Eosinophilic Airway Inflammation and Mepolizumab

• ClinicalTrials.gov Identifier: NCT00802438
• Recruitment Status: Completed
• First Posted: December 5, 2008
• Results First Posted: December 12, 2017
• Last Update Posted: April 10, 2019
• Sponsor: University of Wisconsin, Madison
• Information provided by (Responsible Party): University of Wisconsin, Madison

Study Description

Brief Summary:

A drug (mepolizumab) that reduces allergic inflammation will affect the function of allergy cells called eosinophils which are produced by the body in response to allergen exposure.

Condition or disease	Intervention/treatment	Phase
Asthma	Biological: mepolizumab	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 38 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Eosinophilic Airway Inflammation: Relationship to Remodeling and Modulation by Mepolizumab
• Actual Study Start Date: June 1, 2008
• Actual Primary Completion Date: March 1, 2013
• Actual Study Completion Date: March 1, 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: Mepolizumab; up to 3 monthly doses of 750mg i.v. mepolizumab	Biological: mepolizumab; up to three monthly doses of 750mg i.v. mepolizumab; Other Name: anti-interleukin 5

Outcome Measures

Primary Outcome Measures :

1. The Primary Endpoint of the Study is the Percent of Eosinophils in the Bronchoalveolar Lavage Fluid After Segmental Allergen Challenge, Before and After Mepolizumab Administration (Bronchoscopy #2 vs. Bronchoscopy #4). [ Time Frame: before and after up to 3 months of Mepo. ]
   Percent of eosinophils was determined in the bronchoalveolar lavage fluid collected from the participant after segmental allergen challenge. This was done via differential cell count using Hema-3 stain. Cell differentials were determined by counting a total of 1000 cells on two cytospin preparations. The percent eosinophils were done before and after administration of mepolizumab for a specified amount of time (up to 3 months of administration).

Secondary Outcome Measures :

1. Effect of Mepolizumab on Bronchoalveolar Lavage Fluid Concentrations of IL-5 Cytokine Before and After Mepolizumab [ Time Frame: before and after up to 3 months of Mepo ]
   IL-5 was measured via ELISA on bronchoalveolar lavage fluid before and after mepolizumab administration (up to 3 months of administration). Fluid was prepared in LowCross-Buffer to minimize potential matrix effects. A 1/2 dilution of 1X bronchoalveolar fluid was used for IL-5 detection. Data are expressed as pg/mL and are extrapolated to 1X.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Males or females age 18 to 50 yrs,
• History of asthma based upon presence of asthma symptoms such as cough, shortness of breath, wheeze or chest tightness,
• positive skin-prick test to a House Dust Mite extract,
• Forced expiratory volume at one second >70% predicted pre-albuterol, > 80% predicted post albuterol
• >12% increase in Forced expiratory volume at one second following inhaled albuterol (180 µg) and/or
• airway responsiveness to methacholine (PC20 <8mg/ml).
• > 20% immediate drop in FEV1 following inhaled antigen challenge.
• Safety laboratory assessments within normal ranges (labs to include complete blood count with differential, blood urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase, Prothrombin time, Partial Thromboplastin Time, and platelet count)
• Female subjects of child-bearing potential must have a negative urine pregnancy test (urine HCG) within 48 hours of the methacholine challenge at Visit 2 and agree to use a reliable method of birth control for the duration of the study (reliable methods of birth control can include abstinence, barrier methods, oral contraceptives, injection contraceptives or skin absorption contraceptives).
• In the opinion of the investigator, capable and willing to grant written informed consent and cooperate with study procedures and requirements.

Exclusion Criteria:

• Use of inhaled or systemic corticosteroids or leukotriene inhibitors within 1 month of screening.
• Treatment with Omalizumab (anti-IgE) within 9 months of screening visit
• Concomitant use of any other monoclonal antibody
• Respiratory infection within 4 weeks of study
• Unstable asthma as indicated by self-report of increased symptoms or increased beta-agonist use over the previous 2 weeks.
• Female subjects who are pregnant, nursing or have a pregnancy planned during the course of study
• Current smokers (defined as smoked within the last year) or a former smoker with a history of >5 pack years.
• Major health problems such as heart disease, type I and II diabetes or lung diseases other than asthma. Decisions regarding this criteria will be based upon the judgment of the investigator.
• Previous malignancy.
• Medication other than for asthma, allergies or contraception and that the investigator feels may interfere with the conduct of study (e.g. monoamine oxidase inhibitors and B-adrenergic antagonists in any form)
• Known history of allergic reaction to previous antibody administration.
• Prior treatment with an anti-interleukin-5 monoclonal antibody,
• Use of an investigational drug within 30 days of entering the study,
• History of noncompliance with medical regimens or subjects who are considered unreliable.

Contacts and Locations

Locations

United States, Wisconsin

University of Wisconsin- Madison

Madison, Wisconsin, United States, 53792-9988

Sponsors and Collaborators

University of Wisconsin, Madison

Investigators

• Principal Investigator: Nizar N Jarjour, MD; University of Wisconsin, Madison

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kelly EA, Esnault S, Liu LY, Evans MD, Johansson MW, Mathur S, Mosher DF, Denlinger LC, Jarjour NN. Mepolizumab Attenuates Airway Eosinophil Numbers, but Not Their Functional Phenotype, in Asthma. Am J Respir Crit Care Med. 2017 Dec 1;196(11):1385-1395. doi: 10.1164/rccm.201611-2234OC.

• Responsible Party: University of Wisconsin, Madison
• ClinicalTrials.gov Identifier: NCT00802438
• Other Study ID Numbers: H-2007-0311
• First Posted: December 5, 2008
• Results First Posted: December 12, 2017
• Last Update Posted: April 10, 2019
• Last Verified: March 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Keywords provided by University of Wisconsin, Madison:

asthma; allergic inflammation; interleukin-5

Additional relevant MeSH terms:

Inflammation; Pathologic Processes