Any live vaccine in the 3 months or any active infection within the last 4 weeks before study drug administration (that is, randomization).
- Any chronic inflammatory disease that is not adequately controlled or requires immunosuppressive or immunomodulatory therapy.
- T helper cell, cytotoxic T cell, or B cell absolute counts below normal.
- Immunoglobulin (Ig) IgG, IgA, or IgM levels below normal at Screening or Baseline, unless both the Investigator and the Medical Monitor agree that the finding is not clinically significant.
- Clinically significant deviation from normal in physical examination, vital signs, or clinical laboratory tests at Screening or Baseline.
- Exclusionary cardiac factors include: prolonged QT interval greater than 450 millisecond from Electrocardiograms (ECGs); history of risk factors for torsade de pointes or the use of concomitant medications that prolong the QT/corrected QT interval (QTc); left bundle branch block; persistent low or high heart rate; persistent low or high blood pressure; history of cardiac arrhythmias; other clinically significant ECG abnormalities.
- Type 1 or Type 2 diabetes mellitus that is not well controlled.
- Malignant neoplasms within 5 years before Screening (except for basal or squamous cell carcinoma in situ of the skin, or localized prostate cancer that did not require systemic therapy; these do not exclude the participant).
- Medical conditions (example, cardiac, respiratory, gastrointestinal, renal disease) that are not stably controlled, or which, in the opinion of the investigator(s), could affect the participant's safety or interfere with the study assessments.
- Hypopigmentation conditions (example, albinism and vitiligo).
- Known or suspected history of drug or alcohol dependency or abuse within 2 years, current use of recreational drugs or a positive urine drug test.
- Planned surgery that requires general, spinal, or epidural anesthesia that would take place during the study.
- Participation in any other interventional clinical study related to cognitive impairment within 6 months before Screening unless it can be documented that the participant was in a placebo treatment arm.
- Currently enrolled in another clinical study or used any investigational drug or device within 60 days or 5 half-lives of the investigational medication (whichever is longer) proceeding informed consent.
- Hypersensitivity to the study drug or any of the excipients or to other Beta Secretase Cleaving Enzyme (BACE) inhibitors, or to the PET tracer, or components of its formulation.
- Females who are lactating or pregnant. Females of childbearing potential who do not agree to adhere to the protocol specified methods for avoiding pregnancy.
- Males who do not meet the protocol requirements for avoiding their partners becoming pregnant. Sperm donation is not permitted.
Trial locations and contacts
21 sites in 1 country.
21 sites in 1 country
United States21 sites
Study site
Atlanta, Georgia
Study site
Aventura, Florida
Study site
Bellflower, California
Study site
Boca Raton, Florida
Study site
Brooksville, Florida
Study site
Charlotte, North Carolina
Study site
Costa Mesa, California
Study site
Dallas, Texas
Study site
Dayton, Ohio
Study site
Glendale, California
Study site
Irvine, California
Study site
Kalamazoo, Michigan
Study site
Lake Worth, Florida
Study site
Mount Arlington, New Jersey
Study site
Orlando, Florida
Study site
Port Charlotte, Florida
Study site
Port Royal, South Carolina
Study site
San Antonio, Texas
Study site
Savannah, Georgia
Study site
Scotch Plains, New Jersey
Study site
Wichita, Kansas
About this study
Official title: 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
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.
- Conditions
- Alzheimer Disease, Dementia, Alzheimer Type
- Being tested
- E2609, Placebo
- Keywords
- E2609, Mild Cognitive Impairment, Mild to Moderate Dementia, Alzheimer's Disease, Prodromal Alzheimer's Disease
- Medical subject headings
- Alzheimer Disease, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
E2609Drug
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| MCI/Prodromal Cohort: Low Dose | Experimental | A low dose of E2609 will be assessed. Receives: Drug: E2609 |
| MCI/Prodromal Cohort: Middle Dose | Experimental | A middle dose of E2609 will be assessed. Receives: Drug: E2609 |
| MCI/Prodromal Cohort: High Dose | Experimental | A high dose of E2609 will be assessed. Receives: Drug: E2609 |
| MCI/Prodromal Cohort: Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
| Mild to Moderate AD Cohort: Low Dose | Experimental | A low dose of E2609 will be assessed. Receives: Drug: E2609 |
| Mild to Moderate AD Cohort: High Dose | Experimental | A high dose of E2609 will be assessed. Receives: Drug: E2609 |
| Mild to Moderate AD Cohort: Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
| Mild to Moderate AD cohort: Middle Dose | Experimental | A middle dose of E2609 will be assessed. Receives: Drug: E2609 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Measured: Up to 21 months
Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to 34 months
Extension Phase: Number of Participants With Markedly Abnormal Vital Sign Values
Measured: Up to 34 months
Extension Phase: Number of Participants With Markedly Abnormal ECG Findings
QTcF interval means QTc interval calculated using Fridericia's formula.
