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Enhanced pharmacokinetic properties of a glycoPEGylated recombinant factor IX: a first human dose trial in patients with hemophilia B

Negrier, Claude ; Knobe, Karin LU ; Tiede, Andreas ; Giangrande, Paul and Moss, Judi (2011) In Blood 118(10). p.2695-2701
Abstract
Replacement therapy with factor IX (FIX) concentrates is the recommended treatment for patients with hemophilia B, an X-linked bleeding disorder occurring in 1: 25 000 male births. N9-GP is a recombinant FIX molecule with a prolonged half-life which is obtained by site-directed glycoPEGylation where a 40-kDa polyethylene glycol molecule is attached to the activation peptide of FIX. This first human dose trial in patients with hemophilia B investigated the safety and pharmacokinetic properties of a single IV dose of N9-GP. Sixteen previously treated patients received one dose of their previous FIX product followed by one dose of N9-GP at the same dose level (25, 50, or 100 U/kg). None of the patients developed inhibitors. One patient... (More)
Replacement therapy with factor IX (FIX) concentrates is the recommended treatment for patients with hemophilia B, an X-linked bleeding disorder occurring in 1: 25 000 male births. N9-GP is a recombinant FIX molecule with a prolonged half-life which is obtained by site-directed glycoPEGylation where a 40-kDa polyethylene glycol molecule is attached to the activation peptide of FIX. This first human dose trial in patients with hemophilia B investigated the safety and pharmacokinetic properties of a single IV dose of N9-GP. Sixteen previously treated patients received one dose of their previous FIX product followed by one dose of N9-GP at the same dose level (25, 50, or 100 U/kg). None of the patients developed inhibitors. One patient developed transient hypersensitivity symptoms during administration of N9-GP and was excluded from pharmacokinetic analyses. In the remaining 15 patients, N9-GP was well-tolerated. The half-life was 93 hours, which was 5 times higher than the patient's previous product. The incremental recovery of N9-GP was 94% and 20% higher compared with recombinant and plasma-derived products, respectively. These results indicate that N9-GP has the potential to reduce dosing frequency while providing effective treatment of bleeding episodes with a single dose. The trial was registered at www.clinicaltrials.gov as NCT00956345. (Blood. 2011;118(10):2695-2701) (Less)
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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
118
issue
10
pages
2695 - 2701
publisher
American Society of Hematology
external identifiers
  • wos:000294801500014
  • scopus:80052669248
  • pmid:21555744
ISSN
1528-0020
DOI
10.1182/blood-2011-02-335596
language
English
LU publication?
yes
id
1eaebcf5-e478-466b-a4c7-6e7266beb21c (old id 2180230)
date added to LUP
2016-04-01 10:51:02
date last changed
2022-04-28 02:02:13
@article{1eaebcf5-e478-466b-a4c7-6e7266beb21c,
  abstract     = {{Replacement therapy with factor IX (FIX) concentrates is the recommended treatment for patients with hemophilia B, an X-linked bleeding disorder occurring in 1: 25 000 male births. N9-GP is a recombinant FIX molecule with a prolonged half-life which is obtained by site-directed glycoPEGylation where a 40-kDa polyethylene glycol molecule is attached to the activation peptide of FIX. This first human dose trial in patients with hemophilia B investigated the safety and pharmacokinetic properties of a single IV dose of N9-GP. Sixteen previously treated patients received one dose of their previous FIX product followed by one dose of N9-GP at the same dose level (25, 50, or 100 U/kg). None of the patients developed inhibitors. One patient developed transient hypersensitivity symptoms during administration of N9-GP and was excluded from pharmacokinetic analyses. In the remaining 15 patients, N9-GP was well-tolerated. The half-life was 93 hours, which was 5 times higher than the patient's previous product. The incremental recovery of N9-GP was 94% and 20% higher compared with recombinant and plasma-derived products, respectively. These results indicate that N9-GP has the potential to reduce dosing frequency while providing effective treatment of bleeding episodes with a single dose. The trial was registered at www.clinicaltrials.gov as NCT00956345. (Blood. 2011;118(10):2695-2701)}},
  author       = {{Negrier, Claude and Knobe, Karin and Tiede, Andreas and Giangrande, Paul and Moss, Judi}},
  issn         = {{1528-0020}},
  language     = {{eng}},
  number       = {{10}},
  pages        = {{2695--2701}},
  publisher    = {{American Society of Hematology}},
  series       = {{Blood}},
  title        = {{Enhanced pharmacokinetic properties of a glycoPEGylated recombinant factor IX: a first human dose trial in patients with hemophilia B}},
  url          = {{http://dx.doi.org/10.1182/blood-2011-02-335596}},
  doi          = {{10.1182/blood-2011-02-335596}},
  volume       = {{118}},
  year         = {{2011}},
}