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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT00951405
First received: August 3, 2009
Last updated: June 26, 2014
Last verified: June 2014
  Purpose

This trial is conducted in Asia, Europe, Japan and North America. The aim of this clinical trial is to investigate the safety and the efficacy of a prophylactic treatment option with long acting coagulation factor VII (LA-rFVIIa) for haemophilia patients with inhibitors.


Condition Intervention Phase
Congenital Bleeding Disorder
Haemophilia A With Inhibitors
Haemophilia B With Inhibitors
Drug: activated recombinant human factor VII, long acting
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: Prevention
Official Title: An Exploratory Multi-Centre, Multi-National, Randomised, Double Blinded, Parallel Arm Trial Evaluating Safety, Pharmacokinetics and Dose-finding of Prophylactic Administration of Long Acting rFVIIa (LA-rFVIIa) in Haemophilia A or B Patients With Inhibitors

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Thrombogenecity [ Time Frame: at all scheduled visits (1 - 9) ] [ Designated as safety issue: Yes ]
  • Immunogenecity: Neutralising Antibody Development [ Time Frame: at all scheduled visits (1 - 9) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 [ Time Frame: at visit 2 and visit 7 until 48 hours after trial product administration ] [ Designated as safety issue: No ]
  • Annualized bleeding rates [ Time Frame: 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 ] [ Designated as safety issue: No ]

Enrollment: 23
Study Start Date: September 2009
Study Completion Date: March 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A Drug: activated recombinant human factor VII, long acting
After an observation period of 3 months, every 2nd day intravenous (i.v.) injection with 25 microgrammes/kg activated recombinant human factor VII, long acting, for 3 months
Other Names:
  • NN7128
  • LA-rFVIIa
Experimental: B Drug: activated recombinant human factor VII, long acting
After an observation period of 3 months, every 2nd day intravenous (i.v.) injection with 100 microgrammes/kg activated recombinant human factor VII, long acting, for 3 months
Experimental: C Drug: activated recombinant human factor VII, long acting
After an observation period of 3 months, every 2nd day intravenous (i.v.) injection with 200 microgrammes/kg activated recombinant human factor VII, long acting, for 3 months

  Eligibility

Ages Eligible for Study:   12 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00951405

Locations
United States, California
Novo Nordisk Clinical Trial Call Center
Los Angeles, California, United States, 90027
United States, Florida
Novo Nordisk Clinical Trial Call Center
Tampa, Florida, United States, 33607
United States, Massachusetts
Novo Nordisk Clinical Trial Call Center
Boston, Massachusetts, United States, 02115
United States, Oregon
Novo Nordisk Clinical Trial Call Center
Portland, Oregon, United States, 97239
United States, Pennsylvania
Novo Nordisk Clinical Trial Call Center
Hershey, Pennsylvania, United States, 17033
France
Paris, France, 75015
Japan
Kashihara-shi, Nara, Japan, 634 8522
Malaysia
Kuala Lumpur, Malaysia, 50400
Serbia
Belgrade, Serbia, 11000
South Africa
Parktown Johannesburg, Gauteng, South Africa, 2193
Sweden
Malmö, Sweden, 205 02
Turkey
Istanbul, Turkey, 34098
United Kingdom
London, United Kingdom, SE1 7EH
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: NCT00951405     History of Changes
Other Study ID Numbers: NN7128-1907, 2008-006424-54, JapicCTI-090860, U1111-1111-8584
Study First Received: August 3, 2009
Last Updated: June 26, 2014
Health Authority: Sweden: Medical Products Agency
Malaysia: Ministry of Health
Serbia: Agency for Drugs and Medicinal Devices
United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Turkey: Ministry of Health
Japan: Ministry of Health, Labor and Welfare
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
South Africa: Medicines Control Council

Additional relevant MeSH terms:
Hemophilia B
Hemophilia A
Blood Coagulation Disorders
Hemostatic Disorders
Hemorrhagic Disorders
Hemorrhage
Hematologic Diseases
Vascular Diseases
Cardiovascular Diseases
Blood Coagulation Disorders, Inherited
Coagulation Protein Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Pathologic Processes
Factor VIII
Coagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 27, 2014