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Clinical evaluation (phase I) of a combination of two human monoclonal antibodies to HBV: Safety and antiviral properties
Author(s) -
Galun Eithan,
Eren Rachel,
Safadi Rifaat,
Ashour Yaffa,
Terrault Norah,
Keeffe Emmet B.,
Matot Edith,
Mizrachi Sara,
Terkieltaub Dov,
Zohar Merav,
Lubin Ido,
Gopher Judith,
Shouval Daniel,
Dagan Shlomo
Publication year - 2002
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1053/jhep.2002.31867
Subject(s) - hbsag , medicine , lamivudine , hepatitis b virus , tolerability , monoclonal antibody , virology , antibody , hepatitis b , epitope , immunology , titer , virus , adverse effect
Treatment of chronic hepatitis B virus (HBV) infection with interferon alfa and lamivudine is characterized by lack of viral clearance, loss of response, or emergence of drug‐resistant mutants. Thus, new and multiple drug approaches are needed. We have developed two fully human monoclonal antibodies, directed against different epitopes of hepatitis B surface antigen (HBsAg) that bind to all major HBV subtypes. A phase I clinical study was conducted to evaluate the safety, tolerability, and efficacy of a mixture of these two monoclonal antibodies, HBV‐AB XTL . A total of 27 chronic HBV patients were enrolled. In part A of the study 15 patients in 5 cohorts received a single intravenous infusion of antibodies with doses ranging from 0.26 mg (260 IU) to 40 mg (40,000 IU). All patients completed 16 weeks of follow‐up. In the second part of the study (part B), 12 patients in 4 cohorts received 4 weekly infusions of 10, 20, 40, or 80 mg each of HBV‐AB XTL and were followed for 4 additional weeks. Administration of antibodies was well tolerated. Patients administered doses at an Ab:Ag molar ratio of 1:2 to 1:20 showed a rapid and significant decrease in HBsAg to undetectable levels, with a corresponding reduction of HBV‐DNA levels. In part B, HBV‐AB XTL induced a significant reduction in both HBsAg and HBV‐DNA levels repeatedly after administration. In conclusion, these data suggest that HBV‐AB XTL binds HBV particles and reduces serum viral titers and HBsAg levels. HBV‐AB XTL could be combined with other monotherapies that are currently used to treat HBV carriers. (H EPATOLOGY 2002;35:673‐679.)