Antiviral activity of TMC435 monotherapy in patients infected with HCV genotypes 2-6: TMC435-C202, a phase IIa, open-label study

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• 作者：Christophe Moreno¹ ; ^{Christophe.Moreno@erasme.ulb.ac.be} ; Thomas Berg² ; Tawesak Tanwandee³ ; Satawat Thongsawat⁴ ; Hans Van Vlierberghe⁵ ; Stefan Zeuzem⁶ ; Oliver Lenz⁷ ; Monika Peeters⁷ ; Vanitha Sekar⁸ ; Goedele De Smedt⁷
• 关键词：HCV ; hepatitis C virus ; PegIFN ; peginterferon ; RBV ; weight-based ribavirin ; SVR ; sustained virologic response ; AE ; adverse event ; DAA ; direct-acting antiviral ; q.d. ; once daily ; RVR ; rapid virologic response ; IC ; inhibitory concentration ; ECG ; electrocard
• 刊名：Journal of Hepatology
• 出版年：2012
• 期刊代码：162_01688278
• 类别：med
• 出版时间：June, 2012
• 卷：56
• 期：6
• 页码：1247-1253
• 文件大小：689 K

摘要

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Background & Aims

TMC435 is an investigational, once-daily, oral NS3/4A protease inhibitor currently in phase III development for the treatment of hepatitis C virus (HCV) infection. Phase I and II studies in patients infected with HCV genotype 1 have demonstrated that TMC435 is generally well tolerated, has a pharmacokinetic profile that supports once daily dosing, and demonstrates potent antiviral activity. This phase IIa study (TMC435-C202; ) was conducted to investigate the antiviral activity, safety, tolerability, and pharmacokinetics of TMC435 in treatment-na褩ve patients infected with HCV genotypes 2-6.

Methods

The study consisted of 7 days of monotherapy with TMC435 (200 mg once daily). Patients could begin treatment with pegylated interferon/ribavirin from day 8 with a follow-up period up to days 37-42.

Results

Thirty-seven patients were enrolled in Germany, Belgium and Thailand. For the primary end point at day 8, the mean (卤 standard error) change in plasma HCV ribonucleic acid (log₁₀ IU/ml) from baseline was the greatest for genotypes 6 (鈭?.35 卤 0.29) and 4 (鈭?.52 卤 0.43), followed by genotypes 2 (鈭?.73 卤 0.71) and 5 (鈭?.19 卤 0.39). No antiviral activity was evident for genotype 3. Viral breakthrough occurred in six patients during the monotherapy phase and in six additional patients during PegIFN/RBV-only period. All adverse events were mild or moderate and there were no discontinuations during the TMC435 monotherapy period.

Conclusions

The results of this phase IIa proof-of-concept trial provide evidence that TMC435 has a spectrum of activity against multiple HCV genotypes, except for genotype 3. In this study, TMC435 was generally safe and well tolerated.