Dose-Finding Study To Evaluate Safety, Tolerability, and Efficacy of E2609 in Participants With Mild Cognitive Impairment Due to Alzheimer's Disease (Prodromal Alzheimer's Disease) and Mild to Moderate Dementia Due to Alzheimer's Disease

NCT ID: NCT02322021

Last Updated: 2021-03-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-11-26
• Study Completion Date: 2019-12-20

Brief Summary

This is a Phase 2 study to evaluate safety and efficacy in participants with Mild Cognitive Impairment due to Alzheimer's Disease/Prodromal Alzheimer's Disease (referred to as MCI/Prodromal) and mild to moderate dementia due to Alzheimer's Disease (referred to as mild to moderate AD). This study will have a Core Phase and an Extension Phase.

Conditions

Alzheimer Disease; Dementia, Alzheimer Type

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

MCI/Prodromal Cohort: Low Dose

A low dose of E2609 will be assessed.

Group Type: EXPERIMENTAL

E2609

Intervention Type: DRUG

Each participant will receive 2 tablets, which when combined will make up the required doses of E2609 or placebo, to be administered orally once per day (QD) with food.

MCI/Prodromal Cohort: Middle Dose

A middle dose of E2609 will be assessed.

Group Type: EXPERIMENTAL

E2609

Intervention Type: DRUG

Each participant will receive 2 tablets, which when combined will make up the required doses of E2609 or placebo, to be administered orally once per day (QD) with food.

MCI/Prodromal Cohort: High Dose

A high dose of E2609 will be assessed.

Group Type: EXPERIMENTAL

E2609

Intervention Type: DRUG

Each participant will receive 2 tablets, which when combined will make up the required doses of E2609 or placebo, to be administered orally once per day (QD) with food.

MCI/Prodromal Cohort: Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Each participant will receive 2 tablets, which when combined will make up the required doses of E2609 or placebo, to be administered orally once per day (QD) with food.

Mild to Moderate AD Cohort: Low Dose

A low dose of E2609 will be assessed.

Group Type: EXPERIMENTAL

E2609

Intervention Type: DRUG

Each participant will receive 2 tablets, which when combined will make up the required doses of E2609 or placebo, to be administered orally once per day (QD) with food.

Mild to Moderate AD Cohort: High Dose

A high dose of E2609 will be assessed.

Group Type: EXPERIMENTAL

E2609

Intervention Type: DRUG

Each participant will receive 2 tablets, which when combined will make up the required doses of E2609 or placebo, to be administered orally once per day (QD) with food.

Mild to Moderate AD Cohort: Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Each participant will receive 2 tablets, which when combined will make up the required doses of E2609 or placebo, to be administered orally once per day (QD) with food.

Mild to Moderate AD cohort: Middle Dose

A middle dose of E2609 will be assessed.

Group Type: EXPERIMENTAL

E2609

Intervention Type: DRUG

Each participant will receive 2 tablets, which when combined will make up the required doses of E2609 or placebo, to be administered orally once per day (QD) with food.

Interventions

E2609

Each participant will receive 2 tablets, which when combined will make up the required doses of E2609 or placebo, to be administered orally once per day (QD) with food.

Intervention Type: DRUG

Placebo

Each participant will receive 2 tablets, which when combined will make up the required doses of E2609 or placebo, to be administered orally once per day (QD) with food.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Participants must meet all of the following criteria to be included in this study:

1. Meets the core clinical research criteria of the National Institute on Aging-Alzheimer's Association (NIA-AA) for MCI due to AD (which is consistent with Prodromal AD) or AD dementia and is 'staged' or classified as either MCI or mild to moderate dementia.

2. Amyloid positive Positron Emission Tomography (PET) image based on centralized PET scan reading.

3. Male or female, age 50 to 85 years, inclusive at time of consent.

4. Must have an identified caregiver or informant who is willing and able to provide follow-up information on the participant throughout the course of the study.

5. If receiving an Acetylcholinesterase Inhibitor (AChEI) or memantine, must have been on a stable dose for at least 12 weeks before the Baseline cognitive assessments, with no plans for dose adjustment in the foreseeable future. Treatment-naive participants can be entered into the study but there should be no plans to initiate treatment with AChEIs or memantine at the time of entry into the study.

6. Must have been on stable doses of all other permitted chronically used concomitant medications (that is, not related to their cognitive decline) for at least 4 weeks before randomization.

Exclusion Criteria

Participants who meet any of the following criteria will be excluded from this study:

1. Any neurological condition that may be contributing to cognitive impairment above and beyond that caused by the participant's AD pathology, including any co-morbidities such as cerebrovascular disease, detected by medical history, neurological examination, or magnetic resonance imaging (MRI).

