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:

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.
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:

* 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
D: Inclusion Criteria:

* Adult patients, 18 to 75 years of age inclusive
* Body weight \>/= 40 kg
* Physician's diagnosis of asthma for at least 12 months
* Evidence of documented bronchodilator reversibility as defined by protocol
* Prebronchodilator FEV1 \>/= 40% and \</= 80% predicted at Visit 1
* Required daily use of ICS and a second controller for a minimum of 3 consecutive months prior to Visit 1
* History of at least one protocol-defined asthma exacerbation in the 18 months prior to Visit 1
* Inadequately controlled asthma despite compliance with asthma controller therapy

Exclusion Criteria:

* Asthma exacerbation requiring systemic steroids in the 30 days prior to Visit 1
* Pre-existing active lung disease other than asthma
* Any infection
* Clinically significant medical disease that is uncontrolled despite treatment or is likely to require a change in therapy during study or is of unknown etiology
* Known immunodeficiency, including but not limited to HIV infection, regardless of treatment status
* Current substance abuse
* Former smoker with \>10 pack-year history or current smoker; former smokers must have stopped smoking more than 12 months prior to Visit 1
* History of anaphylaxis
* Pregnant and lactating women

Answer: B