Trial Outcomes & Findings for Study Evaluating The Efficacy And Safety Of Bapineuzumab In Alzheimer Disease Patients (NCT NCT00667810)

Last Updated: 2016-01-08

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

901 participants

Primary outcome timeframe

78 weeks

Results posted on

2016-01-08

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	269	264	346	11
Overall Study Treated	267	263	344	11
Overall Study COMPLETED	102	94	124	9
Overall Study NOT COMPLETED	167	170	222	2

Reasons for withdrawal

Reasons for withdrawal
Measure	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.
Overall Study Adverse Event	13	14	19	1
Overall Study Death	1	1	3	0
Overall Study Lack of Efficacy	1	0	2	0
Overall Study Lost to Follow-up	1	4	2	0
Overall Study Physician Decision	1	1	2	0
Overall Study Protocol Violation	0	2	0	0
Overall Study Withdrawal by Subject	14	20	29	1
Overall Study Discontinuation of Study by Sponsor	130	118	155	0
Overall Study Failed to Return	0	0	2	0
Overall Study Loss of Caregiver	0	1	3	0
Overall Study Vasogenic Edema Recurrence	0	3	0	0
Overall Study Other	6	6	5	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bapineuzumab 0.5 mg/kg n=267 Participants 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 n=263 Participants 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 n=344 Participants 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 n=11 Participants 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 n=885 Participants Total of all reporting groups
Age, Continuous	71.4 Years STANDARD_DEVIATION 9.38 • n=5 Participants	70.8 Years STANDARD_DEVIATION 9.73 • n=7 Participants	69.9 Years STANDARD_DEVIATION 9.76 • n=5 Participants	66.5 Years STANDARD_DEVIATION 7.94 • n=4 Participants	70.6 Years STANDARD_DEVIATION 9.63 • n=21 Participants
Age, Customized <65 years	73 Years n=5 Participants	81 Years n=7 Participants	115 Years n=5 Participants	6 Years n=4 Participants	275 Years n=21 Participants
Age, Customized ≥65 years	194 Years n=5 Participants	182 Years n=7 Participants	229 Years n=5 Participants	5 Years n=4 Participants	610 Years n=21 Participants
Sex: Female, Male Female	151 Participants n=5 Participants	150 Participants n=7 Participants	199 Participants n=5 Participants	4 Participants n=4 Participants	504 Participants n=21 Participants
Sex: Female, Male Male	116 Participants n=5 Participants	113 Participants n=7 Participants	145 Participants n=5 Participants	7 Participants n=4 Participants	381 Participants n=21 Participants

PRIMARY outcome

Timeframe: 78 weeks

Population: 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.

Outcome measures

Outcome measures
Measure	Bapineuzumab 0.5 mg/kg n=255 Participants 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 n=253 Participants 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 n=328 Participants 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.
The Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)/11 Total Score at Week 78	6.05 Units on a scale Standard Error 0.71	8.07 Units on a scale Standard Error 0.73	7.88 Units on a scale Standard Error 0.64	—

PRIMARY outcome

Timeframe: 78 weeks

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Bapineuzumab 0.5 mg/kg n=255 Participants 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 n=253 Participants 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 n=328 Participants 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.
The Change From Baseline in the Disability Assessment for Demential (DAD) Total Score at Week 78	-14.58 Units on a scale Standard Error 1.50	-15.07 Units on a scale Standard Error 1.55	-16.08 Units on a scale Standard Error 1.36	—

SECONDARY outcome

Timeframe: 71 Weeks

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Bapineuzumab 0.5 mg/kg n=6 Participants 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 n=11 Participants 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 n=13 Participants 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 n=17 Participants Participants in the bapineuzumab 0.5 and 1.0 mg/kg groups were combined to form the Pooled Bapineuzumab group.
The Change From Baseline in Brain Amyloid Burden at Week 71.	-0.04 SUVr Standard Error 0.08	0.00 SUVr Standard Error 0.05	0.02 SUVr Standard Error 0.04	-0.01 SUVr Standard Error 0.04

SECONDARY outcome

Timeframe: 71 Weeks

Population: 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).

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.

Outcome measures

Outcome measures
Measure	Bapineuzumab 0.5 mg/kg n=21 Participants 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 n=22 Participants 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 n=33 Participants 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 n=43 Participants Participants in the bapineuzumab 0.5 and 1.0 mg/kg groups were combined to form the Pooled Bapineuzumab group.
The Change From Baseline in Phospho-tau Levels in the Cerebrospinal Fluid (CSF) at Week 71.	-6.62 pg/mL Standard Error 3.90	-6.35 pg/mL Standard Error 3.73	0.70 pg/mL Standard Error 3.03	-6.48 pg/mL Standard Error 2.67

SECONDARY outcome

Timeframe: 71 Weeks

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Bapineuzumab 0.5 mg/kg n=122 Participants 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 n=121 Participants 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 n=153 Participants 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.
The Change From Baseline in Brain Volume at Week 71	18.55 mL/year Standard Error 0.97	18.60 mL/year Standard Error 1.00	17.54 mL/year Standard Error 0.86	—

SECONDARY outcome

Timeframe: 39 Weeks

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Bapineuzumab 0.5 mg/kg n=583 Participants 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 n=581 Participants 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.
Divergence of Effect on the ADAS-Cog/11 Total Scores From Week 39 to Week 78	-1.32 Units/Year Standard Error 1.06	0.38 Units/Year Standard Error 1.09	—	—

SECONDARY outcome

Timeframe: 39 weeks

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.

Outcome measures

Outcome measures
Measure	Bapineuzumab 0.5 mg/kg n=583 Participants 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 n=581 Participants 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.
Divergence of Effect on the DAD Total Scores From Week 39 to Week 78	3.20 Units/Years Standard Error 2.22	2.01 Units/Years Standard Error 2.27	—	—

SECONDARY outcome

Timeframe: 78 Weeks

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.

Outcome measures

Outcome measures
Measure	Bapineuzumab 0.5 mg/kg n=255 Participants 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 n=253 Participants 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 n=328 Participants 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.
Time to Median Placebo Deterioration on ADAS-Cog/11 Total Score (European Union [EU] Analysis Plan)	546.0 Days Interval 546.0 to Value was not calculable due to the large number of censored event times	462.0 Days Interval 455.0 to 546.0	540.0 Days Interval 462.0 to 546.0	—

SECONDARY outcome

Timeframe: 78 weeks

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.

Outcome measures

Outcome measures
Measure	Bapineuzumab 0.5 mg/kg n=255 Participants 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 n=253 Participants 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 n=328 Participants 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.
Time to First Clinically Meaningful Deterioration on ADAS-Cog/11 Total Score (United States [US] Analysis Plan)	546.0 Days Interval 546.0 to Values were not calculable due to the large number of censored event times	546.0 Days Interval 455.0 to 546.0	546.0 Days Interval 476.0 to 546.0	—

SECONDARY outcome

Timeframe: 78 Weeks

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.

Outcome measures

Outcome measures
Measure	Bapineuzumab 0.5 mg/kg n=255 Participants 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 n=253 Participants 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 n=328 Participants 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.
Time to Median Placebo Deterioration on DAD Total Score	541.0 Days Interval 455.0 to 546.0	534.0 Days Interval 372.0 to Values were not calculable due to the large number of censored event times	463.0 Days Interval 453.0 to 546.0	—

SECONDARY outcome

Timeframe: 78 Weeks

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.

Outcome measures

Outcome measures
Measure	Bapineuzumab 0.5 mg/kg n=255 Participants 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 n=253 Participants 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 n=328 Participants 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.
Time to First Clinically Meaningful Deterioration on DAD Total Score (US Analysis Plan)	542.0 Days Interval 456.0 to 546.0	539.0 Days Interval 450.0 to Value was not calculable due to the large number of censored event times	540.0 Days Interval 453.0 to 546.0	—

SECONDARY outcome

Timeframe: 78 Weeks

Percentage of participants whose increase (worsening) in ADAS-Cog/11 total score from baseline to Week 78 was at most 0, 3, 7 points.

Outcome measures

Outcome measures
Measure	Bapineuzumab 0.5 mg/kg n=255 Participants 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 n=253 Participants 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 n=328 Participants 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.
Percentage of Participants With Worsening From Baseline in ADAS-Cog/11 Total Score at Week 78 (European Union Analysis Plan) Worsening of 0 points	10.6 Number of participants Interval 7.1 to 15.0	8.7 Number of participants Interval 5.5 to 12.9	7.3 Number of participants Interval 4.7 to 10.7	—
Percentage of Participants With Worsening From Baseline in ADAS-Cog/11 Total Score at Week 78 (European Union Analysis Plan) Worsening of 3 points	16.1 Number of participants Interval 11.8 to 21.2	13.4 Number of participants Interval 9.5 to 18.3	10.1 Number of participants Interval 7.0 to 13.8	—
Percentage of Participants With Worsening From Baseline in ADAS-Cog/11 Total Score at Week 78 (European Union Analysis Plan) Worsening of 7 points	23.1 Number of participants Interval 18.1 to 28.8	19.0 Number of participants Interval 14.3 to 24.4	19.2 Number of participants Interval 15.1 to 23.9	—

SECONDARY outcome

Timeframe: 78 Weeks

Percentage of participants whose increase (worsening) from baseline to Week 78 in ADAS-Cog/11 total score is \<7.

Outcome measures

Outcome measures
Measure	Bapineuzumab 0.5 mg/kg n=255 Participants 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 n=253 Participants 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 n=328 Participants 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.
Percentage of Participants With Worsening From Baseline in ADAS-Cog/11 Total Score at Week 78 (US Analysis Plan)	22.4 Percentage of participants	18.6 Percentage of participants	18.6 Percentage of participants	—

SECONDARY outcome

Timeframe: 78 Weeks

Percentage of participants whose decrease (worsening) from baseline to Week 78 in DAD total score was at most 0, 6, 12 points.

Outcome measures

Outcome measures
Measure	Bapineuzumab 0.5 mg/kg n=255 Participants 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 n=253 Participants 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 n=328 Participants 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.
Percentage of Participants With Worsening From Baseline in DAD Total Score at Week 78 (European Union Analysis Plan) Worsening of 0 points	10.2 Percentage of participants Interval 6.8 to 14.6	11.9 Percentage of participants Interval 8.1 to 16.5	9.1 Percentage of participants Interval 6.3 to 12.8	—
Percentage of Participants With Worsening From Baseline in DAD Total Score at Week 78 (European Union Analysis Plan) Worsening of 6 points	15.7 Percentage of participants Interval 11.4 to 20.7	16.6 Percentage of participants Interval 12.2 to 21.8	14.3 Percentage of participants Interval 10.7 to 18.6	—
Percentage of Participants With Worsening From Baseline in DAD Total Score at Week 78 (European Union Analysis Plan) Worsening of 12 points	20.0 Percentage of participants Interval 15.3 to 25.4	22.1 Percentage of participants Interval 17.2 to 27.8	19.5 Percentage of participants Interval 15.4 to 24.2	—

SECONDARY outcome

Timeframe: 78 weeks

Percentage of participants whose decrease (worsening) from baseline to Week 78 in DAD total score was \<12.

Outcome measures

Outcome measures
Measure	Bapineuzumab 0.5 mg/kg n=255 Participants 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 n=253 Participants 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 n=328 Participants 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.
Percentage of Participants With Worsening From Baseline in DAD Total Score at Week 78 (US Analysis Plan)	20.0 Percentage of participants	22.1 Percentage of participants	19.5 Percentage of participants	—

SECONDARY outcome

Timeframe: 78 Weeks

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.

Outcome measures

Outcome measures
Measure	Bapineuzumab 0.5 mg/kg n=255 Participants 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 n=253 Participants 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 n=328 Participants 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.
Change From Baseline in Dependence Scale Total Score at Week 78	1.29 Units on a scale Standard Error 0.19	1.16 Units on a scale Standard Error 0.19	1.45 Units on a scale Standard Error 0.17	—

SECONDARY outcome

Timeframe: 78 Weeks

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.

Outcome measures

Outcome measures
Measure	Bapineuzumab 0.5 mg/kg n=255 Participants 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 n=253 Participants 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 n=328 Participants 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.
Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SOB) Total Score at Week 78	2.23 Units on a scale Standard Error 0.23	2.41 Units on a scale Standard Error 0.23	2.59 Units on a scale Standard Error 0.20	—

Adverse Events

Bapineuzumab 0.5 mg/kg

Serious events: 32 serious events

Other events: 109 other events

Deaths: 0 deaths

Bapineuzumab 1.0 mg/kg

Serious events: 34 serious events

Other events: 123 other events

Deaths: 0 deaths

Placebo

Serious events: 53 serious events

Other events: 124 other events

Deaths: 0 deaths

Bapineuzumab 2.0 mg/kg

Serious events: 2 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER