E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Wegener's granulomatosis (WG) Microscopic polyangiitis (MPA) Vasculitis |
granulomatosi di Wegener (WG) poliangioite microscopica (MPA) Vasculite |
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E.1.1.1 | Medical condition in easily understood language |
Wegener's granulomatosis (WG) Microscopic polyangiitis (MPA) Vasculitis |
Granulomatosi di Wegener (WG) Poliangioite microscopica (MPA) Vasculite |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.1 |
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 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.1 |
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 |
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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 efficacy of belimumab in the maintenance of remission following a standard induction regimen in subjects with Wegener's granulomatosis (WG) or microscopic polyangiitis (MPA). •To evaluate the safety of belimumab in subjects with WG or MPA. |
Valutare l'efficacia di belimumab nel mantenimento della remissione in seguito a un regime di induzione standard in soggetti affetti da granulomatosi di Wegener (Wegener’s granulomatosis, WG) o poliangioite microscopica (microscopic polyangiitis, MPA). Valutare la sicurezza di belimumab in soggetti affetti da WG o MPA. |
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E.2.2 | Secondary objectives of the trial |
Non applicabile |
Non Applicabile |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
PHARMACOGENETIC: Vers: Date:2012/06/22 Title:Pharmacogenetic Research Objectives:• Relationship between genetic variants and the pharmacokinetics of belimumab. • Relationship between genetic variants and safety and/or tolerability of belimumab. • Relationship between genetic variants and efficacy of belimumab.
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FARMACOGENETICA: Vers: Data:2012/06/22 Titolo:Ricerca Farmacogenetica Obiettivi:- relazione tra le varianti genetiche e la farmacocinetica di belimumab -- relazione tra le varianti genetiche e la sicurezza e/o tollerabilità dei belimumab - relazione tra le varinati genetiche e l'efficacia di belimumab.
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E.3 | Principal inclusion criteria |
•Clinical diagnosis Wegener's granulomatosis or microscopic polyangiitis by Chapel Hill criteria. •Disease flare in the past 26 weeks requiring treatment with high dose corticosteroids and 1 of the following medications: rituximab, oral cyclophosphamide OR IV cyclophosphamide. •Tested positive for anti-proteinase 3 (anti-PR3) or anti-myeloperoxidase (anti-MPO) antibodies at any time prior to enrollment. •Achieve remission no more than 26 weeks after first dose of induction treatment. Remission is defined as a Birmingham Vasculitis Activity (BVAS) score of 0 and receiving less than 10 mg/day of oral prednisone (or equivalent) on 2 consecutive visits 21 to 35 days apart. •Maintenance therapy on this study must start no more than 2 weeks after confirmation of remission. |
- Diagnosi di granulomatosi di Wegener (WG) o una diagnosi di poliangioite microscopica (MPA) secondo i criteri diagnostici della Chapel Hill. - Riacutizzazione della patologia nelle 26 settimane precedenti la randomizziazione che abbia richiesto un trattamento con corticosteroidi a dosi elevate ed uno dei seguenti regimi: rituximamb, ciclofosfamide orale o per via endovenosa. -Evidenza documentata di anti-proteinasi 3 (anti-PR3) o anti-mieloperossidasi (anti-MPO) prima dell'arruolamento. - Raggiungimento della remissione non oltre le 26 settimane successive alla prima dose del trattamento d'induzione. La remissione è definita con un punteggio sulla scala di valutazione dell'attività della vasculite di Birmingham (Birmingham Vasculitis Activity Score, BVAS) pari a 0 e attuale assunzione di < 10 mg/die di prednisone (o equivalente) per via orale in occasione di 2 misurazioni consecutive a distanza di 21-35 giorni l'una dall'altra. - La terapia di mantenimento deve iniziare non oltre 2 settimane dopo la conferma della remissione. |
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E.4 | Principal exclusion criteria |
•Pregnant or nursing. •Receipt of a B cell targeted therapy (other than rituximab) at anytime •Receipt of an investigational biological agent within the 60 days. •Required management of acute or chronic infections within the past 60 days. •Current drug or alcohol abuse or dependence. •Current or past positive test for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C. •History of severe allergic reaction to contrast agents or biological medicines. |
-Gravidanza o allattamento -Precedente trattamento a base di una terapia mirata alle cellule B (diversa da rituximab) -Precedente trattamento a base di un agente biologico sperimentale nei 60 giorni che precedono la randomizzazione; Attuale abuso o dipendenza da droghe o alcool; Precedente o attuale positività al test per HIV, epatite B o epatite C; - Storie di reazione allergica severa ad agenti di contrasto o biologici. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is time from Day 0 to the first relapse, defined as: •At least 1 major BVAS item OR •A minimum total BVAS score of 6 OR •Receipt of protocol prohibited medications. |
L'endpoint di efficacia primario è rappresentato dal tempo intercorso tra il Giorno 0 e il primo episodio di recidiva, definito come segue: • almeno 1 voce BVAS significativa; OPPURE • un punteggio totale minimo BVAS di 6; OPPURE • prescrizione di farmaci non consentiti. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At least 66 subjects have experienced a relapse and at least 12 months have elapsed after the last subject is randomised. |
L'analisi primaria di efficacia sarà condotta dopo che almeno 66 soggetti abbiano subito un episodio di recidiva e siano trascorsi almeno 12 mesi dalla randomizzazione dell'ultimo soggetto. |
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E.5.2 | Secondary end point(s) |
Time from Day 0 to the first major relapse (defined as experiencing at least 1 major BVAS item) |
Tempo intercorso tra il Giorno 0 e il primo episodio di recidiva significativo (definito come il verificarsi di almeno 1 voce BVAS significativa) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
at least 66 subjects have experienced a relapse and at least 12 months have elapsed after the last subject is randomised |
L'analisi secondaria di efficacia sarà condotta dopo che almeno 66 soggetti abbiano subito un episodio di recidiva e siano trascorsi almeno 12 mesi dalla randomizzazione dell'ultimo soggetto |
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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 | 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 | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | 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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 70 |
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 |
European Union |
Australia |
Canada |
India |
Mexico |
Peru |
Russian Federation |
Switzerland |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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 | 45 |
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 | 45 |
E.8.9.2 | In all countries concerned by the trial days | 0 |