title: Efficacy of immunotherapy with TG4040, peg-interferon, and ribavirin in a Phase 2 study of patients with chronic HCV infection.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Internal Medicine, St. Louis University Liver Center, St. Louis, Missouri.
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Di Bisceglie
authors.affiliation: Department of Infectious Diseases, Medical University of Silesia, Chorzow, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Janczweska-Kazek
authors.affiliation: Pôle Hépato-Digestif, Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil, Strasbourg, France.
authors.forename: François
authors.initials: F
authors.lastname: Habersetzer
authors.affiliation: Department of Internal Medicine, Medical University of Silesia, Katowice, Poland.
authors.forename: Wlodzimierz
authors.initials: W
authors.lastname: Mazur
authors.affiliation: Institute of Gastroenterology and Hepatology, Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania.
authors.forename: Carol
authors.initials: C
authors.lastname: Stanciu
authors.affiliation: Foundation for the Study of Viral Hepatitis, Madrid, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Carreno
authors.affiliation: Internal Medicine Clinic, Colentina Clinical Hospital, Bucharest, Romania.
authors.forename: Coman
authors.initials: C
authors.lastname: Tanasescu
authors.affiliation: Department of Infectious Diseases and Hepatology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Robert
authors.initials: R
authors.lastname: Flisiak
authors.affiliation: 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.
authors.forename: Manuel
authors.initials: M
authors.lastname: Romero-Gomez
authors.affiliation: Department of Gastroenterology, Soroka Medical Center, Beersheba, Israel.
authors.forename: Alexander
authors.initials: A
authors.lastname: Fich
authors.affiliation: Transgene, Illkirch, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Bataille
authors.affiliation: Transgene, Illkirch, France.
authors.forename: Myew-Ling
authors.initials: ML
authors.lastname: Toh
authors.affiliation: Transgene, Illkirch, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Hennequi
authors.affiliation: Transgene, Illkirch, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Zerr
authors.affiliation: Transgene, Illkirch, France.
authors.forename: Géraldine
authors.initials: G
authors.lastname: Honnet
authors.affiliation: Transgene, Illkirch, France.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Inchauspé
authors.affiliation: Transgene, Illkirch, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Agathon
authors.affiliation: Transgene, Illkirch, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Limacher
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany. Electronic address: wedemeyer.heiner@mh-hannover.de.
authors.forename: Heiner
authors.initials: H
authors.lastname: Wedemeyer
mesh_terms: D000328:Adult; D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000378:metabolism; D000998:Antiviral Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects; D016898:Interferon-alpha / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D012254:Ribavirin / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D019444:Vaccines, DNA; D014765:Viral Vaccines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000998:Antiviral Agents; D016898:Interferon-alpha; C560489:MVA vaccine; D011994:Recombinant Proteins; D019444:Vaccines, DNA; D014765:Viral Vaccines; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a
keywords: ELISpot; Immune Response; SVR24; Vaccine