A Study to Evaluate the Efficacy of MEDI-528 on Late Asthmatic Response With Atopic Asthma
Condition: Asthma
MeSH terms: Asthma
Intervention: MEDI-528 9 mg/kg; Placebo
Intervention description: MEDI-528 at a single dose of 9 mg/kg administered as an intravenous infusion; Placebo administered as a single intravenous infusion
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

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

Eligibility criteria:

        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.