Alzheimer Disease
Conditions
Keywords
antibody, immunotherapy
Brief summary
The purpose of this study is to assess the long-term safety and tolerability of bapineuzumab in subjects with Alzheimer Disease who participated in study 3133K1-3001(NCT00676143). Over 250 sites will participate in over 26 countries. Subjects will receive bapineuzumab. Each subject's participation will last approximately 4 years.
Interventions
I.V., 0.5 mg/kg, infusion every 13 weeks for a total of 16 infusions.
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
51 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Subject has completed study 3133K1-3001 (Week 78) and brain magnetic resonance imaging (MRI) scan consistent with the diagnosis of Alzheimer Disease * Mini-Mental Status Examination (MMSE) \>=10 at screening * Caregiver able to attend all clinic visits with subject
Exclusion criteria
* Any medical or psychiatric contraindication or clinically significant abnormality that, in the investigator's judgment, will substantially increase the risk associated with the subject's participation in and completion of the study or could preclude the evaluation of the subject's response. * Any significant brain MRI abnormality. * Use of any investigational drugs or devices, other than bapineuzumab within the last 60 days prior to screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Reporting a Serious Adverse Event | Up to Week 195 | Safety was measured according to standard adverse event collection as described in the Adverse Event Section of the Results. Complete tables of events are provided there. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78. | Base Study Baseline, Weeks 13, 26, 39, 52 and 78 | The ADAS-Cog is a multi-item, objective measure of cognitive function. The scale evaluates memory, language, and praxis with items such as orientation, word recall, word recognition, object identification, comprehension, and the completion of simple tasks. Analysis of the ADAS-Cog for this study was based upon an 11 item score from the following items 1) word recall task, 2) naming objects and fingers, 3) following commands, 4)constructional praxis, 5) ideational praxis, 6) orientation, 7) word recognition, 8)remembering test instructions, 9) spoken language ability, 10) word finding difficulty in spontaneous speech, and 11) comprehension.This scale had to be administered by a trained and certified psychometric rater who did not have access to any information regarding adverse events experienced. The ADAS-Cog/11 ranged from 0 to 70 points, with higher scores indicating a greater degree of impairment. A negative change from baseline indicates a decrease in cognitive impairment. |
| Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78. | Base Study Baseline, Weeks 13, 26, 39, 52 and 78 | The DAD measures instrumental and basic activities of daily living in AD participants. The DAD is administered to the participant's caregiver in the form of an interview. The performance of basic activities of daily living is evaluated in 10 aspects including hygiene, dressing, continence, eating, meal preparation, telephoning, going on an outing, finance and correspondence, medications, leisure, and housework. The caregiver answers 40 questions as yes, no, or not applicable. A one-point score was assigned to each question if the answer is yes and a zero score was assigned if the answer is no. For questions answered as not applicable, no score will be assigned. The DAD total score was calculated as the total number of questions answered as yes divided by the total number of questions answered as yes or no, times 100. The DAD score can range from 0 to 100, with higher scores indicating better function. A positive change indicates improvement from baseline. |
