Eosinophilic Airway Inflammation and Mepolizumab

NCT00802438 | Completed Results DMC

• 1 other identifier: H-2007-0311
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

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.

Conditions

Asthma

Keywords

asthma; allergic inflammation; interleukin-5

Outcome Measures

Primary Outcomes (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).

  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 Outcomes (1)

• Effect of Mepolizumab on Bronchoalveolar Lavage Fluid Concentrations of IL-5 Cytokine Before and After Mepolizumab

  before and after up to 3 months of Mepo

Study Arms (1)

Mepolizumab

EXPERIMENTAL

up to 3 monthly doses of 750mg i.v. mepolizumab

Biological: mepolizumab

Interventions

mepolizumab BIOLOGICAL

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

Also known as: anti-interleukin 5

Mepolizumab

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Wisconsin, Madison: lead

Study Sites (1)

University of Wisconsin- Madison

Madison, Wisconsin, 53792-9988, United States

Location

Related Publications (1)

• 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.

  PMID: 28862877 DERIVED

MeSH Terms

Conditions

Asthma

Interventions

mepolizumab

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Limitations and Caveats

Our small sample size limits any meaningful consideration about the mechanisms of mepolizumab's clinical action. The prolonged time commitment and inclusion of four bronchoscopies affected subject retention and limited the sample size.

Results Point of Contact

• Title: Gina Crisafi, BS
• Organization: UW Madison

gmc@medicine.wisc.edu

608-265-4554

Study Officials

• Nizar N Jarjour, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2008
• First Posted: December 5, 2008
• Study Start: June 1, 2008
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: April 10, 2019
• Results First Posted: December 12, 2017

Record last verified: 2019-03

Locations

US (1)