E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hereditary Angioedema (HAE) |
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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 primary objective is to assess the efficacy of a single treatment (consisting of 1 subcutaneous administration) with the Bradykinin (BK) antagonist Icatibant compared with oral tranexamic acid on the onset of relief of symptoms during moderate to very severe acute cutaneous and/or abdominal angioedema attacks in patients with HAE |
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E.2.2 | Secondary objectives of the trial |
To assess the following parameters of s.c. icatibant compared with oral tranexamic acid in subjects with HAE suffering from cutaneous and/or abdominal oedema attacks: • the rate of response, • time to almost complete relief, • global outcome, • severity of each symptom, • safety • and tolerability
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• • Age >= 18 years; • Documented diagnosis of HAE Type I or II (confirmed by medical history and/ or immunogenic or functional C1-INH deficiency. Inclusion will be permitted initially based on medical history alone if a clear diagnosis has been made on all of the following criteria: Family history; Characteristic attack manifestations, recurrent attacks; Historical functional C1-INH level < 50%; Exclusion of other forms of angioedema; Subsequent confirmation of the diagnosis is to be made by functional C1-INH measured in the central laboratory. If there are any discrepancies between central and local laboratory results, the patient can only be included in the efficacy analysis if diagnosis of HAE has been clearly confirmed clinically and a rationale for the level of C1-INH > 50% can be given; • Current angioedema attack must be in the cutaneous, abdominal and/or laryngeal areas; • Current attack must be moderate to very severe; • Able to complete baseline assessments, and commence treatment no later than 6 hours after the time the current attack becomes moderate; • Women of childbearing potential must have a negative urine pregnancy test and for the duration of the study must use consistently and correctly a highly effective method of birth control (failure rate less than 1% per year), such as implants, injectibles, combined oral contraceptives, reliable intrauterine devices (IUDs), sexual abstinence or vasectomised partner; • Signed written Informed Consent given.
Patients with abdominal and/or cutaneous symptoms only: • VAS (Visual Analogue Scale) for primary symptoms (abdominal pain, or cutaneous pain or swelling) at time of randomization >= 30 mm
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E.4 | Principal exclusion criteria |
• • Diagnosis of angioedema other than HAE, for example, acquired angioedema (AAE); • Participation in a clinical trial of another investigational medicinal product (IMP) within the past month; • Treatment with any pain medication since onset of the current angioedema attack; • Treatment with replacement therapy, including C1-INH products, less than 3 days before onset of the current angioedema attack; • Treatment with tranexamic acid therapy within a week before onset of the current angioedema attack; • Treatment with ACE inhibitors; • Contraindication for tranexamic acid, i.e. known hypersensitivity to tranexamic acid or any of the ingredients, severe renal failure, active thromboembolic disease, massive bleeding in upper urinary tract, impaired colour vision. • Evidence of coronary artery disease based on medical history or screening examination, in particular unstable angina pectoris or severe coronary heart disease. • Congestive heart failure (class 3 and 4) • Serum creatinine level of > 250μmol/l (>2.82mg/dl) • Serious concomitant illnesses that the physician considers to be a contraindication for participation in the trial; • Pregnancy and/or breast-feeding; • Mental condition rendering the patients, in the opinion of the investigator, unable to understand the nature, scope and possible consequences of the study; • Unlikely to comply with the protocol, for example, uncooperative attitude, inability to return for follow-up visits, or unlikely to complete the study for any reason.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy endpoint:
• time to onset of symptom relief assessed by the patient using a VAS scale.
For the cutaneous cohort, the time to onset of symptom relief will be assessed based on 'cutaneous swelling' or 'pain (skin)', taking the most severe. If both are equally severe 'pain' is used. For the abdominal cohort of patients, the time to onset of symptom relief will be assessed based on abdominal pain
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
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 | Yes |
E.6.13 | Others | Information not present in EudraCT |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
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 | Yes |
E.8.2.3.1 | Comparator description |
double blind, double dummy trial active vs. comparator with corresponding placebos |
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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.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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 | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |