E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prophylaxis of Angioedema Attacks on Patients with Hereditary Angioedema (HAE) |
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E.1.1.1 | Medical condition in easily understood language |
Prevention of Angioedema in adults and adolescents with hereditary angioedema (HAE) due to C1 esterase inhibitor deficiency |
Prevence záchvatů angioedému u dospělých a mladistvých pacientů s vrozeným angioedémem (HAE) vlivem nedostatku inhibitoru C1 esterázy |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10027664 |
E.1.2 | Term | Congenital and hereditary disorders NEC |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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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 |
The primary objective of this study is: To evaluate the efficacy of rhC1INH in the prophylaxis of angioedema attacks in patients with HAE.
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E.2.2 | Secondary objectives of the trial |
The secondary objective of this study is: To evaluate the safety and immunogenicity of rhC1INH in the prophylaxis of angioedema attacks in patients with HAE
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Males or non-pregnant females, 13 years of age or older 2. Laboratory confirmed diagnosis of HAE (functional C1 inhibitor level < 50% of normal using a chromogenic assay) 3. A history of frequent HAE attacks (at least 4 attacks per month across a minimum of 3 consecutive months). HAE attack history to be confirmed in the patient’s medical record or during intake of HAE attack history at Screening. 4. Female patients of childbearing potential who are sexually active must be willing to use an acceptable form of contraception. Acceptable forms of contraception are defined as those with a failure rate < 1% when properly applied and include: a combination oral pill, some intra-uterine devices, and a sterilized partner in a stable relationship. Female patients must not be pregnant, planning to become pregnant, or be actively breastfeeding through the entire study period. 5. Provided written informed consent (and written assent for minors) 6. Willingness and ability to comply with all protocol procedures.
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E.4 | Principal exclusion criteria |
1. Patients with medical history of allergy to rabbits or rabbit-derived products (including rhC1INH) 2. Diagnosis of acquired angioedema (AAE) including positive anti-C1INH antibodies with a low C1q level and/or clinical features suggestive of AAE 3. Patients who are pregnant, or breastfeeding, or are currently intending to become pregnant 4. Treatment with any investigational drug in the past 30 days 5. Patients with any condition or treatment that, in the opinion of the Investigator, might interfere with the evaluation of study objectives 6. Patients currently treated with angiotensin-converting enzyme (ACE) inhibitors 7. Patients who are using pdC1INH for prophylaxis or acute treatment of HAE attacks will need to discontinue therapy for at least 7 days prior to their first visit of Period 1. Patients may treat any HAE attacks between Screening and Randomization with open-label rhC1INH, HAE-specific medications (icatibant, ecallantide), or other symptomatic medications (narcotics, anti-emetics) as required. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the number of HAE attacks per 28 day period. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
All endpoints will be evaluated in each study period. |
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E.5.2 | Secondary end point(s) |
Secondary endpoint is the proportion of subjects who experience a clinical response, defined as a ≥50% reduction in the number of attacks from treatment with saline to treatment with rhC1INH. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
All endpoints will be evaluated in each study period. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
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 | No |
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 |
Canada |
Czech Republic |
Israel |
Italy |
Macedonia, the former Yugoslav Republic of |
Poland |
Romania |
Serbia |
United States |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
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 |