Pharmacokinetics, safety, and efficacy of glecaprevir/pibrentasvir in children with chronic hepatitis C virus: part 2 of the DORA study.

BACKGROUND AND AIMS Glecaprevir/pibrentasvir (GLE/PIB) has shown high efficacy and safety in chronic hepatitis C virus (HCV)-infected adults and adolescents; data in children were limited. DORA part 2 is a phase 2/3, nonrandomized, open-label study evaluating the pharmacokinetics, efficacy, and safety of a pediatric formulation of glecaprevir (GLE) and pibrentasvir (PIB) in children ages 3 - < 12 years old. APPROACH AND RESULTS Children with chronic HCV infection, genotype (GT) 1-6, with or without compensated cirrhosis, were divided into 3 cohorts by age, cohort 2 (9 - < 12 years), cohort 3 (6 - < 9 years), and cohort 4 (3 - < 6 years) and given weight-based doses of GLE and PIB for 8, 12, or 16 weeks. Primary endpoints were SVR12 and steady-state exposure; secondary endpoints were rates of persistent viremia, relapse, and reinfection. Safety and laboratory abnormalities were assessed. Final pediatric dosages determined to be efficacious were 250 mg GLE + 100 mg PIB (in children weighing ≥ 30 kg to < 45 kg), 200 mg GLE + 80 mg PIB (≥ 20 kg to < 30 kg), and 150 mg GLE + 60 mg PIB (12 kg to < 20 kg). Of 80 participants enrolled and dosed, 96% (77/80) achieved SVR12. One participant, on the initial dose ratio, relapsed by post-treatment week 4; no participants had virologic failures on the final dose ratio of GLE 50 mg/PIB 20 mg. Two non-responders prematurely discontinued the study. Most adverse events (AEs) were mild; no drug-related serious AEs occurred. Pharmacokinetic exposures were comparable to adults. CONCLUSIONS A pediatric formulation of GLE/PIB was highly efficacious and well-tolerated in chronic HCV-infected children 3 - < 12 years old.