Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Gastroenterology (New York, N.Y. 1943), 2014-07, Vol.147 (1), p.119-131.e3

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2014

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.