Safety and Mode of Action of a Single Dose and Multiple Doses of Long Acting Activated Recombinant Human Factor VII in Patients With Haemophilia A and B

Study Overview
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Brief Summary
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This trial is conducted in Europe. The aim of this clinical trial is to investigate the safety and pharmacokinetics (the effect of the body on the investigated drug) of long acting activated recombinant human factor VII (LA-rFVIIa) in patients with haemophilia.

Official Title
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An Open, Non-Randomised Single and Multiple Dose Trial Investigating the Safety and Pharmacokinetics of Intravenous Administration of Long Acting rFVIIa (LA-rFVIIa) in Patients With Haemophilia A and B

Conditions
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Congenital Bleeding Disorder, Haemophilia A, Haemophilia B

Intervention / Treatment
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* Drug: activated recombinant human factor VII, long acting
* Drug: activated recombinant human factor VII, long acting


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Haemophilia A or B Bodyweight max 100 kg Body Mass Index (BMI) max 30 kg/m2 Adequate venous access Exclusion Criteria: Known or suspected allergy to trial product(s) or related products (including NovoSeven®) The receipt of any investigational product within 30 days prior to enrolment in this trial Receipt of Immune Tolerance Induction (ITI) within the last 1 month prior to participation in this trial The receipt of any haemostatic treatment for control of a bleeding episode within the last 5 days prior to administration of trial product Receipt of FVIII or FIX replacement therapy within 48 hours prior to trial product administration Known pseudo tumours Congenital or acquired coagulation disorders other than haemophilia A or B Any major and/or orthopaedic surgery within one month prior to trial start Advanced atherosclerotic disease (defined as known history of ischemic heart disease, ischemic stroke, etc.) Clinical signs of renal dysfunction Use of platelet inhibitors, including NSAIDs, one week prior to administration of trial drug Use of non-prescribed opiate substances

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: activated recombinant human factor VII, long acting<br>* Single dose of 0,2 mg/kg LA-rFVIIa injected i.v. (intravenous) of 2 minutes duration<br>|
| Experimental: B<br> | Drug: activated recombinant human factor VII, long acting<br>* Multiple doses of 100 mg/kg LA-rFVIIa injected i.v. (intravenous) of 2 minutes duration every 48 hours<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of adverse events |  | after 1 and 2 weeks after dosing | 
| Frequency of serious adverse events |  | after 1, 2 and 6-10 weeks after dosing | 
| Frequency of MESIs (Medical Event of Special Interest) |  | after 1, 2 and 6-10 weeks after dosing | 
| Frequency of ocurrence of neutralising antibodies against FVII and/or LA-rFVIIa |  | after 2 and 6-10 weeks after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters based on FVIIa activity. The pharmacokinetic parameters to be reported are: AUC(0-48h), AUC(0-t) and AUC, C10min, Vz, CL, and t½ |  | from time of dosing up to 72 hours after the last dose |