Study Evaluating Bapineuzumab In Alzheimer Disease Subjects

Study Overview
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Brief Summary
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The study will evaluate the safety and effectiveness of bapineuzumab for the treatment of mild to moderate Alzheimer disease. Subjects will be in the study for six months and will receive subcutaneous injections once per week.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Safety, Tolerability, Reactogenicity, And Pharmacokinetic Study Of Bapineuzumab (AAB 001) Administered Subcutaneously In Subjects With Mild To Moderate AD

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Drug: bapineuzumab
* Drug: bapineuzumab
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of probable Alzheimer Disease according to National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria Mini-Mental State Examination (MMSE) score 16-26 Exclusion Criteria: Magnetic Resonance Imaging (MRI) showing other brain abnormalities Other diagnosed neurological or psychiatric disorders

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 89 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: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>5 mg/week | Drug: bapineuzumab<br>* 5 mg bapineuzumab subcutaneous injection once per week for 6 months<br>|
| Experimental: B<br>10 mg/week | Drug: bapineuzumab<br>* 10 mg bapineuzumab subcutaneous injection once per week for 6 months<br>|
| Experimental: C<br>Placebo | Drug: placebo<br>* Placebo subcutaneous injection once per week for 6 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 30 days after Week 25 dose that were absent before treatment or that worsened relative to pretreatment state. | Baseline up to 30 days after Week 25 dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Serum Concentration (Cmax) |  | Predose, 4 hours [hrs] postdose, 72 hrs postdose on Day 3 of Week 0 and 25; Predose on Day 7 (Week 1), Week 10, 14, 16, 18, 22, 26, 30; Predose and 4 hrs postdose on Week 12 | 
| Average Serum Concentration at Steady State (Cavg,ss) | Average plasma concentration at steady state (Cavg,ss) = AUCtau divided by dosing interval (1 week). AUCtau is the area under the plasma concentration time curve (AUC) at steady state from time zero (pre-dose) to end of dosing interval (tau), here dosing interval is 1 week. | Predose, 4 hrs postdose, 72 hrs postdose on Day 3 of Week 0 and 25; Predose on Day 7 (Week 1), Week 10, 14, 16, 18, 22, 26, 30; Predose and 4 hrs postdose on Week 12 | 
| Serum Decay Half-Life (t1/2) | Serum decay half-life is the time measured for the serum concentration to decrease by one half. | Predose, 4 hrs postdose, 72 hrs postdose on Day 3 of Week 0 and 25; Predose on Day 7 (Week 1), Week 10, 14, 16, 18, 22, 26, 30; Predose and 4 hrs postdose on Week 12 | 
| Time to Reach Maximum Observed Serum Concentration (Tmax) |  | Predose, 4 hrs postdose, 72 hrs postdose on Day 3 of Week 0 and 25; Predose on Day 7 (Week 1), Week 10, 14, 16, 18, 22, 26, 30; Predose and 4 hrs postdose on Week 12 | 
| Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) | AUCtau is the area under the serum concentration time curve (AUC) at steady state from time zero (pre-dose) to end of dosing interval (tau), here dosing interval is 1 week. | Predose, 4 hrs postdose, 72 hrs postdose on Day 3 of Week 0 and 25; Predose on Day 7 (Week 1), Week 10, 14, 16, 18, 22, 26, 30; Predose and 4 hrs postdose on Week 12 | 
| Apparent Systemic Clearance (CL/F) | Clearance (CL) of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after subcutaneous dose (apparent systemic clearance) is influenced by the fraction (F) of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. Steady-state apparent systemic clearance (CL/F) was calculated as dose/AUC tau. | Predose, 4 hrs postdose, 72 hrs postdose on Day 3 of Week 0 and 25; Predose on Day 7 (Week 1), Week 10, 14, 16, 18, 22, 26, 30; Predose and 4 hrs postdose on Week 12 | 

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