A Study to Evaluate the Effect of a Single-Dose Intravenous Administration of MEDI-528

Study Overview
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Brief Summary
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To evaluate the effect of MEDI-528 in adults with atopic asthma.

Detailed Description
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To evaluate the effect of MEDI-528 on the change in biologically active IL-9 levels in BAL fluid following segmental allergen challenge in adults with atopic asthma.

Official Title
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A Phase2A, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Effect of a Single-Dose Intravenous Administration of MEDI-528, A Humanized Anti-Interleukin-9 Monoclonal Antibody, on Allergen-Induced Interleukin-9 Levels in Bronchoalveolar Lavage Fluid in Adults With Atopic Asthma

Conditions
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Asthma

Intervention / Treatment
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* Other: PLACEBO
* Biological: MEDI528 9 mg/kg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female adults, age 18 through 50 years of age at time of screening; Written informed consent obtained from the patient prior to receipt of any study medication or beginning any study procedures; Previously documented diagnosis of asthma based on episodic symptoms of airflow obstruction such as wheezing or chest tightness, with alternative diagnoses (eg, chronic obstructive pulmonary disease) ruled out; Forced expiratory volume in one second (FEV1) ≥ 70% of predicted value; A positive skin prick or intradermal test to cat allergen extract, short ragweed allergen extract, or dust mite allergen extracts. A positive skin test is defined as the indurations of skin test wheal being at least 2 mm greater in diameter than that of the indurations of the control skin wheal; History of asthmatic symptoms upon exposure to at least one of the allergens (cat allergen extract, short ragweed allergen extract, or dust mite allergen extracts) that induces a positive skin prick test; AHR on methacholine inhalation challenge test, with PC20 ≤ 8 mg/mL (Crapo, 2000); No significant changes in regular asthma medications and no acute asthma exacerbations requiring oral corticosteroids or doubling of ICS dosage, hospitalization, emergency room visits, or unscheduled health care provider visits for asthma for at least 6 weeks prior to screening and up through the time of study drug administration; No history of intubation or admission to an intensive care unit for asthma; Sexually active women, unless surgically sterile or at least 1 year post-menopausal, must have used an effective method of avoiding pregnancy (including oral or implanted contraceptives, intrauterine device, female condom, diaphragm with spermicide, cervical cap, abstinence, use of a condom by the sexual partner or sterile sexual partner) for 21 days prior to the study drug administration on Study Day 0, and must agree to continue using such precautions through Study Day 126. Cessation of birth control after this point should be discussed with a responsible physician. Sexually active men, unless surgically sterile, must likewise use an effective method of birth control (condom) and must agree to continue using such precautions through Study Day 126; Able to follow study procedures including the ability to provide spirometry readings that meet American Thoracic Society (ATS)/European Respiratory Society (ERS) standards (Miller, 2005); Ability to complete the study period, including follow-up period, of up to 126 days; and Willing to forego other forms of experimental treatment and study procedures during study. Exclusion Criteria: Receipt of MEDI-528 in any previous clinical study; History of allergy or reaction to any component of the study drug formulation or other medications, such as topical lidocaine, administered during bronchoscopy; Lung disease other than allergic asthma (eg, chronic bronchitis); FEV1 < 70% of predicted values; Use of systemic immunosuppressive drugs including systemic corticosteroids (topical corticosteroids are permitted), ICS at doses > 800 μg/day budesonide or equivalent, long-acting β2 agonists (eg, salmeterol), leukotriene antagonists, cromolyn sodium, nedocromil sodium, theophylline, omalizumab, or any other medication for asthma except short-acting β2 agonist (as needed) within the 4 weeks prior to screening up through administration of study drug; Current use of any β-adrenergic antagonist (eg, propranolol); Any disease or illness, other than asthma, that may require the use of systemic corticosteroids during the study period; Upper or lower respiratory tract infections within 8 weeks before screening; Acute illnesses or evidence of clinically significant active infection, such as fever ≥ 38.0°C (100.5°F) at screening and through the time of the study drug administration on Study Day 0; Current allergy vaccination therapy (desensitization immunotherapy) with less than 3 months of stable maintenance doses prior to the baseline segmental allergen challenge. The allergy vaccination must not include desensitization to the allergen that will be used in the segmental allergen challenge; Receipt of any investigational drug therapy within 30 days or any biologic(s) within 5 half-lives of the agent prior to study drug administration through Study Day 126; Receipt of any therapy with a leukocyte-depleting agent (eg, rituximab, alemtuzumab) unless recovery in white cell count has been documented before screening; Pregnancy (sexually active females must have negative serum and urine pregnancy tests at screening and a negative urine pregnancy test prior to study drug administration on Study Day 0); Is a nursing mother at the time of screening; Evidence of infection with hepatitis B or C virus, or HIV-1 or HIV-2, or active infection with hepatitis A; History of significant systemic disease (eg, cancer, infection, hematological, renal, hepatic, coronary artery disease or other cardiovascular disease, endocrinologic, neurologic, rheumatologic, or gastrointestinal disease); History of cancer other than basal cell carcinoma or cervical carcinoma-in-situ treated with apparently successful curative therapy (remission for ≥ 1 year prior to screening); History of primary immunodeficiency; History of pancreatitis or currently active gastroduodenal ulcer; History of coagulation disorders or abnormal PT and PTT test results at screening; History of life-long urinary retention; History of use of tobacco products of more than one cigarette per month or equivalent within 1 year prior to screening or history of smoking of ≥ 10 pack-years; History of anaphylaxis; Elective surgery planned from the time of screening through Study Day 126; Clinically significant abnormalities (other than asthma) upon physical examination prior to study drug administration on Study Day 0; Clinically significant abnormality, as determined by the investigator, on 12-lead ECG or chest radiograph at the time of screening; At the time of screening, any of the following: hemoglobin, total white blood cell count (WBC), platelet count, sodium (Na), potassium (K), chloride (Cl), or carbon dioxide (CO2)out of the normal range; aspartate transaminase (AST), alanine transaminase (ALT), blood urea nitrogen (BUN), amylase, lipase, or serum creatinine above the upper limits of normal (ULN); or other abnormal laboratory values in the screening panel that are judged by the principal investigator to be clinically significant; or No detectable levels of IL-9 in the Baseline Visit 2' BAL sample, or any finding upon physical examination or history of any disease that, in the opinion of the principal investigator or medical monitor, may compromise the safety of the patient in the study or confound the analysis of the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MEDI528 9 mg/kg<br>MEDI-528 at a dose of 9 mg/kg administered as a single intravenous infusion | Biological: MEDI528 9 mg/kg<br>* MEDI-528 at a dose of 9 mg/kg administered as a single intravenous infusion<br>|
| Placebo Comparator: PLACEBO<br>Placebo administered as a single intravenous infusion | Other: PLACEBO<br>* Placebo administered as a single intravenous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Listing of Total Interleukin-9 (IL-9) Counts by Enzyme-linked Immunosorbent Assay in Bronchoalveolar Lavage Fluid (BAL) | The response of biologically active IL-9 in BAL fluid to the segmental allergen challenge, 1-2 days after the applying the allergen, prior to and 2 weeks after investigational product administration. | Baseline (2 to 4 weeks prior to Day 0) and Day 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events | Number of participants experiencing adverse events (includes both adverse events and serious adverse events) | Days 0 - 126 | 
| Incidence of Serious Adverse Events | Number of participants experiencing serious adverse events | Days 0 - 126 | 
| Incidence of Anti-drug Antibodies (ADA) to MEDI-528 | Number of participants with ADA to MEDI-528 | Days 0, 28, 56, 84, and 126 | 
| Time to Peak Concentration (Tmax) | Tmax of MEDI-528 | Days 0, 1, 7, 14, 15, 28, 56, 84, and 126 | 
| Peak Concentration (Cmax) | Cmax of MEDI-528 | Days 0, 1, 7, 14, 15, 28, 56, 84, and 126 | 
| Area Under the Concentration Curve From Time Zero to Last Measurable Concentration [AUC(0-t)] | AUC(0-t) of MEDI-528 | Days 0, 1, 7, 14, 15, 28, 56, 84, and 126 | 
| Area Under the Concentration Curve From Time Zero to Infinity [AUC(0-infinity)] | AUC(0-infinity) of MEDI-528 | Days 0, 1, 7, 14, 15, 28, 56, 84, and 126 | 
| Percent of Total Area Under the Concentration Curve Extrapolated From Last Measurable Time to Infinity [AUC(Ext)] | AUC(ext) of MEDI-528 | Days 0, 1, 7, 14, 15, 28, 56, 84, and 126 | 
| Clearance (CL) | CL of MEDI-528 | Days 0, 1, 7, 14, 15, 28, 56, 84, and 126 | 
| Terminal Half-life (T1/2) | T1/2 of MEDI-528 | Days 0, 1, 7, 14, 15, 28, 56, 84, and 126 | 
| Volume at Steady State (Vss) | Vss of MEDI-528 | Days 0, 1, 7, 14, 15, 28, 56, 84, and 126 | 
| Volume at Distribution (Vz) | Vz of MEDI-528 | Days 0, 1, 7, 14, 15, 28, 56, 84, and 126 |