| Change From Extension Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78. | Base Study Baseline, Weeks 13, 26, 39, 52 and 78 | The DAD measures instrumental and basic activities of daily living in AD participants. The DAD is administered to the participant's caregiver in the form of an interview. The performance of basic activities of daily living is evaluated in 10 aspects including hygiene, dressing, continence, eating, meal preparation, telephoning, going on an outing, finance and correspondence, medications, leisure, and housework. The caregiver answers 40 questions as yes, no, or not applicable. A one-point score was assigned to each question if the answer is yes and a zero score was assigned if the answer is no. For questions answered as not applicable, no score will be assigned. The DAD total score was calculated as the total number of questions answered as yes divided by the total number of questions answered as yes or no, times 100. The DAD score can range from 0 to 100, with higher scores indicating better function. A positive change indicates improvement from baseline. |
| Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78 | Base Study Baseline, Weeks 13, 26, 39, 52 and 78 | The ADAS-Cog is a multi-item, objective measure of cognitive function. The scale evaluates memory, language, and praxis with items such as orientation, word recall, word recognition, object identification, comprehension, and the completion of simple tasks. Analysis of the ADAS-Cog for this study was based upon an 11 item score from the following items 1) word recall task, 2) naming objects and fingers, 3) following commands, 4)constructional praxis, 5) ideational praxis, 6) orientation, 7) word recognition, 8 remembering test instructions, 9) spoken language ability, 10) word finding difficulty in spontaneous speech, and 11) comprehension.This scale had to be administered by a trained and certified psychometric rater who did not have access to any information regarding adverse events experienced. The ADAS-Cog/11 ranged from 0 to 70 points, with higher scores indicating a greater degree of impairment. A negative change from baseline indicates a decrease in cognitive impairment. |
| Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78. | Base Study Baseline, Weeks 26, 52 and 78 | NPI:12-domain caregiver assessment of behavioral disturbances occurring in dementia: delusions, hallucinations, agitation/ aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/ indifference, disinhibition, irritability/lability, motor disturbance, appetite/eating, nighttime behavior. Severity(1=Mild to 3=Severe),frequency (1=occasionally to 4=very frequently) scales recorded for each domain; frequency\*severity=each domain score(range 0-12). The NPI total score ranges from 0 to 144 with higher NPI scores indicate greater impairment. A negative change indicates improvement from baseline. |
| Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78. | Base Study Baseline, Weeks 6, 19, 32, 45 and 78 | MMSE measured general cognitive functioning: orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two intersecting polygons. The MMSE total score can range from 0 to 30, with lower scores indicating a greater degree of impairment. A positive change indicates improvement from baseline. |
| Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78. | Base Study Baseline, Weeks 6, 19, 32, 45 and 78 | MMSE measured general cognitive functioning: orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two intersecting polygons. The MMSE total score can range from 0 to 30, with lower scores indicating a greater degree of impairment. A positive change indicates improvement from baseline. |
| Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78. | Base Study Baseline, Weeks 26, 52 and 78 | NPI:12-domain caregiver assessment of behavioral disturbances occurring in dementia: delusions, hallucinations, agitation/ aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/ indifference, disinhibition, irritability/lability, motor disturbance, appetite/eating, nighttime behavior. Severity(1=Mild to 3=Severe),frequency (1=occasionally to 4=very frequently) scales recorded for each domain; frequency\*severity=each domain score(range 0-12). The NPI total score ranges from 0 to 144 with higher NPI scores indicate greater impairment. A negative change indicates improvement from baseline. |
Countries
Argentina, Australia, Belgium, Chile, Finland, France, Italy, Japan, Netherlands, New Zealand, Poland, Portugal, Slovakia, South Africa, Spain, Sweden, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
This study was conducted at 147 centers in 19 countries. The study was terminated early by the sponsor on 06 August 2012. Subjects who had not completed the final follow-up visit prior to 06 August 2012 were asked to complete an early termination visit.
