Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group, Dose Ranging Study to Determine the Effect of Mepolizumab on Exacerbation Rates in Subjects With Severe Uncontrolled Refractory Asthma
Brief Summary: The purpose of this study is to show whether mepolizumab given every 4 weeks intravenously (i.v.) can reduce the frequency of asthma exacerbations in subjects with severe asthma despite receiving high doses of standard asthma medications. The study will look at different doses of mepolizumab in comparison to a placebo.


Options:
A: 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
B: Inclusion Criteria:

* Male or female
* Aged 12 to 65 years inclusive
* Minimum weight 45kg
* Clinical features of severe refractory asthma
* Well documented requirement for high dose inhaled corticosteroids (ICS) \[i.e. \>= 880mcg/day fluticasone propionate or equivalent daily\] for at least 12 months
* Using additional controller medication in addition to high dose ICS for at least 12 months
* Persistent airflow obstruction indicated by a pre-bronchodilator FEV1\<80% predicted at visit 1 or 2 or peak flow diurnal variability of \>20% on 3 or more days during the run-in
* Airway inflammation which is likely to be eosinophilic in nature demonstrated by either raised peripheral blood eosinophils (\>=300/microL), sputum eosinophils (\>=3%), exhaled nitric oxide (\>=50ppb) or prompt deterioration of asthma control following a \<=25% reduction in regular maintenance dose of inhaled or oral corticosteroids (OCS)
* History of 2 or more exacerbations requiring systemic corticosteroids in the previous 12 months
* Evidence of asthma documented by airway reversibility, airway hyperresponsiveness or airflow variability
* ECG assessment demonstrating QTc\<450msec or QTc\<480msec for patients with bundle branch block
* Liver function tests demonstrating ALT\<2xUpper Limit of Normal (ULN), AST\<2xULN, Alk Phos \<=1.5xULN, bilirubin \<=1.5xULN
* Female of non-child-bearing potential or child-bearing potential with a negative pregnancy test at screening and prepared to agree to an acceptable method of contraception
* Able to give written informed consent
* Able to read, comprehend and write at a sufficient level to complete study materials

Exclusion Criteria:

* Current smokers or smoking history of \>=10 pack years
* Clinically important lung condition other than asthma
* Diagnosis of malignancy or in the process of investigation
* Unstable liver disease
* Churg-Strauss syndrome
* Using methotrexate, troleandomycin, oral gold, cyclosporine, azathioprine or any experimental anti-inflammatory therapy within 3 months of screening
* Omalizumab (Xolair) or any other biological for the treatment of inflammatory disease within 6 months of Visit 1
* Regular use of oral or systemic corticosteroids for diseases other than asthma within 12 months or any intra-articular, short-acting intramuscular corticosteroid within 1 month or intramuscular, long-acting depot corticosteroid within 3 months
* Allergy/intolerance to the excipients in the mepolizumab formulation
* Any investigational drug within 30 days or 5 terminal half-lives, whichever is longer
* Pregnant or breastfeeding or planning to become pregnant
* Clinically significant disease which is uncontrolled with standard treatment
* History of alcohol misuse or substance abuse
* Parasitic infestation within previous 6 months
* Known immunodeficiency
* Unable to follow instructions, use the electronic diary or peak flow meter
* Known evidence of lack of adherence to controller medications and/or follow physician's recommendations
* Previous participation in a study of mepolizumab and received study medication within 90 days
C: Inclusion Criteria:

Inclusion Criteria:

* generally healthy, men and women with mild allergic asthma, aged 18 to 60 years
* only asthma med is short-acting bronchodilator used not more than twice weekly
* FEV1 greater than 70% predicted and a demonstrated baseline late response to allergen induction

Exclusion Criteria:
D: Inclusion Criteria:

* Age: At least 12 years of age at the time of signing the informed consent/assent (For those countries where local regulations permit enrolment of adults only, participant recruitment will be restricted to those who are \>=18 years of age)
* Inhaled Corticosteroid: A well-documented requirement for regular treatment with high dose inhaled corticosteroid (ICS) in the 12 months prior to Visit 1 with or without maintenance oral corticosteroids (OCS). For participants \>=18 years old: ICS dose must be \>=880 micrograms (mcg)/day fluticasone propionate (FP) (exactuator) or equivalent daily. For ICS/long-acting beta-2-agonist (LABA) combination preparations, the highest approved maintenance dose in the local country will meet this ICS criterion. For participants \>=12 to \<=17 years old: ICS dose must be \>=440 mcg/day FP (ex-actuator) or equivalent daily. For ICS/LABA combination preparations, the mid-strength approved maintenance dose in the local country will meet this ICS criterion
* Controller Medication: Current treatment with an additional controller medication, besides ICS, for at least 3 months or a documented failure in the past 12 months of an additional controller medication for at least 3 successive months (e.g. LABA, leukotriene receptor antagonist \[LTRA\], or theophylline)
* Eosinophilic asthma: Prior documentation of eosinophilic asthma or high likelihood of eosinophilic asthma as per Randomisation Criteria 1 and 2
* FEV1: Persistent airflow obstruction as indicated by : For participants \>=18 years of age at visit 1, a pre-bronchodilator FEV1 \<80% predicted (National Health and Nutrition Examination Survey \[NHANES III\]) recorded at Visit 1. For participants 12-17 years of age at Visit 1: A pre-bronchodilator FEV1 \<90% predicted (NHANES III) recorded at Visit 1 OR FEV1:FVC ratio \<0.8 recorded at Visit 1
* Exacerbation history: Previously confirmed history of two or more exacerbations requiring treatment with systemic Corticosteroid (CS) (intramuscular, intravenous, or oral), in the 12 months prior to visit 1, despite the use of high-dose inhaled corticosteroids (ICS). For participants receiving maintenance CS, the CS treatment for the exacerbations must have been a two-fold dose increase or greater.
* Gender: Male or Eligible Female. To be eligible for entry into the study, females of childbearing potential must commit to consistent and correct use of an acceptable method of birth control listed in the protocol for the duration of the trial and for 4 months after the last study drug administration.
* Informed Consent/Assent: Able to give written informed consent/assent prior to participation in the core study, which will include the ability to comply with the requirements and restrictions listed in the consent/assent form and in this protocol. Participants must be able to read, comprehend, and write at a level sufficient to complete study related materials. Written informed consent must be obtained from ALL patients/legally authorized representative(s); for patients 12-17 years old, written informed assent must be obtained in addition to the legally authorized representative(s)' consent.
* French participants: In France, a participant will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Exclusion Criteria:

* Smoking history: Current smokers or former smokers with a smoking history of \>=10 pack years (number of pack years = (number of cigarettes per day/20) x number of years smoked). A former smoker is defined as a participant who quit smoking at least 6 months prior to Visit 1.
* Concurrent Respiratory Disease: Presence of a known pre-existing, clinically important lung condition other than asthma. This includes current infection, bronchiectasis, pulmonary fibrosis, bronchopulmonary aspergillosis, or diagnoses of emphysema or chronic bronchitis (chronic obstructive pulmonary disease other than asthma) or a history of lung cancer.
* Malignancy: A current malignancy or previous history of cancer in remission for less than 12 months prior to screening (Participants that had localized carcinoma of the skin which was resected for cure will not be excluded).
* Liver Disease: Known, pre-existing, unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices or persistent jaundice), cirrhosis, and known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
* Cardiovascular: Participants who have severe or clinically significant cardiovascular disease uncontrolled with standard treatment. Including but not limited to: (a) known ejection fraction of \<30% OR (b) severe heart failure meeting New York Heart Association Class IV classification OR (c) hospitalised in the 12 months prior to Visit 1 for severe heart failure meeting New York Heart Association Class III OR (d) angina diagnosed less than 3 months prior to Visit 1 or at Visit 1.
* Other Concurrent Medical Conditions: Participants who have known, pre-existing, clinically significant endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, haematological or any other system abnormalities that are uncontrolled with standard treatment.
* Eosinophilic Diseases: Participants with other conditions that could lead to elevated eosinophils such as Hypereosinophilic Syndromes, including Churg-Strauss Syndrome (Eosinophilic Granulomatosis with Polyangiitis \[EGPA\]), or Eosinophilic Esophagitis. Participants with a known, pre-existing parasitic infestation within 6 months prior to Visit 1 are also to be excluded.
* Electrocardiogram (ECG) Assessment: QT interval corrected for heart rate by Fridericia's formula (QTc(F)) \>=450 milliseconds (msec) or QTc(F) \>=480 msec for participants with Bundle Branch Block at Visit 1.
* Alcohol/Substance Abuse: A history (or suspected history) of alcohol misuse or substance abuse within 2 years prior to Visit 1.
* Immunodeficiency: A known immunodeficiency (e.g. human immunodeficiency virus \[HIV\]), other than that explained by the use of corticosteroids taken as therapy for asthma.
* Xolair: Participants who have received omalizumab (Xolair) within 130 days of Visit 1.
* Other Monoclonal Antibodies: Participants who have received any monoclonal antibody (other than Xolair) to treat inflammatory disease within 5 half-lives of Visit 1.
* Investigational Medications: Participants who have received treatment with an investigational drug within the past 30 days or five terminal phase half-lives of the drug whichever is longer, prior to Visit 1 (this also includes investigational formulations of marketed products).
* Hypersensitivity: Participants with allergy/intolerance to a monoclonal antibody or biologic.
* Pregnancy: Participants who are pregnant or breastfeeding. Patients should not be enrolled if they plan to become pregnant during the time of study participation. A urine pregnancy test is required of all women of child bearing potential. This test will be performed at the time points specified in the Time and Events Schedule in protocol.
* Adherence: Participants who have known evidence of lack of adherence to controller medications and/or ability to follow physician's recommendations.
* Previous participation: Previously participated in any study with mepolizumab and received investigational product (including placebo)

Answer: B