E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute renal severe to moderate failure with Wegener`s Granulomatosis or microscopic polyangiitis |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10003816 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10018378 |
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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 |
1. To determine the efficacy of PLEX in addition to immunosuppressive therapy and GC in reducing death and end-stage renal disease (ESRD) 2. To determine the non-inferiority of a reduced-dose GC regimen in reducing death and ESRD |
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E.2.2 | Secondary objectives of the trial |
For both of i) PLEX in addition to immunosuppressive therapy and GC compared to immunosuppressive therapy and GC alone; and ii) reduced-dose GC compared to standard-dose GC: 1. To determine the effect on disease activity 2. To determine the effect on mortality 3. To determine the effect on ESRD 4. To determine safety 5. To determine effects on health related quality of life |
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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 |
ALTRI SOTTOSTUDI: 1.Sottostudi su campioni di biopsia renale 2.Sottostudi con indagini a carattere genetico/biochimico (campioni campioni di DNA, RNA, siero, plasma)
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E.3 | Principal inclusion criteria |
1. New or previous clinical diagnosis of Wegeners granulomatosis or microscopic polyangiitis consistent with the Chapel-Hill consensus definitions AND
2. Positive test for proteinase 3-ANCA or myeloperoxidase-ANCA AND
3. Severe vasculitis defined by at least one of the following: a. Renal involvement with both: i. Renal biopsy demonstrating focal necrotizing glomerulonephritis or active urine sediment characterized by glomerular haematuria or red cell casts and proteinuria AND ii. eGFR <50 ml/min/1.73 m2 b. Pulmonary hemorrhage due to active vasculitis defined by: i. A compatible chest x-ray or CT scan (diffuse pulmonary infiltrates) AND ii. The absence of an alternative explanation for all pulmonary infiltrates (e.g. volume overload or pulmonary infection) AND iii. At least one of the following: 1. Evidence of alveolar hemorrhage on bronchoscopic examination or increasingly bloody returns with bronchoalveolar lavage 2. Observed hemoptysis 3. Unexplained anemia (<10 g/dL) or documented drop in hemoglobin (>1 g/dL) 4. Increased diffusing capacity of carbon dioxide
4. Provision of informed consent by patient or a surrogate decision maker |
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E.4 | Principal exclusion criteria |
1. A diagnosis of vasculitis other than Wegeners granulomatosis or microscopic polyangiitis 2. Positive anti-glomerular basement membrane antibody test or renal biopsy demonstrating linear glomerular immunoglobulin deposition 3. Receipt of dialysis for >21 days immediately prior to randomization or prior renal transplant 4. Age <15 years (age <18 years at centres that do not treat pediatric patients) 5. Pregnancy 6. Inability or unwillingness to comply with birth control/abstinence 7. Treatment with >1 IV dose of cyclophosphamide and/or >14 days of oral cyclophosphamide and/or >14 days of prednisone/prednisolone (>30 mg/day) and/or >1 dose of rituximab within the 28 days immediately prior to randomization 8. A comorbidity that, in the opinion of the investigator, precludes the use of cyclophosphamide, glucocorticoids, or plasma exchange or absolutely mandates the use of plasma exchange |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for this trial is a composite of all-cause mortality or end-stage renal disease. |
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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 | 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) | 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 | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Studio con procedura di device extracorporeo (plasmaferesi) |
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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 | Yes |
E.8.2.3.1 | Comparator description |
gruppi paralleli con trattamento plasmaferetico - same IMP used at different dosage |
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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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 23 |
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 |
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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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Sono previste due analisi ad interim di efficacia una volta raggiunti il 40% e il 75% dei pazienti da arruolare. Utilizzato approccio statistico secondo Haybittle-Peto di superiorita` terapeutica per interruzione |
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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 | 7 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 0 |