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Completed

NCT Number: NCT00486278

Haemophilia Patients With Inhibitors Being Treated for Acute Joint Bleeds

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.

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Key information

Conditions

Congenital Bleeding Disorder Blood Coagulation Disorders Blood Coagulation Disorders, Inherited Coagulation Protein Disorders Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Genetic Diseases, X-Linked Haemophilia A Haemophilia B Hematologic Diseases Hemic and Lymphatic Diseases Hemophilia A Hemophilia B Hemorrhagic Disorders

Age range

12 year and older

Sex eligibility

Male

Study type

Interventional

Phase

Phase 2

Primary location

Novo Nordisk Investigational Site, Ciudad Autónoma de Bs. As., Argentina

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

eptacog alfa (activated)

Drug

90 mcg/kg, injected i.v.

vatreptacog alfa (activated)

Drug

5 mcg/kg, injected i.v.

Primary outcomes

  1. 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

  1. Activated Recombinant Human Factor VII Analogue Activity in the Blood

    Time frame: 0-24 hours after trial product administration

  2. Prothrombin Time (PT)

    Time frame: pre-dose - 12 hours after trial product administration

    The test measures the clotting time of plasma following the activation of tissue factor (TF also called thromboplastin) and calcium to hypocalcemic plasma. PT was provided in percent based on the measured PT in seconds and related/converted with the relevant standard curve. The percent value was derived based on the hyperbolic relation between PT (sec) and % PT activity.

  3. F1 + 2 (Prothrombin Fragments 1+2)

    Time frame: pre-dose - 12 hours after trial product administration

    Thrombin and F1+2 are formed in equimolar quantities by the enzymatic cleavage of prothrombin (FII), and F1+2 thus indicate that thrombin has been generated.

  4. Activated Partial Thromboplastin Time (aPTT)

    Time frame: pre-dose - 12 hours after trial product administration

    The aPTT time measured in clinical samples reflects both the effect of the drugs (generation of thrombin and FXa) and the presence of rFVIIa /rFVIIa analogue in the plasma samples causing a dose dependent shortening of the clotting time.

  5. Cessation of Bleeding: Number of Doses Needed to Control Bleeding

    Time frame: 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)

  6. Number of Subjects With Need for Additional Haemostatic Agents

    Time frame: within 24 hours after successful control of bleeding episode with trial product

  7. Pharmacokinetic Parameters Based on FVIIa Activity: AUC 0-t (Area Under the Plasma FVIIa Activity-time Curve From Time Zero to the Time (t) )

    Time frame: 0-24 hours after trial product administration

  8. Pharmacokinetic Parameters Based on FVIIa Activity: AUC(0-inf) (Area Under the Plasma FVIIa Activity-time Curve From Time Zero to Infinity)

    Time frame: 0-24 hours after trial product administration

  9. Pharmacokinetic Parameters Based on FVIIa Activity: MRT (Mean Residence Time)

    Time frame: 0-24 hours after trial product administration

  10. Pharmacokinetic Parameters Based on FVIIa Activity: t½ (Terminal Half-life)

    Time frame: 0-24 hours after trial product administration

  11. Pharmacokinetic Parameters Based on FVIIa Activity: CL (Total Clearance)

    Time frame: 0-24 hours after trial product administration

  12. Pharmakokinetic Parameters Based on FVIIa Activity: Vss (Distribution Volume at Steady State)

    Time frame: 0-24 hours after trial product administration

  13. Immunogenicity (Inhibitor Development)

    Time frame: Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product.

    Immunogenicity was tested by formation of neutralising antibodies towards vatreptacog alfa and/or rFVIIa.

  14. Biochemistry: ALAT (Alanine Aminotransferase)

    Time frame: screening visit, pre-dose and 12 hours after dosing

  15. Biochemistry: Creatinine

    Time frame: screening visit, pre-dose and 12 hours after dosing

  16. Haematology: Haemoglobin

    Time frame: screening visit, pre-dose and 12 hours after dosing

  17. Haematology: Red Cell Count

    Time frame: screening visit, pre-dose and 12 hours after dosing

  18. Haematology: Packed Cell Volume

    Time frame: screening visit, pre-dose and 12 hours after dosing

  19. Haematology: White Cell Count

    Time frame: screening visit, pre-dose and 12 hours after dosing

  20. Haematology: Platelet Count

    Time frame: screening visit, pre-dose and 12 hours after dosing

Sponsors and collaborators

Lead sponsor

Novo Nordisk A/S

Industry

Registry information

Official study title

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

Important dates

Study start
2007
Primary completion
2010
Study completion
2010
First posted
Jun 14, 2007
Registry last updated
Mar 7, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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