Pharmacokinetic properties of IB1001, an investigational recombinant factor IX, in patients with haemophilia B: Repeat pharmacokinetic evaluation and sialylation analysis

U. Martinowitz, A. Shapiro, D. V. Quon, M. Escobar, C. Kempton, P. W. Collins, P. Chowdary, M. Makris, P. M. Mannucci, M. Morfini, L. A. Valentino, E. Gomperts, M. Lee

Research output: Contribution to journalArticle

19 Citations (Scopus)

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 AUC0-t and AUC0-∞ (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.

Original languageEnglish
Pages (from-to)881-887
Number of pages7
JournalHaemophilia
Volume18
Issue number6
DOIs
Publication statusPublished - Nov 2012

Fingerprint

Hemophilia B
Factor IX
Pharmacokinetics
IB1001
Cross-Over Studies

Keywords

  • Blood coagulation factor
  • Haemophilia B
  • IB1001
  • Pharmacokinetics
  • Recombinant factor IX
  • Sialylation

ASJC Scopus subject areas

  • Hematology
  • Genetics(clinical)

Cite this

Pharmacokinetic properties of IB1001, an investigational recombinant factor IX, in patients with haemophilia B : Repeat pharmacokinetic evaluation and sialylation analysis. / Martinowitz, U.; Shapiro, A.; Quon, D. V.; Escobar, M.; Kempton, C.; Collins, P. W.; Chowdary, P.; Makris, M.; Mannucci, P. M.; Morfini, M.; Valentino, L. A.; Gomperts, E.; Lee, M.

In: Haemophilia, Vol. 18, No. 6, 11.2012, p. 881-887.

Research output: Contribution to journalArticle

Martinowitz, U, Shapiro, A, Quon, DV, Escobar, M, Kempton, C, Collins, PW, Chowdary, P, Makris, M, Mannucci, PM, Morfini, M, Valentino, LA, Gomperts, E & Lee, M 2012, 'Pharmacokinetic properties of IB1001, an investigational recombinant factor IX, in patients with haemophilia B: Repeat pharmacokinetic evaluation and sialylation analysis', Haemophilia, vol. 18, no. 6, pp. 881-887. https://doi.org/10.1111/j.1365-2516.2012.02897.x
Martinowitz, U. ; Shapiro, A. ; Quon, D. V. ; Escobar, M. ; Kempton, C. ; Collins, P. W. ; Chowdary, P. ; Makris, M. ; Mannucci, P. M. ; Morfini, M. ; Valentino, L. A. ; Gomperts, E. ; Lee, M. / Pharmacokinetic properties of IB1001, an investigational recombinant factor IX, in patients with haemophilia B : Repeat pharmacokinetic evaluation and sialylation analysis. In: Haemophilia. 2012 ; Vol. 18, No. 6. pp. 881-887.
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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 AUC0-t and AUC0-∞ (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.",
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