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Completed

NCT Number: NCT00666406

Pharmacokinetic Comparison of Advate rAHF-PFM With Recombinate rAHF in Patients With Severe Hemophilia A

The purpose of this study is to compare the pharmacokinetic parameters and safety of Advate rAHF-PFM versus Recombinate rAHF in well described previously treated patients with severe hemophilia A (factor VIII level < 1%).

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Key information

Conditions

Hemophilia A Blood Coagulation Disorders Blood Coagulation Disorders, Inherited Coagulation Protein Disorders Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhagic Disorders

Age range

15 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Bonn, 53127, Germany

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Signed informed consent obtained from participant or legally authorized representative
  • 15-60 years old
  • Factor VIII level < 1% as documented by previously measured factor VIII and genotyping
  • Previously treated with factor VIII concentrate(s) for a minimum of at least 150 exposure days (as documented by the study site investigator) prior to study entry
  • Observed decrease of efficacy by subject and/or treating physician after being switched from Recombinate rAHF to Advate rAHF-PFM

Exclusion criteria

  • The participant has a detectable factor VIII inhibitor at screening, with a titer >= 0.4 Bethesda Unit (BU) (Nijmegen modification of the Bethesda Assay) measured at the local and the central laboratory
  • The participant has a known hypersensitivity to mouse or hamster proteins
  • The participant is participating in another investigational drug study within 30 days prior to screening
  • The participant is identified by the investigator as being unable or unwilling to cooperate with study procedures

Treatment and study plan

Antihemophilic Factor (Recombinant) - Plasma/Albumin Free Method (rAHF-PFM)

Drug

Infusion of 50 +/- 5 IU/kg bodyweight

Other names: Advate rAHF-PFM, Recombinant Protein-Free Factor VIII (rAHF-PFM)

Recombinant Factor VIII (rAHF)

Drug

Infusion of 50 +/- 5 IU/kg bodyweight

Other names: Recombinate rAHF, Antihemophilic Factor (Recombinant)

Primary outcomes

  1. Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to 48 Hours. One-Stage Activated Partial Thromboplastin Time (aPTT) -Based Assay Performed at Central Laboratory (Medical University Vienna)

    Time frame: 0-30 minutes before infusion up to 48 hours post-infusion

    AUC estimated by linear trapezoidal method. The linear trapezoidal method is a numerical method used to approximate the area under a curve.

  2. Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to 48 Hours. Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site)

    Time frame: 0-30 minutes before infusion up to 48 hours post-infusion

    AUC estimated by linear trapezoidal method. The linear trapezoidal method is a numerical method used to approximate the area under a curve.

  3. Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to 48 Hours. FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site)

    Time frame: 0-30 minutes before infusion up to 48 hours post-infusion

    AUC estimated by linear trapezoidal method. The linear trapezoidal method is a numerical method used to approximate the area under a curve.

  4. Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to 48 Hours. FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site)

    Time frame: 0-30 minutes before infusion up to 48 hours post-infusion

    AUC estimated by linear trapezoidal method. The linear trapezoidal method is a numerical method used to approximate the area under a curve.

Secondary outcomes

  1. Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to Infinity. One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna)

    Time frame: 0-30 minutes before infusion up to 48 hours post-infusion

    AUC estimated by linear trapezoidal method. The linear trapezoidal method is a numerical method used to approximate the area under a curve. FVIII activity measurement

  2. Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to Infinity. Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site)

    Time frame: 0-30 minutes before infusion up to 48 hours post-infusion

    AUC estimated by linear trapezoidal method. The linear trapezoidal method is a numerical method used to approximate the area under a curve.

  3. Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to Infinity. FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site)

    Time frame: 0-30 minutes before infusion up to 48 hours post-infusion

    AUC estimated by linear trapezoidal method. The linear trapezoidal method is a numerical method used to approximate the area under a curve.

  4. Area Under the Plasma Concentration Versus Time Curve (AUC) From 0 to Infinity. FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site)

    Time frame: 0-30 minutes before infusion up to 48 hours post-infusion

    AUC estimated by linear trapezoidal method. The linear trapezoidal method is a numerical method used to approximate the area under a curve.

  5. Systemic Clearance (Cl). One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna)

    Time frame: 0-30 minutes before infusion up to 48 hours post-infusion

    Systemic clearance in mL/kg/h will be calculated as the dose in IU/kg divided by the total area under the curve.

  6. Systemic Clearance (Cl). Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site)

    Time frame: 0-30 minutes before infusion up to 48 hours post-infusion

    Systemic clearance in mL/kg/h will be calculated as the dose in IU/kg divided by the total area under the curve.

  7. Systemic Clearance (Cl). FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site)

    Time frame: 0-30 minutes before infusion up to 48 hours post-infusion

    Systemic clearance in mL/kg/h will be calculated as the dose in IU/kg divided by the total area under the curve.

  8. Systemic Clearance (Cl). FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site)

    Time frame: 0-30 minutes before infusion up to 48 hours post-infusion

    Systemic clearance in mL/kg/h will be calculated as the dose in IU/kg divided by the total area under the curve.

  9. Maximum Plasma Concentration (C-max). One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna)

    Time frame: 0-30 minutes before infusion up to 48 hours post-infusion

    C-max will be calculated as the maximum concentration following infusion of either Advate or Recombinate.

  10. Maximum Plasma Concentration (C-max). Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site)

    Time frame: 0-30 minutes before infusion up to 48 hours post-infusion

    C-max will be calculated as the maximum concentration following infusion of either Advate or Recombinate.

  11. Maximum Plasma Concentration (C-max). FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site)

    Time frame: 0-30 minutes before infusion up to 48 hours post-infusion

    C-max will be calculated as the maximum concentration following infusion of either Advate or Recombinate.

