Efficacy and Safety of Ombitasvir, Paritaprevir, and Ritonavir in an Open-Label Study of Patients With Genotype 1b Chronic Hepatitis C Virus Infection With and Without Cirrhosis

Gastroenterology. 2015 Oct;149(4):971-80.e1. doi: 10.1053/j.gastro.2015.07.001. Epub 2015 Jul 11.

Abstract

Background & aims: Interferon-free treatment options are rapidly evolving for patients with chronic hepatitis C virus (HCV) genotype 1b (GT1b) infection with cirrhosis and for nonresponders to prior pegylated interferon and ribavirin therapy. We performed a phase 2b, open-label trial of the combination of ombitasvir (a NS5A replication complex inhibitor), paritaprevir, and ritonavir (an NS3/4A protease inhibitor)-an interferon- and ribavirin-free regimen-in difficult-to-treat patients, including prior null responders and patients with cirrhosis.

Methods: In an international study, 82 patients without cirrhosis (42 treatment-naive and 40 prior null responders) and 99 with cirrhosis (47 treatment-naive and 52 treatment-experienced with prior relapse or a null or partial response) with chronic HCV GT1b infection received ombitasvir (25 mg), paritaprevir (150 mg), and ritonavir (100 mg) once daily for 12 weeks (without cirrhosis) or 24 weeks (with cirrhosis). The primary efficacy endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12).

Results: In treatment-naive and null responder patients without cirrhosis, rates of SVR12 were 95.2% and 90.0%, respectively. In treatment-naive and treatment-experienced patients with cirrhosis, rates of SVR12 were 97.9% and 96.2%, respectively. No clinically meaningful differences in rates of SVR12 were observed between patients with or without cirrhosis. Virologic relapse occurred in 3 null responders without cirrhosis and 1 with cirrhosis; virologic breakthrough occurred in 1 null responder without cirrhosis. Common adverse events included headache, asthenia, pruritus, and diarrhea. One patient discontinued taking the drugs because of treatment-related adverse events.

Conclusions: An interferon- and ribavirin-free regimen of ombitasvir, paritaprevir, and ritonavir, achieved high rates of SVR12 in patients with HCV GT1b infection with and without cirrhosis. This regimen was well tolerated and was associated with low rates of treatment discontinuation. ClinicalTrials.gov no: NCT01685203.

Keywords: Direct-Acting Antivirals; HCV Genotype 1b; Interferon-Free/Ribavirin-Free.

Publication types

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

MeSH terms

  • Administration, Oral
  • Aged
  • Anilides / administration & dosage
  • Anilides / adverse effects
  • Anilides / therapeutic use*
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Carbamates / administration & dosage
  • Carbamates / adverse effects
  • Carbamates / therapeutic use*
  • Carrier Proteins / antagonists & inhibitors
  • Cyclopropanes
  • Drug Resistance, Viral
  • Drug Therapy, Combination
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / adverse effects
  • Enzyme Inhibitors / therapeutic use*
  • Europe
  • Female
  • Genotype
  • Hepacivirus / drug effects*
  • Hepacivirus / enzymology
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / diagnosis
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Lactams, Macrocyclic
  • Liver Cirrhosis / diagnosis
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / virology
  • Macrocyclic Compounds / administration & dosage
  • Macrocyclic Compounds / adverse effects
  • Macrocyclic Compounds / therapeutic use*
  • Male
  • Middle Aged
  • Proline / analogs & derivatives
  • Recurrence
  • Remission Induction
  • Ritonavir / administration & dosage
  • Ritonavir / adverse effects
  • Ritonavir / therapeutic use*
  • Sulfonamides
  • Time Factors
  • Treatment Outcome
  • United States
  • Valine
  • Viral Nonstructural Proteins / antagonists & inhibitors

Substances

  • Anilides
  • Antiviral Agents
  • Carbamates
  • Carrier Proteins
  • Cyclopropanes
  • Enzyme Inhibitors
  • Intracellular Signaling Peptides and Proteins
  • Lactams, Macrocyclic
  • Macrocyclic Compounds
  • NS3 protein, hepatitis C virus
  • NS4A cofactor peptide, Hepatitis C virus
  • Sulfonamides
  • Viral Nonstructural Proteins
  • ombitasvir
  • Proline
  • NS-5 protein, hepatitis C virus
  • Valine
  • Ritonavir
  • paritaprevir

Associated data

  • ClinicalTrials.gov/NCT01685203