Enhanced pharmacokinetic properties of a glycoPEGylated recombinant factor IX: a first human dose trial in patients with hemophilia B
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2180230
- author
- Negrier, Claude ; Knobe, Karin LU ; Tiede, Andreas ; Giangrande, Paul and Moss, Judi
- organization
- publishing date
- 2011
- 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}}, }