A Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of E2511 in Participants With Early Alzheimer's Disease (AD)

NCT07768592 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: E2511-A001-102
• Study Type: interventional
• Target: 32
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary purpose of this study is to evaluate proof of mechanism (POM) and long-term safety and tolerability of E2511 in participants with Early AD. The study consists of 2 parts. In Part A, participants will be randomly assigned to receive either E2511 or donepezil. In Part B, participants will receive E2511 only. Once Part A and Part B participants complete the Core Trial (which includes Pretreatment and Treatment phases) they will have the option to enter the Extension Phase where they will receive E2511 for 18 months.

Conditions

Alzheimers Disease

Outcome Measures

Primary Outcomes (8)

• Part A (Core Trial): Change from Baseline in [11C]MK-6884 Positron Emission Tomography (PET) Using Non-Displaceable Binding Potential (BPND) at 14 Days

  Baseline up to Day 14

• Part A and B (Extension Phase): Number of Participants With Adverse Events (AEs)

  Up to 91 weeks

• Part A and B (Extension Phase): Number of Participants With Clinically Significant Changes in Vital Sign Values

  From Week 13 up to Week 91

• Part A and B (Extension Phase): Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values

  From Week 13 up to Week 91

• Part A and B (Extension Phase): Number of Participants With Clinically Significant Changes in Physical Exam

  From Week 13 up to Week 91

• Part A and B (Extension Phase): Number of Participants With Clinically Significant Changes in Neurological Exam

  From Week 13 up to Week 91

• Part A and B (Extension Phase): Number of Participants With Clinically Significant Changes in Laboratory Safety Tests Values

  From Week 13 up to Week 91

• Part A and B (Extension Phase): Number of Participants With Suicidality as Assessed by Columbia - Suicide Severity Rating Scale (C-SSRS)

  The C-SSRS is an interview-based rating scale to systematically assess any suicidality, suicidal behavior, or suicidal ideation. Any suicidality is emergence of any suicidal ideation or suicidal behavior. Any suicidal behavior is indicated when response is "yes" for any these questions- actual attempt to suicide, engaged in non-suicidal self-injurious behavior, interrupted attempt, aborted attempt, preparatory acts. Any suicidal ideation is indicated when response is "yes" for any of these questions- wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent to suicide.

  Up to 91 weeks

Secondary Outcomes (15)

• Part A and B (Core Trial): Number of Participants With AEs

  Part A: Up to 21 weeks; Part B: Up to 17 weeks

• Part A and B (Core Trial): Number of Participants With Clinically Significant Changes in Vital Sign Values

  Part A: Up to 21 weeks; Part B: Up to 17 weeks

• Part A and B (Core Trial): Number of Participants With Clinically Significant Changes in ECG Values

  Part A: Up to 21 weeks; Part B: Up to 17 weeks

• Part A and B (Core Trial): Number of Participants With Clinically Significant Changes in Laboratory Safety Tests Values

  Part A: Up to 21 weeks; Part B: Up to 17 weeks

• Part A and B (Core Trial): Number of Participants With Clinically Significant Changes in Physical Exam

  Part A: Up to 21 weeks; Part B: Up to 17 weeks

Study Arms (3)

Part A: E2511 Dose A

EXPERIMENTAL

Drug: E2511

Part A: Donepezil Dose A

EXPERIMENTAL

Drug: Donepezil

Part B: E2511 Dose B

EXPERIMENTAL

Drug: E2511

Interventions

E2511 DRUG

E2511 oral tablets.

Part A: E2511 Dose A; Part B: E2511 Dose B

Donepezil DRUG

Donepezil oral tablets.

Also known as: Aricept

Part A: Donepezil Dose A

Eligibility Criteria

• Age: 50 Years - 85 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 and the 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 and Baseline.
• 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 and Baseline.
• Mini Mental State Examination (MMSE) score \>=22 and less than or equal to (\<=) 30 at Screening.
• Evidence of brain amyloid pathology as indicated by one of the following:
• Plasma phosphorylated tau217 (p-tau217) assay performed at Screening.
• Historical plasma p-tau217 assay performed before screening.
• Historical cerebrospinal fluid (CSF) or amyloid PET assessment performed before Screening.
• Nonsmoking and nonvaping, male or female, aged \>=50 years and \<=85 years old, at the time of informed consent.
• Body Mass Index (BMI) greater than 17 and less than 35 at Screening.
• Able to undergo CSF lumbar puncture and not receiving any anticoagulant therapy or currently suffering from a medical condition that may require initiation of any anticoagulant therapy at Screening.
• Provide written informed consent. If a participant lacks the capacity to consent in the investigator's opinion, the participant's 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).

You may not qualify if:

• Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin \[β-hCG\] or human chorionic gonadotropin \[hCG\] test with a minimum sensitivity of 25 International Units per Liter \[IU/L\] or equivalent units of β-hCG \[or hCG\]). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of trial drug.
• Females of childbearing potential who:
• Within 28 days before trial entry, did not use a highly effective method of contraception, which includes any of the following:
• total abstinence (if it is their preferred and usual lifestyle)
• an intrauterine device or intrauterine hormone-releasing system (IUS)
• a contraceptive implant
• an oral contraceptive (participant must have been on a stable dose of the same oral contraceptive product for at least 28 days before dosing and must agree to stay on the same dose of the oral contraceptive throughout the trial and for 28 days after trial drug discontinuation)
• have a vasectomized partner with confirmed azoospermia.
• Do not agree to use a highly effective method of contraception (as described above) throughout the entire trial period and for 28 days after trial drug discontinuation.
• NOTE: It is permissible that if a highly effective method of contraception is not appropriate or acceptable to the participant, then the participant must agree to use a medically acceptable method of contraception, i.e., double-barrier methods of contraception such as latex or synthetic condom plus diaphragm or cervical/vault cap with spermicide. All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (i.e., bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing).
• Any neurological condition that may be contributing to cognitive impairment above and beyond that caused by the participant's MCI or AD.
• History of transient ischemic attacks, stroke, or seizures within 12 months of Screening.
• Any lifetime history of psychiatric disease (including but not limited to depression or other mood disorders, bipolar disorder, psychotic disorders, including schizophrenia, panic attacks, anxiety disorders).
• Any suicidal ideation with intent with or without a plan at Screening or within 6 months of Screening (i.e., answering "Yes" to questions 4 or 5 on the Suicidal Ideation section of the C-SSRS).
• Any lifetime suicidal behavior (per the Suicidal Behavior Section of the C-SSRS).

Sponsors & Collaborators

• Eisai Inc.: lead

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Donepezil

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds

Central Study Contacts

Eisai Medical Information

CONTACT

+1-888-274-2378; esi_medinfo@eisai.com

Study Design

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

Study Record Dates

• First Submitted: August 12, 2026
• First Posted: August 17, 2026
• Study Start (Estimated): October 15, 2026
• Primary Completion (Estimated): May 6, 2030
• Study Completion (Estimated): May 6, 2030
• Last Updated: August 17, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share