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

被引：602

作者：

Salloway, S. ^{[1
]}

Sperling, R. ^{[2
]}

Gilman, S. ^{[3
]}

Fox, N. C. ^{[4
]}

Blennow, K. ^{[5
]}

Raskind, M. ^{[6
]}

Sabbagh, M. ^{[7
]}

Honig, L. S. ^{[8
]}

Doody, R. ^{[9
]}

van Dyck, C. H. ^{[10
]}

Mulnard, R. ^{[11
]}

Barakos, J. ^{[12
]}

Gregg, K. M. ^{[13
]}

Liu, E. ^{[13
]}

Lieberburg, I. ^{[13
]}

Schenk, D. ^{[13
]}

Black, R. ^{[14
]}

Grundman, M. ^{[13
]}

机构：

[1] Brown Univ, Butler Hosp, Warren Alpert Med Sch, Providence, RI 02906 USA

[2] Brigham & Womens Hosp, Boston, MA 02115 USA

[3] Univ Michigan, Ann Arbor, MI 48109 USA

[4] UCL, Inst Neurol, London, England

[5] Univ Goteborg, Sahlgrenska Univ Hosp, Molndal, Sweden

[6] VA Med Ctr, Seattle, WA USA

[7] Sun Hlth Res Inst, Cleo Roberts Ctr Clin Res, Sun City, AZ USA

[8] Columbia Univ, New York, NY USA

[9] Baylor Coll Med, Houston, TX 77030 USA

[10] Yale Univ, Sch Med, New Haven, CT USA

[11] Univ Calif Irvine, Irvine, CA USA

[12] Calif Pacific Med Ctr, San Francisco, CA USA

[13] Elan Pharmaceut, San Francisco, CA USA

[14] Wyeth Ayerst Res, Collegeville, PA USA

来源：

NEUROLOGY | 2009年 / 73卷 / 24期

关键词：

REVERSIBLE ENCEPHALOPATHY SYNDROME; CEREBRAL AMYLOID ANGIOPATHY; CEREBROSPINAL-FLUID; CLINICAL-TRIALS; BETA-PEPTIDE; RATING-SCALE; MOUSE MODEL; IMMUNIZATION; PROTEIN; SAFETY;

D O I：

10.1212/WNL.0b013e3181c67808

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background: Bapineuzumab, a humanized anti-amyloid-beta (A beta) 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 epsilon 4 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 epsilon 4 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 epsilon 4 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. Neurology (R) 2009; 73: 2061-2070

引用

页码：2061 / 2070

页数：10

共 34 条

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