E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
granulomatosis with polyangiitis (Wegener's) and microscopic polyangiitis |
granulomatosi con poliangite (di Wegener) e poliangite microscopica |
|
E.1.1.1 | Medical condition in easily understood language |
ANCA-associated vasculitis |
vasculite ANCA-associata |
|
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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10047888 |
E.1.2 | Term | Wegener's granulomatosis |
E.1.2 | System Organ Class | 10047065 - Vascular disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10063344 |
E.1.2 | Term | Microscopic polyangiitis |
E.1.2 | System Organ Class | 10047065 - Vascular disorders |
|
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 evaluate the safety, tolerability and pharmacokinetic parameters of rituximab in pediatric patients with severe granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). |
Valutare la sicurezza, la tollerabilità e i parametri farmacocinetici di rituximab in pazienti pediatrici affetti da grave granulomatosi con poliangite (GPA) o poliangite microscopica (MPA). |
|
E.2.2 | Secondary objectives of the trial |
To explore the efficacy of rituximab for the induction of remission in pediatric patients with severe GPA or MPA; to explore the pharmacodynamics parameters of rituximab in pediatric patients with GPA or MPA; to explore the effect of rituximab on patient quality of life and disability/functioning, as
assessed using the CHQ and CHAQ questionnaires, respectively. |
Esplorare l'efficacia di rituximab per l'induzione della remissione in pazienti pediatrici affetti da grave GPA o MPA; esplorare i parametri farmacodinamici di rituximab in pazienti pediatrici affetti da grave GPA o MPA; valutare l'effetto di rituximab sulla qualità della vita e sulla disabilità/funzione dei pazienti mediante il questionario CHQ e CHAQ rispettivamente. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age at screening between ≥2 and < 18 years • Diagnosis of GPA (EULAR/PRINTO/PRES 2008, Ankara criteria for childhood WG [Özen et al. 2010]) or diagnosis of MPA (according to the Chapel Hill Consensus Conference [Jennette 1994]) • Newly diagnosed patients or patients with relapsing disease according to the following definition: The recurrence or new onset of potentially organ- or life-threatening disease (i.e., one or more major BVAS/WG items or disease severe enough to require treatment with cyclophosphamide). |
•Età allo screening compresa tra ≥2 e <18 anni • Diagnosi di GPA (EULAR/PRINTO/PRES 2008, criteri di Ankara per la granulomatosi di Wegner [WG] nell'infanzia) o diagnosi di MPA (secondo la Chapel Hill Consensus Conference) • Pazienti di nuova diagnosi o pazienti con malattia recidivante secondo la seguente definizione: ricorrenza o nuova insorgenza di malattia che potrebbe mettere in pericolo gli organi o la vita [ovvero una o più caratteristiche principali della scala BVAS (Birmingham Vasculitis Activity Score, Punteggio di Birmingham dell'attività della vasculite)/WG riportate nella seguente tabella oppure malattia sufficientemente grave da necessitare un trattamento con CYC]. |
|
E.4 | Principal exclusion criteria |
• Diagnosis of Churg-Strauss Syndrome, as defined by the Chapel Hill Consensus Conference (Jennette 1994) • Limited disease that would not normally be treated with cyclophosphamide • Severe disease requiring mechanical ventilation due to alveolar hemorrhage • Requirement for plasmapheresis or dialysis at screening. Please, refer to protocol for further exclusions criteria related to general health, related to medications and related to laboratory findings. |
• Diagnosi di sindrome di Churg-Strauss, definita in base alla Chapel Hill Consensus Conference • Malattia limitata che non sarebbe trattata normalmente con CYC • Malattia grave che necessiti di ventilazione meccanica, dovuta a emorragia alveolare • Necessità di plasmaferesi o dialisi allo screening. Far riferimento al protocollo per ulteriori criteri di esclusione correlati allo stato di salute generale, correlati ai farmaci e correlati ai risultati di laboratorio. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
- to evaluate safety and PK parameters. The primary PK parameters will be clearance and volume of distribution estimated from population PK model. The safety outcome measures are frequency, nature and severity of adverse events, and frequency of laboratory abnormalities. |
- valutazione della sicurezza e dei parametri di farmacocinetica. I parametri farmacocinetici primari saranno clearance e volume di distribuzione. La sicurezza e la tollerabilità di rituximab saranno valutate sulla base di eventi avversi e delle anomalie di laboratorio. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
PK is evaluated up to month 6. Safety is assessed throughout the trial. |
La farmacocinetica è valutata fino a 6 mesi. La sicurezza verrà valutata durante il corso dello studio. |
|
E.5.2 | Secondary end point(s) |
Exploratory efficacy outcomes including induction of remission, numbers of major or minor relapses/flares, cumulative glucocorticoid dose, Exploratory pharmacodynamic outcome measures include circulating CD19-positive B cell counts. Other exploratory measures include patient reported outcomes, and vasculitis damage. |
Gli endpoint esplorativi di efficacia comprenderanno l'induzione della remissione, il numero di recidive/riacutizzazioni maggiori o minori, dose cumulativa di glucocorticoidi, endpoint farmacodinamici esplorativi che comprendono la conta dei linfociti B CD19 positivi circolanti. Altri endpoint esplorativi comprendono gli esiti riferiti dal paziente e la valutazione del danno della vasculite. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Key time-points for exploratory efficacy evaluations include months 6, 12 and 18. |
I tempi di rilevazione degli endpoint espolarivi di efficacia includono i mesi 6, 12 e 18. |
|
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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | 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 | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 |
|
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
|
The end of the study will occur when the last participating patient completes the final scheduled visit (inclusive of extended follow-up). |
Lo studio terminerà quando l'ultimo paziente avrà completato la visita finale pianificata (compreso il follow up di estensione) |
|
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 | 44 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 44 |
E.8.9.2 | In all countries concerned by the trial days | 0 |