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Abstract Details
Randomized study of asunaprevir plus peginterferon alfa and ribavirin for previously untreated genotype 1 chronic hepatitis C
Bronowicki JP, Pol S, Thuluvath PJ, Larrey D, Martorell CT, Rustgi VK, Morris DW, Younes Z, Fried MW, Bourlière M, Hézode C, Reddy KR, Massoud O, Abrams GA, Ratziu V, He B, Eley T, Ahmad A, Cohen D, Hindes R, McPhee F, Reilly B, Mendez P, Hughes E. Antivir Ther. 2013 Jun 26. doi: 10.3851/IMP2660. [Epub ahead of print]
Source
INSERM 954, Centre Hospitalier Universitaire de Nancy, Université de Lorraine, Vandoeuvre les Nancy, France. jp.bronowicki@chu-nancy.fr.
Abstract
BACKGROUND:
Asunaprevir is a selective NS3 protease inhibitor with in vitro activity against hepatitis C virus (HCV) genotypes 1 and 4.
METHODS:
In this phase 2a, double-blind study, treatment-naïve HCV genotype 1-infected patients in the United States and France were randomly assigned 1:1:1:1 to placebo or asunaprevir 200 mg twice-daily, 600 mg twice-daily, or 600 mg once-daily in combination with peginterferon alfa-2a (peginterferon) and ribavirin for 48 weeks. The primary efficacy endpoint was undetectable HCV RNA at weeks 4 and 12 (eRVR). Other endpoints included safety and undetectable HCV RNA at 24 weeks post-treatment (SVR24).
RESULTS:
Forty-seven patients were randomized and treated. eRVR was achieved by 75% (9/12), 75% (9/12), and 92% (11/12) of patients in the asunaprevir 200-mg twice-daily, 600-mg twice-daily, and 600-mg once-daily groups vs 0% (0/11) in the placebo group. Corresponding SVR24 rates were 83% (10/12), 83% (10/12), and 92% (11/12) in the asunaprevir groups and 46% (5/11) in the placebo group. There was no virologic breakthrough in any asunaprevir group. Following the 12-week analysis, the 600-mg doses were reduced to 200 mg twice daily because of a greater frequency of transaminase elevations at the 600-mg dose. The most common grade 3-4 laboratory abnormalities were consistent with those reported for peginterferon and ribavirin.
CONCLUSIONS:
Asunaprevir plus peginterferon and ribavirin achieved higher response rates than placebo plus peginterferon and ribavirin, with a tolerable adverse event profile at the 200-mg twice-daily dose. This dose is being evaluated in the phase 2b and phase 3 studies.