2. History of transient ischemic attacks or stroke within 12 months of Screening.

3. History of epilepsy.

4. Evidence of depression on a rating scale at Screening or any psychiatric diagnosis or symptoms, (example, hallucinations, major depression, etc.) that could confound the diagnosis or could interfere with study assessments or procedures. This includes suicidal ideation or suicidal behavior within 6 months prior to Screening, or hospitalization or treatment for suicidal behavior in the past 5 years.

5. Abnormally low serum vitamin B12.

6. Thyroid stimulating hormone above the normal range. This applies to all participants regardless of whether or not they are taking thyroid supplements.

7. Participants with liver disease (hepatic impairment), at Screening or Baseline. Participant with Gilbert's syndrome need not be excluded.

8. Not able to have a MRI, PET scanning, or cerebrospinal fluid (CSF) collection by Lumbar Puncture (LP).

9. Severe visual or hearing impairment that would prevent the participant from performing psychometric tests accurately.

10. History of immunodeficiency disorders.

11. Participants with chronic viral hepatitis.

12. History of Tuberculosis (TB). Participants with no history of TB will be tested for previous TB exposure and a positive test will be exclusionary.

13. History of ophthalmic shingles or ocular Herpes Simplex Virus (HSV) infection.

14. Any live vaccine in the 3 months or any active infection within the last 4 weeks before study drug administration (that is, randomization).

15. Any chronic inflammatory disease that is not adequately controlled or requires immunosuppressive or immunomodulatory therapy.

16. T helper cell, cytotoxic T cell, or B cell absolute counts below normal.

17. Immunoglobulin (Ig) IgG, IgA, or IgM levels below normal at Screening or Baseline, unless both the Investigator and the Medical Monitor agree that the finding is not clinically significant.

18. Clinically significant deviation from normal in physical examination, vital signs, or clinical laboratory tests at Screening or Baseline.

19. Exclusionary cardiac factors include: prolonged QT interval greater than 450 millisecond from Electrocardiograms (ECGs); history of risk factors for torsade de pointes or the use of concomitant medications that prolong the QT/corrected QT interval (QTc); left bundle branch block; persistent low or high heart rate; persistent low or high blood pressure; history of cardiac arrhythmias; other clinically significant ECG abnormalities.

20. Type 1 or Type 2 diabetes mellitus that is not well controlled.

21. Malignant neoplasms within 5 years before Screening (except for basal or squamous cell carcinoma in situ of the skin, or localized prostate cancer that did not require systemic therapy; these do not exclude the participant).

22. Medical conditions (example, cardiac, respiratory, gastrointestinal, renal disease) that are not stably controlled, or which, in the opinion of the investigator(s), could affect the participant's safety or interfere with the study assessments.

23. Hypopigmentation conditions (example, albinism and vitiligo).

24. Known or suspected history of drug or alcohol dependency or abuse within 2 years, current use of recreational drugs or a positive urine drug test.

25. Planned surgery that requires general, spinal, or epidural anesthesia that would take place during the study.

26. Participation in any other interventional clinical study related to cognitive impairment within 6 months before Screening unless it can be documented that the participant was in a placebo treatment arm.

27. Currently enrolled in another clinical study or used any investigational drug or device within 60 days or 5 half-lives of the investigational medication (whichever is longer) proceeding informed consent.

28. Hypersensitivity to the study drug or any of the excipients or to other Beta Secretase Cleaving Enzyme (BACE) inhibitors, or to the PET tracer, or components of its formulation.

29. Females who are lactating or pregnant. Females of childbearing potential who do not agree to adhere to the protocol specified methods for avoiding pregnancy.

30. Males who do not meet the protocol requirements for avoiding their partners becoming pregnant. Sperm donation is not permitted.

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Biogen

INDUSTRY

Sponsor Role: collaborator

Eisai Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Bellflower, California, United States

Costa Mesa, California, United States

Glendale, California, United States

Irvine, California, United States

Aventura, Florida, United States

Boca Raton, Florida, United States

Brooksville, Florida, United States

Lake Worth, Florida, United States

Orlando, Florida, United States

Port Charlotte, Florida, United States

Atlanta, Georgia, United States

Savannah, Georgia, United States

Wichita, Kansas, United States

Kalamazoo, Michigan, United States

Mount Arlington, New Jersey, United States

Scotch Plains, New Jersey, United States

Charlotte, North Carolina, United States

Dayton, Ohio, United States

Port Royal, South Carolina, United States

Dallas, Texas, United States

San Antonio, Texas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2014-002723-94

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

E2609-G000-202

Identifier Type: -

Identifier Source: org_study_id