Vaniprevir plus peginterferon alfa-2b and ribavirin in treatment-naive Japanese patients with hepatitis C virus genotype 1 infection: a randomized phase III study

Norio Hayashi, Makoto Nakamuta, Tetsuo Takehara, Hiromitsu Kumada, Akiko Takase, Anita Yee Mei Howe, Steven W Ludmerer, Niloufar Mobashery, Norio Hayashi, Makoto Nakamuta, Tetsuo Takehara, Hiromitsu Kumada, Akiko Takase, Anita Yee Mei Howe, Steven W Ludmerer, Niloufar Mobashery

Abstract

Background: Vaniprevir is a potent macrocyclic hepatitis C virus (HCV) nonstructural protein 3/4A protease inhibitor. This phase III study evaluated the safety and efficacy of vaniprevir in combination with peginterferon alfa-2b and ribavirin (PR) for 24 weeks compared with PR alone for 48 weeks in treatment-naive Japanese patients with HCV genotype 1 infection.

Methods: Treatment-naive Japanese patients with HCV genotype 1 infection were randomly assigned to receive vaniprevir (300 mg twice daily) plus PR for 12 weeks then PR alone for 12 weeks, vaniprevir (300 mg twice daily) plus PR for 24 weeks, or PR alone for 48 weeks. The primary end point was sustained virologic response 24 weeks after completion of treatment (SVR24).

Results: In total, 294 patients were randomly assigned to receive treatment. Most patients had HCV genotype 1b infection (98 %, 288 of 294 patients). SVR24 was achieved in 83.7, 84.5, and 55.1 % of the patients in the vaniprevir 12-week, vaniprevir 24-week, and control arms, respectively. The difference in SVR24 rates between each vaniprevir arm and the control arm was statistically significant (p < 0.001 for both). Relapse was commoner in the control arm (29.5 %) than in the vaniprevir arms (8.6 % and 10.5 % for the 12-week and 24-week arms, respectively). Commonly reported adverse events were generally similar across treatment arms, with the exception of an increase in the incidence of gastrointestinal adverse events such as nausea, diarrhea, and vomiting in patients receiving vaniprevir. These events were considered manageable.

Conclusion: Vaniprevir is a valuable addition to the therapeutic options available to Japanese patients with HCV genotype 1 infection who are eligible for interferon-based treatment. CLINICALTRIALS.

Gov identifier: NCT01370642.

Keywords: Hepatitis C virus; Japan; Peginterferon; Ribavirin; Vaniprevir.

Figures

Fig. 1
Fig. 1
Study disposition. HCV hepatitis C virus

References

    1. Chung H, Ueda T, Kudo M. Changing trends in hepatitis C infection over the past 50 years in Japan. Intervirology. 2010;53(1):39–43. doi: 10.1159/000252782.
    1. American Association for the Study of Liver Diseases, Infectious Diseases Society of America. Recommendations for testing, managing, and treating hepatitis C. (2014). Accessed 26 May 2015.
    1. European Association for the Study of the Liver EASL clinical practice guidelines: management of hepatitis C virus infection. J Hepatol. 2014;60(2):392–420. doi: 10.1016/j.jhep.2013.11.003.
    1. Lemoine M, Thursz M. Hepatitis C, a global issue: access to care and new therapeutic and preventive approaches in resource-constrained areas. Semin Liver Dis. 2014;34(1):89–97. doi: 10.1055/s-0034-1371082.
    1. Hayashi N, Izumi N, Kumada H, et al. Simeprevir with peginterferon/ribavirin for treatment-naive hepatitis C genotype 1 patients in Japan: CONCERTO-1, a phase III trial. J Hepatol. 2014;61(2):219–227. doi: 10.1016/j.jhep.2014.04.004.
    1. Kumada H, Toyota J, Okanoue T, et al. Telaprevir with peginterferon and ribavirin for treatment-naive patients chronically infected with HCV of genotype 1 in Japan. J Hepatol. 2012;56(1):78–84. doi: 10.1016/j.jhep.2011.07.016.
    1. Hayashi N, Seto C, Kato M, et al. Once-daily simeprevir (TMC435) with peginterferon/ribavirin for treatment-naive hepatitis C genotype 1-infected patients in Japan: the DRAGON study. J Gastroenterol. 2014;49(1):138–147. doi: 10.1007/s00535-013-0875-1.
    1. Editors of the Drafting Committee for Hepatitis Management Guidelines: the Japan Society of Hepatology Guidelines for the management of hepatitis C virus infection: first edition, May 2012, the Japan Society of Hepatology. Hepatol Res. 2013;43(1):1–34. doi: 10.1111/hepr.12020.
    1. Drafting Committee for Hepatitis Management Guidelines, the Japan Society of Hepatology JSH guidelines for the management of hepatitis C virus infection: a 2014 update for genotype 1. Hepatol Res. 2014;44(Suppl S1):59–70. doi: 10.1111/hepr.12272.
    1. Kumada H, Suzuki Y, Ikeda K, et al. Daclatasvir plus asunaprevir for chronic HCV genotype 1b infection. Hepatology. 2014;59(6):2083–2091. doi: 10.1002/hep.27113.
    1. McCauley JA, McIntyre CJ, Rudd MT, et al. Discovery of vaniprevir (MK-7009), a macrocyclic hepatitis C virus NS3/4a protease inhibitor. J Med Chem. 2010;53(6):2443–2463. doi: 10.1021/jm9015526.
    1. Liverton NJ, Carroll SS, Dimuzio J, et al. MK-7009, a potent and selective inhibitor of hepatitis C virus NS3/4A protease. Antimicrob Agents Chemother. 2010;54(1):305–311. doi: 10.1128/AAC.00677-09.
    1. Olsen DB, Davies ME, Handt L, et al. Sustained viral response in a hepatitis C virus-infected chimpanzee via a combination of direct-acting antiviral agents. Antimicrob Agents Chemother. 2011;55(2):937–939. doi: 10.1128/AAC.00990-10.
    1. Manns MP, Gane E, Rodriguez-Torres M, et al. Vaniprevir with peginterferon alfa-2a and ribavirin in treatment-naive patients with chronic hepatitis C: a randomized phase 2 study. Hepatology. 2012;56(3):884–893. doi: 10.1002/hep.25743.
    1. Lawitz E, Rodriguez-Torres M, Stoehr A, et al. A phase 2B study of MK-7009 (vaniprevir) in patients with genotype 1 HCV infection who have failed previous pegylated interferon and ribavirin treatment. J Hepatol. 2013;59(1):11–17. doi: 10.1016/j.jhep.2013.02.008.
    1. Rodriguez-Torres M, Stoehr A, Gane EJ, et al. Combination of vaniprevir with peginterferon and ribavirin significantly increases the rate of sustained viral response in treatment-experienced patients with chronic HCV genotype 1 infection and cirrhosis. Clin Gastroenterol Hepatol. 2014;12(6):1029–1037. doi: 10.1016/j.cgh.2013.09.067.
    1. Hayashi N, Mobashery N, Izumi N. Vaniprevir plus peginterferon alfa-2a and ribavirin in treatment-experienced Japanese patients with hepatitis C virus genotype 1 infection: a randomized phase II study. J Gastroenterol. 2015;50(2):238–248. doi: 10.1007/s00535-014-0979-2.
    1. Miettinen O, Nurminen M. Comparative analysis of two rates. Stat Med. 1985;4(2):213–226. doi: 10.1002/sim.4780040211.
    1. Ito K, Higami K, Masaki N, et al. The rs8099917 polymorphism, when determined by a suitable genotyping method, is a better predictor for response to pegylated alpha interferon/ribavirin therapy in Japanese patients than other single nucleotide polymorphisms associated with interleukin-28B. J Clin Microbiol. 2011;49:1853–1860. doi: 10.1128/JCM.02139-10.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi