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Abstract Details
Pharmacokinetics, safety, and efficacy of glecaprevir/pibrentasvir in children with chronic hepatitis C virus: part 2 of the DORA study
Hepatology. 2021 Apr 2. doi: 10.1002/hep.31841. Online ahead of print.
Maureen M Jonas1, Susan Rhee2, Deirdre A Kelly3, Antonio Del Valle-Segarra4, Cornelia Feiterna-Sperling5, Susan Gilmour6, Regino P Gonzalez-Peralta7, Loreto Hierro8, Daniel H Leung9, Simon C Ling10, Yuri Lobzin11, Steven Lobritto12, Tatsuki Mizuochi13, Michael R Narkewicz14, Vishakha Sabharwal15, Jessica Wen16, Hoi Kei Lon2, John Marcinak2, Andrew Topp2, Rakesh Tripathi2, Etienne Sokal17
Author information
1Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, United States.
2AbbVie Inc, North Chicago, Illinois, United States.
3The Liver Unit, Birmingham Women's & Children's Hospital, University of Birmingham, Birmingham, United Kingdom.
4San Jorge Children's Hospital, San Juan, Puerto Rico.
5Department of Pediatric Pulmonology, Immunology, and Intensive Care Medicine, Berlin, Germany.
6Stollery Children's Hospital, University of Alberta, Alberta, Canada.
7AdventHealth for Children, AdventHealth Transplant Institute, Orlando, Florida, United States.
8Hospital Universitario La Paz, Madrid, Spain.
9Division of Gastroenterology, Hepatology, and Nutrition, Texas Children's Hospital, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, United States.
10Division of Gastroenterology, Hepatology, and Nutrition, The Hospital for Sick Children, Department of Paediatrics, University of Toronto, Toronto, Canada.
11Pediatric Research and Clinical Center for Infectious Diseases, Russian Federation, North-Western State Medical University named after I.I. Mechnikov, Russian Federation, St Petersburg, Russia.
12Morgan Stanley Children's Hospital of NY, Columbia University Irving Medical Center, New York, New York, United States.
13Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan.
14Digestive Health Institute, Children's Hospital Colorado, Section of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Colorado School of Medicine, Aurora Colorado, United States.
15Division of Pediatrics Infectious Diseases, Department of Pediatrics, Boston University Medical Center, Boston, Massachusetts, United States.
16The Children's Hospital Philadelphia and University of Pennsylvania, Philadelphia, Pennsylvania, United States.
17Université Catholique de Louvain, Cliniques Universitaires Saint Luc, Division of Pediatric Gastroenterology and Hepatology, Brussels, Belgium.
Abstract
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.