The pharmacokinetics, antigenicity, and fusion-inhibition activity of RSHZ19, a humanized monoclonal antibody to respiratory syncytial virus, in healthy volunteers

J Infect Dis. 1996 Sep;174(3):463-9. doi: 10.1093/infdis/174.3.463.

Abstract

Single ascending doses of RSHZ19 (also known as SB 209763), a humanized monoclonal antibody (MAb) directed to the fusion protein of respiratory syncytial virus, were administered to healthy men to evaluate the safety, pharmacokinetics, antigenicity, and fusion inhibition (FI) activity of RSHZ19. Doses of RSHZ19 (0.025-10.0 mg/kg) or placebo were infused over 30 min, and subjects were followed for 10 weeks. Plasma concentrations of RSHZ19 and RSHZ19-specific antibodies were determined by ELISAs. FI titers were used to evaluate the ability of plasma to inhibit virus-induced fusion of VERO cells previously infected with RS Long strain virus. Twenty-six subjects, mean age 24, completed the study. RSHZ19 was safe and well tolerated, and no subject developed antibodies to RSHZ19 during follow-up. RSHZ19 had low plasma clearance and a half-life of approximately 23 days, similar to native IgG. Increases in FI titers relative to pretreatment levels were seen 24 h after MAb administration in all 4 subjects given 10 mg/kg and in 2 of 4 given 5 mg/kg.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Viral / analysis*
  • Antibodies, Viral / blood
  • Humans
  • Male
  • Middle Aged
  • Placebos
  • Respiratory Syncytial Virus Infections / immunology
  • Respiratory Syncytial Virus Infections / therapy
  • Respiratory Syncytial Viruses / immunology*
  • Single-Blind Method
  • Viral Fusion Proteins / immunology

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Viral
  • Placebos
  • RSHZ19 monoclonal antibody
  • Viral Fusion Proteins