PMID- 33811356 OWN - NLM STAT- MEDLINE DCOM- 20220104 LR - 20230921 IS - 1527-3350 (Electronic) IS - 0270-9139 (Print) IS - 0270-9139 (Linking) VI - 74 IP - 1 DP - 2021 Jul TI - Pharmacokinetics, Safety, and Efficacy of Glecaprevir/Pibrentasvir in Children With Chronic HCV: Part 2 of the DORA Study. PG - 19-27 LID - 10.1002/hep.31841 [doi] AB - 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. CI - (c) 2021 by the American Association for the Study of Liver Diseases. FAU - Jonas, Maureen M AU - Jonas MM AD - Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Boston, MA. AD - Department of Pediatrics, Harvard Medical School, Boston, MA. FAU - Rhee, Susan AU - Rhee S AD - AbbVie Inc., North Chicago, IL. FAU - Kelly, Deirdre A AU - Kelly DA AD - The Liver Unit, Birmingham Women's & Children's Hospital and University of Birmingham, Birmingham, United Kingdom. FAU - Del Valle-Segarra, Antonio AU - Del Valle-Segarra A AD - San Jorge Children's Hospital, San Juan, Puerto Rico. FAU - Feiterna-Sperling, Cornelia AU - Feiterna-Sperling C AD - Department of Pediatric Pulmonology, Immunology, and Intensive Care Medicine, Charite-Universitatsmedizin Berlin, Berlin, Germany. FAU - Gilmour, Susan AU - Gilmour S AD - Stollery Children's Hospital and University of Alberta, Edmonton, AB, Canada. FAU - Gonzalez-Peralta, Regino P AU - Gonzalez-Peralta RP AD - AdventHealth for Children, AdventHealth Transplant Institute, Orlando, FL. FAU - Hierro, Loreto AU - Hierro L AD - Hospital Universitario La Paz, Madrid, Spain. FAU - Leung, Daniel H AU - Leung DH AD - Division of Gastroenterology, Hepatology, and Nutrition, Texas Children's Hospital, Houston, TX. AD - Department of Pediatrics, Baylor College of Medicine, Houston, TX. FAU - Ling, Simon C AU - Ling SC AD - Division of Gastroenterology, Hepatology, and Nutrition, The Hospital for Sick Children, Toronto, ON, Canada. AD - Department of Paediatrics, University of Toronto, Toronto, ON, Canada. FAU - Lobzin, Yuri AU - Lobzin Y AD - Pediatric Research and Clinical Center for Infectious Diseases and North-Western State Medical University named after I.I. Mechnikov, Russian Federation, St. Petersburg, Russia. FAU - Lobritto, Steven AU - Lobritto S AUID- ORCID: 0000-0003-1482-1128 AD - Morgan Stanley Children's Hospital of New York, Columbia University Irving Medical Center, New York, NY. FAU - Mizuochi, Tatsuki AU - Mizuochi T AD - Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan. FAU - Narkewicz, Michael R AU - Narkewicz MR AD - Digestive Health Institute, Children's Hospital Colorado, Section of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics University of Colorado School of Medicine, Aurora, CO. FAU - Sabharwal, Vishakha AU - Sabharwal V AD - Division of Pediatric Infectious Diseases, Department of Pediatrics, Boston University Medical Center, Boston, MA. FAU - Wen, Jessica AU - Wen J AD - The Children's Hospital Philadelphia and University of Pennsylvania, Philadelphia, PA. FAU - Kei Lon, Hoi AU - Kei Lon H AD - AbbVie Inc., North Chicago, IL. FAU - Marcinak, John AU - Marcinak J AD - AbbVie Inc., North Chicago, IL. FAU - Topp, Andrew AU - Topp A AD - AbbVie Inc., North Chicago, IL. FAU - Tripathi, Rakesh AU - Tripathi R AD - AbbVie Inc., North Chicago, IL. FAU - Sokal, Etienne AU - Sokal E AUID- ORCID: 0000-0001-5597-4708 AD - Division of Pediatric Gastroenterology and Hepatology, Universite Catholique de Louvain, Cliniques Universitaires Saint Luc, Brussels, Belgium. LA - eng SI - ClinicalTrials.gov/NCT03067129 PT - Clinical Trial, Phase II PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't PL - United States TA - Hepatology JT - Hepatology (Baltimore, Md.) JID - 8302946 RN - 0 (Antiviral Agents) RN - 0 (Benzimidazoles) RN - 0 (Drug Combinations) RN - 0 (Pyrrolidines) RN - 0 (Quinoxalines) RN - 0 (Sulfonamides) RN - 0 (glecaprevir and pibrentasvir) SB - IM MH - Antiviral Agents/administration & dosage/adverse effects/*pharmacokinetics MH - Benzimidazoles/administration & dosage/adverse effects/*pharmacokinetics MH - Child MH - Child, Preschool MH - Drug Combinations MH - Female MH - Genotyping Techniques MH - Hepacivirus/genetics/isolation & purification MH - Hepatitis C, Chronic/diagnosis/*drug therapy/virology MH - Humans MH - Male MH - Pyrrolidines/administration & dosage/adverse effects/*pharmacokinetics MH - Quinoxalines/administration & dosage/adverse effects/*pharmacokinetics MH - Sulfonamides/administration & dosage/adverse effects/*pharmacokinetics MH - Treatment Outcome PMC - PMC8548879 EDAT- 2021/04/04 06:00 MHDA- 2022/01/05 06:00 PMCR- 2021/10/27 CRDT- 2021/04/03 05:56 PHST- 2021/02/25 00:00 [revised] PHST- 2020/12/07 00:00 [received] PHST- 2021/03/22 00:00 [accepted] PHST- 2021/04/04 06:00 [pubmed] PHST- 2022/01/05 06:00 [medline] PHST- 2021/04/03 05:56 [entrez] PHST- 2021/10/27 00:00 [pmc-release] AID - HEP31841 [pii] AID - 10.1002/hep.31841 [doi] PST - ppublish SO - Hepatology. 2021 Jul;74(1):19-27. doi: 10.1002/hep.31841.