Measured: Up to 34 months
Extension Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values
Measured: 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.
Measured: Up to 34 months
Secondary outcomes (10)
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.
Measured: Month 1 (Week 5) and Month 18 (Week 79)
Core Phase: Mean Concentration of Elenbecestat in CSF
Measured: Month 1 (Week 5) and Month 18 (Week 79)
Core Phase: Mean Concentration of Elenbecestat in Plasma
Measured: 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.
Measured: 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.
Measured: 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
The measurement of the amyloid protein Abeta(1-x), in plasma has been shown to be an important biomarker for alzheimer's disease.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Month 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Dec 2014 (estimated)
- Study start26 Nov 2014
- Primary completion20 Dec 2019
- Study completion20 Dec 2019
Why it stopped: This study was terminated early by the sponsor on the recommendation of an independent data safety monitoring board following review of unblinded data from the Phase 3 studies E2609-G000-301 (NCT02956486) and E2609-G000-302 (NCT03036280).
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by Eisai Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eisai Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Biogen
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02322021
- Sponsor's protocol ID
- E2609-G000-202
- Other IDs
- 2014-002723-94, 2014
- Status last verified
- Mar 2021
- First submitted
- 17 Dec 2014
- Last updated
- 5 Mar 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02322021
- Acronym / sponsor ID
- E2609-G000-202
- Conditions
- Alzheimer Disease, Dementia, Alzheimer Type
- Keywords
- E2609, Mild Cognitive Impairment, Mild to Moderate Dementia, Alzheimer's Disease, Prodromal Alzheimer's Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: This study was terminated early by the sponsor on the recommendation of an independent data safety monitoring board following review of unblinded data from the Phase 3 studies E2609-G000-301 (NCT02956486) and E2609-G000-302 (NCT03036280).
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Eisai Inc.Industry (pharma, biotech, devices)
- Collaborators
- Biogen
- Study start
- 26 Nov 2014 (actual)
- Primary completion
- 20 Dec 2019 (actual)
- Study completion
- 20 Dec 2019 (actual)
- First posted
- 22 Dec 2014 (estimated)
- Results
- Posted 5 Mar 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| MCI/Prodromal Cohort: Low Dose | Experimental | Drug: E2609A low dose of E2609 will be assessed. |
| MCI/Prodromal Cohort: Middle Dose | Experimental | Drug: E2609A middle dose of E2609 will be assessed. |
| MCI/Prodromal Cohort: High Dose | Experimental | Drug: E2609A high dose of E2609 will be assessed. |
| MCI/Prodromal Cohort: Placebo | Placebo comparator | Drug: Placebo |
| Mild to Moderate AD Cohort: Low Dose | Experimental | Drug: E2609A low dose of E2609 will be assessed. |
| Mild to Moderate AD Cohort: High Dose | Experimental | Drug: E2609A high dose of E2609 will be assessed. |
| Mild to Moderate AD Cohort: Placebo | Placebo comparator | Drug: Placebo |
| Mild to Moderate AD cohort: Middle Dose | Experimental | Drug: E2609A middle dose of E2609 will be assessed. |
Who may qualify
- Ages
- 50 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Meets the core clinical research criteria of the National Institute on Aging-Alzheimer's Association (NIA-AA) for MCI due to AD (which is consistent with Prodromal AD) or AD dementia and is 'staged' or classified as either MCI or mild to moderate dementia.
- Amyloid positive Positron Emission Tomography (PET) image based on centralized PET scan reading.