Participants by arm
| Arm | Count |
|---|---|
| Placebo/Bapineuzumab Participants received placebo in the base study and bapineuzumab in this extension study. In this extension study Bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195. | 215 |
| Bapineuzumab/Bapineuzumab Participants received Bapinezumab in both the base and extension studies. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195. | 275 |
| Total | 490 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 17 | 12 |
| Overall Study | Death | 3 | 1 |
| Overall Study | Discontinuation of Study by Sponsor | 164 | 217 |
| Overall Study | Failed to Return | 1 | 1 |
| Overall Study | Lack of Efficacy | 3 | 6 |
| Overall Study | Loss of Caregiver | 0 | 3 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Other | 4 | 4 |
| Overall Study | Physician Decision | 3 | 3 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Recurrent Episode of vasogenic edema | 1 | 0 |
| Overall Study | Withdrawal by Subject | 19 | 25 |
Baseline characteristics
| Characteristic | Placebo/Bapineuzumab | Bapineuzumab/Bapineuzumab | Total |
|---|---|---|---|
| Age, Continuous | 71.4 Years STANDARD_DEVIATION 8.14 | 72.1 Years STANDARD_DEVIATION 7.47 | 71.8 Years STANDARD_DEVIATION 7.77 |
| Age, Customized < 65 years | 44 Participants | 42 Participants | 86 Participants |
| Age, Customized >= 65 years | 171 Participants | 233 Participants | 404 Participants |
| Sex: Female, Male Female | 135 Participants | 186 Participants | 321 Participants |
| Sex: Female, Male Male | 80 Participants | 89 Participants | 169 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 57 / 215 | 45 / 275 |
| serious Total, serious adverse events | 35 / 215 | 33 / 275 |
Outcome results
Primary
Number of Participants Reporting a Serious Adverse Event
Safety was measured according to standard adverse event collection as described in the Adverse Event Section of the Results. Complete tables of events are provided there.
Time frame: Up to Week 195
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo/Bapineuzumab | Number of Participants Reporting a Serious Adverse Event | 35 Number of Participants |
| Bapineuzumab/Bapineuzumab | Number of Participants Reporting a Serious Adverse Event | 33 Number of Participants |
Secondary
Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78
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: Base Study Baseline, Weeks 13, 26, 39, 52 and 78
Population: The Modified Intent-to-Treat (mITT) Population was defined as all randomly assigned participants who received investigational product in the base study, had a baseline for the base study, had at least one valid post-baseline assessment of the ADAS-Cog and DAD total score in the base study and signed informed consent in the extension study.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo/Bapineuzumab | Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78 | Week 26 (N = 154, 221) | 7.41 Units on a scale | Standard Error 0.63 |
| Placebo/Bapineuzumab | Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78 | Week 52 (N = 91, 139) | 10.12 Units on a scale | Standard Error 0.75 |
| Placebo/Bapineuzumab | Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78 | Week 39 (N = 121, 184) | 8.83 Units on a scale | Standard Error 0.72 |
| Placebo/Bapineuzumab | Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78 | Week 78 (N = 52, 80) | 13.91 Units on a scale | Standard Error 0.96 |
| Placebo/Bapineuzumab | Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78 | Week 13 (N= 197, 253) | 5.53 Units on a scale | Standard Error 0.57 |
| Bapineuzumab/Bapineuzumab | Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78 | Week 78 (N = 52, 80) | 12.70 Units on a scale | Standard Error 0.8 |
| Bapineuzumab/Bapineuzumab | Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78 | Week 13 (N= 197, 253) | 6.28 Units on a scale | Standard Error 0.5 |
| Bapineuzumab/Bapineuzumab | Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78 | Week 26 (N = 154, 221) | 7.70 Units on a scale | Standard Error 0.54 |
| Bapineuzumab/Bapineuzumab | Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78 | Week 39 (N = 121, 184) | 8.87 Units on a scale | Standard Error 0.61 |
| Bapineuzumab/Bapineuzumab | Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78 | Week 52 (N = 91, 139) | 10.11 Units on a scale | Standard Error 0.63 |
Comparison: Change from baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog) at week 13p-value: 0.32495% CI: [-0.74, 2.23]Mixed Models Analysis
Comparison: Change from baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog) at week 26p-value: 0.72395% CI: [-1.33, 1.92]Mixed Models Analysis
Comparison: Change from baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog) at week 39p-value: 0.96695% CI: [-1.81, 1.89]Mixed Models Analysis
Comparison: Change from baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog) at week 52p-value: 0.99695% CI: [-1.93, 1.92]Mixed Models Analysis
Comparison: Change from baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog) at week 78p-value: 0.33695% CI: [-3.67, 1.26]Mixed Models Analysis
Secondary
Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.
