Clinical trial NCT00527566: Mepolizumab As a Steroid-sparing Treatment Option in the Churg Strauss Syndrome
Official title: Mepolizumab As a Steroid Sparing Treatment Option in the Churg Strauss Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Churg Strauss Syndrome
Keywords: Churg Strauss Syndrome
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2007-09-11
Enrollment: 10
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether Mepolizumab (a monoclonal antibody against interleukin-5) is a safe and well-tolerated therapy that will allow for steroid tapering in patients with steroid-dependent Churg-Strauss Syndrome (CSS).

Detailed description: Specific Aims:

1. Document the safety of mepolizumab therapy in patients with CSS.
2. Demonstrate the steroid sparing effect of mepolizumab therapy by decreasing corticosteroid dosage while using this anti-IL5 therapy.
3. Demonstrate the efficacy of anti-IL5 therapy in improving the signs and symptoms of CSS by:

   1. Measuring serum markers of CSS disease activity, including: peripheral eosinophilia, erythrocyte sedimentation rate, anti- neutrophil cytoplasmic antigen, C-reactive protein and IgE levels.
   2. Assessing the activity level of vasculitis via the Birmingham Vasculitis Activity Score
   3. Evaluating asthmatic response via serial peak flow and FEV1 measurements as well as asthma symptom scores using the Juniper scale.
   4. Assessing changes in novel parameters such as fractional excretion of nitric oxide and IL-5 levels.

Eligibility criteria: Inclusion Criteria:

* Age \>18 years old
* Diagnosis of Churg Strauss Syndrome
* Maintained on stable corticosteroid dose of at least prednisone 10mg daily (or equivalent) prior to enrollment in study
* If on cyclophosphamide, azathioprine or methotrexate, must be on a stable dose and be able to maintain that dose for the duration of the study

Exclusion Criteria:

* Hypereosinophilic Syndrome
* Wegener's Granulomatosis
* Malignancy
* Parasitic Disease
* Pregnant or nursing
* If female and of child-bearing potential, must have negative pregnancy test prior to each infusion of study medication and must adhere to acceptable method of contraception (with \<1% failure rate)
* Any other medical illness that precludes study involvement

Primary outcomes:
measure: Number of Participants With Indicated Side Effects
timeFrame: Participants were followed for the duration of the study, approximately 44 weeks
measure: Number of Participants Who Experienced Specific Symptoms
timeFrame: 44 weeks
Secondary outcomes:
measure: Steroid Dosing During Trial
timeFrame: 20 weeks
measure: Evaluate Overall Positive Change in Churg-Strauss Syndrome Via the Measures Outlined in Study Aims
timeFrame: 20 weeks
measure: Efficacy- Exacerbation Rate
timeFrame: Treatment period (12 weeks)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Michael Wechsler, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Martin RM, Wilton LV, Mann RD. Prevalence of Churg-Strauss syndrome, vasculitis, eosinophilia and associated conditions: retrospective analysis of 58 prescription-event monitoring cohort studies. Pharmacoepidemiol Drug Saf. 1999 May;8(3):179-89. doi: 10.1002/(SICI)1099-1557(199905/06)8:33.0.CO;2-K.
citation: Harrold LR, Andrade SE, Go AS, Buist AS, Eisner M, Vollmer WM, Chan KA, Frazier EA, Weller PF, Wechsler ME, Yood RA, Davis KJ, Platt R. Incidence of Churg-Strauss syndrome in asthma drug users: a population-based perspective. J Rheumatol. 2005 Jun;32(6):1076-80.
citation: Hellmich B, Csernok E, Gross WL. Proinflammatory cytokines and autoimmunity in Churg-Strauss syndrome. Ann N Y Acad Sci. 2005 Jun;1051:121-31. doi: 10.1196/annals.1361.053.
citation: Garrett JK, Jameson SC, Thomson B, Collins MH, Wagoner LE, Freese DK, Beck LA, Boyce JA, Filipovich AH, Villanueva JM, Sutton SA, Assa'ad AH, Rothenberg ME. Anti-interleukin-5 (mepolizumab) therapy for hypereosinophilic syndromes. J Allergy Clin Immunol. 2004 Jan;113(1):115-9. doi: 10.1016/j.jaci.2003.10.049. Epub 2003 Dec 12.
citation: Stein ML, Collins MH, Villanueva JM, Kushner JP, Putnam PE, Buckmeier BK, Filipovich AH, Assa'ad AH, Rothenberg ME. Anti-IL-5 (mepolizumab) therapy for eosinophilic esophagitis. J Allergy Clin Immunol. 2006 Dec;118(6):1312-9. doi: 10.1016/j.jaci.2006.09.007. Epub 2006 Nov 7.
citation: Plotz SG, Simon HU, Darsow U, Simon D, Vassina E, Yousefi S, Hein R, Smith T, Behrendt H, Ring J. Use of an anti-interleukin-5 antibody in the hypereosinophilic syndrome with eosinophilic dermatitis. N Engl J Med. 2003 Dec 11;349(24):2334-9. doi: 10.1056/NEJMoa031261. No abstract available.
citation: Menzies-Gow A, Flood-Page P, Sehmi R, Burman J, Hamid Q, Robinson DS, Kay AB, Denburg J. Anti-IL-5 (mepolizumab) therapy induces bone marrow eosinophil maturational arrest and decreases eosinophil progenitors in the bronchial mucosa of atopic asthmatics. J Allergy Clin Immunol. 2003 Apr;111(4):714-9. doi: 10.1067/mai.2003.1382.