  12. Maximum Plasma Concentration (C-max). FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site)

    Time frame: 0-30 minutes before infusion up to 48 hours post-infusion

    C-max will be calculated as the maximum concentration following infusion of either Advate or Recombinate.

  13. Terminal Half-life. One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna)

    Time frame: 0-30 minutes before infusion up to 48 hours post-infusion

    Computed from the terminal or disposition rate constant obtained from log-linear fitting using the least squares deviation to the last five quantifiable concentrations (9 to 48 hours).

  14. Terminal Half-life. Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site)

    Time frame: 0-30 minutes before infusion up to 48 hours post-infusion

    Computed from the terminal or disposition rate constant obtained from log-linear fitting using the least squares deviation to the last five quantifiable concentrations.

  15. Terminal Half-life. FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site)

    Time frame: 0-30 minutes before infusion up to 48 hours post-infusion

    Computed from the terminal or disposition rate constant obtained from log-linear fitting using the least squares deviation to the last five quantifiable concentrations.

  16. Terminal Half-life. FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site)

    Time frame: 0-30 minutes before infusion up to 48 hours post-infusion

    Computed from the terminal or disposition rate constant obtained from log-linear fitting using the least squares deviation to the last five quantifiable concentrations.

  17. Incremental Recovery. One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna)

    Time frame: 0-30 minutes before infusion up to 48 hours post-infusion

    Increase in factor VIII concentration from pre- to post-infusion.

  18. Incremental Recovery. Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site)

    Time frame: 0-30 minutes before infusion up to 48 hours post-infusion

    Computed from the terminal or disposition rate constant obtained from log_e -linear fitting using the least squares deviation to the last five quantifiable concentrations.

  19. Incremental Recovery. FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site)

    Time frame: 0-30 minutes before infusion up to 48 hours post-infusion

    Increase in factor VIII concentration from pre- to post-infusion

  20. Incremental Recovery. FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site)

    Time frame: 0-30 minutes before infusion up to 48 hours post-infusion

    Increase in factor VIII concentration from pre- to post-infusion

  21. Mean Residence Time (MRT). One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna)

    Time frame: 0-30 minutes before infusion up to 48 hours post-infusion

    The MRT in hours will be calculated as total area under the moment curve divided by the total area under the curve.

  22. Mean Residence Time (MRT). Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site)

    Time frame: 0-30 minutes before infusion up to 48 hours post-infusion

    The MRT in hours will be calculated as total area under the moment curve divided by the total area under the curve.

  23. Mean Residence Time (MRT). FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site)

    Time frame: 0-30 minutes before infusion up to 48 hours post-infusion

    The MRT in hours will be calculated as total area under the moment curve divided by the total area under the curve.

  24. Mean Residence Time (MRT). FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site)

    Time frame: 0-30 minutes before infusion up to 48 hours post-infusion

    The MRT in hours will be calculated as total area under the moment curve divided by the total area under the curve.

  25. Time to Reach the Maximum Plasma Concentration (Tmax). One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna)

    Time frame: 0-30 minutes before infusion up to 48 hours post-infusion

    Tmax in hours was defined as the minimum time to reach Maximum plasma concentration (Cmax).

  26. Time to Reach the Maximum Plasma Concentration (Tmax). Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site)

    Time frame: 0-30 minutes before infusion up to 48 hours post-infusion

    Tmax in hours was defined as the minimum time to reach Maximum plasma concentration (Cmax).

  27. Time to Reach the Maximum Plasma Concentration (Tmax). FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site)

    Time frame: 0-30 minutes before infusion up to 48 hours post-infusion

    Tmax in hours was defined as the minimum time to reach Maximum plasma concentration (Cmax).

  28. Time to Reach the Maximum Plasma Concentration (Tmax). FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site)

    Time frame: 0-30 minutes before infusion up to 48 hours post-infusion

    Tmax in hours was defined as the minimum time to reach Maximum plasma concentration (Cmax).

  29. Volume of Distribution at Steady State (Vss). One-Stage aPTT-Based Assay Performed at Central Laboratory (Medical University Vienna)

    Time frame: 0-30 minutes before infusion up to 48 hours post-infusion

    Computed as weight-adjusted Clearance * Mean Residence Time

  30. Volume of Distribution at Steady State (Vss). Chromogenic Assay Performed at Local Laboratory (i.e., University of Bonn, the Study Site)

    Time frame: 0-30 minutes before infusion up to 48 hours post-infusion

    Computed as weight-adjusted Clearance (CL) * Mean Residence Time

  31. Volume of Distribution at Steady State (Vss). FVIII One-Stage Clotting Assay (Bonn Method) Performed at Local Laboratory (i.e., University of Bonn, the Study Site)

    Time frame: 0-30 minutes before infusion up to 48 hours post-infusion

    Computed as weight-adjusted CL * Mean Residence Time

  32. Volume of Distribution at Steady State (Vss). FVIII Clotting Assay. Performed at Local Laboratory (i.e., University of Bonn, the Study Site)

    Time frame: 0-30 minutes before infusion up to 48 hours post-infusion

    Computed as weight-adjusted CL * Mean Residence Time

Sponsors and collaborators

Lead sponsor

Baxalta now part of Shire

Industry

Registry information

Official study title

Pharmacokinetic Comparison of Advate rAHF-PFM With Recombinate rAHF in Patients With Severe Hemophilia A: a Phase IV, Prospective, Randomized, Controlled, Cross-over, Single Center Study

Important dates

Study start
2008
Primary completion
2009
Study completion
2009
First posted
Apr 24, 2008
Registry last updated
May 19, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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