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

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 3x 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.

• Authors: 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
• Journal: Journal of hepatology (J Hepatol) Vol. 46 Issue 1 Pg. 37-44 (Jan 2007) ISSN: 0168-8278 [Print] Netherlands
• PMID: 17112624 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antiviral Agents
• DNA Primers
• Hepatitis C Antibodies
• RNA, Viral

Topics

• Adolescent
• Adult
• Aged
• Animals
• Antibodies, Monoclonal (adverse effects, therapeutic use)
• Antiviral Agents (adverse effects, therapeutic use)
• Base Sequence
• DNA Primers (genetics)
• Drug Tolerance
• Female
• Hepacivirus (genetics, immunology)
• Hepatitis C Antibodies (adverse effects, therapeutic use)
• Hepatitis C, Chronic (therapy, virology)
• Humans
• Male
• Mice
• Middle Aged
• RNA, Viral (blood, genetics)
• Safety