E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with severe Haemophilia A with a high responding inhibitor (more than 5 BU/ml) |
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MedDRA Classification |
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 |
The study is aimed at evaluating whether FVIII/VWF concentrates can induce more frequently or more rapidly immune tolerance to FVIII in haemophilia A patients with high-responding inhibitors at high risk to fail in comparison with VWF-free concentrates |
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E.2.2 | Secondary objectives of the trial |
1) Maintenance of immune tolerance which is defined as an absence of relapse, assayed up to 12 months after the achievement of tolerance. 2) Time to achieve success, either partial or complete (as defined). 3) Safety, the assessment and evaluation of any adverse events occurring during the treatment. 4) Cost of care |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Severe haemophilia A (FVIII less than 1% of normal) 2) Males of any age 3) High responders (peak titre more than 5 BU/ml) 4) Any inhibitor at time of enrolment 5) At least one of the following risk factors for ITI failure - peak inhibitor titre more than 200 BU/ml - inhibitor titre at start of treatment more than 10 BU/ml - more than 7 years of age - more than 2 years between inhibitor occurrence and ITI
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E.4 | Principal exclusion criteria |
1)concomitant systemic treatment with drugs with immunosuppressive side effects (eg corticosteroids, if used more 5 days every 3 months and/or at a dose of more than 2mg/kg or 60mg/day), azathioprine, cyclophosphamide, high dose immunoglobulin) 2) use of a protein A column or plasmapheresis 3) treatment with interferons 4) concomitant experimental treatment 5) previous ITI attempt 6) previous history of myocardial infarction and/or cerebral stroke 7) high risk of cardiovascular, cerebrovascular or other thrombembolic events as deemed by the treating physician 8) patients with known hypersensitivity to anu of the the constituents of any of the FVIII products that can be used in the study |
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E.5 End points |
E.5.1 | Primary end point(s) |
The study is aimed at evaluating whether FVIII/VWF concentrates can induce more frequently or more rapidly immune tolerance to FVIII in haemophilia A patients with high-responding inhibitors at high risk to fail in comparison with VWF-free concentrates |
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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 | 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) | 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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
on demand treatment or prophylaxis |
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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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
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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As defined in the protocol |
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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 | 6 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |