Clinical evaluation of an advanced category antihaemophilic factor prepared using a plasma/albumin-free method: pharmacokinetics, efficacy, and safety in previously treated patients with haemophilia A. Academic Article uri icon

Overview

abstract

  • The efficacy and safety of an advanced category recombinant antihaemophilic factor produced by a plasma- and albumin-free method (rAHF-PFM) was studied in 111 previously treated subjects with haemophilia A. The study comprised a randomized, double-blinded, crossover pharmacokinetic comparison of rAHF-PFM and RECOMBINATE rAHF (R-FVIII); prophylaxis (three to four times per week with 25-40 IU kg(-1) rAHF-PFM) for at least 75 exposure days; and treatment of episodic haemorrhagic events. Median age was 18 years, 96% of subjects had baseline factor VIII <1%, and 108 received study drug. Bioequivalence, based on area under the plasma concentration vs. time curve and adjusted in vivo recovery, was demonstrated for rAHF-PFM and R-FVIII. Mean (+/-SD) half-life for rAHF-PFM was 12.0 +/- 4.3 h. Among 510 bleeding events, 473 (93%) were managed with one or two infusions of rAHF-PFM and 439 (86%) had efficacy ratings of excellent or good. Subjects who were less adherent to the prophylactic regimen had a higher bleeding rate (9.9 episodes subject(-1) year(-1)) than subjects who were more adherent (4.4 episodes subject(-1) year(-1); P < 0.03). One subject developed a low titre, non-persistent inhibitor (2.0 BU) after 26 exposure days. These data demonstrate that rAHF-PFM is bioequivalent to R-FVIII, and suggest that rAHF-PFM is efficacious and safe, without increased immunogenicity, for the treatment of haemophilia A.

authors

  • DiMichele, Donna
  • Tarantino, M D
  • Collins, P W
  • Hay, C R M
  • Shapiro, A D
  • Gruppo, R A
  • Berntorp, Erik
  • Bray, G L
  • Tonetta, S A
  • Schroth, P C
  • Retzios, A D
  • Rogy, S S
  • Sensel, M G
  • Ewenstein, B M

publication date

  • September 1, 2004

Research

keywords

  • Factor VIII
  • Hemophilia A

Identity

Scopus Document Identifier

  • 4944263724

Digital Object Identifier (DOI)

  • 10.1111/j.1365-2516.2004.00932.x

PubMed ID

  • 15357767

Additional Document Info

volume

  • 10

issue

  • 5