Please select the eligibility criteria that correspond to the clinical trial below.
Title: A 1 Year, Randomized, Double-blind, Parallel-group, Placebo-controlled, Multicenter Evaluation of Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Omalizumab in Children (6 - < 12 Years) With Moderate-severe, Persistent, Inadequately Controlled Allergic Asthma
Brief Summary: A substance called immunoglobulin E (IgE), which is naturally produced by our body, has a key role in generating asthma attacks. In patients with allergies, there is an exaggerated production of IgE in response to specific substances such as pollens. Omalizumab is a new drug that inactivates IgE. This study tested the safety and efficacy of omalizumab against asthma attacks in children with allergic asthma.


Options:
A: Inclusion Criteria:

* At least 12 years of age at study visit.
* Participants eligible for enrolment and entry into the study must meet the following definition of severe asthma, which is based on the definition of severe asthma described in the European Respiratory Society/ American Thoracic Society (ERS/ATS) Guidelines for severe asthma: Asthma which requires treatment with guideline suggested medications for Global Initiative for Asthma (GINA) steps 4-5 asthma for the previous year (i.e., at least 12 months).

Patients must be treated with high dose ICS PLUS at least one of the following: LABA, leukotriene modifier, theophylline, or continuous or near continuous systemic corticosteroid (i.e., maintenance systemic corticosteroid for ≥50% of the previous year).

SPECIAL CIRCUMSTANCE: If patient is on a fixed dose combination medication, then the maximum recommended dose of the ICS/LABA combination per local label is acceptable.

* Able to give written informed consent prior to participation in the study, which will include the ability to comply with the requirements and restrictions listed in the consent form. Participants must be able to read, comprehend, and write at a level sufficient to complete study related materials. A parent or legal guardian must provide informed consent for participants less than 18 years of age at study visit (or less than minimum age to be considered an adult per local laws).

Exclusion Criteria:

Participants who have participated in an interventional clinical trial for asthma within the past 12 months prior to Visit 1 (NOTE: subjects participating in an observational study where an investigational product or procedure is not administered will not be subject to this exclusion criteria)
B: Inclusion Criteria:

* Male or female adults, 18 through 65 years of age at time of randomization;
* Written informed consent obtained from the subject prior to beginning study procedures or receipt of any study medication;
* Previously documented diagnosis of asthma of ≥ 1 year duration, based on episodic symptoms of airflow obstruction; post-bronchodilator reversibility of airflow obstruction ≥ 12% (in USA only - if subject does not achieve this during screening, proof of ≥12% reversibility within 1 year of randomization is acceptable) or proof of a positive response to a methacholine challenge during screening with prior approval from MedImmune (in USA only - within 1 year of randomization is acceptable) as represented by a provoking concentration of methacholine to cause a 20% fall in FEV1 (PC20) \< 8 mg/ml \[American Thoracic Society (ATS), 2000)\]; and exclusion of alternative pulmonary diagnoses (eg, cystic fibrosis, COPD);
* Asthma symptoms are adequately controlled on a therapeutic regimen that has not changed in the last 4 weeks prior to Study Day 0, and the subject is willing to maintain the same therapeutic regimen and doses from the time of screening to the time of the first follow-up bronchoscopy with airway mucosal biopsies (Study Day 28 for Cohort 1; Study Day 84 for Cohort 2);
* Pre-bronchodilator FEV1/forced vital capacity (FVC) ratio that is below the age-adjusted normal limit as defined by the 2007 National Heart Lung and Blood Institute Asthma guidelines (Appendix D) and post-bronchodilator FEV1 ≥ 65% at screening;
* Must have ≥ 2.5% eosinophils in sputum;
* Have had no hospitalizations due to asthma in the last year prior to screening;
* Women of childbearing potential, unless surgically sterile or at least 1 year post-menopausal, must use 2 effective methods of avoiding pregnancy
* Able to complete the follow-up period as required by the protocol;
* Willing to forego other forms of experimental treatment and study procedures during the study and during an 84-day period after the last dose of study drug;
* Able to provide spirometric readings that meet ATS standards

