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

Congenital Bleeding Disorder Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00951405
• Other study ID #: NN7128-1907
• Secondary ID: 2008-006424-54Ja
• Status: Completed
• Phase: Phase 2
• Start date: September 1, 2009
• Est. completion date: March 29, 2011

Study information

• Verified date: September 2018
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: March 29, 2011
• Est. primary completion date: March 29, 2011
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 12 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Blood Coagulation Disorders
• Congenital Bleeding Disorder
• Haemophilia A With Inhibitors
• Haemophilia B With Inhibitors
• Hemophilia A
• Hemophilia B
• Hemostatic Disorders

Intervention

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
• 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
• 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

Locations

Country	Name	City	State
Brazil	Novo Nordisk Investigational Site	Rio de Janeiro
Former Serbia and Montenegro	Novo Nordisk Investigational Site	Belgrade
France	Novo Nordisk Investigational Site	Le Kremlin Bicetre
France	Novo Nordisk Investigational Site	Paris
Japan	Novo Nordisk Investigational Site	Kashihara-shi, Nara
Japan	Novo Nordisk Investigational Site	Kitakyusyu, Fukuoka
Japan	Novo Nordisk Investigational Site	Nishinomiya-shi
Japan	Novo Nordisk Investigational Site	Shinjuku-ku, Tokyo
Malaysia	Novo Nordisk Investigational Site	Kuala Lumpur
Serbia	Novo Nordisk Investigational Site	Belgrade
South Africa	Novo Nordisk Investigational Site	Durban	KwaZulu-Natal
South Africa	Novo Nordisk Investigational Site	Parktown Johannesburg	Gauteng
Sweden	Novo Nordisk Investigational Site	Malmö
Turkey	Novo Nordisk Investigational Site	Ankara
Turkey	Novo Nordisk Investigational Site	Istanbul
United Kingdom	Novo Nordisk Investigational Site	London
United Kingdom	Novo Nordisk Investigational Site	London
United Kingdom	Novo Nordisk Investigational Site	Oxford
United States	Novo Nordisk Investigational Site	Boston	Massachusetts
United States	Novo Nordisk Investigational Site	Hershey	Pennsylvania
United States	Novo Nordisk Investigational Site	Little Rock	Arkansas
United States	Novo Nordisk Investigational Site	Los Angeles	California
United States	Novo Nordisk Investigational Site	Orange	California
United States	Novo Nordisk Investigational Site	Portland	Oregon
United States	Novo Nordisk Investigational Site	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Brazil,  Former Serbia and Montenegro,  France,  Japan,  Malaysia,  Serbia,  South Africa,  Sweden,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Thrombogenecity		at all scheduled visits (1 - 9)
Primary	Immunogenecity: Neutralising Antibody Development		at all scheduled visits (1 - 9)
Secondary	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		at visit 2 and visit 7 until 48 hours after trial product administration
Secondary	Annualized bleeding rates		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

External Links

•   Clinical Trials at Novo Nordisk