A phase 2a trial of 12-week interferon-free therapy with two direct-acting antivirals (ABT-450/r, ABT-072) and ribavirin in IL28B C/C patients with chronic hepatitis C genotype 1

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• 作者：Eric Lawitz¹ ; Fred Poordad¹ ; Kris V. Kowdley² ; Daniel E. Cohen³ ; ^{daniel.cohen@abbvie.com} ; Thomas Podsadecki³ ; Sara Siggelkow³ ; Lois Larsen³ ; Rajeev Menon³ ; Gennadiy Koev³ ; Rakesh Tripathi³ ; Tami Pilot-Matias³ ; Barry Bernstein³
• 关键词：HCV ; hepatitis C virus ; CYP3A4 ; cytochrome P450 isoform 3A4 ; RNA ; ribonucleic acid ; IL28B ; interleukin-28B ; LiPA ; Versant® ; HCV Genotype Inno-LiPA Assay ; version 2.0 ; MedDRA ; Medical Dictionary for Regulatory Activities ; OATP1B1 ; organic anion transpor
• 刊名：Journal of Hepatology
• 出版年：2013
• 出版时间：July, 2013
• 年：2013
• 卷：59
• 期：1
• 页码：18-23
• 全文大小：530 K

文摘

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Background & Aims

ABT-450 (combined with low-dose ritonavir, ABT-450/r) is a potent HCV NS3 protease inhibitor, and ABT-072 is a non-nucleoside NS5B polymerase inhibitor. The goal of this study was to evaluate the safety, tolerability, and efficacy of the peginterferon-free combination of ABT-450/r and ABT-072 with ribavirin in treatment-na?ve patients with IL28B CC genotype, infected with HCV genotype 1.

Methods

This was a phase 2a, multicenter, open-label, single-arm study in 11 treatment-na?ve, non-cirrhotic HCV GT1-infected patients with IL28B rs12979860 genotype CC. Patients received ABT-450/r 150/100 mg once daily and ABT-072 400 mg once daily with weight-based ribavirin 1000-1200 mg/day dosed twice daily for 12 weeks.

Results

Eight (73 % ) patients were male, 9 (82 % ) were Caucasian (including 3 who self-identified as Hispanic); mean baseline HCV RNA was 6.9 log₁₀ IU/ml (range 6.5-7.3 log₁₀ IU/ml). All 11 patients completed 12 weeks of treatment and maintained HCV RNA <25 IU/ml from weeks 4 through 12 of treatment. Ten patients (91 % ) achieved sustained virologic response 24 weeks post-treatment, with a second patient relapsing 36 weeks post-treatment. There were no deaths, serious or severe adverse events, or premature discontinuations. Adverse events were mostly mild and the most frequent were headache, fatigue, nausea, and dry skin.

Conclusions

A 12-week regimen of ABT-450/r and ABT-072 with ribavirin was well tolerated with 9/11 patients achieving sustained virologic response through 36 weeks of post-treatment observation. These findings suggest that peginterferon-free regimens may have the potential to cure a high proportion of HCV genotype 1-infected patients.