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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

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

KEYWORDS:

ELISpot; Immune Response; SVR24; Vaccine

PMID:
24657484
DOI:
10.1053/j.gastro.2014.03.007
[Indexed for MEDLINE]

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