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

NCT06602258 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: E2814-G000-202
• Study Type: interventional
• Target: 105
• Locations: 2 countries
• Sites: 26

Brief Summary

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 6 months in cerebrospinal fluid (CSF) microtubule-binding region (MTBR)-tau-243 in participants with early Alzheimer's disease (AD).

Conditions

Alzheimer's Disease

Keywords

Early Alzheimer's Disease; E2814; Lecanemab

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in CSF MTBR-tau-243 at 6 Months

  Baseline at 6 months

Secondary Outcomes (10)

• Change From Baseline in Tau Positron Emission Tomography (PET) up to 24 Months

  Baseline up to 24 months

• Change From Baseline in Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) up to 24 Months

  Baseline up to 24 months

• Change From Baseline in Alzheimers Disease Cooperative Scale-Activities of Daily Living Mild Cognitive Impairment Version (ADCS MCI-ADL) up to 24 Months

  Baseline up to 24 months

• Serum Anti-E2814 Antibody (ADA) Concentration

  Baseline up to 27 months

• AUC: Area Under the Serum Concentration Versus Time Curve of E2814

  Baseline up to 27 months

Study Arms (5)

E2814 Dose A + Lecanemab

EXPERIMENTAL

Participants will receive E2814 Dose A administered as an intravenous (IV) infusion, every four weeks (Q4W) along with lecanemab administered as a subcutaneous (SC) injection, every week (QW).

Drug: E2814; Drug: Lecanemab

E2814 Dose B + Lecanemab

EXPERIMENTAL

Participants will receive E2814 Dose B administered as an IV infusion, Q4W along with lecanemab administered as a SC injection, QW.

Drug: E2814; Drug: Lecanemab

E2814 Dose C + Lecanemab

EXPERIMENTAL

Participants will receive E2814 Dose C administered as an IV infusion, Q4W along with lecanemab administered as a SC injection, QW.

Drug: E2814; Drug: Lecanemab

E2814 Dose D + Lecanemab

EXPERIMENTAL

Participants will receive E2814 Dose D administered as an IV infusion, Q4W along with lecanemab administered as a SC injection, QW.

Drug: E2814; Drug: Lecanemab

Placebo + Lecanemab

EXPERIMENTAL

Participants will receive placebo administered as an IV infusion, Q4W along with lecanemab administered as a SC injection, QW.

Drug: Lecanemab; Drug: Placebo

Interventions

E2814 DRUG

E2814 IV infusion.

E2814 Dose A + Lecanemab; E2814 Dose B + Lecanemab; E2814 Dose C + Lecanemab; E2814 Dose D + Lecanemab

Lecanemab DRUG

Lecanemab SC injection.

Also known as: BAN2401, LEQEMBI

E2814 Dose A + Lecanemab; E2814 Dose B + Lecanemab; E2814 Dose C + Lecanemab; E2814 Dose D + Lecanemab; Placebo + Lecanemab

Placebo DRUG

Placebo IV infusion.

Placebo + Lecanemab

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For participants diagnosed with mild cognitive impairment (MCI) due to AD-intermediate likelihood:
• Meet the National Institute on Aging-Alzheimer's Association (NIA-AA) core clinical criteria for MCI due to AD-intermediate likelihood
• 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
• For participants diagnosed with mild AD dementia:
• Meet the NIA-AA core clinical criteria for probable AD dementia
• Have a global CDR score of 0.5 to 1.0 and a CDR Memory Box score of \>=0.5 at Screening
• Mini Mental State Examination (MMSE) score \>=22 at Screening and less than or equal to (\<=) 30 at Screening
• 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
• Male or female participants aged between \>=50 years and \<=80 years, at the time of informed consent
• 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
• 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).
• 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)
• Willing and able to comply with all aspects of the protocol including multiple CSF collections

You may not qualify if:

• Any neurological condition that may be contributing to cognitive impairment above and beyond that caused by the participant's AD
• History of transient ischemic attacks, stroke, or seizures within 12 months of Screening
• 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
• 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
• 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 \[ms\])
• 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
• 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
• 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)
• 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
• Hypersensitivity to lecanemab, E2814, or any of the excipients
• 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
• 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
• Known to be human immunodeficiency virus positive
• 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
• Severe visual or hearing impairment that would prevent the participant from performing psychometric tests accurately

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (26)

Banner Sun Health Research

Phoenix, Arizona, 85006, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06510, United States

Location

Bradenton Research Center

Bradenton, Florida, 34205, United States

Location

K2 Medical Research

Clermont, Florida, 34711, United States

Location

Advanced Clinical Research Network

Miami, Florida, 33165, United States

Location

Renstar Medical Research

Ocala, Florida, 34470, United States

Location

Progressive Medical Research

Port Orange, Florida, 32124, United States

Location

Alzheimer's Research and Treatment Center-Stuart

Stuart, Florida, 34997, United States

Location

Axiom Brain Health

Tampa, Florida, 33609, United States

Location

Charter Research

The Villages, Florida, 32162, United States

Location

Alzheimer's Research and Treatment Center

Wellington, Florida, 33467, United States

Location

Columbus Memory Center, PC

Columbus, Georgia, 31909, United States

Location

Hattiesburg Clinic

Hattiesburg, Mississippi, 39401, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Abington Neurological Associates LTD

Abington, Pennsylvania, 19001, United States

Location

Neurology Clinic, P.C.

Cordova, Tennessee, 38018, United States

Location

Kerwin Memory Center

Dallas, Texas, 75231, United States

Location

National Clinical Research-Richmond, Inc

Richmond, Virginia, 23294, United States

Location

National Center for Geriatrics and Gerontology

Ōbu, Aichi-ken, 474-8511, Japan

Location

National Hospital Organization Hiroshima-Nishi Medical Center

Ōtake, Hiroshima, 739-0696, Japan

Location

Keimei Memorial Hospital

Honjō, Miyazaki, 880-1111, Japan

Location

Rijikai Medical Corporation Katayama Medical Clinic

Kurashiki, Okayama-ken, 710-0813, Japan

Location

Tokyo Medical University Hospital

Shinjuku, Tokyo, 160-0023, Japan

Location

Keio University Hospital

Shinjuku, Tokyo, 160-8582, Japan

Location

Osaka Metropolitan University Hospital

Osaka, 545-8586, Japan

Location

Yamagata Tokushukai Hospital

Yamagata, 990-0834, Japan

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

lecanemab

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2024
• First Posted: September 19, 2024
• Study Start: September 30, 2024
• Primary Completion (Estimated): December 3, 2026
• Study Completion (Estimated): August 18, 2027
• Last Updated: February 11, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

US (18); JP (8)