E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with hereditary angioedema (HAE) suffer from recurring and mostly unforeseeable attacks of acute oedema of subcutaneous tisses of various organs. The pathophysiological correlate of this disease is a deficiency in functionally active C1-Esterase Inhibitor (C1-INH). The defects in active C1-Esterase Inhibitor are inherited as an autosomal dominant trait. |
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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 investigate and compare pharmacokinetics of study medication (Berinert P) in subjects with hereditary angioedema after subcutaneous and intravenous administration |
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E.2.2 | Secondary objectives of the trial |
Documentation of adverse events Screening for C1-Inhibitor antibodies Investigation of virus markers
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects with an established diagnosis of Hereditary Angioedema (HAE)type I (C1-Inhibitor activity <50% and C1-Inhibitor antigen < 15.4 mg/dl) or HAE type II (C1-Inhibitor activity < 50% and C1-Inhibitor antigen in normal or elevated concentration of dysfunctional protein). Male and female subjects with an age of 18 years Subjects providing an informed consent
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E.4 | Principal exclusion criteria |
Subjects without an established diagnosis of HAE Last C1-INH administration less than 7 days ago and/or acute attack Subjects with acquired angioedeme (AAE) All other types of angioedema not associated with C1-INH deficiency Treatment with any investigational drug (exclusive drugs appropriate for the treatment of acute angioedema) 30 days before study treatment Treatment with any other drug appropriate for the treatment of acute angioedema within 2 weeks before start of study treatment at each phase Danazol prophylaxis Prophylaxis with antifibrinolytics, EACA, tranexamic acid Subjects with a known hypersensitivity to study medication (Berinert P) Pregnant women (pregnancy rapid assay required for women with childbearing potential), women currently breast-feeding, or with the intention to breast-feed Subjects with malignant diseases Subjects with immunodeficiencies such as established acquired immunodeficiency syndrome Subjects with concurrent serious or acute illness or infection as per investigators judgement. Subjects with mental conditions which render the subject or its legally acceptable representative unable to understand the nature, scope and possible consequences of the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
To investigate and compare pharmacokinetics of study medication (Berinert P) in HAE subjects after subcutaneous and intravenous administration Individual courses of C1-inhibitor levels, from these will be derived:
Area under the curve (AUC; for dose of 1,000 U per subject [(U x hour)/mL] Time to maximum concentration (Tmax; hours) Maximum concentration (Cmax) Terminal elimination half-life (t1/2) Mean residence time (MRT; hours) Total clearance (Cl; mL/[kg x hour]) Volume of distribution at steady state (Vss; mL/kg) In-vivo recovery (IVR) Classical IVR (% rise/U/ml) Incremental IVR (response) (% rise/U/kg body weight)
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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 | Information not present in EudraCT |
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) | Yes |
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 | 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 | Yes |
E.8.1.7 | Other | Information not present in EudraCT |
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 |
Comparison of subcutaneous application versus authorised intraveneous application mode |
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E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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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The end of the study is defined as 3 months after the last subject receiving the last 1,000 U of Berinert P (the end of observation period) |
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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 | |
E.8.9.1 | In the Member State concerned days | |