Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of Lebrikizumab in Patients With Uncontrolled Asthma Who Are on Inhaled Corticosteroids and A Second Controller Medication
Brief Summary: This randomized, multicenter, double-blind, placebo-controlled, parallel-group study will assess the efficacy and safety of lebrikizumab in patients with asthma whose disease remains uncontrolled despite daily therapy with an inhaled corticosteroid and a second controller medication. Patients will be randomized in a 1:1:1:1 ratio to receive double-blind treatment with subcutaneous lebrikizumab ("highest", "middle", "lowest" dose) or placebo every 4 weeks for 52 weeks, in addition to their standard-of-care therapy. This will be followed by a 52-week double-blind active treatment extension. The anticipated time on study treatment is up to 104 weeks. There will be a safety follow-up of 24 weeks after the last dose of study drug for all patients.


Options:
A: 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
B: Inclusion Criteria:

* Able to give written informed consent prior to participation in the study
* At least 12 years of age at visit 1 and a minimum weight of 45 kilogram (kg)
* A well-documented requirement for regular treatment with high dose inhaled corticosteroid (ICS) in the 12 months prior to Visit 1 with or without maintenance oral corticosteroids (OCS)
* Current treatment with an additional controller medication, besides ICS, for at least 3 months or a documented failure in the past 12 months of an additional controller medication for at least 3 successive months
* Prior documentation of eosinophilic asthma or high likelihood of eosinophilic asthma
* At Visit 1, a pre-bronchodilator FEV1 \<80% (for subjects \>= 18 years of age), a pre-bronchodilator FEV1 \<90% or FEV1:FVC ratio \<0.8 (for subjects 12-17 years of age).
* Previously confirmed history of two or more exacerbations requiring treatment with systemic CS
* Male or Eligible Female (females of childbearing potential must commit to consistent and correct use of an acceptable method of birth control)
* French subjects will be included only if either affiliated to or a beneficiary of a social security category.

Exclusion Criteria:

* Current smokers or former smokers with a smoking history of \>=10 pack years
* Presence of a known pre-existing, clinically important lung condition other than asthma
* A current malignancy or previous history of malignancy in less than 12 months
* Known, pre-existing, unstable liver disease cirrhosis and known biliary abnormalities
* Known, pre-existing severe or clinically significant cardiovascular disease
* known, pre-existing other concurrent clinically significant medical conditions that are uncontrolled with standard treatment
* Subjects with any eosinophilic diseases
* QTc(F) ≥450msec or QTc(F) ≥480 msec
* A history of alcohol/substance abuse
* Subject with known immunodeficiency
* Subjects who have received omalizumab within 130 days of Visit 1 or any monoclonal antibody (other than Xolair) to treat inflammatory disease within 5 half-lives of Visit 1
* 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
* Subjects with allergy/intolerance to a monoclonal antibody or biologic.
* Subjects who are pregnant or breastfeeding
* Subjects who have known evidence of lack of adherence to controller medications and/or ability to follow physician's recommendations
* Previously participated in any study with mepolizumab and received investigational product (including placebo)
C: Inclusion Criteria:

Patients who met the following criteria were included:

* Males or females of any race, who were 12-75 years of age
* A body weight ≥ 20 kg and ≤ 150 kg and with a total serum IgE level ≥ 30 to ≤ 700 IU/ml
* A diagnosis of allergic asthma ≥ 1 year duration according to American Thoracic Society (ATS) criteria and at screening a history consistent with GINA (2204) step 3 or 4 clinical features
* A positive prick skin test (diameter of wheal \>= 3 mm) to at least one perennial allergen documented within the past 2 years or taken at visit 1
* Increase in FEV1 ≥12% over baseline value within 30 minutes of taking 2 to 4 puffs (2-4x100µg) salbutamol (albuterol) or nebulized salbutamol up to 5mg
* An FEV1 ≥ 40 and ≤ 80% of the predicted normal value for the patient at randomization
* Receiving moderate to high dose inhaled corticosteroid ≥ 800 µg BDP or equivalent and a regular inhaled long acting B-2 agonists for at least 3 months prior to screening and \> 1000 µg (BDP) and a LABA for at least 4 weeks during the run-in and at randomization
* Patients who have suffered multiple (i.e. at least two) independent documented severe asthma exacerbations while receiving high doses of ICS (≥ 800 µg BDP or equivalent) plus regular inhaled LABA
* Evidence of poor asthma control at screening (based on patient history) and for at least 4 weeks immediately prior to randomisation

Exclusion Criteria:

Patients who met the following criteria were excluded:

* Had received systemic corticosteroids for reasons other than asthma within 4 weeks of Visit 1
* A smoking history \>10 pack years
* An active lung disease other than allergic asthma
* Elevated serum IgE levels for reasons other than allergy
* Patients with significant underlying medical conditions
D: Inclusion Criteria:

1. Written informed consent 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 aged 12 to 75 years inclusively, at the time of visit 1. For those patients, who are 17 on the day of Visit 1 but will turn 18 after this day, will be considered an adolescent for the purposes of this trial.
3. History of physician-diagnosed asthma requiring treatment with medium-to-high dose ICS (\>250μg fluticasone dry powder formulation equivalents total daily dose) and a LABA, for at least 12 months prior to Visit 1
4. Documented treatment with ICS and LABA for at least 3 months prior to Visit 1 with or without oral corticosteroids and additional asthma controllers.

   * For subjects 18 years of age and older, the ICS dose must be \>500 mcg/day fluticasone propionate dry powder formulation or equivalent daily.
   * For subjects ages 12-17, the ICS dose must be ≥500 mcg /day fluticasone propionate dry powder formulation or equivalent daily.

Exclusion criteria:

1. Clinically important pulmonary disease other than asthma (e.g. 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 (e.g. allergic bronchopulmonary aspergillosis/mycosis, Churg- Strauss syndrome, hypereosinophilic syndrome)
2. 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
3. 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
4. Any clinically significant abnormal findings in physical examination, vital signs, haematology, clinical chemistry, or urinalysis during screening/run-in 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

Answer: A