A Long-Term Safety And Tolerability Study Of Bapineuzumab In Alzheimer Disease Patients

This study has been terminated.
(The study was terminated on August 6, 2012, because 2 large Phase 3 studies showed no clinical benefit. This decision was not based on any new safety concerns.)
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00996918
First received: October 14, 2009
Last updated: November 12, 2013
Last verified: November 2013
  Purpose

The purpose of this study is to assess the long-term safety and tolerability of bapineuzumab in subjects with Alzheimer Disease who participated in study 3133K1-3000 (NCT00667810). Over 250 sites will participate in over 26 countries. Subjects will receive bapineuzumab. Each subject's participation will last approximately 4 years.


Condition Intervention Phase
Alzheimer Disease
Drug: Bapineuzumab 0.5 mg/kg
Drug: Bapineuzumab 1.0 m/kg
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3 Extension, Multicenter, Double-Blind, Long-Term Safety And Tolerability Trial Of Bapineuzumab (AAB-001, ELN115727) In Subjects With Alzheimer Disease Who Are Apolipoprotein E e4 Noncarriers And Participated In Study 3133K1-3000

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Number of Participants Reporting a Serious Adverse Event. [ Time Frame: Up to Week 195 ] [ Designated as safety issue: Yes ]
    Safety was measured according to standard adverse event collection as described in the Adverse Event Section of the Results. Complete tables of events are provided there.


Secondary Outcome Measures:
  • Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78. [ Time Frame: Weeks 13, 26, 39, 52 and 78 ] [ Designated as safety issue: No ]
    The ADAS-Cog is a multi-item, objective measure of cognitive function. The scale evaluates memory, language, and praxis with items such as orientation, word recall, word recognition, object identification, comprehension, and the completion of simple tasks. Analysis of the ADAS-Cog for this study was based upon an 11 item score from the following items 1) word recall task, 2) naming objects and fingers, 3) following commands, 4) constructional praxis, 5) ideational praxis, 6) orientation, 7) word recognition, 8) remembering test instructions, 9) spoken language ability, 10) word finding difficulty in spontaneous speech, and 11) comprehension.This scale had to be administered by a trained and certified psychometric rater who did not have access to any information regarding adverse events experienced. The ADAS-Cog/11 ranged from 0 to 70 points, with higher scores indicating a greater degree of impairment. A negative change from baseline indicates a decrease in cognitive impairment.

  • Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78. [ Time Frame: Weeks 13, 26, 39, 52 and 78 ] [ Designated as safety issue: No ]
    The ADAS-Cog is a multi-item, objective measure of cognitive function. The scale evaluates memory, language, and praxis with items such as orientation, word recall, word recognition, object identification, comprehension, and the completion of simple tasks. Analysis of the ADAS-Cog for this study was based upon an 11 item score from the following items 1) word recall task, 2) naming objects and fingers, 3) following commands, 4) constructional praxis, 5) ideational praxis, 6) orientation, 7) word recognition, 8) remembering test instructions, 9) spoken language ability, 10) word finding difficulty in spontaneous speech, and 11) comprehension.This scale had to be administered by a trained and certified psychometric rater who did not have access to any information regarding adverse events experienced. The ADAS-Cog/11 ranged from 0 to 70 points, with higher scores indicating a greater degree of impairment. A negative change from baseline indicates a decrease in cognitive impairment.

  • Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78. [ Time Frame: Weeks 13, 26, 39, 52 and 78 ] [ Designated as safety issue: No ]
    The DAD measures instrumental and basic activities of daily living in participants with Alzheimer's Disease (AD). The DAD is administered to the participants'caregiver in the form of an interview. This scale had to be administered by a trained and certified psychometric rater who did not have access to any information regarding adverse events experienced by the participant. This scale assesses a participants' ability to initiate, plan, and perform activities related to hygiene, dressing, continence, eating, meal preparation, telephoning, going on an outing, finance and correspondence, medications, leisure, and housework. Each item can be scored as 1 = yes, 0 = no, non applicable = NA. A total score is obtained by adding the rating for each question and converting this total score out of 100. Higher scores indicate better function; a positive change from baseline indicates an improvement

  • Change From Extension Study Baseline in DAD Score at Weeks 13, 26, 39, 52 and 78 [ Time Frame: Weeks 13, 26, 39, 52 and 78 ] [ Designated as safety issue: No ]
    The DAD measures instrumental and basic activities of daily living in participants with AD. The DAD is administered to the participants'caregiver in the form of an interview. This scale had to be administered by a trained and certified psychometric rater who did not have access to any information regarding adverse events experienced by the participant. This scale assesses a participants' ability to initiate, plan, and perform activities related to hygiene, dressing, continence, eating, meal preparation, telephoning, going on an outing, finance and correspondence, medications, leisure, and housework. Each item can be scored as 1 = yes, 0 = no, non applicable = NA. A total score is obtained by adding the rating for each question and converting this total score out of 100. Higher scores indicate better function; a positive change from baseline indicates an improvement

  • Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78. [ Time Frame: Weeks 26, 52 and 78 ] [ Designated as safety issue: No ]
    NPI:12-domain caregiver assessment of behavioral disturbances occurring in dementia: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, appetite/eating, nighttime behavior. Severity (1=Mild to 3=Severe), frequency (1=occasionally to 4=very frequently) scales recorded for each domain; frequency*severity=each domain score(range 0-12). Total score=sum of each domain score (range 0-144); higher score=greater behavioral disturbances; negative change score from baseline=improvement.

  • Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78. [ Time Frame: Weeks 26, 52 and 78 ] [ Designated as safety issue: No ]
    NPI:12-domain caregiver assessment of behavioral disturbances occurring in dementia: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, appetite/eating, night-time behavior. Severity (1=Mild to 3=Severe), frequency (1=occasionally to 4=very frequently) scales recorded for each domain; frequency*severity=each domain score(range 0-12). Total score=sum of each domain score(range 0-144); higher score=greater behavioral disturbances; negative change score from baseline=improvement.

  • Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78. [ Time Frame: Weeks 6, 19, 32, 45 and 78 ] [ Designated as safety issue: No ]
    MMSE measured general cognitive functioning: orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two intersecting polygons. Total score derived from sub-scores; total ranged from 0 to 30, higher score indicates better cognitive state.

  • Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78. [ Time Frame: Weeks 6, 19, 32, 45 and 78 ] [ Designated as safety issue: No ]
    MMSE measured general cognitive functioning: orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two intersecting polygons. Total score derived from sub-scores; total ranged from 0 to 30, higher score indicates better cognitive state


Enrollment: 198
Study Start Date: December 2009
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bapineuzumab 0.5 mg/kg
bapineuzumab
Drug: Bapineuzumab 0.5 mg/kg
Bapineuzumab I.V., 0.5 mg/kg, infusion every 13 weeks for a total of 16 infusions.
Other Name: AAB-001
Experimental: Bapineuzumab 1.0 m/kg
bapineuzumab
Drug: Bapineuzumab 1.0 m/kg
I.V., 1.0 mg/kg, infusion every 13 weeks for a total of 16 infusions.
Other Name: AAB-001

  Eligibility

Ages Eligible for Study:   51 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject has completed study 3133K1-3000 and brain magnetic resonance imaging (MRI) scan consistent with the diagnosis of Alzheimer Disease
  • Mini-Mental Status Examination (MMSE) >=10 at screening
  • Caregiver able to attend all clinic visits with subject

Exclusion Criteria:

  • Any medical or psychiatric contraindication or clinically significant abnormality that, in the investigator's judgment, will substantially increase the risk associated with the subject's participation in and completion of the study or could preclude the evaluation of the subject's response.
  • Any significant brain MRI abnormality.
  • Use of any investigational drugs or devices, other than bapineuzumab within the last 60 days prior to screening
  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: NCT00996918

  Hide Study Locations
Locations
Australia, New South Wales
Pfizer Investigational Site
Hornsby, New South Wales, Australia, 2077
Australia, South Australia
Pfizer Investigational Site
Adelaide, South Australia, Australia, 5000
Pfizer Investigational Site
Woodville South, South Australia, Australia, 5011
Australia, Victoria
Pfizer Investigational Site
Heidelberg Heights, Victoria, Australia, 3081
Australia, Western Australia
Pfizer Investigational Site
Nedlands, Western Australia, Australia, 6009
Belgium
Pfizer Investigational Site
Antwerpen, Belgium, 2020
Pfizer Investigational Site
Brussels, Belgium, 1200
Pfizer Investigational Site
Edegem, Belgium, 2650
Chile
Pfizer Investigational Site
Santiago, Chile, 7630000
Pfizer Investigational Site
Santiago, Chile, 7530193
Finland
Pfizer Investigational Site
Kuopio, Finland, FIN-70210
Pfizer Investigational Site
Turku, Finland, 20520
France
Pfizer Investigational Site
Caen, France, 14033
Pfizer Investigational Site
Dijon, France, 21000
Pfizer Investigational Site
Lille, France, 59037
Pfizer Investigational Site
Marseille, France, 13000
Pfizer Investigational Site
Marseille, France, 13885
Pfizer Investigational Site
Montpellier, France, 34295
Pfizer Investigational Site
Nantes - Saint Herblain, France, 44093
Pfizer Investigational Site
Nice, France, 06000
Pfizer Investigational Site
Paris, France, 75013
Pfizer Investigational Site
Poitiers, France, 86021
Pfizer Investigational Site
Rennes, France, 35000
Pfizer Investigational Site
Rouen, France, 76031
Pfizer Investigational Site
Toulouse, France, 31059
Italy
Pfizer Investigational Site
Milano, Italy, 20133
Pfizer Investigational Site
Roma, Italy, 00179
Japan
Pfizer Investigational Site
Aichi, Japan
Pfizer Investigational Site
Chiba, Japan
Pfizer Investigational Site
Fukuoka, Japan
Pfizer Investigational Site
Hiroshima, Japan
Pfizer Investigational Site
Hyogo, Japan
Pfizer Investigational Site
Kagawa, Japan
Pfizer Investigational Site
Kanagawa, Japan
Pfizer Investigational Site
Kyoto, Japan
Pfizer Investigational Site
Nagano, Japan
Pfizer Investigational Site
Okayama, Japan
Pfizer Investigational Site
Osaka, Japan
Pfizer Investigational Site
Shizuoka, Japan
Pfizer Investigational Site
Tokyo, Japan
Netherlands
Pfizer Investigational Site
's-Hertogenbosch, Netherlands, 5223 GZ
Pfizer Investigational Site
Leeuwarden, Netherlands, 8934 AD
New Zealand
Pfizer Investigational Site
North Shore, NZ, New Zealand, 622
Poland
Pfizer Investigational Site
Bydgoszcz, Poland, 85-796
Pfizer Investigational Site
Krakow, Poland, 31-531
Pfizer Investigational Site
Poznan, Poland, 61-289
Pfizer Investigational Site
Warszawa, Poland, 02-097
Pfizer Investigational Site
Warszawa, Poland, 01-211
Portugal
Pfizer Investigational Site
Amadora, Portugal, 2700-276
Pfizer Investigational Site
Coimbra, Portugal, 3000-075
Pfizer Investigational Site
Lisboa, Portugal, 1649-028
Slovakia
Pfizer Investigational Site
Bratislava, Slovakia, 825 56
Pfizer Investigational Site
Rimavska Sobota, Slovakia, 979 12
South Africa
Pfizer Investigational Site
Johannesburg, Gauteng, South Africa, 2196
Pfizer Investigational Site
Pretoria, Gauteng, South Africa, 0081
Spain
Pfizer Investigational Site
Elche, Alicante, Spain, 03203
Pfizer Investigational Site
Terrasa, Barcelona, Spain, 08221
Pfizer Investigational Site
Plasencia, Caceres, Spain, 10600
Pfizer Investigational Site
Palma de Mallorca, Islas Baleares, Spain, 07014
Pfizer Investigational Site
Palma de Mallorca, Islas Baleares, Spain, 07010
Pfizer Investigational Site
Barcelona, Spain, 08014
Pfizer Investigational Site
Barcelona, Spain, 08034
Pfizer Investigational Site
Barcelona, Spain, 08041
Pfizer Investigational Site
Barcelona, Spain, 08003
Pfizer Investigational Site
Burgos, Spain, 09006
Pfizer Investigational Site
Madrid, Spain, 28040
Pfizer Investigational Site
Madrid, Spain, 28034
Pfizer Investigational Site
Madrid, Spain, 28046
Pfizer Investigational Site
Madrid, Spain, 28041
Pfizer Investigational Site
Madrid, Spain, 28006
Sweden
Pfizer Investigational Site
Malmo, Sweden, SE-205 02
Switzerland
Pfizer Investigational Site
Basel, BS, Switzerland, CH-4031
United Kingdom
Pfizer Investigational Site
Brighton, United Kingdom, BN2 5BE
Pfizer Investigational Site
Glasgow, United Kingdom, G20 OXA
Pfizer Investigational Site
London, United Kingdom, SE5 9RS
Pfizer Investigational Site
London, United Kingdom, W6 8RF
Pfizer Investigational Site
Newcastle upon Tyne, United Kingdom, NE4 5PL
Pfizer Investigational Site
Penarth, United Kingdom, CF64 2XX
Pfizer Investigational Site
Sheffield, United Kingdom, S35 8QS
Pfizer Investigational Site
Sheffield, United Kingdom, S10 2JF
Pfizer Investigational Site
Swindon, United Kingdom, SN3 6BW
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00996918     History of Changes
Other Study ID Numbers: 3133K1-3002, B2521003
Study First Received: October 14, 2009
Results First Received: November 12, 2013
Last Updated: November 12, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
antibody

Additional relevant MeSH terms:
Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Dementia
Mental Disorders
Nervous System Diseases
Neurodegenerative Diseases
Tauopathies

ClinicalTrials.gov processed this record on October 20, 2014