title: Enhanced pharmacokinetic properties of a glycoPEGylated recombinant factor IX: a first human dose trial in patients with hemophilia B.
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.
authors.affiliation: Hôpital Edouard Herriot, Centre Régional de Traitement de l'Hémophilie, Université Claude Bernard Lyon 1, Lyon, France. claude.negrier@chu-lyon.fr
authors.forename: Claude
authors.initials: C
authors.lastname: Negrier
authors.forename: Karin
authors.initials: K
authors.lastname: Knobe
authors.forename: Andreas
authors.initials: A
authors.lastname: Tiede
authors.forename: Paul
authors.initials: P
authors.lastname: Giangrande
authors.forename: Judi
authors.initials: J
authors.lastname: Møss
mesh_terms: D000328:Adult; D004305:Dose-Response Relationship, Drug; D005164:Factor IX / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D006031:Glycosylation; D002836:Hemophilia B / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000737:chemistry*; D011994:Recombinant Proteins / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D014018:Tissue Distribution; D055815:Young Adult
chemical_list: D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D005164:Factor IX