Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 2b, Randomized Study to Evaluate the Efficacy and Safety of Subcutaneous MEDI-528 in Adults With Uncontrolled Asthma
Brief Summary: To study the effectiveness and safety of multiple-doses of MEDI-528 on asthma control in adult participants with uncontrolled, moderate-to-severe, persistent asthma.


Options:
A: 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)
B: Inclusion Criteria

Subjects must meet all of the following criteria:

1. Male or female
2. Age 18 through 65 years at the time of screening
3. Written informed consent and any locally required authorization obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
4. Female subjects of childbearing potential who are sexually active with non-sterilized male partner must use adequate contraception from screening through the end of the study. An acceptable method of contraception is defined as one that has no higher than a 1% failure rate. Sustained abstinence is an acceptable practice; however, periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception

   1. Non-sterilized males who are sexually active with a female of child-bearing potential must use adequate contraception from screening through the end of the study
   2. Females or female partners not of childbearing potential must have been surgically sterilized (eg, hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or postmenopausal (defined as at least 1 year since last regular menses)
   3. Sterilized males must be at least 1-year post vasectomy and have obtained documentation of the absence of sperm in the ejaculate
5. Weight ≥ 45 kg but ≤ 120 kg and body mass index (BMI) between 18 and 35 kg/m2
6. Physician-diagnosed asthma by medical chart
7. Currently taking inhaled corticosteroids (ICS) or is a candidate to receive ICS per Expert Panel Report (EPR)-3
8. Pre-bronchodilator forced expiratory volume in 1 second (FEV1) value ≥ 40% at Day -28 and Day 1
9. A post-bronchodilator increase in FEV1 and/or FVC ≥ 12% and ≥ 200 mL at Day -28 OR meeting any one of the following criteria:

   1. Proof of post-bronchodilator reversibility of airflow obstruction ≥ 12% documented within 36 months prior to randomization or proof of a positive response to a methacholine challenge documented within 36 months prior to randomization; OR
   2. Proof of partial reversibility of ≥ 8% to \< 12% improvement in post-bronchodilator FEV1 on Day -28 and achievement of ≥ 12% reversibility at a second time between Day -27 and Day -15; OR
   3. If a) and b) are not met and all other inclusion/exclusion criteria are met, subjects with a FEV1 of ≥ 1.5 L and ≥ 60% on Day -14 will be eligible to undergo a methacholine challenge. If the subject achieves a positive response to this methacholine challenge, then this criterion is met
10. Uncontrolled asthma consistent with EPR-3. In the 28 days before screening, subjects should have a history of one or more of the following:

    * Daytime asthma symptoms ≥ 2 days/week
    * Nighttime awakening ≥ 1 night/week
    * Albuterol/salbutamol use ≥ 2 days/week
11. An Asthma Control Questionnaire (ACQ) score ≥ 1.5 at Day -28 and at Day 1.
12. At least one asthma exacerbation in the 12 months before screening that required intake of systemic corticosteroids after an unscheduled medical encounter or as agreed with a physician based on an asthma action plan that defines when oral steroids can be taken by the subject
13. Ability and willingness to complete the follow-up period through Day 323 as required by the protocol.

Exclusion Criteria

Any of the following would exclude the subject from participation in the study:

1. Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results
2. Concurrent enrollment in another clinical study
3. Employees of the clinical study site or any other individuals involved with the conduct of the study, or immediate family members of such individuals
4. Known history of allergy or reaction to any component of the investigational product formulation
5. History of anaphylaxis to other biologic therapy
6. Lung disease other than asthma (eg, chronic obstructive pulmonary disease \[COPD\], cystic fibrosis)
7. Severe depression as measured by a depression score \> 15 on the Hospital Anxiety and Depression Scale (HADS) at either Day-28 or Day 1.
8. History of suicidal behavior in the previous 3 years as measured by the Columbia Suicide Severity Rating Scale (C-SSRS) at Day -28.
9. Acute illness other than asthma at the screening and randomization visits
10. History of an active infection within 28 days before and during the screening period, or evidence of clinically significant active infection, including ongoing chronic infection
11. History of ingestion of untreated water in a location known to be infected with parasites, resulting in acute or chronic diarrhea; history of recent travel to areas where parasite infestations are endemic within 6 months before screening; or a diagnosis of parasitic infection within 6 months before screening
12. Use of immunosuppressive medication (except oral prednisone up to a dose of 20 mg every other day or equivalent \[eg, 10 mg a day or 5 mg twice a day\] and inhaled and topical corticosteroids) within 28 days before randomization
13. Receipt of immunoglobulin or blood products within 28 days before randomization
14. Plans to donate blood during the entire study period
15. Donated blood or has had a blood transfusion within 28 days before screening
16. Receipt of any non-biological study drugs or interventional therapy (including surgical procedures) within 28 days of the first dose of investigational product in this study
17. Receipt of any biologicals including MEDI-528 within 5 half-lives before the first dose of investigational product in this study
18. History of any known immunodeficiency disorder
19. A positive hepatitis B surface antigen, or hepatitis C virus antibody, as determined by medical history and/or subject's verbal report
20. A positive human immunodeficiency virus test or is taking antiretroviral medications, as determined by medical history and/or subject's verbal report
21. A live attenuated vaccination received within 28 days before screening
22. History of clinically significant abnormality on electrocardiogram (ECG) in the opinion of the investigator
23. Breastfeeding or lactating
24. History of treatment for alcohol or drug abuse within the past year
25. History suggestive of COPD or of tobacco smoking ≥ 10 pack-years
26. Evidence of any uncontrolled systemic disease upon physical examination
27. History of cancer, apart from basal cell carcinoma or in situ carcinoma of the cervix treated with apparent success with curative therapy ≥ 1 year before Day 1 or other malignancies treated with apparent success with curative therapy ≥ 5 years before screening
28. Any noninfectious disease involving multiple organs (eg, cystic fibrosis, systemic lupus erythematosus, hemophilia, multiple sclerosis, etc.) that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results
29. Individuals who are legally institutionalized
C: Inclusion Criteria:

* Able to give written informed consent prior to participation in the study
* At least 12 years of age at visit 1 and a minimum weight of 45 kilogram (kg)
* 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)
* 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
* Prior documentation of eosinophilic asthma or high likelihood of eosinophilic asthma
* At Visit 1, a pre-bronchodilator FEV1 \<80% (for subjects \>= 18 years of age), a pre-bronchodilator FEV1 \<90% or FEV1:FVC ratio \<0.8 (for subjects 12-17 years of age).
* Previously confirmed history of two or more exacerbations requiring treatment with systemic CS
* Male or Eligible Female (females of childbearing potential must commit to consistent and correct use of an acceptable method of birth control)
* French subjects will be included only if either affiliated to or a beneficiary of a social security category.

Exclusion Criteria:

* Current smokers or former smokers with a smoking history of \>=10 pack years
* Presence of a known pre-existing, clinically important lung condition other than asthma
* A current malignancy or previous history of malignancy in less than 12 months
* Known, pre-existing, unstable liver disease cirrhosis and known biliary abnormalities
* Known, pre-existing severe or clinically significant cardiovascular disease
* known, pre-existing other concurrent clinically significant medical conditions that are uncontrolled with standard treatment
* Subjects with any eosinophilic diseases
* QTc(F) ≥450msec or QTc(F) ≥480 msec
* A history of alcohol/substance abuse
* Subject with known immunodeficiency
* Subjects who have received omalizumab within 130 days of Visit 1 or any monoclonal antibody (other than Xolair) to treat inflammatory disease within 5 half-lives of Visit 1
* Subjects 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
* Subjects with allergy/intolerance to a monoclonal antibody or biologic.
* Subjects who are pregnant or breastfeeding
* Subjects who have known evidence of lack of adherence to controller medications and/or ability to follow physician's recommendations
* Previously participated in any study with mepolizumab and received investigational product (including placebo)
D: Inclusion Criteria:

