A randomized trial of daclatasvir with peginterferon alfa-2b and ribavirin for
HCV genotype 1 infection.
Author(s): Suzuki F(1), Toyota J, Ikeda K, Chayama K, Mochida S, Hayashi N, Ishikawa H,
Miyagoshi H, Hu W, McPhee F, Hughes EA, Kumada H.
Affiliation(s): Author information:
(1)Toranomon Hospital, Tokyo, Japan. fumitakas@toranomon.gr.jp.
Publication date & source: 2014, Antivir Ther. , 19(5):491-9
BACKGROUND: Daclatasvir-containing regimens have the potential to address
limitations of current regimens combining peginterferon alfa and ribavirin with
first-generation protease inhibitors for treatment of chronic HCV genotype 1
infection.
METHODS: In this randomized, double-blind study, 27 Japanese treatment-naive
patients received once-daily daclatasvir 10 mg or 60 mg or placebo, each combined
with peginterferon alfa-2b/ribavirin; 18 prior null (n=9) or partial (n=9)
responders received the same daclatasvir-containing regimens without a placebo
arm. Daclatasvir recipients with protocol-defined response (HCV RNA<15 IU/ml at
week 4, undetectable at week 12) were treated for 24 weeks; those without
protocol-defined response and placebo recipients continued treatment to week 48.
RESULTS: Sustained virological response 24 weeks post-treatment (SVR24) was
achieved by 66.7%, 90.0% and 62.5% of treatment-naive patients in the daclatasvir
10 mg, 60 mg and placebo groups, respectively. Prior non-responders had more
frequent virological failure; 22.2% and 33.3% of daclatasvir 10 mg and 60 mg
recipients, respectively, achieved SVR24. Adverse events were similar across
groups and were typical of peginterferon alfa-2b/ribavirin. Pyrexia, headache,
alopecia, decreased appetite and malaise were the most common adverse events; two
daclatasvir recipients discontinued due to adverse events.
CONCLUSIONS: Daclatasvir 60 mg combined with peginterferon alfa-2b and ribavirin
achieved a high rate of SVR24 in treatment-naive patients with HCV genotype 1
infection, with tolerability similar to that of peginterferon alfa-2b/ribavirin
alone. However, regimens with greater antiviral potency are needed for prior
non-responders.
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