Please select the eligibility criteria that correspond to the clinical trial below.
Title: Safety and Effectiveness of the Alair® System for the Treatment of Asthma: A Multicenter Randomized Clinical Trial(Asthma Intervention Research (AIR2) Trial)
Brief Summary: The objective of this randomized, double blind, sham-controlled study is to demonstrate the safety and effectiveness of the Alair System in a population of subjects with severe asthma who are still symptomatic despite being managed on conventional therapy of high doses of inhaled corticosteroids and long-acting β2-agonists.

The primary efficacy endpoint will be the difference between Study groups in the change in Asthma Quality of Life Questionnaire (AQLQ) score from Baseline and the average score from the 6-, 9-, and 12-month follow-up visits.

All other outcome measures assessed at 12 months post-treatment.

This will be a multicenter, randomized, double-blind, sham-controlled study comparing the effects of treatment with the Alair System to conventional therapy of inhaled corticosteroids (ICS) and long-acting β2-agonists (LABA).

A Bayesian adaptive approach to sample size selection is used with a randomization scheme of 2:1 (two Alair Group Subjects for every one Control Group Subject).


Options:
A: Inclusion Criteria:

* Body weight 40 kg--150 kg
* Chest radiograph with no evidence of clinically significant abnormality
* Uncontrolled asthma

Exclusion Criteria:

* Asthma exacerbation during screening
* Known malignancy
* Known immunodeficiency
* Pre-existing lung disease other than asthma
* Uncontrolled clinically significant medical disease
* Current smoker
* History of substance abuse that may impair or risk the patient's full participation in the study, in the judgment of the investigator
* Prior allergic reaction to a monoclonal antibody
* Patients (men and women) of reproductive potential who are not willing to use contraception
* Pregnancy
B: Inclusion Criteria:

Patients must meet all of the following criteria:

* Male or female adults, age 18 through 50 years at the time of screening;
* Weight 50-100 kg and body mass index ≤ 35;
* Written informed consent obtained from the patient prior to receipt of any study medication or beginning study procedures;
* Documented clinical history of asthma and receiving stable treatment for ≥ 1 month prior to Study Day 0;
* Airway hyperresponsiveness (AHR) on methacholine inhalation challenge testing at screening (or a documented history within the past 6 months), with provoking concentration of methacholine to cause a 20% fall in FEV1(subscript) (PC20) ≤ 8 mg/mL (Crapo, 2000);
* Exercise-induced bronchoconstriction (EIB) with a decrease in FEV1 (subscript) of ≥ 15% from pre-exercise challenge testing level at screening;
* Able to provide spirometry readings that meet American Thoracic Society (ATS) and European Respiratory Society (ERS) standards (Miller, 2005);
* Women of childbearing potential, unless surgically sterile or at least 1 year post-menopausal, must use two effective methods of avoiding pregnancy (including oral, transdermal, or implanted contraceptives, intrauterine device, female condom, spermicide, diaphragm, cervical cap, abstinence, contraceptive foam, or use of a condom by the sexual partner or sterile sexual partner) from screening through Study Day 0, 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. Men, unless surgically sterile, must likewise use an effective method of birth control (condom with spermicide) and must agree to continue using such precautions from screening through Study Day 150;
* Able to complete the study period, including follow-up period, of up to approximately 150 days; and
* Willing to forego other forms of experimental treatment and study procedures during the study and for 30 days after the follow-up period is completed.

Exclusion Criteria:

Patients must have none of the following criteria:

* Receipt of MEDI-528 in any previous clinical study;
* History of allergy or reaction to any component of the study drug formulation;
* Lung disease other than asthma (eg, chronic obstructive pulmonary disease, cystic fibrosis);
* Forced expiratory volume in 1 second (FEV1-subscript) \< 70% of predicted values at screening;
* Use of systemic immunosuppressive drugs including systemic corticosteroids, ICS with doses \> 800 μg/day budesonide (or another ICS of equivalent dose), long-acting β2 agonists, cromolyn sodium, nedocromil sodium, leukotriene receptor antagonists, theophylline, or omalizumab from screening through Study Day 150;
* Current use of any β-adrenergic antagonist (eg, propranolol);
* Any disease or illness, other than asthma, that is likely to 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) from screening through Study Day 0;
* Current allergy vaccination therapy (desensitization immunotherapy);
* Receipt of any investigational drug therapy within 30 days or any biologic(s) within 5 half-lives of the agent prior to screening;
* Pregnancy (women of child bearing potential, unless surgically sterile or at least 1 year postmenopausal, must have a negative serum and urine pregnancy test at screening before methacholine inhalation challenge testing and a negative urine pregnancy test prior to study drug administration on Study Day 0);
* Breastfeeding or lactating woman;
* Evidence of infection with hepatitis B or C virus or HIV-1 or HIV-2, or active infection with hepatitis A; must have negative HIV-1, HIV-2, hepatitis A, B, and C tests at screening;
* History of cancer other than basal cell carcinoma of the skin or cervical carcinoma-in-situ treated with apparent success with curative therapy more than 1 year prior to Study Day 0;
* History of primary immunodeficiency
* History of pancreatitis or currently active gastroduodenal ulcer;
* Current use of tobacco products or a 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;
* History of life-long urinary retention;
* History of anaphylaxis (defined as immediate life-threatening event requiring medical invention);
* Elective surgery planned from screening through Study Day 150;
* Clinically significant abnormality, as determined by the investigator, on 12-lead ECG or chest radiograph at screening;
* History of any disease, evidence of any current disease (other than asthma), any finding upon physical examination, or any laboratory abnormality, 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
* Any employee of the research site who is involved with the conduct of the study.
C: Inclusion Criteria:

* Subject is an adult between the ages of 18 to 65 years.
* Subject has asthma and is taking regular maintenance medication that includes Inhaled corticosteroid (ICS) AND long acting ß2-agonist (LABA).
* Subject has a Pre-bronchodilator Forced Expiratory Volume in one second (FEV1) of greater than or equal to 60% of predicted after medication stabilization during the Baseline Period.
* Subject has a PC20 \< 8 mg/ml per methacholine inhalation test using standardized methods. PC20 is a provocative concentration of Provocholine® (a brand of methacholine chloride) resulting in a drop of FEV1 of 20% or more from Baseline.
* Subject has at least two days of asthma symptoms during the 4-weeks of the Baseline Diary Period.
* Subject is a non-smoker for 1 year or greater (if former smoker, less than 10 pack years total smoking history).

Exclusion Criteria:

* Subject has a Post-bronchodilator FEV1 of less than 65%.
* Subject has 3 or more hospitalizations for exacerbations of asthma in the previous year; OR a history of life-threatening asthma, defined by past intubations for asthma, or ICU admission for asthma within the prior 24 months.
* Subject has a history of recurrent lower respiratory tract infections requiring antibiotics (more than 3 in the past 12 months).
* Subject has a history of recurrent oral steroid use for asthma (4 or more pulses of oral steroids in the past 12 months).
* Subject has a known sensitivity to medications required to perform bronchoscopy (such as lidocaine, atropine and benzodiazepines).
* Subject has known systemic hypersensitivity or contraindication to Methacholine chloride or other parasympathomimetic agents.
* Subject has other medical criteria.
D: Inclusion criteria:

* Parent or legal guardian was informed of the study procedures and medications and gave written informed consent.
* Outpatient males and females aged 6 - \< 12 years on study entry, with body weight between 20 and 150 kg.
* Total serum IgE level ≥ 30 to ≤ 1300 IU.
* Diagnosis of allergic asthma ≥ 1 year duration, according to American Thoracic Society (ATS) criteria, and a screening history consistent with clinical features of moderate or severe persistent asthma according to National Heart Lung and Blood Institute (NHLBI) guidelines.
* Positive prick skin test to at least one perennial allergen, documented within the past 2 years or taken at Screening. A radioallergosorbent test (RAST) could have been performed for patients with a borderline skin prick test result after consultation with Novartis clinical personnel.
* Patients with ≥ 12% increase in forced expiratory volume in 1 second (FEV1) over starting value within 30 minutes of taking up to 4 puffs (4x100 µg) salbutamol (albuterol) or nebulized salbutamol up to 5 mg (or equivalent of alternative B2-agonist) documented within the past year, at screening, during the run-in period, or prior to randomization. Patients were not to take their long acting B2-agonist (LABA) medication within 12 hours of reversibility testing.
* Clinical features of moderate or severe persistent asthma (at least step 3) despite therapy at step 3 or 4 (at least medium dose inhaled corticosteroid (ICS) - fluticasone dry-powder inhaler (DPI) ≥ 200 mg/day or equivalent with or without other controller medications).
* Documented history of experiencing asthma exacerbations and demonstrated inadequate symptom control during the last 4 weeks of run-in despite receiving an equivalent dose of fluticasone DPI ≥ 200 mg/day total daily ex-valve dose.

Exclusion criteria:

* Patients who received systemic corticosteroids for reasons other than asthma, beta-adrenergic antagonists by any route, anticholinergics within 24 hours of Screening, methotrexate, gold salts, cyclosporin or troleandomycin, or had received desensitization therapy with less than 3 months of stable maintenance doses prior to Screening.
* Patients with a history of food or drug related severe anaphylactoid or anaphylactic reaction, a history of allergy to antibiotics, with aspirin or other non-steroidal anti-inflammatory drugs (NSAID)-related asthma (unless the NSAID could be avoided), with active lung disease or acute sinusitis/chest infection, elevated serum IgE levels for other reasons, presence/history of a clinically significant uncontrolled systemic disease, cancer, abnormal, electrocardiogram (ECG) in the previous month, or platelets ≤ 100 x 109/L or clinically significant laboratory abnormalities at Screening.

Answer: C