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

Journal of Hepatology
Volume 59, Issue 1 , Pages 18-23, July 2013

Eric Lawitzl Fred Poordad, Kris V. Kowdley,Daniel E. Cohen, Thomas Podsadecki,  Sara Siggelkow, Lois Larsen, Rajeev Menon, Gennadiy Koev, Rakesh Tripathi, Tami Pilot-Matias, Barry Bernstein

Received 26 December 2012; received in revised form 6 February 2013; accepted 12 February 2013. published online 25 February 2013.

Abstract

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-naïve 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-naïve, non-cirrhotic HCV GT1-infected patients with IL28B rs12979860 genotype CC. Patients received ABT-450/r 150/100mg once daily and ABT-072 400mg once daily with weight-based ribavirin 1000–1200mg/day dosed twice daily for 12weeks.

Results

Eight (73%) patients were male, 9 (82%) were Caucasian (including 3 who self-identified as Hispanic); mean baseline HCV RNA was 6.9log₁₀IU/ml (range 6.5–7.3log₁₀IU/ml). All 11 patients completed 12weeks of treatment and maintained HCV RNA <25IU/ml from weeks 4 through 12 of treatment. Ten patients (91%) achieved sustained virologic response 24weeks post-treatment, with a second patient relapsing 36weeks 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 36weeks 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.

Abbreviations: 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 transporting polypeptide 1B1

Keywords: Hepatitis C virus, Interferon-free therapy, Direct-acting antiviral, Sustained virologic response

Source