Daclatasvir and asunaprevir plus peginterferon alfa and ribavirin in HCV genotype 1 or 4 non-responders

J Hepatol. 2015 Jul;63(1):30-7. doi: 10.1016/j.jhep.2015.02.018. Epub 2015 Feb 19.

Abstract

Background & aims: Improved therapies for peginterferon/ribavirin null or partial responders are needed. This study evaluated daclatasvir (NS5A inhibitor) and asunaprevir (NS3 protease inhibitor) plus peginterferon alfa-2a and ribavirin in this patient population.

Methods: This open-label, phase 3 study (HALLMARK-QUAD; NCT01573351) treated patients with chronic hepatitis C virus (HCV) genotype 1 (n=354) or 4 (n=44) infection who had a prior null or partial response to peginterferon/ribavirin. Patients received daclatasvir 60 mg once-daily plus asunaprevir 100mg twice-daily, with weekly peginterferon alfa-2a and weight-based ribavirin for 24 weeks. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12) among genotype 1-infected patients.

Results: Daclatasvir plus asunaprevir and peginterferon/ribavirin demonstrated SVR12 rates of 93% (95% CI 90-96) in prior non-responders infected with HCV genotype 1. SVR12 rates among genotype 4-infected patients were 98% (95% CI 93-100); one patient had a missing post-treatment week-12 HCV-RNA measurement, but achieved an SVR at post-treatment week 24, yielding a 100% SVR rate in genotype 4 patients. Prior peginterferon/ribavirin response, sex, age, IL28B genotype, or cirrhosis status did not influence SVR12 rates. Serious adverse events occurred in 6% of patients; 5% discontinued treatment due to an adverse event. Grade 3/4 laboratory abnormalities included neutropenia (22%), lymphopenia (16%), anemia (6%), thrombocytopenia (4%), and ALT/AST elevations (3% each).

Conclusions: Daclatasvir plus asunaprevir and peginterferon/ribavirin demonstrated high rates of SVR12 in genotype 1- or 4-infected prior null or partial responders. The combination was well tolerated and no additional safety and tolerability concerns were observed compared with peginterferon/ribavirin regimens.

Keywords: Asunaprevir; Daclatasvir; Direct-acting antiviral; NS5A; Null; Partial; Peginterferon alfa.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / administration & dosage
  • DNA, Viral / genetics*
  • Drug Administration Schedule
  • Drug Carriers
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Genotype
  • Hepacivirus / genetics*
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology
  • Humans
  • Imidazoles / administration & dosage*
  • Interferon-alpha / administration & dosage*
  • Isoquinolines / administration & dosage*
  • Male
  • Middle Aged
  • Polyethylene Glycols / administration & dosage*
  • Recombinant Proteins / administration & dosage
  • Ribavirin / administration & dosage*
  • Sulfonamides / administration & dosage*
  • Treatment Outcome
  • Viral Load / genetics
  • Young Adult

Substances

  • Antiviral Agents
  • DNA, Viral
  • Drug Carriers
  • Imidazoles
  • Interferon-alpha
  • Isoquinolines
  • Recombinant Proteins
  • Sulfonamides
  • Polyethylene Glycols
  • Ribavirin
  • daclatasvir
  • peginterferon alfa-2a
  • asunaprevir

Associated data

  • ClinicalTrials.gov/NCT01573351