title: 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.
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.affiliation: Comprehensive Bleeding Disorders Center, Peoria, IL 61614, USA. mdtara@hemophilia-ctr-peoria.com
authors.forename: M D
authors.initials: MD
authors.lastname: Tarantino
authors.forename: P W
authors.initials: PW
authors.lastname: Collins
authors.forename: C R M
authors.initials: CR
authors.lastname: Hay
authors.forename: A D
authors.initials: AD
authors.lastname: Shapiro
authors.forename: R A
authors.initials: RA
authors.lastname: Gruppo
authors.forename: E
authors.initials: E
authors.lastname: Berntorp
authors.forename: G L
authors.initials: GL
authors.lastname: Bray
authors.forename: S A
authors.initials: SA
authors.lastname: Tonetta
authors.forename: P C
authors.initials: PC
authors.lastname: Schroth
authors.forename: A D
authors.initials: AD
authors.lastname: Retzios
authors.forename: S S
authors.initials: SS
authors.lastname: Rogy
authors.forename: M G
authors.initials: MG
authors.lastname: Sensel
authors.forename: B M
authors.initials: BM
authors.lastname: Ewenstein
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D004311:Double-Blind Method; D005169:Factor VIII / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006467:Hemophilia A / Q000188:drug therapy*; D006470:Hemorrhage / Q000517:prevention & control; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D008875:Middle Aged; D011994:Recombinant Proteins; D016896:Treatment Outcome
chemical_list: D011994:Recombinant Proteins; C078147:F8 protein, human; D005169:Factor VIII