Haemophilia Patients With Inhibitors Being Treated for Acute Joint Bleeds

• Adverse events: Non-serious adverse events occurring from the first administration of trial product [ Time Frame: until 7 days after first trial product administration. ] [ Designated as safety issue: Yes ]
• Serious adverse events are collected form the first trial product administration of trial product [ Time Frame: to the end of subjects participation (up to maximum 24 months) ] [ Designated as safety issue: No ]

• 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 ]

• Pharmacokinetic parameter: Activated recombinant human factor VII analogue activity in the blood (IU/ml) [ Time Frame: 0-24 hours after trial product administration ] [ Designated as safety issue: No ]
• Coagulation related parameter- Prothrombin Time (PT) [ Time Frame: predose- 24 hours after trial product administration ] [ Designated as safety issue: No ]
• Coagulation related parameter: F1 + 2 (Prothrombin Fragments 1+2) [ Time Frame: predose- 24 hours after trial product administration ] [ Designated as safety issue: No ]
• Coagulation related parameter- activated Partial Thromboplastin Time (aPTT) [ Time Frame: Predose- 24 hours after trial product administration ] [ Designated as safety issue: No ]
• Cessation of bleeding: Number of doses needed to control bleeding. Need evaluated after each of 1-3 doses [ 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) ] [ Designated as safety issue: No ]
• Need for additional haemostatic agents [ Time Frame: within 24 hours after succesful control of bleeding episode with trial product ] [ Designated as safety issue: No ]
• Pharmakokinetic parameters based on FVlla activity: AUC 0-t (Area under the plasma FVIIa activity-time curve from time zero to the time (t) ) and AUC (Area under the plasma FVIIa activity-time curve from time zero to infinity) [ Time Frame: 0-24 hours after trial product administration ] [ Designated as safety issue: No ]
• Pharmakokinetic parameters based on FVlla activity: MRT (Mean residence time) [ Time Frame: 0-24 hours after trial product administration ] [ Designated as safety issue: No ]
• Pharmakokinetic parameters based on FVlla activity: t½ (Terminal half-life) [ Time Frame: 0-24 hours after trial product administration ] [ Designated as safety issue: No ]
• Pharmakokinetic parameters based on FVlla activity: CL (Total clearance) [ Time Frame: 0-24 hours after trial product administration ] [ Designated as safety issue: No ]
• Pharmakokinetic parameters based on FVlla activity: Vss (Distribution volume at steady state) [ Time Frame: 0-24 hours after trial product administration ] [ Designated as safety issue: No ]
• Immunogenicity (inhibitor development) [ Time Frame: screening visit, predose, 7 days after dosing and 28 after dosing ] [ Designated as safety issue: No ]
• Biocemistry: ALAT (Alanine aminotransferase) [ Time Frame: screening visit, predose and 12 hours after dosing ] [ Designated as safety issue: No ]
• Biocemestry: Creatine [ Time Frame: screening visit, predose and 12 hours after dosing ] [ Designated as safety issue: No ]
• Haematology: Haemoglobin (g/dL) [ Time Frame: screening visit, predose and 12 hours after dosing ] [ Designated as safety issue: No ]
• Haematology: Red cell count (x 10^12/L) [ Time Frame: screening visit, predose and 12 hours after dosing ] [ Designated as safety issue: No ]
• Haematology: Packed cell volume (%) [ Time Frame: screening visit, predose and 12 hours after dosing ] [ Designated as safety issue: No ]
• Haematology: White cell count (x 10^9/L) [ Time Frame: screening visit, predose and 12 hours after dosing ] [ Designated as safety issue: No ]
• Haematology: Platelet count (x 10^9/L) [ Time Frame: screening visit, predose and 12 hours after dosing ] [ Designated as safety issue: No ]

• Pharmacokinetic parameters
• Coagulation related parameters
• Cessation of bleeding

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 in haemophilia patients with inhibitors.

• Congenital Bleeding Disorder
• Haemophilia A
• Haemophilia B

• Drug: activated recombinant human factor VII
  90 mcg/kg, injected i.v.
• Drug: activated recombinant human factor VII analogue
  5 mcg/kg, injected i.v.
• Drug: activated recombinant human factor VII analogue
  10 mcg/kg, injected i.v.
• Drug: activated recombinant human factor VII analogue
  20 mcg/kg, injected i.v.
• Drug: activated recombinant human factor VII analogue
  40 mcg/kg, injected i.v.
• Drug: activated recombinant human factor VII analogue
  80 mcg/kg, injected i.v.

• Experimental: A
  Intervention: Drug: activated recombinant human factor VII analogue
• Experimental: B
  Intervention: Drug: activated recombinant human factor VII analogue
• Experimental: C
  Intervention: Drug: activated recombinant human factor VII analogue
• Experimental: D
  Intervention: Drug: activated recombinant human factor VII analogue
• Experimental: E
  Intervention: Drug: activated recombinant human factor VII analogue
• Active Comparator: F
  Intervention: Drug: activated recombinant human factor VII

Inclusion Criteria:

• Congenital haemophilia patients with inhibitors
• Age eligible for trial participation: 12 years and above. For Croatia, France and United Kingdom: 18 years and above.
• Haemophilia patients with high bleeding frequency
• Historical peak inhibitor titre of at least 5 Bethesda Units

Exclusion Criteria:

• Known active pseudo tumours
• Platelet count lower than 50,000 mm^3
• Severe liver disease
• Known allergy to trial product(s) or related products
• Recent surgery
• Any history of thromboembolic events
• Advanced atherosclerotic disease