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

• ClinicalTrials.gov Identifier: NCT00527566
• Recruitment Status: Completed
• First Posted: September 11, 2007
• Results First Posted: March 22, 2017
• Last Update Posted: March 22, 2017
• Sponsor: Brigham and Women's Hospital
• Collaborator: GlaxoSmithKline
• Information provided by (Responsible Party): Michael Wechsler, MD, Brigham and Women's Hospital

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Churg Strauss Syndrome	Biological: Mepolizumab	Phase 1; Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Mepolizumab As a Steroid Sparing Treatment Option in the Churg Strauss Syndrome
• Study Start Date: September 2007
• Actual Primary Completion Date: August 2009
• Actual Study Completion Date: August 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: Mepolizumab; Subjects will receive open-label mepolizumab	Biological: Mepolizumab; IV mepolizumab, 750 mg; Other Name: Anti IL-5

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Indicated Side Effects [ Time Frame: Participants were followed for the duration of the study, approximately 44 weeks ]
   Side effects experienced by participants 1 to 2 days after Mepolizumab infusion.
2. Number of Participants Who Experienced Specific Symptoms [ Time Frame: 44 weeks ]
   Number of participants who experienced specific symptoms during the trial.

Secondary Outcome Measures :

1. Steroid Dosing During Trial [ Time Frame: 20 weeks ]
2. Evaluate Overall Positive Change in Churg-Strauss Syndrome Via the Measures Outlined in Study Aims [ Time Frame: 20 weeks ]
   The Asthma Control Questionnaire (ACQ) was one measure used to assess the prevalence of asthma symptoms the participant was having during the study. It is a series of 7 questions assessing how often, over the past two weeks, the participant wakes up from their asthma, how bad their symptoms were, etc. The greater the prevalence of symptoms, the higher the score. Each of the 7 questions is scored 0-6. The total score is calculated by adding the individual question scores and dividing the sum by 7.
3. Efficacy- Exacerbation Rate [ Time Frame: Treatment period (12 weeks) ]
   Quantified the exacerbation rate (total number of exacerbations per day) of the participants during treatment with mepolizumab and without treatment. Exacerbations were characterized as any worsening of clinical disease requiring an increase of systemic corticosteroid therapy (e.g. prednisone) for asthma, respiratory symptoms, or underlying vasculitis.

Eligibility Criteria

• Ages Eligible for Study: 19 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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

Study Data/Documents: Publication 

Identifier: PubMed ID: 20513524

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.

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.

Plötz 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.

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 Wechsler, MD, Assistant Professor of Medicine at Harvard Medical School and Brigham and Women's Hospital, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT00527566
• Other Study ID Numbers: 2007-P-000012/1;BWH
• First Posted: September 11, 2007
• Results First Posted: March 22, 2017
• Last Update Posted: March 22, 2017
• Last Verified: February 2017

Keywords provided by Michael Wechsler, MD, Brigham and Women's Hospital:

Churg Strauss Syndrome

Additional relevant MeSH terms:

Churg-Strauss Syndrome; Syndrome; Disease; Pathologic Processes; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Granuloma; Lymphoproliferative Disorders; Lymphatic Diseases; Autoimmune Diseases; Immune System Diseases