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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: January 23, 2017
Last verified: January 2017
  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
Intervention Model: Parallel Assignment
Masking: Participant, 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. ]
    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 ]
  • 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.

  • 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.

  • 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.

  • 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) ]
  • Number of Subjects With Need for Additional Haemostatic Agents [ Time Frame: 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) ) [ Time Frame: 0-24 hours after trial product administration ]
  • 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 ]
  • Pharmacokinetic Parameters Based on FVIIa Activity: MRT (Mean Residence Time) [ Time Frame: 0-24 hours after trial product administration ]
  • Pharmacokinetic Parameters Based on FVIIa Activity: t½ (Terminal Half-life) [ Time Frame: 0-24 hours after trial product administration ]
  • Pharmacokinetic Parameters Based on FVIIa Activity: CL (Total Clearance) [ Time Frame: 0-24 hours after trial product administration ]
  • Pharmakokinetic Parameters Based on FVIIa Activity: Vss (Distribution Volume at Steady State) [ Time Frame: 0-24 hours after trial product administration ]
  • 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.

  • Biochemistry: ALAT (Alanine Aminotransferase) [ Time Frame: screening visit, pre-dose and 12 hours after dosing ]
  • Biochemistry: Creatinine [ Time Frame: screening visit, pre-dose and 12 hours after dosing ]
  • Haematology: Haemoglobin [ Time Frame: screening visit, pre-dose and 12 hours after dosing ]
  • Haematology: Red Cell Count [ Time Frame: screening visit, pre-dose and 12 hours after dosing ]
  • Haematology: Packed Cell Volume [ Time Frame: screening visit, pre-dose and 12 hours after dosing ]
  • Haematology: White Cell Count [ Time Frame: screening visit, pre-dose and 12 hours after dosing ]
  • Haematology: Platelet Count [ Time Frame: screening visit, pre-dose and 12 hours after dosing ]

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   (Child, Adult, Senior)
Sexes 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

  Hide Study Locations
Locations
United States, California
Novo Nordisk Investigational Site
Los Angeles, California, United States, 90027
United States, Georgia
Novo Nordisk Investigational Site
Augusta, Georgia, United States, 30912
United States, Illinois
Novo Nordisk Investigational Site
Chicago, Illinois, United States, 60612-3833
United States, Indiana
Novo Nordisk Investigational Site
Indianapolis, Indiana, United States, 46260
United States, Iowa
Novo Nordisk Investigational Site
Iowa City, Iowa, United States, 52242
United States, Massachusetts
Novo Nordisk Investigational Site
Boston, Massachusetts, United States, 02115
United States, Michigan
Novo Nordisk Investigational Site
Ann Arbor, Michigan, United States, 48109-5235
United States, Minnesota
Novo Nordisk Investigational Site
Minneapolis, Minnesota, United States, 55455
United States, New York
Novo Nordisk Investigational Site
New York, New York, United States, 10029
United States, North Carolina
Novo Nordisk Investigational Site
Chapel Hill, North Carolina, United States, 27599-7035
United States, Ohio
Novo Nordisk Investigational Site
Cincinnati, Ohio, United States, 45229
United States, Oregon
Novo Nordisk Investigational Site
Portland, Oregon, United States, 97239-3011
Argentina
Novo Nordisk Investigational Site
Ciudad Autónoma de Bs. As., Argentina, C1425ASU
Brazil
Novo Nordisk Investigational Site
Campinas, Sao Paulo, Brazil, 13081970
Novo Nordisk Investigational Site
Rio de Janeiro, Brazil, 20211-030
Novo Nordisk Investigational Site
São Paulo, Brazil, 04024-002
Canada, Alberta
Novo Nordisk Investigational Site
Edmonton, Alberta, Canada, T6G 2B7
Croatia
Novo Nordisk Investigational Site
Zagreb, Croatia, 10 000
France
Novo Nordisk Investigational Site
Lyon, France, 69003
Hungary
Novo Nordisk Investigational Site
Budapest, Hungary, H-1134
Novo Nordisk Investigational Site
Debrecen, Hungary, 4012
Israel
Novo Nordisk Investigational Site
Tel-Hashomer, Israel, 52621
Italy
Novo Nordisk Investigational Site
Castelfranco Veneto, Italy, 31033
Novo Nordisk Investigational Site
Firenze, Italy, 50134
Novo Nordisk Investigational Site
Milano, Italy, 20124
Japan
Novo Nordisk Investigational Site
Hiroshima-shi, Hiroshima, Japan, 734 8551
Novo Nordisk Investigational Site
Itabashi-ku, Tokyo, Japan, 173 8606
Novo Nordisk Investigational Site
Kashihara-shi, Nara, Japan, 634 8522
Novo Nordisk Investigational Site
Nagoya-shi, Aichi, Japan, 466 8560
Novo Nordisk Investigational Site
Nishinomiya-shi, Japan, 663 8051
Malaysia
Novo Nordisk Investigational Site
Kuala Lumpur, Malaysia, 50400
Poland
Novo Nordisk Investigational Site
Warszawa, Poland, 02-776
South Africa
Novo Nordisk Investigational Site
Parktown Johannesburg, Gauteng, South Africa, 2193
Novo Nordisk Investigational Site
Durban, KwaZulu-Natal, South Africa, 4013
Novo Nordisk Investigational Site
Cape Town, South Africa, 7925
Spain
Novo Nordisk Investigational Site
Madrid, Spain, 28046
Taiwan
Novo Nordisk Investigational Site
Changhua, Taiwan, 500
Novo Nordisk Investigational Site
Taipei, Taiwan, 100
Thailand
Novo Nordisk Investigational Site
Bangkok, Thailand, 10400
Turkey
Novo Nordisk Investigational Site
Adana, Turkey, 01130
Novo Nordisk Investigational Site
Ankara, Turkey, 06100
Novo Nordisk Investigational Site
Antalya, Turkey, 01010
Novo Nordisk Investigational Site
Bornova-IZMIR, Turkey, 35100
United Kingdom
Novo Nordisk Investigational Site
London, United Kingdom, SE1 7EH
Novo Nordisk Investigational Site
Manchester, United Kingdom, M13 9WL
Sponsors and Collaborators
Novo Nordisk A/S
Investigators
Study Director: Global Clinical Registry (GCR, 1452) Novo Nordisk A/S
  More Information

Additional Information:
Publications:
Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT00486278     History of Changes
Other Study ID Numbers: NN1731-1804
2006-004879-35 ( EudraCT Number )
CTI-080612 ( Other Identifier: JAPIC )
Study First Received: June 13, 2007
Results First Received: September 27, 2013
Last Updated: January 23, 2017

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

ClinicalTrials.gov processed this record on July 24, 2017