TY - JOUR
T1 - Efficacy of immunotherapy with TG4040, peg-interferon, and ribavirin in a phase 2 study of patients with chronic HCV infection
AU - Di Bisceglie, Adrian M.
AU - Janczweska-Kazek, Ewa
AU - Habersetzer, François
AU - Mazur, Wlodzimierz
AU - Stanciu, Carol
AU - Carreno, Vicente
AU - Tanasescu, Coman
AU - Flisiak, Robert
AU - Romero-Gomez, Manuel
AU - Fich, Alexander
AU - Bataille, Vincent
AU - Toh, Myew Ling
AU - Hennequi, Marie
AU - Zerr, Patricia
AU - Honnet, Géraldine
AU - Inchauspé, Geneviève
AU - Agathon, Delphine
AU - Limacher, Jean Marc
AU - Wedemeyer, Heiner
PY - 2014/1/1
Y1 - 2014/1/1
N2 - 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.
AB - 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.
KW - ELISpot
KW - Immune Response
KW - SVR24
KW - Vaccine
UR - http://www.scopus.com/inward/record.url?scp=84902991292&partnerID=8YFLogxK
U2 - 10.1053/j.gastro.2014.03.007
DO - 10.1053/j.gastro.2014.03.007
M3 - Article
C2 - 24657484
AN - SCOPUS:84902991292
SN - 0016-5085
VL - 147
SP - 119-131.e3
JO - Gastroenterology
JF - Gastroenterology
IS - 1
ER -
