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

Solms, Alexander ; Shah, Anita ; Berntorp, Erik LU ; Tiede, Andreas ; Iorio, Alfonso ; Linardi, Camila ; Ahsman, Maurice ; Mancuso, Maria Elisa ; Zhivkov, Tihomir and Lissitchkov, Toshko (2020) In Annals of Hematology 99(11). p.2689-2698
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... (More)

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 batch-specific 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

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Extended half-life, Factor VIII, Head-to-head study, Hemophilia A, PEGylated, Population pharmacokinetics
in
Annals of Hematology
volume
99
issue
11
pages
10 pages
publisher
Springer
external identifiers
  • scopus:85091411760
  • pmid:32974838
ISSN
0939-5555
DOI
10.1007/s00277-020-04280-3
language
English
LU publication?
yes
id
2f76e790-943d-4045-b482-0bc37665e8a2
date added to LUP
2021-01-14 17:39:21
date last changed
2022-06-14 17:26:32
@article{2f76e790-943d-4045-b482-0bc37665e8a2,
  abstract     = {{<p>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 &lt; 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 (AUC<sub>0–tlast</sub>, primary parameter), dose-normalized AUC (AUC<sub>norm</sub>), 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 batch-specific 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]) AUC<sub>norm</sub> 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 &lt; 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</p>}},
  author       = {{Solms, Alexander and Shah, Anita and Berntorp, Erik and Tiede, Andreas and Iorio, Alfonso and Linardi, Camila and Ahsman, Maurice and Mancuso, Maria Elisa and Zhivkov, Tihomir and Lissitchkov, Toshko}},
  issn         = {{0939-5555}},
  keywords     = {{Extended half-life; Factor VIII; Head-to-head study; Hemophilia A; PEGylated; Population pharmacokinetics}},
  language     = {{eng}},
  month        = {{11}},
  number       = {{11}},
  pages        = {{2689--2698}},
  publisher    = {{Springer}},
  series       = {{Annals of Hematology}},
  title        = {{Direct comparison of two extended half-life PEGylated recombinant FVIII products : a randomized, crossover pharmacokinetic study in patients with severe hemophilia A}},
  url          = {{http://dx.doi.org/10.1007/s00277-020-04280-3}},
  doi          = {{10.1007/s00277-020-04280-3}},
  volume       = {{99}},
  year         = {{2020}},
}