Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Multicenter, Randomized, Double-blind, Parallel Group, Placebo-controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Benralizumab in Adult Patients With Mild to Moderate Persistent Asthma.
Brief Summary: The purpose of this trial is to confirm the safety and clinical benefit of benralizumab administration in asthma patients with mild to moderate persistent asthma in order to gain an understanding of the benefit/risk of benralizumab across the spectrum of asthma disease.


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:

* Men aged 18 - 65 years inclusive, or women aged 18 - 50 years inclusive.
* Female subjects must be of non-childbearing potential,
* Male subjects must agree to abstain from sexual intercourse or use adequate contraception during sexual intercourse with pregnant or lactating females, in addition to their female partner using another form of contraception. This criterion must be followed from the time of the first dose of study medication until 84 days after the last dose of study medication.
* Body weight ≥ 50 kg and BMI within the range 19 - 29.9 kg/m2.
* Non-smoker as verified by urinary cotinine levels below 300 ng/mL at screening or ex-smokers who have given up smoking for \>12 months with a history \<10 pack years \[Pack yrs = (No of cigarettes/day x No of years smoked)/20\]
* Available to complete all study measurements.
* Able to read, comprehend, and write English at a sufficient level to complete study related materials.
* Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form

Additional Inclusion Criteria for Subjects in Part I

• Healthy as determined by a responsible physician, based on a medical evaluation including history, physical examination, laboratory tests, cardiac monitoring.

Additional Inclusion Criteria for Subjects in Part II

* History of asthma for at least 6 months prior to the screening visit currently requiring no treatment or intermittent treatment with inhaled short-acting beta2-agonist only. Subject must not have received low dose inhaled corticosteroids within three months prior to Day 0.
* Pre-bronchodilator FEV1 \>70% but \<90% of predicted at screening with ≥12% reversibility after short-acting beta2-agonist or If the subject has a pre-bronchodilator FEV1 ≥90% at screening but has a history of asthma or if the subject meets the FEV1 criteria but does not demonstrate ≥12% reversibility after short-acting beta2-agonist administration, then the subject may be considered eligible if a Bronchial Provocation Test for asthma is positive (and after consultation with Medical Monitor and Principal Investigator). The bronchial provocation will be considered positive when the standard criteria for a positive response with the given challenge agent are met.
* Skin prick test positive for an allergen that is appropriate for nasal challenge

Exclusion criteria:

* As a result of medical interview, physical examination or screening investigations, the responsible physician deemed the subject unsuitable for the study.
* History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the physician responsible, contraindicates their participation.
* Previous exposure to humanised antibody therapy for any reason.
* A strong family history of Th1 cytokine-related inflammatory disorders, including but not limited to, Type I diabetes mellitus, multiple sclerosis, Crohn's disease, rheumatoid arthritis, sarcoidosis.
* Known history of active or latent tuberculosis, or recent (within 6 months of study enrolment) exposure to a person with active tuberculosis. Previous medical history and letter from the subject's physician (GP) should exclude this.
* A history of chronic urogenital infections or other chronic infections.
* Subjects who have received any type of vaccination in the last two months.
* The subject has participated in a clinical trial and has received a drug or a new chemical entity within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug(whichever is longer) prior to the first dose of current study medication
* Where participation in study would result in donation of blood in excess of 500 mL within a 56 day period
* Exposure to more than four new chemical entities within 12 months prior to the first dosing day
* Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John'sWort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and sponsor the medication will not interfere with the study procedures or compromise subject safety.
* History of alcohol/drug abuse or dependence within 12 months of the study:
* Abuse of alcohol defined as an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males) or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females). 1 unit is equivalent to a half-pint (220mL) of beer or 1 (25ml) measure of spirits or 1 glass (125ml) of wine
* A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
* A positive test for human immunodeficiency virus (HIV) antibodies.
* The subject has a positive pre-study urine drug/ urine alcohol screen. A minimum list of drugs that will be screened for include Amphetamines, Barbiturates, Cocaine, Opiates, Cannabinoids and Benzodiazepines.
* ECG that is outside of ranges as defined by the protocol
* Those who, in the opinion of the Investigator, have a risk of non-compliance with study procedures.
* The subject has a history of confirmed or active parasitic infection.
* The subject is unable to refrain from travelling to countries with a high prevalence of infectious (especially parasitic) disease from when the first dose is administered until the expected washout period is complete (plasma levels below LLQ) or the last follow-up visit, which ever is later
C: Inclusion Criteria:

Written informed consent for study participation must be obtained prior to any study related procedures being performed and according to international guidelines and/or applicable European Union (EU) guidelines.

