Author information

¹Boston Children's Hospital, Boston, Massachusetts, USA.

²Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, Georgia, USA.

³Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of California San Francisco, Benioff Children's Hospital, San Francisco, California, USA.

⁴Children's Hospital Los Angeles, Los Angeles, California, USA.

⁵Università di Bologna, Bologna, Italy.

⁶University of Pennsylvania and The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

⁷Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

⁸Cook Children's Health Care System, Fort Worth, Texas, USA.

⁹King's College Hospital, London, UK.

¹⁰Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA.

¹¹School of Medicine and Children's Hospital of Colorado, University of Colorado, Aurora, Colorado, USA.

¹²AdventHealth for Children and AdventHealth Transplant Institute, Orlando, Florida, USA.

¹³Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.

¹⁴Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

¹⁵Riley Hospital for Children, Indiana University School of Medicine, Indiana, Indianapolis, USA.

¹⁶Gilead Sciences Inc., Foster City, California, USA.

¹⁷Cleveland Clinic Children's Hospital, Cleveland, Ohio, USA.

¹⁸Cliniques Universitaires Saint-Luc, Service de Gastroentérologie Hépatologie Pédiatrique, Université Catholique de Louvain, Bruxelles, Belgique.

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.