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

Last updated: January 20, 2025
Sponsor: Eisai Inc.
Overall Status: Active - Recruiting

Phase

2

Condition

Memory Loss

Alzheimer's Disease

Dementia

Treatment

E2814

Placebo

Lecanemab

Clinical Study ID

NCT06602258
E2814-G000-202
  • Ages 50-80
  • All Genders

Study 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).

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. For participants diagnosed with mild cognitive impairment (MCI) due toAD-intermediate likelihood:

  2. Meet the National Institute on Aging-Alzheimer's Association (NIA-AA) coreclinical criteria for MCI due to AD-intermediate likelihood.

  3. Have a global Clinical Dementia Rating Scale (CDR) score of 0.5 and a CDRMemory Box score of greater than or equal to (>=) 0.5 at Screening and Baseline

  4. For participants diagnosed with mild AD dementia:

  5. Meet the NIA-AA core clinical criteria for probable AD dementia

  6. Have a global CDR score of 0.5 to 1.0 and a CDR Memory Box score of >=0.5 atScreening and Baseline

  7. Mini Mental State Examination (MMSE) score >=22 at Screening and Baseline and lessthan or equal to (<=) 30 at Screening and Baseline

  8. Able to have CSF lumbar puncture performed and not on, or have a medical conditionthat may require initiation of, any anticoagulant therapy at Screening

  9. Male or female participants aged between >=50 years and <=80 years, at the time ofinformed consent

  10. If receiving an approved AD symptomatic treatment (such as acetylcholinesteraseinhibitors (AchEIs), memantine, or both) for AD, participants must be on a stabledose for at least 12 weeks before Visit 1. Treatment-naïve participants for ADmedications can be enrolled into the study. Unless otherwise stated, participantsmust have been on stable doses of all other (that is, non AD-related) permittedconcomitant medications for at least 4 weeks before Baseline. Use of memantine willnot be allowed at screening for participants in Japan

  11. Have an identified study partner (defined as a person able to support theparticipant for the duration of the study and who spends at least 8 hours per weekwith the participant).

  12. Provide written informed consent. If a participant lacks the capacity to consent inthe Investigator's opinion, the participants' assent should be obtained, if requiredin accordance with local laws, regulations, and customs, plus the written informedconsent of a legal representative should be obtained (capacity to consent anddefinition of legal representative should be determined in accordance withapplicable local laws and regulations)

  13. Willing and able to comply with all aspects of the protocol including multiple CSFcollections

Exclusion

Exclusion Criteria:

  1. Any neurological condition that may be contributing to cognitive impairment aboveand beyond that caused by the participant's AD

  2. History of transient ischemic attacks, stroke, or seizures within 12 months ofScreening

  3. Any psychiatric diagnosis or symptoms (example, hallucinations, major depression, ordelusions) that could interfere with study procedures in the participants. Psychoticdisorder(s) or unstable recurrent affective disorder(s) evident by use ofantipsychotics 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 thoseapproved as safe for use in MRI scanners). Evidence of other clinically significantlesions on brain MRI at Screening that could indicate a dementia diagnosis otherthan AD. Other significant pathological findings on brain MRI at Screening,including but not limited to: greater than 4 microhemorrhages (defined as 10millimeter (mm) or less at the greatest diameter); a single intracerebral hemorrhagegreater than 10 mm at greatest diameter; an area of superficial siderosis; evidenceof vasogenic edema; evidence of cerebral contusion, encephalomalacia, aneurysms,vascular malformations, or infective lesions; evidence of multiple lacunar infarctsor stroke involving a major vascular territory, severe small vessel, or white matterdisease; space occupying lesions; or brain tumors (however, lesions diagnosed asmeningiomas or arachnoid cysts and less than 1 cm at their greatest diameter neednot be exclusionary). Other minor or clinically insignificant magnetic resonanceimaging (MRI) abnormalities, as agreed by the medical monitor and after discussionwith the investigator, may not be exclusionary

  5. Malignant neoplasms within 3 years of Screening (except for basal or squamous cellcarcinoma in situ of the skin, or localized prostate cancer in male participants, orlocalized breast cancer in female participants). Participants who had malignantneoplasms but who have had at least 3 years of documented uninterrupted remissionbefore Screening need not be excluded

  6. A clinically significant ECG abnormality, including a marked prolonged corrected QTinterval (Fridericia's Correction Formula; QTcF) interval (example, a repeateddemonstration of a QTcF interval greater than (>) 450 milliseconds [ms])

  7. Participants with a bleeding disorder that is not under adequate control (includinga platelet count <50,000 or international normalized ratio [INR] >1.5). Anyparticipants who are on anticoagulant therapy are not permitted to be enrolled

  8. Have thyroid-stimulating hormone above normal range. Other tests of thyroid functionwith results outside the normal range should only be exclusionary if they areconsidered clinically significant by the investigator. This applies to allparticipants whether or not they are taking thyroid supplements

  9. Abnormally low serum vitamin B12 levels for the testing laboratory (if participantis taking vitamin B12 injections, level should be at or above the lower limit ofnormal for the testing laboratory). Levels of vitamin B12 may be confirmed withreflex testing to include methylmalonic acid analysis, if available in region

  10. Any suicidal ideation with intent with or without a plan at Screening, Baseline, orwithin 6 months of Screening (that is, answering "Yes" to questions 4 or 5 on theSuicidal 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 forsuicidal 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. Anyother medical conditions (example, cardiac, respiratory, gastrointestinal, and renaldisease) that are not stably and adequately controlled or that in the opinion of theinvestigator(s) could affect the participant's safety or interfere with the studyassessments

