ACTIVE_NOT_RECRUITING

A Study of E2814 With Concurrent Lecanemab Treatment in Participants With Early Alzheimer's Disease

Conditions

Alzheimer's Disease Early Alzheimer's Disease E2814 Lecanemab

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The primary objective of the study is to determine the dose response of E2814, when concurrently administered with lecanemab, on the change from baseline at 18 months in cerebrospinal fluid (CSF) microtubule-binding region (MTBR)-tau-243 in participants with early Alzheimer's disease (AD).

Official Title

A Phase 2, Placebo-Controlled, Double-Blind, Parallel-Group, Dose-Finding Study to Evaluate Safety, Tolerability, and Biomarker Efficacy of E2814 With Concurrent Lecanemab Treatment in Subjects With Early Alzheimer's Disease

Quick Facts

Study Start:2024-09-30

Study Completion:2027-08-19

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT06602258

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:50 Years to 80 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. For participants diagnosed with mild cognitive impairment (MCI) due to AD-intermediate likelihood: 1. Meet the National Institute on Aging-Alzheimer's Association (NIA-AA) core clinical criteria for MCI due to AD-intermediate likelihood 2. Have a global Clinical Dementia Rating Scale (CDR) score of 0.5 and a CDR Memory Box score of greater than or equal to (\>=) 0.5 at Screening 2. For participants diagnosed with mild AD dementia: 1. Meet the NIA-AA core clinical criteria for probable AD dementia 2. Have a global CDR score of 0.5 to 1.0 and a CDR Memory Box score of \>=0.5 at Screening 3. Mini Mental State Examination (MMSE) score \>=22 at Screening and less than or equal to (\<=) 30 at Screening 4. Able to have CSF lumbar puncture performed and not on, or have a medical condition that may require initiation of, any anticoagulant therapy at Screening 5. Male or female participants aged between \>=50 years and \<=80 years, at the time of informed consent 6. If receiving an approved AD symptomatic treatment (such as acetylcholinesterase inhibitors (AchEIs), memantine, or both) for AD, participants must be on a stable dose for at least 12 weeks before Baseline. Treatment-naïve participants for AD medications can be enrolled into the study. Unless otherwise stated, participants must have been on stable doses of all other (that is, non AD-related) permitted concomitant medications for at least 4 weeks before Baseline. Use of memantine will not be allowed at screening for participants in Japan 7. Have an identified study partner (defined as a person able to support the participant for the duration of the study and who spends at least 8 hours per week with the participant). 8. Provide written informed consent. If a participant lacks the capacity to consent in the Investigator's opinion, the participants' assent should be obtained, if required in accordance with local laws, regulations, and customs, plus the written informed consent of a legal representative should be obtained (capacity to consent and definition of legal representative should be determined in accordance with applicable local laws and regulations) 9. Willing and able to comply with all aspects of the protocol including multiple CSF collections	1. Any neurological condition that may be contributing to cognitive impairment above and beyond that caused by the participant's AD 2. History of transient ischemic attacks, stroke, or seizures within 12 months of Screening 3. Any psychiatric diagnosis or symptoms (example, hallucinations, major depression, or delusions) that could interfere with study procedures in the participants. Psychotic disorder(s) or unstable recurrent affective disorder(s) evident by use of antipsychotics within 2 years before Screening 4. Contraindications to MRI scanning, including cardiac pacemaker/defibrillator, ferromagnetic metal implants (example, in skull and cardiac devices other than those approved as safe for use in MRI scanners). Evidence of other clinically significant lesions on brain MRI at Screening that could indicate a dementia diagnosis other than AD. Other significant pathological findings on brain MRI at Screening, including but not limited to: greater than 4 microhemorrhages (defined as 10 millimeter (mm) or less at the greatest diameter); a single intracerebral hemorrhage greater than 10 mm at greatest diameter; an area of superficial siderosis; evidence of vasogenic edema; evidence of cerebral contusion, encephalomalacia, aneurysms, vascular malformations, or infective lesions; evidence of multiple lacunar infarcts or stroke involving a major vascular territory, severe small vessel, or white matter disease; space occupying lesions; or brain tumors (however, lesions diagnosed as meningiomas or arachnoid cysts and less than 1 cm at their greatest diameter need not be exclusionary). Other minor or clinically insignificant magnetic resonance imaging (MRI) abnormalities, as agreed by the medical monitor and after discussion with the investigator, may not be exclusionary 5. Malignant neoplasms within 3 years of Screening (except for basal or squamous cell carcinoma in situ of the skin, or localized prostate cancer in male participants, or localized breast cancer in female participants). Participants who had malignant neoplasms but who have had at least 3 years of documented uninterrupted remission before Screening need not be excluded 6. A clinically significant ECG abnormality, including a marked prolonged corrected QT interval (Fridericia's Correction Formula; QTcF) interval (example, a repeated demonstration of a QTcF interval greater than (\>) 450 milliseconds \[ms\]) 7. Participants with a bleeding disorder that is not under adequate control (including a platelet count \<50,000 or international normalized ratio \[INR\] \>1.5). Any participants who are on anticoagulant therapy are not permitted to be enrolled 8. Have thyroid-stimulating hormone above normal range. Other tests of thyroid function with results outside the normal range should only be exclusionary if they are considered clinically significant by the investigator. This applies to all participants whether or not they are taking thyroid supplements 9. Abnormally low serum vitamin B12 levels for the testing laboratory (if participant is taking vitamin B12 injections, level should be at or above the lower limit of normal for the testing laboratory). Levels of vitamin B12 may be confirmed with reflex testing to include methylmalonic acid analysis, if available in region 10. Any suicidal ideation with intent with or without a plan at Screening, Baseline, or within 6 months of Screening (that is, answering "Yes" to questions 4 or 5 on the Suicidal Ideation section of the Columbia-Suicide Severity Rating Scale \[C-SSRS\]) Type 4 or 5, or any suicidal behavior assessment within 6 months before Screening, at Screening, or at the Baseline Visit, or has been hospitalized or treated for suicidal behavior in the past 5 years before Screening) 11. Evidence of clinically significant disease (example, cardiac, respiratory, gastrointestinal, and renal disease) that in the opinion of the investigator(s) could affect the participants safety or interfere with the study assessments. Any other medical conditions (example, cardiac, respiratory, gastrointestinal, and renal disease) that are not stably and adequately controlled or that in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments 12. Hypersensitivity to lecanemab, E2814, or any of the excipients 13. Any immunological disease, that is not adequately controlled, or that requires treatment with immunoglobulins, systemic monoclonal antibodies (mAbs) (or derivatives of mAbs), systemic immunosuppressants, or plasmapheresis during the study 14. Any history of or concomitant medical condition that in the opinion of the investigator(s) would compromise the participant's ability to safely complete the study 15. Planned surgery that requires general, spinal, or epidural anesthesia that would take place during the study. Planned surgery that requires only local anesthesia and that can be undertaken as a day case without inpatient stay postoperatively need not result in exclusion if in the opinion of the investigator this operation does not interfere with study procedures and participant safety 16. Known to be human immunodeficiency virus positive 17. Known or suspected history of drug or alcohol abuse or dependence within 2 years before Screening or a positive urine drug test at Screening. Participants who test positive for benzodiazepines or opioids in urine drug testing need not be excluded if in the clinical opinion of the investigator, this is due to the participant taking prior/concomitant medications containing benzodiazepines or opioids for a medical condition and not due to drug abuse 18. Severe visual or hearing impairment that would prevent the participant from performing psychometric tests accurately

