Alemtuzumab for ANCA Associated Refractory Vasculitis

Study Overview
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Brief Summary
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Overview: This open label, randomized, multi-centre study will enroll and treat 24 patients with refractory AAV. Aims: To determine the clinical response and severe adverse event rates associated with alemtuzumab therapy among patients with relapsing or refractory ANCA associated vasculitis (AAV). Hypothesis: Treatment with alemtuzumab induces sustained remission in AAV and will reduce immunosuppressive and steroid exposure.

Official Title
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Alemtuzumab for ANCA Associated Refractory Vasculitis - a Study of Safety and Efficacy

Conditions
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Vasculitis, Microscopic Polyangiitis, Granulomatosis With Polyangiitis, Wegener's

Intervention / Treatment
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* Drug: Alemtuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A diagnosis of AAV, according to a standardized definition Active vasculitis with at least one severe or three non severe items of BVAS/WG activity (equivalent to BVAS/WG>3) Previous therapy with either cyclophosphamide or methotrexate, in combination with prednisolone for at least 3 months. Exclusion Criteria: Age less than 18 or greater than 60 years Creatinine > 150μmol/l (1.7mg/dl) Total white count < 4x109/l or lymphocyte count < 0.5x109/l, or IgG < 5g/L, or neutrophil count < 1.5x109/l. Severe lung haemorrhage with hypoxia (<85% on room air) Severe gastrointestinal, central nervous system or cardiac vasculitis Previous therapy with: Alemtuzumab at any time IVIg, infliximab, etanercept, adalimumab, abatacept, anti-thymocyte globulin or plasma exchange in past three months Rituximab within the past 6 months Intensive care unit requirement Active infection with HIV, hepatitis B or hepatitis C or other infection requiring parenteral or long-term oral antibiotics History of ITP or platelet count at screening below 50,000 x 106/l Pregnancy or inadequate contraception in pre-menopausal women Breast feeding Any condition judged by the investigator that would cause the study to be detrimental to the patient. Any other multisystem autoimmune disease including Churg Strauss angiitis, systemic lupus erythematosus, anti-GBM disease and cryoglobulinaemia Any previous or current history of malignancy (other than resected basal cell carcinoma)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alemtuzumab - high dose (60mg)<br>Alemtuzumab 30mg will be administered on Day 1 and Day 2 at 0 and 6 months | Drug: Alemtuzumab<br>* Alemtuzumab will be administered on Day 1 and Day 2 at 0 and 6 months<br>* Other names: Campath 1H;|
| Experimental: Alemtuzumab - low dose (30mg)<br>Alemtuzumab 15mg will be administered on Day 1 and Day 2 at 0 and 6 months | Drug: Alemtuzumab<br>* Alemtuzumab will be administered on Day 1 and Day 2 at 0 and 6 months<br>* Other names: Campath 1H;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with a vasculitis response at 6 months | Response includes patients in complete and partial remission. Complete remission (CR) is defined as a BVAS/WG of 0 for at least one month. Partial response (PR) is the absence of severe BVAS/WG items and at least 50% fall in BVAS/WG score from baseline. | 6 months | 
| Proportion of patients with a severe adverse event |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with treatment failure | Treatment failure is defined as the failure to achieve a vasculitis response by six months or a vasculitis relapse between 6 and 12 months | 12 months | 
| Combined damage assessment (CDA) scores |  | 12 months | 
| Non severe adverse events |  | 12 months | 
| Cumulative dose of corticosteroids |  | 12 months | 
| Time to remission | Complete and partial | 6 months | 
| Relapse |  | 12 months | 
| Change in SF-36 |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vasculitis, ANCA, Refractory