Clinical Trial: Haemophilia Patients With Inhibitors Being Treated for Acute Joint Bleeds

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

Official Title: A Multi-centre, Randomised, Double-blinded, Controlled, Dose-escalation Trial on Safety and Efficacy of Activated Recombinant FVII Analogue (NN1731) in the Treatment of Joint Ble

Brief Summary:

This trial is conducted in Africa, Asia, Europe, Japan, and North and South America.

The aim of this trial is to evaluate the safety and efficacy of activated recombinant human factor VII analogue (vatreptocog alfa (activated)) in haemophilia patients with inhibitors.


Detailed Summary:
Sponsor: Novo Nordisk A/S

Current Primary Outcome: Number of Adverse Events (AEs) [ Time Frame: Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. ]

Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.


Original Primary Outcome:

  • Adverse events: Non-serious adverse events occurring from the first administration of trial product [ Time Frame: until 7 days after first trial product administration. ]
  • Adverse events: Serious adverse events are collected from the first administration of trial product [ Time Frame: to the end of subjects' participation in the trial ]


Current Secondary Outcome:

  • Activated Recombinant Human Factor VII Analogue Activity in the Blood [ Time Frame: 0-24 hours after trial product administration ]
  • Prothrombin Time (PT) [ Time Frame: pre-dose - 12 hours after trial product administration ]
    The test measures the clotting time of plasma following the activation of tissue factor (TF also called thromboplastin) and calcium to hypocalcemic plasma. PT was provided in percent based on the measured PT in seconds and related/converted with the relevant standard curve. The percent value was derived based on the hyperbolic relation between PT (sec) and % PT activity.
  • F1 + 2 (Prothrombin Fragments 1+2) [ Time Frame: pre-dose - 12 hours after trial product administration ]
    Thrombin and F1+2 are formed in equimolar quantities by the enzymatic cleavage of prothrombin (FII), and F1+2 thus indicate that thrombin has been generated.
  • Activated Partial Thromboplastin Time (aPTT) [ Time Frame: pre-dose - 12 hours after trial product administration ]
    The aPTT time measured in clinical samples reflects both the effect of the drugs (generation of thrombin and FXa) and the presence of rFVIIa /rFVIIa analogue in the plasma samples causing a dose dependent shortening of the clotting time.
  • Cessation of Bleeding: Number of Doses Needed to Control Bleeding [ Time Frame: Within 9 hours after first trial product administration or need of additional haemostatic medication within 9 hours after first trial administration additional haemostatic agents required to control bleed (treatment failure) ]
  • Number of Subjects With Need for Additional Haemostatic Agents [ Time Frame: within 24 hours after successful control of bleeding episode with trial product ]
  • Pharmacokinetic Parameters Based on FVIIa Activity: AUC 0-t (Area Under the Plasma FVIIa Activity-time Curve From Time Zero to the Time (t) ) [ Time Frame: 0-24 hours after trial product administration ]
  • Pharmacokinetic Parameters Based on FVIIa Activity: AUC(0-inf) (Area Under the Plasma FVIIa Activity-time Curve From Time Zero to Infinity) [ Time Frame: 0-24 hours after trial product administration ]
  • Pharmacokinetic Parameters Based on FVIIa Activity: MRT (Mean Residence Time) [ Time Frame: 0-24 hours after trial product administration ]
  • Pharmacokinetic Parameters Based on FVIIa Activity: t½ (Terminal Half-life) [ Time Frame: 0-24 hours after trial product administration ]
  • Pharmacokinetic Parameters Based on FVIIa Activity: CL (Total Clearance) [ Time Frame: 0-24 hours after trial product administration ]
  • Pharmakokinetic Parameters Based on FVIIa Activity: Vss (Distribution Volume at Steady State) [ Time Frame: 0-24 hours after trial product administration ]
  • Immunogenicity (Inhibitor Development) [ Time Frame: Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product. ]
    Immunogenicity was tested by formation of neutralising antibodies towards vatreptacog alfa and/or rFVIIa.
  • Biochemistry: ALAT (Alanine Aminotransferase) [ Time Frame: screening visit, pre-dose and 12 hours after dosing ]
  • Biochemistry: Creatinine [ Time Frame: screening visit, pre-dose and 12 hours after dosing ]
  • Haematology: Haemoglobin [ Time Frame: screening visit, pre-dose and 12 hours after dosing ]
  • Haematology: Red Cell Count [ Time Frame: screening visit, pre-dose and 12 hours after dosing ]
  • Haematology: Packed Cell Volume [ Time Frame: screening visit, pre-dose and 12 hours after dosing ]
  • Haematology: White Cell Count [ Time Frame: screening visit, pre-dose and 12 hours after dosing ]
  • Haematology: Platelet Count [ Time Frame: screening visit, pre-dose and 12 hours after dosing ]


Original Secondary Outcome:

  • Pharmacokinetic parameters
  • Coagulation related parameters
  • Cessation of bleeding


Information By: Novo Nordisk A/S

Dates:
Date Received: June 13, 2007
Date Started: June 2007
Date Completion:
Last Updated: January 23, 2017
Last Verified: January 2017