Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase II, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study to Evaluate the Efficacy and Safety of MILR1444A in the Prevention of Allergen-Induced Airway Obstruction in Adults With Mild Allergic Asthma
Brief Summary: This is a multicenter, randomized, double-blind, placebo-controlled study designed to demonstrate the safety and efficacy of MILR1444A compared with placebo in reducing the airway reaction to an inhaled aeroallergen solution in adult patients with mild allergic asthma. The study will randomize approximately 24 patients at five study centers. In the event of patient discontinuation from the study, additional patients may be enrolled at the discretion of the Sponsor.


Options:
A: * INCLUSION CRITERIA:

A subject will be eligible for participation in the study only if all of the following criteria apply:

1. Male or female subject greater than or equal to18 and less than or equal to 75 years of age at screening.
2. A female subject is eligible for this study only if she is not pregnant or breast-feeding and one of the following:

   1. Of childbearing potential but agrees to practice effective contraception, as determined by the PI, or abstinence throughout the study and for 3 months after administration of the last dose of investigational study drug
   2. Of non-child-bearing potential

Females of non-child-bearing potential are defined as females with functioning ovaries with a documented history of tubal ligation or hysterectomy or females who are post-menopausal, as defined by 12 months of spontaneous amenorrhea with an appropriate clinical profile, e.g. age appropriate, \>45 years, in the absence of hormone replacement therapy. In questionable cases, a blood sample for follicle stimulating hormone and estradiol will be obtained to confirm child-bearing potential.

Acceptable methods of contraception may include one or more of the following:

1) male partner who is sterile prior to the female subject s entry into the study and is the sole sexual partner for the female subject; 2) implants of levonorgestrel; 3) injectable progestogen, 4) an intrauterine device with a documented failure rate of \<1%; and 5) double barrier methods including diaphragm or condom with a spermicide.

3) A male subject is eligible for this study only if he is one of the following:

1. Surgically sterile
2. Agrees to practice effective contraception (see above) or abstinence throughout the study and for 3 months after the last administration of the investigational study drug

   4) Documented diagnosis of HES (history of persistent eosinophilia \>1500/(micro) L without secondary cause and evidence of end organ manifestations attributable to the eosinophilia)

   5) Signs or symptoms of HES and AEC \>1000/(micro) L on stable HES therapy for greater than or equal to 1 month at the time of enrollment

   6) Participation in protocol 94-I-0079 (Activation and function of eosinophils in conditions with blood or tissue eosinophilia)

   7) Agrees to storage of samples for study

   Participation of Women:

   Contraception: The effects of benralizumab on the developing human fetus are unknown. For this reason, men and women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Females of childbearing-age must have a negative pregnancy test result prior to receiving benralizumab. During the course of the study, if a woman becomes pregnant or suspects she is pregnant, she should inform the study staff and her primary care physician immediately. If a subject becomes pregnant, the investigational drug will be discontinued immediately, and the subject will be counselled as to how to resume approved therapeutic options in consultation with an obstetric provider.

   EXCLUSION CRITERIA:

   A subject will be excluded from participation in the study if any of the following criteria apply at the time of enrollment:
   1. Subjects with life-threatening or other serious illness or clinical manifestation of HES deemed inappropriate for inclusion in study per the principal investigator, including but not restricted to severe cardiac involvement and prior thromboembolic disease.
   2. Human immunodeficiency virus (HIV) or other known immunodeficiency
   3. 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
   4. Presence of FIP1L1/PDGFRA or another known imatinib-sensitive mutation
   5. Diagnosis of systemic mastocytosis or serum tryptase level \>40 ng/mL
   6. Known lymphoma, hematological malignancy, advanced and metastatic solid tumors and/or subjects who are under chemotherapy, radiotherapy or interleukin 2 treatment
   7. Known history of allergic or anaphylactic reaction to previous antibody therapy, including intravenous immunoglobulin and licensed or experimental monoclonal antibodies.
   8. A helminth parasitic infection diagnosed within 24 weeks prior to the date informed consent is obtained
   9. Acute bacterial or viral infection (subjects may be enrolled once the acute infection has resolved).
   10. Receipt of intravenous immunoglobulin (IVIG) within 30 days prior to the date informed consent is obtained
   11. Receipt of any marketed (eg omalizumab) or investigational biologic within 4 months or 5 half-lives prior to the date informed consent is obtained, whichever is longer
   12. Receipt of live attenuated vaccines 30 days prior to the date of randomization
   13. Receipt of inactive/killed vaccinations (e.g. inactive influenza) are allowed provided they are not administered within 1 week before/after any study visit
   14. Receipt of any investigational nonbiologic within 30 days or 5 half-lives prior to the date informed consent is obtained, whichever is longer
   15. History of alcohol or drug abuse within 12 months prior to the date informed consent is obtained
   16. Previous treatment with benralizumab (MEDI-563).

