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Alzheimer DiseasePhase 1/2NCT04971733

A Study to Assess Safety and Target Engagement of E2814 in Participants With Mild to Moderate Cognitive Impairment Due to Dominantly Inherited Alzheimer's Disease

A Phase 1/2 study testing E2814 in people with Alzheimer Disease, run by Eisai Inc. at 3 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The primary objective of the study is to assess the safety and tolerability of intravenous (IV) infusions of E2814 in participants with dominantly inherited Alzheimer's disease (DIAD), and to evaluate target engagement (TE) of E2814 on microtubule binding region (MTBR)-tau species in cerebrospinal fluid (CSF) in… Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Alzheimer Disease
What is being tested?
E2814
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
3 sitesin 2 countries
Study dates
28 Jun 2021to 24 May 2024
Phase
Phase 1/2
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 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female, age 18 to 80 years at the time of informed consent
  • Individuals who are confirmed to be mutation positive for presenilin 1 (PSEN1), amyloid precursor protein (APP), or presenilin 2 (PSEN2) gene that is associated with DIAD
  • Clinical Dementia Rating - Sum of Boxes (CDR-SB) score 5 to 12 at Screening
  • Able to undergo magnetic resonance imaging (MRI), lumbar puncture (LP), PET, and complete all study-related testing and evaluations
  • Has a study partner who in the investigator's judgment is able to provide accurate information as to the participant's cognitive and functional abilities, who agrees to provide information at the study visits which require informant input for scale completion

Who cannot join

  • Clinically significant illness that required medical treatment within 8 weeks before the 1st dose or a clinically significant infection that required medical treatment within 4 weeks before 1st dose
  • Females who are breastfeeding or pregnant at Screening or Baseline
  • Females of childbearing potential who:
  • Within 3 months before screening, did not use a highly effective method of contraception
  • Any neurological condition that may be contributing to cognitive impairment above and beyond that caused by the participant's Alzheimer's disease (AD)
  • History of transient ischemic attacks, stroke, or seizures within 12 months of Screening
Show all 29Show fewer
  • History of clinically important carotid or vertebrobasilar stenosis, plaque, or other prominent risk factor for stroke or cerebral haemorrhage (including atrial fibrillation and anticoagulation). Low dose aspirin (less than or equal to [<=] 325 milligram [mg] daily) is not exclusionary
  • Any current psychiatric diagnosis or symptoms, (example, hallucinations, major depression, or delusions) that could interfere with study procedures in the participant
  • Geriatric Depression Scale (GDS) score greater than or equal to 8 at Screening
  • Contraindications to MRI scanning, including but not limited to pacemaker/cardiac defibrillator, neurostimulators, 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
  • Hypersensitivity to E2814 or any of the excipients, or to any monoclonal antibody (mAb) treatment
  • Any immunological disease which is not adequately controlled, or which requires treatment with immunoglobulins, systemic monoclonal antibodies (or derivatives of monoclonal antibodies), systemic immunosuppressants, or plasmapheresis during the study
  • With a bleeding disorder of current chronic use of anticoagulants (example, warfarin, dabigatran, rivaroxaban or apixaban) or of clopidogrel is exclusionary. Limited (occasional or isolated) use of anticoagulants/antiplatelet compounds in cases such as surgical procedures
  • Have thyroid stimulating hormone outside of 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
  • Hemoglobin A1c (HgbA1c) greater than (>) 8 percent (%) (retesting is permitted if slightly elevated) or poorly controlled insulin-dependent diabetes (including hypoglycemic episodes). Participants may be rescreened after 3 months to allow optimization of diabetic control
  • Abnormally low serum vitamin B12 levels for the testing laboratory
  • History of human immunodeficiency virus (HIV) infection, history of hepatitis B infection within the past year, history of hepatitis C infection which has not been adequately treated, or history of spirochete infection of the central nervous system (example, syphilis, Lyme, or borreliosis)
  • Any other clinically significant abnormalities in physical examination, vital signs, laboratory tests, or ECG at Screening or Baseline which in the opinion of the investigator require further investigation or treatment or which may interfere with study procedures or safety
  • 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 participant, or localized breast cancer in female participants)
  • Answers "yes" to Columbia-Suicide Severity Rating Scale (C-SSRS) suicidal ideation 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 any suicidal behavior in lifetime
  • Known or suspected history of drug or alcohol abuse or dependence within 2 years before Screening or a positive urine drug test at Screening
  • Any other medical conditions (example, cardiac, respiratory, gastrointestinal, renal disease) which are not stably and adequately controlled, or which in the opinion of the investigator could affect the participant's safety or interfere with the study assessments
  • Concurrent participation in a clinical study involving any anti-amyloid therapies (including any mAb therapies) within 6 months before Screening
  • Concurrent participation in a clinical study involving any anti-tau therapies
  • Participated in any other investigational medication or device study in the 3 months or 5 half-lives (whichever is longer) of the medication before Screening
  • Planned surgery which requires general anesthesia that would take place during the study
  • Visual or hearing impairment that would prevent the participant from performing psychometric tests accurately

Trial locations and contacts

3 sites in 2 countries.

3 sites in 2 countries

United States2 sites

  • Indiana University School of Medicine, Health Partners, Adult Neurology Clinic

    Indianapolis, Indiana, 46202

  • UC San Diego Altman Clinical and Translational Research Insititute Clinic

    La Jolla, California, 92037

Other trials in United States

United Kingdom1 site

  • National Hospital for Neurology and Neurosurgery (NHNN) University College London(UCL) Hospitals NHS Foundation Trust

    London, WC1N 3BG

Other trials in United Kingdom

About this study

Official title: An Open-Label Phase 1b/2 Study to Assess Safety and Target Engagement of E2814 in Subjects With Mild to Moderate Cognitive Impairment Due to Dominantly Inherited Alzheimer's Disease

The primary objective of the study is to assess the safety and tolerability of intravenous (IV) infusions of E2814 in participants with dominantly inherited Alzheimer's disease (DIAD), and to evaluate target engagement (TE) of E2814 on microtubule binding region (MTBR)-tau species in cerebrospinal fluid (CSF) in participants with DIAD.

Being tested
E2814
Keywords
E2814, Alzheimer disease, Dominantly inherited Alzheimer disease, Mild and moderate cognitive impairment, Central nervous system disease
Medical subject headings
Alzheimer Disease, Lymphoma, Follicular, Central Nervous System Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • E2814Drug

    E2814 intravenous infusion.

Study groups in NCT04971733
Study groupRoleWhat they receive
Cohort A, Phase 1b and 2: E2814ExperimentalParticipants will receive E2814 as an intravenous infusion at set intervals over 12 weeks in Phase 1b and over 96 weeks in Phase 2.
Receives: Drug: E2814
Cohort B: E2814ExperimentalParticipants will receive E2814 as an intravenous infusion at set intervals over 52 weeks.
Receives: Drug: E2814

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs

    A TEAE was defined as adverse event (AE) that started at or after the time of administration of study drug or a worsening of severity from Baseline on or after 1st dose up to last assessment. An AE was any untoward medical occurrence in a participant or clinical investigation participant administered an investigational product. An AE did not necessarily have a causal relationship with the medicinal product. SAE was any untoward medical occurrence that at any dose: resulted in death; was life-threatening (that is, the participant was at immediate risk of death from the AE as it occurred; this did not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug).

    Measured: From first dose of study drug up to 120 weeks

  2. Number of Participants With Markedly Abnormal Laboratory Values

    Clinical laboratory tests included hematology, clinical chemistry, and urinalysis assessments. Markedly abnormal value was defined as a post-baseline value with an increase from baseline to a grade of 2 or higher on Common Terminology Criteria for Adverse events (CTCAE) Version 5.0 scale.

    Measured: From first dose of study drug up to 120 weeks

  3. Number of Participants With Clinically Significant Change in Vital Signs Values

    Vital sign measurements included systolic and diastolic blood pressure, pulse, respiratory rate, body temperature, height and weight assessment. The clinically significant assessment was based on investigator judgement.

    Measured: From first dose of study drug up to 120 weeks

  4. Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings

    The clinically significant assessment was based on investigator judgement.

    Measured: From first dose of study drug up to 120 weeks

  5. Cohort A: Change From Baseline in Cerebrospinal Fluid (CSF) Free, CSF Bound and Total Microtubule Binding Region of Tau (MTBR-tau; Starting at Amino Acid 354 and 299) at 12 Weeks

    Total MTBR-Tau was the total of bound MTBR-Tau + free MTBR-Tau. CSF samples were collected for the assessment.

    Measured: Pre-dose at Week 12

Secondary outcomes (13)

  1. Cohort A, Cmax: Maximum Observed Plasma Concentration for E2814

    The concentration of E2814 were measured by validated electrochemiluminescence assay methods and/or by a validated immunoprecipitation/purification followed by liquid chromatography with tandem mass spectrometry methods.

    Measured: Cohort A, E2814 750 mg: Day 1 pre-dose up to 25 hours post-dose; Cohort A, E2814 1500 mg: Day 85 pre-dose up to 25 hours post-dose

  2. Cohort A, Tmax: Time to Reach the Maximum Plasma Concentration for E2814

    The concentration of E2814 was measured by validated electrochemiluminescence assay methods and/or by a validated immunoprecipitation/purification followed by liquid chromatography with tandem mass spectrometry methods.

    Measured: Cohort A, E2814 750 mg: Day 1 pre-dose up to 25 hours post-dose; Cohort A, E2814 1500 mg: Day 85 pre-dose up to 25 hours post-dose

  3. Cohort A, AUC(0-672h): Area Under the Plasma Concentration-time Curve From Zero Time to 672 Hours for E2814

    The concentration of E2814 was measured by validated electrochemiluminescence assay methods and/or by a validated immunoprecipitation/purification followed by liquid chromatography with tandem mass spectrometry methods.

