Ledipasvir-Sofosbuvir for 12 Weeks in Children 3 to <6 Years Old With Chronic Hepatitis C

Hepatology. 2020 Feb;71(2):422-430. doi: 10.1002/hep.30830. Epub 2019 Aug 19.

Abstract

For children under 12 years of age who have chronic hepatitis C virus (HCV) infection, there are currently no approved treatments with direct-acting antiviral agents. We therefore evaluated the safety and efficacy of ledipasvir-sofosbuvir in HCV-infected children aged 3 to <6 years. In an open-label study, patients 3 to <6 years old chronically infected with HCV genotype 1 (n = 33) or 4 (n = 1) received weight-based doses of combined ledipasvir-sofosbuvir as granules (33.75 mg/150 mg for weights <17 kg or 45 mg/200 mg for weights ≥17 kg) for 12 weeks. The primary endpoint was sustained virological response 12 weeks after treatment (SVR12). For the first 14 patients, intensive pharmacokinetic sampling was done on day 10 of treatment. All patients had been infected through perinatal transmission and were treatment naïve. No patients had known cirrhosis. Ten patients (29%) weighed <17 kg. SVR12 was achieved in 97% of patients (33 of 34); the patient who did not achieve SVR12 was 3 years old and discontinued treatment after 5 days because of an adverse event "abnormal drug taste." The most common adverse events were vomiting (24% of patients), cough (21%), and pyrexia (21%). No patients experienced a serious adverse event. Intensive pharmacokinetic analysis of 13 patients for whom data were evaluable confirmed that the doses selected were appropriate. Conclusion: Ledipasvir-sofosbuvir was well tolerated and highly effective in children 3 to <6 years old with chronic HCV infection.

Trial registration: ClinicalTrials.gov NCT02249182.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / adverse effects
  • Benzimidazoles / administration & dosage*
  • Benzimidazoles / adverse effects
  • Child
  • Child, Preschool
  • Female
  • Fluorenes / administration & dosage*
  • Fluorenes / adverse effects
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Male
  • Sofosbuvir
  • Sustained Virologic Response
  • Time Factors
  • Treatment Outcome
  • Uridine Monophosphate / administration & dosage
  • Uridine Monophosphate / adverse effects
  • Uridine Monophosphate / analogs & derivatives*

Substances

  • Antiviral Agents
  • Benzimidazoles
  • Fluorenes
  • ledipasvir, sofosbuvir drug combination
  • Uridine Monophosphate
  • Sofosbuvir

Associated data

  • ClinicalTrials.gov/NCT02249182
  • EudraCT/2014‐003578‐17