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Trial record 6 of 31 for:    alzheimer dijon

Study Evaluating The Efficacy And Safety Of Bapineuzumab In Alzheimer Disease Patients

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: NCT00667810
Recruitment Status : 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.)
First Posted : April 28, 2008
Results First Posted : January 8, 2016
Last Update Posted : January 8, 2016
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Alzheimer Disease
Interventions: Drug: bapineuzumab
Drug: placebo

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study was terminated on 06 August 2012 due to lack of clinical efficacy observed in completed studies ELN115727-301 (ApoE4 non-carriers) and ELN115727-302. A total of 329 participants had completed the study up to and including Week 78 before the decision was taken to terminate the study.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The study originally included bapineuzumab 2.0 mg/kg dose level, which was discontinued on 02 April 2009 based on input from independent safety monitoring committee. It was estimated at the time that about 10 participants received 2.0mg/kg. These participants are not included in the efficacy analyses.

Reporting Groups
  Description
Bapineuzumab 0.5 mg/kg Participants received 0.5 mg/kg bapineuzumab by intravenous (IV) infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Bapineuzumab 1.0 mg/kg Participants received 1.0 mg/kg bapineuzumab by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Placebo Participants received placebo by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Bapineuzumab 2.0 mg/kg Participants received 2.0 mg/kg bapineuzumab by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.

Participant Flow:   Overall Study
    Bapineuzumab 0.5 mg/kg   Bapineuzumab 1.0 mg/kg   Placebo   Bapineuzumab 2.0 mg/kg
STARTED   269   264   346   11 
Treated   267   263   344   11 
COMPLETED   102   94   124   9 
NOT COMPLETED   167   170   222   2 
Adverse Event                13                14                19                1 
Death                1                1                3                0 
Lack of Efficacy                1                0                2                0 
Lost to Follow-up                1                4                2                0 
Physician Decision                1                1                2                0 
Protocol Violation                0                2                0                0 
Withdrawal by Subject                14                20                29                1 
Discontinuation of Study by Sponsor                130                118                155                0 
Failed to Return                0                0                2                0 
Loss of Caregiver                0                1                3                0 
Vasogenic Edema Recurrence                0                3                0                0 
Not specified                6                6                5                0 



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety population included all randomized participants who received at least one infusion or portion of an infusion of study drug.

Reporting Groups
  Description
Bapineuzumab 0.5 mg/kg Participants received 0.5 mg/kg bapineuzumab by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Bapineuzumab 1.0 mg/kg Participants received 1.0 mg/kg bapineuzumab by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Placebo Participants received placebo by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Bapineuzumab 2.0 mg/kg Participants received 2.0 mg/kg bapineuzumab by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Total Total of all reporting groups

Baseline Measures
   Bapineuzumab 0.5 mg/kg   Bapineuzumab 1.0 mg/kg   Placebo   Bapineuzumab 2.0 mg/kg   Total 
Overall Participants Analyzed 
[Units: Participants]
 267   263   344   11   885 
Age 
[Units: Years]
Mean (Standard Deviation)
 71.4  (9.38)   70.8  (9.73)   69.9  (9.76)   66.5  (7.94)   70.6  (9.63) 
Age, Customized 
[Units: Years]
         
<65 years   73   81   115   6   275 
≥65 years   194   182   229   5   610 
Gender 
[Units: Number of participants]
         
Female   151   150   199   4   504 
Male   116   113   145   7   381 


  Outcome Measures

1.  Primary:   The Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)/11 Total Score at Week 78   [ Time Frame: 78 weeks ]

Measure Type Primary
Measure Title The Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)/11 Total Score at Week 78
Measure Description 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.
Time Frame 78 weeks  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The modified intent-to-treat (mITT) included all randomized participants who received at least one infusion or portion of an infusion of study drug and who had a baseline and at least one post-baseline assessment of the ADAS-Cog/11 total score and Disability Assessment for Dementia (DAD) total score.

Reporting Groups
  Description
Bapineuzumab 0.5 mg/kg Participants received 0.5 mg/kg bapineuzumab by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Bapineuzumab 1.0 mg/kg Participants received 1.0 mg/kg bapineuzumab by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Placebo Participants received placebo by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.

Measured Values
   Bapineuzumab 0.5 mg/kg   Bapineuzumab 1.0 mg/kg   Placebo 
Participants Analyzed   255   253   328 
The Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)/11 Total Score at Week 78 
[Units: Units on a scale]
Least Squares Mean (Standard Error)
 6.05  (0.71)   8.07  (0.73)   7.88  (0.64) 


Statistical Analysis 1 for The Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)/11 Total Score at Week 78
Groups [1] Bapineuzumab 0.5 mg/kg vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.057
Mean Difference (Final Values) [5] -1.83
95% Confidence Interval -3.71 to 0.05
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from baseline in ADAS-Cog/11 total score was analyzed using a restricted maximum likelihood (REML) based mixed model for repeated-measures (MMRM). The number of participants in each group provided approximately 90% power to detect a 2.65 point advantage at Week 78. This calculation was based on a 2-sided test with alpha set at 0.05, the use of the Hochberg procedure to control for multiplicity.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  The p-value is not adjusted for multiple comparison. The Hochberg approach is used to control for multiplicity between the two dose levels (0.5 mg/kg and 1.0 mg/kg) of bapineuzumab.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for The Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)/11 Total Score at Week 78
Groups [1] Bapineuzumab 1.0 mg/kg vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.848
Mean Difference (Final Values) [5] 0.19
95% Confidence Interval -1.73 to 2.10
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from baseline in ADAS-Cog/11 total score was analyzed using a REML based MMRM. The number of participants in each group provided approximately 90% power to detect a 2.65 point advantage at Week 78. This calculation was based on a 2-sided test with alpha set at 0.05, the use of the Hochberg procedure to control for multiplicity.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  The p-value is not adjusted for multiple comparison. The Hochberg approach is used to control for multiplicity between the two dose levels (0.5 mg/kg and 1.0 mg/kg) of bapineuzumab.
[5] Other relevant estimation information:
  No text entered.



