A Study to Evaluate the Safety and Tolerability of the Administration of MEDI-528 When Administered in Multiple Doses to Adults With Mild Persistent Asthma

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the safety and tolerability of escalating multiple SC doses of MEDI-528 in adult patients with mild persistent asthma.

Detailed Description
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The secondary objectives of this study are to: Assess the PK of MEDI-528; and Assess the IM of MEDI-528 in this patient population.

Official Title
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A Phase 2A, Randomized, Double-Blind, Placebo-Controlled,Dose-Escalation Study to Evaluate the Safety and Tolerability of Multiple-Dose Subcutaneous Administration of MEDI-528, A Humanized Anti-Interleukin-9 Monoclonal Antibody,When Administered to Adults With Mild Persistent Asthma

Conditions
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Asthma

Intervention / Treatment
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* Biological: MEDI528 0.3 mg/kg
* Biological: MEDI528 1 mg/kg
* Biological: MEDI528 3 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 time of screening; Weight ≤ 100 kg and body mass index ≤ 35; Written informed consent obtained from the patient prior to receipt of any study medication or beginning study procedures; Previously documented diagnosis of asthma based on episodic symptoms of airflow obstruction such as wheezing or chest tightness, with alternative diagnoses (e.g., chronic obstructive pulmonary disease) ruled out; Currently receiving treatment with short-acting β2 agonists, ICS at doses ≤ 264 μg/day fluticasone or equivalent, or both (National Heart, Lung, and Blood Institute [NHLBI], 2002); FEV1 or peak expiratory flow (PEF) ≥ 80% of predictable value; Have had a diagnosis of mild persistent asthma, defined as having asthma symptoms with a frequency of more than twice a week but less than once daily, or nighttime symptoms with a frequency of more than twice a month but less than once a week (NHLBI, 2002); Have AHR based on documented clinical history of either methacholine inhalation challenge with PC20 ≤ 16 mg/mL or partial reversibility of ≤ 12% in FEV1 within the past 18 months (including screening); Able to provide spirometry readings that meet American Thoracic Society/European Respiratory Society standards (Miller, 2005); Sexually active females, unless surgically sterile or at least 1 year post-menopausal, must use an effective method of avoiding pregnancy (including oral, implanted, or transdermal 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, and must agree to continue using such precautions through Study Day 150. Cessation of birth control after this point should be discussed with a responsible physician. Sexually active males, unless surgically sterile, must likewise use an effective method of birth control (condom) and must agree to continue using such precautions through Study Day 150; Ability to complete the study period, including follow-up period, of up to 150 days; and Willing to forego other forms of experimental treatment and study procedures during the study. Exclusion Criteria: Receipt of MEDI-528 in any previous clinical study or prior randomization into the trial; History of allergy or reaction to any component of the MEDI-528 formulation; Lung disease other than persistent asthma (e.g. chronic bronchitis); FEV1 < 80% of predicted values; History of severe asthma or asthma exacerbation requiring intubation; Use of systemic immunosuppressive drugs including systemic corticosteroids or ICS with doses > 264 μg/day fluticasone or equivalent within 4 weeks prior to Study Day 0; Use of long-acting β2 agonists, theophylline, cromolyn sodium, nedocromil sodium, leukotriene receptor antagonists, or any other inhaled or systemic medication for asthma (except short-acting β2 agonists or ICS at doses ≤ 264 μg/day fluticasone or equivalent) within the 2 weeks prior to 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 significant active infection, such as fever ≥ 38.0°C (100.5°F) at screening and up through time of the first dose of study drug; Current allergy vaccination therapy (desensitization immunotherapy), with less than 3 months of stable maintenance doses prior to screening; 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); Lactating or breastfeeding woman; Evidence of infection with hepatitis B or C virus, or human immunodeficiency virus-1 or -2 (HIV-1 or HIV-2), or active infection with hepatitis A; History of significant systemic disease (e.g., cancer, infection, hematological, renal, hepatic, coronary artery disease or other cardiovascular disease, endocrinologic, neurologic, rheumatologic, or gastrointestinal disease); History of cancer other than non-melanoma skin cancer or cervical carcinoma-in-situ treated with apparent success with curative therapy (remission for ≥ 1 year prior to screening); History of primary immunodeficiency; History of pancreatitis; History of use of tobacco products of more than one cigarette per month or equivalent within 1 year prior to randomization or history of smoking of ≥ 10 pack-years; Elective surgery planned during the study period through Study Day 150; Clinically significant abnormalities on physical examination (other than asthma) prior to the first dose of study drug (including but not limited to splenomegaly); Clinically significant abnormality, as determined by the investigator, on 12-lead ECG, MRI, or chest radiograph at the time of screening; At the time of screening, any abnormality of the following measurements: hemoglobin, total white blood cell count (WBC), platelet count, aspartate transaminase (AST), alanine transaminase (ALT), amylase, or serum creatinine above the upper limits of normal (ULN); or other abnormal laboratory values in the screening panel that, in the opinion of the principal investigator, are judged to be clinically significant; 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 investigator or medical monitor, may compromise the safety of the patient in the study or confound the analysis of the study; or Employees of the clinical study site or any other individuals involved with the conduct of the study, or family members of such individuals.

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: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MEDI528 0.3 mg/kg<br>MEDI-528 at a dose of 0.3 mg/kg administered twice weekly as a subcutaneous (SC) dose for 4 weeks | Biological: MEDI528 0.3 mg/kg<br>* MEDI-528 at a dose of 0.3 mg/kg administered twice weekly as a subcutaneous (SC) dose for 4 weeks<br>|
| Experimental: MEDI528 1 mg/kg<br>MEDI-528 at a dose of 1 mg/kg administered twice weekly as a subcutaneous (SC) dose for 4 weeks | Biological: MEDI528 1 mg/kg<br>* MEDI-528 at a dose of 1 mg/kg administered twice weekly as a subcutaneous (SC) dose for 4 weeks<br>|
| Experimental: MEDI528 3 mg/kg<br>MEDI-528 at a dose of 3 mg/kg administered twice weekly as a subcutaneous (SC) dose for 4 weeks | Biological: MEDI528 3 mg/kg<br>* MEDI-528 at a dose of 3 mg/kg administered twice weekly as a subcutaneous (SC) dose for 4 weeks<br>|
| Placebo Comparator: PLACEBO<br>Placebo administered twice weekly as a subcutaneous (SC) dose for 4 weeks | Other: PLACEBO<br>* Placebo administered twice weekly as a subcutaneous (SC) dose for 4 weeks<br>|

What is the study measuring?
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Primary 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 - 150 | 
| Incidence of Abnormal Troponin Levels | Number of participants with troponin levels greater than upper limit of normal | Days 0, 14, 28, 56, 84, and 150 | 
| Incidence of Abnormal Clinically Significant Electrocardiogram (ECG) Results | Number of participants with abnormal clinically significant ECG results | Days -14 to -1, 14, 28, 56, 84, and 150 | 
| Incidence of Abnormal Clinically Significant Magnetic Resonance Imaging (MRI) Results | Number of participants experiencing abnormal clinically significant MRI results | Days -14 to -1 and 28 | 
| Incidence of Serious Adverse Events | Number of participants experiencing serious adverse events | Days 0 - 150 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Anti-drug Antibodies (ADA) to MEDI-528 | Number of participants with ADA to MEDI-528 | Days 0, 28, 56, 84, 119, and 150 | 
| Time to Observed Maximum Serum Concentration (Tmax) | Tmax of MEDI-528 | Days 0, 3, 7, 10, 14, 17, 21, 24, 26, 28, 31, 35, 42, 49, 56, 70, 84, 119, and 150 | 
| Observed Maximum Serum Concentration (Cmax) | Cmax of MEDI-528 | Days 0, 3, 7, 10, 14, 17, 21, 24, 26, 28, 31, 35, 42, 49, 56, 70, 84, 119, and 150 | 
| Terminal Phase Half-life (T1/2) | T1/2 of MEDI-528 | Days 0, 3, 7, 10, 14, 17, 21, 24, 26, 28, 31, 35, 42, 49, 56, 70, 84, 119, and 150 |