Bapineuzumab in Patients With Mild to Moderate Alzheimer's Disease (ApoE4 Carrier)

A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy and Safety Trial of Bapineuzumab (AAB-001, ELN115727) In Patients With Mild to Moderate Alzheimer's Disease Who Are Apolipoprotein E4 Carriers.

This is a multicenter, double-blind, placebo controlled, randomized, outpatient, multiple dose study in male and female patients ages 50 to less than 89 years with mild to moderate AD. Approximately 200 study sites in the US and Canada will be involved. Patients will be randomized to receive either bapineuzumab or placebo. Each patient's participation will last approximately 1.5 years.

Bapineuzumab is a humanized monoclonal antibody, which binds to and clears beta amyloid peptide, and is designed to provide antibodies to beta amyloid directly to the patient.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: Placebo Control; Drug: Bapineuzumab 0.5 mg/kg; Drug: Bapineuzumab 1.0 m/kg

• Study Type: Interventional
• Enrollment (Actual): 1121
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • University of Alabama Hospital (UAB)
  • Arizona
    • Goodyear, Arizona, United States, 85395
      • Dedicated Clinical Research, Inc.
    • Phoenix, Arizona, United States, 85006
      • Banner Alzheimer's Institute
    • Phoenix, Arizona, United States, 85050
      • HOPE Research Institute, LLC
    • Sun City, Arizona, United States, 85351
      • Banner Research Institute
    • Tucson, Arizona, United States, 85724
      • University of Arizona College of Medicine, Health Sciences Center
    • Tucson, Arizona, United States, 85741
      • Northwest NeuroSpecialists, PLLC
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Clinical Trials Inc.
  • California
    • Berkeley, California, United States, 94705
      • East Bay Physicians Medical Group
    • Carson, California, United States, 90746
      • AVI Clinical Research
    • Costa Mesa, California, United States, 92626
      • ATP Clinical Research, Inc
    • Encino, California, United States, 91316
      • Pharmacology Research Institute
    • Fresno, California, United States, 93720
      • Margolin Brain Institute
    • Fullerton, California, United States, 92835
      • Neurology Center of North Orange County
    • La Jolla, California, United States, 92037
      • University of California San Diego
    • La Jolla, California, United States, 92037
      • Coordinated Clinical Research
    • Laguna Hills, California, United States, 92653
      • Senior Clinical Trials, Inc
    • Long Beach, California, United States, 90806
      • Collaborative Neuroscience Network, Inc.
    • Los Alamitos, California, United States, 90720
      • Pharmacology Research Institute
    • Los Angeles, California, United States, 90095
      • UCLA Department of Neurology
    • Los Angeles, California, United States, 90035
      • Vintage Institute for Clinical Research, Inc
    • Newport Beach, California, United States, 92660
      • Pharmacology Research Institute
    • Oceanside, California, United States, 92056
      • Neurology Center
    • Orange, California, United States, 92868
      • University of California Irvine Medical Center
    • Pasadena, California, United States, 91105
      • Neuro-Therapeutics Inc.
    • Sacramento, California, United States, 95816
      • Sutter Neuroscience Medical Group
    • Sacramento, California, United States, 95817
      • University of California Davis Alzheimer's Disease Research Center
    • San Diego, California, United States, 92123
      • Sharp Mesa Vista Hospital
    • San Diego, California, United States, 92123
      • Artemis Institute for Clinical Research
    • San Francisco, California, United States, 94109
      • San Francisco Clinical Research Center
    • San Francisco, California, United States, 94117
      • University of California at San Francisco Medical Center at Parnassus
    • Santa Monica, California, United States, 90404
      • Neurological Research Institute
    • Sherman Oaks, California, United States, 91403
      • Schuster Medical Research Institute
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research, Inc.
  • Colorado
    • Boulder, Colorado, United States, 80304
      • Alpine Clinical Research Center
    • Denver, Colorado, United States, 80218
      • Mile High Research Center
    • Fort Collins, Colorado, United States, 80528
      • Advanced Neurosciences Research, LLC
  • Connecticut