2.  Primary:   The Change From Baseline in the Disability Assessment for Demential (DAD) Total Score at Week 78   [ Time Frame: 78 weeks ]

Measure Type Primary
Measure Title The Change From Baseline in the Disability Assessment for Demential (DAD) Total Score at Week 78
Measure Description 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 global 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.
Time Frame 78 weeks  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Modified Intent-to-Treat (mITT) population included as all randomized participants who received at least one infusion or portion of an infusion of study drug and who had a baseline and at least one post-baseline assessment of the ADAS-Cog/11 total score and DAD total score.

Reporting Groups
  Description
Bapineuzumab 0.5 mg/kg Participants received 0.5 mg/kg bapineuzumab by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Bapineuzumab 1.0 mg/kg Participants received 1.0 mg/kg bapineuzumab by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Placebo Participants received placebo by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.

Measured Values
   Bapineuzumab 0.5 mg/kg   Bapineuzumab 1.0 mg/kg   Placebo 
Participants Analyzed   255   253   328 
The Change From Baseline in the Disability Assessment for Demential (DAD) Total Score at Week 78 
[Units: Units on a scale]
Least Squares Mean (Standard Error)
 -14.58  (1.50)   -15.07  (1.55)   -16.08  (1.36) 


Statistical Analysis 1 for The Change From Baseline in the Disability Assessment for Demential (DAD) Total Score at Week 78
Groups [1] Bapineuzumab 0.5 mg/kg vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.459
Mean Difference (Final Values) [5] 1.51
95% Confidence Interval -2.48 to 5.49
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from baseline in DAD total score was analyzed using a REML based MMRM. The number of participants in each group provided approximately 90% power to detect a 6.56 point advantage at Week 78. This calculation was based on a 2-sided test with alpha set at 0.05, the use of the Hochberg procedure to control for multiplicity.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  The p-value is not adjusted for multiple comparison. The Hochberg approach is used to control for multiplicity between the two dose levels (0.5 mg/kg and 1.0 mg/kg) of bapineuzumab.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for The Change From Baseline in the Disability Assessment for Demential (DAD) Total Score at Week 78
Groups [1] Bapineuzumab 1.0 mg/kg vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.623
Mean Difference (Final Values) [5] 1.01
95% Confidence Interval -3.04 to 5.07
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from baseline in DAD total score was analyzed using a REML based MMRM. The number of participants in each group provided approximately 90% power to detect a 6.56 point advantage at Week 78. This calculation was based on a 2-sided test with alpha set at 0.05, the use of the Hochberg procedure to control for multiplicity.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  The p-value is not adjusted for multiple comparison. The Hochberg approach is used to control for multiplicity between the two dose levels (0.5 mg/kg and 1.0 mg/kg) of bapineuzumab.
[5] Other relevant estimation information:
  No text entered.



3.  Secondary:   The Change From Baseline in Brain Amyloid Burden at Week 71.   [ Time Frame: 71 Weeks ]

Measure Type Secondary
Measure Title The Change From Baseline in Brain Amyloid Burden at Week 71.
Measure Description Brain amyloid burden as imaged by 11C-Pittsburgh compound B (PiB) positron emission tomography (PET). The latter is a semiquantitative measure of the extent of fibrillar amyloid in the brain. PIB PET measurements were made in cortical regions found to have the highest burden of fibrillar amyloid at autopsy in participants diagnosed as having Alzheimer’s pathology, and also regions reported to have the highest average retention of PIB signal in previous PET studies enrolling participants with probable AD. This parameter reflects overall brain amyloid deposition as indexed by imaging. The change from baseline was measured as average standard uptake value ratio (SUVr) in prespecified regions of interest (ROI) assessed by PIB PET imaging in a subset of participants.
Time Frame 71 Weeks  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PiB PET population included all randomized participants who enrolled in the PET substudies and who met the following criteria: a) received at least one infusion or portion of an infusion of study drug, b) had a baseline and at least one post baseline PiB PET assessment, and c) had an SUVr for the global cortical average (GCA) ROI≥1.35 at baseline.

Reporting Groups
  Description
Bapineuzumab 0.5 mg/kg Participants received 0.5 mg/kg bapineuzumab by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Bapineuzumab 1.0 mg/kg Participants received 1.0 mg/kg bapineuzumab by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Placebo Participants received placebo by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Pooled Bapineuzumab 0.5/1.0 mg/kg Participants in the bapineuzumab 0.5 and 1.0 mg/kg groups were combined to form the Pooled Bapineuzumab group.

