Efficacy of the protease inhibitor BI 201335, polymerase inhibitor BI 207127, and ribavirin in patients with chronic HCV infection

Gastroenterology. 2011 Dec;141(6):2047-55; quiz e14. doi: 10.1053/j.gastro.2011.08.051. Epub 2011 Sep 16.

Abstract

Background & aims: Therapeutic regimens are being developed for patients with hepatitis C virus (HCV) infection that do not include the combination of peginterferon alfa and ribavirin. We investigated the antiviral effect and safety of BI 201335 (an inhibitor of the NS3/4A protease) and BI 207127 (an inhibitor of the NS5B non-nucleoside polymerase) with ribavirin.

Methods: Thirty-two treatment-naïve patients with chronic HCV genotype 1 infection were randomly assigned to groups that were given 400 mg or 600 mg BI 207127 3 times daily plus 120 mg BI 201335 once daily and 1000 to 1200 mg/day ribavirin for 4 weeks. The primary efficacy end point was virologic response (HCV RNA level <25 IU/mL at week 4). Thirty-two patients received treatment; 31 completed all 4 weeks of assigned combination therapy.

Results: In the group given BI 207127 400 mg 3 times daily, the rates of virologic response were 47%, 67%, and 73% at days 15, 22, and 29; a higher rate of response was observed in patients with genotype-1b compared with genotype-1a infections. In the group given BI 207127 600 mg 3 times daily, the rates of virologic response were 82%, 100%, and 100%, respectively, and did not differ among genotypes. One patient in the group given 400 mg 3 times daily had virologic breakthrough (≥1 log(10) rebound in HCV RNA) at day 22. The most frequent adverse events were mild gastrointestinal disorders, rash, and photosensitivity. There were no severe or serious adverse events; no patients discontinued therapy prematurely.

Conclusions: The combination of the protease inhibitor BI 201335, the polymerase inhibitor BI 207127, and ribavirin has rapid and strong activity against HCV genotype-1 and did not cause serious or severe adverse events.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Acrylates / adverse effects
  • Acrylates / therapeutic use*
  • Aminoisobutyric Acids
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Benzimidazoles / adverse effects
  • Benzimidazoles / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Genotype
  • Hepacivirus / drug effects*
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology
  • Humans
  • Leucine / analogs & derivatives
  • Male
  • Middle Aged
  • Oligopeptides / adverse effects
  • Oligopeptides / therapeutic use*
  • Proline / analogs & derivatives
  • Protease Inhibitors / adverse effects
  • Protease Inhibitors / therapeutic use
  • Quinolines
  • RNA, Viral / analysis
  • RNA, Viral / blood
  • RNA, Viral / drug effects
  • RNA-Dependent RNA Polymerase / antagonists & inhibitors*
  • Ribavirin / adverse effects
  • Ribavirin / therapeutic use*
  • Thiazoles / adverse effects
  • Thiazoles / therapeutic use*
  • Treatment Outcome
  • Viral Load
  • Viral Nonstructural Proteins / antagonists & inhibitors

Substances

  • Acrylates
  • Aminoisobutyric Acids
  • Antiviral Agents
  • Benzimidazoles
  • Oligopeptides
  • Protease Inhibitors
  • Quinolines
  • RNA, Viral
  • Thiazoles
  • Viral Nonstructural Proteins
  • Ribavirin
  • deleobuvir
  • faldaprevir
  • Proline
  • NS-5 protein, hepatitis C virus
  • RNA-Dependent RNA Polymerase
  • Leucine