E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Haemophilia A (Factor VIII) or B with Inhibitors |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10018939 |
E.1.2 | Term | Haemophilia B (Factor IX) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060612 |
E.1.2 | Term | Hemophilia A |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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.
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E.2.2 | Secondary objectives of the trial |
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 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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E.4 | Principal 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. CD4+ lymphocyte count ≤ 200/µl if HIV positive (based on medical records within 6 months or lab screening at screening visit) 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
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E.5 End points |
E.5.1 | 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 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |