Please select the eligibility criteria that correspond to the clinical trial below.
Title: MEA115588 A Randomised, Double-blind, Double-dummy, Placebo-controlled, Parallel-group, Multi-centre Study of the Efficacy and Safety of Mepolizumab Adjunctive Therapy in Subjects With Severe Uncontrolled Refractory Asthma
Brief Summary: This study will evaluate two dose regimens of mepolizumab \[75mg intravenous (i.v.) or 100mg subcutaneous (SC) every 4 weeks\] compared with placebo over a 32 week treatment period in subjects with severe refractory asthma with elevated blood eosinophils. Efficacy will be measured by a reduction in the frequency of asthma exacerbations. Additional efficacy assessments will include measurements of lung function, symptom scores, and quality of life. Safety will be assessed by clinical laboratory samples, ECGs, immunogenicity and adverse events.

This study is intended to replicate the Phase IIb/III study MEA112997. Subjects in MEA115588, who meet all eligibility criteria at screening visit, will enter the run-in period. Those subjects that are not able/eligible to be randomised at the end of the 6 week run-in period will be deemed run-in failures. Subjects will remain on their current maintenance therapy throughout the run-in, double-blind treatment administration and follow-up periods. Subjects who meet the randomisation eligibility criteria will be randomised in a 1:1:1 ratio to receive one of the following treatments every 4 weeks for a total of 8 doses: Mepolizumab 75 miligram (mg) i.v. and placebo SC, or Mepolizumab 100 mg SC and placebo i.v. or Placebo i.v. and placebo SC.

Subjects that receive all 8 doses of double-blind treatment, and meet the eligibility criteria for the Open-Label Extension (OLE) Study, will be offered the opportunity to participate in the OLE trial.


Options:
A: Inclusion criteria

1. Informed consent (and/or assent as applicable locally) for study participation must be obtained prior to any study related procedures being performed (local regulations are to be followed in determining the assent/consent requirements for children and parent(s)/guardian(s)) and according to international guidelines and/or applicable European Union guidelines.
2. Female and male patients who completed the double-blind treatment period in a predecessor study on benralizumab or matching placebo.
3. Women of childbearing potential (WOCBP) must agree to use an effective form of birth control throughout the study duration and for 16 weeks after last dose of Investigational Product (IP).
4. For WOCBP only: Have a negative urine pregnancy test prior to administration of Investigational Product (IP) at Visit 1.
5. All male patients who are sexually active must agree to use a double barrier method of contraception (condom with spermicide) from the first dose of IP until 16 weeks after their last dose.

Exclusion criteria

1. Any disorder including but not limited to cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric or major physical impairment that is not stable in the opinion of the Investigator and could:

   * Affect the safety of the patient throughout the study
   * Influence the findings of the studies or their interpretations
   * Impede the patient's ability to complete the entire duration of study
2. A helminth parasitic infection diagnosed during a predecessor study that has either not been treated, has been incompletely treated or has failed to respond to standard of care therapy
3. Any clinically significant change in physical examination, vital signs, electrocardiogram (ECG), haematology, clinical chemistry, or urinalysis during a predecessor study which in the opinion of the investigator may put the patient at risk because of his/her participation in the study, or may influence the results of the study, or interfere with the patient's ability to complete the entire duration of the study
4. Current malignancy or malignancy that developed during a predecessor study (subjects that had basal cell carcinoma, localized squamous cell carcinoma of the skin which was resected for cure, or in situ carcinoma of the cervix that has been treated/cured will not be excluded).
5. Receipt of live attenuated vaccines within 30 days prior to initiation of treatment in this study, during the treatment period, and for 16 weeks (5 half-lives) after the last dose of the investigational product
6. Receipt of immunoglobulin or blood products within 30 days prior to Visit 1
7. Planned major surgical procedures during the conduct of the study
8. Previous participation in the present study
9. Concurrent enrolment in another clinical trial
10. AstraZeneca staff involved in the planning and/or conduct of the study
11. Employees of the study centre or any other individuals involved with the conduct of the study or immediate family members of such individuals
12. Patients with major protocol deviations in any of the predecessor studies at the discretion of the Sponsor
B: Inclusion Criteria:

* Weight between 50 and 125 kg
* Mild, stable allergic asthma
* History of episodic wheeze and shortness of breath
* FEV1 at baseline ≥ 70% of the predicted value
* For women of childbearing potential, agreement to use an effective means of contraception while enrolled in the study
* For men with partners of childbearing potential, willingness to use condoms with spermicide during treatment
* Ability to comprehend and follow all required study procedures
* Positive skin prick test to common aeroallergens (e.g., cat, dust, mite, grass, and pollen)
* Positive allergen-induced early and late airway bronchoconstriction

Exclusion Criteria:

