E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prophilaxis of Angioedema Attacks on Patients with Hereditary Angioedema (HAE). |
Profilassi degli attacchi di Angioedema in pazienti con Angioedema Ereditario (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 inhibitor deficiency. |
Prevenzione di angioedema in adulti e adolescenti con Angioedema Ereditario (HAE) dovuto alla mancanza del C1 inibitore. |
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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 | 23.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10019860 |
E.1.2 | Term | Hereditary angioedema |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
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 |
To evaluate the efficacy of rhC1INH in the prophylaxis of angioedema attacks in patients with HAE. |
Valutare l'efficacia di C1 inibitore ricombinante umano (rhC1INH) nella profilassi degli attacchi di angioedema in pazienti affetti da angioedema ereditario. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety of rhC1INH in the prophylaxis of angioedema attacks in patients with HAE. |
Valutare la sicurezza e l'immunogenicit¿ di C1 inibitore ricombinante umano nella profilassi degli attacchi di angioedema in pazienti affetti da angioedema ereditario. |
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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 C1INH 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 |
1.Maschi e femmine non in stato di gravidanza, dai 13 anni di età in avanti. 2.Diagnosi di HAE confermata dall’analisi di laboratorio (livello funzionale di C1INH <50% del normale utilizzando un dosaggio cromogenico). 3.Storia di attacchi frequenti di HAE (almeno 4 attacchi al mese per un minimo di 3 mesi consecutivi).La storia di attacchi di HAE deve essere confermata nelle cartelle cliniche del paziente o dalle informazioni sugli attacchi di HAE raccolte durante lo screening. 4.Le donne in età fertile sessualmente attive devono essere disposte a utilizzare un metodo contraccettivo accettabile. Forme accettabili di contraccezione sono definite quelle con un tasso di insuccesso <1%, quando utilizzate in modo appropriato e includono: una combinazione di pillola orale, alcuni dispositivi intrauterini e un compagno sterile in una relazione stabile. Le pazienti femmine non devono essere in stato di gravidanza, non devono programmare una gravidanza o non devono allattare al seno per tutta la durata dello studio. 5.del Fornire il modulo di consenso firmato (e assenso scritto per i minori). 6.Volontà e capacità di rispettare tutte le procedure del protocollo. |
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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. |
1.Pazienti con storia di allergia a coniglio o derivati da coniglio (compreso rhC1INH). 2.Diagnosi di angioedema acquisito (AAE), comprese positività per gli anticorpi anti-C1INH con un basso livello di C1q e/o caratteristiche cliniche che fanno sospettare AAE. 3.Pazienti in stato di gravidanza o che allattano al seno o che al momento intendono iniziare una gravidanza. 4.Trattamento con qualsiasi farmaco sperimentale nei 30 giorni precedenti. 5.Pazienti con qualsiasi condizione o trattamento che, secondo il giudizio dello Sperimentatore, potrebbe interferire con la valutazione degli obiettivi dello studio. 6.Pazienti al momento trattati con inibitori dell’enzima di conversione dell’angiotensina (ACE). 7.I pazienti che stanno utilizzando pdC1INH per profilassi o trattamento acuto degli attacchi di HAE dovranno interrompere la terapia almeno 7 giorni prima della prima visita del periodo 1. I pazienti potranno trattare gli attacchi di HAE tra lo screening e la randomizzazione con rhC1INH in aperto, medicinali specifici per HAE (icatibant, ecallantide) o medicinali sintomatici (narcotici, antiemetici), se necessario. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the number of HAE attacks during each 28 days treatment period. |
L’endpoint primario è il numero di attacchi di HAE, durante ciascun periodo di trattamento di 28 giorni. |
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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. |
Tutti gli endpoint verranno valutati in ciascun periodo di studio. |
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E.5.2 | Secondary end point(s) |
The secondary endpoint the proportion of subjects who experience a clinical response, defined as a = 50% reduction in the number of attacks from the placebo treatment period to the active study drug treatment period. |
L¿endpoint secondario ¿ la proporzione di soggetti che rilevano una risposta clinica, definita come una riduzione =50% del numero di attacchi nel periodo di trattamento con placebo rispetto al periodo di trattamento con il farmaco attivo. |
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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. |
Tutti gli endpoint saranno valutati in ciascun periodo di trattamento. |
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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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
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 |
Canada |
Israel |
North Macedonia |
Serbia |
United States |
Czechia |
Italy |
Poland |
Romania |
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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 |