Clinical trial NCT00951405: Safety and Efficacy of 3 Different Doses of Long Acting Factor VII in Haemophilia A or B Patients With Inhibitors
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Congenital Bleeding Disorder
Haemophilia A With Inhibitors
Haemophilia B With Inhibitors
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2009-08-04
Enrollment: 23
Sex: MALE
Minimum age (years): 12
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.


Eligibility 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

Primary outcomes:
measure: Thrombogenecity
timeFrame: at all scheduled visits (1 - 9)
measure: Immunogenecity: Neutralising Antibody Development
timeFrame: at all scheduled visits (1 - 9)
Secondary outcomes:
measure: 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
timeFrame: at visit 2 and visit 7 until 48 hours after trial product administration
measure: Annualized bleeding rates
timeFrame: 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
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Novo Nordisk Investigational Site
state: Arkansas
city: Los Angeles
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Orange
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Tampa
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Boston
country: United States
facility: Novo Nordisk Investigational Site
state: Massachusetts
city: Portland
country: United States
facility: Novo Nordisk Investigational Site
state: Oregon
city: Hershey
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: Rio de Janeiro
country: Brazil
facility: Novo Nordisk Investigational Site
city: Belgrade
country: Former Serbia and Montenegro
facility: Novo Nordisk Investigational Site
city: Le Kremlin Bicetre
country: France
facility: Novo Nordisk Investigational Site
city: Paris
country: France
facility: Novo Nordisk Investigational Site
city: Kashihara-shi, Nara
country: Japan
facility: Novo Nordisk Investigational Site
city: Kitakyusyu, Fukuoka
country: Japan
facility: Novo Nordisk Investigational Site
city: Nishinomiya-shi
country: Japan
facility: Novo Nordisk Investigational Site
city: Shinjuku-ku, Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Kuala Lumpur
country: Malaysia
facility: Novo Nordisk Investigational Site
city: Belgrade
country: Serbia
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: Malmö
country: Sweden
facility: Novo Nordisk Investigational Site
city: Ankara
country: Turkey
facility: Novo Nordisk Investigational Site
city: Istanbul
country: Turkey
facility: Novo Nordisk Investigational Site
city: London
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: London
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Oxford
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: Ljung R, Karim FA, Saxena K, Suzuki T, Arkhammar P, Rosholm A, Giangrande P; Pioneer1 Investigators. 40K glycoPEGylated, recombinant FVIIa: 3-month, double-blind, randomized trial of safety, pharmacokinetics and preliminary efficacy in hemophilia patients with inhibitors. J Thromb Haemost. 2013 Jul;11(7):1260-8. doi: 10.1111/jth.12237.