E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Haemophilia A is an X-linked recessive clotting disorder in which the clotting factor, factor VIII (FVIII), is deficient or inactive. Patients with low levels of FVIII have an increased tendency to bleed and is characterised by recurrent haemorrhages due to trauma, surgery or spontaneous haemorrhaging when the condition is severe. |
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MedDRA Classification |
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 |
To describe the patterns of antibodies and associated epitopes in a subset of patients with hemophilia A, who meet the protocol entry criteria, using the methodology described in the protocol. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inhibitor positive hemophilia A patients: 1. Written informed consent or assent, as applicable. 2. Patients with moderate or severe congenital hemophilia A (FVIII:C <5%) . 3. Patients with at least one positive de novo* inhibitor result (> the upper limit of normal as defined by the laboratory performing the assay), attributable by the Investigator to the patient’s current FVIII product, at the time of study visit and a positive inhibitor result confirmed by the central laboratory. 4. Patients with exposure to at least two different FVIII products during their lifetime. 5. Patients with > 50 cumulative ED to FVIII products. 6. Patients able to comply with a 72-hour FVIII washout period.
*de novo inhibitor is defined as no known history of FVIII inhibitor titer.
Comparison group (inhibitor-free patients): 1. Written informed consent / assent, as applicable. 2. Patients with moderate or severe congenital hemophilia A (FVIII:C < 5%). 3. Patients with exposure to at least two different FVIII products during their lifetime. 4. Patients with > 50 cumulative exposure days to FVIII products. 5. Documented negative FVIII BIA at the time of the study visit (< the upper limit of normal as defined by the laboratory performing the assay).
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E.4 | Principal exclusion criteria |
Inhibitor positive hemophilia A patients: 1. Patients with a negative FVIII inhibitor result (< or equal to the upper limit of normal as defined by the laboratory performing the assay) at the study visit. 2. Patients with known history of an inhibitor (> the upper limit of normal as defined by the laboratory performing the assay) prior to their current inhibitor. 3. Patients who have not had at least 1 FVIII BIA performed during the last 5 years prior to their visit for this study. 4. Patients who have received FVIII immune tolerance therapy at any time. 5. Patients, who as of the study visit, have taken only one FVIII product during their lifetime. 6. For patients whose current inhibitor is attributable to treatment with ReFacto; treatment with ReFacto prior to their previous product. In other words patients who were previously treated with ReFacto, then switched to another product, then switched back to ReFacto. 7. Patients with immune disorders (e.g., HIV, myeloma, lymphoma).
Comparison group (inhibitor-free patients): 1. Patients with a positive FVIII inhibitor result (> the upper limit of normal as defined by the laboratory performing the assay) at the time of the study visit. 2. Patients with a prior history of FVIII inhibitor (> the upper limit of normal as defined by the laboratory performing the assay). 3. Patients with immune disorders (e.g., HIV, myeloma, lymphoma).
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E.5 End points |
E.5.1 | Primary end point(s) |
The endpoint will be a descriptive presentation of epitope regions of FVIII in samples from the three patient groups, using the methodology described in the protocol. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Information not present in EudraCT |
E.6.5 | Efficacy | Information not present in EudraCT |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Phase IV study requested by EMEA to understand inhibitor development in haemophilia patients |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
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) | No |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
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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The study will remain open for 36 months, or until 9 patients are enrolled in each of the three groups, whichever comes first. |
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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 | 3 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |