E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
ANCA-associated vasculitis (AAV) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10050894 |
E.1.2 | Term | Anti-neutrophil cytoplasmic antibody positive vasculitis |
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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 |
There are 2 principal questions that this research will address: 1) Does alemtuzumab control ANCA associated vasculitis and provide a treatment free sustained remission, in patients that have disease resistant to current standard therapy? 2) Is this achieved with an acceptable level of serious adverse events (at or below levels seen with standard therapy)? |
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E.2.2 | Secondary objectives of the trial |
Secondary endpoints include: 1. The proportion of patients with treatment failure 2. The accrual of damage 3. The time to partial remission, time to complete remission and time to flare 4. Cumulative glucocorticoid exposure 5. The proportion of subjects with non-severe adverse events 6. Impact on quality of life assessments 7. Biomarker studies - including lymphocyte phenotyping of recovering cells and gene expression profiling.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) A diagnosis of ANCA associated vasculitis 2) Active vasculitis with a least one severe or three non-severe items of BVAS/WG activity (a validated disease activity measure) 3) Previous therapy with either cyclophosphamide or methotrexate, in combination with prednisolone, for at least 3 months 4) Written informed consent |
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E.4 | Principal exclusion criteria |
1) Age less than 18 years or greater than 60 years 2) Creatinine > 150μmol/l 3) Total white cell count < 4x10^9/l or lymphocyte count < 0.5x10^9/l or neutrophil count < 1.5x10^9/l or IgG < 5g/l 4) Severe lung haemorrhage with hypoxia (oxygen saturations < 85% on room air) 5) Severe gastrointestinal, central nervous system or cardiac vasculitis 6) Previous therapy with: a) Alemtuzumab at any time b) IVIg, infliximab, etanercept, adalimumab, abatacept, anti-thymocyte globulin or plasma exchange in the past 3 months c) Rituximab within the past 6 months 7) Intensive care unit requirement 8) Active infection with HIV, hepatitis B or C or other infection requiring parenteral or long term oral antibiotics 9) History of ITP or platelet count at screening below 50,000 x10^6/l 10) Pregnancy or inadequate contraception in pre-menopausal women 11) Breast feeding 12) Previous history of malignancy 13) Any other mulitsystem autoimmune disease, including Churg Strauss angiitis, systemic lupus erythematosus, anti-GBM disease and cryoglobulinaemia 14) Any condition judged by the investigator that would cause the study to be detrimental to the patient
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E.5 End points |
E.5.1 | Primary end point(s) |
1) Proportion of subjects with a severe adverse event - assessed at 6 and 12 months 2) Proportion of subjects with a vasculitis response at 6 months (Response is defined by a >50% reduction in BVAS/WG score from baseline which is sustained for at least 1 month)
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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 | Yes |
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 | 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) | 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 | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
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 | 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
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The end of the trial will be 12 months after the final patient (24th patient) has received their first course of alemtuzumab. |
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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 | 2 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |