Asthma
Conditions
Keywords
asthma, allergic inflammation, interleukin-5
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.
Interventions
BIOLOGICALmepolizumab
up to three monthly doses of 750mg i.v. mepolizumab
Sponsors
University of Wisconsin, Madison
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
Countries
United States
Participant flow
Recruitment details
The recruitment period lasted two years (July 2008 through November 2010. Participants were recruited from our Recruitment Database, through local advertisements and the local allergy/asthma clinics.
Pre-assignment details
After a participant signs a consent form, he/she goes through an extensive screening process that includes 4 research visits to the clinic before being assigned to their treatment. The inclusion/exclusion criteria for this study was long and many subjects screen failed prior to being assigned to a treatment.
Participants by arm
| Arm | Count |
|---|---|
| Mepolizumab up to 3 monthly doses of 750mg i.v. mepolizumab
mepolizumab: up to three monthly doses of 750mg i.v. mepolizumab | 38 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 1 |
| Overall Study | Screen Failure | 20 |
| Overall Study | Withdrawal by Subject | 7 |
Baseline characteristics
| Characteristic | Mepolizumab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 38 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 36 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 34 Participants |
| Region of Enrollment United States | 38 Participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 38 |
| other Total, other adverse events | 8 / 38 |
| serious Total, serious adverse events | 0 / 38 |
Outcome results
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).
Time frame: before and after up to 3 months of Mepo.
Population: Participants had mild allergic asthma with a positive skin-prick test to house dust mite, ragweed, or a standardized extract of cat, a pre-180 4g albuterol FEV1 ≥70%, a post-albuterol FEV1 ≥ 80%; airway reversibility to albuterol (180 4g) ≥12% and/or airway hyper-reactivity to methacholine (PC20 ≤8 mg/ml).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Mepolizumab | 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). | Pre Mepolizumab | 73 percent of bronchoalveolar eosinophils |
| Mepolizumab | 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). | Post Mepolizumab | 31 percent of bronchoalveolar eosinophils |
Comparison: Summaries of log-transformed data were back-transformed to the original scale and reported as geometric mean with 95% confidence interval or median within 1st and 3rd quartiles. Outcomes are summarized using least squares means with 95% confidence intervals or median with 1st and 3rd quartiles.p-value: <0.0001t-test, 2 sided
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.
Time frame: before and after up to 3 months of Mepo
Population: Participants had mild allergic asthma with a positive skin-prick test to house dust mite, ragweed, or a standardized extract of cat, a pre-180 4g albuterol FEV1 ≥70%, a post-albuterol FEV1 ≥ 80%; airway reversibility to albuterol (180 4g) ≥12% and/or airway hyper-reactivity to methacholine (PC20 ≤8 mg/ml).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Mepolizumab | Effect of Mepolizumab on Bronchoalveolar Lavage Fluid Concentrations of IL-5 Cytokine Before and After Mepolizumab | Pre Mepolizumab | 409 pg/ml |
| Mepolizumab | Effect of Mepolizumab on Bronchoalveolar Lavage Fluid Concentrations of IL-5 Cytokine Before and After Mepolizumab | Post Mepolizumab | 447 pg/ml |
p-value: 0.01t-test, 2 sided