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

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 23

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
C	activated recombinant human factor VII, long acting	-
A	activated recombinant human factor VII, long acting	-
B	activated recombinant human factor VII, long acting	-

Primary Outcome Measures

Name	Time	Method
Thrombogenecity	at all scheduled visits (1 - 9)
Immunogenecity: Neutralising Antibody Development	at all scheduled visits (1 - 9)

Secondary Outcome Measures

Name	Time	Method
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