Haemophilia Patients With Inhibitors Being Treated for Acute Joint Bleeds

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT00486278
First received: June 13, 2007
Last updated: February 23, 2015
Last verified: February 2015
  Purpose

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.


Condition Intervention Phase
Congenital Bleeding Disorder
Haemophilia A
Haemophilia B
Drug: eptacog alfa (activated)
Drug: vatreptacog alfa (activated)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official 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

Resource links provided by NLM:


Further study details as provided by Novo Nordisk A/S:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Activated Recombinant Human Factor VII Analogue Activity in the Blood [ Time Frame: 0-24 hours after trial product administration ] [ Designated as safety issue: No ]
  • Prothrombin Time (PT) [ Time Frame: pre-dose - 12 hours after trial product administration ] [ Designated as safety issue: No ]
    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.

  • F1 + 2 (Prothrombin Fragments 1+2) [ Time Frame: pre-dose - 12 hours after trial product administration ] [ Designated as safety issue: No ]
    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.

  • Activated Partial Thromboplastin Time (aPTT) [ Time Frame: pre-dose - 12 hours after trial product administration ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
  • Number of Subjects With Need for Additional Haemostatic Agents [ Time Frame: within 24 hours after successful control of bleeding episode with trial product ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Pharmacokinetic Parameters Based on FVIIa Activity: MRT (Mean Residence Time) [ Time Frame: 0-24 hours after trial product administration ] [ Designated as safety issue: No ]
  • Pharmacokinetic Parameters Based on FVIIa Activity: t½ (Terminal Half-life) [ Time Frame: 0-24 hours after trial product administration ] [ Designated as safety issue: No ]
  • Pharmacokinetic Parameters Based on FVIIa Activity: CL (Total Clearance) [ Time Frame: 0-24 hours after trial product administration ] [ Designated as safety issue: No ]
  • Pharmakokinetic Parameters Based on FVIIa Activity: Vss (Distribution Volume at Steady State) [ Time Frame: 0-24 hours after trial product administration ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
    Immunogenicity was tested by formation of neutralising antibodies towards vatreptacog alfa and/or rFVIIa.

  • Biochemistry: ALAT (Alanine Aminotransferase) [ Time Frame: screening visit, pre-dose and 12 hours after dosing ] [ Designated as safety issue: No ]
  • Biochemistry: Creatinine [ Time Frame: screening visit, pre-dose and 12 hours after dosing ] [ Designated as safety issue: No ]
  • Haematology: Haemoglobin [ Time Frame: screening visit, pre-dose and 12 hours after dosing ] [ Designated as safety issue: No ]
  • Haematology: Red Cell Count [ Time Frame: screening visit, pre-dose and 12 hours after dosing ] [ Designated as safety issue: No ]
  • Haematology: Packed Cell Volume [ Time Frame: screening visit, pre-dose and 12 hours after dosing ] [ Designated as safety issue: No ]
  • Haematology: White Cell Count [ Time Frame: screening visit, pre-dose and 12 hours after dosing ] [ Designated as safety issue: No ]
  • Haematology: Platelet Count [ Time Frame: screening visit, pre-dose and 12 hours after dosing ] [ Designated as safety issue: No ]

Enrollment: 51
Study Start Date: June 2007
Study Completion Date: June 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: vatreptacog alfa 5 mcg/kg Drug: vatreptacog alfa (activated)
5 mcg/kg, injected i.v.
Experimental: vatreptacog alfa 10 mcg/kg Drug: vatreptacog alfa (activated)
10 mcg/kg, injected i.v.
Experimental: vatreptacog alfa 20 mcg/kg Drug: vatreptacog alfa (activated)
20 mcg/kg, injected i.v.
Experimental: vatreptacog alfa 40 mcg/kg Drug: vatreptacog alfa (activated)
40 mcg/kg, injected i.v.
Experimental: vatreptacog alfa 80 mcg/kg Drug: vatreptacog alfa (activated)
80 mcg/kg, injected i.v.
Experimental: rFVIIa 90 mcg/kg Drug: eptacog alfa (activated)
90 mcg/kg, injected i.v.

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00486278

  Show 25 Study Locations
Sponsors and Collaborators
Novo Nordisk A/S
Investigators
Study Director: Global Clinical Registry (GCR, 1452) Novo Nordisk A/S
  More Information

Additional Information:
No publications provided by Novo Nordisk A/S

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT00486278     History of Changes
Other Study ID Numbers: NN1731-1804, 2006-004879-35, CTI-080612
Study First Received: June 13, 2007
Results First Received: September 27, 2013
Last Updated: February 23, 2015
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia
Brazil: National Health Surveillance Agency
Canada: Health Canada
Croatia: Ministry of Health and Social Care
Hungary: National Institute of Pharmacy
Israel: Ministry of Health
Italy: The Italian Medicines Agency
Japan: Ministry of Health, Labour and Welfare (MHLW)
Malaysia: Drug Control Authority (DCA)
Poland: The Office for Reg. of Medicinal Products, Medical Devices and Biocidal Products - Central Register of Clinical Trials
South Africa: Medicines Control Council
Spain: Spanish Drug Agency and Medicinal Products
Taiwan: Department of Health
Thailand: Ministry of Public Health
Turkey: Ministry of Health Drug and Pharmaceutical Department
United Kingdom: Medicines and Healthcare Products Regulatory
United States: Food and Drug Administration

Additional relevant MeSH terms:
Hemophilia B
Blood Coagulation Disorders
Blood Coagulation Disorders, Inherited
Coagulation Protein Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Hematologic Diseases
Hemorrhagic Disorders

ClinicalTrials.gov processed this record on March 31, 2015