The DAD measures instrumental and basic activities of daily living in AD participants. The DAD is administered to the participant's caregiver in the form of an interview. The performance of basic activities of daily living is evaluated in 10 aspects including hygiene, dressing, continence, eating, meal preparation, telephoning, going on an outing, finance and correspondence, medications, leisure, and housework. The caregiver answers 40 questions as yes, no, or not applicable. A one-point score was assigned to each question if the answer is yes and a zero score was assigned if the answer is no. For questions answered as not applicable, no score will be assigned. The DAD total score was calculated as the total number of questions answered as yes divided by the total number of questions answered as yes or no, times 100. The DAD score can range from 0 to 100, with higher scores indicating better function. A positive change indicates improvement from baseline.
Time frame: Base Study Baseline, Weeks 13, 26, 39, 52 and 78
Population: The Modified Intent-to-Treat (mITT) Population was defined as all randomly assigned participants who received investigational product in the base study, had a baseline for the base study, had at least one valid post-baseline assessment of the ADAS-Cog and DAD total score in the base study and signed informed consent in the extension study.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo/Bapineuzumab | Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78. | Week 26 (N = 151, 222) | -15.37 Units on a scale | Standard Error 1.29 |
| Placebo/Bapineuzumab | Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78. | Week 52 (N = 89, 137) | -20.96 Units on a scale | Standard Error 1.65 |
| Placebo/Bapineuzumab | Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78. | Week 39 (N = 119, 180) | -17.74 Units on a scale | Standard Error 1.47 |
| Placebo/Bapineuzumab | Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78. | Week 78 (N = 50, 81) | -26.33 Units on a scale | Standard Error 2.18 |
| Placebo/Bapineuzumab | Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78. | Week 13 (N = 194, 247) | -12.33 Units on a scale | Standard Error 1.27 |
| Bapineuzumab/Bapineuzumab | Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78. | Week 78 (N = 50, 81) | -29.11 Units on a scale | Standard Error 1.75 |
| Bapineuzumab/Bapineuzumab | Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78. | Week 13 (N = 194, 247) | 15.32 Units on a scale | Standard Error 1.11 |
| Bapineuzumab/Bapineuzumab | Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78. | Week 26 (N = 151, 222) | -18.04 Units on a scale | Standard Error 1.11 |
| Bapineuzumab/Bapineuzumab | Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78. | Week 39 (N = 119, 180) | -21.33 Units on a scale | Standard Error 1.24 |
| Bapineuzumab/Bapineuzumab | Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78. | Week 52 (N = 89, 137) | -22.72 Units on a scale | Standard Error 1.36 |
Comparison: Change from base study baseline in DAD score at Week 13p-value: 0.07795% CI: [-6.3, 0.33]Mixed Models Analysis
Comparison: Change from base study baseline in DAD score at Week 26p-value: 0.11795% CI: [-6.02, 0.67]Mixed Models Analysis
Comparison: Change from base study baseline in DAD score at Week 39p-value: 0.06395% CI: [-7.38, 0.19]Mixed Models Analysis
Comparison: Change from base study baseline in DAD score at Week 52p-value: 0.41295% CI: [-5.95, 2.44]Mixed Models Analysis
Comparison: Change from base study baseline in DAD score at Week 78p-value: 0.32195% CI: [-8.28, 2.73]Mixed Models Analysis
Secondary
Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.
MMSE measured general cognitive functioning: orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two intersecting polygons. The MMSE total score can range from 0 to 30, with lower scores indicating a greater degree of impairment. A positive change indicates improvement from baseline.
