Pharmacokinetics, Safety, and Efficacy of Glecaprevir/Pibrentasvir in Children With Chronic HCV: Part 2 of the DORA Study

• Published in: Hepatology (Baltimore, Md.) Vol. 74; no. 1; pp. 19 - 27
• Main Authors: Jonas, Maureen M., Rhee, Susan, Kelly, Deirdre A., Del Valle‐Segarra, Antonio, Feiterna‐Sperling, Cornelia, Gilmour, Susan, Gonzalez‐Peralta, Regino P., Hierro, Loreto, Leung, Daniel H., Ling, Simon C., Lobzin, Yuri, Lobritto, Steven, Mizuochi, Tatsuki, Narkewicz, Michael R., Sabharwal, Vishakha, Wen, Jessica, Kei Lon, Hoi, Marcinak, John, Topp, Andrew, Tripathi, Rakesh, Sokal, Etienne
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.07.2021; John Wiley and Sons Inc
• Subjects: Adverse events; Antiviral Agents - administration & dosage; Antiviral Agents - adverse effects; Antiviral Agents - pharmacokinetics; Benzimidazoles - administration & dosage; Benzimidazoles - adverse effects; Benzimidazoles - pharmacokinetics; Child; Child, Preschool; Children; Chronic infection; Cirrhosis; Dosage; Drug Combinations; Female; Genotypes; Genotyping Techniques; Hepacivirus - genetics; Hepacivirus - isolation & purification; Hepatitis C, Chronic - diagnosis; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - virology; Hepatology; Humans; Liver cirrhosis; Male; Pediatrics; Pharmacokinetics; Pyrrolidines - administration & dosage; Pyrrolidines - adverse effects; Pyrrolidines - pharmacokinetics; Quinoxalines - administration & dosage; Quinoxalines - adverse effects; Quinoxalines - pharmacokinetics; Rapid Communication; Safety; Sulfonamides - administration & dosage; Sulfonamides - adverse effects; Sulfonamides - pharmacokinetics; Treatment Outcome; Viremia
• ISSN: 0270-9139; 1527-3350
• DOI: 10.1002/hep.31841

Background and Aims Glecaprevir/pibrentasvir (GLE/PIB) has shown high efficacy and safety in chronic 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 GLE and PIB in children ages 3 to < 12 years. Approach and Results Children with chronic HCV infection, genotype 1‐6, with or without compensated cirrhosis, were divided into three cohorts by age—cohort 2 (9 to < 12 years), cohort 3 (6 to < 9 years), and cohort 4 (3 to < 6 years)—and given weight‐based doses of GLE and PIB for 8, 12, or 16 weeks. Primary endpoints were sustained virologic response at posttreatment week 12 (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 to < 45 kg), 200 mg GLE + 80 mg PIB (≥ 20 to < 30 kg), and 150 mg GLE + 60 mg PIB (12 to < 20 kg). Of 80 participants enrolled and dosed, 96% (77/80) achieved SVR12. One participant, on the initial dose ratio, relapsed by posttreatment week 4; no participants had virologic failures on the final dose ratio of GLE 50 mg/PIB 20 mg. Two nonresponders prematurely discontinued the study. Most adverse events (AEs) were mild; no drug‐related serious AEs occurred. Pharmacokinetic exposures were comparable to those of adults. Conclusions A pediatric formulation of GLE/PIB was highly efficacious and well tolerated in chronic HCV‐infected children 3 to < 12 years old.