Clinical trial NCT00802438: Eosinophilic Airway Inflammation and Mepolizumab
Official title: Eosinophilic Airway Inflammation: Relationship to Remodeling and Modulation by Mepolizumab
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Asthma
Keywords: asthma
allergic inflammation
interleukin-5
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
First posted: 2008-12-05
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.


Eligibility 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.

Primary outcomes:
measure: 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).
timeFrame: before and after up to 3 months of Mepo.
Secondary outcomes:
measure: Effect of Mepolizumab on Bronchoalveolar Lavage Fluid Concentrations of IL-5 Cytokine Before and After Mepolizumab
timeFrame: before and after up to 3 months of Mepo
Other outcomes:
Locations:
city: Madison
country: United States
facility: University of Wisconsin- Madison
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Nizar N Jarjour, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.