Inclusion Criteria

Exclusion Criteria

1. For participants diagnosed with mild cognitive impairment (MCI) due to AD-intermediate likelihood:
1. Meet the National Institute on Aging-Alzheimer's Association (NIA-AA) core clinical criteria for MCI due to AD-intermediate likelihood
2. Have a global Clinical Dementia Rating Scale (CDR) score of 0.5 and a CDR Memory Box score of greater than or equal to (\>=) 0.5 at Screening
2. For participants diagnosed with mild AD dementia:
1. Meet the NIA-AA core clinical criteria for probable AD dementia
2. Have a global CDR score of 0.5 to 1.0 and a CDR Memory Box score of \>=0.5 at Screening
3. Mini Mental State Examination (MMSE) score \>=22 at Screening and less than or equal to (\<=) 30 at Screening
4. Able to have CSF lumbar puncture performed and not on, or have a medical condition that may require initiation of, any anticoagulant therapy at Screening
5. Male or female participants aged between \>=50 years and \<=80 years, at the time of informed consent
6. If receiving an approved AD symptomatic treatment (such as acetylcholinesterase inhibitors (AchEIs), memantine, or both) for AD, participants must be on a stable dose for at least 12 weeks before Baseline. Treatment-naïve participants for AD medications can be enrolled into the study. Unless otherwise stated, participants must have been on stable doses of all other (that is, non AD-related) permitted concomitant medications for at least 4 weeks before Baseline. Use of memantine will not be allowed at screening for participants in Japan
7. Have an identified study partner (defined as a person able to support the participant for the duration of the study and who spends at least 8 hours per week with the participant).
8. Provide written informed consent. If a participant lacks the capacity to consent in the Investigator's opinion, the participants' assent should be obtained, if required in accordance with local laws, regulations, and customs, plus the written informed consent of a legal representative should be obtained (capacity to consent and definition of legal representative should be determined in accordance with applicable local laws and regulations)
9. Willing and able to comply with all aspects of the protocol including multiple CSF collections

1. Any neurological condition that may be contributing to cognitive impairment above and beyond that caused by the participant's AD
2. History of transient ischemic attacks, stroke, or seizures within 12 months of Screening
3. Any psychiatric diagnosis or symptoms (example, hallucinations, major depression, or delusions) that could interfere with study procedures in the participants. Psychotic disorder(s) or unstable recurrent affective disorder(s) evident by use of antipsychotics within 2 years before Screening
4. Contraindications to MRI scanning, including cardiac pacemaker/defibrillator, ferromagnetic metal implants (example, in skull and cardiac devices other than those approved as safe for use in MRI scanners). Evidence of other clinically significant lesions on brain MRI at Screening that could indicate a dementia diagnosis other than AD. Other significant pathological findings on brain MRI at Screening, including but not limited to: greater than 4 microhemorrhages (defined as 10 millimeter (mm) or less at the greatest diameter); a single intracerebral hemorrhage greater than 10 mm at greatest diameter; an area of superficial siderosis; evidence of vasogenic edema; evidence of cerebral contusion, encephalomalacia, aneurysms, vascular malformations, or infective lesions; evidence of multiple lacunar infarcts or stroke involving a major vascular territory, severe small vessel, or white matter disease; space occupying lesions; or brain tumors (however, lesions diagnosed as meningiomas or arachnoid cysts and less than 1 cm at their greatest diameter need not be exclusionary). Other minor or clinically insignificant magnetic resonance imaging (MRI) abnormalities, as agreed by the medical monitor and after discussion with the investigator, may not be exclusionary
5. Malignant neoplasms within 3 years of Screening (except for basal or squamous cell carcinoma in situ of the skin, or localized prostate cancer in male participants, or localized breast cancer in female participants). Participants who had malignant neoplasms but who have had at least 3 years of documented uninterrupted remission before Screening need not be excluded
6. A clinically significant ECG abnormality, including a marked prolonged corrected QT interval (Fridericia's Correction Formula; QTcF) interval (example, a repeated demonstration of a QTcF interval greater than (\>) 450 milliseconds \[ms\])
7. Participants with a bleeding disorder that is not under adequate control (including a platelet count \<50,000 or international normalized ratio \[INR\] \>1.5). Any participants who are on anticoagulant therapy are not permitted to be enrolled
8. Have thyroid-stimulating hormone above normal range. Other tests of thyroid function with results outside the normal range should only be exclusionary if they are considered clinically significant by the investigator. This applies to all participants whether or not they are taking thyroid supplements
9. Abnormally low serum vitamin B12 levels for the testing laboratory (if participant is taking vitamin B12 injections, level should be at or above the lower limit of normal for the testing laboratory). Levels of vitamin B12 may be confirmed with reflex testing to include methylmalonic acid analysis, if available in region
10. Any suicidal ideation with intent with or without a plan at Screening, Baseline, or within 6 months of Screening (that is, answering "Yes" to questions 4 or 5 on the Suicidal Ideation section of the Columbia-Suicide Severity Rating Scale \[C-SSRS\]) Type 4 or 5, or any suicidal behavior assessment within 6 months before Screening, at Screening, or at the Baseline Visit, or has been hospitalized or treated for suicidal behavior in the past 5 years before Screening)
11. Evidence of clinically significant disease (example, cardiac, respiratory, gastrointestinal, and renal disease) that in the opinion of the investigator(s) could affect the participants safety or interfere with the study assessments. Any other medical conditions (example, cardiac, respiratory, gastrointestinal, and renal disease) that are not stably and adequately controlled or that in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments
12. Hypersensitivity to lecanemab, E2814, or any of the excipients
13. Any immunological disease, that is not adequately controlled, or that requires treatment with immunoglobulins, systemic monoclonal antibodies (mAbs) (or derivatives of mAbs), systemic immunosuppressants, or plasmapheresis during the study
14. Any history of or concomitant medical condition that in the opinion of the investigator(s) would compromise the participant's ability to safely complete the study
15. Planned surgery that requires general, spinal, or epidural anesthesia that would take place during the study. Planned surgery that requires only local anesthesia and that can be undertaken as a day case without inpatient stay postoperatively need not result in exclusion if in the opinion of the investigator this operation does not interfere with study procedures and participant safety
16. Known to be human immunodeficiency virus positive
17. Known or suspected history of drug or alcohol abuse or dependence within 2 years before Screening or a positive urine drug test at Screening. Participants who test positive for benzodiazepines or opioids in urine drug testing need not be excluded if in the clinical opinion of the investigator, this is due to the participant taking prior/concomitant medications containing benzodiazepines or opioids for a medical condition and not due to drug abuse
18. Severe visual or hearing impairment that would prevent the participant from performing psychometric tests accurately