    • Danbury, Connecticut, United States, 06810
      • Associated Neurologists, PC
    • Fairfield, Connecticut, United States, 06824
      • Associated Neurologists of Southern CT, P.C.
    • New Haven, Connecticut, United States, 06510
      • Yale University School Of Medicine
    • New Haven, Connecticut, United States, 06510
      • Institute for Neurodegenerative Disorders
    • Norwalk, Connecticut, United States, 06851
      • Research Center for Clinical Studies, Inc
    • Waterbury, Connecticut, United States, 06708
      • Chase Medical Research, LLC
  • Delaware
    • Newark, Delaware, United States, 19713
      • Christiana Care Health Services
  • District of Columbia
    • Washington, District of Columbia, United States, 20057
      • Georgetown University Medical Center
  • Florida
    • Atlantis, Florida, United States, 33462
      • JEM Research, LLC
    • Bradenton, Florida, United States, 34205
      • Bradenton Research Center, Inc
    • Deerfield Beach, Florida, United States, 33064
      • Quantum Laboratories, Inc.
    • Delray Beach, Florida, United States, 33445
      • Brain Matters Research
    • Fort Lauderdale, Florida, United States, 33308
      • Neurologic Consultants, P.A.
    • Fort Myers, Florida, United States, 33916
      • Clinical Physiology Associates, Inc.
    • Fort Walton Beach, Florida, United States, 32547
      • Emerald Coast Mood & Memory, PA.
    • Ft. Myers, Florida, United States, 33912
      • Neuropsychiatric Research Center of Southwest Florida
    • Hallandale Beach, Florida, United States, 33009
      • MD Clinical
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic College of Medicine
    • Maitland, Florida, United States, 32751
      • Neurology Associates
    • Melbourne, Florida, United States, 32901
      • Melbourne Internal Medicine Associates, MIMA
    • Miami, Florida, United States, 33137
      • Miami Jewish Health Systems
    • Miami, Florida, United States, 33126
      • Pharmax Research Clinic, LLC
    • Miami, Florida, United States, 33156
      • Allied Clinical Trials, Inc.
    • Ocala, Florida, United States, 34471
      • Renstar Medical Research
    • Orlando, Florida, United States, 32806
      • Compass Research, LLC
    • Palm Beach Gardens, Florida, United States, 33418
      • Palm Beach Neurological Center/Advanced Research Consultants
    • Port Charlotte, Florida, United States, 33952
      • Neurostudies, Inc
    • Sarasota, Florida, United States, 34243
      • The Roskamp Institute, Inc
    • South Miami, Florida, United States, 33143
      • Miami Research Associates
    • St Petersburg, Florida, United States, 33713
      • Suncoast Neuroscience Associates, Inc.
    • St. Petersburg, Florida, United States, 33709
      • Meridien Research
    • Tampa, Florida, United States, 33609
      • Axiom Clinical Research of Florida
    • Tampa, Florida, United States, 33613
      • Stedman Clinical Trials, LLC
    • Tampa, Florida, United States, 33613
      • Johnnie B. Byrd Sr. Alzheimer's Center and Research Institute
    • Tampa, Florida, United States, 33613
      • University of South Florida Suncoast Alzheimer's and Gerontology Center
    • West Palm Beach, Florida, United States, 33407
      • Premiere Research Institute
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • NeuroTrials Research, Inc.
    • Atlanta, Georgia, United States, 30322
      • Emory University, School of Medicine
    • Atlanta, Georgia, United States, 30327
      • Multiple Sclerosis Center of Atlanta
    • Columbus, Georgia, United States, 31909
      • Medical Research and Health Educational Foundation, Inc
    • Decatur, Georgia, United States, 30033
      • Dekalb Neurology Associates, LLC
    • Lawrenceville, Georgia, United States, 30045
      • Gwinnett Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University Of Chicago Medical Center
    • Elk Grove Village, Illinois, United States, 60007
      • Alexian Brothers Neurosciences Institute
    • Springfield, Illinois, United States, 62794
      • Southern Illinois University, School of Medicine
  • Indiana
    • Elkhart, Indiana, United States, 46514
      • Elkhart Clinic, LLC
    • Indianapolis, Indiana, United States, 46202
      • Indiana University School of Medicine
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
    • Lenexa, Kansas, United States, 66214
      • Mid America Neuroscience Institute
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky
    • Lexington, Kentucky, United States, 40513
      • Associates in Neurology, PSC
    • Paducah, Kentucky, United States, 42003
      • Four Rivers Clinical Research, Inc
  • Louisiana
    • Lake Charles, Louisiana, United States, 70629
      • Lake Charles Clinical Trials
    • Shreveport, Louisiana, United States, 71104
      • J. Gary Booker, MD, APMC
    • Shreveport, Louisiana, United States, 70112
      • Louisiana State University Health Sciences Center
  • Maine
    • Scarborough, Maine, United States, 04074
      • Maine Medical Partners Neurology
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins University School Of Medicine
  • Massachusetts
    • Belmont, Massachusetts, United States, 02478
      • Mclean Hospital
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02118
      • Boston University School of Medicine
    • Haverhill, Massachusetts, United States, 01830
      • Activmed Practices and Research, Inc
    • Newton, Massachusetts, United States, 02459
      • Neurocare, Inc
    • Pittsfield, Massachusetts, United States, 01201
      • Neuroscience Research of the Berkshires
    • Plymouth, Massachusetts, United States, 02360
      • Donald S. Marks, MD, P.C.
    • Springfield, Massachusetts, United States, 01104
      • Springfield Neurology Associates
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • University of Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • East Lansing, Michigan, United States, 48824
      • Michigan State University
    • Grand Rapids, Michigan, United States, 49503
      • Saint Mary's Health Care
    • Kalamazoo, Michigan, United States, 49048
      • Borgess Medical Center/Borgess Research Institute
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Mississippi
    • Hattiesburg, Mississippi, United States, 39401
      • Hattiesburg Clinic
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • The Center for Pharmaceutical Research
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Hospital, Mid America Brain and Stroke Institute
    • St. Louis, Missouri, United States, 63108
      • Washington University School of Medicine
    • St. Louis, Missouri, United States, 63104
      • St. Louis University School of Medicine
  • Montana
    • Billings, Montana, United States, 59101
      • Deaconess Billings Clinical Research Center
    • Great Falls, Montana, United States, 59405
      • Advanced Neurology Specialists
  • Nebraska
    • Omaha, Nebraska, United States, 68198-2045
      • University of Nebraska Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Cleveland Clinic Lou Ruvo Center for Brain Health
  • New Jersey
    • Eatontown, New Jersey, United States, 07724
      • Memory Enhancement Center of America, Inc.
    • Manchester, New Jersey, United States, 08759
      • Alzheimer's Research Corporation (ARC)
    • Mount Arlington, New Jersey, United States, 07856
      • The NeuroCognitive Institute
    • Princeton, New Jersey, United States, 08540
      • Princeton Medical Institute
    • Stratford, New Jersey, United States, 08084
      • University of Medicine and Dentistry of New Jersey
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Albuquerque Neuroscience, Inc.
  • New York
    • Albany, New York, United States, 12205
      • Upstate Clinical Research, LLC
    • Albany, New York, United States, 12208
      • Neuroscience Research Center at Albany Medical Center
    • Albany, New York, United States, 12208
      • Neurological Associates Albany PC
    • Cedarhurst, New York, United States, 11516
      • Five Towns Neuroscience Research
    • Elmsford, New York, United States, 10523
      • Advanced BioBehavioral Sciences
    • Latham, New York, United States, 12110
      • Empire Neurology, PC
    • Liverpool, New York, United States, 13088
      • Neurological Care of CNY
    • New Hyde Park, New York, United States, 11040
      • Parker Jewish Institute for Health Care & Rehabilitation
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10029
      • Mt. Sinai School of Medicine
    • New York, New York, United States, 10016
      • NYU School of Medicine/Psychiatry
    • Orangeburg, New York, United States, 10962
      • Nathan S. Kline Institute for Psychiatric Research
    • Rochester, New York, United States, 14620
      • University of Rochester Medical Center @ Monroe Community Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Hickory, North Carolina, United States, 28601
      • Clinical Trials of America, Inc
