Daclatasvir combined with peginterferon alfa-2a and ribavirin in Japanese patients infected with hepatitis C genotype 1

作者：Izumi Namiki^*; Yokosuka Osamu; Kawada Norifumi; Osaki Yukio; Yamamoto Kazuhide; Sata Michio; Ishikawa Hiroki; Ueki Tomoko; Hu Wenhua; McPhee Fiona; Hughes Eric A; Kumada Hiromitsu

来源：Antiviral Therapy, 2014, 19(5): 501-510.

DOI：10.3851/IMP2731

Background: New direct-acting antiviral agents are currently being developed to treat chronic HCV. The efficacy and safety of daclatasvir combined with peginterferon alfa-2a (alfa-2a) and ribavirin were assessed in a randomized, double-blind Phase IIa study of Japanese patients with chronic HCV genotype-1 infection. %26lt;br%26gt;Methods: Japanese patients who were treatment-naive (n=25) or prior null (n=12) or partial (n=5) responders received once-daily daclatasvir 10 mg or 60 mg or placebo in combination with alfa-2a and ribavirin. Daclatasvir recipients with a protocol-defined response (HCV RNA%26lt;15 IU/ml at week 4 and undetectable at week 12) were treated for 24 weeks; placebo recipients and patients without a protocol-defined response were treated for 48 weeks. %26lt;br%26gt;Results: Sustained virological response at 24 weeks post-treatment (SVR24) was achieved by 89% and 100% of treatment-naive patients receiving daclatasvir 10 mg and 60 mg, respectively, versus 75% in placebo recipients. Virological failure was more frequent in prior non-responder patients, with 50% and 78% achieving SVR24 in daclatasvir 10 mg and 60 mg groups, respectively. Adverse events occurred with similar frequency among treatment groups and were consistent with the adverse event profile of alfa-2a/ribavirin alone. The most commonly reported adverse events included pyrexia, alopecia, anaemia, lymphopenia, neutropenia, pruritus and diarrhoea. Three patients discontinued treatment due to anaemia. %26lt;br%26gt;Conclusions: Daclatasvir combined with alfa-2a/ribavirin in treatment-naive patients showed greater efficacy than alfa-2a/ribavirin alone and was generally well tolerated. The 60-mg dose of daclatasvir achieved the highest rates of SVR24 in both treatment-naive and non-responder populations and will be evaluated in a Phase III clinical trial.

• 出版日期2014