title: Clinical evaluation (phase I) of a combination of two human monoclonal antibodies to HBV: safety and antiviral properties.
abstract: 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.
authors.affiliation: Goldyne Savad Institute of Gene Therapy, Hadassah University Hospital, Jerusalem, Israel.
authors.forename: Eithan
authors.initials: E
authors.lastname: Galun
authors.forename: Rachel
authors.initials: R
authors.lastname: Eren
authors.forename: Rifaat
authors.initials: R
authors.lastname: Safadi
authors.forename: Yaffa
authors.initials: Y
authors.lastname: Ashour
authors.forename: Norah
authors.initials: N
authors.lastname: Terrault
authors.forename: Emmet B
authors.initials: EB
authors.lastname: Keeffe
authors.forename: Edith
authors.initials: E
authors.lastname: Matot
authors.forename: Sara
authors.initials: S
authors.lastname: Mizrachi
authors.forename: Dov
authors.initials: D
authors.lastname: Terkieltaub
authors.forename: Merav
authors.initials: M
authors.lastname: Zohar
authors.forename: Ido
authors.initials: I
authors.lastname: Lubin
authors.forename: Judith
authors.initials: J
authors.lastname: Gopher
authors.forename: Daniel
authors.initials: D
authors.lastname: Shouval
authors.forename: Shlomo
authors.initials: S
authors.lastname: Dagan
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006510:Hepatitis B Antibodies / Q000008:administration & dosage*; D006514:Hepatitis B Surface Antigens / Q000032:analysis / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000628:therapy* / Q000821:virology; D006801:Humans; D007136:Immunoglobulins / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged
chemical_list: D000911:Antibodies, Monoclonal; D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D007136:Immunoglobulins; C045213:hepatitis B hyperimmune globulin