Clinical Trial: Pharmacokinetic, Efficacy, and Safety Study of Octafibrin Compared to Haemocomplettan/Riastap

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Prospective, Controlled, Randomised, Crossover Study Investigating the Pharmacokinetic Properties, Surrogate Efficacy and Safety of Octafibrin Compared to Haemocomplettan® P/RiaSTAPTM in Patien

Brief Summary: The purpose of this study is to investigate pharmacokinetic properties, surrogate efficacy and safety of Octafibrin compared to Haemocomplettan® P/RiaSTAPTM in patients with congenital fibrinogen deficiency

Detailed Summary:
Sponsor: Octapharma

Current Primary Outcome:

  • Fibrinogen Activity Normalized Area Under the Curve Standardized [ Time Frame: Baseline to 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment ]
    Fibrinogen activity was determined via a validated Clauss assay (fibrinogen activity) and fibrinogen-specific enzyme-linked immunosorbent assay (ie, fibrinogen antigen) using paired antibodies for fibrinogen antigen. All determinations were performed on frozen plasma samples in a central laboratory. The Clauss assay was modified and validated to achieve a limit of quantification of 0.2 g/L. The pharmacokinetic analysis was assessed individually using a non-compartmental model. Plasma levels were measured at Baseline, 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment. The normalized area under the curve was standardized to a dose of 70 mg/kg.
  • Comparison of Maximum Clot Firmness Between Octafibrin and Haemocomplettan P/RiaSTAP at 1 hr Post Infusion [ Time Frame: Baseline to 1 hour post-treatment ]
    Thromboelastography (TEG) using rotational thromboelastometry (ROTEM®) was used to measure maximum clot firmness. Rotational thromboelastometry is a method for the continuous measurement of clot formation. Maximum clot firmness is a functional parameter that depends on the activation of coagulation, the platelet and fibrinogen content of the blood sample, and the polymerisation and cross-linking of the fibrin network. In order to obtain comparable results from all study centres, maximum clot firmness data were assessed from frozen citrated plasma samples in a central laboratory. As these samples did not contain platelets that would be found in the whole blood assay, only the fibrinogen content defined the maximum clot firmness.


Original Primary Outcome: Pharmacokinetics [ Time Frame: 1 year ]

A comparison of the area under the curve (AUC) between Octafibrin and Haemocomplettan/Riastap


Current Secondary Outcome:

  • Fibrinogen Activity Normalized Area Under the Curve Unstandardized [ Time Frame: Baseline to 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment ]
    fibrinogen-specific enzyme-linked immunosorbent assay (ie, fibrinogen antigen) using paired antibodies for fibrinogen antigen. All determinations were performed on frozen plasma samples in a central laboratory. The Clauss assay was modified and validated to achieve a limit of quantification of 0.2 g/L. The pharmacokinetic analysis was assessed individually using a non-compartmental model. Plasma levels were measured at Baseline, 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment.
  • Incremental in Vivo Recovery [ Time Frame: Baseline to 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment ]
    Incremental in vivo recovery was calculated as the maximum increase in plasma fibrinogen (fibrinogen activity assay data) within 4 hours post-treatment as compared with pre-treatment (expressed as an absolute mg/dL concentration in plasma), divided by the exact dose of Octafibrin or Haemocomplettan® P or RiaSTAPTM (expressed as mg/kg dosed).
  • Terminal Half-life (t½) [ Time Frame: Baseline to 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment ]
    Fibrinogen activity was determined via a validated Clauss assay (fibrinogen activity) and fibrinogen-specific enzyme-linked immunosorbent assay (ie, fibrinogen antigen) using paired antibodies for fibrinogen antigen. All determinations were performed on frozen plasma samples in a central laboratory. The Clauss assay was modified and validated to achieve a limit of quantification of 0.2 g/L. The pharmacokinetic analysis was assessed individually using a non-compartmental model. Plasma levels were measured at Baseline, 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment.
  • Clearance [ Time Frame: Baseline to 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment ]
    Fibrinogen activity was determined via a validated Clauss assay (fibrinogen activity) and fibrinogen-specific enzyme-linked immunosorbent assay (ie, fibrinogen antigen) using paired antibodies for fibrinogen antigen. All determinations were performed on frozen plasma samples in a central laboratory. The Clauss assay was modified and validated to achieve a limit of quantification of 0.2 g/L. The pharmacokinetic analysis was assessed individually using a non-compartmental model. Plasma levels were measured at Baseline, 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment.


Original Secondary Outcome: Efficacy [ Time Frame: 1 year ]

Comparison of MCF between Octafibrin and Haemocomplettan/Riastap at 1 hour post infusion


Information By: Octapharma

Dates:
Date Received: April 9, 2012
Date Started: June 2013
Date Completion:
Last Updated: October 5, 2016
Last Verified: October 2016