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Home > Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer's disease.

TitleTwo phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer's disease.
Publication TypeJournal Article
Year of Publication2014
AuthorsSalloway, S, Sperling, R, Fox, NC, Blennow, K, Klunk, W, Raskind, M, Sabbagh, M, Honig, LS, Porsteinsson, AP, Ferris, S, Reichert, M, Ketter, N, Nejadnik, B, Guenzler, V, Miloslavsky, M, Wang, D, Lu, Y, Lull, J, Tudor, ICristina, Liu, E, Grundman, M, Yuen, E, Black, R, H Brashear, R
Corporate AuthorsBapineuzumab 301 and 302 Clinical Trial Investigators
JournalN Engl J Med
Volume370
Issue4
Pagination322-33
Date Published2014 Jan 23
ISSN1533-4406
KeywordsAged, Aged, 80 and over, Alzheimer Disease, Amyloid beta-Peptides, Antibodies, Monoclonal, Humanized, Apolipoproteins E, Biomarkers, Brain, Cognition, Double-Blind Method, Edema, Female, Humans, Intention to Treat Analysis, Male, Middle Aged, Neuropsychological Tests, Phosphorylation, Positron-Emission Tomography, Severity of Illness Index, tau Proteins, Treatment Failure
Abstract

BACKGROUND: Bapineuzumab, a humanized anti-amyloid-beta monoclonal antibody, is in clinical development for the treatment of Alzheimer's disease.

METHODS: We conducted two double-blind, randomized, placebo-controlled, phase 3 trials involving patients with mild-to-moderate Alzheimer's disease--one involving 1121 carriers of the apolipoprotein E (APOE) ε4 allele and the other involving 1331 noncarriers. Bapineuzumab or placebo, with doses varying by study, was administered by intravenous infusion every 13 weeks for 78 weeks. The primary outcome measures were scores on the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog11, with scores ranging from 0 to 70 and higher scores indicating greater impairment) and the Disability Assessment for Dementia (DAD, with scores ranging from 0 to 100 and higher scores indicating less impairment). A total of 1090 carriers and 1114 noncarriers were included in the efficacy analysis. Secondary outcome measures included findings on positron-emission tomographic amyloid imaging with the use of Pittsburgh compound B (PIB-PET) and cerebrospinal fluid phosphorylated tau (phospho-tau) concentrations.

RESULTS: There were no significant between-group differences in the primary outcomes. At week 78, the between-group differences in the change from baseline in the ADAS-cog11 and DAD scores (bapineuzumab group minus placebo group) were -0.2 (P=0.80) and -1.2 (P=0.34), respectively, in the carrier study; the corresponding differences in the noncarrier study were -0.3 (P=0.64) and 2.8 (P=0.07) with the 0.5-mg-per-kilogram dose of bapineuzumab and 0.4 (P=0.62) and 0.9 (P=0.55) with the 1.0-mg-per-kilogram dose. The major safety finding was amyloid-related imaging abnormalities with edema among patients receiving bapineuzumab, which increased with bapineuzumab dose and APOE ε4 allele number and which led to discontinuation of the 2.0-mg-per-kilogram dose. Between-group differences were observed with respect to PIB-PET and cerebrospinal fluid phospho-tau concentrations in APOE ε4 allele carriers but not in noncarriers.

CONCLUSIONS: Bapineuzumab did not improve clinical outcomes in patients with Alzheimer's disease, despite treatment differences in biomarkers observed in APOE ε4 carriers. (Funded by Janssen Alzheimer Immunotherapy and Pfizer; Bapineuzumab 301 and 302 ClinicalTrials.gov numbers, NCT00575055 and NCT00574132, and EudraCT number, 2009-012748-17.).

DOI10.1056/NEJMoa1304839
Alternate JournalN. Engl. J. Med.
PubMed ID24450891
PubMed Central IDPMC4159618
Grant ListK24 AG035007 / AG / NIA NIH HHS / United States
MR/K013041/1 / / Medical Research Council / United Kingdom
P30 AG008051 / AG / NIA NIH HHS / United States
P50 AG005134 / AG / NIA NIH HHS / United States
P50 AG005136 / AG / NIA NIH HHS / United States
P50 AG008702 / AG / NIA NIH HHS / United States
R01 NS080820 / NS / NINDS NIH HHS / United States
Top50 Topics: 
Biomarkers, Clinical Trials
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Source URL: https://www.j-alz.com/content/two-phase-3-trials-bapineuzumab-mild-moderate-alzheimers-disease