Sofosbuvir–velpatasvir in children 3–17 years old with hepatitis C virus infection

Maureen M. Jonas, Rene Romero, Philip Rosenthal, Chuan Hao Lin, Gabriella Verucchi, Jessica Wen, William F. Balistreri, Suzanne Whitworth, Sanjay Bansal, Daniel H. Leung, Michael R. Narkewicz, Regino P. Gonzalez-Peralta, Alessandra Mangia, Wikrom Karnsakul, Girish S. Rao, Jiang Shao, Jan de Jong, Bandita Parhy, Anu Osinusi, Kathryn KerseyKaren F. Murray, Etienne M. Sokal, Kathleen B. Schwarz

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The safety and efficacy of sofosbuvir–velpatasvir in children aged 3–17 years with chronic hepatitis C virus (HCV) infection of any genotype were evaluated. Methods: In this Phase 2, multicenter, open-label study, patients received once daily for 12 weeks either sofosbuvir–velpatasvir 400/100 mg tablet (12–17 years), 200/50 mg low dose tablet or oral granules (3–11 years and ≥17 kg), or 150/37.5 mg oral granules (3–5 years and <17 kg). The efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Dose appropriateness was confirmed by intensive pharmacokinetics in each age group. Findings: Among 216 patients treated, 76% had HCV genotype 1% and 12% had genotype 3. Rates of SVR12 were 83% (34/41) among 3–5-year-olds, 93% (68/73) among 6–11-year-olds, and 95% (97/102) among 12–17-year-olds. Only two patients experienced virologic failure. The most common adverse events were headache, fatigue, and nausea in 12–17-year-olds; vomiting, cough, and headache in 6–11-year-olds; and vomiting in 3–5-year-olds. Three patients discontinued treatment because of adverse events. Four patients had serious adverse events; all except auditory hallucination (n = 1) were considered unrelated to study drug. Exposures of sofosbuvir, its metabolite GS-331007, and velpatasvir were comparable to those in adults in prior Phase 2/3 studies. Population pharmacokinetic simulations supported weight-based dosing for children in this age range. Interpretation: The pangenotypic regimen of sofosbuvir–velpatasvir is highly effective and safe in treating children 3–17 years with chronic HCV infection.

Original languageEnglish (US)
Pages (from-to)1342-1354
Number of pages13
JournalJournal of pediatric gastroenterology and nutrition
Volume78
Issue number6
DOIs
StatePublished - Jun 2024

Keywords

  • direct-acting antiviral
  • pediatrics
  • pharmacokinetics
  • polymerase inhibitor

ASJC Scopus subject areas

  • Gastroenterology
  • Pediatrics, Perinatology, and Child Health

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