Study assesses the subcutaneously administration of monoclonal antibodies VRC07-523LS and PGT121
The results of the CAPRISA 012A trial showed that monoclonal antibodies VRC07-523LS and PGT121 administered subcutaneously individually and in combination at high doses were safe and well tolerated.
The study, Safety and Pharmacokinetics of Monoclonal Antibodies VRC07-523LS and PGT121 Administered Subcutaneously for Human Immunodeficiency Virus Prevention, was published in the Journal of Infectious Diseases.
The study a randomised, double-blinded, placebo-controlled, dose-escalation phase 1 trial, assessed the safety, tolerability, pharmacokinetics, neutralization activity and anti-drug antibody levels of monoclonal antibodies VRC07-523LS and PGT121 in 45 HIV-negative women enrolled at the CAPRISA eThekwini Research clinic in Durban South Africa.
Pharmacokinetic modelling was conducted to predict steady-state concentrations for 16- and 24-weekly dosing intervals. Most common reactogenicity events were injection site tenderness and headaches. Nine product-related adverse events were mild and transient. Median VRC07-523LS concentrations following 20mg/kg doses were 9.65μg/ml and 3.86μg/ml at 16 and 24 weeks.
The median week 8 concentration following the 10mg/kg PGT121 dose was 8.26μg/ml. Modelling of PGT121 at 20mg/kg showed median concentrations of 1.37μg/ml and 0.22μg/ml at 16 and 24 weeks (Figure 1). Half-lives of VRC07-523LS and PGT121 were 29 and 20 days. The antibodies retained neutralizing activity post administration and no anti-drug antibodies were detected.
It showed that 24-week dosing of VRC07-523LS SC produced drug levels above the target concentration, while more frequent dosing is needed for PGT121.
Thanks to the VRC, IAVI and Dan Barouch for their collaboration in this study.
For further reading see: Mahomed S, et al. JID 2022. doi: 10.1093/infdis/jiac041. https://pubmed.ncbi.nlm.nih.gov/35134995/
Figure 1: A) Observed median VRC07-523LS concentrations following 5, 10 and 20mg/kg subcutaneous administrations in the CAPRISA 012A trial and median concentrations following 5mg/kg subcutaneous administration in the VRC605 clinical trial. B) Observed median PGT121 concentrations following 3 and 10mg/kg subcutaneous administrations in the CAPRISA 012A trial.