  12. Hypersensitivity to lecanemab, E2814, or any of the excipients

  13. Any immunological disease, that is not adequately controlled, or that requirestreatment with immunoglobulins, systemic monoclonal antibodies (mAbs) (orderivatives of mAbs), systemic immunosuppressants, or plasmapheresis during thestudy

  14. Any history of or concomitant medical condition that in the opinion of theinvestigator(s) would compromise the participant's ability to safely complete thestudy

  15. Planned surgery that requires general, spinal, or epidural anesthesia that wouldtake place during the study. Planned surgery that requires only local anesthesia andthat can be undertaken as a day case without inpatient stay postoperatively need notresult in exclusion if in the opinion of the investigator this operation does notinterfere 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 yearsbefore Screening or a positive urine drug test at Screening. Participants who testpositive for benzodiazepines or opioids in urine drug testing need not be excludedif in the clinical opinion of the investigator, this is due to the participanttaking prior/concomitant medications containing benzodiazepines or opioids for amedical condition and not due to drug abuse

  18. Severe visual or hearing impairment that would prevent the participant fromperforming psychometric tests accurately

Study Design

Total Participants: 90
Treatment Group(s): 3
Primary Treatment: E2814
Phase: 2
Study Start date:
September 30, 2024
Estimated Completion Date:
August 19, 2027

Connect with a study center

  • National Center for Geriatrics and Gerontology

    Obu, Aichi 474-8511
    Japan

    Active - Recruiting

  • National Hospital Organization Hiroshima-Nishi Medical Center

    Otake, Hiroshima 739-0696
    Japan

    Active - Recruiting

  • Keimei Memorial Hospital

    Higashimorokatagun, Miyazaki 880-1111
    Japan

    Active - Recruiting

  • Rijikai Medical Corporation Katayama Medical Clinic

    Kurashiki, Okayama 710-0813
    Japan

    Active - Recruiting

  • Nippon Medical School Hospital

    Kanagawa, 2118533
    Japan

    Active - Recruiting

  • Osaka Metropolitan University Hospital

    Osaka, 545-8586
    Japan

    Site Not Available

  • Keio University Hospital

    Tokyo, 160-8582
    Japan

    Site Not Available

  • Tokyo Medical University Hospital

    Tokyo, 160-0023
    Japan

    Site Not Available

  • Tokyo Metropolitan Institute for Geriatrics and Gerontology

    Tokyo, 1730015
    Japan

    Site Not Available

  • Yamagata Tokushukai Hospital

    Yamagata, 9900834
    Japan

    Active - Recruiting

  • Banner Sun Health Research Institute

    Sun City, Arizona 85351
    United States

    Site Not Available

  • Sharp Neurocognitive Research Center at Sharp Mesa Vista Hospital

    San Diego, California 92123
    United States

    Site Not Available

  • University of California at San Francisco/UCSF

    San Francisco, California 94158-2549
    United States

    Site Not Available

  • Yale University School of Medicine

    New Haven, Connecticut 06510
    United States

    Site Not Available

  • Bradenton Research Center

    Bradenton, Florida 34205
    United States

    Active - Recruiting

  • K2 Medical Research

    Clermont, Florida 34711
    United States

    Active - Recruiting

  • Charter Research

    Lady Lake, Florida 32159
    United States

    Active - Recruiting

  • Advanced Clinical Research Network

    Miami, Florida 33135
    United States

    Active - Recruiting

  • Renstar Medical Research

    Ocala, Florida 34470
    United States

    Active - Recruiting

  • Progressive Medical Research

    Port Orange, Florida 32127
    United States

    Active - Recruiting

  • Alzheimer's Research and Treatment Center

    Stuart, Florida 34997
    United States

    Active - Recruiting

  • Axiom Brain Health

    Tampa, Florida 33609
    United States

    Site Not Available

  • ClinCloud Research, LLC

    Viera, Florida 32940
    United States

    Active - Recruiting

  • Alzheimer's Research and Treatment Center

    Wellington, Florida 33414
    United States

    Active - Recruiting

  • Columbus Memory Center, PC

    Columbus, Georgia 31909
    United States

    Site Not Available

  • Memory Center/Hattiesburg Clinic

    Hattiesburg, Mississippi 39401
    United States

    Site Not Available

  • Washington University School of Medicine

    Saint Louis, Missouri 63110
    United States

    Active - Recruiting

  • Advanced Memory Research Institute

    Toms River, New Jersey 08755
    United States

    Site Not Available

  • AMC Research LLC, Formerly Alzheimer's Memory Center

    Matthews, North Carolina 28105
    United States

    Site Not Available

  • Cleveland Clinic

    Cleveland, Ohio 44113
    United States

    Site Not Available

  • Abington Neurological Associates Ltd

    Abington, Pennsylvania 19001
    United States

    Active - Recruiting

  • Keystone Clinical Research LLC

    Plymouth Meeting, Pennsylvania 19462
    United States

    Active - Recruiting

  • Neurology Clinical, P.C.

    Cordova, Tennessee 38018
    United States

    Active - Recruiting

  • Kerwin Medical Center

    Dallas, Texas 75231-4350
    United States

    Active - Recruiting

  • National Clinical Research-Richmond, Inc

    Richmond, Virginia 23294
    United States

    Active - Recruiting

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