    • Hickory, North Carolina, United States, 28601
      • New Hope Clinical Research
    • Raleigh, North Carolina, United States, 27607
      • Raleigh Neurology Associates
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Ohio
    • Beachwood, Ohio, United States, 44122
      • University Hospitals of Cleveland, Case Medical Center, Memory and Cognition Center
    • Canton, Ohio, United States, 44718
      • Neuro-Behavioral Clinical Research, Inc
    • Canton, Ohio, United States, 44718
      • NeuroCare Center, Inc
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
    • Dayton, Ohio, United States, 45417
      • Neurology Specialists, Inc.
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Lynn Health Science Institute
    • Oklahoma City, Oklahoma, United States, 73112
      • Red River Medical Research Center, LLC
  • Oregon
    • Medford, Oregon, United States, 97504
      • Providence Medical Group-Medford Neurology
    • Portland, Oregon, United States, 97239
      • Oregon Health & Sciences University
    • Portland, Oregon, United States, 97225
      • Providence Health Service System, AD Center, Brain Institute
    • Portland, Oregon, United States, 97210
      • Summit Research Group, LLC
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Neurological Assoc
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Valley Health Network
    • Jenkintown, Pennsylvania, United States, 19046
      • The Clinical Trial Center, LLC
    • Philadelphia, Pennsylvania, United States, 19102
      • Drexel University College of Medicine
    • Philadelphia, Pennsylvania, United States, 19104
      • Penn Memory Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Jefferson Hospital for Neuroscience
    • Pittsburgh, Pennsylvania, United States, 15206
      • Clinical Trials Research Services, LLC
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Virginia
    • Pittsburgh, Pennsylvania, United States, 15213
      • Universtiy of Pittsburgh
  • Rhode Island
    • East Providence, Rhode Island, United States, 02914
      • Rhode Island mood and memory research institute
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
    • Providence, Rhode Island, United States, 02906
      • Butler Hospital
  • South Carolina
    • N. Charleston, South Carolina, United States, 29406
      • Medical University of South Carolina
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Avera Research Institute
  • Tennessee
    • Cordova, Tennessee, United States, 38018
      • Neurology Clinic, PC
    • Franklin, Tennessee, United States, 37067
      • Psychiatric Consultants, PC
    • Johnson City, Tennessee, United States, 37614-1707
      • East Tennessee State University
    • Knoxville, Tennessee, United States, 37920
      • Volunteer Research Group
  • Texas
    • Dallas, Texas, United States, 75214
      • Texas Neurology, PA
    • Fort Worth, Texas, United States, 76106
      • University of North Texas/Health Sciences Center-Fort Worth
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • San Antonio, Texas, United States, 78229
      • Innovative Clinical Trials
    • San Antonio, Texas, United States, 78231
      • Integra Clinical Research, Llc
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Wasatch Clinical Research
    • Salt Lake City, Utah, United States, 84108
      • University of Utah, Dept. of Neurology
  • Vermont
    • Bennington, Vermont, United States, 05201
      • The Memory Clinic
    • Burlington, Vermont, United States, 05401
      • Fletcher Allen Health Care
  • Virginia
    • Alexandria, Virginia, United States, 22304
      • Innovative Clinical Research Center
    • Richmond, Virginia, United States, 23230
      • Alliance Research Group, LLC
  • Washington
    • Seattle, Washington, United States, 98108
      • University of Washington Veterans Affairs
    • Seattle, Washington, United States, 98144
      • Pacific Medical Centers
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • University of Wisconsin School of Medicine and Public Health
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 88 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of probable AD
• Age from 50 to less than 89
• Mini-Mental Status Exam score of 16-26 inclusive
• Brain magnetic resonance imaging (MRI) scan consistent with the diagnosis of AD
• Stable doses of medications (cholinesterase inhibitors and memantine allowed)
• Caregiver able to attend all clinic visits with patient

