A Study to Evaluate the Efficacy of MEDI-528 on Late Asthmatic Response With Atopic Asthma

Study Overview
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Brief Summary
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This is a Phase 2a, randomized multicenter study to evaluate the efficacy of MEDI-528 on LAR in adult patients with atopic asthma.

Detailed Description
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This study (MI-CP138) is a Phase 2a, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy of MEDI-528 on LAR in adult patients with atopic asthma. Approximately three investigative sites in Canada will participate in this study, with up to 40 evaluable patients randomized in a 1:1 ratio to receive MEDI-528 (9.0 mg/kg) or placebo as a single IV infusion.

Official Title
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A Phase 2A, Randomized, Double-Blind, Placebo-Controlled Multicenter Study to Evaluate the Efficacy of MEDI-528, a Humanized Anti-Interleukin-9 Monoclonal Antibody, on Late Asthmatic Response Induced By Allergen Inhalation In Adults With Atopic Asthma

Conditions
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Asthma

Intervention / Treatment
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* Biological: MEDI-528 9 mg/kg
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female adults, age 18 through 65 years of age at the time of screening; Written informed consent obtained from the patient prior to receipt of any study medication or beginning study procedures; Previously documented diagnosis of asthma of > 1 year duration, based on episodic symptoms of airflow obstruction, at least partial reversibility of airflow obstruction, with alternative diagnoses (e.g., chronic obstructive pulmonary disease) ruled out; AHR in the methacholine challenge test with a PC20 (provoking concentration of methacholine to cause a 20% fall in FEV1) ≤ 16 mg/mL (Crapo, 2000); Have dual response of EAR, defined as a decrease in FEV1 ≥ 20% at 0 to 3 hours after inhalation, and LAR, defined as a decrease in FEV1 ≥ 15% 3 to 7 hours after inhalation, to inhaled allergen; Asthma symptoms are adequately controlled on short-acting β2 agonists (e.g., albuterol) alone; Have had no significant changes in regular asthma medications and no acute asthma exacerbations requiring corticosteroid rescue, hospitalization, or emergency department visits for at least 4 weeks prior to screening and up through the time of the first dose of study drug on Study Day 0. 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 first dose of study drug 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 complete the follow-up period through Study Day 126, as required by the protocol. Willing to forego other forms of experimental treatment and study procedures during the study; and Able to provide spirometric readings that meet American Thoracic Society (ATS) standards (ATS, 1995). Exclusion Criteria: Receipt of MEDI-528 in any previous clinical study; History of allergy or adverse reactions to any component of the MEDI-528 formulation; Lung disease other than allergic asthma (e.g. chronic bronchitis); Current use of any systemic or inhaled immunosuppressive drugs, including systemic and inhaled corticosteroids (topical corticosteroids are permitted), long-acting β2 agonists, leukotriene antagonists, cromolyn sodium, nedocromil sodium, theophylline or any inhaled or systemic medication for asthma other than short-acting β2 agonists, for at least 4 weeks prior to study drug administration on Study Day 0. Current use of any β-adrenergic antagonist (e.g. propranolol). Any disease or illness, other than asthma, that may require the use of systemic corticosteroids during the study period. Acute illnesses or evidence of clinically significant active infection, such as fever ³ 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 (i.e., desensitization immunotherapy) with less than 3 months of stable maintenance doses prior to the baseline allergen inhalation challenge; Receipt of any investigational drug therapy within 30 days or any biologic(s) within 5 half-lives of the agent prior to the first dose of study drug through Study Day 150; Receipt of any therapy with a leukocyte-depleting agent unless recovery in white cell count has been documented before screening; Pregnancy (sexually active females must have a negative serum pregnancy test 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 study enrollment; 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 (e.g., cancer; infection; coronary artery disease or other cardiovascular disease; or hematological, renal, hepatic, endocrinologic, neurologic, rheumatologic, or gastrointestinal disease); History of cancer other than nonmelanoma skin cancer or cervical carcinoma-in-situ that have been treated successfully with curative therapy; History of primary immunodeficiency; History of pancreatitis; History of use of tobacco products within 2 years of baseline or history of smoking >= 10 pack-years; 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 abnormalities: aspartate transaminase (AST), alanine transaminase (ALT), or amylase > 1.5 × above the upper limits of normal (ULN); or serum creatinine > 1.3 × ULN; or any other abnormal laboratory values in the screening panel that, in the opinion of the principal investigator (PI), are judged to be clinically significant; or Evidence of any systemic disease or respiratory disease (other than asthma), any finding upon physical examination or history of any disease that, in the opinion of the PI 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: 65 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 single dose of 9 mg/kg administered as an intravenous infusion | Biological: MEDI-528 9 mg/kg<br>* MEDI-528 at a single dose of 9 mg/kg administered as an 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 |
| --- | --- | --- |
| Effect of MEDI-528 on Late Asthmatic Response (LAR) After Inhaled Allergen Challenge at Day 7 | Change from baseline (percent reduction) in mean maximum decline of forced expiratory volume in one second (FEV1) during LAR at 3 to 7 hours after an inhaled allergen challenge. | Day 7 | 
| Effect of MEDI-528 on LAR After Inhaled Allergen Challenge at Day 28 | Change from baseline (percent reduction) in mean maximum decline of FEV1 during LAR at 3 to 7 hours after an inhaled allergen challenge. | Day 28 | 
| Effect of MEDI-528 on LAR After Inhaled Allergen Challenge at Day 56 | Change from baseline (percent reduction) in mean maximum decline of FEV1 during LAR at 3 to 7 hours after an inhaled allergen challenge. | Day 56 | 
| Effect of MEDI-528 on LAR After Inhaled Allergen Challenge at Day 7 | Change from baseline (percent reduction) in mean maximum decline of area under the concentration-time curve (AUC) of the participants FEV1 during LAR at 3 to 7 hours after an inhaled allergen challenge. | Day 7 | 
| Effect of MEDI-528 on LAR After Inhaled Allergen Challenge at Day 28 | Change from baseline (percent reduction) in mean maximum decline of AUC of the participants FEV1 during LAR at 3 to 7 hours after an inhaled allergen challenge. | Day 28 | 
| Effect of MEDI-528 on LAR After Inhaled Allergen Challenge at Day 56 | Change from baseline (percent reduction) in mean maximum decline of AUC of the participants FEV1 during LAR at 3 to 7 hours after an inhaled allergen challenge. | Day 56 | 

