Daclatasvir plus simeprevir with or without ribavirin for the treatment of chronic hepatitis C virus genotype 1 infection

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• 作者：Stefan Zeuzem¹ ; ^{zeuzem@em.uni-frankfurt.de" class="auth_mail" title="E-mail the corresponding author} ; Christophe Hé ; zode² ; Jean-Pierre Bronowicki³ ; Veronique Loustaud-Ratti⁴ ; Francisco Gea⁵ ; Maria Buti⁶ ; Antonio Olveira⁵ ; Tivadar Banyai⁷ ; M. Tarek Al-Assi⁸ ; Joerg Petersen⁹ ; Dominique Thabut¹⁰ ; Adrian Gadano¹¹ ; Ronald Pruitt¹² ; Mihá ; ly Makara¹³ ; Marc Bourli&egrave ; re¹⁴ ; Stanislas Pol¹⁵ ; Maria Beumont-Mauviel¹⁶ ; Sivi Ouwerkerk-Mahadevan¹⁷ ; Gaston Picchio¹⁸ ; Marc Bifano¹⁹ ; Fiona M^cPhee²⁰ ; Navdeep Boparai¹⁹ ; Kin Cheung²⁰ ; Eric A. Hughes¹⁹ ; Stephanie Noviello¹⁹ ; on behalf of the LEAGUE-1 Study Team
• 关键词：HCV ; hepatitis C virus ; SMV ; simeprevir ; PegIFN ; peginterferon ; RBV ; ribavirin ; DCV ; daclatasvir ; ASV ; asuneprevir ; SVR ; sustained virologic response ; LLOQ ; lower limit of quantitation ; AE ; adverse event ; SVR12 ; sustained virologic response at posttreatment week 12 ; RAV ; resistance-associated variant ; ULN ; upper limit of normal
• 刊名：Journal of Hepatology
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：64
• 期：2
• 页码：292-300
• 全文大小：831 K

文摘

We evaluated the combination of daclatasvir (pan-genotypic NS5A inhibitor) and simeprevir (NS3/4A protease inhibitor), with or without ribavirin, in hepatitis C virus genotype 1–infected patients.

Methods

This phase II, open-label study enrolled treatment-naive patients or prior null responders with genotype 1b (n = 147) or 1a (n = 21) infection. Genotype 1b–infected patients were randomized 1:1 to receive daclatasvir 30 mg plus simeprevir 150 mg once daily with or without ribavirin; those who completed the initial 12–week treatment were re-randomized 1:1 to stop treatment or continue treatment through to week 24. Genotype 1a–infected patients received daclatasvir plus simeprevir with ribavirin for 24 weeks. The primary endpoint was the proportion of patients with sustained virologic response at posttreatment week 12 (SVR12).

Results

For genotype 1b, 84.9% (45/53) and 74.5% (38/51) of treatment-naive patients and 69.6% (16/23) and 95.0% (19/20) of prior null responders to peginterferon and ribavirin achieved SVR12 with daclatasvir plus simeprevir alone and with ribavirin, respectively. Treatment duration did not have a well-defined impact on response. For genotype 1a, daclatasvir plus simeprevir with ribavirin provided a 66.7% (8/12) response rate in treatment-naive patients and was not effective in prior null responders. Data suggest that baseline resistance polymorphisms influenced SVR12 rates. Daclatasvir plus simeprevir was well tolerated with or without ribavirin with low incidences of serious adverse events and adverse events leading to discontinuation.

Conclusions

Daclatasvir plus simeprevir, with or without ribavirin, was effective with a 12- or 24-week duration in genotype 1b–infected patients and was well tolerated. v%20identifier">ClinicalTrials.gov identifier: v" data-locatorKey="NCT01628692">NCT01628692.