Time frame: Base Study Baseline, Weeks 6, 19, 32, 45 and 78
Population: The Modified Intent-to-Treat (mITT) Population was defined as all randomly assigned participants who received investigational product in the base study, had a baseline for the base study, had at least one valid post-baseline assessment of the ADAS-Cog and DAD total score in the base study and signed informed consent in the extension study.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo/Bapineuzumab | Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78. | Week 19 (N = 184, 241) | -3.13 Units on a scale | Standard Error 0.22 |
| Placebo/Bapineuzumab | Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78. | Week 45 (N = 117, 171) | -4.44 Units on a scale | Standard Error 0.26 |
| Placebo/Bapineuzumab | Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78. | Week 32 (N = 141, 204) | -3.75 Units on a scale | Standard Error 0.24 |
| Placebo/Bapineuzumab | Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78. | Week 78 (N = 65, 94) | -5.50 Units on a scale | Standard Error 0.32 |
| Placebo/Bapineuzumab | Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78. | Week 6 (N= 197, 255) | -2.61 Units on a scale | Standard Error 0.22 |
| Bapineuzumab/Bapineuzumab | Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78. | Week 78 (N = 65, 94) | -5.54 Units on a scale | Standard Error 0.26 |
| Bapineuzumab/Bapineuzumab | Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78. | Week 6 (N= 197, 255) | -2.55 Units on a scale | Standard Error 0.19 |
| Bapineuzumab/Bapineuzumab | Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78. | Week 19 (N = 184, 241) | -3.01 Units on a scale | Standard Error 0.19 |
| Bapineuzumab/Bapineuzumab | Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78. | Week 32 (N = 141, 204) | -3.65 Units on a scale | Standard Error 0.2 |
| Bapineuzumab/Bapineuzumab | Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78. | Week 45 (N = 117, 171) | -4.26 Units on a scale | Standard Error 0.21 |
Comparison: Change from base study baseline in MMSE score at Week 6.p-value: 0.81195% CI: [-0.49, 0.63]Mixed Models Analysis
Comparison: Change from base study baseline in MMSE score at Week 19.p-value: 0.68195% CI: [-0.45, 0.69]Mixed Models Analysis
Comparison: Change from extension study baseline in MMSE score at Week 32.p-value: 0.74295% CI: [-0.51, 0.72]Mixed Models Analysis
Comparison: Change from extension study baseline in MMSE score at Week 45.p-value: 0.59895% CI: [-0.48, 0.83]Mixed Models Analysis
Comparison: Change from extension study baseline in MMSE score at Week 78.p-value: 0.92295% CI: [-0.85, 0.77]Mixed Models Analysis
Secondary
Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78.
NPI:12-domain caregiver assessment of behavioral disturbances occurring in dementia: delusions, hallucinations, agitation/ aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/ indifference, disinhibition, irritability/lability, motor disturbance, appetite/eating, nighttime behavior. Severity(1=Mild to 3=Severe),frequency (1=occasionally to 4=very frequently) scales recorded for each domain; frequency\*severity=each domain score(range 0-12). The NPI total score ranges from 0 to 144 with higher NPI scores indicate greater impairment. A negative change indicates improvement from baseline.
Time frame: Base Study Baseline, Weeks 26, 52 and 78
Population: The Modified Intent-to-Treat (mITT) Population was defined as all randomly assigned participants who received investigational product in the base study, had a baseline for the base study, had at least one valid post-baseline assessment of the ADAS-Cog and DAD total score in the base study and signed informed consent in the extension study.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo/Bapineuzumab | Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78. | Week 78 (N = 51, 81) | 6.95 Units on a scale | Standard Error 1.7 |
| Placebo/Bapineuzumab | Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78. | Week 26 (N = 176, 240) | 2.84 Units on a scale | Standard Error 0.97 |
| Placebo/Bapineuzumab | Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78. | Week 52 (N = 110, 163) | 4.32 Units on a scale | Standard Error 0.96 |
| Bapineuzumab/Bapineuzumab | Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78. | Week 52 (N = 110, 163) | 3.52 Units on a scale | Standard Error 0.8 |
| Bapineuzumab/Bapineuzumab | Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78. | Week 78 (N = 51, 81) | 4.93 Units on a scale | Standard Error 1.36 |
| Bapineuzumab/Bapineuzumab | Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78. | Week 26 (N = 176, 240) | 2.95 Units on a scale | Standard Error 0.83 |
Comparison: Change from base study baseline in NPI score at week 26.p-value: 0.93195% CI: [-2.4, 2.62]Mixed Models Analysis
Comparison: Change from base study baseline in NPI score at week 52.p-value: 0.52495% CI: [-3.26, 1.67]Mixed Models Analysis
Comparison: Change from base study baseline in NPI score at week 78.p-value: 0.35395% CI: [-6.32, 2.27]Mixed Models Analysis
Secondary
Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.