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, 27, 55, 84, and 126 | 
| Time to Observed Maximum Serum Concentration (Tmax) | Tmax of MEDI-528 in serum | Days 0, 6, 7, 27, 55, 84, and 126 | 
| Time to Observed Maximum Sputum Concentration (Tmax) | Tmax of MEDI-528 in sputum | Days -21 to -7, 7, 28, and 56 | 
| Time to Observed Maximum Nasal Lavage Concentration (Tmax) | Tmax of MEDI-528 in nasal lavage | Days -6 to -1, 8, 29, and 57 | 
| Observed Maximum Serum Concentration (Cmax) | Cmax of MEDI-528 in serum | Days 0, 6, 7, 27, 55, 84, and 126 | 
| Observed Maximum Sputum Concentration (Cmax) | Cmax of MEDI-528 in sputum | Days -21 to -7, 7, 28, and 56 | 
| Observed Maximum Nasal Lavage Concentration (Cmax) | Cmax of MEDI-528 in nasal lavage | Days -6 to -1, 8, 29, and 57 | 
| Area Under the Concentration Curve From Time Zero to Last Measurable Concentration [AUC(0-t)] | AUC(0-t) of MEDI-528 in serum | Days 0, 6, 7, 27, 55, 84, and 126 | 
| Area Under the Concentration Curve From Time Zero to Last Measurable Concentration [AUC(0-t)] | AUC(0-t) of MEDI-528 in sputum | Days -21 to -7, 7, 28, and 56 | 
| Area Under the Concentration Curve From Time Zero to Last Measurable Concentration [AUC(0-t)] | AUC(0-t) of MEDI-528 in nasal lavage | Days -6 to -1, 8, 29, and 57 | 
| Area Under the Concentration Curve From Time Zero to Infinity [AUC(0-infinity)] | AUC(0-infinity) of MEDI-528 in serum | Days 0, 6, 7, 27, 55, 84, and 126 | 
| Area Under the Concentration Curve From Time Zero to Infinity [AUC(0-infinity)] | AUC(0-infinity) of MEDI-528 in sputum | Days -21 to -7, 7, 28, and 56 | 
| Area Under the Concentration Curve From Time Zero to Infinity [AUC(0-infinity)] | AUC(0-infinity) of MEDI-528 in nasal lavage | Days -6 to -1, 8, 29, and 57 | 
| Percent of Total Area Under the Concentration Curve Extrapolated From Last Measurable Time to Infinity [AUC(Ext)] | AUC(ext) of MEDI-528 in serum | Days 0, 6, 7, 27, 55, 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 in sputum | Days -21 to -7, 7, 28, and 56 | 
| Percent of Total Area Under the Concentration Curve Extrapolated From Last Measurable Time to Infinity [AUC(Ext)] | AUC(ext) of MEDI-528 in nasal lavage | Days -6 to -1, 8, 29, and 57 | 
| Terminal Phase Half-Life (T1/2) | T1/2 of MEDI-528 in serum | Days 0, 6, 7, 27, 55, 84, and 126 | 
| Terminal Phase Half-Life (T1/2) | T1/2 of MEDI-528 in sputum | Days -21 to -7, 7, 28, and 56 | 
| Terminal Phase Half-Life (T1/2) | T1/2 of MEDI-528 in nasal lavage | Days -6 to -1, 8, 29, and 57 | 
| Total Body Clearance (CL) | CL of MEDI-528 in serum | Days 0, 6, 7, 27, 55, 84, and 126 | 
| Terminal Phase Volume of Distribution (Vz) | Vz of MEDI-528 in serum | Days 0, 6, 7, 27, 55, 84, and 126 |