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

doi:10.1016/j.jhep.2006.08.019

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 journal › Article › peer-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 language	English
Pages (from-to)	37-44
Number of pages	8
Journal	Journal of Hepatology
Volume	46
Issue number	1
DOIs	https://doi.org/10.1016/j.jhep.2006.08.019
State	Published - Jan 2007
Externally published	Yes

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.jhep.2006.08.019

Cite this

Galun, E., Terrault, N. A., Eren, R., Zauberman, A., Nussbaum, O., Terkieltaub, D., Zohar, M., Buchnik, R., Ackerman, Z., Safadi, R., Ashur, Y., Misrachi, S., Liberman, Y., Rivkin, L., & Dagan, S. (2007). Clinical evaluation (Phase I) of a human monoclonal antibody against hepatitis C virus: Safety and antiviral activity. Journal of Hepatology, 46(1), 37-44. https://doi.org/10.1016/j.jhep.2006.08.019

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title = "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 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.",

keywords = "HCV neutralizing antibodies, HCV prevention, HCV viral load, Immunotherapy, Liver transplantation",

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

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.",

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month = jan,

doi = "10.1016/j.jhep.2006.08.019",

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Galun, E, Terrault, NA, Eren, R, Zauberman, A, Nussbaum, O, Terkieltaub, D, Zohar, M, Buchnik, R, Ackerman, Z, Safadi, R, Ashur, Y, Misrachi, S, Liberman, Y, Rivkin, L & Dagan, S 2007, 'Clinical evaluation (Phase I) of a human monoclonal antibody against hepatitis C virus: Safety and antiviral activity', Journal of Hepatology, vol. 46, no. 1, pp. 37-44. https://doi.org/10.1016/j.jhep.2006.08.019

TY - JOUR

T1 - Clinical evaluation (Phase I) of a human monoclonal antibody against hepatitis C virus

T2 - Safety and antiviral activity

AU - Galun, Eithan

AU - Terrault, Norah A.

AU - Eren, Rachel

AU - Zauberman, Arie

AU - Nussbaum, Ofer

AU - Terkieltaub, Dov

AU - Zohar, Meirav

AU - Buchnik, Rachel

AU - Ackerman, Zvi

AU - Safadi, Rifaat

AU - Ashur, Yaffa

AU - Misrachi, Sara

AU - Liberman, Yael

AU - Rivkin, Ludmila

AU - Dagan, Shlomo

N1 - 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.

PY - 2007/1

Y1 - 2007/1

N2 - 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.

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KW - HCV prevention

KW - HCV viral load

KW - Immunotherapy

KW - Liver transplantation

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

Abstract

Bibliographical note

Keywords

UN SDGs

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