Anti-Cytokine Therapy for Vasculitis

Study Overview
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Brief Summary
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The purpose of this study is to determine whether Infliximab (monoclonal anti-tumour necrosis factor alpha antibodies) are safe and effective in the treatment of anti-neutrophil cytoplasm antibody (ANCA) associated vasculitis.

Detailed Description
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Anti-neutrophil cytoplasm antibody (ANCA) associated vasculitis is a life-threatening systemic inflammatory autoimmune disease. Current treatment regimes using corticosteroids and cyclophosphamide have improved patient survival but are associated with treatment associated morbidity and mortality. Tumour necrosis factor alpha (TNF) is a proinflammatory cytokine which has been implicated in the pathogenesis of ANCA vasculitis. Anti-TNF therapies have been used successfully in the management of other inflammatory autoimmune diseases. This phase II cohort study has been designed to investigate the safety and efficacy of anti-TNF monoclonal antibody (Infliximab) therapy for patients with ANCA associated vasculitis when used in addition to standard immunosuppressive therapy.

Official Title
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Phase II Pilot Cohort Study to Investigate the Safety and Efficacy of Infliximab as Additional Therapy in the Treatment if Anti-Neutrophil Cytoplasm Antibody Associated Vasculitis

Conditions
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Wegener's Granulomatosis, Renal Limited Vasculitis, Microscopic Polyangiitis

Intervention / Treatment
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* Biological: Infliximab
* Drug: Cyclophosphamide
* Drug: Prednisolone
* Drug: Azathioprine
* Procedure: Plasma exchange
* Drug: Mycophenolate mofetil
* Drug: Methylprednisolone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Either newly diagnosed or relapsed ANCA associated vasculitis (Wegener's granulomatosis, microscopic polyangiitis, renal limited vasculitis) Exclusion Criteria: Active infection Malignancy Pregnancy Diagnosis of Churg-Strauss syndrome or anti-glomerular basement membrane antibody disease

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Patients with active vasculitis who receive infliximab in addition to standard immunosuppressive therapy | Biological: Infliximab<br>* 5 mg/kg intravenous infusion at weeks 0, 2, 6 and 10 of study<br>* Other names: Remicade;Drug: Cyclophosphamide<br>* Daily oral 2 mg/kg or pulsed intravenous 15mg/kg every 2-3 weeks for 3-6 months (until patient has been in remission for 3 months).<br>Drug: Prednisolone<br>* Daily oral 1mg/kg tapered over 12 months<br>Drug: Azathioprine<br>* Daily oral 2 mg/kg started once patient is in remission and cyclophosphamide has been discontinued.<br>Drug: Mycophenolate mofetil<br>* Daily oral up to 1.5 g twice daily as tolerated. Used as alternative to azathioprine at lead physicians discretion.<br>Drug: Methylprednisolone<br>* 500 mg intravenous infusion daily for three days at lead physicians discretion.<br>|
| Active Comparator: 2<br>Patients with active ANCA associated vasculitis who receive standard immunosuppression but no infliximab | Drug: Cyclophosphamide<br>* Daily oral 2 mg/kg or pulsed intravenous 15mg/kg every 2-3 weeks for 3-6 months (until patient has been in remission for 3 months).<br>Drug: Prednisolone<br>* Daily oral 1mg/kg tapered over 12 months<br>Drug: Azathioprine<br>* Daily oral 2 mg/kg started once patient is in remission and cyclophosphamide has been discontinued.<br>Procedure: Plasma exchange<br>* Additional therapy for patients with severe vasculitis (creatinine > 500 mcmol/L or pulmonary haemorrhage). 7x 4L exchanges over 10 days.<br>Drug: Mycophenolate mofetil<br>* Daily oral up to 1.5 g twice daily as tolerated. Used as alternative to azathioprine at lead physicians discretion.<br>Drug: Methylprednisolone<br>* 500 mg intravenous infusion daily for three days at lead physicians discretion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to clinical remission (Birmingham Vasculitis Activity Score 0 or 1) |  | 0, 6, 10, 14, 26, 39 and 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events |  | Weeks 2, 6, 10, 14, 26, 39, 52 | 
| Vasculitis Damage Index Score |  | Weeks 0, 14, 26, 39, 52 | 
| Renal function |  | Weeks 0, 2, 6, 10, 14, 26, 39, 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Infliximab, Vasculitis, antitnf monoclonal antibody