Sofosbuvir (GS-7977) plus peginterferon/ribavirin in treatment-na?ve patients with HCV genotype 1: A randomized, 28-day, dose-ranging trial

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• 作者：Maribel Rodriguez-Torres¹ ; ^{mrodrigueztorres@fdipr.com} ; Eric Lawitz² ; Kris V. Kowdley³ ; David R. Nelson⁴ ; Edwin DeJesus⁵ ; John G. McHutchison⁶ ; Melanie T. Cornpropst⁷ ; ^&dagger ; ; Michael Mader⁶ ; ^&dagger ; ; Efsevia Albanis⁶ ; ^&dagger ; ; Deyuan Jiang⁶ ; Christy M. Hebner⁶ ; William T. Symonds⁶ ; ^&dagger ; ; Michelle M. Berrey⁸ ; ^&dagger ; ; Jay Lalezari⁹
• 关键词：HCV ; hepatitis C virus ; PegIFN ; pegylated interferon ; RBV ; ribavirin ; RVR ; rapid virologic response ; SVR ; sustained virologic response ; IL ; interleukin ; LOD ; limit of detection ; MedDRA ; Medical Dictionary for Regulatory Activities ; ECG ; electrocardiogram
• 刊名：Journal of Hepatology
• 出版年：2013
• 出版时间：April, 2013
• 年：2013
• 卷：58
• 期：4
• 页码：663-668
• 全文大小：646 K

文摘

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Background & Aims

Sofosbuvir (formerly GS-7977) is a pyrimidine nucleotide analog inhibitor of the hepatitis C virus (HCV) NS5B polymerase. We assessed the safety, tolerability, antiviral activity, and pharmacokinetics of sofosbuvir plus pegylated-interferon (PegIFN)/ribavirin (RBV) in a 28-day, dose-ranging trial in treatment-na?ve patients infected with genotype 1 HCV.

Methods

In this double-blind study, 64 patients were randomized (1:1:1:1) to receive one of three once-daily doses of oral sofosbuvir (100, 200, or 400 mg) or placebo plus PegIFN/RBV for 28 days, after which all patients continued to receive PegIFN/RBV alone for a further 44 weeks.

Results

Patients in the sofosbuvir/PegIFN/RBV groups experienced mean reductions in HCV RNA >5 log₁₀ IU/ml (?5.3 for 100 mg, ?5.1 for 200 mg and ?5.3 for 400 mg) vs. ?2.8 log₁₀ IU/ml for placebo/PegIFN/RBV after 28 days. Rapid virologic response (RVR) rates were markedly higher after sofosbuvir treatment (88-94 % ) than placebo (21 % ), as were rates of sustained virologic response (SVR) at post-treatment Week 24 (56 % , 83 % , and 80 % for sofosbuvir 100, 200, and 400 mg, respectively, vs. 43 % for placebo). The number of patients experiencing virologic breakthrough and post-treatment relapse was higher in the sofosbuvir 100 mg group than sofosbuvir 200 and 400 mg groups. Sofosbuvir was well tolerated; the most frequent adverse events were fatigue and nausea.

Conclusions

These results support further studies with sofosbuvir at 200 mg and 400 mg to determine the optimal dose and treatment duration of sofosbuvir in HCV genotype 1.