Was this posted before? Liver conference 4/2. Abstract accepted:
Poster Presentations
Session Title: Category 08d: Viral Hepatitis C: Clinical (new compounds, resistance)
Presentation Date: 02 APR, 2011
ESCALATING REPEAT-DOSE STUDY OF BAVITUXIMAB IN PATIENTS CO-INFECTED WITH CHRONIC HEPATITIS C VIRUS (HCV) AND HUMAN IMMUNODEFICIENCY VIRUS
J. Slim1, M.S. Sulkowski2*, J.S. Shan3
1Infectious Diseases, Saint Michael's Medical Center, Newark, NJ, 2Center for Viral Hepatitis, John's Hopkins University, Baltimore, MD, 3Peregrine Pharmaceuticals, Inc., Tustin, CA, USA. *msulkowski@jhmi.edu
Background: Bavituximab, an investigational monoclonal antibody, targets phosphatidylserine (PS) on the surface of virus infected cells and enveloped viruses. Preclinical models show PS-targeting antibodies to bind viral particles and infected cells, inhibit viral replication, and enhance innate immune reponses. In prior studies, single and twice weekly intravenous (IV) infusions up to 6 mg/kg were well-tolerated and showed transient antiviral activity in chronic HCV patients.
Methods: To determine the safety and tolerability and characterize the pharmacokinetics and viral kinetics of bavituximab, sequential cohorts of 6 patients were given up to 8 weekly 90 min IV infusions at 0.3, 1, 3 or 6 mg/kg and followed until week 12. Patients may be replaced if withdrawn prior to receiving 4 doses of study drug. Vital signs, physical exams, safety laboratory parameters, bavituximab levels, HCV and HIV viral titers and T-cell activation profiles were obtained.
Results: Twenty-three patients (13 female, mean age 47) have been enrolled to date. Mean baseline HCV viral load is 4,000,000 copies/mL (100 - 50,000,000) and 6,900 (150 - 280,000) copies/mL for HIV. The majority of patients (18/23) have genotype 1 HCV. Mean CD4 count at study entry is 490 cells/mm^3 (212 - 1239). One patient (0.3 mg/kg) experienced related non-serious grade 3 blurred vision, hypertension and cardiac arrhythmia during the 8th infusion, but extensive cardiac work-up was negative for evidence of thromboembolism. Three serious adverse events have been reported; grade 2 sinusitis (unrelated), grade 3 urticaria (related) and grade 3 hypersensitivity (related), all at the 3 mg/kg dose level. All other adverse events (AEs) were mild or moderate and transient. Preliminary data for the first 3 cohorts exhibit on therapy HIV and HCV antiviral activity (=0.5 log10 reduction) at all dose levels.
Conclusions: Up to 8 weekly IV doses of bavituximab have been generally well-tolerated to date in HCV/HIV co-infected individuals. No dose-related increase in incidence or severity of AEs are observed. Signs of antiviral activity have been observed at all dose levels analyzed. Enrollment is near completion and pharmacokinetic and T-cell activation data will be analyzed at the end of the study and correlated with antiviral response.