Contacts and Locations

Study Locations (Sites)

Banner Sun Health Research Institute

Sun City, Arizona, 85351

United States

Yale University School of Medicine

New Haven, Connecticut, 06510

United States

Bradenton Research Center

Bradenton, Florida, 34205

United States

K2 Medical Research

Clermont, Florida, 34711

United States

Charter Research

Lady Lake, Florida, 32159

United States

Advanced Clinical Research Network

Miami, Florida, 33135

United States

Renstar Medical Research

Ocala, Florida, 34470

United States

Progressive Medical Research

Port Orange, Florida, 32127

United States

Alzheimer's Research and Treatment Center

Stuart, Florida, 34997

United States

Axiom Brain Health

Tampa, Florida, 33609

United States

Alzheimer's Research and Treatment Center

Wellington, Florida, 33414

United States

Columbus Memory Center, PC

Columbus, Georgia, 31909

United States

Memory Center/Hattiesburg Clinic

Hattiesburg, Mississippi, 39401

United States

Washington University School of Medicine

Saint Louis, Missouri, 63110

United States

Abington Neurological Associates Ltd

Abington, Pennsylvania, 19001

United States

Neurology Clinical, P.C.

Cordova, Tennessee, 38018

United States

Kerwin Medical Center

Dallas, Texas, 75231-4350

United States

National Clinical Research-Richmond, Inc

Richmond, Virginia, 23294

United States

Collaborators and Investigators

Sponsor: Eisai Inc.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-09-30

Study Completion Date2027-08-19

Study Record Updates

Study Start Date2024-09-30

Study Completion Date2027-08-19

Terms related to this study

Keywords Provided by Researchers

Early Alzheimer's Disease
E2814
Lecanemab

Additional Relevant MeSH Terms

Alzheimer's Disease