ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study to Evaluate Safety, Tolerability, and Efficacy of BAN2401 in Subjects With Early 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: NCT01767311
Recruitment Status : Active, not recruiting
First Posted : January 14, 2013
Last Update Posted : February 15, 2018
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.

Brief Summary:
This is a multinational, multicenter, double-blind, placebo-controlled, parallel-group study using a Bayesian design with response adaptive randomization across placebo or 5 active arms of BAN2401 to determine clinical efficacy and to explore the dose response of BAN2401 using a composite clinical score (ADCOMS). BAN2401-G000-201 is an 18-month study in which 3 dose levels (2.5, 5, and 10 mg/kg) are given biweekly (once every 2 weeks) to separate groups of participants and 2 dose levels (5 and 10 mg/kg) are given monthly to separate groups of participants. Participants will be from 2 clinical subgroups: mild cognitive impairment (MCI) due to Alzheimer's disease (AD) or mild Alzheimer's disease dementia. Frequent interim analyses will be conducted to continually update randomization allocation on the basis of the primary clinical endpoint. In the event of early success in the Core Study at any interim analysis (IA) or at the Bayesian analysis at 12 months of treatment, an open label extension (OLE) Phase will be implemented to allow for up to 60 months (5 years) of additional treatment. The OLE will not be conducted if early success is not achieved at any IA or at the Bayesian analysis at 12 months of treatment.

Condition or disease Intervention/treatment Phase
Alzheimer's Disease Drug: BAN2401 2.5 mg/kg Drug: BAN2401 5.0 mg/kg Drug: BAN2401 10 mg/kg Drug: Placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 856 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Placebo-controlled, Double-blind, Parallel-group, Bayesian Adaptive Randomization Design and Dose Regimen-finding Study to Evaluate Safety, Tolerability and Efficacy of BAN2401 in Subjects With Early Alzheimer's Disease
Actual Study Start Date : December 2012
Estimated Primary Completion Date : July 2018
Estimated Study Completion Date : November 2018

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: BAN2401 2.5 mg/kg biweekly
2.5 mg/kg biweekly
Drug: BAN2401 2.5 mg/kg
2.5 mg/kg biweekly (once every 2 weeks) administered as a 60 minute i.v. infusion
Experimental: BAN2401 5.0 mg/kg biweekly
5.0 mg/kg biweekly
Drug: BAN2401 5.0 mg/kg
5.0 mg/kg biweekly (once every 2 weeks) administered as a 60 minute i.v. infusion
Experimental: BAN2401 10 mg/kg biweekly
10 mg/kg biweekly
Drug: BAN2401 10 mg/kg
10 mg/kg biweekly (once every 2 weeks) administered as a 60 minute i.v. infusion
Experimental: BAN2401 5.0 mg/kg monthly
5.0 mg/kg monthly
Drug: BAN2401 5.0 mg/kg
5.0 mg/kg monthly (once every 4 weeks) administered as a 60 minute i.v. infusion. All participants will receive biweekly infusions, participants will have placebo infusion alternating with BAN2401
Experimental: BAN2401 10 mg/kg monthly
10 mg/kg monthly
Drug: BAN2401 10 mg/kg
10 mg/kg monthly (once every 4 weeks) administered as a 60 minute i.v. infusion. All participants will receive biweekly infusions, participants will have placebo infusion alternating with BAN2401
Placebo Comparator: Placebo
Matching placebo biweekly
Drug: Placebo
biweekly (once every 2 weeks) administered as a 60 minute i.v. infusion



Primary Outcome Measures :
  1. Core Study: Change from Baseline in the Alzheimer's Disease Composite Score (ADCOMS) at 12 months [ Time Frame: Baseline and 12 months ]
  2. Core Study and Extension Phase: Safety will be assessed by monitoring and recording all adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: From the time the participant signs the informed consent form until 3 months after the last dose of study drug or through the last visit, whichever is longer; up to 78 months ]
    Safety assessments will consist of monitoring and recording all AEs and SAEs; regular monitoring of hematology, blood chemistry, and urine values; periodic measurement of vital signs and electrocardiograms (ECGs); safety magnetic resonance imaging (MRI); and performance of physical examinations.


