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

  Show 81 Study Locations
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
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders

ClinicalTrials.gov processed this record on July 23, 2014