Clinical evaluation (Phase I) of a human monoclonal antibody against hepatitis C virus: Safety and antiviral activity

Eithan Galun, Norah A. Terrault, Rachel Eren, Arie Zauberman, Ofer Nussbaum, Dov Terkieltaub, Meirav Zohar, Rachel Buchnik, Zvi Ackerman, Rifaat Safadi, Yaffa Ashur, Sara Misrachi, Yael Liberman, Ludmila Rivkin, Shlomo Dagan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Background/Aims: HCV-AB68, a human monoclonal antibody against the envelope protein of hepatitis C virus (HCV), neutralizes HCV in cell-culture and in the HCV-Trimera mouse model. A Phase 1 clinical trial was designed to test safety, tolerability, and antiviral activity of HCV-AB68 in patients with chronic HCV-infection. Methods/Results: Single doses of HCV-AB68, 0.25-40 mg, administered to 15 patients were well tolerated with no moderate or serious adverse events (SAEs) reported. In six patients, HCV-RNA levels transiently decreased by 2- to 100-fold immediately following infusion and rebound to baseline in 24-48 h. Multiple doses of HCV-AB68, 10-120 mg, were administered to 25 patients. Doses were given weekly for 3 weeks, then 3× a week during the fourth week, after which patients were followed for 3 months. No drug-related SAEs were reported and no specific pattern of adverse events was evident. Eight out of 25 patients had at least a 1-log reduction and 17 had at least a 0.75-log reduction in HCV-RNA levels from baseline at one or more time points following HCV-AB68 infusion. Conclusions: These data support the investigation of HCV-AB68 in the prevention of recurrent HCV-infection in patients who had received hepatic allografts for end-stage liver disease.

Original languageAmerican English
Pages (from-to)37-44
Number of pages8
JournalJournal of Hepatology
Volume46
Issue number1
DOIs
StatePublished - Jan 2007
Externally publishedYes

Bibliographical note

Funding Information:
This work was also supported by the Israeli Ministry of Science, through a grant from the National Gene Therapy Knowledge Center and through Grants LSHB-CT-2004-512034 (MOLEDA) and LSHB-CT-2005-018961 (INTHER). Further support was received through grants from the Blum, the Harold Grinspoon, the Horowitz and the Wolfson Foundations.

Keywords

  • HCV neutralizing antibodies
  • HCV prevention
  • HCV viral load
  • Immunotherapy
  • Liver transplantation

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