Secondary Outcome Measures :
  1. Core Study: Change from baseline in the ADCOMS at 18 months [ Time Frame: Baseline and 18 months ]
  2. Core Study: Change from Baseline in total hippocampal volume at 6, 12, and 18 Months using volumetric magnetic resonance imaging (vMRI) [ Time Frame: Baseline and 6, 12, and 18 months ]
  3. Core Study: Change from Baseline at 12 and 18 months in brain amyloid levels as measured by amyloid Positron Emission Tomography (PET) [ Time Frame: Baseline and 12 and 18 months ]
  4. Extension Phase: Change from Baseline in ADCOMS at each visit [ Time Frame: Baseline and up to 60 months ]


Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   50 Years to 90 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria for Mild Cognitive Impairment due to Alzheimer's Disease

- Intermediate likelihood:

  1. Subjects who meet the National Institute of Aging - Alzheimer's Association (NIA-AA) core clinical criteria for mild cognitive impairment due to Alzheimer's disease - intermediate likelihood
  2. Subjects who have a CDR score of 0.5 and a Memory Box score of 0.5 or greater at Screening and Baseline
  3. Subjects who report a history of subjective memory decline with gradual onset and slow progression over the last one year before Screening; MUST be corroborated by an informant

Key Inclusion Criteria for Mild Alzheimer's Disease Dementia:

  1. Subjects who meet the NIA-AA core clinical criteria for probable Alzheimer's disease dementia
  2. Subjects who have a CDR score of 0.5-1.0 and a Memory Box score of 0.5 or greater at Screening and Baseline

Inclusion Criteria that must be met by all subjects:

  1. Subjects with objective impairment in episodic memory as indicated by at least 1 standard deviation below age-adjusted mean in the Wechsler Memory Scale - IV Logical Memory II (WMS-IV LMII):

    1. Less than or equal to 15 for age 50 to 64 years
    2. Less than or equal to 12 for age 65 to 69 years
    3. Less than or equal to 11 for age 70 to 74 years
    4. Less than or equal to 9 for age 75 to 79 years
    5. Less than or equal to 7 for age 80 to 90 years
  2. Positive amyloid load as indicated by PET or CSF assessment
  3. Age between 50 and 90 years, inclusive
  4. Mini Mental State Examination (MMSE) score equal to or greater than 22, and equal to or less than 30, at Screening and Baseline
  5. Body Mass Index (BMI) greater than 17 and less than 35 at Screening
  6. Females must not be pregnant or lactating, and specified contraceptive precautions must be followed
  7. Subjects on acetylcholinesterase inhibitor or memantine therapy for Alzheimer's disease (AD) must be on a stable dose for at least 12 weeks prior to baseline
  8. Subjects must have identified caregivers/informants
  9. Subjects must provide written informed consent

Extension Phase:

- Have completed Visit 42 (Week 79) of the Core Study and fall within a 4-month window from Visit 40 (Week 75) beginning at the time the decision is made to proceed with the extension

Key Exclusion Criteria:

  1. Any neurological condition that may be contributing to cognitive impairment above and beyond that caused by the subject's AD
  2. History of transient ischemic attacks (TIA), stroke, or seizures within 12 months of Screening
  3. Any psychiatric diagnosis or symptoms, (e.g., hallucinations, major depression, or delusions) that could interfere with study procedures in the subject
  4. Contraindications to MRI scanning, including cardiac pacemaker/ defibrillator, ferromagnetic metal implants, e,g., in skull and cardiac devices other than those approved as safe for use in MR scanners
  5. Evidence of other clinically significant lesions that could indicate a dementia diagnosis other than AD on brain MRI at Screening, or other significant pathological findings on brain MRI at Screening
  6. A prolonged QT/QTc interval (QTc greater than 450 ms) as demonstrated by a repeated electrocardiogram (ECG)
  7. Certain other specified medical conditions
  8. Severe visual or hearing impairment that would prevent the subject from performing psychometric tests accurately

Extension Phase:

Participants who previously completed the Core Study prior to the implementation of the open label extension (OLE), or those who discontinue from the study drug or from the Core Study are not eligible to participate in the OLE Phase.


