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Elbasvir/grazoprevir in children aged 3-18 years with chronic HCV genotype 1 or 4 infection: a pharmacokinetic

Regino P Gonzalez-Peralta1, Stefan Wirth2, Robert H Squires3

  • 1AdventHealth for Children and AdventHealth Transplant Institute, Orlando, Florida, USA.

Hepatology Communications
|February 15, 2023
PubMed

Insights

Pediatric elbasvir/grazoprevir (EBR/GZR) doses were determined using pharmacokinetic modeling to effectively treat chronic hepatitis C virus (HCV) infection in children and adolescents. This age-appropriate dosing ensures safety and efficacy, mirroring adult treatment outcomes.

Area of Science:

  • Hepatology
  • Pharmacology
  • Clinical Trials

Background:

  • Chronic hepatitis C virus (HCV) infection affects approximately 3.5 million children and adolescents globally.
  • Existing HCV treatments require dose adjustments for pediatric populations.

Purpose of the Study:

  • To identify pediatric doses of elbasvir/grazoprevir (EBR/GZR) using pharmacokinetic modeling.
  • To achieve plasma concentrations in children comparable to those in adults on EBR/GZR.

Main Methods:

  • A nonrandomized, single-arm, open-label phase 2b trial was conducted in 57 participants aged 3 to <18 years with chronic HCV genotypes 1 or 4.
  • Pharmacokinetic data were used to bridge adult efficacy and safety data to pediatric cohorts.
  • Participants were enrolled in age-based cohorts: 12 to <18 years, 7 to <12 years, and 3 to <7 years.

Main Results:

  • Daily dosing of EBR/GZR achieved steady-state plasma exposures within comparability bounds established for adults by week 4.
  • All participants achieved sustained virologic response 12 weeks post-treatment.
  • The most common treatment-related adverse events were headache, fatigue, and nausea, all mild or moderate; no discontinuations occurred.

Conclusions:

  • Pediatric pharmacokinetic models for EBR/GZR were successfully developed from adult models.
  • Age-related doses of EBR/GZR demonstrated safety and efficacy in pediatric and adolescent participants with HCV infection.
Abstract

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