Efficacy of Immunotherapy With TG4040, Peg-Interferon, and Ribavirin in a Phase 2 Study of Patients With Chronic HCV Infection

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 interfer...

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Published in:	Gastroenterology (New York, N.Y. 1943) Vol. 147; no. 1; pp. 119 - 131.e3
Main Authors:	Di Bisceglie, Adrian M, Janczweska–Kazek, Ewa, Habersetzer, François, Mazur, Wlodzimierz, Stanciu, Carol, Carreno, Vicente, Tanasescu, Coman, Flisiak, Robert, Romero–Gomez, Manuel, Fich, Alexander, Bataille, Vincent, Toh, Myew–Ling, Hennequi, Marie, Zerr, Patricia, Honnet, Géraldine, Inchauspé, Geneviève, Agathon, Delphine, Limacher, Jean–Marc, Wedemeyer, Heiner
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-07-2014 Elsevier
Subjects:	Adult Aged Antibodies, Anti-Idiotypic - metabolism Antiviral Agents - adverse effects Antiviral Agents - pharmacology Antiviral Agents - therapeutic use Drug Therapy, Combination ELISpot Female Gastroenterology and Hepatology Genotype Hepacivirus - drug effects Hepatitis C, Chronic - drug therapy Hepatitis C, Chronic - genetics Hepatitis C, Chronic - immunology Human health and pathology Humans Immune Response Immunotherapy - adverse effects Interferon-alpha - adverse effects Interferon-alpha - pharmacology Interferon-alpha - therapeutic use Life Sciences Male Middle Aged Polyethylene Glycols - adverse effects Polyethylene Glycols - pharmacology Polyethylene Glycols - therapeutic use Recombinant Proteins - adverse effects Recombinant Proteins - pharmacology Recombinant Proteins - therapeutic use Ribavirin - adverse effects Ribavirin - pharmacology Ribavirin - therapeutic use SVR24 Treatment Outcome Vaccine Viral Vaccines - adverse effects Viral Vaccines - pharmacology Viral Vaccines - therapeutic use ETR ITT intent-to-treat PEG-IFNα ELISpot SVR cEVR serious adverse event hepatitis C virus complete early virologic response sustained virologic response LOD ribavirin AE Immune Response RBV SVR24 adverse event Vaccine limit of detection PBMC modified vaccinia Ankara end of treatment SAE MVA HCV pegylated interferon alpha-2a peripheral blood mononuclear cell
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Summary:	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.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 ObjectType-News-3 content type line 23
ISSN:	0016-5085 1528-0012
DOI:	10.1053/j.gastro.2014.03.007