Eosinophilic Airway Inflammation and Mepolizumab

Asthma Clinical Trial

Official title:

Eosinophilic Airway Inflammation: Relationship to Remodeling and Modulation by Mepolizumab

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00802438
• Other study ID #: H-2007-0311
• Status: Completed
• Phase: N/A
• Start date: June 1, 2008
• Est. completion date: March 1, 2013

Study information

• Verified date: March 2019
• Source: University of Wisconsin, Madison
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: March 1, 2013
• Est. primary completion date: March 1, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Asthma
• Inflammation

Intervention

Biological:
• mepolizumab
up to three monthly doses of 750mg i.v. mepolizumab

Locations

Country	Name	City	State
United States	University of Wisconsin- Madison	Madison	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
University of Wisconsin, Madison

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	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).	before and after up to 3 months of Mepo.
Secondary	Effect of Mepolizumab on Bronchoalveolar Lavage Fluid Concentrations of IL-5 Cytokine Before and After Mepolizumab	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.	before and after up to 3 months of Mepo