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

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• 作者：Adrian M. Di Bisceglie¹ ; Ewa Janczweska&ndash ; Kazek² ; Franç ; ois Habersetzer³ ; Wlodzimierz Mazur⁴ ; Carol Stanciu⁵ ; Vicente Carreno⁶ ; Coman Tanasescu⁷ ; Robert Flisiak⁸ ; Manuel Romero&ndash ; Gomez⁹ ; Alexander Fich¹⁰ ; Vincent Bataille¹¹ ; Myew&ndash ; Ling Toh¹¹ ; Marie Hennequi¹¹ ; Patricia Zerr¹¹ ; Gé ; raldine Honnet¹¹ ; Geneviè ; ve Inchauspé ; ¹¹ ; Delphine Agathon¹¹ ; Jean&ndash ; Marc Limacher¹¹ ; Heiner Wedemeyer¹² ; ^{wedemeyer.heiner@mh-hannover.de" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Vaccine ; ELISpot ; Immune Response ; SVR24
• 刊名：Gastroenterology
• 出版年：2014
• 出版时间：July 2014
• 年：2014
• 卷：147
• 期：1
• 页码：119-131.e3
• 全文大小：2675 K

文摘

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.