E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
atypical Hemolytic-Uremic Syndrome (aHUS) |
Sindrome emolitico-uremica atipica (SEUa) |
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E.1.1.1 | Medical condition in easily understood language |
Sindrome emolitico-uremica atipica (SEUa) |
atypical Hemolytic-Uremic Syndrome (aHUS) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019515 |
E.1.2 | Term | Hemolytic uremic syndrome |
E.1.2 | System Organ Class | 100000004851 |
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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 assess TMA disease manifestations in patients with aHUS with or without ongoing eculizumab treatment in a real-world setting. |
Valutare la manifestazione della MAT nei pazienti affetti da SEUa che abbiano o meno in corso un trattamento con eculizumab nel mondo reale. |
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E.2.2 | Secondary objectives of the trial |
To evaluate potential clinical predictors of disease manifestation and progression, including clinical characteristics and genetic profiling to evaluate disease activity and relationship to treatment as determined by levels of biomarkers associated with complement activation, and the use of associated supportive interventions such as PE/PI, dialysis, blood transfusions, and renal transplantation. |
Valutazione dei potenziali fattori clinici predittivi di manifestazione e progressione della malattia, incluse le caratteristiche cliniche e il profilo genetico, per valutare l’attività della malattia e la relazione con il trattamento, in base ai livelli dei biomarcatori associati all’attivazione del complemento, nonché l’uso di interventi di sostegno associati, quali scambio di plasma/infusione di plasma (SP/IP), dialisi, trasfusioni di sangue e trapianto renale. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Currently receiving eculizumab treatment in the M11-001 aHUS Registry 2. Two normal platelet counts at least 4 weeks apart 3. Two normal LDH levels at least 4 weeks apart 4. Willing, committed, and able to return for all clinic visits and complete all study related procedures 5. Patient or patient's parent/legal guardian must be willing and able to give written informed consent. Patient (if minor) must be willing to give written informed assent (if applicable as determined by the central Institutional Review Boards/Independent Ethics Committees [IRB/IEC]). |
1. Attualmente in trattamento con eculizumab nel M11-001 aHUS Registry. 2. Due conte piastriniche normali (es. >150.000/μL) ad almeno 4 settimane di distanza. 3. Due livelli normali di LDH (es. < 1,5 x LSN) ad almeno 4 settimane di distanza. 4. Volontà, impegno e possibilità di presentarsi a TUTTE le visite cliniche e completare tutte le procedure relative allo studio. 5. Volontà e possibilità del paziente o del genitore/tutore legale del paziente di fornire un consenso informato scritto. Volontà del paziente (se minore) di fornire un assenso informato scritto (se applicabile, come determinato dal Comitato etico indipendente [CEI]).
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E.4 | Principal exclusion criteria |
1. Any prior intentional discontinuation of eculizumab treatment 2. On chronic dialysis (defined as ≥3 months on dialysis) 3. Currently participating in another complement inhibitor trial 4. With life expectancy of <6 months 5. Patient or patient's parent/legal guardian unable to give written informed consent. Patient (if minor) unable to give written informed assent (if applicable as determined by the central Institutional Review Boards/Independent Ethics Committees [IRB/IEC]). |
1. Qualsiasi interruzione intenzionale precedente del trattamento con eculizumab. 2. Dialisi cronica (definita come ≥ 3 mesi in dialisi). 3. Attuale partecipazione a un’altra sperimentazione su un inibitore del complemento. 4. Aspettativa di vita < 6 mesi. 5. Impossibilità del paziente o del genitore/tutore legale del paziente di fornire un consenso informato scritto. Impossibilità del paziente (se minore) di fornire un assenso informato scritto (se applicabile, come determinato dal Comitato etico indipendente [CEI]).
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E.5 End points |
E.5.1 | Primary end point(s) |
Rate of TMA manifestations, where TMA includes: 1. Hematologic or renal events due to aHUS 2. Extra-renal clinical signs and symptoms of aHUS 3. Tissue (eg, kidney transplant) biopsy demonstrating TMA due to aHUS |
Tasso di manifestazione della MAT, dove la MAT include: 1. Eventi ematologici o renali dovuti alla SEUa. 2. Segni e sintomi clinici extrarenali della SEUa. 3. Biopsia tessutale (ad es. trapianto renale) che dimostra una MAT dovuta alla SEUa.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From week 2 up to month 47 |
Da due settimane fino al mese 47 |
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E.5.2 | Secondary end point(s) |
• Change in estimated Glomerular Filtration Rate (eGFR) over time • Rate of TMA manifestations • Incidence of PE/PI |
• Variazione nella velocità di filtrazione glomerulare stimata (VFGs) nel tempo; • Tasso di manifestazione della MAT: • Incidenza di SP/IP
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
From week 2 up to month 47 |
Da due settimane al mese 47 |
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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 | No |
E.6.5 | Efficacy | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Evaluation of potential predictors of disease progression |
Valutazione di fattori predittivi di progressione della malattia |
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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) | No |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
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.8.2.4 | Number of treatment arms in the trial | 1 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 167 |
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 |
Australia |
Belgium |
Canada |
Czech Republic |
Germany |
Israel |
Italy |
Norway |
Poland |
Russian Federation |
Spain |
United Arab Emirates |
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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 |
E.8.9.2 | In all countries concerned by the trial days | 0 |