The Combination of MK-5172, Peginterferon, and Ribavirin Is Effective in Treatment-Naive Patients With Hepatitis C Virus Genotype 1 Infection Without Cirrhosis

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• 作者：Michael P. Manns¹ ; ⁹ ; ^{manns.michael@mh-hannover.de" class="auth_mail" title="E-mail the corresponding author} ; John M. Vierling² ; Bruce R. Bacon³ ; Savino Bruno⁴ ; Oren Shibolet⁵ ; Yaacov Baruch⁶ ; Patrick Marcellin⁷ ; Luzelena Caro⁸ ; Anita Y.M. Howe⁸ ; Christine Fandozzi⁸ ; Jacqueline Gress⁸ ; Christopher L. Gilbert⁸ ; Peter M. Shaw⁸ ; Michael P. Cooreman⁸ ; Michael N. Robertson⁸ ; Peggy Hwang⁸ ; Frank J. Dutko⁸ ; Janice Wahl⁸ ; Niloufar Mobashery⁸
• 关键词：Response-Guided Therapy ; Sustained Virologic Response ; Chronic HCV ; Protease Inhibitor
• 刊名：Gastroenterology
• 出版年：2014
• 出版时间：August 2014
• 年：2014
• 卷：147
• 期：2
• 页码：366-376.e6
• 全文大小：1658 K

文摘

MK-5172 is an inhibitor of the hepatitis C virus (HCV) nonstructural protein 3/4A protease; MK-5172 is taken once daily and has a higher potency and barrier to resistance than licensed protease inhibitors. We investigated the efficacy and tolerability of MK-5172 with peginterferon and ribavirin (PR) in treatment-naive patients with chronic HCV genotype 1 infection without cirrhosis.

Methods

We performed a multicenter, double-blind, randomized, active-controlled, dose-ranging, response-guided therapy study. A total of 332 patients received MK-5172 (100, 200, 400, or 800 mg) once daily for 12 weeks in combination with PR. Patients in the MK-5172 groups received PR for an additional 12 or 36 weeks, based on response at week 4. Patients in the control group (n = 66) received a combination of boceprevir and PR, dosed in accordance with boceprevir's US product circular.

Results

At 24 weeks after the end of therapy, sustained virologic responses were achieved in 89%, 93%, 91%, and 86% of the patients in the groups given the combination of PR and MK-5172 (100, 200, 400, or 800 mg), respectively, vs 61% of controls. In the MK-5172 group receiving 100 mg, 91% of patients had undetectable levels of HCV RNA at week 4 and qualified for the short duration of therapy. The combination of MK-5172 and PR generally was well tolerated. Transient increases in transaminase levels were noted in the MK-5172 groups given 400 and 800 mg, at higher frequencies than in the MK-5172 groups given 100 or 200 mg, or control groups.

Conclusions

Once-daily MK-5172 (100 mg) with PR for 24 or 48 weeks was highly effective and well tolerated among treatment-naive patients with HCV genotype 1 infection without cirrhosis. Studies are underway to evaluate interferon-free MK-5172–based regimens. ClinicalTrials.gov number: NCT01353911.