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

Hepatology. 2015 May;61(5):1523-32. doi: 10.1002/hep.27705. Epub 2015 Mar 23.

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.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anilides / administration & dosage*
  • Antiviral Agents / administration & dosage*
  • Carbamates / administration & dosage*
  • Cyclopropanes
  • Drug Therapy, Combination
  • Female
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Interferons
  • Lactams, Macrocyclic
  • Liver Cirrhosis
  • Macrocyclic Compounds / administration & dosage*
  • Male
  • Middle Aged
  • Proline / analogs & derivatives
  • Ribavirin
  • Ritonavir / administration & dosage*
  • Sulfonamides
  • Valine
  • Young Adult

Substances

  • Anilides
  • Antiviral Agents
  • Carbamates
  • Cyclopropanes
  • Lactams, Macrocyclic
  • Macrocyclic Compounds
  • Sulfonamides
  • ombitasvir
  • Ribavirin
  • Interferons
  • Proline
  • Valine
  • Ritonavir
  • paritaprevir