Safety and Efficacy of 3 Different Doses of Long Acting Factor VII in Haemophilia A or B Patients With Inhibitors

Study Overview
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Brief Summary
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This trial is conducted in Asia, Europe, Japan and North America. The aim of this clinical trial is to investigate the safety and the efficacy of a prophylactic treatment option with long acting coagulation factor VII (LA-rFVIIa) for haemophilia patients with inhibitors.

Official Title
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An Exploratory Multi-Centre, Multi-National, Randomised, Double Blinded, Parallel Arm Trial Evaluating Safety, Pharmacokinetics and Dose-finding of Prophylactic Administration of Long Acting rFVIIa (LA-rFVIIa) in Haemophilia A or B Patients With Inhibitors

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

Intervention / Treatment
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* Drug: activated recombinant human factor VII, long acting
* 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: Male haemophilia A or B patients with inhibitors Willing to undergo a bleeding preventive regimen of 3 months' duration and a total trial length of approximately 8 months Historical or ongoing high titre inhibitor (more than or equal to 5 BU) based on either medical records, laboratory report reviews, patient and/or care provider interviews At least 2 bleeding episodes requiring bypassing haemostatic-drug-based treatment within the last month or 12 bleeding episodes within the last 6 months prior to observation period Body weight between 30 and 100 kg (both inclusive) Exclusion Criteria: Body Mass Index (BMI) above 30 kg/m2 Immune tolerance induction therapy within the last month prior to entering observation phase period Known active pseudo tumours Platelet count less than 50,000 platelets/microL (based on local laboratory value at screening visit) Congenital or acquired coagulation disorders other than haemophilia A or B Surgery within one month prior to the observation period. Catheter, stents and dental extractions do not count as surgeries, i.e. they will not exclude the patient. Port insertion is classified as surgery Scheduled major and/or orthopaedic surgery, during the trial period until Follow up visit. Catheter, stents and dental extractions do not count as surgeries and will not exclude the patient. Port insertion is classified as surgery Advanced atherosclerotic disease (i.e. known history of ischemic heart disease, or ischemic stroke) Any clinical signs or known history of thromboembolic events incl. known deep vein thrombosis (DVT) Known or clinically suspected allergy to activated recombinant human factor VII (NovoSeven®/NovoSeven RT®/Niastase®) Prothrombin Time (PT) prolongation (30% above normal limits, or more than 5 seconds compared to control or International Normalised Range (INR) more than 1.7 as defined by local laboratory ranges at screening visit Severe liver disease (ALAT more than 4 times of the upper limit of normal reference range) (as defined by local laboratory ranges) within a year of enrolment or at the screening Clinical signs of renal dysfunction (dialysis) and/or creatinine levels more than or equal to 20% above upper normal limit (according to local laboratory range at the screening visit) Dosing of any investigational drug within the last 30 days prior to the present trial Any disease or condition which, according to the investigator's judgement, could imply a potential hazard to the subject, interfere with the trial participation or trial outcome HIV positive patients who either have low CD4+ lymphocyte count ( 200/microL or less based on medical records within 6 months or laboratory screening at screening visit), or who are HCV-PCR positive (based on medical records), or who both have low CD4+ lymphocyte count (200/microL or less) and are HCV-PCR positive. If HCV-PCR testing is not locally available, a HIV positive patient who is HCV antibody positive cannot be included Need to use other PEGylated pharmaceutical drug during the trial period

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 65 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: activated recombinant human factor VII, long acting<br>* After an observation period of 3 months, every 2nd day intravenous (i.v.) injection with 25 microgrammes/kg activated recombinant human factor VII, long acting, for 3 months<br>* Other names: LA-rFVIIa;|
| Experimental: B<br> | Drug: activated recombinant human factor VII, long acting<br>* After an observation period of 3 months, every 2nd day intravenous (i.v.) injection with 100 microgrammes/kg activated recombinant human factor VII, long acting, for 3 months<br>* Other names: LA-rFVIIa;|
| Experimental: C<br> | Drug: activated recombinant human factor VII, long acting<br>* After an observation period of 3 months, every 2nd day intravenous (i.v.) injection with 200 microgrammes/kg activated recombinant human factor VII, long acting, for 3 months<br>* Other names: LA-rFVIIa;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Thrombogenecity |  | at all scheduled visits (1 - 9) | 
| Immunogenecity: Neutralising Antibody Development |  | at all scheduled visits (1 - 9) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC(0-48h) and AUC: Area under the FVIIa activity-time profile in the given time period, which is a measure of total blood exposure |  | at visit 2 and visit 7 until 48 hours after trial product administration | 
| Annualized bleeding rates |  | During observation period; from visit 1 until visit 2 and treatment period; from visit 2 until visit 7. In total a period of 6 to 8 months |