Haemophilia Patients With Inhibitors Being Treated for Acute Joint Bleeds

Congenital Bleeding Disorder Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00486278
• Other study ID #: NN1731-1804
• Secondary ID: 2006-004879-35CT
• Status: Completed
• Phase: Phase 2
• First received: June 13, 2007
• Last updated: April 15, 2015
• Start date: June 2007
• Est. completion date: June 2010

Study information

• Verified date: April 2015
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Health authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y TecnologiaBrazil: National Health Surveillance AgencyCanada: Health CanadaCroatia: Ministry of Health and Social CareHungary: National Institute of PharmacyIsrael: Ministry of HealthItaly: The Italian Medicines AgencyJapan: 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 TrialsSouth Africa: Medicines Control CouncilSpain: Spanish Drug Agency and Medicinal ProductsTaiwan: Department of HealthThailand: Ministry of Public HealthTurkey: Ministry of Health Drug and Pharmaceutical DepartmentUnited Kingdom: Medicines and Healthcare Products RegulatoryUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: June 2010
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 12 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• eptacog alfa (activated)
90 mcg/kg, injected i.v.
• vatreptacog alfa (activated)
5 mcg/kg, injected i.v.
• vatreptacog alfa (activated)
10 mcg/kg, injected i.v.
• vatreptacog alfa (activated)
20 mcg/kg, injected i.v.
• vatreptacog alfa (activated)
40 mcg/kg, injected i.v.
• vatreptacog alfa (activated)
80 mcg/kg, injected i.v.

Locations

Country	Name	City	State
United States	Novo Nordisk Clinical Trial Call Center	Boston	Massachusetts
United States	Novo Nordisk Clinical Trial Call Center	Chapel Hill	North Carolina
United States	Novo Nordisk Clinical Trial Call Center	Chicago	Illinois
United States	Novo Nordisk Clinical Trial Call Center	Indianapolis	Indiana
United States	Novo Nordisk Clinical Trial Call Center	Iowa City	Iowa
United States	Novo Nordisk Clinical Trial Call Center	Los Angeles	California
United States	Novo Nordisk Clinical Trial Call Center	Minneapolis	Minnesota
United States	Novo Nordisk Clinical Trial Call Center	New York	New York
United States	Novo Nordisk Clinical Trial Call Center	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Canada,  Croatia,  Hungary,  Israel,  Italy,  Japan,  Malaysia,  Poland,  South Africa,  Spain,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Adverse Events (AEs)	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.	Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product.	No
Secondary	Activated Recombinant Human Factor VII Analogue Activity in the Blood		0-24 hours after trial product administration	No
Secondary	Prothrombin Time (PT)	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.	pre-dose - 12 hours after trial product administration	No
Secondary	F1 + 2 (Prothrombin Fragments 1+2)	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.	pre-dose - 12 hours after trial product administration	No
Secondary	Activated Partial Thromboplastin Time (aPTT)	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.	pre-dose - 12 hours after trial product administration	No
Secondary	Cessation of Bleeding: Number of Doses Needed to Control Bleeding		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)	No
Secondary	Number of Subjects With Need for Additional Haemostatic Agents		within 24 hours after successful control of bleeding episode with trial product	No
Secondary	Pharmacokinetic Parameters Based on FVIIa Activity: AUC 0-t (Area Under the Plasma FVIIa Activity-time Curve From Time Zero to the Time (t) )		0-24 hours after trial product administration	No
Secondary	Pharmacokinetic Parameters Based on FVIIa Activity: AUC(0-inf) (Area Under the Plasma FVIIa Activity-time Curve From Time Zero to Infinity)		0-24 hours after trial product administration	No
Secondary	Pharmacokinetic Parameters Based on FVIIa Activity: MRT (Mean Residence Time)		0-24 hours after trial product administration	No
Secondary	Pharmacokinetic Parameters Based on FVIIa Activity: t½ (Terminal Half-life)		0-24 hours after trial product administration	No
Secondary	Pharmacokinetic Parameters Based on FVIIa Activity: CL (Total Clearance)		0-24 hours after trial product administration	No
Secondary	Pharmakokinetic Parameters Based on FVIIa Activity: Vss (Distribution Volume at Steady State)		0-24 hours after trial product administration	No
Secondary	Immunogenicity (Inhibitor Development)	Immunogenicity was tested by formation of neutralising antibodies towards vatreptacog alfa and/or rFVIIa.	Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product.	No
Secondary	Biochemistry: ALAT (Alanine Aminotransferase)		screening visit, pre-dose and 12 hours after dosing	No
Secondary	Biochemistry: Creatinine		screening visit, pre-dose and 12 hours after dosing	No
Secondary	Haematology: Haemoglobin		screening visit, pre-dose and 12 hours after dosing	No
Secondary	Haematology: Red Cell Count		screening visit, pre-dose and 12 hours after dosing	No
Secondary	Haematology: Packed Cell Volume		screening visit, pre-dose and 12 hours after dosing	No
Secondary	Haematology: White Cell Count		screening visit, pre-dose and 12 hours after dosing	No
Secondary	Haematology: Platelet Count		screening visit, pre-dose and 12 hours after dosing	No

External Links

•   Clinical Trials at Novo Nordisk