* A worsening of asthma or a respiratory tract infection within 6 weeks preceding study entry
* Acute infection (including viral infection) within the 6 weeks preceding dosing (8 weeks for respiratory infections) or any ongoing chronic infection
* History of recurrent bacterial infection as an adult or history or presence of any chronic infectious condition, including (but not limited to), tuberculosis, parasitic infection, etc.
* Lung disease other than mild allergic asthma
* History of heart, lung, kidney, liver, neurologic or chronic infectious disease
* Concomitant disease or condition, which could interfere with the conduct of the study, including, but not limited to, cancer, alcoholism, drug dependency or abuse, or psychiatric disease
* History of serious adverse reaction or hypersensitivity to any drug
* Pregnancy or lactation or positive serum pregnancy test at screening
* Chronic use of any other medication for treatment of allergic lung disease other than short-acting β2-agonists or ipratropium bromide
* Current (or history of) treatment with a monoclonal antibody or chimeric biomolecule within the past 5 months (5 half-lives of the drug), including omalizumab
* Regular use of tobacco products of any kind or within the previous 6 months, or smoking history \> 10 pack-years
C: Inclusion criteria:

Patients are included in the study if all of the following criteria are met:

* The patient is a man or woman, 18 through 65 years of age, with a diagnosis of asthma.
* The patient has an ACQ score of at least 1.5.
* At screening, the patient has airway reversibility of at least 12% to beta-agonist administration.
* The patient is currently taking fluticasone at a dosage of at least 440 µg daily (or equivalent). Patients' baseline asthma therapy regimens (including but not limited to inhaled corticosteroids, leukotriene antagonists, 5-lipoxygenase inhibitors, cromolyn) must be stable for 30 days before screening and continue without dosage changes throughout study.
* Female patients must be surgically sterile, 2 years postmenopausal, or must have a negative beta-human chorionic gonadotropin (ßHCG) result for a pregnancy test at screening (serum) and baseline (urine).
* Female patients of childbearing potential (not surgically sterile or 2 years postmenopausal), must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study and for 30 days after participation in the study. Acceptable methods of contraception include barrier method with spermicide, abstinence, intrauterine device (IUD), or steroidal contraceptive (oral, transdermal, implanted, and injected).
* Written informed consent is obtained.
* The patient is in reasonable health (except for diagnosis of asthma) as judged by the investigator, and as determined by a medical history, medical examination, electrocardiogram (ECG) evaluation, serum chemistry, hematology, urinalysis, and serology.
* The patient must be willing and able to comply with study restrictions and to remain at the clinic for the required duration during the study period, and be willing to return to the clinic for the follow-up evaluation as specified in this protocol.

Exclusion Criteria:

Patients are excluded from participating in this study if 1 or more of the following criteria are met:

* The patient has another confounding underlying lung disorder (eg, chronic obstructive pulmonary disease, pulmonary fibrosis, lung cancer). The patient has other pulmonary conditions with symptoms of asthma and blood eosinophilia (eg, Churg-Strauss syndrome, allergic bronchopulmonary aspergillosis).
* The patient has a clinically meaningful comorbidity that would interfere with the study schedule or procedures, or compromise the patient's safety.
* The patient has known hypereosinophilic syndrome (HES).
* The patient is a current smoker (ie, has smoked within the last 6 months prior to screening).
* The patient has a history of use of systemic immunosuppressive or immunomodulating agents (anti-immunoglobulin E \[anti-IgE\] mAb, methotrexate, cyclosporin, interferon-α, anti-tumor necrosis factor mAb, or omalizumab) within 6 months prior to study entry (randomization).
* The patient is currently using or has used systemic corticosteroids (includes use of oral corticosteroids) within 30 days prior to the screening visit.
* The patient is expected to be poorly compliant with study drug administration, study procedures, or visits.
* The patient has any aggravating factors that are inadequately controlled, and thus would aggravate asthma symptoms (eg, gastroesophageal reflux disease).
* The patient has participated in any investigative drug or device study within 30 days prior to screening.
* The patient has participated in any investigative biologics study within 90 days prior to screening.
* The patient has previously received reslizumab or other anti-hIL-5 mAbs (eg, mepolizumab).
* The patient is a pregnant or lactating woman. (Any women becoming pregnant during the study will be withdrawn from the study.)
* The patient has a current infection or disease that may preclude assessment of asthma.
* The patient has a history of concurrent immunodeficiency (human immunodeficiency, acquired immunodeficiency syndrome, or congenital immunodeficiency).
* The patient is suspected of current drug or alcohol abuse as specified in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria.
* The patient has presence of or suspected parasitic infestation/infection.
* Patients may not have received any live attenuated vaccine within the 12-week period before study entry.
D: 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)

Answer: D