Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir Mini-Tabs Plus Ribavirin for Children Aged 3-11 Years with Hepatitis C Genotype 1a

Adv Ther. 2020 Jul;37(7):3299-3310. doi: 10.1007/s12325-020-01389-9. Epub 2020 May 25.

Abstract

Introduction: To assess the safety, efficacy, and pharmacokinetics of mini-tablet formulations of ombitasvir (OBV), paritaprevir (PTV), ritonavir, and dasabuvir (DSV) with or without ribavirin for 12 weeks in children infected with chronic hepatitis C virus (HCV) genotype (GT) 1.

Methods: This is an ongoing, open-label, Phase 2/3 study in children 3-11 years old infected with HCV GT1 who were HCV treatment-naïve and non-cirrhotic. Pediatric mini-tablet formulations of OBV, PTV, ritonavir, and DSV plus ribavirin oral solution were administered for 12 weeks based on body weight. Endpoints included SVR12, adverse events (AEs), and pharmacokinetic parameters.

Results: Overall, 26 children received OBV, PTV, ritonavir, and DSV plus ribavirin; 14 were 3-8 years old and 12 were 9-11 years old; 35% were male; and all had chronic HCV GT1a infection. The SVR12 rate was 96% (25/26; 95% CI 81.1-99.3), with 1 child failing to achieve SVR12 due to non-adherence and treatment discontinuation. Treatment-emergent AEs of Grade ≥ 3 occurred in 3 children; 2 events in 1 child were considered serious; and none were considered treatment-related. No AEs led to discontinuation of study treatment. The most common AEs were headache (27%), fatigue (23%), pyrexia (19%), and vomiting (19%). Pharmacokinetic results showed mini-tablet formulations of OBV, PTV, DSV, and ritonavir drug exposures were comparable to the adult formulation.

Conclusion: The mini-tablet combination of OBV, PTV, ritonavir, and DSV plus ribavirin to treat HCV GT1a infection for 12 weeks was highly effective and suitable in children 3-11 years of age.

Trial registration: ClinicalTrials.gov identifier, NCT02486406.

Keywords: Efficacy; Hepatology; Interferon-free DAA regimens; Pediatrics; Pharmacokinetics; Safety.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Naphthylamine
  • Anilides / therapeutic use*
  • Antiviral Agents / therapeutic use*
  • Carbamates / therapeutic use*
  • Child
  • Child, Preschool
  • Cyclopropanes / therapeutic use*
  • Cytochrome P-450 CYP3A Inhibitors / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Genotype
  • Hepacivirus / drug effects
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Lactams, Macrocyclic / therapeutic use*
  • Male
  • Proline / analogs & derivatives*
  • Proline / therapeutic use
  • Ribavirin / therapeutic use*
  • Ritonavir / therapeutic use*
  • Sulfonamides / therapeutic use*
  • Tablets
  • Uracil / analogs & derivatives*
  • Uracil / therapeutic use
  • Valine

Substances

  • Anilides
  • Antiviral Agents
  • Carbamates
  • Cyclopropanes
  • Cytochrome P-450 CYP3A Inhibitors
  • Lactams, Macrocyclic
  • Sulfonamides
  • Tablets
  • ombitasvir
  • Ribavirin
  • Uracil
  • Proline
  • 2-Naphthylamine
  • dasabuvir
  • Valine
  • Ritonavir
  • paritaprevir

Associated data

  • ClinicalTrials.gov/NCT02486406