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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04971733
Recruitment Status : Active, not recruiting
First Posted : July 21, 2021
Last Update Posted : May 25, 2022
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.

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.

Condition or disease Intervention/treatment Phase
Alzheimer Disease Drug: E2814 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 8 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 28, 2021
Estimated Primary Completion Date : September 13, 2024
Estimated Study Completion Date : September 13, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Phase 1b: E2814
Participants will receive E2814 as an intravenous infusion at set intervals over 12 weeks in Phase 1b.
Drug: E2814
E2814 intravenous infusion.

Experimental: Phase 2: E2814
Participants will receive E2814 as an intravenous infusion at set intervals over 96 weeks in Phase 2.
Drug: E2814
E2814 intravenous infusion.




Primary Outcome Measures :
  1. Number of Participants With Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Screening up to 16 weeks after the last dose of study drug (approximately 124 Weeks) ]
  2. Number of Participants With Serious Adverse Events (SAEs) [ Time Frame: Screening up to 14 weeks after the last dose of study drug (approximately 122 Weeks) ]
  3. Number of Participants With Markedly Abnormal Laboratory Values [ Time Frame: Up to Week 120 ]
  4. Number of Participants With Clinically Significant Vital Signs Values [ Time Frame: Up to Week 120 ]
  5. Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings [ Time Frame: Baseline up to Week 120 ]
  6. Change From Baseline in CSF Free and Bound MTBR-tau at 12 Weeks [ Time Frame: Baseline up to Week 12 ]
  7. Change From Baseline in Total MTBR-tau at 12 Weeks [ Time Frame: Baseline up to Week 12 ]

Secondary Outcome Measures :
  1. Cmax: Maximum Observed Plasma Concentration for E2814 on Days 1 and 85 [ Time Frame: Days 1 and 85: 0-24 hours post-infusion ]
  2. Tmax: Time to Reach the Maximum Plasma Concentration for E2814 on Days 1 and 85 [ Time Frame: Days 1 and 85: 0-24 hours post-infusion ]
  3. AUC(0-672h): Area Under the Plasma Concentration-time Curve From Zero Time to 672 Hours for E2814 on Days 1 and 85 [ Time Frame: Days 1 and 85: 0-672 hours post-infusion ]
  4. Cmax Serum: Maximum Observed Serum Concentration for E2814 on Days 1 and 85 [ Time Frame: Days 1 and 85: 0-24 hours post-infusion ]
  5. Tmax Serum: Time to Reach the Maximum Serum Concentration for E2814 on Days 1 and 85 [ Time Frame: Days 1 and 85: 0-24 hours post-infusion ]
  6. AUC(0-672h) Serum: Area Under the Serum Concentration-time Curve From Zero Time to 672 Hours for E2814 on Days 1 and 85 [ Time Frame: Days 1 and 85: 0-672 hours post-infusion ]
  7. CSF Concentrations of E2814 [ Time Frame: Up to Week 108 ]
  8. Serum anti-E2814 Antibody Concentration [ Time Frame: Up to Week 120 ]
  9. Plasma anti-E2814 Antibody Concentration [ Time Frame: Up to Week 120 ]
  10. Change From Baseline in CSF Concentrations of Total tau (t-tau) and Phosphorylated tau (p-tau) [ Time Frame: Baseline up to Week 108 ]
  11. Change From Baseline in tau Positron Emission Tomography (PET) Signal [ Time Frame: Baseline up to Week 108 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female, age 18 to 80 years at the time of informed consent
  2. 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
  3. Clinical Dementia Rating - Sum of Boxes (CDR-SB) score 5 to 12 at Screening
  4. Evidence of positive amyloid status based on historical or screening amyloid PET
  5. Able to undergo magnetic resonance imaging (MRI), lumbar puncture (LP), PET, and complete all study-related testing and evaluations
  6. 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

Exclusion Criteria:

  1. Clinically significant illness that required medical treatment within 8 weeks before the first dose or a clinically significant infection that required medical treatment within 4 weeks before first dose
  2. Females who are breastfeeding or pregnant at Screening or Baseline
  3. Females of childbearing potential who:

    Within 3 months before screening, did not use a highly effective method of contraception

  4. Any neurological condition that may be contributing to cognitive impairment above and beyond that caused by the participant's Alzheimer's disease (AD)
  5. History of transient ischemic attacks, stroke, or seizures within 12 months of Screening
  6. 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
  7. Any current psychiatric diagnosis or symptoms, (example, hallucinations, major depression, or delusions) that could interfere with study procedures in the participant
  8. Geriatric Depression Scale (GDS) score greater than or equal to 8 at Screening
  9. 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)
  10. Evidence of other clinically significant lesions on brain MRI at Screening that could indicate a dementia diagnosis other than AD
  11. Other significant pathological findings on brain MRI at Screening
  12. Hypersensitivity to E2814 or any of the excipients, or to any monoclonal antibody (mAb) treatment
  13. 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
  14. 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
  15. 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
  16. 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
  17. Abnormally low serum vitamin B12 levels for the testing laboratory
  18. 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)
  19. 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
  20. 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)
  21. 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
  22. Known or suspected history of drug or alcohol abuse or dependence within 2 years before Screening or a positive urine drug test at Screening
  23. 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
  24. Concurrent participation in a clinical study involving any anti-amyloid therapies (including any mAb therapies) within 6 months before Screening
  25. Concurrent participation in a clinical study involving any anti-tau therapies
  26. 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
  27. Planned surgery which requires general anesthesia that would take place during the study
  28. Visual or hearing impairment that would prevent the participant from performing psychometric tests accurately

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04971733


Locations
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United States, California
UC San Diego Altman Clinical and Translational Research Insititute Clinic
La Jolla, California, United States, 92037
United States, Indiana
Indiana University School of Medicine, Health Partners, Adult Neurology Clinic
Indianapolis, Indiana, United States, 46202
United Kingdom
National Hospital for Neurology and Neurosurgery (NHNN) University College London(UCL) Hospitals NHS Foundation Trust
London, United Kingdom, WC1N 3BG
Sponsors and Collaborators
Eisai Inc.
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Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT04971733    
Other Study ID Numbers: E2814-G000-103
2020-005728-12 ( EudraCT Number )
First Posted: July 21, 2021    Key Record Dates
Last Update Posted: May 25, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Eisai Inc.:
E2814
Central Nervous System Diseases
Mild Alzheimer's disease
Mental Disorders
Neurocognitive Disorders
Additional relevant MeSH terms:
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Alzheimer Disease
Cognitive Dysfunction
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Cognition Disorders