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

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.).

Figures

Fig 1

Disposition of subjects in the four treatment cohorts.

Fig 2

Dose proportionality of mota-YTE and motavizumab maximum concentration and area under the curve.

Fig 3

Means (± standard deviations) of mota-YTE and motavizumab serum concentrations after a single dose. d, days.

Fig 4

(A) Predose baseline anti-RSV neutralizing antibody titers. (B) Postdose anti-RSV neutralizing activity of mota-YTE and motavizumab. EC50, half-maximal effective concentration. aSpiked concentrations were derived by protein quantification normalized to dilution.