Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Double-blind, Placebo-controlled, Multiple Dose Phase 2 Study to Determine the Safety and Efficacy of AMG 317 in Subjects With Moderate to Severe Asthma
Brief Summary: A Multi-center, Randomized, Placebo, Multi-Dose study to evaluate the efficacy of AMG 317 compared with placebo as measured by change in Asthma Control Questionnaire (ACQ) symptom scores from baseline to week 12.


Options:
A: 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.
B: Inclusion Criteria:

Severe persistent asthma with the following characteristics:

* Uncontrolled according to Global Initiative for Asthma (GINA) 2007 guidelines and at least 2 exacerbations having required systemic corticosteroid and/or at least 1 hospitalization or emergency room visit in the past year.
* Treated with high-dose inhaled corticosteroid (i.e. \> 1,000 µg beclometasone dipropionate equivalent per day) plus inhaled long-acting β2 agonist (with or without maintenance oral corticosteroid).
* Non-atopic, i.e. negative blood multiallergic testing and negative Aspergillus-specific IgE-radio allergosorbent blood test and negative skin prick tests to a battery of common aeroallergens

Exclusion Criteria:

* Current smokers or smoking history stopped for less than 3 years or \> 10 pack years.
* Asthma exacerbation during the 4 weeks prior to randomization.
* Active lung disease other than non-atopic asthma.
* Patients with an active cancer, a suspicion of cancer or any history of cancer with less than 5 disease free years.
* Pregnant or nursing (lactating) women.
* Treatment with omalizumab.

Other protocol-defined inclusion/exclusion criteria may apply
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:

* Males or females 18 to 65 years of age at the time of screening
* Baseline percent of predicted FEV1 ≥ 50% to ≤ 80% at screening
* At least 12% reversibility over baseline FEV1 with beta agonist inhalation, which can be demonstrated in the office or documented by medical record within the past 12 months
* Inhaled corticosteroid (ICS) ≥ 200 and ≤ 1000 µg/day fluticasone or equivalent. Stable ICS dose for ≥ 30 days before screening and dose expected to remain stable during treatment with investigational agent. Must have used ICS for at least the last 3 consecutive months before screening
* If receiving allergen immunotherapy, a stable dose for \> 3 months before screening and anticipated to remain stable for the duration of the study
* Positive to skin prick or RAST
* Ongoing asthma symptoms with ACQ score at screening and baseline ≥ 1.5 points
* Nonsmoker or ex-smoker with \< 10 pack-years (eg, 1 pack per day for 10 years) who stopped ≥ 1 year ago

Exclusion Criteria:

* Acute asthma exacerbation requiring emergency room (ER) treatment or hospitalization within 3 months
* History of endotracheal intubation for asthma-related exacerbation within 3 years of screening
* Respiratory illness within 4 weeks of screening
* History of chronic obstructive pulmonary disease (COPD) or other chronic pulmonary condition other than asthma
* Received long-acting beta agonist, theophylline, inhaled anticholinergics, oral beta 2 agonists, or cromolyn therapeutics within 1 week of first run-in visit.
* Leukotriene antagonists within 2 weeks before first run-in visit
* Oral or parenteral corticosteroids within 6 weeks before first run-in visit
* Live/attenuated vaccinations within 4 weeks of screening or during the study
* Any uncontrolled, clinically significant systemic disease (eg, chronic renal failure, uncontrolled hypertension, liver disease)

Answer: D