Measured Values
   Bapineuzumab 0.5 mg/kg   Bapineuzumab 1.0 mg/kg   Placebo   Pooled Bapineuzumab 0.5/1.0 mg/kg 
Participants Analyzed   6   11   13   17 
The Change From Baseline in Brain Amyloid Burden at Week 71. 
[Units: SUVr]
Least Squares Mean (Standard Error)
 -0.04  (0.08)   0.00  (0.05)   0.02  (0.04)   -0.01  (0.04) 


Statistical Analysis 1 for The Change From Baseline in Brain Amyloid Burden at Week 71.
Groups [1] Placebo vs. Pooled Bapineuzumab 0.5/1.0 mg/kg
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.654
Mean Difference (Final Values) [5] -0.03
95% Confidence Interval -0.15 to 0.09
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis is based on the pooled bapineuzumab (with subjects in the bapineuzumab 0.5 and 1.0 mg/kg groups combined) treatment difference estimated at Week 71. The number of participants gave 90% power to detect a 0.186 unit advantage for a bapineuzumab dose group over placebo for PiB PET binding at Week 71. The calculations were based on 2-sided tests with alpha set at 0.05 and the use of the Hochberg procedure to control for multiplicity for 2 individual doses.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.



4.  Secondary:   The Change From Baseline in Phospho-tau Levels in the Cerebrospinal Fluid (CSF) at Week 71.   [ Time Frame: 71 Weeks ]

Measure Type Secondary
Measure Title The Change From Baseline in Phospho-tau Levels in the Cerebrospinal Fluid (CSF) at Week 71.
Measure Description Biomarkers CSF phospho-tau (p-tau) is an indicator of neuronal injury and neurodegeneration. An elevation in levels of tau, as well as specific p-tau species, is thought to be a marker for progressive cellular degeneration in AD. Accordingly, a reduction from baseline in levels of CSF tau in participants who received bapineuzumab compared with participants who received placebo may be indicative of a reduction in neuronal loss in participants treated with bapineuzumab.
Time Frame 71 Weeks  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
CSF population included all randomized participants who enrolled in the CSF substudies, received at least one infusion or portion of an infusion of study drug, and had a baseline and at least one postbaseline CSF measurement (CSF phospho-tau).

Reporting Groups
  Description
Bapineuzumab 0.5 mg/kg Participants received 0.5 mg/kg bapineuzumab by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Bapineuzumab 1.0 mg/kg Participants received 1.0 mg/kg bapineuzumab by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Placebo Participants received placebo by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Pooled Bapineuzumab 0.5/1.0 mg/kg Participants in the bapineuzumab 0.5 and 1.0 mg/kg groups were combined

Measured Values
   Bapineuzumab 0.5 mg/kg   Bapineuzumab 1.0 mg/kg   Placebo   Pooled Bapineuzumab 0.5/1.0 mg/kg 
Participants Analyzed   21   22   33   43 
The Change From Baseline in Phospho-tau Levels in the Cerebrospinal Fluid (CSF) at Week 71. 
[Units: pg/mL]
Least Squares Mean (Standard Error)
 -6.62  (3.90)   -6.35  (3.73)   0.70  (3.03)   -6.48  (2.67) 


Statistical Analysis 1 for The Change From Baseline in Phospho-tau Levels in the Cerebrospinal Fluid (CSF) at Week 71.
Groups [1] Placebo vs. Pooled Bapineuzumab 0.5/1.0 mg/kg
Statistical Test Type [2] Superiority or Other
Statistical Method [3] ANCOVA
P Value [4] 0.085
Mean Difference (Final Values) [5] -7.18
95% Confidence Interval -15.38 to 1.02
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis is based on the pooled bapineuzumab (with subjects in the bapineuzumab 0.5 and 1.0 mg/kg groups combined) treatment difference estimated at Week 71. The number of participants gave 90% power to detect a 15 ng/L advantage in p-tau for a bapineuzumab dose group over placebo at Week 71. The calculations were based on 2-sided tests with alpha set at 0.05 and the use of the Hochberg procedure to control for multiplicity for 2 individual doses.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.



5.  Secondary:   The Change From Baseline in Brain Volume at Week 71   [ Time Frame: 71 Weeks ]

Measure Type Secondary
Measure Title The Change From Baseline in Brain Volume at Week 71
Measure Description Brain volume was examined in a subset of participants by Magnetic Resonance Imaging Brain Boundary Shift Integral (MRI BBSI). Cerebral atrophy correlates closely with the gradual cognitive decline in AD and can be visualized by MRI. The BBSI technique involves positional matching of serial 3-dimensional MRI brain images, such that brain MRI-image volumes were first registered and then subtracted from each other. Atrophy rates would generally be expected to be lower if the underlying disease was attenuated by effective treatment.
Time Frame 71 Weeks  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The vMRI population Included all randomized participants who enrolled in the vMRI substudies, received at least one infusion or portion of an infusion of study drug, and had a baseline and at least one postbaseline vMRI that passed quality control and was satisfactory for volumetric analysis.

Reporting Groups
  Description
Bapineuzumab 0.5 mg/kg Participants received 0.5 mg/kg bapineuzumab by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Bapineuzumab 1.0 mg/kg Participants received 1.0 mg/kg bapineuzumab by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Placebo Participants received placebo by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.