* Male or female subjects
* Age 18 to 65 years at the time of Screening
* Subjects must have a body mass index (BMI) between 18 and 40 kilogram per square meter (kg/m\^2)
* Written informed consent obtained from the subject prior to performing any protocol related procedures, including Screening evaluations
* Physician-diagnosed moderate-to-severe, persistent asthma requiring treatment with appropriate asthma controller medication
* Shows forced expiratory volume in 1 second (FEV1) reversibility postbronchodilator of greater than or equal to (\>=)12 percent and \>=200 milliliter (mL) or have shown such values in a previous test within the last year, or have a positive airway hyperresponsiveness (AHR) test result in the last year
* Pre-bronchodilator FEV 1 value \>=40 percent of individual predicted value at Visits 1 and 3
* Uncontrolled asthma consistent with Expert Panel Report (EPR)-3. In the 2 to 4 weeks preceding Screening, subjects should have a history of 1 or more of the following: Daytime asthma symptoms \>=2 days/week, Nighttime awakening \>=1 night/week, Salbutamol use \>=2 days/week
* An Asthma control questionnaire (ACQ) score \>=1.5 at Visits 1 and 3
* At least 1 occurrence of asthma exacerbation in the past year that required an unscheduled medical encounter
* Men, unless surgically sterile, must likewise practice 2 effective methods of birth control (condom with spermicide) and must use such precautions from Day 1 through Study Day 169
* Otherwise healthy by medical history and physical examination for that age group
* A chest x-ray or computed tomography (CT) scan within the previous 12 months with no findings suggestive of acute or chronic respiratory pathology other than asthma
* Ability and willingness to complete the follow-up period until Day 169 as required by the protocol.

Exclusion Criteria:

* Known history of allergy or reaction to any component of the investigational product formulation
* Acute illness other than asthma at the start of the study
* History of an active infection within 4 weeks prior to Screening, or evidence of clinically significant active infection, including ongoing chronic infection
* History of ingestion of untreated water in a location known to be infected with parasites, resulting in acute or chronic diarrhea; or a diagnosis of parasitic infection within 6 months prior to Screening
* Use of immunosuppressive medication (except oral prednisone up to 10 milligram/day (mg/day) and inhaled and topical corticosteroids) within 30 days before randomization into the study
* Receipt of immunoglobulin or blood products within 30 days before randomization into the study
* Receipt of any investigational drug therapy or use of any biologicals including omalizumab within 6 months before the first dose of investigational product in this study or within 5 half-lives of an investigational agent or biologic, whichever is longer
* History of any known immunodeficiency disorder
* A positive hepatitis B surface antigen, or hepatitis C virus antibody
* A positive human immunodeficiency virus test or is taking antiretroviral medications, as determined by medical history and/or subject's verbal report
* A live or attenuated vaccination received within 4 weeks prior to Screening
* Previous medical history, or evidence, of an intercurrent illness that may compromise the safety of the subject in the study
* History of clinically significant abnormality on electrocardiogram (ECG) in the opinion of the investigator
* Lactation (women)
* History of treatment for alcohol or drug abuse within the past year
* History suggestive of chronic obstructive pulmonary disease (COPD) and of cigarette smoking \>=10 pack-years
* Evidence of any systemic disease on physical examination
* History of cancer, apart from basal cell carcinoma or in situ carcinoma of the cervix treated with apparent success with curative therapy less than or equal to (\<=)1 year prior to Study Day 1 or other malignancies treated with apparent success with curative therapy \<=5 years prior to entry
* Known exposure to inhaled occupational agents or fumes
* Any condition (eg, cystic fibrosis \[CF\] or COPD) that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of study results
* Individuals who are legally institutionalized
* Employees of the clinical study site or any other individuals involved with the conduct of the study, or family members of such individuals.

Answer: B