Clinical evaluation (phase I) of a combination of two human monoclonal antibodies to HBV: Safety and antiviral properties

Eithan Galun, Rachel Eren, Rifaat Safadi, Yaffa Ashour, Norah Terrault, Emmet B. Keeffe, Edith Matot, Sara Mizrachi, Dov Terkieltaub, Merav Zohar, Ido Lubin, Judith Gopher, Daniel Shouval, Shlomo Dagan

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

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-ABXTL. 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-ABXTL 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-ABXTL induced a significant reduction in both HBsAg and HBV-DNA levels repeatedly after administration. In conclusion, these data suggest that HBV-ABXTL binds HBV particles and reduces serum viral titers and HBsAg levels. HBV-ABXTL could be combined with other monotherapies that are currently used to treat HBV carriers.

Original languageAmerican English
Pages (from-to)673-679
Number of pages7
JournalHepatology
Volume35
Issue number3
DOIs
StatePublished - 2002
Externally publishedYes

Bibliographical note

Funding Information:
Abbreviations: HBV, hepatitis B virus; HBsAg, hepatitis B virus surface antigen; HBIG, hepatitis B immunoglobulin; mAb, monoclonal antibody. From the 1Goldyne Savad Institute of Gene Therapy, Hadassah University Hospital; 2XTL Biopharmaceuticals Ltd., Rehovot; 3Liver Unit, Hadassah University Hospital, Jerusalem, Israel; 4University of California at San Francisco, San Francisco, CA, and 5Stanford University Medical Center, Stanford, CA. Received August 1, 2001; accepted December 21, 2001. These studies were carried out in part in the General Clinical Research Center, Moffitt Hospital, University of California, San Francisco, with funds provided by the National Center for Research Resources, 5 M01RR-00079, U.S. Public Health Service. Address reprint requests to: Shlomo Dagan, Ph.D., XTL Biopharmaceuticals Ltd., P.O. Box 370, Kiryat Weizmann Science Park, Rehovot 76100, Israel. E-mail: sdagan@xtlbio.com; fax: (972) 8-9405017. Copyright © 2002 by the American Association for the Study of Liver Diseases. 0270-9139/02/3503-0024$35.00/0 doi:10.1053/jhep.2002.31867

Fingerprint

Dive into the research topics of 'Clinical evaluation (phase I) of a combination of two human monoclonal antibodies to HBV: Safety and antiviral properties'. Together they form a unique fingerprint.

Cite this