title: Results of a phase I/II open-label, safety and efficacy trial of coagulation factor IX (recombinant), albumin fusion protein in haemophilia B patients.
abstract: BACKGROUND
  rIX-FP is a coagulation factor IX (recombinant), albumin fusion protein with more than fivefold half-life prolongation over other standard factor IX (FIX) products available on the market.
  
  
  OBJECTIVE
  This prospective phase II, open-label study evaluated the safety and efficacy of rIX-FP for the prevention of bleeding episodes during weekly prophylaxis and assessed the haemostatic efficacy for on-demand treatment of bleeding episodes in previously treated patients with haemophilia B.
  
  
  METHODS
  The study consisted of a 10-14 day evaluation of rIX-FP pharmacokinetics (PK), and an 11 month safety and efficacy evaluation period with subjects receiving weekly prophylaxis treatment. Safety was evaluated by the occurrence of related adverse events, and immunogenic events, including development of inhibitors. Efficacy was evaluated by annualized spontaneous bleeding rate (AsBR), and the number of injections to achieve haemostasis.
  
  
  RESULTS
  Seventeen subjects participated in the study, 13 received weekly prophylaxis and 4 received episodic treatment only. No inhibitors were detected in any subject. The mean and median AsBR were 1.25, and 1.13 respectively in the weekly prophylaxis arm. All bleeding episodes were treated with 1 or 2 injections of rIX-FP. Three prophylaxis subjects who were treated on demand prior to study entry had >85% reduction in AsBR compared to the bleeding rate prior to study entry.
  
  
  CONCLUSIONS
  This study demonstrated the efficacy for weekly routine prophylaxis of rIX-FP to prevent spontaneous bleeding episodes and for the treatment of bleeding episodes. In addition no safety issues were detected during the study and an improved PK profile was demonstrated.
authors.affiliation: The Israeli National Hemophilia Center, Chaim Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: U
authors.initials: U
authors.lastname: Martinowitz
authors.affiliation: Department of Coagulation Disorders and Anemia, SHAT Joan Pavel, Sofia, Bulgaria.
authors.forename: T
authors.initials: T
authors.lastname: Lissitchkov
authors.affiliation: The Israeli National Hemophilia Center, Chaim Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Lubetsky
authors.affiliation: Department of Coagulation Disorders and Anemia, SHAT Joan Pavel, Sofia, Bulgaria.
authors.forename: G
authors.initials: G
authors.lastname: Jotov
authors.affiliation: The Israeli National Hemophilia Center, Chaim Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: T
authors.initials: T
authors.lastname: Barazani-Brutman
authors.affiliation: CRD, CSL Behring, King of Prussia, PA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Voigt
authors.affiliation: CRD, CSL Behring, King of Prussia, PA, USA.
authors.forename: I
authors.initials: I
authors.lastname: Jacobs
authors.affiliation: PRD, CSL Behring GmbH, Marburg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Wuerfel
authors.affiliation: Maggiore Hospital Policlinico, IRCCS Cà Granda Foundation, Milano, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Santagostino
mesh_terms: D000293:Adolescent; D000328:Adult; D000418:Albumins / Q000235:genetics*; D005164:Factor IX / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D002836:Hemophilia B / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D006470:Hemorrhage / Q000150:complications / Q000517:prevention & control; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D012449:Safety; D055815:Young Adult
chemical_list: D000418:Albumins; D011993:Recombinant Fusion Proteins; D005164:Factor IX
keywords: factor IX; haemophilia B; haemostasis; pharmacokinetics; prophylaxis