Clinical trial NCT00486278: Haemophilia Patients With Inhibitors Being Treated for Acute Joint Bleeds
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Congenital Bleeding Disorder
Haemophilia A
Haemophilia B
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2007-06-14
Enrollment: 51
Sex: MALE
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility 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

Primary outcomes:
measure: Number of Adverse Events (AEs)
timeFrame: Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product.
Secondary outcomes:
measure: Activated Recombinant Human Factor VII Analogue Activity in the Blood
timeFrame: 0-24 hours after trial product administration
measure: Prothrombin Time (PT)
timeFrame: pre-dose - 12 hours after trial product administration
measure: F1 + 2 (Prothrombin Fragments 1+2)
timeFrame: pre-dose - 12 hours after trial product administration
measure: Activated Partial Thromboplastin Time (aPTT)
timeFrame: pre-dose - 12 hours after trial product administration
measure: Cessation of Bleeding: Number of Doses Needed to Control Bleeding
timeFrame: 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)
measure: Number of Subjects With Need for Additional Haemostatic Agents
timeFrame: within 24 hours after successful control of bleeding episode with trial product
measure: Pharmacokinetic Parameters Based on FVIIa Activity: AUC 0-t (Area Under the Plasma FVIIa Activity-time Curve From Time Zero to the Time (t) )
timeFrame: 0-24 hours after trial product administration
measure: Pharmacokinetic Parameters Based on FVIIa Activity: AUC(0-inf) (Area Under the Plasma FVIIa Activity-time Curve From Time Zero to Infinity)
timeFrame: 0-24 hours after trial product administration
measure: Pharmacokinetic Parameters Based on FVIIa Activity: MRT (Mean Residence Time)
timeFrame: 0-24 hours after trial product administration
measure: Pharmacokinetic Parameters Based on FVIIa Activity: t½ (Terminal Half-life)
timeFrame: 0-24 hours after trial product administration
measure: Pharmacokinetic Parameters Based on FVIIa Activity: CL (Total Clearance)
timeFrame: 0-24 hours after trial product administration
measure: Pharmakokinetic Parameters Based on FVIIa Activity: Vss (Distribution Volume at Steady State)
timeFrame: 0-24 hours after trial product administration
measure: Immunogenicity (Inhibitor Development)
timeFrame: Monitoring of adverse events was performed from start of the trial to approximately 4 weeks after administration of trial product.
measure: Biochemistry: ALAT (Alanine Aminotransferase)
timeFrame: screening visit, pre-dose and 12 hours after dosing
measure: Biochemistry: Creatinine
timeFrame: screening visit, pre-dose and 12 hours after dosing
measure: Haematology: Haemoglobin
timeFrame: screening visit, pre-dose and 12 hours after dosing
measure: Haematology: Red Cell Count
timeFrame: screening visit, pre-dose and 12 hours after dosing
measure: Haematology: Packed Cell Volume
timeFrame: screening visit, pre-dose and 12 hours after dosing
measure: Haematology: White Cell Count
timeFrame: screening visit, pre-dose and 12 hours after dosing
measure: Haematology: Platelet Count
timeFrame: screening visit, pre-dose and 12 hours after dosing
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Augusta
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Chicago
country: United States
facility: Novo Nordisk Investigational Site
state: Illinois
city: Indianapolis
country: United States
facility: Novo Nordisk Investigational Site
state: Indiana
city: Iowa City
country: United States
facility: Novo Nordisk Investigational Site
state: Iowa
city: Boston
country: United States
facility: Novo Nordisk Investigational Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Novo Nordisk Investigational Site
state: Michigan
city: Minneapolis
country: United States
facility: Novo Nordisk Investigational Site
state: Minnesota
city: New York
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: Chapel Hill
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Portland
country: United States
facility: Novo Nordisk Investigational Site
state: Oregon
city: Ciudad Autónoma de Bs. As.
country: Argentina
facility: Novo Nordisk Investigational Site
city: Campinas
country: Brazil
facility: Novo Nordisk Investigational Site
state: Sao Paulo
city: Rio de Janeiro
country: Brazil
facility: Novo Nordisk Investigational Site
city: São Paulo
country: Brazil
facility: Novo Nordisk Investigational Site
city: Edmonton
country: Canada
facility: Novo Nordisk Investigational Site
state: Alberta
city: Zagreb
country: Croatia
facility: Novo Nordisk Investigational Site
city: Lyon
country: France
facility: Novo Nordisk Investigational Site
city: Budapest
country: Hungary
facility: Novo Nordisk Investigational Site
city: Debrecen
country: Hungary
facility: Novo Nordisk Investigational Site
city: Tel-Hashomer
country: Israel
facility: Novo Nordisk Investigational Site
city: Castelfranco Veneto
country: Italy
facility: Novo Nordisk Investigational Site
city: Firenze
country: Italy
facility: Novo Nordisk Investigational Site
city: Milano
country: Italy
facility: Novo Nordisk Investigational Site
city: Hiroshima-shi, Hiroshima
country: Japan
facility: Novo Nordisk Investigational Site
city: Itabashi-ku, Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Kashihara-shi, Nara
country: Japan
facility: Novo Nordisk Investigational Site
city: Nagoya-shi, Aichi
country: Japan
facility: Novo Nordisk Investigational Site
city: Nishinomiya-shi
country: Japan
facility: Novo Nordisk Investigational Site
city: Kuala Lumpur
country: Malaysia
facility: Novo Nordisk Investigational Site
city: Warszawa
country: Poland
facility: Novo Nordisk Investigational Site
city: Parktown Johannesburg
country: South Africa
facility: Novo Nordisk Investigational Site
state: Gauteng
city: Durban
country: South Africa
facility: Novo Nordisk Investigational Site
state: KwaZulu-Natal
city: Cape Town
country: South Africa
facility: Novo Nordisk Investigational Site
city: Madrid
country: Spain
facility: Novo Nordisk Investigational Site
city: Changhua
country: Taiwan
facility: Novo Nordisk Investigational Site
city: Taipei
country: Taiwan
facility: Novo Nordisk Investigational Site
city: Bangkok
country: Thailand
facility: Novo Nordisk Investigational Site
city: Adana
country: Turkey
facility: Novo Nordisk Investigational Site
city: Ankara
country: Turkey
facility: Novo Nordisk Investigational Site
city: Antalya
country: Turkey
facility: Novo Nordisk Investigational Site
city: Bornova-IZMIR
country: Turkey
facility: Novo Nordisk Investigational Site
city: London
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Manchester
country: United Kingdom
facility: Novo Nordisk Investigational Site
Study officials:
affiliation: Novo Nordisk A/S
name: Global Clinical Registry (GCR, 1452)
role: STUDY_DIRECTOR
References:
citation: de Paula EV, Kavakli K, Mahlangu J, Ayob Y, Lentz SR, Morfini M, Nemes L, Salek 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. doi: 10.1111/j.1538-7836.2011.04549.x.