Ombitasvir/paritaprevir/ritonavir & dasabuvir ± ribavirin following protease inhibitors failure - a prospective multi-centre trial

BMC Infect Dis. 2020 Apr 3;20(1):264. doi: 10.1186/s12879-020-4921-3.

Abstract

Background: Hepatitis C virus (HCV) infection is a leading cause of chronic liver disease and hepatocellular carcinoma. Treatment with first generation protease inhibitors (PI) + peg-interferon (pegIFN) and ribavirin (RBV) achieved sustained virologic response (SVR) rates of 65-75% but was associated with multiple side effects. The aim of this study was to evaluate safety and efficacy of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir (3D) ± RBV in HCV genotype 1 patients that failed previous treatment with first generation PIs.

Methods: An investigator-initiated, open-label, multi-centre clinical trial. HCV Genotype 1 patients who were previously null/partial responders or relapsers to telaprevir, boceprevir or simepravir+pegIFN/RBV and met eligibility criteria were included. 3D ± RBV were administrated for 12 or 24 weeks according to label. The primary outcome was antiviral response (SVR12); Secondary outcomes were patient reported outcomes, adverse events and resistance associated variants.

Results: Thirty-nine patients initiated treatment according to study protocol (59% men, age 54.0 ± 8.7 years, BMI 28.7 ± 4.5 kg/m2). Thirty-seven (94.9%) completed the study. Thirty-five patients had genotype 1b (9 cirrhotics) and 4 had genotype 1a (2 cirrhotics). Intention-to-treat SVR12 was 92.3% and per-protocol SVR12 was 97.3%. The rate of advanced fibrosis (FibroScan® score F3-4) declined from 46.2 to 25.7% (P = 0.045). Abnormal ALT levels declined from 84.6 to 8.6% (P < 0.001). Seven patients (17.9%) experienced serious adverse events (3 Psychiatric admissions, 1 pneumonia, 1 ankle fracture, 2 palpitations), and 12 patients (30.8%) experienced self-reported adverse events, mostly weakness.

Conclusion: 3D ± RBV is safe and effective in achieving SVR among patients with HCV genotype 1 who failed previous first-generation PI treatment.

Trial registration: NCT02646111 (submitted to ClinicalTrials.gov, December 28, 2015).

Keywords: AbbVie 3D; Direct acting anti-viral agents; HCV; Protease inhibitors failure.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Anilides / adverse effects
  • Anilides / therapeutic use*
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Carbamates / adverse effects
  • Carbamates / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Genotype
  • Hepatitis C / drug therapy*
  • Hepatitis C / virology
  • Humans
  • Macrocyclic Compounds / adverse effects
  • Macrocyclic Compounds / therapeutic use*
  • Male
  • Middle Aged
  • Prospective Studies
  • Protease Inhibitors / adverse effects
  • Protease Inhibitors / therapeutic use*
  • Ribavirin / adverse effects
  • Ribavirin / therapeutic use*
  • Ritonavir / adverse effects
  • Ritonavir / therapeutic use*
  • Sulfonamides / adverse effects
  • Sulfonamides / therapeutic use*
  • Treatment Outcome
  • Uracil / adverse effects
  • Uracil / analogs & derivatives*
  • Uracil / therapeutic use

Substances

  • ABT-267
  • ABT-333
  • Anilides
  • Antiviral Agents
  • Carbamates
  • Macrocyclic Compounds
  • Protease Inhibitors
  • Sulfonamides
  • Ribavirin
  • Uracil
  • Ritonavir
  • paritaprevir

Associated data

  • ClinicalTrials.gov/NCT02646111