Mepolizumab As a Steroid-sparing Treatment Option in the Churg Strauss Syndrome

NCT ID: NCT00527566

Last Updated: 2017-03-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-09-30
• Study Completion Date: 2009-08-31

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.

Conditions

Churg Strauss Syndrome

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Mepolizumab

Subjects will receive open-label mepolizumab

Group Type: EXPERIMENTAL

Mepolizumab

Intervention Type: BIOLOGICAL

IV mepolizumab, 750 mg

Interventions

Mepolizumab

IV mepolizumab, 750 mg

Intervention Type: BIOLOGICAL

Other Intervention Names

Anti IL-5

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

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Michael Wechsler, MD

Assistant Professor of Medicine at Harvard Medical School and Brigham and Women's Hospital

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michael Wechsler, MD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

Brigham and Women's Hospital

Boston, Massachusetts, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 15073927 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15940771 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16126951 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 14699394 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17157662 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 14668459 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 12704348 (View on PubMed)

Study Documents

Document Type: Publication

Mepolizumab as a steroid-sparing treatment option in patients with Churg-Strauss syndrome. Kim S, Marigowda G, Oren E, Israel E, Wechsler ME. J Allergy Clin Immunol. 2010 Jun;125(6):1336-43. doi:10.1016/j.jaci.2010.03.028.

View Document

Other Identifiers

2007-P-000012/1;BWH

Identifier Type: -

Identifier Source: org_study_id