Results from a large multinational clinical trial (guardian™3) using prophylactic treatment with turoctocog alfa in paediatric patients with severe haemophilia A

Safety, efficacy and pharmacokinetics

R. Kulkarni, F. A. Karim, S. Glamocanin, D. Janic, V. Vdovin, M. Ozelo, L. Rageliene, E. Carboni, P. Laguna, G. Dobaczewski, S. Seremetis, A. Lindblom, E. Santagostino

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Recombinant factor VIII (rFVIII) products provide a safe and efficacious replacement therapy for prophylaxis and treatment of bleeding episodes in patients with severe haemophilia A. This multinational, open-label, non-controlled trial investigated the safety, efficacy and pharmacokinetics (PK) of turoctocog alfa, a new rFVIII product, in a paediatric population. The primary objective was to evaluate safety. A total of 31 younger children (0-5 years) and 32 older children (6-11 years), with ≥50 exposure days to any factor VIII (FVIII) product and no history of inhibitors, received prophylaxis with turoctocog alfa (25-50 IU kg-1 every second day or 25-60 IU kg-1 three times weekly). PK assessments of turoctocog alfa and the patients' previous FVIII product were performed in 28 patients. Mean exposure to turoctocog alfa was 60 exposure days per patient. This corresponds to approximately 4.5 months in the trial. None of the patients developed inhibitors (≥0.6 BU) and no safety concerns were raised. A total of 120 bleeding episodes (95%) were controlled with 1-2 infusions of turoctocog alfa. Based on patient reports, the success rate (defined as 'excellent' or 'good' haemostatic response) for treatment of bleeding episodes was 92%. Overall, the median annualized bleeding rate was 3.0 (interquartile range: 8.5) bleeds patient-1 year-1. PK parameters were comparable between the two age groups. In conclusion, the present large global clinical trial showed that turoctocog alfa was safe, effective in treatment of bleeding episodes and had a prophylactic effect in paediatric patients.

Original languageEnglish
Pages (from-to)698-705
Number of pages8
JournalHaemophilia
Volume19
Issue number5
DOIs
Publication statusPublished - Sep 2013

Fingerprint

Hemophilia A
Pharmacokinetics
Clinical Trials
Pediatrics
Safety
Factor VIII
Hemorrhage
Therapeutics
recombinant factor VIII N8
Hemostatics
Age Groups
Population

Keywords

  • Haemophilia A
  • Paediatric population
  • Pharmacokinetics
  • Prophylaxis
  • Recombinant factor VIII
  • Turoctocog alfa

ASJC Scopus subject areas

  • Hematology
  • Genetics(clinical)

Cite this

Results from a large multinational clinical trial (guardian™3) using prophylactic treatment with turoctocog alfa in paediatric patients with severe haemophilia A : Safety, efficacy and pharmacokinetics. / Kulkarni, R.; Karim, F. A.; Glamocanin, S.; Janic, D.; Vdovin, V.; Ozelo, M.; Rageliene, L.; Carboni, E.; Laguna, P.; Dobaczewski, G.; Seremetis, S.; Lindblom, A.; Santagostino, E.

In: Haemophilia, Vol. 19, No. 5, 09.2013, p. 698-705.

Research output: Contribution to journalArticle

Kulkarni, R, Karim, FA, Glamocanin, S, Janic, D, Vdovin, V, Ozelo, M, Rageliene, L, Carboni, E, Laguna, P, Dobaczewski, G, Seremetis, S, Lindblom, A & Santagostino, E 2013, 'Results from a large multinational clinical trial (guardian™3) using prophylactic treatment with turoctocog alfa in paediatric patients with severe haemophilia A: Safety, efficacy and pharmacokinetics', Haemophilia, vol. 19, no. 5, pp. 698-705. https://doi.org/10.1111/hae.12165
Kulkarni, R. ; Karim, F. A. ; Glamocanin, S. ; Janic, D. ; Vdovin, V. ; Ozelo, M. ; Rageliene, L. ; Carboni, E. ; Laguna, P. ; Dobaczewski, G. ; Seremetis, S. ; Lindblom, A. ; Santagostino, E. / Results from a large multinational clinical trial (guardian™3) using prophylactic treatment with turoctocog alfa in paediatric patients with severe haemophilia A : Safety, efficacy and pharmacokinetics. In: Haemophilia. 2013 ; Vol. 19, No. 5. pp. 698-705.
@article{30cc4e5a3ff743fa80d99999e40cc055,
title = "Results from a large multinational clinical trial (guardian™3) using prophylactic treatment with turoctocog alfa in paediatric patients with severe haemophilia A: Safety, efficacy and pharmacokinetics",
abstract = "Recombinant factor VIII (rFVIII) products provide a safe and efficacious replacement therapy for prophylaxis and treatment of bleeding episodes in patients with severe haemophilia A. This multinational, open-label, non-controlled trial investigated the safety, efficacy and pharmacokinetics (PK) of turoctocog alfa, a new rFVIII product, in a paediatric population. The primary objective was to evaluate safety. A total of 31 younger children (0-5 years) and 32 older children (6-11 years), with ≥50 exposure days to any factor VIII (FVIII) product and no history of inhibitors, received prophylaxis with turoctocog alfa (25-50 IU kg-1 every second day or 25-60 IU kg-1 three times weekly). PK assessments of turoctocog alfa and the patients' previous FVIII product were performed in 28 patients. Mean exposure to turoctocog alfa was 60 exposure days per patient. This corresponds to approximately 4.5 months in the trial. None of the patients developed inhibitors (≥0.6 BU) and no safety concerns were raised. A total of 120 bleeding episodes (95{\%}) were controlled with 1-2 infusions of turoctocog alfa. Based on patient reports, the success rate (defined as 'excellent' or 'good' haemostatic response) for treatment of bleeding episodes was 92{\%}. Overall, the median annualized bleeding rate was 3.0 (interquartile range: 8.5) bleeds patient-1 year-1. PK parameters were comparable between the two age groups. In conclusion, the present large global clinical trial showed that turoctocog alfa was safe, effective in treatment of bleeding episodes and had a prophylactic effect in paediatric patients.",
keywords = "Haemophilia A, Paediatric population, Pharmacokinetics, Prophylaxis, Recombinant factor VIII, Turoctocog alfa",
author = "R. Kulkarni and Karim, {F. A.} and S. Glamocanin and D. Janic and V. Vdovin and M. Ozelo and L. Rageliene and E. Carboni and P. Laguna and G. Dobaczewski and S. Seremetis and A. Lindblom and E. Santagostino",
year = "2013",
month = "9",
doi = "10.1111/hae.12165",
language = "English",
volume = "19",
pages = "698--705",
journal = "Haemophilia",
issn = "1351-8216",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "5",

}

TY - JOUR

T1 - Results from a large multinational clinical trial (guardian™3) using prophylactic treatment with turoctocog alfa in paediatric patients with severe haemophilia A

T2 - Safety, efficacy and pharmacokinetics

AU - Kulkarni, R.

AU - Karim, F. A.

AU - Glamocanin, S.

AU - Janic, D.

AU - Vdovin, V.

AU - Ozelo, M.

AU - Rageliene, L.

AU - Carboni, E.

AU - Laguna, P.

AU - Dobaczewski, G.

AU - Seremetis, S.

AU - Lindblom, A.

AU - Santagostino, E.

PY - 2013/9

Y1 - 2013/9

N2 - Recombinant factor VIII (rFVIII) products provide a safe and efficacious replacement therapy for prophylaxis and treatment of bleeding episodes in patients with severe haemophilia A. This multinational, open-label, non-controlled trial investigated the safety, efficacy and pharmacokinetics (PK) of turoctocog alfa, a new rFVIII product, in a paediatric population. The primary objective was to evaluate safety. A total of 31 younger children (0-5 years) and 32 older children (6-11 years), with ≥50 exposure days to any factor VIII (FVIII) product and no history of inhibitors, received prophylaxis with turoctocog alfa (25-50 IU kg-1 every second day or 25-60 IU kg-1 three times weekly). PK assessments of turoctocog alfa and the patients' previous FVIII product were performed in 28 patients. Mean exposure to turoctocog alfa was 60 exposure days per patient. This corresponds to approximately 4.5 months in the trial. None of the patients developed inhibitors (≥0.6 BU) and no safety concerns were raised. A total of 120 bleeding episodes (95%) were controlled with 1-2 infusions of turoctocog alfa. Based on patient reports, the success rate (defined as 'excellent' or 'good' haemostatic response) for treatment of bleeding episodes was 92%. Overall, the median annualized bleeding rate was 3.0 (interquartile range: 8.5) bleeds patient-1 year-1. PK parameters were comparable between the two age groups. In conclusion, the present large global clinical trial showed that turoctocog alfa was safe, effective in treatment of bleeding episodes and had a prophylactic effect in paediatric patients.

AB - Recombinant factor VIII (rFVIII) products provide a safe and efficacious replacement therapy for prophylaxis and treatment of bleeding episodes in patients with severe haemophilia A. This multinational, open-label, non-controlled trial investigated the safety, efficacy and pharmacokinetics (PK) of turoctocog alfa, a new rFVIII product, in a paediatric population. The primary objective was to evaluate safety. A total of 31 younger children (0-5 years) and 32 older children (6-11 years), with ≥50 exposure days to any factor VIII (FVIII) product and no history of inhibitors, received prophylaxis with turoctocog alfa (25-50 IU kg-1 every second day or 25-60 IU kg-1 three times weekly). PK assessments of turoctocog alfa and the patients' previous FVIII product were performed in 28 patients. Mean exposure to turoctocog alfa was 60 exposure days per patient. This corresponds to approximately 4.5 months in the trial. None of the patients developed inhibitors (≥0.6 BU) and no safety concerns were raised. A total of 120 bleeding episodes (95%) were controlled with 1-2 infusions of turoctocog alfa. Based on patient reports, the success rate (defined as 'excellent' or 'good' haemostatic response) for treatment of bleeding episodes was 92%. Overall, the median annualized bleeding rate was 3.0 (interquartile range: 8.5) bleeds patient-1 year-1. PK parameters were comparable between the two age groups. In conclusion, the present large global clinical trial showed that turoctocog alfa was safe, effective in treatment of bleeding episodes and had a prophylactic effect in paediatric patients.

KW - Haemophilia A

KW - Paediatric population

KW - Pharmacokinetics

KW - Prophylaxis

KW - Recombinant factor VIII

KW - Turoctocog alfa

UR - http://www.scopus.com/inward/record.url?scp=84883055547&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84883055547&partnerID=8YFLogxK

U2 - 10.1111/hae.12165

DO - 10.1111/hae.12165

M3 - Article

VL - 19

SP - 698

EP - 705

JO - Haemophilia

JF - Haemophilia

SN - 1351-8216

IS - 5

ER -