E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with severe or moderate B Haemophilia, previously treated with rFIX. |
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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 | SOC |
E.1.2 | Classification code | 10010331 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary endpoint of the study will be the evaluation of the variability of pharmacokinetic parameters (in vivo recovery, AUC, clearance, MRT, terminal half life, Cmax, elimination k, volume of distribution) of a new formulation of recombinant factor IX in patients with severe or moderate B haemophilia, previously treated with rFIX. |
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E.2.2 | Secondary objectives of the trial |
Secondary endpoints of the study will be the evaluation and the characterization of:
1) Pharmacokinetic parameters using a simplified pharmacokinetic evaluation model, and validation of the method used against the standard method (Morfini M., Haemophilia 12, Suppl. 4, 2006);
2) Pharmacokinetic parameters in the paediatric population subgroup (6-12);
3) Evaluation of the correlations between pharmacokinetic profile of the single patient and the causative mutation;
4) Efficacy of the drug administration both in prophylaxis and in on demand regimen of the new formulation of recombinant factor IX;
5) Evaluation of adverse events according to the standard method;
6) Evaluation of the variability in the drug consumption of the new formulation of recombinant FIX (International Units/Kg) in the study period, per single patient; |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Severe or moderate B haemophilia (factor IX activity < 5 %);
2. Male patients older than 6 years;
3. Patients previously treated with rFIX.
4. Written informed consent |
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E.4 | Principal exclusion criteria |
1. Patients ongoing treatment with plasmaderived factor IX (pd-FIX);
2. For patients with documented HIV infection, CD4 count <200 and/or in HAART therapy;
3. Patients with liver or renal disease (ALT and AST 2.5x ULN, bilirubin >2 mg/dL, seric albumin <3.5 g/L seric creatinin >1.25 x ULN);
4. Prothrombin Time >1.5 x ULN;
5. Platelet count < 150.000/µL;
6. Patients with current or past inhibitors to factor IX;
7. Patients with history of hypersensitivity to FIX or to eccipients, or to Hamster proteins;
8 Exposure to other experimental drugs, eccept BeneFIX, in the 30 days prior to the sign of the informed consent of this study;
9. Patients with coagulation disorders/diseases different from B haemophilia;
10. Inflammatory disease documented and still present, which could, judjed by the investigator, be confounding the study results (e.g. systemic eritematosus lupus, rheumatoid arthritis, inflammatory bowel disease);
11. Patients showing low compliance to the study procedures, patients with difficult venous access, and all those patients who are judged (by the investigator) to be inadequate for this study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The evaluation of the study product will be performed on the base of the following variables:
Efficacy
The efficacy of the on demand treatment with reformulated rFIX will be evaluated by the number of infusions needed and the total amount of rFIX used for the complete resolution of each bleeding episode
The efficacy of the prophylaxis treatment with reformulated rFIX will be evaluated by the number of bleeding episodes elapsed during the treatment, by the time from last infusion, and by the number of infusions needed and the total amount of rFIX used for the complete resolution of each bleeding episode.
The efficacy of the treatment with reformulated rFIX in surgery will nbe evaluated by the investigator through the daily detection of Hb levels and through transfusion needs.
Investigators (and/or surgeons) will use a 5 points scale to evacuate the efficacy of the reformulated rFIX in prophylaxis. The evaluation will be performed both for the intra-operatory and for the post operatory efficacy.
Evaluation of safety and tolerability
Safety and toleability of reformulated rFIX will be determined through the evaluation of clinical and routine laboratory paramenters and through the report of all the adverse events, the serious adverse events and the special adverse events (inhibitors to FIX, thrombotic events, hypersensitivity reactions to FIX, red blood cells agglutination). Inhibitors presence will be evaluated before the starting of the study and at 6 months. |
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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 | Yes |
E.6.3 | Therapy | Yes |
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 | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 31 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |