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

NCT04971733 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: E2814-G000-1032020-005728-12
• Study Type: interventional
• Target: 8
• Locations: 2 countries
• Sites: 3

Brief 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 participants with DIAD.

Conditions

Alzheimer Disease

Keywords

E2814; Alzheimer disease; Dominantly inherited Alzheimer disease; Mild and moderate cognitive impairment; Central nervous system disease

Outcome Measures

Primary Outcomes (5)

• 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).

  From first dose of study drug up to 120 weeks

• 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.

  From first dose of study drug up to 120 weeks

• 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.

  From first dose of study drug up to 120 weeks

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

  The clinically significant assessment was based on investigator judgement.

  From first dose of study drug up to 120 weeks

• 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.

  Pre-dose at Week 12

Secondary Outcomes (13)

• Cohort A, Cmax: Maximum Observed Plasma Concentration for E2814

  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

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

  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

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

  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

• Cohort A, Cmax: Maximum Observed Serum Concentration for E2814

  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

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

  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

Study Arms (2)

Cohort A, Phase 1b and 2: E2814

EXPERIMENTAL

Participants will receive E2814 as an intravenous infusion at set intervals over 12 weeks in Phase 1b and over 96 weeks in Phase 2.

Drug: E2814

Cohort B: E2814

EXPERIMENTAL

Participants will receive E2814 as an intravenous infusion at set intervals over 52 weeks.

Drug: E2814

Interventions

E2814 DRUG

E2814 intravenous infusion.

Cohort A, Phase 1b and 2: E2814; Cohort B: E2814

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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
• 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
• 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

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (3)

UC San Diego Altman Clinical and Translational Research Insititute Clinic

La Jolla, California, 92037, United States

Location

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

Indianapolis, Indiana, 46202, United States

Location

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

London, WC1N 3BG, United Kingdom

Location

MeSH Terms

Conditions

Alzheimer Disease; Lymphoma, Follicular; Central Nervous System Diseases

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Eisai Medical Information
• Organization: Eisai Inc.

esi_medinfo@eisai.com

+1-888-274-2378

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2021
• First Posted: July 21, 2021
• Study Start: June 28, 2021
• Primary Completion: May 24, 2024
• Study Completion: May 24, 2024
• Last Updated: June 10, 2025
• Results First Posted: June 10, 2025

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share

Locations

US (2); GB (1)