Churg-Strauss-Syndrome MedDRA version: 9.1 Level: LLT Classification code 10009164 Term: Churg Strauss syndrome
Conditions
Interventions
Product Name: Mepolizumab
Product Code: SB-240563
Pharmaceutical Form: Powder for solution for injection
CAS Number: 196078-29-2
Current Sponsor code: SB-240563
Concentration unit: mg milligram(s)
Con
Sponsors
University Hospital of Schleswig-Holstein (UKSH), Campus Lübeck
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. informed consent 2. documented history of Churg Strauss Syndrome: a. previous or currently active vasculitis either on biopsy or based on the following surrogate parameters proposed by the EMEA group on the classification of primary systemic vasculitides for epidemiological studies [33]: dysmorphic red cells or erythrocyte casts indicative of glomerulonephritis, rapidly progressive neuropathy, alveolar hemorrhage demonstrated on bronchoalveolar lavage, episcleritis. b. In agreement with recommendations of the EMEA working group on the classification of primary systemic vasculitides for epidemiological studies the criteria of the American College of Rheumatology are used for classification of Churg Strauss Syndrome, as in contrast to other criteria (Lanham, CHCC) the ACR criteria are data-driven and not based on expert opinion alone. Four or more of the seven (ACR) for classification of Churg-Strauss syndrome need to be fulfilled (see [34] for definitions) in order to yield a sensitivity of 85% and specificity of 99.7 %: i. Asthma ii. Eosinophilia > 10 % on peripheral blood white cell count iii. History of allergy iv. Mononeuropathy or Polyneuropathy v. Pulmonary infiltrates, non-fixed vi. Paranasal sinus abnormality vii. Extravascular eosinophils on tissue biopsy 3. active disease defined as either a. active vasculitis (BVAS > 3) and/or b. symptomatic tissue eosinophilia and c. a prednisolone demand of >- 12.5 mg/day to control disease 4. Subjects must complete screening and baseline assessment as outlined below 5. stable corticosteroid dose of > 12.5 mg prednisolone for at least one week 6. treatment with cyclophosphamide (pulse or daily oral) or methotrexate in a stable dose for at least 4 weeks 7. Male or female, 18-80 years of age. A female patient may be included only if i. She is not pregnant or nursing ii. Of non-childbearing potential iii. Are of child-bearing potential but have a negative pregnancy test and agree to practice birth control Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Life threatening disease or other critical illness deemed inappropriate for inclusion in the study by the principal investigator. Among others, the following manifestations of CSS are considered potentially life-threatening: a. severe alveolar hemorrhage requiring blood transfusions or mechanical respiratory support b. rapid progressive glomerulonephritis requiring dialysis c. severe gastrointestinal involvement (i.e. gangrene, GI-bleeding requiring transfusions) d. severe CNS involvement (i.e. ischemic stroke) e. severe cardiac involvement (i.e. life-threatening arrhythmias or cardiac failure as outlined below) 2. Treatment with other immunosuppressive agents within 4 weeks prior to randomisation. Leflunomide must have been washed out according to current guidelines (cholestyramine for 11 days) before entry of the study. MTX or CYC are allowed if their dosage has not been changed within the last 4 weeks. 3. Corticosteroid pulse of > 60 mg within the last three weeks prior to randomisation. 4. known secondary cause of eosinophilia: drug eruption, parasitic infection, HIV infection, history of graft versus host disease, acute/chronic eosinophilic leukemia, 5. no history or clinical features of vasculitis, suggesting a diagnosis of hypereosinophilic syndrome rather than Churg Strauss Syndrome 6. Diagnosis of other primary systemic vasculitis: Wegener’s granulomatosis, microscopic polyangiitis etc. 7. currently active malignant disease 8. abnormal laboratory values: a. serum creatinine >- 3 times institutional upper normal limit (UNL) b. AST or ALT > UNL c. Platelet count < 50.000/µL 9. Impaired cardiac function defined as: a. Left ventricular ejection fraction < 20 % b. NYHA class IIIb or IV c. Myocardial infarction 10. history of allergic reaction due to monoclonal antibodies 11. prior treatment with anti-hIL-5 monoclonal antibody 12. exposure to investigational drug within 30 days prior to randomisation 13. positive pregnancy test
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Induction of remission, defined as BVAS = 0 and a daily prednisolone dose of -- 1 in patients who had previously attained remission - Blood eosinophil count - Frequency of all AEs and SAEs *according to consensus definitions of the EUVAS/EULAR Working group on recommendations for conducting clinical trials in systemic vasculitis ;Primary end point(s): Attaining remission (BVAS Score = 0 and prednisolone dose of -< 7.5 mg/d). | — |
Countries
Germany
Outcome results
None listed