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): NCT01767311


  Hide Study Locations
Locations
United States, Alabama
Facility #1
Birmingham, Alabama, United States
United States, Arizona
Facility #1
Phoenix, Arizona, United States
Facility #1
Tucson, Arizona, United States
United States, California
Facility #1
Carson, California, United States
Facility #1
Lomita, California, United States
Facility #1
Long Beach, California, United States
Facility #1
Los Alamitos, California, United States
Facility #1
Orange, California, United States
Facility #1
Oxnard, California, United States
Facility #1
San Diego, California, United States
United States, Colorado
Facility #1
Denver, Colorado, United States
United States, Connecticut
Facility #1
New Haven, Connecticut, United States
Facility #2
New Haven, Connecticut, United States
United States, Florida
Facility #1
Atlantis, Florida, United States
Facility #1
Bradenton, Florida, United States
Facility #1
Deerfield Beach, Florida, United States
Facility #1
Delray Beach, Florida, United States
Facility #1
Fort Myers, Florida, United States
Facility #1
Hialeah, Florida, United States
Facility #1
Lake Worth, Florida, United States
Facility #1
Miami Springs, Florida, United States
Facility #1
Miami, Florida, United States
Facility #2
Miami, Florida, United States
Facility #3
Miami, Florida, United States
Facility #1
Ocala, Florida, United States
Facility #1
Orlando, Florida, United States
Facility #1
Palm Beach Gardens, Florida, United States
Facility #1
Sunrise, Florida, United States
Facility #2
Tampa, Florida, United States
Facility #3
Tampa, Florida, United States
Facility #1
The Villages, Florida, United States
United States, Georgia
Facility #1
Atlanta, Georgia, United States
Facility #2
Atlanta, Georgia, United States
Facility #1
Columbus, Georgia, United States
Facility #1
Decatur, Georgia, United States
United States, Illinois
Facility #1
Chicago, Illinois, United States
Facility #1
Elk Grove Village, Illinois, United States
United States, Indiana
Facility #1
Elkhart, Indiana, United States
Facility #1
Indianapolis, Indiana, United States
United States, Kansas
Facility #1
Wichita, Kansas, United States
United States, Kentucky
Facility #1
Lexington, Kentucky, United States
United States, Massachusetts
Facility #1
Boston, Massachusetts, United States
Facility #2
Boston, Massachusetts, United States
Facility #1
Burlington, Massachusetts, United States
United States, Michigan
Facility #1
Ann Arbor, Michigan, United States
Facility #1
East Lansing, Michigan, United States
Facility #1
Farmington Hills, Michigan, United States
United States, New Jersey
Facility #1
Eatontown, New Jersey, United States
Facility #1
Toms River, New Jersey, United States
United States, New York
Facility #1
Albany, New York, United States
Facility #1
Amherst, New York, United States
Facility #1
Latham, New York, United States
Facility #1
New York, New York, United States
Facility #1
Rochester, New York, United States
Facility #2
Rochester, New York, United States
United States, North Carolina
Facility #1
Charlotte, North Carolina, United States
United States, Ohio
Facility #1
Centerville, Ohio, United States
United States, Oklahoma
Facility #1
Oklahoma City, Oklahoma, United States
Facility #2