- Male or female, age 50 to 85 years, inclusive at time of consent.
- Must have an identified caregiver or informant who is willing and able to provide follow-up information on the participant throughout the course of the study.
- If receiving an Acetylcholinesterase Inhibitor (AChEI) or memantine, must have been on a stable dose for at least 12 weeks before the Baseline cognitive assessments, with no plans for dose adjustment in the foreseeable future. Treatment-naive participants can be entered into the study but there should be no plans to initiate treatment with AChEIs or memantine at the time of entry into the study.
Key exclusion criteria (31 listed)
- Any neurological condition that may be contributing to cognitive impairment above and beyond that caused by the participant's AD pathology, including any co-morbidities such as cerebrovascular disease, detected by medical history, neurological examination, or magnetic resonance imaging (MRI).
- History of transient ischemic attacks or stroke within 12 months of Screening.
- History of epilepsy.
- Evidence of depression on a rating scale at Screening or any psychiatric diagnosis or symptoms, (example, hallucinations, major depression, etc.) that could confound the diagnosis or could interfere with study assessments or procedures. This includes suicidal ideation or suicidal behavior within 6 months prior to Screening, or hospitalization or treatment for suicidal behavior in the past 5 years.
- Abnormally low serum vitamin B12.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| E2609Each 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. | Drug | MCI/Prodromal Cohort: High Dose, MCI/Prodromal Cohort: Low Dose, MCI/Prodromal Cohort: Middle Dose, Mild to Moderate AD Cohort: High Dose, Mild to Moderate AD Cohort: Low Dose, Mild to Moderate AD cohort: Middle Dose |
| PlaceboEach 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. | Drug | MCI/Prodromal Cohort: Placebo, Mild to Moderate AD Cohort: Placebo |
Primary outcome
Core Phase: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Time frame: 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.
Core Phase: Number of Participants With Serious Adverse Events (SAEs)
Time frame: 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
Time frame: Up to 21 months
Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values
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
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.
Core Phase: Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Findings
Time frame: Up to 21 months
QTcF interval means corrected QT interval (QTc) calculated using Fridericia's formula.
Extension Phase: Number of Participants With TEAEs and SAEs
Time frame: 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 Vital Sign Values
Time frame: Up to 34 months
Extension Phase: Number of Participants With Markedly Abnormal ECG Findings
Time frame: 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
Time frame: Up to 34 months
Extension Phase: Number of Participants With Abnormal Magnetic Resonance Imaging (MRI) Findings
Time frame: 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.
10 secondary outcomes
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
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
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
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
Time frame: Month 12 and Month 24
Extension Phase: Percent Change From Extension Phase Baseline in Total Hippocampal Volume at Month 24
Time frame: Month 24
Extension Phase: Percent Change From Extension Phase Baseline in Left and Right Hippocampal Volume at Month 24
Time frame: Month 24
Extension Phase: Percent Change From Extension Phase Baseline in Whole Brain Volume at Month 24
Time frame: Month 24
Extension Phase: Percent Change From Extension Phase Baseline in Total Ventricular Volume at Month 24
Time frame: Month 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Alzheimer Disease
RecruitingPhase 1
A First-In-Human Study of LY3954068 in Participants With Early Symptomatic Alzheimer's Disease
Alzheimer Disease
RecruitingPhase 1
An Open Label Dose Escalation Study of VY1706 in Participants With Early Alzheimer's Disease
Alzheimer s Disease
RecruitingPhase 2
Neuroplasticity Enhancement From Cognitive Training Reinforced by Psilocybin
Alzheimer's Disease
RecruitingPhase 1
PET Imaging of Phosphodiesterase-4 (PDE4) in Volunteers With Alzheimer Disease (AD) or Mild Cognitive Impairment (MCI)
Alzheimer s Disease, Mild Cognitive Impairment
RecruitingObservational study
Amyloid PET Imaging in the Baltimore Longitudinal Study of Aging
Aging
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
21 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing E2609 in people with Alzheimer Disease and Dementia, Alzheimer Type, run by Eisai Inc. at 21 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Core Phase: Number of Participants With Treatment Emergent Adverse Events (TEAEs) (time frame: Up to 21 months). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2021.