A phase 2B study of MK-7009 (vaniprevir) in patients with genotype 1 HCV infection who have failed previous pegylated interferon and ribavirin treatment

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• 作者：Eric Lawitz¹ ; Maribel Rodriguez-Torres² ; Albrecht Stoehr³ ; Edward J. Gane⁴ ; Lawrence Serfaty⁵ ; Sanhita Bhanja⁶ ; Richard J. Barnard⁶ ; Di An⁶ ; Jacqueline Gress⁶ ; Peggy Hwang⁶ ; Niloufar Mobashery⁶ ; ^{niloufar_mobashery@merck.com}
• 关键词：Vaniprevir ; HCV ; Direct-acting antivirals
• 刊名：Journal of Hepatology
• 出版年：2013
• 出版时间：July, 2013
• 年：2013
• 卷：59
• 期：1
• 页码：11-17
• 全文大小：698 K

文摘

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Background & Aims

MK-7009 (vaniprevir) is a non-covalent competitive inhibitor of the hepatitis C virus (HCV) NS3/4A protease. This report presents the primary analysis results (safety and sustained viral response) of a phase 2b study of MK-7009 given in combination with peginterferon (PegIFN) alfa2a 180 ¦Ìg weekly and ribavirin (RBV) 1000-1200 mg/day, for 24-48 weeks to non-cirrhotic patients who have failed previous PegIFN and RBV treatment.

Methods

We present results of a randomized, placebo-controlled, double-blind study of MK-7009 administered for 24-48 weeks in combination with PegIFN and RBV in 4 regimens to at least 40 patients per arm. Stratification by prior response to PegIFN and RBV was as follows: null response, partial response, breakthrough and relapse. HCV RNA was determined by Roche Cobas Taqman with a lower limit of detection (LLoD) of 10 IU/ml and a lower limit of quantification (LLoQ) of 25 IU/ml.

Results

SVR₂₄ in patients on MK-7009 + PegIFN and ribavirin (P/R) was statistically superior to placebo + P/R in all treatment groups (p <0.001). MK-7009 at 300 mg b.i.d. and 600 mg b.i.d. is generally well tolerated for use for up to 48 weeks of therapy. Patients in MK-7009 regimens had higher rates of gastrointestinal adverse events as compared to control (mostly mild to moderate). There were no significant differences in rates of anemia and rash between the MK-7009 regimens and control.

Conclusions

In conclusion, patients treated with MK-7009 plus P/R experienced significant improvement in SVR compared to P/R control in a population of GT 1 experienced patients.