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Significant PK variability of plasma-derived FIX concentrates in chinese children with Haemophilia B: A fixed single-dose study of factor IX-CTBB

Year: 2025

Type: article

Abstract: The pharmacokinetics (PK) characters of plasma-derived Factor IX (pdFIX) concentrate in Chinese children with Haemophilia B(HB) have not yet been reported. To assess the PK parameters of pdFIX in children with severe HB and identify factors that influence FIX PK. This non-randomized, open-label PK study enrolled children with severe HB (FIX≤2 %). Patients received 50 IU± 5 IU/kg pdFIX (Human coagulation Factor IX-CTBB) after at least 96 h wash-out period. Blood samples for PK assessments were collected before infusion (pre-dose) and at 15 min, 30 min, 1 h, 3 h, 6 h, 9 h, 24 h, 48 h, 72 h and 96 h post-infusion. FIX activity was measured by a one-stage assay. Twenty patients were enrolled with a median age of 8.3 (range 1.8–15.4) years. The peak plasma levels of FIX: C in all patients were observed within 15 min. Their median terminal half-life (t 1/2 ) was 32.6 (range 23.3–52.0) hours. The median values of in vivo recovery (IVR) at 15 min, clearance (CL), volume of distribution at state (Vss) and area under the curve (AUC) were 1.0 (0.9, 1.2) IU/dL per IU/kg, 5.2 (IQR 4.8, 6.4) mL/h/kg, 207.9 (IQR 183.5, 301.4) mL/kg, 9.77 (IQR 7.76, 11.23) U*h/mL respectively. The t 1/2 , Vss and mean residence time after intravenous injection (MRT) decreased with increasing age and body weight. Changes in CL with body weight were similar to t 1/2 , but no significant correlation exists with age. There is a significant inter-individual variability in PK profiles among Chinese children with severe HB, which is related to age and body weight changes, indicating the necessity of individualized prophylaxis driven by PK.

Source: Global Medical Genetics

DOI: 10.1016/j.gmg.2025.100040