Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase II, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of Daclizumab in Patients With Chronic, Persistent Asthma
Brief Summary: The purpose of the study is to evaluate an investigational medication to treat chronic persistent asthma. The research is being conducted at up to 22 clinical research sites in the US and is open to both men and women ages 18 to 70 years old. Participants in the study will have a number of visits to a research site over a 10-month period. All study-related care and medication is provided to qualified participants at no cost: this includes all visits, examinations and laboratory work.


Options:
A: 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.
B: Inclusion Criteria:

* Meet criteria for the diagnosis of allergic asthma
* Diagnosis of asthma ≥ 6 months
* Currently treated with only intermittent short-acting inhaled β-adrenergic agonists
* Body weight between 40-120 kg
* Normal chest X-ray within 2 years of screening

Exclusion Criteria:

* Require daily controller medication for asthma
* History of hypersensitivity to the study drug or to drugs with similar chemical structures or to any ingredients, including excipients of the study medication or drugs related to MILR1444A (e.g., monoclonal antibodies, polyclonal gamma globulin)
* Documented medical history of anaphylaxis
* Immunotherapy currently or within the past 3 months prior to screening
* Lung disease other than mild allergic asthma
* Previous treatment with other investigational drugs within 30 days or 5 half-lives prior to the screening visit, whichever is longer
* Pregnant or lactating
* Significant concurrent medical illness other than asthma
* Clinically significant abnormality on ECG at the screening visit
* Smoked in the previous 6 months or have a history of smoking more than 10 pack-years
* History of helminthic infection
C: Inclusion Criteria:

* History of asthma for 6 or more months
* History of chronic persistent asthma requiring daily high dose inhaled corticosteroid for 3 or more months prior to enrollment

Exclusion Criteria:

* Patients with 10 or more pack years of smoking history or smoking within 12 months of study enrollment
* No significant disease other than asthma
D: 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.

Answer: C