Trial record 3 of 104 for:    prodromal

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2015 by Eisai Inc.
Sponsor:
Collaborator:
Biogen
Information provided by (Responsible Party):
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT02322021
First received: December 17, 2014
Last updated: November 2, 2015
Last verified: November 2015
  Purpose
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).

Condition Intervention Phase
Alzheimer Disease
Dementia, Alzheimer Type
Drug: E2609
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Placebo-Controlled, Double-Blind, Parallel-Group, Randomized, Proof-of-Concept, Dose-Finding Study To Evaluate Safety, Tolerability, and Efficacy of E2609 in Subjects With Mild Cognitive Impairment Due to Alzheimer's Disease (Prodromal Alzheimer's Disease) and Mild to Moderate Dementia Due to Alzheimer's Disease

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Change from baseline in the derived Alzheimer's Disease Composite Score (ADCOMS) at 18 months of treatment in MCI/Prodromal participants [ Time Frame: At 18 Months of treatment ]
    The derived ADCOMS uses items from the Alzheimer's Disease Assessment Scale - Cognition (ADAS-cog), the Mini Mental State Examination (MMSE), and the Clinical Dementia Rating (CDR).

  • Safety and tolerability by assessing adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: From the time the participant signs the informed consent form until up to 3 months after the last dose of study drug ]

Secondary Outcome Measures:
  • Change from baseline in total hippocampal atrophy at 12 and 18 months of treatment in MCI/Prodromal participants as measured by volumetric Magnetic Resonance Imaging (vMRI) [ Time Frame: At 12 and 18 months of treatment ]
  • Change from baseline in cerebrospinal fluid (CSF) Abeta(1-x) after 4 weeks and 18 months of treatment in MCI/Prodromal participants [ Time Frame: At 4 weeks and 18 months of treatment ]
  • Change from baseline in the derived ADCOMS at 18 months of treatment in mild to moderate AD participants [ Time Frame: At 18 months of treatment ]

Estimated Enrollment: 700
Study Start Date: November 2014
Estimated Study Completion Date: January 2018
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MCI/Prodromal Cohort: Low Dose
A low dose of E2609 will be assessed.
Drug: 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.
Experimental: MCI/Prodromal Cohort: Middle Dose
A middle dose of E2609 will be assessed.
Drug: 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.
Experimental: MCI/Prodromal Cohort: High Dose
A high dose of E2609 will be assessed.
Drug: 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.
Placebo Comparator: MCI/Prodromal Cohort: Placebo 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.
Experimental: Mild to Moderate AD Cohort: Low Dose
A low dose of E2609 will be assessed.
Drug: 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.
Experimental: Mild to Moderate AD Cohort: High Dose
A high dose of E2609 will be assessed.
Drug: 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.
Placebo Comparator: Mild to Moderate AD Cohort: Placebo 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.
Experimental: Mild to Moderate AD cohort: Middle Dose
A middle dose of E2609 will be assessed.
Drug: 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.

  Eligibility

Ages Eligible for Study:   50 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

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

  1. Meets the core clinical research criteria of the 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 subject 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 subjects 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 (ie, not related to their cognitive decline) for at least 4 weeks before randomization.

Exclusion criteria:

Subjects 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 subject's AD pathology, including any co-morbidities such as cerebrovascular disease, detected by medical history, neurological examination, or 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, (eg, 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 subjects regardless of whether or not they are taking thyroid supplements.
  7. Subjects with liver disease (hepatic impairment), at Screening or Baseline. Subjects with Gilbert's syndrome need not be excluded.
  8. Not able to have a MRI, PET scanning, or CSF collection by Lumbar Puncture (LP).
  9. Severe visual or hearing impairment that would prevent the subject from performing psychometric tests accurately.
  10. History of immunodeficiency disorders.
  11. Subjects with chronic viral hepatitis.
  12. History of Tuberculosis (TB). Subjects 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 (i.e. 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 msec from Electrocardiograms (ECGs); history of risk factors for torsade de pointes or the use of concomitant medications that prolong the QT/QTc interval; 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 subject).
  22. Medical conditions (eg, cardiac, respiratory, gastrointestinal, renal disease) that are not stably controlled, or which, in the opinion of the investigator(s), could affect the subject's safety or interfere with the study assessments.
  23. Hypopigmentation conditions (eg, 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 subject 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02322021

Contacts
Contact: Eisai Medical Services 1-888-422-4743

Locations
United States, California
Recruiting
Bellflower, California, United States
Recruiting
Costa Mesa, California, United States
Recruiting
Glendale, California, United States
Recruiting
Irvine, California, United States
United States, Florida
Recruiting
Aventura, Florida, United States
Not yet recruiting
Boca Raton, Florida, United States
Recruiting
Brooksville, Florida, United States
Recruiting
Lake Worth, Florida, United States
Recruiting
Orlando, Florida, United States
Recruiting
Port Charlotte, Florida, United States
United States, Georgia
Recruiting
Atlanta, Georgia, United States
Recruiting
Savannah, Georgia, United States
United States, Kansas
Recruiting
Wichita, Kansas, United States
United States, Michigan
Not yet recruiting
Kalamazoo, Michigan, United States
United States, New Jersey
Recruiting
Mt. Arlington, New Jersey, United States
Recruiting
Scotch Plains, New Jersey, United States
United States, North Carolina
Recruiting
Charlotte, North Carolina, United States
United States, Ohio
Recruiting
Dayton, Ohio, United States
United States, South Carolina
Recruiting
Port Royal, South Carolina, United States
United States, Texas
Recruiting
Dallas, Texas, United States
Recruiting
San Antonio, Texas, United States
Sponsors and Collaborators
Eisai Inc.
Biogen
  More Information

Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT02322021     History of Changes
Other Study ID Numbers: E2609-G000-202 
Study First Received: December 17, 2014
Last Updated: November 2, 2015

Keywords provided by Eisai Inc.:
E2609
Mild Cognitive Impairment
Mild to Moderate Dementia
Alzheimer's Disease
Prodromal Alzheimer's Disease

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Cognition Disorders
Mild Cognitive Impairment
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders

ClinicalTrials.gov processed this record on January 19, 2017