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

• Register: EUCTR
• Last refreshed on: 12 June 2012
• Main ID: EUCTR2008-006424-54-SE
• Date of registration: 11/03/2009
• Prospective Registration: Yes
• Primary sponsor: Novo Nordisk A/S
• Public 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
• Scientific 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
• Date of first enrolment: 23/06/2009
• Target sample size: 24
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-006424-54
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

France, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Informed consent obtained before any trial-related activities (Trial-related activities are any procedure that would not have been performed during normal management of the patient.)
2. Male Haemophilia A or B patients with inhibitors
3. Aged between 12 and 65 years, both inclusive
4. Willing to undergo a bleeding preventive regimen of 3 months duration and a total trial length of approximately 8 months
5. Historical or ongoing high titer inhibitor (= 5 BU) based on either medical records,
laboratory report reviews, patient and/or care provider interviews
6. 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
7. Body weight between 30 and 100 kg (both inclusive)
8. Patient has adequate venous access at the Screening Visit
9. Patient or caregiver is capable of assessing a bleed, capable of home treatment of bleeding episodes and otherwise follow the trial protocol

Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Body Mass Index (BMI)>30 kg/m²
2. Immune tolerance induction therapy within the last 1 month prior to entering observation
phase period
3. Known active pseudo tumours
4. Platelet count < 50,000 platelets/µL (based on local laboratory value at Screening Visit)
5. Congenital or acquired coagulation disorders other than haemophilia A or B
6. 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.
7. 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.
8. Advanced atherosclerotic disease (i.e. known history of ischemic heart disease, or
ischemic stroke)
9. Any clinical signs or known history of thromboembolic events incl. known deep vein
thrombosis (DVT)
10. Known or clinically suspected allergy to rFVIIa (NovoSeven®/NovoSeven
RT®/Niastase®)
11. PT prolongation (30% above normal limits, or >5 seconds compared to control or INR >1.7 as defined by local laboratory ranges at screening visit)
12. Severe liver disease (ALAT > 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
13. Clinical signs of renal dysfunction (dialysis) and/or creatinine levels = 20% above upper normal limit (according to local laboratory range at the screening visit)
14. Dosing of any investigational drug within the last 30 days prior to the present trial
15. 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
16. HIV positive patients; who either have low CD4+ lymphocyte count (= 200/µl based on medical records within 6 months or lab screening at screening visit), or who are HCV-PCR positive (based on medical records), or who both have low CD4+ lymphocyte count (= 200/µl) 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.
17. Need to use other PEGylated pharmaceutical drug during the trial period.
18. Mental incapacity, unwillingness or a language barrier precluding adequate
understanding and cooperation





Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Haemophilia A (Factor VIII) or B with Inhibitors
MedDRA version: 9.1 Level: LLT Classification code 10018939 Term: Haemophilia B (Factor IX)
MedDRA version: 9.1 Level: LLT Classification code 10060612 Term: Hemophilia A

Intervention(s)

Product Name: LA-rFVIIa
Product Code: NN7128
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: eptacgo alfa pegol (activated)
CAS Number: 944130-77-2
Current Sponsor code: NN7128
Other descriptive name: Long Acting recombinant activated Factor VII (LA-rFVIIa), PEGylated rFVIIa
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2-
Pharmaceutical form of the placebo: Powder and solvent for solution for injection
Route of administration of the placebo: Intravenous bolus use (Noncurrent)

Primary Outcome(s)

Main Objective: The primary objective is to determine the safety including the potential immunogenicity of LArFVIIa intravenously administered to haemophilia patients with inhibitors every second day for 12 weeks at three dose levels 25 µg/kg, 100 µg/kg and 200 µg/kg.

Secondary Objective: To evaluate the preliminary efficacy of LA-rFVIIa in reducing the bleeding frequency in
haemophilia A and B patients with inhibitors, and to identify the dose(s) suitable for further
development.
To investigate the pharmacokinetic properties of multiple intravenous doses of three dose levels of
LA-rFVIIa.
To investigate the effect of LA-rFVIIa on health economic (HE)/Patient Reported Outcomes (PRO) parameters

Primary end point(s): • Frequency of AE, SAE and Medical Events of Special Interest (MESI as defined in section 12.2.1) reported during the trial period
• Neutralising antibodies towards FVII and/or LA-rFVIIa
• Coagulation related parameters: D-dimers, Prothrombin Fragment 1+2, Fibrinogen, PT, aPTT and AT
• Platelet count, haematology
• Biochemistry
• ECG and Troponin T
• Urinalysis
• Vital signs, physical examination
• Injection site inspection

Secondary ID(s)

NN7128-1907