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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: December 15, 2014
Last verified: December 2014

June 13, 2007
December 15, 2014
June 2007
June 2010   (final data collection date for primary outcome measure)
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.
  • Adverse events: Non-serious adverse events occurring from the first administration of trial product [ Time Frame: Until 7 days after first trial product administration. ]
  • Adverse events: Serious adverse events are collected from the first administration of trial product [ Time Frame: To the end of subjects' participation in the trial ]
Complete list of historical versions of study NCT00486278 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Pharmacokinetic parameters
  • Coagulation related parameters
  • Cessation of bleeding
Not Provided
Not Provided
 
Haemophilia Patients With Inhibitors Being Treated for Acute Joint Bleeds
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

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.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
  • Congenital Bleeding Disorder
  • Haemophilia A
  • Haemophilia B
  • Drug: eptacog alfa (activated)
    90 mcg/kg, injected i.v.
  • Drug: vatreptacog alfa (activated)
    5 mcg/kg, injected i.v.
  • Drug: vatreptacog alfa (activated)
    10 mcg/kg, injected i.v.
  • Drug: vatreptacog alfa (activated)
    20 mcg/kg, injected i.v.
  • Drug: vatreptacog alfa (activated)
    40 mcg/kg, injected i.v.
  • Drug: vatreptacog alfa (activated)
    80 mcg/kg, injected i.v.
  • Experimental: vatreptacog alfa 5 mcg/kg
    Intervention: Drug: vatreptacog alfa (activated)
  • Experimental: vatreptacog alfa 10 mcg/kg
    Intervention: Drug: vatreptacog alfa (activated)
  • Experimental: vatreptacog alfa 20 mcg/kg
    Intervention: Drug: vatreptacog alfa (activated)
  • Experimental: vatreptacog alfa 40 mcg/kg
    Intervention: Drug: vatreptacog alfa (activated)
  • Experimental: vatreptacog alfa 80 mcg/kg
    Intervention: Drug: vatreptacog alfa (activated)
  • Experimental: rFVIIa 90 mcg/kg
    Intervention: Drug: eptacog alfa (activated)
de Paula EV, Kavakli K, Mahlangu J, Ayob Y, Lentz SR, Morfini M, Nemes L, Šalek SZ, Shima M, Windyga J, Ehrenforth S, Chuansumrit A; 1804 (adept(TM)1) Investigators. Recombinant factor VIIa analog (vatreptacog alfa [activated]) for treatment of joint bleeds in hemophilia patients with inhibitors: a randomized controlled trial. J Thromb Haemost. 2012 Jan;10(1):81-9.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
51
June 2010
June 2010   (final data collection date for primary outcome measure)

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
Male
12 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   Brazil,   Canada,   Croatia,   Hungary,   Israel,   Italy,   Japan,   Malaysia,   Poland,   South Africa,   Spain,   Taiwan,   Thailand,   Turkey,   United Kingdom
France
 
NCT00486278
NN1731-1804, 2006-004879-35, CTI-080612
Yes
Novo Nordisk A/S
Novo Nordisk A/S
Not Provided
Study Director: Global Clinical Registry (GCR, 1452) Novo Nordisk A/S
Novo Nordisk A/S
December 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP