A novel investigational Fc-modified humanized monoclonal antibody, motavizumab-YTE, has an extended half-life in healthy adults

Antimicrob Agents Chemother. 2013 Dec;57(12):6147-53. doi: 10.1128/AAC.01285-13. Epub 2013 Sep 30.

Abstract

The study objective was to evaluate the pharmacokinetics (PK), antidrug antibody (ADA), and safety of motavizumab-YTE (motavizumab with amino acid substitutions M252Y/S254T/T256E [YTE]), an Fc-modified anti-respiratory syncytial virus (RSV) monoclonal antibody. Healthy adults (n = 31) were randomized to receive a single intravenous (i.v.) dose of motavizumab-YTE or motavizumab (0.3, 3, 15, or 30 mg/kg) and followed for 240 days. Clearance of motavizumab-YTE was significantly lower (71% to 86%) and the half-life (t1/2) was 2- to 4-fold longer than with motavizumab. However, similar peak concentrations and volume-of-distribution values, indicative of similar distribution properties, were seen at all dose levels. The sustained serum concentrations of motavizumab-YTE were fully functional, as shown by RSV neutralizing activity that persisted for 240 days with motavizumab-YTE versus 90 days postdose for motavizumab. Safety and incidence of ADA were comparable between groups. In this first study of an Fc-modified monoclonal antibody in humans, motavizumab-YTE was well tolerated and exhibited an extended half-life of up to 100 days. (This study has been registered at ClinicalTrials.gov under registration no. NCT00578682.).

Publication types

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

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Humanized / blood
  • Antibodies, Monoclonal, Humanized / pharmacokinetics*
  • Antiviral Agents / blood
  • Antiviral Agents / pharmacokinetics*
  • Double-Blind Method
  • Drugs, Investigational / pharmacokinetics*
  • Female
  • Half-Life
  • Humans
  • Immunoglobulin Fc Fragments / chemistry*
  • Injections, Intravenous
  • Male
  • Metabolic Clearance Rate

Substances

  • Antibodies, Monoclonal, Humanized
  • Antiviral Agents
  • Drugs, Investigational
  • Immunoglobulin Fc Fragments
  • motavizumab

Associated data

  • ClinicalTrials.gov/NCT00578682