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Gastroenterology. 2014 Jul;147(1):119-131.e3. doi: 10.1053/j.gastro.2014.03.007. Epub 2014 Mar 18.

Efficacy of immunotherapy with TG4040, peg-interferon, and ribavirin in a Phase 2 study of patients with chronic HCV infection.

Author information

  • 1Department of Internal Medicine, St. Louis University Liver Center, St. Louis, Missouri.
  • 2Department of Infectious Diseases, Medical University of Silesia, Chorzow, Poland.
  • 3Pôle Hépato-Digestif, Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil, Strasbourg, France.
  • 4Department of Internal Medicine, Medical University of Silesia, Katowice, Poland.
  • 5Institute of Gastroenterology and Hepatology, Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania.
  • 6Foundation for the Study of Viral Hepatitis, Madrid, Spain.
  • 7Internal Medicine Clinic, Colentina Clinical Hospital, Bucharest, Romania.
  • 8Department of Infectious Diseases and Hepatology, Medical University of Bialystok, Bialystok, Poland.
  • 9Unit for the Clinical Management of Digestive Diseases and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Valme University Hospital, Sevilla, Spain.
  • 10Department of Gastroenterology, Soroka Medical Center, Beersheba, Israel.
  • 11Transgene, Illkirch, France.
  • 12Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany. Electronic address: wedemeyer.heiner@mh-hannover.de.

Abstract

BACKGROUND & AIMS:

TG4040 is a modified vaccinia Ankara (MVA) virus that expresses the hepatitis C virus (HCV) proteins NS3, NS4, and NS5B. We performed a phase II open-label study to determine the efficacy, safety, and immunotherapeutic properties of TG4040 in combination with pegylated interferon α-2a and ribavirin (PEG-IFNα/RBV) in patients with chronic HCV infection.

METHODS:

Treatment-naive patients with HCV genotype 1 infection were assigned randomly to 1 of the following groups: PEG-IFNα/RBV for 48 weeks (group A, n = 31), PEG-IFNα/RBV for 4 weeks followed by PEG-IFNα/RBV for 44 weeks with 6 injections of TG4040 (group B, n = 63), or TG4040 for 12 weeks (7 injections) followed by PEG-IFNα/RBV for 48 weeks with 6 injections of TG4040 (group C, n = 59). The primary end point was complete early virologic response (cEVR), defined as HCV-RNA level less than 10 IU/mL after 12 weeks of PEG-IFNα/RBV treatment.

RESULTS:

In group C, 64.2% of evaluable patients achieved cEVR, compared with 30.0% in group A and 45.9% in group B (P = .0003 for group C vs A). A higher percentage of patients achieved a sustained virologic response 24 weeks after therapy ended in group C (58.2%) than in groups A (48.4%) or B (50.8%). HCV- and MVA-specific T-cell responses were observed predominantly in group C. As expected, most patients given injections of TG4040 developed anti-MVA antibodies. The combination of TG4040 and PEG-IFNα/RBV was reasonably well tolerated. However, PEG-IFNα-associated thrombocytopenia developed in 3 patients who carried the class II HLA allele DRB01*04.

CONCLUSIONS:

A higher percentage of patients with chronic HCV infection who received immunotherapy with TG4040 followed by TG4040 and PEG-IFNα/RBV achieved a cEVR compared with patients who received only PEG-IFNα/RBV therapy. These findings show that immunotherapies that activate T cells are effective in patients with chronic HCV infection. ClinicalTrials.gov number, NCT01055821.

Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

KEYWORDS:

ELISpot; Immune Response; SVR24; Vaccine

PMID:
24657484
[PubMed - indexed for MEDLINE]
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