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:

* 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
B: Inclusion Criteria:

* Males or infertile females
* Subjects with asthma, well controlled on inhaled corticosteroid and taken as required (PRN) short acting beta 2 agonist therapy only
* Unchanged dose of inhaled corticosteroid for 3 months prior to Day 0 and no expected need for change in dose during study
* Forced expiratory volume in 1 second (FEV1) greater than or equal to 80% predicted at Screening (Baseline)
* 18-60 years
* General Practitioner diagnosis of asthma of 1 year's minimum duration (with respect to Day 0)
* No significant abnormality on clinical examination or medical history (excluding atopic skin signs, symptoms and history)
* 12-lead electrocardiogram with no clinical significant abnormality
* Clinical chemistry hematology and urinalysis results within the laboratory reference ranges or deemed not clinically significant by the Investigator
* A negative screen for drugs of abuse and alcohol
* Body weight between 50-120 kg
* Subjects aged between 18-40 years inclusive must have body mass index (BMI) 18-32 kilogram per square meter (kg/m\^2) inclusive. Subjects aged between 41-60 years must have BMI between 18-30 kg/m\^2 inclusive.

Exclusion Criteria:

* Active concomitant disease, with exception of eczema
* Expected onset of seasonal allergy before the administration of the last dose of study medication
* History of severe exacerbation within 3 years of Day 0
* Recorded use of inhaled short acting beta 2 agonist medication for symptoms within 14 days of Day 0 of: More than 6 doses per day on any 1 day or more than 3 doses per day on 6 or more days
* Any medication other than: inhaled short-acting beta 2 agonist, inhaled corticosteroids, topic eczema treatments (with the exception of fluorinated corticosteroid, dermatological preparations which are not permitted), hormone replacement therapy, vitamin preparation/food supplements, occasional use of proton pump inhibitors, ranitidine, cimetidine, antacids or over-the-counter analgesics
* Treatment within 6 months of Day 0 with any of the following: methylxanthines, inhaled cromones, leukotriene modifiers, anti- immunoglobulin E (IgE), anticholinergics, ketotifen, oral short acting B2 agonists, long-acting B2 agonists, oral or injected corticosteroids
* Treatment of atopic symptoms, other than eczema, within 4 weeks of Day 0
* History of medication that might carry-over effects into the study
* Previously received monoclonal antibody, or a similar related protein, that might sensitize to CAT-354
* Participation in another study within three months of the start of the study or 5 half lives of the previously administered investigational medicinal product (IMP), whichever is longer
* Lower respiratory tract infection within 4 weeks of Day-14
* Any acute illness in the two weeks before Day 0
* Current smokers, those who have smoked in previous year, and those with smoking history of greater than or equal to 10 pack years
* Considered by the investigator to be at risk of transmitting, through blood, the agents responsible for infectious diseases
* Blood donation (550 ml) in the previous 2 months
* Excessive intake of alcohol (more than 21 units a week for females or 28 units a week for males)
* The subject's general practitioner has suggested a reason the subject should not participate in the study
* The Investigator considers the subject should not take part for any reason.
C: Inclusion criteria:

Medical diagnosis of persistent asthma for at least 12 months whose:

* airway inflammation likely to be eosinophilic,
* asthma partially controlled or uncontrolled on ICS plus LABA therapy.
* On a stable dose of either Fluticasone/Salmeterol, Budesonide/Formoterol, Mometasone/Formoterol combination therapy for at least 1 month prior to screening.
* Signed an Informed Consent Form and Health Insurance Portability and Accountability Act (HIPAA) Authorization Form.

Exclusion criteria:

* Less than 18 years or greater than 65 years of age.
* Clinically relevant abnormal laboratory values suggesting an unknown disease and requiring further evaluation.
* Chronic obstructive pulmonary disease and/or other lung diseases impairing Pulmonary Function Tests.
* Beta-adrenergic receptor blockers required for any reason.
* Current smoker or cessation of smoking within the 6 months prior to screening.
* Previous smoking with a smoking history \>10 cigarette pack/years.
* Participation in another study within 6 months prior to screening if the study medication was an antibody or within 30 days prior to screening for all other study medications.
* Known or suspected non-compliance, alcohol or drug abuse.
* Inability to follow the procedures of the study (e.g, due to language problems, psychological disorders).
* Concomitant severe diseases or diseases for which the use of ICS or LABA were contraindicated.
* Known allergy to doxycycline or related compounds.
* Pregnancy or intention to become pregnant during the course of the study, breast feeding, or unwillingness to use a highly effective method of contraception throughout the study in women of childbearing potential.
* Recent history of a parasitic infection or travel to a parasitic endemic area within 6 months prior to screening.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
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: A