Randomized trial of interferon- and ribavirin-free ombitasvir/paritaprevir/ritonavir in treatment-experienced hepatitis C virus-infected patients

Abstract

Approximately 2 million Japanese individuals are infected with hepatitis C virus and are at risk for cirrhosis, end-stage liver disease, and hepatocellular carcinoma. Patients in whom interferon (IFN)/ribavirin (RBV) therapy has failed remain at risk as effective therapeutic options are limited. This phase 2, randomized, open-label study evaluated an IFN- and RBV-free regimen of once-daily ombitasvir (ABT-267), an NS5A inhibitor, plus paritaprevir (ABT-450), an NS3/4A protease inhibitor dosed with ritonavir (paritaprevir/ritonavir), in pegylated IFN/RBV treatment-experienced Japanese patients with hepatitis C virus subtype 1b or genotype 2 infection. Patients without cirrhosis (aged 18-75 years) with subtype 1b infection received ombitasvir 25 mg plus paritaprevir/ritonavir 100/100 mg or 150/100 mg for 12 or 24 weeks; patients with genotype 2 infection received ombitasvir 25 mg plus paritaprevir/ritonavir 100/100 mg or 150/100 mg for 12 weeks. Sustained virologic response (SVR) at posttreatment week 24 (SVR24 ) was the primary endpoint. Adverse events were collected throughout the study. One hundred ten patients received ≥1 dose of study medication. In the subtype 1b cohort, SVR24 rates were high (88.9%-100%) regardless of paritaprevir dose or treatment duration. In the genotype 2 cohort, SVR24 rates were 57.9% and 72.2% with 100 mg and 150 mg of paritaprevir, respectively. The SVR24 rate was higher in patients with subtype 2a (90%) than 2b (27%). Concordance between SVR12 and SVR24 was 100%. The most common adverse events overall were nasopharyngitis (29%) and headache (14%).

Conclusion: In this difficult-to-treat population of patients in whom prior pegylated IFN/RBV had failed, ombitasvir/paritaprevir/ritonavir demonstrated potent antiviral activity with a favorable safety profile among Japanese patients with hepatitis C virus genotype 1b or 2a infection.

© 2015 The Authors. HEPATOLOGY published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.

Figures

Figure 1

Study design. *Patients not achieving a 2 log10 IU/mL reduction in HCV RNA at week 12 after ≥10 weeks of pegIFN/RBV. †Patients who achieved a ≥2 log10 IU/mL reduction in HCV RNA at week 12 after ≥20 weeks of pegIFN/RBV but had HCV RNA levels above the lower limit of detection at treatment end. ‡Patients with undetectable levels of HCV RNA after one or more courses of pegIFN/RBV treatment who had detectable HCV RNA within 24 weeks. §Dose: 25 mg QD. Abbreviations: OBV, ombitasvir; PTV, paritaprevir; QD, once daily; r, ritonavir.

Figure 2

Patient disposition. Abbreviations: OBV, ombitasvir; PTV, paritaprevir; r, ritonavir. *Dose: 25 mg.

Figure 3

Efficacy of ombitasvir/paritaprevir/ritonavir in patients with HCV infection. Virologic response by treatment group for patients classified according to LiPA 2.0 analysis as having HCV subtype 1b (A) or HCV genotype 2 (B) infection and by subtype of genotype 2 according to phylogenetic analysis (C). Error bars represent 95% confidence intervals. Two patients identified as genotype 2 by LiPA 2.0 analysis were found to be HCV subtype 1b during phylogenetic analysis; both of these patients achieved SVR12 and SVR24. *Dose: 25 mg. Abbreviations: EOTR, end‐of‐treatment response; GT1b, HCV subtype 1b; OBV, ombitasvir; PTV, paritaprevir; r, ritonavir; RVR, rapid virologic response.