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: Base Study Baseline, Weeks 13, 26, 39, 52 and 78
Population: The Modified Intent-to-Treat (mITT) Population was defined as all randomly assigned participants who received investigational product in the base study, had a baseline for the base study, had at least one valid post-baseline assessment of the ADAS-Cog and DAD total score in the base study and signed informed consent in the extension study.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo/Bapineuzumab | Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78. | Week 39 (N = 121, 184) | 4.26 Units on a scale | Standard Error 0.5 |
| Placebo/Bapineuzumab | Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78. | Week 13 (N = 197, 253) | 0.89 Units on a scale | Standard Error 0.36 |
| Placebo/Bapineuzumab | Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78. | Week 52 (N = 91, 139) | 5.42 Units on a scale | Standard Error 0.55 |
| Placebo/Bapineuzumab | Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78. | Week 78 (N = 52, 80) | 9.21 Units on a scale | Standard Error 0.82 |
| Placebo/Bapineuzumab | Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78. | Week 26 (N = 154, 221) | 2.87 Units on a scale | Standard Error 0.42 |
| Bapineuzumab/Bapineuzumab | Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78. | Week 78 (N = 52, 80) | 7.07 Units on a scale | Standard Error 0.66 |
| Bapineuzumab/Bapineuzumab | Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78. | Week 26 (N = 154, 221) | 2.19 Units on a scale | Standard Error 0.35 |
| Bapineuzumab/Bapineuzumab | Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78. | Week 39 (N = 121, 184) | 3.35 Units on a scale | Standard Error 0.42 |
| Bapineuzumab/Bapineuzumab | Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78. | Week 52 (N = 91, 139) | 4.51 Units on a scale | Standard Error 0.45 |
| Bapineuzumab/Bapineuzumab | Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78. | Week 13 (N = 197, 253) | 0.73 Units on a scale | Standard Error 0.32 |
Comparison: Change from extension study baseline in ADAS-Cog at week 13p-value: 0.73795% CI: [-1.11, 0.79]Mixed Models Analysis
Comparison: Change from extension study baseline in ADAS-Cog at week 26p-value: 0.21395% CI: [-1.76, 0.4]Mixed Models Analysis
Comparison: Change from extension study baseline in ADAS-Cog at week 39p-value: 0.16895% CI: [-2.19, 0.38]Mixed Models Analysis
Comparison: Change from extension study baseline in ADAS-Cog at week 52p-value: 0.19795% CI: [-2.3, 0.48]Mixed Models Analysis
Comparison: Change from extension study baseline in ADAS-Cog at week 78p-value: 0.04495% CI: [-4.21, 0.06]Mixed Models Analysis
Secondary
Change From Extension Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.
The DAD measures instrumental and basic activities of daily living in AD participants. The DAD is administered to the participant's caregiver in the form of an interview. The performance of basic activities of daily living is evaluated in 10 aspects including hygiene, dressing, continence, eating, meal preparation, telephoning, going on an outing, finance and correspondence, medications, leisure, and housework. The caregiver answers 40 questions as yes, no, or not applicable. A one-point score was assigned to each question if the answer is yes and a zero score was assigned if the answer is no. For questions answered as not applicable, no score will be assigned. The DAD total score was calculated as the total number of questions answered as yes divided by the total number of questions answered as yes or no, times 100. The DAD score can range from 0 to 100, with higher scores indicating better function. A positive change indicates improvement from baseline.
