title: Pharmacokinetic properties of IB1001, an investigational recombinant factor IX, in patients with haemophilia B: repeat pharmacokinetic evaluation and sialylation analysis.
abstract: IB1001 trenacog alfa is an investigational recombinant factor IX (FIX) for the treatment and prevention of bleeding in individuals with haemophilia B. To compare the pharmacokinetics (PK) of IB1001 with nonacog alfa in individuals with haemophilia B and to assess the relationship between sialylation and PK of IB1001 (NCT00768287). A randomized, double-blind, non-inferiority, cross-over study conducted in participants aged ≥ 12 years weighing ≥ 40 kg, with severe or moderately severe haemophilia B (FIX activity ≤ 2 IU dL (-1) ). PK parameters were derived using observed FIX concentration levels and actual PK sampling times, and repeated in a subset of participants who had received IB1001 prophylaxis for 4-18 months. A retrospective analysis was conducted in subgroups according to the sialylation levels of IB1001 (50.8, 57.8-59.0%, or 71.7%). In the 32 adolescent and adult males evaluated, there were no clinically meaningful differences in PK parameters between those receiving IB1001 75 IU kg(-1) or nonacog alfa. The lower limit of the one-sided 95% confidence interval for the ratio of AUC(0-t) and AUC(0-∞) (IB1001/nonacog alfa) was 0.90, establishing non-inferiority. Terminal phase half-lives were similar (29.7 ± 18.2 h for IB1001 and 33.4 ± 21.2 h for nonacog alfa). The PK results were stable for up to 18 months of IB1001 exposure; the impact of sialylation levels was not clinically meaningful. There were no clinically meaningful PK differences between IB1001 and nonacog alfa. IB1001 was well tolerated and without safety concerns. The non-inferiority of IB1001 to nonacog alfa supports IB1001 becoming a useful alternative recombinant agent for the management of haemophilia B.
authors: Institute of Thrombosis and Hemostasis and the National Hemophilia Center, Sheba Medical Center, Tel Hashomer, Israel.
authors: U
authors: U
authors: Martinowitz
authors: A
authors: A
authors: Shapiro
authors: D V
authors: DV
authors: Quon
authors: M
authors: M
authors: Escobar
authors: C
authors: C
authors: Kempton
authors: P W
authors: PW
authors: Collins
authors: P
authors: P
authors: Chowdary
authors: M
authors: M
authors: Makris
authors: P M
authors: PM
authors: Mannucci
authors: M
authors: M
authors: Morfini
authors: L A
authors: LA
authors: Valentino
authors: E
authors: E
authors: Gomperts
authors: M
authors: M
authors: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005164:Factor IX / Q000032:analysis / Q000235:genetics / Q000493:pharmacokinetics*; D006207:Half-Life; D002836:Hemophilia B / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics / Q000493:pharmacokinetics*; D012189:Retrospective Studies; D012794:Sialic Acids / Q000032:analysis*; D055815:Young Adult
chemical_list: C579324:IB1001; D011994:Recombinant Proteins; D012794:Sialic Acids; D005164:Factor IX