Please select the eligibility criteria that correspond to the clinical trial below.
Title: A 12-Month, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Reslizumab (3.0 mg/kg) in the Reduction of Clinical Asthma Exacerbations in Patients (12-75 Years of Age) With Eosinophilic Asthma
Brief Summary: The primary objective of this study is to determine whether reslizumab is more effective than placebo in reducing the number of clinical asthma exacerbations (CAEs) in patients with eosinophilic asthma.


Options:
A: Inclusion Criteria:

* The patient is male or female, 12 through 75 years of age, with a previous diagnosis of asthma. Patients 12 through 17 years of age are excluded from participating in Germany, India, Argentina, and Korea; patients 66 through 75 years of age are excluded from participating in India and Korea.
* The patient has had at least 1 asthma exacerbation requiring oral, intramuscular (im), or intravenous (iv) corticosteroid use for at least 3 days over the past 12 months before screening.
* The patient has a current blood eosinophil level of at least 400/μL.
* The patient has airway reversibility of at least 12% to beta-agonist administration.
* The patient has an ACQ score of at least 1.5 5 at the screening and baseline (before the 1st dose of study drug) visits.
* The patient is taking inhaled fluticasone at a dosage of at least 440 μg, or equivalent, daily. Chronic oral corticosteroid use (no more than 10 mg/day prednisone or equivalent) is allowed. If a patient is on a stable dose, eg, 2 weeks or more of oral corticosteroid treatment at the time of study enrollment, the patient must remain on this dose throughout the study. The patient's baseline asthma therapy regimen (including, but not limited to, inhaled corticosteroids, oral corticosteroids up to a maximum dose of 10 mg prednisone daily or equivalent, leukotriene antagonists, 5-lipoxygenase inhibitors, or cromolyn) must be stable for 30 days prior to screening and baseline and must continue without dosage changes throughout the study.
* All female patients must be surgically sterile, 2 years postmenopausal, or must have a negative pregnancy test (ß-human chorionic gonadotropin \[ß-HCG\]) 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). NOTE: Partner sterility alone is not acceptable for inclusion in the study.
* Written informed consent is obtained. Patients 12 through 17 years old, where participating, must provide assent.
* 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, ECG evaluation (at screening), serum chemistry, hematology, and urinalysis.
* The patient must be willing and able to understand and comply with study restrictions, requirements, and procedures, as specified by the study center, and to remain at the study center for the required duration during the study period, and willing to return to the study center for the follow-up evaluation as specified in this protocol.
* Patients who experience an asthma exacerbation during the screening period will be considered to have failed screening and cannot be randomly assigned to study drug. Patients may be rescreened 1 time only.

Exclusion Criteria:

* The patient has a clinically meaningful co-morbidity that would interfere with the study schedule or procedures, or compromise the patient's safety.
* The patient has known hypereosinophilic syndrome.
* The patient has another confounding underlying lung disorder (eg, chronic obstructive pulmonary disease, pulmonary fibrosis, or lung cancer). Patients with pulmonary conditions with symptoms of asthma and blood eosinophilia (eg, Churg-Strauss syndrome, allergic bronchopulmonary aspergillosis) will also be excluded.
* The patient is a current smoker (ie, has smoked within the last 6 months prior to screening).
* The patient is using systemic immunosuppressive, immunomodulating, or other biologic agents (including, but not limited to, anti-immunoglobulin E (IgE) mAb, methotrexate, cyclosporin, interferon-α, or anti-tumor necrosis factor \[anti-TNF\] mAb) within 6 months prior to screening.
* The patient has previously received an anti-hIL-5 monoclonal antibody (eg, reslizumab, mepolizumab, or benralizumab).
* The patient has any aggravating medical factors that are inadequately controlled (eg, rhinitis, gastroesophageal reflux disease, and uncontrolled diabetes).
* 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 6 months prior to screening.
* Other exclusion criteria apply.
B: Inclusion Criteria:

1. Female and male patients aged 18 to 75 years inclusively at the time of Visit 1 with a history of physician-diagnosed asthma requiring treatment with medium-to-high dose Inhaled Corticosteroids (ICS) plus asthma controller, for at least 12 months prior to Visit 1.
2. Documented current treatment with high daily doses of ICS plus at least one other asthma controller for at least 3 months prior to Visit 1.
3. History of at least 2 asthma exacerbations while on ICS plus another asthma controller that required treatment with systemic corticosteroids (IM, IV, or oral) in the 12 months prior to Visit 1.
4. ACQ6 score ≥1.5 at Visit 1.
5. Screening pre-bronchodilator (pre-BD) FEV1 of \<80% predicted at Visit 2.
6. Excessive variability in lung function by satisfying ≥ 1 of the following criteria:

   1. Airway reversibility (FEV1 ≥12%) using a short-acting bronchodilator demonstrated at Visit 2 or Visit 3.
   2. Airway reversibility to short-acting bronchodilator (FEV1 ≥12%) documented during the 12 months prior to enrolment Visit 1.
   3. Daily diurnal peak flow variability of \>10% when averaged over 7 continuous days during the study run-in period
   4. An increase in FEV1 of ≥12% and 200 mL after a therapeutic trial of systemic corticosteroid (eg, OCS), given outside of an asthma exacerbation, documented in the 12 months prior enrolment Visit 1.
   5. Airway hyper-responsiveness (methacholine: PC20 of \<8 mg/mL, histamine: PD20 of \<7.8 μmol, mannitol: decrease in FEV1 as per the labelled product instructions) documented in the 24 months prior to randomization Visit 4.
7. Peripheral blood eosinophil count either:

   * 300 cells/μL assessed by central laboratory at either Visit 1 or Visit 2

OR

≥150 to \<300 cells/μL assessed by central laboratory at either Visit 1 or Visit 2, IF ≥1 of the following 5 clinical criteria (a to e) is met:

1. Using maintenance OCS (daily or every other day OCS requirement in order to maintain asthma control; maximum total daily dose 20 mg prednisone or equivalent) at screening
2. History of nasal polyposis
3. Age of asthma onset ≥18 years
4. Three or more documented exacerbations requiring systemic corticosteroid treatment during the 12 months prior to screening
5. Pre-bronchodilator forced vital capacity \<65% of predicted, as assessed at Visit 2 (note that screening pre-BD FEV1 Inclusion Criterion #6 must still be satisfied)

For inclusion in the open label ANDHI IP sub study patients should meet the following criteria:

1. Patients study must have completed ANDHI EOT Visit 11.
2. Written informed consent must also be obtained prior to any study related procedures being performed in the open label ANDHI IP sub study.
3. Patients who have received any approved or investigational targeted biologic for the treatment of asthma (e.g. commercial mepolizumab, reslizumab, benralizumab) may be included if the last dose is ≥ 2 months of Visit 13.

Exclusion Criteria:

1. Clinically important pulmonary disease other than asthma
2. Acute upper or lower respiratory infections within 30 days prior to the date informed consent.
3. A helminth parasitic infection diagnosed within 24 weeks prior to the date informed consent is obtained that has not been treated with, or has failed to respond to, standard of care therapy.
4. History of alcohol or drug abuse within 12 months prior to the date informed consent is obtained.
5. A history of known immunodeficiency disorder.
6. Current smokers or former smokers with a smoking history of ≥10 pack years.
7. Previously received benralizumab (MEDI-563).
8. Receipt of any investigational medication as part of a research study within approximately 5 half-lives prior to randomization.
9. Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained.
10. Receipt of live attenuated vaccines 30 days prior to the date of randomization; other types of vaccines are allowed.
11. Concurrent enrolment in another interventional or post-authorization safety study

Exclusion criteria for the open label ANDHI IP sub study:

Patients should not enter the open label ANDHI IP sub study if any of the following exclusion criteria are fulfilled. Each exclusion criterion should be reviewed in all potential participants, including those who transition directly from the double-blind period and those with a delay between completing the EOT Visit 11 and the first open label visit (Visit 13).

1. Patients who participated in the double-blind period but failed to complete the ANDHI EOT Visit 11. Patients who completed the ANDHI FU Visit 12 are not excluded from participation in the ANDHI IP sub study.
2. Unable to commit to the monthly visits as required by the protocol, or unable to commit to undergoing protocol guided reductions in asthma therapy, as directed by the Investigator.
3. Patients who experienced a severe or serious treatment-related AE during the double-blind period and, and those whom Investigator judges it is not in the patient's best interest to extend possible treatment with benralizumab.
4. Approved or off-label use of systemic immunosuppressive medications within 3 months prior to the first open label visit (Visit 13). These include but are not limited to small molecules such as methotrexate, cyclosporine, azathioprine, and immunosuppressive/immunomodulating biologics such as tumour necrosis factor (TNF) blockers. Regular use of systemic OCS is also excluded except for the indication of asthma.
5. Receipt of live attenuated vaccines 30 days prior to the first visit in the open label ANDHI IP sub study (Visit 13); other types of vaccines are allowed.
6. Planned surgical procedures during the conduct of the study.
7. Positive urine pregnancy test at Visit 13, or currently breastfeeding or lactating women.
C: Inclusion Criteria:

* Written informed consent is obtained.
* The participant is male or female, 12 years of age and older, with a diagnosis of asthma.
* The participant has Forced Expiratory Volume in 1 Second (FEV1) reversibility according to standard American Thoracic Society (ATS) or European Respiratory Society (ERS) protocol.
* The participant has required an inhaled corticosteroid.
* The participant has required an additional asthma controller medication besides inhaled corticosteroids.
* The participant has a history of asthma exacerbation.
* The participant must be willing and able to comply with study restrictions, perform requisite procedures and 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.

  * Additional criteria may apply, please contact the investigator for more information

Exclusion Criteria:

* The participant has any clinically significant, uncontrolled medical condition (treated or untreated) that would interfere with the study schedule or procedures, interpretation of efficacy results, or compromise the patient's safety.
* The participant has another confounding underlying lung disorder
* The participant has a known hypereosinophilic syndrome.
* The participant has a diagnosis of malignancy within 5 years of the screening visit, except for treated and cured non-melanoma skin cancers.
* The participant is a pregnant or lactating woman, or intends to become pregnant during the study. Any woman becoming pregnant during the study will be withdrawn from the study.
* The participant is a current smoker or has a smoking history.
* The participated in a clinical trial within 30 days or 5 half-lives of the investigational drug before screening, whichever is longer.
* The participant was previously exposed to reslizumab.
* The participant has a history of an immunodeficiency disorder including human immunodeficiency virus (HIV).
* The participant has current or suspected drug and alcohol abuse.
* The participant has an active helminthic parasitic infection or was treated for one within 6 months of screening.
* The participant has a history of allergic reaction or hypersensitivity to any component of the study drug.

  * Additional criteria may apply, please contact the investigator for more information
D: Inclusion Criteria:

1. Healthy men and women 18 to 60 yrs with mild allergic asthma
2. only asthma med is short-acting bronchodilator used not more than twice weekly
3. FEV1 greater than 70% predicted and a demonstrated baseline late response to allergen induction

Exclusion Criteria:

1. Upper respiratory infection or asthma exacerbation with 4 weeks of screening
2. Serious infection requiring parenteral antibiotics or hospitalization with 4 weeks of test article administration
3. Positive radiographic findings indicative of respiratory disease other than asthma

Answer: A