当前位置： SCI文献检索 > NEUROLOGY期刊下所有文献 > A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease.

A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease.

Abstract：

BACKGROUND:Bapineuzumab, a humanized anti-amyloid-beta (Abeta) monoclonal antibody for the potential treatment of Alzheimer disease (AD), was evaluated in a multiple ascending dose, safety, and efficacy study in mild to moderate AD. METHODS:The study enrolled 234 patients, randomly assigned to IV bapineuzumab or placebo in 4 dose cohorts (0.15, 0.5, 1.0, or 2.0 mg/kg). Patients received 6 infusions, 13 weeks apart, with final assessments at week 78. The prespecified primary efficacy analysis in the modified intent-to-treat population assumed linear decline and compared treatment differences within dose cohorts on the Alzheimer's Disease Assessment Scale-Cognitive and Disability Assessment for Dementia. Exploratory analyses combined dose cohorts and did not assume a specific pattern of decline. RESULTS:No significant differences were found in the primary efficacy analysis. Exploratory analyses showed potential treatment differences (p < 0.05, unadjusted for multiple comparisons) on cognitive and functional endpoints in study "completers" and APOE epsilon4 noncarriers. Reversible vasogenic edema, detected on brain MRI in 12/124 (9.7%) bapineuzumab-treated patients, was more frequent in higher dose groups and APOE epsilon4 carriers. Six vasogenic edema patients were asymptomatic; 6 experienced transient symptoms. CONCLUSIONS:Primary efficacy outcomes in this phase 2 trial were not significant. Potential treatment differences in the exploratory analyses support further investigation of bapineuzumab in phase 3 with special attention to APOE epsilon4 carrier status. CLASSIFICATION OF EVIDENCE:Due to varying doses and a lack of statistical precision, this Class II ascending dose trial provides insufficient evidence to support or refute a benefit of bapineuzumab.

journal_name

Neurology

journal_title

Neurology

authors

Salloway S,Sperling R,Gilman S,Fox NC,Blennow K,Raskind M,Sabbagh M,Honig LS,Doody R,van Dyck CH,Mulnard R,Barakos J,Gregg KM,Liu E,Lieberburg I,Schenk D,Black R,Grundman M,Bapineuzumab 201 Clinical Trial Investigator

doi

10.1212/WNL.0b013e3181c67808

subject

Has Abstract

pub_date

2009-12-15 00:00:00

pages

2061-70

issue

eissn

0028-3878

issn

1526-632X

pii

WNL.0b013e3181c67808

journal_volume

pub_type

杂志文章,多中心研究,随机对照试验

在线工具

A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease.