Safety and Efficacy Study of Mepolizumab in Churg Strauss Syndrome

Study Overview
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Brief Summary
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Churg-Strauss syndrome is a rare type of systemic vasculitis which occurs almost exclusively in patients with asthma and which is characterized by prominent blood and tissue eosinophilia. The disease has a chronic smoldering course with a permanent need for medium to high corticosteroid doses. Available unselective immunosuppressive agents are often insufficient to reduce corticosteroid doses, to induce complete remission and to protect patients from disease flares which occur in more than 50 % of cases. Interleukin-5 is the most potent cytokine regulating the production of eosinophil granulocytes which are the major effector cells in Churg-Strauss syndrome. Recently, an increased production of interleukin-5 was demonstrated in Churg-Strauss syndrome. Mepolizumab is a monoclonal IgG antibody targeting interleukin-5 and is effective in the treatment of the HES. The hypothesis of this study is, that mepolizumab will induce remission and allow for steroid reduction.

Official Title
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A Phase II, Single Center Open Label, Prospective Trial to Evaluate the Efficacy and Safety of Mepolizumab for Patients With Refractory or Relapsing Churg Strauss Syndrome

Conditions
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Churg Strauss Syndrome

Intervention / Treatment
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* Drug: mepolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: informed consent documented history of Churg Strauss Syndrome active disease subjects must complete screening and baseline assessment stable corticosteroid dose of > 12.5 mg prednisolone for at least one week treatment with cyclophosphamide (pulse or daily oral) or methotrexate or azathioprin or leflunomide in a stable dose for at least 4 weeks not pregnant or nursing negative pregnancy test and agree to practice birth control Exclusion Criteria: life threatening disease or other critical illness deemed inappropriate for inclusion in the study by the principal investigator treatment with other immunosuppressive agents within 4 weeks prior to randomisation corticosteroid pulse of > 60 mg within the last three weeks prior to randomisation known secondary cause of eosinophilia no history or clinical features of vasculitis diagnosis of other primary systemic vasculitis currently active malignant disease abnormal laboratory values impaired cardiac function history of allergic reaction due to monoclonal antibodies prior treatment with anti-hIL-5 monoclonal antibody exposure to investigational drug within 30 days prior to randomisation positive pregnancy test

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: mepolizumab|750 mg mepolizumab iv q4wk until week 32|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary endpoint is the percentage of patients with Churg-Strauss Syndrome that attain remission |  | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in BVAS score |  | 52 weeks | 
| Change in Disease Extent Index score |  | 52 weeks | 
| Permanent End organ damage assessed by the Vasculitis Damage Index |  | 52 weeks | 
| Time to remission |  | 52 weeks | 
| Response, defined as a 50 % reduction of the BVAS score |  | 52 weeks | 
| Time to response |  | 52 weeks | 
| The frequency of relapses |  | 52 weeks | 
| Blood eosinophil count |  | 52 weeks | 
| Frequency of all AEs and SAEs |  | 52 weeks |