Safety and Efficacy Study of Mepolizumab in Churg Strauss Syndrome (MEPOCHUSS)

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

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.

Study Overview

• Status: Completed
• Conditions: Churg Strauss Syndrome
• Intervention / Treatment: Drug: mepolizumab

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • SH
    • Bad Bramstedt, SH, Germany, 24576
      • University Hospital Schleswig Holstein, Rheumaklinik Bad Bramstetd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: University Hospital Schleswig-Holstein
• Collaborators: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: July 14, 2008
• First Submitted That Met QC Criteria: July 14, 2008
• First Posted (Estimate): July 16, 2008

Study Record Updates

• Last Update Posted (Estimate): June 15, 2012
• Last Update Submitted That Met QC Criteria: June 14, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Autoimmune Diseases; Disease; Vasculitis; Systemic Vasculitis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Granuloma; Syndrome; Churg-Strauss Syndrome
• Other Study ID Numbers: RBB1; EudraCT 2006-001791-20