Direct comparison of two extended half-life PEGylated recombinant FVIII products: a randomized, crossover pharmacokineti
- PDF / 859,851 Bytes
- 10 Pages / 595.276 x 790.866 pts Page_size
- 55 Downloads / 177 Views
ORIGINAL ARTICLE
Direct comparison of two extended half-life PEGylated recombinant FVIII products: a randomized, crossover pharmacokinetic study in patients with severe hemophilia A Alexander Solms 1 & Anita Shah 2 & Erik Berntorp 3 & Andreas Tiede 4 & Alfonso Iorio 5,6 & Camila Linardi 2 & Maurice Ahsman 7 & Maria Elisa Mancuso 8 & Tihomir Zhivkov 9 & Toshko Lissitchkov 9 Received: 10 July 2020 / Accepted: 17 September 2020 # The Author(s) 2020
Abstract An open-label, crossover randomized study was performed to compare the pharmacokinetics (PK) of damoctocog alfa pegol and rurioctocog alfa pegol, two recombinant factor VIII (FVIII) products indicated in patients with hemophilia A, both conjugated to polyethylene glycol to reduce clearance and extend time in circulation. Adult patients (N = 18) with severe hemophilia A (FVIII < 1 IU/dL), previously treated with any FVIII product for ≥ 150 exposure days, were randomized to receive a single 50 IU/kg infusion of damoctocog alfa pegol followed by rurioctocog alfa pegol, or vice versa, with ≥ 7-day washout between doses. FVIII activity was measured using the one-stage clotting assay. PK parameters, including area under the curve from time 0 to the last data point (AUC0–tlast, primary parameter), dose-normalized AUC (AUCnorm), and time to threshold, were calculated based on 11 time points between 0.25 and 120 h post-dose and evaluated using a noncompartmental model. Due to differences in batchspecific vial content used for the study, actual administered median doses were 54.3 IU/kg for damoctocog alfa pegol and 61.4 IU/kg for rurioctocog alfa pegol. Based on actual dosing, a significantly higher geometric mean (coefficient of variation [%CV]) AUCnorm was observed for damoctocog alfa pegol (43.8 h kg/dL [44.0]) versus rurioctocog alfa pegol (36.0 h kg/dL [40.1, P < 0.001]). Based on population PK modeling, median time to reach 1 IU/dL was 16 h longer for damoctocog alfa pegol compared with rurioctocog alfa pegol. No adverse events or any immunogenicity signals were observed. Overall, damoctocog alfa pegol had a superior PK profile versus rurioctocog alfa pegol. Trial registration number: NCT04015492 (ClinicalTrials.gov identifier). Date of registration: July 9, 2019 Keywords Factor VIII . Extended half-life . Hemophilia A . PEGylated . Head-to-head study . Population pharmacokinetics
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00277-020-04280-3) contains supplementary material, which is available to authorized users. * Alexander Solms [email protected]
5
McMaster-Bayer Endowed Research Chair in Clinical Epidemiology of Congenital Bleeding Disorders, Department of Medicine, McMaster University, Hamilton, Canada
1
Clinical Pharmacometrics, Pharmaceuticals Research & Development, Bayer AG, 13353 Berlin, Germany
6
Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Canada
2
Bayer, Whippany, NJ, USA
7
LAP&P Consultants BV, Leiden, the Netherlands
3
Centre for Thromb
Data Loading...