* Female and male aged 18 to 75 years, inclusively, at the time of Visit 1.
* Weight of ≥40 kg.
* Evidence of asthma as documented by post-bronchodilator (post-BD) reversibility in FEV1 of ≥ 12% demonstrated at Visit 2.
* Documented use of 1 of the following types of asthma therapy at time of informed consent: Low- to medium-dose ICS (ie, 100 to 500 μg fluticasone dry powder formulation equivalents total daily dose) with or without other controller medications, eg, an LTRA and/or theophylline or Low-dose ICS/LABA fixed combination therapy (eg, the lowest regular maintenance dose approved in the local country will meet this criterion)
* Morning pre-bronchodilator (pre-BD) FEV1 of \> 50% to ≤ 90% predicted at Visit 2.

Exclusion Criteria:

* Clinically important pulmonary disease other than asthma (eg, active lung infection, COPD, bronchiectasis, pulmonary fibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, lung cancer, alpha 1 anti-trypsin deficiency, and primary ciliary dyskinesia) or ever been diagnosed with pulmonary or systemic disease, other than asthma, that are associated with elevated peripheral eosinophil counts (eg, allergic bronchopulmonary aspergillosis/mycosis, Churg-Strauss syndrome, hypereosinophilic syndrome).
* Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, 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
* nfluence the findings of the studies or their interpretations,- Impede the patient's ability to complete the entire duration of study.
* Known history of allergy or reaction to the investigational product formulation.
* History of anaphylaxis to any biologic therapy.- History of Guillain-Barré syndrome.
* 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.- Acute upper or lower respiratory infections requiring antibiotics or antiviral medication within 30 days prior to the date informed consent is obtained or during the screening/run-in period.
* Any clinically significant abnormal findings in physical examination, vital signs, hematology, clinical chemistry, or urinalysis during screening period, 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 the patient's ability to complete entire duration of the study.
* Positive hepatitis B surface antigen, or hepatitis C virus antibody serology, or a positive medical history for hepatitis B or C. Patients with a history of hepatitis B vaccination without history of hepatitis B are allowed to enroll.
* A history of known immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test.
* History of cancer:
* Patients who have had basal cell carcinoma, localized squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible provided that the patient is in remission and curative therapy was completed at least 12 months prior to the date informed consent was obtained.
* Patients who have had other malignancies are eligible provided that the patient is in remission and curative therapy was completed at least 5 years prior to the date informed consent was obtained
D: Inclusion Criteria:

1. The patient is male or female, 12 years of age and older, with a previous diagnosis of asthma.
2. Written informed consent is obtained.
3. The patient requires daily maintenance dose of prednisone or equivalent for asthma of between 5 and 40 mg during the 3 months prior to screening.
4. The patient has a documented elevated blood eosinophils at screening or during the previous 12 months.
5. The patient has required high dose ICS plus another asthma controller for at least 6 months prior to screening.
6. The patient has FEV1 reversibility to inhaled SABA or historical reversibility within the previous 24 months.

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

Exclusion Criteria:

1. The patient has any clinically significant, uncontrolled medical condition that would interfere with the study schedule or procedures and interpretation of efficacy results or would compromise the patient's safety.
2. The patient has another confounding underlying lung disorder.
3. The patient has a known hypereosinophilic syndrome.
4. The patient has a history of any malignancy within 5 years of the screening visit, except for treated and cured non-melanoma skin cancers.
5. The patient is pregnant or intends to become pregnant during the study or is lactating.
6. The patient required treatment for an asthma exacerbation within 4 weeks of screening.
7. The patient is a current smoker or has a smoking history ≥10 pack-years.
8. The patient is currently using any systemic immunosuppressive or immunomodulatory biologic except maintenance OCS for the treatment of asthma.
9. The patient participated in a clinical study within 30 days or 5 half-lives of the investigational drug before screening, whichever is longer.
10. The patient was previously exposed to benralizumab within 12 months of screening.
11. The patient was previously exposed to reslizumab.
12. The patient has a history of immunodeficiency disorder including human immunodeficiency virus.
13. The patient has current suspected drug and/or alcohol abuse.
14. The patient has had an active helminthic parasitic infection or was treated for one within 6 months of screening.
15. The patient has a history of allergic reactions or hypersensitivity to any component of the study drug.

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

Answer: C