Mepolizumab As a Steroid-Sparing Treatment Option in the Churg Strauss Syndrome - Full Text View

Sponsor:	Brigham and Women's Hospital
Collaborator:	GlaxoSmithKline
Information provided by:	Brigham and Women's Hospital
ClinicalTrials.gov Identifier:	NCT00527566

Purpose

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).

Condition	Intervention	Phase
Churg Strauss Syndrome	Biological: Mepolizumab	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Mepolizumab As a Steroid Sparing Treatment Option in the Churg Strauss Syndrome

Further study details as provided by Brigham and Women's Hospital:

Primary Outcome Measures:

Safety and tolerability of mepolizumab [ Time Frame: 44 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Demonstrate the steroid sparing effect of mepolizumab [ Time Frame: 44 weeks ] [ Designated as safety issue: No ]
Evaluate overall improvement in CSS via the measures outlined in Study Aims [ Time Frame: 44 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	10
Study Start Date:	September 2007
Estimated Study Completion Date:	August 2009
Estimated Primary Completion Date:	August 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Single arm Subjects will receive open-label mepolizumab	Biological: Mepolizumab IV mepolizumab, 750 mg Other Name: Anti IL-5

Detailed Description:

Specific Aims:

Document the safety of mepolizumab therapy in patients with CSS.
Demonstrate the steroid sparing effect of mepolizumab therapy by decreasing corticosteroid dosage while using this anti-IL5 therapy.
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

Ages Eligible for Study:	19 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00527566

Locations

United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115

Sponsors and Collaborators

Brigham and Women's Hospital

GlaxoSmithKline

Investigators

Principal Investigator:

Michael Wechsler, MD

Brigham and Women's Hospital

More Information

Publications:

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.

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.

Hellmich B, Csernok E, Gross WL. Proinflammatory cytokines and autoimmunity in Churg-Strauss syndrome. Ann N Y Acad Sci. 2005 Jun;1051:121-31. Review.

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. Epub 2003 Dec 12.

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. Epub 2006 Nov 7.

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. No abstract available.

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.

Responsible Party:	Michael E. Wechsler, MD, Brigham and Women's Hospital
ClinicalTrials.gov Identifier:	NCT00527566 History of Changes
Other Study ID Numbers:	2007-P-000012/1;BWH
Study First Received:	September 7, 2007
Last Updated:	April 16, 2009
Health Authority:	United States: Food and Drug Administration United States: Institutional Review Board

Keywords provided by Brigham and Women's Hospital:

Churg Strauss Syndrome

Additional relevant MeSH terms:

Churg-Strauss Syndrome
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Systemic Vasculitis
Vasculitis
Vascular Diseases
Cardiovascular Diseases

Granuloma
Lymphoproliferative Disorders
Lymphatic Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on May 22, 2012