NCT00486278
Completed
Phase 2
A Multi-centre, Randomised, Double-blinded, Controlled, Dose-escalation Trial on Safety and Efficacy of Activated Recombinant FVII Analogue (NN1731) in the Treatment of Joint Bleeds in Congenital Haemophilia Patients With Inhibitors
Overview
- Phase
- Phase 2
- Intervention
- vatreptacog alfa (activated)
- Conditions
- Congenital Bleeding Disorder
- Sponsor
- Novo Nordisk A/S
- Enrollment
- 51
- Locations
- 1
- Primary Endpoint
- Number of Adverse Events (AEs)
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
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 (vatreptocog alfa (activated)) in haemophilia patients with inhibitors.
Investigators
Eligibility Criteria
Inclusion Criteria
- •12 years of age or older (at least 18 years in Croatia, France and United Kingdom (UK))
- •Clinical diagnosis of congenital haemophilia A or B with a current positive inhibitor titre and a known peak inhibitor of above 5 Bethesda units (BU) (present or in the past) to human FVIII or IX and known antihuman FVIII or IX anamnestic response
- •Minimum of 2 joint bleeds (haemarthroses of ankles, knees, or elbows) requiring haemostatic drug treatment within the previous 6 months, or at least 4 joint bleeds (hemarthroses of ankles, knees, or elbows) requiring haemostatic drug treatment within the previous 12 months at trial entry
Exclusion Criteria
- •Known allergy to rFVIIa, and/or suspected allergy to trial product
- •Platelet count lower than 50,000 mm\^3 based on medical records at trial entry (visit 1)
- •Any clinical signs or history of thromboembolic events
- •Advanced atherosclerotic disease
- •Severe liver disease based on medical records within the past 12 months at trial entry (Visit 1), as defined by alanine aminotransferase (ALAT) above 3 times the upper limit of normal reference range
- •Known active pseudo tumours (documented bleeding requiring treatment within the last 3 months
- •Subject had any (major) surgical procedure in the 30 days prior to screening into the trial. a. Catheter, ports and dental extractions do not count as surgeries and will not exclude the subject
Arms & Interventions
vatreptacog alfa 5 mcg/kg
Intervention: vatreptacog alfa (activated)
vatreptacog alfa 10 mcg/kg
Intervention: vatreptacog alfa (activated)
vatreptacog alfa 20 mcg/kg
Intervention: vatreptacog alfa (activated)
vatreptacog alfa 40 mcg/kg
Intervention: vatreptacog alfa (activated)
vatreptacog alfa 80 mcg/kg
Intervention: vatreptacog alfa (activated)
rFVIIa 90 mcg/kg
Intervention: eptacog alfa (activated)
Outcomes
Primary Outcomes
Number of Adverse Events (AEs)
Time Frame: Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product.
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Secondary Outcomes
- F1 + 2 (Prothrombin Fragments 1+2)(pre-dose - 12 hours after trial product administration)
- Prothrombin Time (PT)(pre-dose - 12 hours after trial product administration)
- Biochemistry: ALAT (Alanine Aminotransferase)(screening visit, pre-dose and 12 hours after dosing)
- Activated Recombinant Human Factor VII Analogue Activity in the Blood(0-24 hours after trial product administration)
- Number of Subjects With Need for Additional Haemostatic Agents(within 24 hours after successful control of bleeding episode with trial product)
- Pharmacokinetic Parameters Based on FVIIa Activity: AUC 0-t (Area Under the Plasma FVIIa Activity-time Curve From Time Zero to the Time (t) )(0-24 hours after trial product administration)
- Activated Partial Thromboplastin Time (aPTT)(pre-dose - 12 hours after trial product administration)
- Cessation of Bleeding: Number of Doses Needed to Control Bleeding(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))
- Pharmacokinetic Parameters Based on FVIIa Activity: AUC(0-inf) (Area Under the Plasma FVIIa Activity-time Curve From Time Zero to Infinity)(0-24 hours after trial product administration)
- Pharmacokinetic Parameters Based on FVIIa Activity: MRT (Mean Residence Time)(0-24 hours after trial product administration)
- Pharmacokinetic Parameters Based on FVIIa Activity: t½ (Terminal Half-life)(0-24 hours after trial product administration)
- Pharmacokinetic Parameters Based on FVIIa Activity: CL (Total Clearance)(0-24 hours after trial product administration)
- Pharmakokinetic Parameters Based on FVIIa Activity: Vss (Distribution Volume at Steady State)(0-24 hours after trial product administration)
- Haematology: Packed Cell Volume(screening visit, pre-dose and 12 hours after dosing)
- Immunogenicity (Inhibitor Development)(Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product.)
- Biochemistry: Creatinine(screening visit, pre-dose and 12 hours after dosing)
- Haematology: Haemoglobin(screening visit, pre-dose and 12 hours after dosing)
- Haematology: Platelet Count(screening visit, pre-dose and 12 hours after dosing)
- Haematology: Red Cell Count(screening visit, pre-dose and 12 hours after dosing)
- Haematology: White Cell Count(screening visit, pre-dose and 12 hours after dosing)
Study Sites (1)
Loading locations...
Similar Trials
Completed
Phase 2
Efficacy and Safety of Activated Recombinant Human Factor VII in Severely Injured Trauma PatientsAcquired Bleeding DisorderTraumaNCT01563523Novo Nordisk A/S283
Completed
Phase 2
Efficacy and Safety of Activated Recombinant Human Factor VII in Treatment of Bleeding in Patients Following Allogeneic Stem Cell TransplantationAcquired Bleeding DisorderBleeding During/Following SurgeryNCT01562158Novo Nordisk A/S100
Completed
Phase 3
Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome ResultsDiabetesDiabetes Mellitus, Type 2NCT01179048Novo Nordisk A/S9,341
Completed
Phase 2
Efficacy of NovoSeven® in Bleeding Prophylaxis in HemophiliaCongenital Bleeding DisorderHaemophilia A With InhibitorsHaemophilia B With InhibitorsNCT00108758Novo Nordisk A/S23
Completed
Phase 2
A Trial Evaluating the Efficacy and Safety of Prophylactic Administration of Concizumab in Haemophilia A and B Patients With InhibitorsCongenital Bleeding DisorderHaemophilia A With InhibitorsHaemophilia B With InhibitorsNCT03196284Novo Nordisk A/S26