Time frame: Base Study Baseline, Weeks 13, 26, 39, 52 and 78
Population: The Modified Intent-to-Treat (mITT) Population was defined as all randomly assigned participants who received investigational product in the base study, had a baseline for the base study, had at least one valid post-baseline assessment of the ADAS-Cog and DAD total score in the base study and signed informed consent in the extension study.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo/Bapineuzumab | Change From Extension Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78. | Week 26 (N = 151, 222) | -5.76 Units on scale | Standard Error 1.01 |
| Placebo/Bapineuzumab | Change From Extension Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78. | Week 52 (N = 89, 137) | -11.82 Units on scale | Standard Error 1.34 |
| Placebo/Bapineuzumab | Change From Extension Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78. | Week 39 (N = 119, 180) | -8.17 Units on scale | Standard Error 1.22 |
| Placebo/Bapineuzumab | Change From Extension Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78. | Week 78 (N = 50, 81) | -17.34 Units on scale | Standard Error 1.94 |
| Placebo/Bapineuzumab | Change From Extension Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78. | Week 13 (N = 194, 247) | -2.63 Units on scale | Standard Error 0.83 |
| Bapineuzumab/Bapineuzumab | Change From Extension Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78. | Week 78 (N = 50, 81) | -17.48 Units on scale | Standard Error 1.56 |
| Bapineuzumab/Bapineuzumab | Change From Extension Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78. | Week 13 (N = 194, 247) | -3.71 Units on scale | Standard Error 0.73 |
| Bapineuzumab/Bapineuzumab | Change From Extension Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78. | Week 26 (N = 151, 222) | -6.46 Units on scale | Standard Error 0.86 |
| Bapineuzumab/Bapineuzumab | Change From Extension Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78. | Week 39 (N = 119, 180) | -9.72 Units on scale | Standard Error 1.02 |
| Bapineuzumab/Bapineuzumab | Change From Extension Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78. | Week 52 (N = 89, 137) | -11.11 Units on scale | Standard Error 1.1 |
Comparison: Change from extension study baseline in DAD score at Week 13p-value: 0.32995% CI: [-3.24, 1.09]Mixed Models Analysis
Comparison: Change from extension study baseline in DAD score at Week 26p-value: 0.60195% CI: [-3.31, 1.92]Mixed Models Analysis
Comparison: Change from extension study baseline in DAD score at Week 39p-value: 0.32895% CI: [-4.67, 1.56]Mixed Models Analysis
Comparison: Change from extension study baseline in DAD score at Week 52p-value: 0.6895% CI: [-2.7, 4.13]Mixed Models Analysis
Comparison: Change from extension study baseline in DAD score at Week 78p-value: 0.95495% CI: [-5.05, 4.77]Mixed Models Analysis
Secondary
Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.
MMSE measured general cognitive functioning: orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two intersecting polygons. The MMSE total score can range from 0 to 30, with lower scores indicating a greater degree of impairment. A positive change indicates improvement from baseline.
Time frame: Base Study Baseline, Weeks 6, 19, 32, 45 and 78
Population: The Modified Intent-to-Treat (mITT) Population was defined as all randomly assigned participants who received investigational product in the base study, had a baseline for the base study, had at least one valid post-baseline assessment of the ADAS-Cog and DAD total score in the base study and signed informed consent in the extension study.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo/Bapineuzumab | Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78. | Week 19 (N = 182, 241) | -1.16 Units on a scale | Standard Error 0.21 |
| Placebo/Bapineuzumab | Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78. | Week 45 (N = 116, 171) | -2.57 Units on a scale | Standard Error 0.28 |
| Placebo/Bapineuzumab | Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78. | Week 32 (N = 140, 204) | -1.85 Units on a scale | Standard Error 0.24 |
| Placebo/Bapineuzumab | Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78. | Week 78 (N = 64, 94) | -3.69 Units on a scale | Standard Error 0.39 |
| Placebo/Bapineuzumab | Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78. | Week 6 (N = 195, 255) | -0.67 Units on a scale | Standard Error 0.19 |
| Bapineuzumab/Bapineuzumab | Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78. | Week 78 (N = 64, 94) | -3.42 Units on a scale | Standard Error 0.32 |
| Bapineuzumab/Bapineuzumab | Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78. | Week 6 (N = 195, 255) | -0.26 Units on a scale | Standard Error 0.16 |
| Bapineuzumab/Bapineuzumab | Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78. | Week 19 (N = 182, 241) | -0.69 Units on a scale | Standard Error 0.18 |
| Bapineuzumab/Bapineuzumab | Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78. | Week 32 (N = 140, 204) | -1.40 Units on a scale | Standard Error 0.2 |
| Bapineuzumab/Bapineuzumab | Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78. | Week 45 (N = 116, 171) | -2.05 Units on a scale | Standard Error 0.24 |
Comparison: Change from extension study baseline in MMSE score at Week 6.p-value: 0.09995% CI: [-0.08, 0.9]Mixed Models Analysis
Comparison: Change from extension study baseline in MMSE score at Week 19.p-value: 0.08995% CI: [-0.07, 1.01]Mixed Models Analysis
Comparison: Change from extension study baseline in MMSE score at Week 32.p-value: 0.15295% CI: [-0.17, 1.08]Mixed Models Analysis
Comparison: Change from extension study baseline in MMSE score at Week 45.p-value: 0.1695% CI: [-0.21, 1.25]Mixed Models Analysis
Comparison: Change from extension study baseline in MMSE score at Week 78.p-value: 0.60395% CI: [-0.73, 1.26]Mixed Models Analysis
Secondary
Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78.
NPI:12-domain caregiver assessment of behavioral disturbances occurring in dementia: delusions, hallucinations, agitation/ aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/ indifference, disinhibition, irritability/lability, motor disturbance, appetite/eating, nighttime behavior. Severity(1=Mild to 3=Severe),frequency (1=occasionally to 4=very frequently) scales recorded for each domain; frequency\*severity=each domain score(range 0-12). The NPI total score ranges from 0 to 144 with higher NPI scores indicate greater impairment. A negative change indicates improvement from baseline.
Time frame: Base Study Baseline, Weeks 26, 52 and 78
Population: The Modified Intent-to-Treat (mITT) Population was defined as all randomly assigned participants who received investigational product in the base study, had a baseline for the base study, had at least one valid post-baseline assessment of the ADAS-Cog and DAD total score in the base study and signed informed consent in the extension study.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo/Bapineuzumab | Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78. | Week 26 (N = 176, 240) | 2.17 Units on a scale | Standard Error 0.86 |
| Placebo/Bapineuzumab | Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78. | Week 52 (N = 110, 163) | 3.82 Units on a scale | Standard Error 0.95 |
| Placebo/Bapineuzumab | Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78. | Week 78 (N = 51, 81) | 6.60 Units on a scale | Standard Error 1.69 |
| Bapineuzumab/Bapineuzumab | Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78. | Week 26 (N = 176, 240) | 1.47 Units on a scale | Standard Error 0.73 |
| Bapineuzumab/Bapineuzumab | Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78. | Week 52 (N = 110, 163) | 1.98 Units on a scale | Standard Error 0.79 |
| Bapineuzumab/Bapineuzumab | Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78. | Week 78 (N = 51, 81) | 3.29 Units on a scale | Standard Error 1.35 |
Comparison: Change from extension study baseline in NPI score at week 26.p-value: 0.53195% CI: [-2.92, 1.51]Mixed Models Analysis
Comparison: Change from extension study baseline in NPI score at week 52.p-value: 0.13795% CI: [-4.28, 0.59]Mixed Models Analysis
Comparison: Change from extension study baseline in NPI score at week 78.p-value: 0.12895% CI: [-7.6, 0.96]Mixed Models Analysis