Measured Values
   Bapineuzumab 0.5 mg/kg   Bapineuzumab 1.0 mg/kg   Placebo 
Participants Analyzed   122   121   153 
The Change From Baseline in Brain Volume at Week 71 
[Units: mL/year]
Least Squares Mean (Standard Error)
 18.55  (0.97)   18.60  (1.00)   17.54  (0.86) 


Statistical Analysis 1 for The Change From Baseline in Brain Volume at Week 71
Groups [1] Bapineuzumab 0.5 mg/kg vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.437
Mean Difference (Final Values) [5] 1.01
95% Confidence Interval -1.55 to 3.57
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change in MRI BBSI was analyzed using a REML based MMRM. The number of participants gave 90% power to detect a 5.05-cm3 advantage for a bapineuzumab dose group over placebo on reduction in brain volume as measured by the BBSI at Week 71. The calculations were based on 2-sided tests with alpha set at 0.05 and the use of the Hochberg procedure to control for multiplicity for 2 individual doses.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for The Change From Baseline in Brain Volume at Week 71
Groups [1] Bapineuzumab 1.0 mg/kg vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.423
Mean Difference (Final Values) [5] 1.06
95% Confidence Interval -1.54 to 3.66
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change in MRI BBSI was analyzed using a REML based MMRM. The number of participants gave 90% power to detect a 5.05-cm3 advantage for a bapineuzumab dose group over placebo on reduction in brain volume as measured by the BBSI at Week 71. The calculations were based on 2-sided tests with alpha set at 0.05 and the use of the Hochberg procedure to control for multiplicity for 2 individual doses.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.



6.  Secondary:   Divergence of Effect on the ADAS-Cog/11 Total Scores From Week 39 to Week 78   [ Time Frame: 39 Weeks ]

Measure Type Secondary
Measure Title Divergence of Effect on the ADAS-Cog/11 Total Scores From Week 39 to Week 78
Measure Description The MMRM estimated slope (based on linear contrasts) of the differences between bapineuzumab and placebo for the ADAS-Cog/11 total scores from Week 39 to Week 78 was presented.
Time Frame 39 Weeks  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The mITT included all randomized participants who received at least one infusion or portion of an infusion of study drug and who had a baseline and at least one post-baseline assessment of the ADAS-Cog/11 total score and DAD total score.

Reporting Groups
  Description
Bapineuzumab 0.5 mg/kg - Placebo For the ADAS-Cog/11 total score, results are presented from a REML based MMRM.
Bapineuzumab 1.0 mg/kg - Placebo For the ADAS-Cog/11 total score, results are presented from a REML based MMRM.

Measured Values
   Bapineuzumab 0.5 mg/kg - Placebo   Bapineuzumab 1.0 mg/kg - Placebo 
Participants Analyzed   583   581 
Divergence of Effect on the ADAS-Cog/11 Total Scores From Week 39 to Week 78 
[Units: Units/Year]
Mean (Standard Error)
 -1.32  (1.06)   0.38  (1.09) 


Statistical Analysis 1 for Divergence of Effect on the ADAS-Cog/11 Total Scores From Week 39 to Week 78
Groups [1] Bapineuzumab 0.5 mg/kg - Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.212
Mean Difference (Final Values) [5] -1.32
95% Confidence Interval -3.40 to 0.76
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Not specified.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Not specified.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Divergence of Effect on the ADAS-Cog/11 Total Scores From Week 39 to Week 78
Groups [1] Bapineuzumab 1.0 mg/kg - Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.725
Mean Difference (Final Values) [5] 0.38
95% Confidence Interval -1.76 to 2.52
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Not specified.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Not specified.
[5] Other relevant estimation information:
  No text entered.



7.  Secondary:   Divergence of Effect on the DAD Total Scores From Week 39 to Week 78   [ Time Frame: 39 weeks ]

Measure Type Secondary
Measure Title Divergence of Effect on the DAD Total Scores From Week 39 to Week 78
Measure Description The MMRM estimated slope (based on linear contrasts)of the differences between bapineuzumab and placebo for the DAD total scores from Week 39 to Week 78 was presented.
Time Frame 39 weeks  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The mITT included all randomized participants who received at least one infusion or portion of an infusion of study drug and who had a baseline and at least one post-baseline assessment of the ADAS-Cog/11 total score and DAD total score.

Reporting Groups
  Description
Bapineuzumab 0.5 mg/kg - Placebo For the DAD total score, results are presented from a REML-based MMRM.
Bapineuzumab 1.0 mg/kg - Placebo For the DAD total score, results are presented from a REML)-based MMRM.

Measured Values
   Bapineuzumab 0.5 mg/kg - Placebo   Bapineuzumab 1.0 mg/kg - Placebo 
Participants Analyzed   583   581 
Divergence of Effect on the DAD Total Scores From Week 39 to Week 78 
[Units: Units/Years]
Mean (Standard Error)
 3.20  (2.22)   2.01  (2.27) 


Statistical Analysis 1 for Divergence of Effect on the DAD Total Scores From Week 39 to Week 78
Groups [1] Bapineuzumab 0.5 mg/kg - Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.149
Mean Difference (Final Values) [5] 3.20
95% Confidence Interval -1.15 to 7.56
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Not specified.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Not specified.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Divergence of Effect on the DAD Total Scores From Week 39 to Week 78
Groups [1] Bapineuzumab 1.0 mg/kg - Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.375
Mean Difference (Final Values) [5] 2.01
95% Confidence Interval -2.44 to 6.46
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Not specified.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Not specified.
[5] Other relevant estimation information:
  No text entered.



