title: Evaluation of pharmacokinetics, efficacy and safety of Immunate solvent detergent in previously treated patients with severe haemophilia A.
abstract: Immunate Solvent Detergent (S/D) is a plasma derived, purified, human factor VIII (FVIII) - von Willebrand factor (VWF) complex subjected to two virus inactivation/removal processes: S/D and vapor heat treatment. This prospective, multicentre, three-part clinical study evaluated the pharmacokinetics (in comparison to the predecessor product Immunate), efficacy and safety of Immunate S/D in 56 previously treated patients with severe haemophilia A. Subjects received Immunate S/D on-demand, as a prophylactic regimen or both. The results of the pharmacokinetic population demonstrate that Immunate and Immunate S/D were equivalent with respect to the FVIII - and to the retrospectively VWF - parameters assessed. A total of 623 bleeding episodes were reported in 47/56 subjects. The duration of prophylaxis ranged from 0.1-5.2 months with a total of 175.6 months. The median number of bleeds per month in subjects on prophylaxis was 0 (range 0-10). Ninety-six percent of bleeding episodes were rated as having an excellent or good response. For most bleeding episodes (89%), subjects required only one infusion with a mean dose of 29.6 IU kg(-1). No FVIII inhibitory antibodies were observed in any subject. No related serious adverse events were reported. Thus, the introduction of S/D treatment did not alter the PK characteristics and function of VWF and FVIII molecules of Immunate S/D which is effective and safe for treatment of bleeding episodes, management of surgical procedures, and prophylaxis.
authors.affiliation: National Medical Center, National Hemophilia Center, Budapest, Hungary.
authors.forename: L
authors.initials: L
authors.lastname: Nemes
authors.forename: T
authors.initials: T
authors.lastname: Lissitchkov
authors.forename: A
authors.initials: A
authors.lastname: Klukowska
authors.forename: G
authors.initials: G
authors.lastname: Dobaczewski
authors.forename: V
authors.initials: V
authors.lastname: Komrska
authors.forename: R
authors.initials: R
authors.lastname: Zimmermann
authors.forename: G
authors.initials: G
authors.lastname: Auerswald
authors.forename: W
authors.initials: W
authors.lastname: Engl
authors.forename: B
authors.initials: B
authors.lastname: Pavlova
authors.forename: B
authors.initials: B
authors.lastname: Abbühl
authors.forename: H J
authors.initials: HJ
authors.lastname: Ehrlich
mesh_terms: D003902:Detergents / Q000009:adverse effects / Q000493:pharmacokinetics*; D005169:Factor VIII / Q000493:pharmacokinetics*; D006467:Hemophilia A / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006470:Hemorrhage / Q000188:drug therapy / Q000517:prevention & control; D006801:Humans; D010146:Pain / Q000188:drug therapy / Q000517:prevention & control; D011446:Prospective Studies; D012449:Safety; D012997:Solvents / Q000009:adverse effects / Q000493:pharmacokinetics*; D016896:Treatment Outcome; D038301:Virus Inactivation
chemical_list: D003902:Detergents; C523253:Immunate solvent detergent, human; D012997:Solvents; D005169:Factor VIII