Faldaprevir and deleobuvir for HCV genotype 1 infection

N Engl J Med. 2013 Aug 15;369(7):630-9. doi: 10.1056/NEJMoa1213557.

Abstract

Background: Interferon-free regimens would be a major advance in the treatment of patients with chronic hepatitis C virus (HCV) infection.

Methods: In this phase 2b, randomized, open-label trial of faldaprevir (a protease inhibitor) and deleobuvir (a nonnucleoside polymerase inhibitor), we randomly assigned 362 previously untreated patients with HCV genotype 1 infection to one of five groups: faldaprevir at a dose of 120 mg once daily and deleobuvir at a dose of 600 mg three times daily, plus ribavirin, for 16, 28, or 40 weeks (TID16W, TID28W, or TID40W, respectively); faldaprevir at a dose of 120 mg once daily and deleobuvir at a dose of 600 mg twice daily, plus ribavirin, for 28 weeks (BID28W); or faldaprevir at a dose of 120 mg once daily and deleobuvir at a dose of 600 mg three times daily, without ribavirin, for 28 weeks (TID28W-NR). The primary end point was a sustained virologic response 12 weeks after the completion of therapy.

Results: The primary end point was met in 59% of patients in the TID16W group, 59% of patients in the TID28W group, 52% of patients in the TID40W group, 69% of patients in the BID28W group, and 39% of patients in the TID28W-NR group. The sustained virologic response 12 weeks after the completion of therapy did not differ significantly according to treatment duration or dosage among ribavirin-containing regimens. This response was significantly higher with TID28W than with TID28W-NR (P=0.03). Rates of a sustained virologic response 12 weeks after the completion of therapy were 56 to 85% among patients with genotype 1b infection versus 11 to 47% among patients with genotype 1a infection and 58 to 84% among patients with IL28B CC versus 33 to 64% with non-CC genotypes. Rash, photosensitivity, nausea, vomiting, and diarrhea were the most common adverse events.

Conclusions: The rate of a sustained virologic response 12 weeks after the completion of therapy was 52 to 69% among patients who received interferon-free treatment with faldaprevir in combination with deleobuvir plus ribavirin. (Funded by Boehringer Ingelheim; SOUND-C2 ClinicalTrials.gov number, NCT01132313.).

Publication types

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

MeSH terms

  • Adult
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • DNA-Directed RNA Polymerases / antagonists & inhibitors*
  • Enzyme Inhibitors / adverse effects
  • Enzyme Inhibitors / therapeutic use*
  • Female
  • Genotype
  • Hepacivirus / genetics*
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / genetics
  • Hepatitis C, Chronic / virology
  • Humans
  • Male
  • Middle Aged
  • Oligopeptides / adverse effects
  • Oligopeptides / therapeutic use*
  • Protease Inhibitors / adverse effects
  • Protease Inhibitors / therapeutic use
  • Thiazoles / adverse effects
  • Thiazoles / therapeutic use*
  • Viral Load

Substances

  • Antiviral Agents
  • Enzyme Inhibitors
  • N-((cyclopentyloxy)carbonyl)-3-methylvalyl-4-((8-bromo-7-methoxy-2-(2-((2-methylpropanoyl)amino)-1,3-thiazol-4-yl)quinolin-4-yl)oxy)-N-(1-carboxy-2-ethenylcyclopropyl)prolinamide
  • Oligopeptides
  • Protease Inhibitors
  • Thiazoles
  • DNA-Directed RNA Polymerases

Associated data

  • ClinicalTrials.gov/NCT01132313