Posner MR, Cavacini LA, Gambertoglio J, Spino C, Wolfe E, Trapnell C, Ketter N, Hammer S, Samore M; National Conference on Human Retroviruses and Related Infections.
Program Abstr Second Natl Conf Hum Retrovir Relat Infect Natl Conf Hum Retrovir Relat Infect 2nd 1995 Wash DC. 1995 Jan 29-Feb 2; 150.
Harvard Medical School and School of Public Health, Boston, MA.
F105 is an IgGk, human monoclonal antibody reactive with the CD4 binding site of HIV-1 gp120. A Phase Ia study of immunotherapy with F105 was performed in HIV-1 seropositive, asymptomatic volunteers with CD4 counts greater than or equal to 500 and less than or equal to 200/mm3. F105 was given as a single, 1 hour, intravenous infusion. Recipients were monitored for safety and pharmacokinetics over a period of eight weeks. Four subjects, each, were treated at one of two doses, 100 or 500 mg/M2. F105 plasma levels were determined by means of a double anti-idiotype sandwich ELISA which is sensitive to 15 ng/ml. There were no clinical side effects or changes in biochemical tests among the eight volunteers. The first patient treated did not receive the full dose due to an administration error. Mean peak F105 plasma levels for 100 and 500 mg/M2 doses were 44+/-8 and 220+/-45 micrograms/ml, respectively. Mean plasma half life of F105 was 11.8+/-4.5 and 13.7+/-2.8 days, respectively, with a range of 8.7-18.6 days among the 8 volunteers. The volume of distribution was 110 ml/kg. With this small patient population there was no significant difference in pharmacokinetic parameters between the two dosage levels. At 500 mg/M2, plasma levels of F105 greater than or equal to 20 micrograms/ml were maintained for 21 days. We conclude that F105 can be given safely at a dose 500 mg/M2 and, based on in vitro data and theoretical models, sufficient quantities of plasma antibody are present to be effective. A Phase Ib multidose trial to test for efficacy and safety is planned.
Publication Types:
Keywords:
- Animals
- Antibodies, Monoclonal
- Antigens, CD4
- Binding Sites
- Clinical Trials as Topic
- Enzyme-Linked Immunosorbent Assay
- HIV-1
- Humans
- Immunotherapy
- In Vitro
- Safety
- immunology
- pharmacokinetics
Other ID:
UI: 102213495
From Meeting Abstracts