A PHASE I/IIA CLINICAL-STUDY WITH A CHIMERIC MOUSE-HUMAN MONOCLONAL-ANTIBODY TO THE V3 LOOP OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GP120

A phase I/IIA clinical trial with the chimeric mouse-human monoclonal antibody CGP 47 439 to the principal neutralization determinant in the V3 region of human immunodeficiency virus type 1 (HIV-1) strain IIIB envelope protein gp120 is reported. The trial was an uncontrolled single-center, open-label, multidose tolerability, immunogenicity, and pharmacokinetic study in homosexual men with advanced HIV disease. Patient groups were formed on the basis of the reactivity of the antibody with the gp120 of their HIV-1 isolates. Intravenous infusions of 1, 10, acid 25 mg of antibody were followed by seven escalated doses of 50, 100, and 200 mg, every 3 weeks. The antibody was well tolerated; no toxicity was observed. Some patients showed a transient but insignificant antibody response to the antibody with no apparent adverse reactions or accelerated elimination of it. Substantial serum levels of the antibody were maintained with a mean t(1/2)beta of 8-16 days. A virus burden reduction was observed in some patients.