Efficacy of immunotherapy with TG4040, peg-interferon, and ribavirin in a Phase 2 study of patients with chronic HCV infection.
Fiche publication
Date publication
juillet 2014
Auteurs
Membres identifiés du Cancéropôle Est :
Dr HABERSETZER François, Dr LIMACHER Jean-Marc
Tous les auteurs :
Di Bisceglie AM, Janczweska-Kazek E, Habersetzer F, Mazur W, Stanciu C, Carreno V, Tanasescu C, Flisiak R, Romero-Gomez M, Fich A, Bataille V, Toh ML, Hennequi M, Zerr P, Honnet G, Inchauspe G, Agathon D, Limacher JM, Wedemeyer H
Lien Pubmed
Résumé
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 alpha-2a and ribavirin (PEG-IFNalpha/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-IFNalpha/RBV for 48 weeks (group A, n = 31), PEG-IFNalpha/RBV for 4 weeks followed by PEG-IFNalpha/RBV for 44 weeks with 6 injections of TG4040 (group B, n = 63), or TG4040 for 12 weeks (7 injections) followed by PEG-IFNalpha/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-IFNalpha/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-IFNalpha/RBV was reasonably well tolerated. However, PEG-IFNalpha-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-IFNalpha/RBV achieved a cEVR compared with patients who received only PEG-IFNalpha/RBV therapy. These findings show that immunotherapies that activate T cells are effective in patients with chronic HCV infection. ClinicalTrials.gov number, NCT01055821.
Référence
Gastroenterology. 2014 Jul;147(1):119-131.e3