E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The ANCA associated vasculitides (AASV), namely Wegener’s granulomatosis, microscopic polyangiitis, and renal limited vasculitis.
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Information not present in EudraCT |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the rates of preliminary response and sustained remission of AASV following rituximab (on the basis of former studies, 86% sustained remission expected with rituximab compared to 75% in control group).
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E.2.2 | Secondary objectives of the trial |
To assess safety of a rituximab regimen in terms of severe adverse events (in patients receiving standard therapies, adverse advent rate is 45% at 2 years, at least 50% of which are infection relapted. In comparison rituximab use is only rarely associated with infections, therefore 22.5% adverse event rate expected with rituximab compared to 45% at 2 years in control group).
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. A new diagnosis of WG, MP or renal-limited vasculitis (RLV)(appendix 1) 2. Renal involvement attributable to active WG, MP or RLV with at least one of the following: a) Biopsy demonstrating necrotizing glomerulonephritis. b) Red cell casts on urine microscopy or ≥ ++ haematuria 3. ANCA positivity ANCA positivity requires either (a) or (b) (a) PR3-ANCA by ELISA or a typical cANCA pattern by indirect immunofluorescence (IIF), or both. (b) MPO-ANCA by ELISA. A positive pANCA by IIF requires confirmation by MPO-ANCA ELISA. 4 Written informed consent
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E.4 | Principal exclusion criteria |
1. Previous cyclophosphamide, (greater than 2 weeks of an oral or IV pulse cyclophosphamide regimen). 2. Co-existence of another multisystem autoimmune disease, e.g. SLE, Churg Strauss Syndrome, Henoch Schonlein Purpura, rheumatoid vasculitis, essential mixed cryoglobulinaemia, anti-glomerular basement membrane antibody positivity 3. Hepatitis B e antigen positive or Hepatitis C antibody positive. 4. Known HIV positive (HIV testing will not be a requirement for this trial). 5. Previous malignancy (usually exclude unless agreed with trial co-ordinator). 6. Pregnancy, breast feeding or inadequate contraception if female. 7 Allergy to a study medication 8 Live Vaccine within last 4 weeks
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary end points will be assessed upon trial completion at 2 years. However interim analyses will be performed when 1 30 patients have completed 6 weeks, to assess efficacy (treatment response) and safety (severe adverse events). 2 40 patients have completed 6 months to assess efficacy (remission rates) and safety (severe adverse events).
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
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 | Information not present in EudraCT |
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.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Information not present in EudraCT |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |