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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 3 Extension, Multicenter, Long Term Safety And Tolerability Trial Of Bapineuzumab (Aab 001, Eln115727) In Subjects With Alzheimer Disease Who Are Apolipoprotein E 4 Carriers And Participated In Study 3133k1-3001-us Or Study 3133k1-3001-ww.

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Drug: Bapineuzumab 0.5 mg/kg


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 51 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bapineuzumab 0.5 mg/kg<br> | Drug: Bapineuzumab 0.5 mg/kg<br>* I.V., 0.5 mg/kg, infusion every 13 weeks for a total of 16 infusions.<br>* Other names: AAB-001;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to Week 195 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Base Study Baseline, Weeks 13, 26, 39, 52 and 78 | 
| 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. | Base Study Baseline, Weeks 13, 26, 39, 52 and 78 | 
| 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. | Base Study Baseline, Weeks 13, 26, 39, 52 and 78 | 
| 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. | Base Study Baseline, Weeks 13, 26, 39, 52 and 78 | 
| 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. | Base Study Baseline, Weeks 26, 52 and 78 | 
| 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. | Base Study Baseline, Weeks 26, 52 and 78 | 
| 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. | Base Study Baseline, Weeks 6, 19, 32, 45 and 78 | 
| 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. | Base Study Baseline, Weeks 6, 19, 32, 45 and 78 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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antibody, immunotherapy