8.  Secondary:   Time to Median Placebo Deterioration on ADAS-Cog/11 Total Score (European Union [EU] Analysis Plan)   [ Time Frame: 78 Weeks ]

Measure Type Secondary
Measure Title Time to Median Placebo Deterioration on ADAS-Cog/11 Total Score (European Union [EU] Analysis Plan)
Measure Description The time to first median placebo deterioration (for the EU) was defined as the first time a subject experienced an increase from baseline (worsening) in ADAS Cog/11 total score greater than or equal to the median worsening observed at Week 78 in the placebo group. The Kaplan Meier estimate of the median time to first median placebo deterioration in ADAS Cog/11 total score was presented.
Time Frame 78 Weeks  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The mITT included all randomized participants who received at least one infusion or portion of an infusion of study drug and who had a baseline and at least one post-baseline assessment of the ADAS-Cog/11 total score and DAD total score.

Reporting Groups
  Description
Bapineuzumab 0.5 mg/kg Participants received 0.5 mg/kg bapineuzumab by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Bapineuzumab 1.0 mg/kg Participants received 1.0 mg/kg bapineuzumab by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Placebo Participants received placebo by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.

Measured Values
   Bapineuzumab 0.5 mg/kg   Bapineuzumab 1.0 mg/kg   Placebo 
Participants Analyzed   255   253   328 
Time to Median Placebo Deterioration on ADAS-Cog/11 Total Score (European Union [EU] Analysis Plan) 
[Units: Days]
Median (95% Confidence Interval)
 546.0 [1] 
 (546.0 to N/A) 
 462.0 
 (455.0 to 546.0) 
 540.0 
 (462.0 to 546.0) 
[1] Value was not calculable due to the large number of censored event times


Statistical Analysis 1 for Time to Median Placebo Deterioration on ADAS-Cog/11 Total Score (European Union [EU] Analysis Plan)
Groups [1] Bapineuzumab 0.5 mg/kg vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Log Rank
P Value [4] 0.030
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Not specified.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  Not specified.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Not specifed.

Statistical Analysis 2 for Time to Median Placebo Deterioration on ADAS-Cog/11 Total Score (European Union [EU] Analysis Plan)
Groups [1] Bapineuzumab 1.0 mg/kg vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Log Rank
P Value [4] 0.567
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Not specified.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  Not specified.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Not specified.



9.  Secondary:   Time to First Clinically Meaningful Deterioration on ADAS-Cog/11 Total Score (United States [US] Analysis Plan)   [ Time Frame: 78 weeks ]

Measure Type Secondary
Measure Title Time to First Clinically Meaningful Deterioration on ADAS-Cog/11 Total Score (United States [US] Analysis Plan)
Measure Description The time to first clinically meaningful deterioration (for the US) was defined as the first time a participant experienced an increase (worsening) from baseline in ADAS-Cog/11 total score of >=7.
Time Frame 78 weeks  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Bapineuzumab 0.5 mg/kg Participants received 0.5 mg/kg bapineuzumab by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Bapineuzumab 1.0 mg/kg Participants received 1.0 mg/kg bapineuzumab by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Placebo Participants received placebo by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.

Measured Values
   Bapineuzumab 0.5 mg/kg   Bapineuzumab 1.0 mg/kg   Placebo 
Participants Analyzed   255   253   328 
Time to First Clinically Meaningful Deterioration on ADAS-Cog/11 Total Score (United States [US] Analysis Plan) 
[Units: Days]
Median (95% Confidence Interval)
 546.0 [1] 
 (546.0 to N/A) 
 546.0 
 (455.0 to 546.0) 
 546.0 
 (476.0 to 546.0) 
[1] Values were not calculable due to the large number of censored event times


Statistical Analysis 1 for Time to First Clinically Meaningful Deterioration on ADAS-Cog/11 Total Score (United States [US] Analysis Plan)
Groups [1] Bapineuzumab 0.5 mg/kg vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Log Rank
P Value [4] 0.079
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Not specified.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  Not specified.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Not specified.

Statistical Analysis 2 for Time to First Clinically Meaningful Deterioration on ADAS-Cog/11 Total Score (United States [US] Analysis Plan)
Groups [1] Bapineuzumab 1.0 mg/kg vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Log Rank
P Value [4] 0.675
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Not specified.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Not specified.



10.  Secondary:   Time to Median Placebo Deterioration on DAD Total Score   [ Time Frame: 78 Weeks ]

Measure Type Secondary
Measure Title Time to Median Placebo Deterioration on DAD Total Score
Measure Description The time to first median placebo deterioration (for the EU) was defined as the first time a participant experienced a decrease (worsening) in DAD total score greater than or equal to the median worsening at Week 78 in the placebo group.
Time Frame 78 Weeks  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The mITT included all randomized participants who received at least one infusion or portion of an infusion of study drug and who had a baseline and at least one post-baseline assessment of the ADAS-Cog/11 total score and DAD total score.

Reporting Groups
  Description
Bapineuzumab 0.5 mg/kg Participants received 0.5 mg/kg bapineuzumab by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Bapineuzumab 1.0 mg/kg Participants received 1.0 mg/kg bapineuzumab by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Placebo Participants received placebo by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.