    Measured: Cohort A, E2814 750 mg: Day 1 pre-dose up to 672 hours post-dose; Cohort A, E2814 1500 mg: Day 85 pre-dose up to 672 hours post-dose

  4. Cohort A, Cmax: Maximum Observed Serum Concentration for E2814

    The concentration of E2814 was measured by validated electrochemiluminescence assay methods and/or by a validated immunoprecipitation/purification followed by liquid chromatography with tandem mass spectrometry methods.

    Measured: Cohort A, E2814 750 mg: Day 1 pre-dose up to 25 hours post-dose; Cohort A, E2814 1500 mg: Day 85 pre-dose up to 25 hours post-dose

  5. Cohort A, Tmax: Time to Reach the Maximum Serum Concentration for E2814

    The concentration of E2814 was measured by validated electrochemiluminescence assay methods and/or by a validated immunoprecipitation/purification followed by liquid chromatography with tandem mass spectrometry methods.

    Measured: Cohort A, E2814 750 mg: Day 1 pre-dose up to 25 hours post-dose; Cohort A, E2814 1500 mg: Day 85 pre-dose up to 25 hours post-dose

  6. Cohort A, AUC(0-672h): Area Under the Serum Concentration-time Curve From Zero Time to 672 Hours for E2814

    The concentration of E2814 was measured by validated electrochemiluminescence assay methods and/or by a validated immunoprecipitation/purification followed by liquid chromatography with tandem mass spectrometry methods.

    Measured: Cohort A, E2814 750 mg: Day 1 pre-dose up to 672 hours post-dose; Cohort A, E2814 1500 mg: Day 85 pre-dose up to 672 hours post-dose

  7. Cohort A: CSF Concentrations of E2814

    The concentration of E2814 was measured by validated electrochemiluminescence assay methods and/or by a validated immunoprecipitation/purification followed by liquid chromatography with tandem mass spectrometry methods.

    Measured: Pre-dose at Days 1, 84, 85, 169, 253, 421, and 757

  8. Number of Participants With Treatment-emergent Positive Serum Anti-E2814 Antibody

    Anti-E2814 antibodies were measured by validated electrochemiluminescence assay.

    Measured: From first dose of study drug up to 120 weeks

  9. Number of Participants With Treatment-emergent Positive Plasma Anti-E2814 Antibody

    Anti-E2814 antibodies were measured by validated electrochemiluminescence assay.

    Measured: From first dose of study drug up to 120 weeks

  10. Cohort A: Change From Baseline in CSF Concentrations of Total MTBR-tau243

    CSF samples were collected for the assessment.

    Measured: Baseline, and pre-dose at Days 84, 169, 253, 421, 505, 589, and 757

  11. Cohort A: Change From Baseline in CSF Concentrations of Phosphorylated Tau (P-tau) 181, 205, and 217

    CSF samples were collected for the assessment.

    Measured: Baseline, and pre-dose at Days 84, 169, 253, 421, 505, 589, and 757

  12. Cohort A: Change From Baseline in Ratio of CSF Concentrations of p-Tau/Non-phosphorylated (np) Tau for 181, 217, and 205

    CSF samples were collected for the assessment.

    Measured: Baseline, and pre-dose at Days 84, 169, 253, 421, 505, 589, and 757

  13. Cohort A: Change From Baseline in Tau Positron Emission Tomography (PET) Standardized Uptake Value Ratio (SUVR) by Region

    Tau-PET imaging uses radiotracers to visualize tau protein deposits in the brain for regional assessment of tau pathology. SUVR is ratio of tracer uptake in each of the cingulate, frontal, medial, occipital, parietal, whole cortical, meta temporal, and temporal cortices relative to tracer uptake in the cerebellum.

    Measured: Baseline, at Weeks 60 and 108

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jul 2021
  2. Study start28 Jun 2021
  3. Primary completion24 May 2024
  4. Study completion24 May 2024

Resources

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04971733
Sponsor's protocol ID
E2814-G000-103
Other IDs
2020-005728-12
Status last verified
Jul 2024
First submitted
20 Jul 2021
Last updated
10 Jun 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.

Publications

  • Andreozzi E, Yagi T, Wildsmith K, Rawal S, Horie K, Boyd P, Takahashi E, Barthelemy NR, Aluri J, Charil A, Reilhac A, Gordon BA, Flores S, Verbel D, Sauter N, Benzinger TLS, McDade E, Mummery C; Dominantly Inherited Alzheimer Network (DIAN); Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU); Zhou J, Bateman RJ, Reyderman L. Etalanetug (E2814) in dominantly inherited Alzheimer's disease: an open-label phase 1b/2 study to assess safety and target engagement in participants with mild to moderate cognitive impairment. Alzheimers Res Ther. 2026 Apr 10;18(1):87. doi: 10.1186/s13195-026-02047-y.

    PubMed 41964075

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing E2814 in people with Alzheimer Disease, run by Eisai Inc. at 3 sites in 2 countries.

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 5 inclusion and 29 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: finished, as of the sponsor's last update on 10 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States, United Kingdom. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 10 Jun 2025). 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?

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs (time frame: From first dose of study drug up to 120 weeks). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04971733, which also lists 1 linked publication.

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 10 Jun 2025.

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