   Co-enrollment Guidelines: Co-enrollment in other trials is restricted, other than enrollment on observational studies or those evaluating the use of a licensed medication. Study staff should be notified of co-enrollment as it may require the approval of the Investigator.

   Justification for Exclusion of Children:

   Because there are insufficient data regarding dosing or adverse events available in adults with HES to judge the potential risk in children, children are excluded from this study.
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:

* The patient is male or female, 12 through 75 years of age, with a previous diagnosis of asthma.
* 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 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 of 10 mg of prednisone daily or equivalent, leukotriene antagonists, 5-lipooxygenase inhibitors, or cromolyn) must be stable for 30 days prior to screening and baseline, and must continue without dosage changes throughout 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.
* Written informed consent is obtained. Patients 12 through 17 years old 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.

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

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 or immunomodulating or other biologic agents (including, but not limited to, anti-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.
* Female patients who are pregnant, nursing, or, if of childbearing potential, and not using a medically accepted, effective method of birth control (eg, barrier method with spermicide, abstinence, IUD, or steroidal contraceptive \[oral, transdermal, implanted, and injected\]) are excluded from this study. NOTE: Partner sterility alone is not considered an acceptable form of birth control.

  * Other criteria apply; please contact the investigator for more information.
D: Inclusion Criteria:

* Signed Informed Consent Form and an informed assent, if applicable
* Be between the ages of 12 to 75 years
* Have had a history of moderate to severe asthma for at least one year prior to screening
* Have had treatment with a stable regimen of of salmeterol 50 µg twice a day (BID) or formoterol 12 µg BID for at least 8 weeks prior to screening
* Have had treatment with a stable regimen of high-dose inhaled corticosteroids (ICS) for at least 8 weeks prior to screening
* Have inadequately controlled asthma
* Have had at least one asthma exacerbation requiring systemic corticosteroid rescue in the 12 months prior to the screening visit while receiving treatment with high-dose ICS
* Have less than 10 pack-years smoking history
* Have a positive skin test for or a positive, in vitro response to one relevant perennial aeroallergen documented within the 12 months prior to screening
* If a subject has not had a positive skin test or in vitro reactivity in the 12 months prior to screening, the subject must demonstrate a positive response to at least one relevant perennial aeroallergen in a skin or in vitro test prior to randomization
* Female subjects of childbearing potential must use an effective method of contraception from screening through their duration of participation in the study
* For the collection of additional blood samples for future research (optional), provide signed consent and an informed assent, if applicable.

Exclusion Criteria:

* Have had an asthma exacerbation requiring intubation within 12 months prior to screening
* Have active lung disease other than asthma
* Have had an asthma exacerbation requiring treatment with the addition of systemic (oral or intravenous) corticosteroids or an increase in systemic corticosteroids within 30 days prior to screening
* Require chronic immunosuppressive therapy including cyclosporine, methotrexate, etc.
* Have significant medical illness other than asthma
* Have taken methotrexate, gold salts, cyclosporine, or macrolide antibiotics, within 3 months prior to screening
* Have taken other investigational drugs within 30 days prior to screening
* Have been treated with Xolair within the 12 months prior to screening
* Have a history of drug or alcohol abuse that, in the judgment of the investigator, may put the subject at risk for being unable to participate fully in the study for the duration of the study
* Have elevated serum IgE levels for reasons other than allergy
* Are pregnant or lactating

Answer: B