Oklahoma City, Oklahoma, United States
United States, Oregon
Facility #1
Portland, Oregon, United States
Facility #2
Portland, Oregon, United States
United States, Pennsylvania
Facility #1
Abington, Pennsylvania, United States
United States, Rhode Island
Facility #1
East Providence, Rhode Island, United States
United States, Tennessee
Facility #1
Knoxville, Tennessee, United States
United States, Texas
Facility #1
Austin, Texas, United States
Facility #1
Dallas, Texas, United States
Facility #2
Dallas, Texas, United States
Facility #1
Houston, Texas, United States
Facility #1
San Antonio, Texas, United States
Facility #3
San Antonio, Texas, United States
United States, Vermont
Facility #1
Bennington, Vermont, United States
United States, Virginia
Facility #1
Richmond, Virginia, United States
United States, Wisconsin
Facility #1
Milwaukee, Wisconsin, United States
Canada, Ontario
Facility #2
London, Ontario, Canada
Facility #1
Ottawa, Ontario, Canada
Facility #1
Peterborough, Ontario, Canada
Facility #1
Toronto, Ontario, Canada
Canada, Quebec
Facility #1
Greenfield Park, Quebec, Canada
Facility #1
Montreal, Quebec, Canada
France
Facility #1
Paris cedex 10, Paris, France
Germany
Facility #1
Gunzburg, Baden Wuerttemberg, Germany
Facility #1
Berlin, Germany
Facility #2
Berlin, Germany
Italy
Facility #1
Brescia, Italy
Facility #1
Genova, Italy
Facility #1
Milano, Italy
Facility #1
Pisa, Italy
Facility #1
Roma, Italy
Facility #2
Roma, Italy
Japan
Eisai Trial Site #1
Otake-shi, Hiroshima-Ken, Japan
Eisai Trial Site #1
Himeji-shi, Hyogo-Ken, Japan
Eisai Trial Site #2
Himeji-shi, Hyogo-Ken, Japan
Eisai Trial Site #3
Himeji-shi, Hyogo-Ken, Japan
Eisai Trial Site #1
Kobe-shi, Hyogo-Ken, Japan
Eisai Trial Site #1
Nishinomiya-shi, Hyogo-Ken, Japan
Eisai Trial Site #1
Kyoto-shi, Kyoto-Fu, Japan
Eisai Trial Site #1
Kurashiki-shi, Okayama-Ken, Japan
Eisai Trial Site #1
Osaka-shi, Osaka-Fu, Japan
Eisai Trial Site #1
Saitama-shi, Saitama-Ken, Japan
Eisai Trial Site #1
Itabashi-ku, Tokyo-To, Japan
Eisai Trial Site #1
Shinjuku-ku, Tokyo-To, Japan
Eisai Trial Site #2
Shinjuku-ku, Tokyo-To, Japan
Korea, Republic of
Facility #1
Seongnam-si, Gyeonggi-do, Korea, Republic of
Facility #1
Busan, Gyeongsangnam-do, Korea, Republic of
Facility #2
Seoul, Korea, Republic of
Facility #3
Seoul, Korea, Republic of
Facility #4
Seoul, Korea, Republic of
Netherlands
Facility #1
Amsterdam, Netherlands
Spain
Facility #1
Sant Cugat del Valles, Barcelona, Spain
Facility #1
San Sebastian, Guipuzcoa, Spain
Facility #1
Barcelona, Spain
Facility #1
Madrid, Spain
Facility #2
Madrid, Spain
Facility #1
Sevilla, Spain
Sweden
Facility #1
Malmo, Sweden
Facility #1
Molndal, Sweden
Facility #1
Uppsala, Sweden
United Kingdom
Facility #1
Glasgow, Renfrewshire, United Kingdom
Sponsors and Collaborators
Eisai Inc.
Investigators
Study Director: Chad Swanson, PhD Eisai Inc.

Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT01767311     History of Changes
Other Study ID Numbers: BAN2401-G000-201
2012-002843-11 ( EudraCT Number )
First Posted: January 14, 2013    Key Record Dates
Last Update Posted: February 15, 2018
Last Verified: February 2018

Studies a U.S. FDA-regulated Drug Product: Yes

Keywords provided by Eisai Inc.:
Alzheimer's Disease
BAN2401

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