E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Wegener's granulomatosis (WG) Microscopic polyangiitis (MPA) Vasculitis |
Granulomatosis de Wegener (GW) poliangeítis microscópica (PAM) Vasculitis |
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E.1.1.1 | Medical condition in easily understood language |
Wegener's granulomatosis (WG) Microscopic polyangiitis (MPA) Vasculitis |
Granulomatosis de Wegener (GW) poliangeítis microscópica (PAM) Vasculitis |
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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 | 14.1 |
E.1.2 | Level | PT |
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 | 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 |
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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. |
-Evaluar la eficacia de belimumab en el mantenimiento de la remisión luego de un régimen de inducción estándar en sujetos con granulomatosis de Wegener (GW) o poliangeítis microscópica (PAM).
-Evaluar la seguridad de belimumab en sujetos con GW o PAM. |
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E.2.2 | Secondary objectives of the trial |
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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 |
Title: Pharmacogenetic Research Date: 22 June 2012 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. |
Título: Estudio farmacogenético Fecha: 22 Junio 2012 Objetivos: -Relación entre las variantes genéticas y la farmacocinética de belimumab. -Relación entre las variantes genéticas y la seguridad y/o tolerabilidad de belimumab. -Relación entre las variantes genéticas y la eficacia de 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. |
- Presentar un diagnóstico clínico de granulomatosis de Wegener (GW) o un diagnóstico de poliangeítis microscópica (PAM) según los criterios de Chapel Hill -Haber presentado en las 26 semanas previas a la randomización (Día 0) un episodio de GW o PAM moderada a severamente activa que requirió tratamiento con alguno de los siguientes regímenes de inducción: Un curso único de rituximab, Ciclofosfamida oral o IV - Presentar un Puntaje de Actividad de la Vasculitis de Birmingham (BVAS) de 0 y estar recibiendo <10 mg/día de prednisona oral (o equivalente) en 2 mediciones consecutivas con 21 a 35 días de diferencia, dentro de las 26 semanas luego de la primera dosis del tratamiento de inducción. - Presentar evidencia documentada de anti-proteinasa 3 (anti-PR3) o anti-mieloperoxidasa (anti-MPO) antes del Día 0. - Alcanzar remisión no antes de la semana 26 antes de la primera dosis del tratamiento de inducción. La remisión se define como presentar un Puntaje de Actividad de la Vasculitis de Birmingham (BVAS) de 0 y estar recibiendo <10 mg/día de prednisona oral (o equivalente) en 2 mediciones consecutivas con 21 a 35 días de diferencia. - La terapia de mantenimiento de este estudio debe empezar no más de dos semanas después de la confirmación de la remisión. |
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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. |
- Embarazo o lactancia - Haber recibido tratamiento dirigido a las células B (diferente del rituximab) en cualquier momento - Haber recibido un agente en investigación biológico o no biológico dentro de los 60 días - Haber requerido un manejo de infecciones agudas o crónicas en los últimos 60 days. - Abuso o dependencia actual de alcohol o drogas. - Presentar una prueba históricamente positiva o una prueba positiva en la selección para el antígeno de superficie de la hepatitis B, o anticuerpos de la hepatitis C o ser VIH-1 positivo confirmado - Presentar antecedentes de una reacción anafiláctica a la administración parenteral de sustancias de contraste, proteínas humanas o murinas o anticuerpos monoclonales. |
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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. |
El objetivo primario de eficacia se considera desde el día 0 hasta la recaída, definida como. -Por lo menos 1 ítem mayor del BVAS (Apéndice 4), O BIEN -Un puntaje total mínimo del BVAS de 6 (Apéndice 4), O BIEN -Uso de medicamentos prohibidos (que se definen en la Sección 5.5.1). |
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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 |
El análisis primario se realizará luego de que al menos 66 sujetos hayan presentado una recidiva y hayan transcurrido por lo menos 12 meses después de que el último sujeto haya sido aleatorizado. |
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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) |
Tiempo transcurrido desde el Día 0 hasta la primera recidiva mayor (definida como al menos un ítem mayor del BVAS que presenta el sujeto). |
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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 |
Al menos 66 sujetos hayan presentado una recidiva y hayan transcurrido por lo menos 12 meses después de que el último sujeto haya sido aleatorizado |
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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 | 3 |
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 |
Australia |
Austria |
Belgium |
Canada |
Czech Republic |
Finland |
France |
Germany |
India |
Ireland |
Italy |
Mexico |
Peru |
Poland |
Romania |
Russian Federation |
Spain |
Sweden |
Switzerland |
United Kingdom |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 9 |
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 | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |