PB0621 - Population pharmacokinetics model of BAY81-8973 in Chinese children with severe haemophilia A

Monday, June 24, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Co-Author(s)

Yaohan Zhou, MA

student
Beijing Children’s Hospital, Capital Medical University
Beijing, Beijing, China (People's Republic)
Zhenping Chen

Associate professor
Hematologic Diseases Laboratory, Hematology Center, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, ChinaChildren’s Health, Beijing, 100045, China
Beijing, Beijing, China (People's Republic)
KH

Kun Huang

Doctor
Hematology Department II, Beijing Key Laboratory of Pediatric Hematology Oncology; National Key Discipline of Pediatrics (Capital Medical University); Key Laboratory of Major Diseases in Children, Ministry of Education; Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, China
Beijing, Beijing, China (People's Republic)
XC

Xiaoling Cheng

Department of Pharmacy
Beijing Children’s Hospital, Capital Medical University,
Beijing, Beijing, China (People's Republic)
Wanru Yao, MA

Doctor
Haemophilia Comprehensive Care Center, Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology; National Key Discipline of Pediatrics (Capital Medical University); Key Laboratory of Major Diseases in Children, Ministry of Education; Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, China, 100045
Beijing, Beijing, China (People's Republic)

Presenting Author(s)

Runhui Wu, PhD, MD

Professor
Department of Hematology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, China
Beijing, Beijing, China (People's Republic)

Background: Pharmacokinetic (PK) can effectively tailor prophylaxis treatment plans for different patients and new ISTH recommendation rely on the use of population pharmacokinetics (PopPK) models. Kovaltry (BAY81-8973; Bayer, Berkeley, CA, USA) is an unmodified, full length, recombinant factor VIII (FVIII) concentrate, which has been used as the standard treatment for people with haemophilia A. There is currently no research on Kovaltry PopPK model in Chinese children with severe haemophilia A.

Aims: To conduct the first PopPK model of Kovaltry in Chinese children with severe hemophilia A and identify correlates of variability in Kovaltry PK.

Methods: A PopPK model was developed based on 69 children with severe hemophilia A aged 6.1±2.7 [2.0, 13.1] were included. Patients received PK tests after a washout period of at least 72 hours and a single dose of 50 IU/kg coagulation FVIII concentrate. The PopPK model of Kovaltry was described using the nonlinear mixed-effects modeling software package (NONMEM 7.3.0). Covariate analysis was applied to select candidate factors associated with PK parameters. The final model was validated using bootstrap (1000 runs) and visual predictive checks (pc-VPC) method. A two-compartment PK model was developed.

Results: A two-compartment PopPK model adequately described FVIII activity. VWF:Ag and blood type were significant descriptors of clearance (CL) and volume of central compartment (V1). Fat free mass (FFM) was a significant descriptor of CL, volume of peripheral compartment (V1 & V2). The outcome parameters were as follows: CL 0.0787L/h, V1 1.12L.

Conclusion(s): This is the first study to describe a PopPK model of Kovaltry pediatric patients with severe haemophilia A. PopPK model–based dose individualization of Kovaltry and the design of future clinical studies in children will be facilitated by the developed model in this study.