Exclusion Criteria:

• Significant neurological disease other than AD
• Major psychiatric disorder
• Significant systemic illness
• History of stroke or seizure, autoimmune disease, myocardial infarction within the last 2 years
• Smoking greater than 20 cigarettes per day
• Anticonvulsants, anti-Parkinson's, anticoagulant, or narcotic medications
• Prior treatment experimental immunotherapeutics or vaccines for AD
• Women of childbearing potential
• Presence of pacemakers, CSF shunts, or foreign metal objects in the eyes, skin or body

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bapineuzumab 0.5 mg/kg; infusion every 13 weeks for a total of 6 infusions	Drug: Bapineuzumab 0.5 mg/kg; given by infusion every 13 weeks for a total of 6 infusions.; Other Names: AAB-001
Experimental: Bapineuzumab 1.0 m/kg; infusion every 13 weeks for a total of 6 infusions.	Drug: Bapineuzumab 1.0 m/kg; given by infusion every 13 weeks for a total of 6 infusions.; Other Names: AAB-001
Placebo Comparator: Placebo Dose; infusion every 13 weeks for a total of 6 infusions.	Drug: Placebo Control; given by infusion every 13 weeks for a total of 6 infusions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cognitive and Functional	18 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Cognitive and Global	18 months
Imaging and biochemical biomarkers of disease status	18 months

Collaborators and Investigators

• Sponsor: JANSSEN Alzheimer Immunotherapy Research & Development, LLC
• Collaborators: Pfizer

Publications and helpful links

General Publications

• Brashear HR, Ketter N, Bogert J, Di J, Salloway SP, Sperling R. Clinical Evaluation of Amyloid-Related Imaging Abnormalities in Bapineuzumab Phase III Studies. J Alzheimers Dis. 2018;66(4):1409-1424. doi: 10.3233/JAD-180675.
• Ketter N, Brashear HR, Bogert J, Di J, Miaux Y, Gass A, Purcell DD, Barkhof F, Arrighi HM. Central Review of Amyloid-Related Imaging Abnormalities in Two Phase III Clinical Trials of Bapineuzumab in Mild-To-Moderate Alzheimer's Disease Patients. J Alzheimers Dis. 2017;57(2):557-573. doi: 10.3233/JAD-160216.
• Samtani MN, Xu SX, Russu A, Adedokun OJ, Lu M, Ito K, Corrigan B, Raje S, Brashear HR, Styren S, Hu C. Alzheimer's disease assessment scale-cognitive 11-item progression model in mild-to-moderate Alzheimer's disease trials of bapineuzumab. Alzheimers Dement (N Y). 2015 Oct 9;1(3):157-169. doi: 10.1016/j.trci.2015.09.001. eCollection 2015 Nov.
• Liu E, Schmidt ME, Margolin R, Sperling R, Koeppe R, Mason NS, Klunk WE, Mathis CA, Salloway S, Fox NC, Hill DL, Les AS, Collins P, Gregg KM, Di J, Lu Y, Tudor IC, Wyman BT, Booth K, Broome S, Yuen E, Grundman M, Brashear HR; Bapineuzumab 301 and 302 Clinical Trial Investigators. Amyloid-beta 11C-PiB-PET imaging results from 2 randomized bapineuzumab phase 3 AD trials. Neurology. 2015 Aug 25;85(8):692-700. doi: 10.1212/WNL.0000000000001877. Epub 2015 Jul 24.
• Xu SX, Samtani MN, Russu A, Adedokun OJ, Lu M, Ito K, Corrigan B, Raje S, Brashear HR, Styren S, Hu C. Alzheimer's disease progression model using disability assessment for dementia scores from bapineuzumab trials. Alzheimers Dement (N Y). 2015 Jul 21;1(2):141-149. doi: 10.1016/j.trci.2015.06.005. eCollection 2015 Sep.
• Salloway S, Sperling R, Fox NC, Blennow K, Klunk W, Raskind M, Sabbagh M, Honig LS, Porsteinsson AP, Ferris S, Reichert M, Ketter N, Nejadnik B, Guenzler V, Miloslavsky M, Wang D, Lu Y, Lull J, Tudor IC, Liu E, Grundman M, Yuen E, Black R, Brashear HR; Bapineuzumab 301 and 302 Clinical Trial Investigators. Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer's disease. N Engl J Med. 2014 Jan 23;370(4):322-33. doi: 10.1056/NEJMoa1304839.

Study record dates

Study Major Dates

• Study Start: December 1, 2007
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: December 10, 2007
• First Submitted That Met QC Criteria: December 13, 2007
• First Posted (Estimate): December 17, 2007

Study Record Updates

• Last Update Posted (Estimate): November 25, 2013
• Last Update Submitted That Met QC Criteria: October 30, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: ELN115727-302