Direct comparison of two extended-half-life recombinant FVIII products: a randomized, crossover pharmacokinetic study in patients with severe hemophilia A

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

BAY 94-9027 is an extended-half-life, recombinant factor VIII (rFVIII) product conjugated with a 60-kDa branched polyethylene glycol (PEG) molecule indicated for use in previously treated patients (aged ≥ 12 years) with hemophilia A. This randomized, open-label, two-way crossover study compared the pharmacokinetics (PK) of BAY 94-9027 and rFVIII Fc fusion protein (rFVIIIFc) in patients with hemophilia A. Patients aged 18–65 years with FVIII < 1% and ≥ 150 exposure days to FVIII were randomized to receive intravenous single-dose BAY 94-9027 60 IU/kg followed by rFVIIIFc 60 IU/kg or vice versa, with ≥ 7-day wash-out between doses. FVIII activity was measured by one-stage assay. PK parameters, including area under the curve from time 0 to the last data point (AUClast, primary parameter), half-life, and clearance were calculated. Eighteen patients were randomized and treated. No adverse events were observed. In the analysis set excluding one outlier, geometric mean (coefficient of variation [%CV, 95% confidence interval {CI}]) AUClast was significantly higher for BAY 94-9027 versus rFVIIIFc (2940 [37.8, 2440–3550] IU h/dL versus 2360 [31.8, 2010–2770] IU h/dL, p = 0.0001). A population PK model was developed to simulate time to reach FVIII threshold levels; median time to 1 IU/dL was approximately 13 h longer for BAY 94-9027 versus rFVIIIFc after a single infusion of 60 IU/kg. In conclusion, BAY 94-9027 had a superior PK profile versus rFVIIIFc. ClinicalTrials.gov: NCT03364998.

Detaljer

Författare
  • Anita Shah
  • Alexander Solms
  • Sara Wiegmann
  • Maurice Ahsman
  • Erik Berntorp
  • Andreas Tiede
  • Alfonso Iorio
  • Maria Elisa Mancuso
  • Tihomir Zhivkov
  • Toshko Lissitchkov
Enheter & grupper
Externa organisationer
  • Bayer Corporation, USA
  • Bayer Pharma AG
  • Hannover Medical School
  • McMaster University
  • Maggiore Hospital Policlinico
  • LAP&P Consultants BV
  • Skåne University Hospital
  • National Specialized Hospital for Active Treatment of Haematologic Diseases
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Hematologi

Nyckelord

Originalspråkengelska
TidskriftAnnals of Hematology
StatusE-pub ahead of print - 2019 jun 24
PublikationskategoriForskning
Peer review utfördJa