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A phase I trial with two human monoclonal antibodies (hMAb 2F5, 2G12) against HIV-1
Christine Armbruster1, Gabriela M Stiegler, Brigitta A Vcelar
12nd Medical Department/SMZ Baumgartner Höhe, University of Vienna, Austria.
Objective:
To study the safety, immunogenicity and pharmacokinetics of two intravenously administered human monoclonal antibodies (hMAb 2F5, 2G12) against HIV-1 in humans.
Design:
Open label clinical phase I trial.
Setting:
Primary institutional care.
Patients:
Seven HIV-1-infected healthy volunteers with > or = 500 x 10(6)CD4 cells/l and < or = 10,000 HIV-1 RNA copies/ml, not treated with highly active antiretroviral therapy (HAART), entered and finished the study.
Interventions:
and main outcome measures: Eight separate infusions of the hMAb were administered over a 4-week period (total dose 14 g). The safety was assessed by physical examination, blood chemistry, complete blood cell count and recording adverse events. 2F5 and 2G12 plasma levels were determined prior to and at the end of each infusion and during the follow-up period of 22 weeks.
Results:
No clinical or laboratory abnormalities were observed throughout the study. The median distribution half-life (t(1/2 alpha)) of 2F5 and 2G12 was 1.02 (range, 0.77-1.47) days and 2.49 (range, 0.92-4.59) days, respectively. The elimination half-life (t(1/2 beta)) was calculated to be 7.94 (range, 3.46-8.31) days for 2F5 and 16.48 (range, 12.84-24.85) days for 2G12. The median plasma concentration immediately after the first infusion was 216 microg/ml (range, 158-409 microg/ml) for 2F5 and 238 microg/ml (range, 197-402 microg/ml) for 2G12. Multiple infusions resulted in maximum plasma concentrations of 374 microg/ml (range, 304-700 microg/ml) and 605 microg/ml (range, 479-897 microg/ml) for 2F5 and 2G12, respectively.
Conclusions:
This study showed that the hMAb 2F5 and 2G12 are safe and well tolerated by HIV-1-infected subjects.