Exclusion Criteria:

* Participation in any previous MEDI-563 clinical study;
* Known history of allergy or adverse reactions to any component of the study drug formulation;
* Lung disease other than asthma (eg, COPD, cystic fibrosis, eosinophilic pneumonia);
* Current use of any systemic or inhaled immunosuppressive drugs \[oral (up to a maximum dose of 10 mg/day or 20 mg every other day) and inhaled corticosteroids are allowed if dose has been stable for at least 4 weeks prior to study drug administration on Study Day 0\].
* Current use of any β-blocker (eg, propranolol);
* Acute illnesses or evidence of clinically significant active infection, such as fever ≥ 38.0ºC (100.5ºF) at screening and through the time of the study drug administration on Study Day 0;
* Receipt of any investigational drug therapy, intravenous immunoglobulin (IVIG), or monoclonal therapy (eg, Xolair) within 30 days or within 5-half lives prior to study drug administration on Study Day 0 through End of Study/Study Termination (Study Day 84 for Cohort 1 or Study Day 140 for Cohort 2);
* Pregnancy (women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test prior to study drug administration on Study Day 0);
* Breastfeeding or lactating;
* History of alcohol or drug abuse \< 1 year prior to Study Day 0;
* History of cancer, apart from basal cell carcinoma or in situ carcinoma of the cervix treated with apparent success with curative therapy \> 1 year prior to Study Day 0;
* History of a previous episode of active TB or a positive TB skin test without completion of an appropriate course of treatment;
* A history of coagulation disorders that would contraindicate mucosal biopsies;
* History of immunodeficiency or infection with HIV-1, HIV-2, or hepatitis A, B, or C virus;
* History of use of tobacco products within 2 years of baseline (Study Day 0) or history of smoking ≥ 10 pack-years;
* Elective surgery planned from the time of screening through first follow-up bronchoscopy with airway mucosal biopsies (Study Day 28 or Study Day 84, as applicable);
* Evidence of any systemic disease or respiratory disease (other than asthma), history of any disease, or any finding upon physical examination, screening laboratory test, chest X-ray (CXR), or ECG that, in the opinion of the investigator or medical monitor, may compromise the safety of the subject in the study or confound the analysis of the study results;
* Any employee of the research site who is involved with the conduct of the study;
* History of lidocaine allergy
C: 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.
D: Inclusion Criteria:

Patients who met the following criteria were included:

* Males or females of any race, who were 12-75 years of age
* A body weight ≥ 20 kg and ≤ 150 kg and with a total serum IgE level ≥ 30 to ≤ 700 IU/ml
* A diagnosis of allergic asthma ≥ 1 year duration according to American Thoracic Society (ATS) criteria and at screening a history consistent with GINA (2204) step 3 or 4 clinical features
* A positive prick skin test (diameter of wheal \>= 3 mm) to at least one perennial allergen documented within the past 2 years or taken at visit 1
* Increase in FEV1 ≥12% over baseline value within 30 minutes of taking 2 to 4 puffs (2-4x100µg) salbutamol (albuterol) or nebulized salbutamol up to 5mg
* An FEV1 ≥ 40 and ≤ 80% of the predicted normal value for the patient at randomization
* Receiving moderate to high dose inhaled corticosteroid ≥ 800 µg BDP or equivalent and a regular inhaled long acting B-2 agonists for at least 3 months prior to screening and \> 1000 µg (BDP) and a LABA for at least 4 weeks during the run-in and at randomization
* Patients who have suffered multiple (i.e. at least two) independent documented severe asthma exacerbations while receiving high doses of ICS (≥ 800 µg BDP or equivalent) plus regular inhaled LABA
* Evidence of poor asthma control at screening (based on patient history) and for at least 4 weeks immediately prior to randomisation

Exclusion Criteria:

Patients who met the following criteria were excluded:

* Had received systemic corticosteroids for reasons other than asthma within 4 weeks of Visit 1
* A smoking history \>10 pack years
* An active lung disease other than allergic asthma
* Elevated serum IgE levels for reasons other than allergy
* Patients with significant underlying medical conditions

Answer: C