Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 1, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability and Effects of MEDI-563, A Humanized Anti-Interleukin-5 Receptor Alpha Monoclonal Antibody, on Airway Eosinophils in Adults With Atopic Asthma
Brief Summary: Evaluate the safety and tolerability of MEDI-563 in adults with asthma and the effects of MEDI-563 on eosinophil counts in airway mucosal biopsies


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 Argentina.
* The patient has an ACQ score of at least 1.5.
* The patient has airway reversibility of at least 12% to beta-agonist administration at screening.
* 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.
* The patient has a blood eosinophil count of at least 400/μL.
* Female patients must be surgically sterile, 2 years postmenopausal, or must have a negative pregnancy test ßHCG 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 the end-of-treatment visit. 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. Patients 12 through 17 years old, where participating, need to provide assent in accordance with local standards.
* Other inclusion criteria apply.

Exclusion Criteria:

* 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 has another confounding underlying lung disorder (eg, chronic obstructive pulmonary disease, pulmonary fibrosis, or lung cancer). The patient has other pulmonary conditions with symptoms of asthma and blood eosinophilia (eg, Churg-Strauss syndrome, allergic bronchopulmonary aspergillosis).
* 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-IgE mAb, methotrexate, cyclosporin, interferon-α, or anti-tumor necrosis factor mAb) within 6 months prior to study entry (screening).
* The patient is currently using systemic corticosteroids (includes use of oral corticosteroids).
* The patient has a current infection or disease that may preclude assessment of asthma.
* 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 (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 anti-hIL-5 monoclonal antibody (eg, mepolizumab).
* Female patients who are pregnant, or nursing, or, if of childbearing potential and not using a medically accepted, effective method of birth control (e.g. spermicide, abstinence, IUD, or steroidal contraceptive \[oral, transdermal, implanted, and injected\]) are excluded from this 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). Patients in Argentina must have documented serology testing for HIV performed during screening.
* Other exclusion criteria apply.
B: Inclusion Criteria:

* Male or female adults, 18 through 65 years of age at time of randomization;
* Written informed consent obtained from the subject prior to beginning study procedures or receipt of any study medication;
* Previously documented diagnosis of asthma of ≥ 1 year duration, based on episodic symptoms of airflow obstruction; post-bronchodilator reversibility of airflow obstruction ≥ 12% (in USA only - if subject does not achieve this during screening, proof of ≥12% reversibility within 1 year of randomization is acceptable) or proof of a positive response to a methacholine challenge during screening with prior approval from MedImmune (in USA only - within 1 year of randomization is acceptable) as represented by a provoking concentration of methacholine to cause a 20% fall in FEV1 (PC20) \< 8 mg/ml \[American Thoracic Society (ATS), 2000)\]; and exclusion of alternative pulmonary diagnoses (eg, cystic fibrosis, COPD);
* Asthma symptoms are adequately controlled on a therapeutic regimen that has not changed in the last 4 weeks prior to Study Day 0, and the subject is willing to maintain the same therapeutic regimen and doses from the time of screening to the time of the first follow-up bronchoscopy with airway mucosal biopsies (Study Day 28 for Cohort 1; Study Day 84 for Cohort 2);
* Pre-bronchodilator FEV1/forced vital capacity (FVC) ratio that is below the age-adjusted normal limit as defined by the 2007 National Heart Lung and Blood Institute Asthma guidelines (Appendix D) and post-bronchodilator FEV1 ≥ 65% at screening;
* Must have ≥ 2.5% eosinophils in sputum;
* Have had no hospitalizations due to asthma in the last year prior to screening;
* Women of childbearing potential, unless surgically sterile or at least 1 year post-menopausal, must use 2 effective methods of avoiding pregnancy
* Able to complete the follow-up period as required by the protocol;
* Willing to forego other forms of experimental treatment and study procedures during the study and during an 84-day period after the last dose of study drug;
* Able to provide spirometric readings that meet ATS standards

Exclusion Criteria:

* Participation in any previous MEDI-563 clinical study;
* Known history of allergy or adverse reactions to any component of the study drug formulation;
* Lung disease other than asthma (eg, COPD, cystic fibrosis, eosinophilic pneumonia);
* Current use of any systemic or inhaled immunosuppressive drugs \[oral (up to a maximum dose of 10 mg/day or 20 mg every other day) and inhaled corticosteroids are allowed if dose has been stable for at least 4 weeks prior to study drug administration on Study Day 0\].
* Current use of any β-blocker (eg, propranolol);
* Acute illnesses or evidence of clinically significant active infection, such as fever ≥ 38.0ºC (100.5ºF) at screening and through the time of the study drug administration on Study Day 0;
* Receipt of any investigational drug therapy, intravenous immunoglobulin (IVIG), or monoclonal therapy (eg, Xolair) within 30 days or within 5-half lives prior to study drug administration on Study Day 0 through End of Study/Study Termination (Study Day 84 for Cohort 1 or Study Day 140 for Cohort 2);
* Pregnancy (women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test prior to study drug administration on Study Day 0);
* Breastfeeding or lactating;
* History of alcohol or drug abuse \< 1 year prior to Study Day 0;
* History of cancer, apart from basal cell carcinoma or in situ carcinoma of the cervix treated with apparent success with curative therapy \> 1 year prior to Study Day 0;
* History of a previous episode of active TB or a positive TB skin test without completion of an appropriate course of treatment;
* A history of coagulation disorders that would contraindicate mucosal biopsies;
* History of immunodeficiency or infection with HIV-1, HIV-2, or hepatitis A, B, or C virus;
* History of use of tobacco products within 2 years of baseline (Study Day 0) or history of smoking ≥ 10 pack-years;
* Elective surgery planned from the time of screening through first follow-up bronchoscopy with airway mucosal biopsies (Study Day 28 or Study Day 84, as applicable);
* Evidence of any systemic disease or respiratory disease (other than asthma), history of any disease, or any finding upon physical examination, screening laboratory test, chest X-ray (CXR), or ECG that, in the opinion of the investigator or medical monitor, may compromise the safety of the subject in the study or confound the analysis of the study results;
* Any employee of the research site who is involved with the conduct of the study;
* History of lidocaine allergy
C: Inclusion Criteria:

* Informed Consent and Study Compliance: Subjects must be able to give written informed consent prior to participation in the study, which will include the ability to comply with the requirements and restrictions listed in the consent form.
* Systemic Corticosteroids: Requirement for regular treatment with maintenance systemic corticosteroids in the 6 months prior to Visit 1 and using a stable oral corticosteroid dose for 4 weeks prior to Visit 1. Subjects must be taking 5.0 to 35 mg/day of prednisone or equivalent at Visit 1 and must agree to switch to study required prednisone/prednisolone as their oral corticosteroid and use it per protocol for the duration of the study.
* Inhaled Corticosteroids: Requirement for regular treatment with high dose inhaled corticosteroid in the 6 months prior to Visit 1. For 18 years of age and older: inhaled corticosteroid (ICS) dose must be \>=880 microgram (µg)/day fluticasone propionate (FP) (ex-actuator) or equivalent daily. For ICS/ long acting beta2 agonist (LABA) combination preparations, the highest approved maintenance dose in the local country will meet this ICS criterion. For ages 12 to 17: ICS dose must be \>=440 μg/day FP (ex-actuator) or equivalent daily.
* Controller Medication: Current treatment with an additional controller medication for at least 3 months OR documentation of having used and failed an additional controller medication for at least 3 successive months during the prior 12 months \[e.g., LABA, leukotriene receptor antagonist (LTRA), or theophylline\].
* Eosinophilic Asthma: Prior documentation of eosinophilic asthma or high likelihood of eosinophilic asthma.
* FEV1: Persistent airflow obstruction as indicated by a pre-bronchodilator FEV1 \<80% predicted.
* Asthma: Evidence of asthma indicated by airway reversibility, hyperresponsiveness or airway variability.

Exclusion Criteria:

* Smoking history: Current smokers or former smokers with a smoking history of \>=10 pack years.
* Concurrent Respiratory Disease: Presence of a clinically important lung condition other than asthma.
* Malignancy: A current malignancy or previous history of cancer in remission for less than 12 months prior screening
* Liver Disease: Unstable liver disease
* Cardiovascular: Subjects who have severe or clinically significant cardiovascular disease uncontrolled with standard treatment.
* Other Concurrent Medical Conditions: Subjects who have known, pre-existing, clinically significant endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, haematological or any other system abnormalities that are uncontrolled with standard treatment.
* Eosinophilic Diseases: Subjects with other conditions that could lead to elevated eosinophils such as Hypereosiniophilic Syndromes, including Churg-Strauss Syndrome, or Eosinophilic Esophaghitis. Subjects with a known, pre-existing parasitic infestation within 6 months prior to Visit 1 are also to be excluded.
* ECG: ECG assessment QTcF \>=450 milliseconds (msec) or QTcF \>= 480 msec for subjects with Bundle Branch Block.
* Immunodeficiency: A known immunodeficiency (e.g. human immunodeficiency virus - HIV), other than that explained by the use of corticosteroids taken as therapy for asthma.
* Omalizumab Use: Subjects who have received omalizumab \[Xolair\] within 130 days of Visit 1.
* Other Monoclonal Antibodies: Subjects who have received any monoclonal antibody (other than Xolair) to treat inflammatory disease within 5 half-lives of Visit 1.
* Investigational Medications: 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, prior to Visit 1 (this also includes investigational formulations of marketed products).
* Hypersensitivity: Subjects with a known allergy or intolerance to a monoclonal antibody or biologic.
* Pregnancy: Subjects who are pregnant or breastfeeding. Patients should not be enrolled if they plan to become pregnant during the time of study participation.
* Alcohol/Substance Abuse: A history (or suspected history) of alcohol misuse or substance abuse within 2 years prior to Visit 1.
* Adherence: Subjects who have known evidence of lack of adherence to controller medications and/or ability to follow physician's recommendations.
* Previous participation: Subjects who have previously any study of mepolizumab and received Investigational Product.
D: Inclusion Criteria:

* Adult patients, 18 to 75 years of age at Visit 1
* Asthma diagnosis for \>/= 12 months prior to the start of screening (Visit 1)
* Bronchodilator response during screening
* Pre-bronchodilator FEV1 40%-80% of predicted during screening
* On ICS (inhaled corticosteroids) 500-2000 mcg/day of fluticasone propionate DPI or equivalent for \>/= 6 months prior to the start of screening (Visit 1) with no anticipated changes throughout the study
* On an eligible second controller medication (LABA, LAMA, LTRA or theophylline within the prescribed dosing range)
* Uncontrolled asthma as defined by protocol both during screening period and at time of randomization
* Chest X-ray or computed tomography (CT) scan obtained within 12 months prior to screening or chest X-ray during screening period confirming the absence of other lung disease
* Demonstrated adherence with controller medication during the screening period

Exclusion Criteria:

* History of severe allergic or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of the lebrikizumab injection
* Use of zileuton or roflumilast within 6 months prior to screening
* Maintenance oral corticosteroid therapy, defined as daily or alternate day oral corticosteroid maintenance therapy within the 3 months prior to Visit 1
* Treatment with systemic (oral, intravenous or intramuscular) corticosteroids within the 4 weeks prior to Visit 1
* Major episode of infection within 4 weeks prior to Visit 1 or treatment with oral antibiotics within 2 weeks prior to Visit 1
* Active parasitic infection within the 6 months prior to Visit 1
* Active tuberculosis requiring treatment within the 12 months prior to Visit 1
* Known immunodeficiency, including, but not limited to, HIV infection
* Evidence of acute or chronic hepatitis or known liver cirrhosis
* History of cystic fibrosis, chronic obstructive pulmonary disease, and/or other clinically significant lung disease other than asthma
* Known malignancy or current evaluation for a potential malignancy
* Current smoker or former smoker with a history \>10 pack years
* History of alcohol, drug or chemical abuse
* Initiation or change in allergen immunotherapy within 3 months prior to Visit 1
* Use of biologic therapy including omalizumab during 6 months prior to Visit 1
* Receipt of live/attenuated vaccine within 4 weeks prior to Visit 1
* Pregnant or lactating women
* Body mass index (BMI) \> 38 kg/m2
* Body weight \< 40 kg

Answer: B