A Trial Investigating the Pharmacokinetics and Pharmacodynamics of rFVIIa in Patients With Haemophilia A or B With or Without Inhibitors

Study Overview
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Brief Summary
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This trial is conducted in Europe. The aim of the trial is to investigate the pharmacokinetics (the exposure of the trial drug in the body) and pharmacodynamics (the effect of the investigated drug on the body) of rFVIIa (activated coagulation factor VII) following one single injection of 270 microg/kg compared to three injections of 90 microg/kg rFVIIa in patients with haemophilia.

Official Title
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An Open-label Single- and Multiple-dose Trial Investigating the Pharmacokinetics and Pharmacodynamics of rFVIIa Following i.v. Administration of One Dose of 270 Microg/kg and Three Doses of 90 Microg/kg in Patients With Haemophilia A or B With or Without Inhibitors

Conditions
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Congenital Bleeding Disorder, Haemophilia A, Haemophilia A With Inhibitors, Haemophilia B, Haemophilia B With Inhibitors

Intervention / Treatment
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* Drug: eptacog alfa (activated)
* Drug: eptacog alfa (activated)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial Male patients with confirmed diagnosis of severe congenital haemophilia A or B (higher than 1% FVIII or FIX) with or without inhibitors to coagulation factors VIII or IX, based on medical records Exclusion Criteria: Congenital or acquired coagulation disorder other than congenital haemophilia A or B Any clinical signs or known history of arterial thrombotic events or previous deep vein thrombosis or pulmonary embolism (as defined by available medical records) Use of any anticoagulant (e.g. un-fractionated or low molecular weight heparin, vitamin-K antagonists, direct thrombin inhibitors or factor Xa inhibitors) Bleeding prophylactic treatment or FVIII or FIX immune tolerance induction (ITI) treatment during the trial period

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 270 microg/kg rFVIIa<br>Each subject will receive one single injection of 270 microg/kg and three injections of 90 microg/kg rFVIIa (one injection every 3 hours) in a randomised order. The two administration days will be separated by a wash-out period of at least 48 hours | Drug: eptacog alfa (activated)<br>* Subject will receive a single injection (i.v.) of 270 microg/kg rFVIIa (NovoSeven®)<br>|
| Active Comparator: 3x90 microg/kg rFVIIa<br>Each subject will receive one single injection of 270 microg/kg and three injections of 90 microg/kg rFVIIa (one injection every 3 hours) in a randomised order. The two administration days will be separated by a wash-out period of at least 48 hours | Drug: eptacog alfa (activated)<br>* Subject will receive 3 injections (i.v.) of 90 microg/kg rFVIIa (NovoSeven®) over a 6 hour period (each injection will be separated by 3 hours)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Thromboelastography (TEG) parameter Maximum Thrombosis Generation (MTG;'maximum velocity') |  | 10 minutes post-dose for 270 microg/kg and 10 minutes after the first injection of 90 microg/kg | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TEG parameters r-time, MTG, alpha angle, and maximum amplitude (MA) |  | Prior to and 24 hours following the administrtion of 270 microg/kg and each of the 3 administrations of 90 microg/kg |