Measured Values
   Bapineuzumab 0.5 mg/kg   Bapineuzumab 1.0 mg/kg   Placebo 
Participants Analyzed   255   253   328 
Time to Median Placebo Deterioration on DAD Total Score 
[Units: Days]
Median (95% Confidence Interval)
 541.0 
 (455.0 to 546.0) 
 534.0 [1] 
 (372.0 to N/A) 
 463.0 
 (453.0 to 546.0) 
[1] Values were not calculable due to the large number of censored event times


Statistical Analysis 1 for Time to Median Placebo Deterioration on DAD Total Score
Groups [1] Bapineuzumab 0.5 mg/kg vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Log Rank
P Value [4] 0.846
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Not spsecified.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  Not specified.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Not specified.

Statistical Analysis 2 for Time to Median Placebo Deterioration on DAD Total Score
Groups [1] Bapineuzumab 1.0 mg/kg vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Log Rank
P Value [4] 0.797
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Not specified.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  Not specified.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Not specified



11.  Secondary:   Time to First Clinically Meaningful Deterioration on DAD Total Score (US Analysis Plan)   [ Time Frame: 78 Weeks ]

Measure Type Secondary
Measure Title Time to First Clinically Meaningful Deterioration on DAD Total Score (US Analysis Plan)
Measure Description The time to first clinically meaningful deterioration was defined as the first time a participant experienced a decrease (worsening)from baseline in DAD total score of >=12.
Time Frame 78 Weeks  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The mITT included all randomized participants who received at least one infusion or portion of an infusion of study drug and who had a baseline and at least one post-baseline assessment of the ADAS-Cog/11 total score and DAD total score.

Reporting Groups
  Description
Bapineuzumab 0.5 mg/kg Participants received 0.5 mg/kg bapineuzumab by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Bapineuzumab 1.0 mg/kg Participants received 1.0 mg/kg bapineuzumab by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Placebo Participants received placebo by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.

Measured Values
   Bapineuzumab 0.5 mg/kg   Bapineuzumab 1.0 mg/kg   Placebo 
Participants Analyzed   255   253   328 
Time to First Clinically Meaningful Deterioration on DAD Total Score (US Analysis Plan) 
[Units: Days]
Median (95% Confidence Interval)
 542.0 
 (456.0 to 546.0) 
 539.0 [1] 
 (450.0 to N/A) 
 540.0 
 (453.0 to 546.0) 
[1] Value was not calculable due to the large number of censored event times


Statistical Analysis 1 for Time to First Clinically Meaningful Deterioration on DAD Total Score (US Analysis Plan)
Groups [1] Bapineuzumab 0.5 mg/kg vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Log Rank
P Value [4] 0.933
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Not specified.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  Not specified.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Not specified.

Statistical Analysis 2 for Time to First Clinically Meaningful Deterioration on DAD Total Score (US Analysis Plan)
Groups [1] Bapineuzumab 1.0 mg/kg vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Log Rank
P Value [4] 0.714
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Not specified
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Not specified.



12.  Secondary:   Percentage of Participants With Worsening From Baseline in ADAS-Cog/11 Total Score at Week 78 (European Union Analysis Plan)   [ Time Frame: 78 Weeks ]

Measure Type Secondary
Measure Title Percentage of Participants With Worsening From Baseline in ADAS-Cog/11 Total Score at Week 78 (European Union Analysis Plan)
Measure Description Percentage of participants whose increase (worsening) in ADAS-Cog/11 total score from baseline to Week 78 was at most 0, 3, 7 points.
Time Frame 78 Weeks  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The mITT included all randomized participants who received at least one infusion or portion of an infusion of study drug and who had a baseline and at least one post-baseline assessment of the ADAS-Cog/11 total score and DAD total score.

Reporting Groups
  Description
Bapineuzumab 0.5 mg/kg Participants received 0.5 mg/kg bapineuzumab by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Bapineuzumab 1.0 mg/kg Participants received 1.0 mg/kg bapineuzumab by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Placebo Participants received placebo by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.

Measured Values
   Bapineuzumab 0.5 mg/kg   Bapineuzumab 1.0 mg/kg   Placebo 
Participants Analyzed   255   253   328 
Percentage of Participants With Worsening From Baseline in ADAS-Cog/11 Total Score at Week 78 (European Union Analysis Plan) 
[Units: Number of participants]
Number (95% Confidence Interval)
     
Worsening of 0 points   10.6 
 (7.1 to 15.0) 
 8.7 
 (5.5 to 12.9) 
 7.3 
 (4.7 to 10.7) 
Worsening of 3 points   16.1 
 (11.8 to 21.2) 
 13.4 
 (9.5 to 18.3) 
 10.1 
 (7.0 to 13.8) 
Worsening of 7 points   23.1 
 (18.1 to 28.8) 
 19.0 
 (14.3 to 24.4) 
 19.2 
 (15.1 to 23.9) 

No statistical analysis provided for Percentage of Participants With Worsening From Baseline in ADAS-Cog/11 Total Score at Week 78 (European Union Analysis Plan)



13.  Secondary:   Percentage of Participants With Worsening From Baseline in ADAS-Cog/11 Total Score at Week 78 (US Analysis Plan)   [ Time Frame: 78 Weeks ]

Measure Type Secondary
Measure Title Percentage of Participants With Worsening From Baseline in ADAS-Cog/11 Total Score at Week 78 (US Analysis Plan)
Measure Description Percentage of participants whose increase (worsening) from baseline to Week 78 in ADAS-Cog/11 total score is <7.
Time Frame 78 Weeks  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The mITT included all randomized participants who received at least one infusion or portion of an infusion of study drug and who had a baseline and at least one post-baseline assessment of the ADAS-Cog/11 total score and DAD total score.

Reporting Groups
  Description
Bapineuzumab 0.5 mg/kg Participants received 0.5 mg/kg bapineuzumab by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Bapineuzumab 1.0 mg/kg Participants received 1.0 mg/kg bapineuzumab by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Placebo Participants received placebo by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.

Measured Values
   Bapineuzumab 0.5 mg/kg   Bapineuzumab 1.0 mg/kg   Placebo 
Participants Analyzed   255   253   328 
Percentage of Participants With Worsening From Baseline in ADAS-Cog/11 Total Score at Week 78 (US Analysis Plan) 
[Units: Percentage of participants]
 22.4   18.6   18.6 


Statistical Analysis 1 for Percentage of Participants With Worsening From Baseline in ADAS-Cog/11 Total Score at Week 78 (US Analysis Plan)
Groups [1] Bapineuzumab 0.5 mg/kg vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Cochran-Mantel-Haenszel
P Value [4] 0.277
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Not specified.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  Not specified.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Not specified.

Statistical Analysis 2 for Percentage of Participants With Worsening From Baseline in ADAS-Cog/11 Total Score at Week 78 (US Analysis Plan)
Groups [1] Bapineuzumab 1.0 mg/kg vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Cochran-Mantel-Haenszel
P Value [4] 0.996
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Not specified.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  Not specified.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Not specified.



14.  Secondary:   Percentage of Participants With Worsening From Baseline in DAD Total Score at Week 78 (European Union Analysis Plan)   [ Time Frame: 78 Weeks ]

Measure Type Secondary
Measure Title Percentage of Participants With Worsening From Baseline in DAD Total Score at Week 78 (European Union Analysis Plan)
Measure Description Percentage of participants whose decrease (worsening) from baseline to Week 78 in DAD total score was at most 0, 6, 12 points.
Time Frame 78 Weeks  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The mITT included all randomized participants who received at least one infusion or portion of an infusion of study drug and who had a baseline and at least one post-baseline assessment of the ADAS-Cog/11 total score and DAD total score.

Reporting Groups
  Description
Bapineuzumab 0.5 mg/kg Participants received 0.5 mg/kg bapineuzumab by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Bapineuzumab 1.0 mg/kg Participants received 1.0 mg/kg bapineuzumab by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Placebo Participants received placebo by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.

Measured Values
   Bapineuzumab 0.5 mg/kg   Bapineuzumab 1.0 mg/kg   Placebo 
Participants Analyzed   255   253   328 
Percentage of Participants With Worsening From Baseline in DAD Total Score at Week 78 (European Union Analysis Plan) 
[Units: Percentage of participants]
Number (95% Confidence Interval)
     
Worsening of 0 points   10.2 
 (6.8 to 14.6) 
 11.9 
 (8.1 to 16.5) 
 9.1 
 (6.3 to 12.8) 
Worsening of 6 points   15.7 
 (11.4 to 20.7) 
 16.6 
 (12.2 to 21.8) 
 14.3 
 (10.7 to 18.6) 
Worsening of 12 points   20.0 
 (15.3 to 25.4) 
 22.1 
 (17.2 to 27.8) 
 19.5 
 (15.4 to 24.2) 

No statistical analysis provided for Percentage of Participants With Worsening From Baseline in DAD Total Score at Week 78 (European Union Analysis Plan)



15.  Secondary:   Percentage of Participants With Worsening From Baseline in DAD Total Score at Week 78 (US Analysis Plan)   [ Time Frame: 78 weeks ]

Measure Type Secondary
Measure Title Percentage of Participants With Worsening From Baseline in DAD Total Score at Week 78 (US Analysis Plan)
Measure Description Percentage of participants whose decrease (worsening) from baseline to Week 78 in DAD total score was <12.
Time Frame 78 weeks  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The mITT included all randomized participants who received at least one infusion or portion of an infusion of study drug and who had a baseline and at least one post-baseline assessment of the ADAS-Cog/11 total score and DAD total score.

Reporting Groups
  Description
Bapineuzumab 0.5 mg/kg Participants received 0.5 mg/kg bapineuzumab by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Bapineuzumab 1.0 mg/kg Participants received 1.0 mg/kg bapineuzumab by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Placebo Participants received placebo by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.

Measured Values
   Bapineuzumab 0.5 mg/kg   Bapineuzumab 1.0 mg/kg   Placebo 
Participants Analyzed   255   253   328 
Percentage of Participants With Worsening From Baseline in DAD Total Score at Week 78 (US Analysis Plan) 
[Units: Percentage of participants]
 20.0   22.1   19.5 


Statistical Analysis 1 for Percentage of Participants With Worsening From Baseline in DAD Total Score at Week 78 (US Analysis Plan)
Groups [1] Bapineuzumab 0.5 mg/kg vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Cochran-Mantel-Haenszel
P Value [4] 0.855
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Not specified.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Not specified.

Statistical Analysis 2 for Percentage of Participants With Worsening From Baseline in DAD Total Score at Week 78 (US Analysis Plan)
Groups [1] Bapineuzumab 1.0 mg/kg vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Cochran-Mantel-Haenszel
P Value [4] 0.423
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Not specified.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  Not specified.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Not specified.



16.  Secondary:   Change From Baseline in Dependence Scale Total Score at Week 78   [ Time Frame: 78 Weeks ]

Measure Type Secondary
Measure Title Change From Baseline in Dependence Scale Total Score at Week 78
Measure Description The Dependence Scale (DS) is a 13-item, caregiver-rated instrument for determining the amount of support required by a participant with AD. The DS total score ranges from 0 to 15, with higher scores indicating more need for assistance. The DS was administered as an interview to the caregiver at scheduled study visits.
Time Frame 78 Weeks  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The mITT included all randomized participants who received at least one infusion or portion of an infusion of study drug and who had a baseline and at least one post-baseline assessment of the ADAS-Cog/11 total score and DAD total score.

Reporting Groups
  Description
Bapineuzumab 0.5 mg/kg Participants received 0.5 mg/kg bapineuzumab by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Bapineuzumab 1.0 mg/kg Participants received 1.0 mg/kg bapineuzumab by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Placebo Participants received placebo by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.

Measured Values
   Bapineuzumab 0.5 mg/kg   Bapineuzumab 1.0 mg/kg   Placebo 
Participants Analyzed   255   253   328 
Change From Baseline in Dependence Scale Total Score at Week 78 
[Units: Units on a scale]
Least Squares Mean (Standard Error)
 1.29  (0.19)   1.16  (0.19)   1.45  (0.17) 


Statistical Analysis 1 for Change From Baseline in Dependence Scale Total Score at Week 78
Groups [1] Bapineuzumab 0.5 mg/kg vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.516
Mean Difference (Final Values) [5] -0.16
95% Confidence Interval -0.65 to 0.33
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change in DS score was analyzed using a REML based MMRM.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  Not specified.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Not specified.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change From Baseline in Dependence Scale Total Score at Week 78
Groups [1] Bapineuzumab 1.0 mg/kg vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.257
Mean Difference (Final Values) [5] -0.29
95% Confidence Interval -0.79 to 0.21
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change in DS score was analyzed using a REML based MMRM.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Not specified.
[5] Other relevant estimation information:
  No text entered.



17.  Secondary:   Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SOB) Total Score at Week 78   [ Time Frame: 78 Weeks ]

Measure Type Secondary
Measure Title Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SOB) Total Score at Week 78
Measure Description The CDR-SOB is a global clinical staging instrument that sums 6 clinical ratings: 1) memory, 2) orientation, 3) judgment and problem solving, 4) involvement in community affairs, 5) home and hobbies, and 6) personal care based on the Clinical Dementia Rating Scale (CDR) interview. The CDR includes discussions with the participant and caregiver using a structured format. This scale had to be administered by a trained and certified global rater who did not have access to any information regarding adverse events experienced by the participant. CDR-SOB total score range is 0 (least impairment) to 18 (most impairment); a negative change from baseline indicates an improvement.
Time Frame 78 Weeks  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The mITT included all randomized participants who received at least one infusion or portion of an infusion of study drug and who had a baseline and at least one post-baseline assessment of the ADAS-Cog/11 total score and DAD total score.

Reporting Groups
  Description
Bapineuzumab 0.5 mg/kg Participants received 0.5 mg/kg bapineuzumab by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Bapineuzumab 1.0 mg/kg Participants received 1.0 mg/kg bapineuzumab by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Placebo Participants received placebo by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.

Measured Values
   Bapineuzumab 0.5 mg/kg   Bapineuzumab 1.0 mg/kg   Placebo 
Participants Analyzed   255   253   328 
Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SOB) Total Score at Week 78 
[Units: Units on a scale]
Least Squares Mean (Standard Error)
 2.23  (0.23)   2.41  (0.23)   2.59  (0.20) 


Statistical Analysis 1 for Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SOB) Total Score at Week 78
Groups [1] Bapineuzumab 0.5 mg/kg vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.238
Mean Difference (Final Values) [5] -0.36
95% Confidence Interval -0.96 to 0.24
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change in CDR-SOB total score was analyzed using a REML based MMRM.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Not specified.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SOB) Total Score at Week 78
Groups [1] Bapineuzumab 1.0 mg/kg vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.564
Mean Difference (Final Values) [5] -0.18
95% Confidence Interval -0.78 to 0.43
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change in CDR-SOB total score was analyzed using a REML based MMRM.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The impact of study termination, the shorter observational periods and the resulting small sample size coupled with not having enough participants with post baseline assessments for various reasons were limiting factors for data interpretation.


  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.gov_Inquiries@pfizer.com


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00667810     History of Changes
Obsolete Identifiers: NCT00909623
Other Study ID Numbers: 3133K1-3000
B2521001 ( Other Identifier: Alias Study Number )
2007-005994-79 ( EudraCT Number )
First Submitted: April 24, 2008
First Posted: April 28, 2008
Results First Submitted: October 22, 2013
Results First Posted: January 8, 2016
Last Update Posted: January 8, 2016