A single ascending dose study of bapineuzumab in patients with Alzheimer disease

Alzheimer Dis Assoc Disord. 2010 Apr-Jun;24(2):198-203. doi: 10.1097/WAD.0b013e3181c53b00.

Abstract

The safety, tolerability, and pharmacokinetics (PKs) of bapineuzumab (AAB-001), a humanized monoclonal antibody to amyloid beta, were evaluated in patients with mild-to-moderate Alzheimer disease in a phase 1, randomized, third-party unblinded, placebo-controlled, single ascending dose trial. Thirty patients received bapineuzumab infusion of 0.5, 1.5, or 5 mg/kg or placebo (6 active, 2 placebo for 0.5 and 1.5-mg/kg cohorts; 10 active, 4 placebo for 5.0-mg/kg cohort). Three patients in the highest dose cohort (5.0 mg/kg) developed magnetic resonance imaging abnormalities consistent with vasogenic edema, predominantly high signal abnormalities on fluid-attenuated inversion recovery sequences, all of which resolved over time. Plasma amyloid beta was elevated from baseline, peaking approximately 24 hours after infusion. PK analysis demonstrated a half-life of 21 to 26 days, supporting a 13-week dosing interval for bapineuzumab. This small, single-dose study demonstrated the safety profile and PK characteristics of bapineuzumab and was used to design later safety and efficacy trials.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / immunology*
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal, Humanized
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Nootropic Agents / administration & dosage*
  • Nootropic Agents / adverse effects

Substances

  • Amyloid beta-Peptides
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Nootropic Agents
  • bapineuzumab