title: Efficacy, safety and pharmacokinetic profiles of a plasma-derived VWF/FVIII concentrate (VONCENTO®) in subjects with haemophilia A (SWIFT-HA study).
abstract: BACKGROUND
  VONCENTO® (CSL Behring) is a plasma-derived, high-concentration, low-volume, high-purity concentrate,which contains a high level of von Willebrand factor (VWF) high-molecular-weight multimers and aVWF/factor VIII (FVIII) ratio of ~2.4:1, similar to Haemate® P (CSL Behring).
  
  
  METHODS
  The pharmacokinetic, efficacy and safety profiles of VONCENTO® were investigated in this multicentre,double-blind, randomised study. Subjects aged ≥ 12 years with haemophilia A who required treatment of nonsurgical bleeds, treatment during surgical events or who were receiving prophylaxis were included. Pharmacokinetics were investigated with a single dose of 50 IU FVIII/kg body weight of either VONCENTO® or BIOSTATE® reference product (Biostate-RP) (Day 1; Day 8 [n= 16], repeated on Day 180 [VONCENTO® only; n=15]). Efficacy and safety analyses were performed either during on-demand treatment (n=52) or prophylaxis (n=29)for ≥ 6 months and ≥ 50 exposure days, respectively.
  
  
  RESULTS
  Besides the confirmation of bioequivalence between VONCENTO® and Biostate-RP, which displayed comparable PK profiles, haemostatic efficacy was rated by the investigators as either 'excellent' or 'good' in 96.4% of all bleeding events (96.5% spontaneous, 96.6% traumatic, 96.9% joint bleeds) as well as in 80% of major and 100% of minor surgical procedures at discharge. The median number of annualised bleeding events per subject [range] was significantly lower in the prophylaxis group (2.0 [0.0-34.6]) than in the on-demand group (14.0 [0.0-87.8], p = 0.0013).VONCENTO® was well tolerated and no inhibitory antibodies were identified during the study period.
  
  
  CONCLUSIONS
  This study demonstrated the bioequivalence of VONCENTO® to Biostate-RP, and its excellent efficacy and safety profile in haemophilia A subjects.
authors.affiliation: Department of Haematology, Krakow University Hospital, Krakow, Poland. Electronic address: alekskot@cm-uj.krakow.pl.
authors.forename: Aleksander
authors.initials: A
authors.lastname: Skotnicki
authors.affiliation: Specialized Hospital for Active Treatment (SHAT) 'Joan Pavel', Sofia, Bulgaria.
authors.forename: Toshko J
authors.initials: TJ
authors.lastname: Lissitchkov
authors.affiliation: Russian National Hematology Research Center, Moscow, Russian Federation.
authors.forename: Vasily
authors.initials: V
authors.lastname: Mamonov
authors.affiliation: GOUVPO Altaysky State Medical University of Roszdrav, Barnaul, Russian Federation.
authors.forename: Evgeny
authors.initials: E
authors.lastname: Buevich
authors.affiliation: Independent Public Clinical Hospital No. 1, Wroclaw, Poland.
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Kuliczkowski
authors.affiliation: UMHAT 'Sveti Georgi', Plovdiv, Bulgaria.
authors.forename: Stefcho
authors.initials: S
authors.lastname: Goranov
authors.affiliation: Department of Hematology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Kłoczko
authors.affiliation: Department of Pediatrics, Hematology and Oncology of Warsaw Medical University, Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Klukowska
authors.affiliation: University Clinic of Hematology, Skopje, Macedonia.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Stankovic
authors.affiliation: MHAT 'Sveta Marina', Varna, Bulgaria.
authors.forename: Liana
authors.initials: L
authors.lastname: Gercheva
authors.affiliation: FGU Kirov Scientific Research Institute of Hematology and Blood Transfusion, Kirov, Russian Federation.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Chernova
authors.affiliation: Department of Hematology, Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Hellmann
authors.affiliation: Independent Public Clinical Hospital No. 1, Lublin, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Dmoszyńska
authors.affiliation: Dept. of Hematology, J. Strus Hospital, Poznan, Poland.
authors.forename: Krystyna
authors.initials: K
authors.lastname: Zawilska
authors.affiliation: CSL Behring, Clinical Research & Development, Marburg, Germany.
authors.forename: Alex
authors.initials: A
authors.lastname: Veldman
authors.affiliation: CSL Behring, Clinical Research & Development, Marburg, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Joch
authors.affiliation: CSL Behring, Clinical Research & Development, Marburg, Germany.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Seifert
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D004338:Drug Combinations; D005060:Europe; D005169:Factor VIII / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D005260:Female; D006467:Hemophilia A / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D006490:Hemostatics / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry; D016896:Treatment Outcome; D055815:Young Adult; D014841:von Willebrand Factor / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*
chemical_list: D004338:Drug Combinations; D006490:Hemostatics; D014841:von Willebrand Factor; D005169:Factor VIII
keywords: Annual bleeding rate; Hemostatic efficacy; Hemostatic safety; On-demand therapy; Prophylaxis; Surgery