Efficacy and Safety Study of Mepolizumab Adjunctive Therapy in Participants With Severe Eosinophilic Asthma on Markers of Asthma Control
Efficacy and Safety Study of Mepolizumab Adjunctive Therapy in Participants With Severe Eosinophilic Asthma on Markers of Asthma Control
This is a multi-centre, placebo-controlled, double-blind, parallel-group study to evaluate
 the efficacy and safety of mepolizumab adjunctive therapy in participants with severe
 eosinophilic asthma on markers of asthma control. The overall intent of the current study is
 to more fully explore the impact of mepolizumab on health-related quality of life (HR-QoL)
 and other measures of asthma control, including lung function.

 Participants who meet the predefined criteria will be randomised to receive either
 mepolizumab or placebo in addition to standard of care asthma treatment. Approximately 780
 participants with severe eosinophilic asthma will be screened to ensure the randomisation of
 544 participants (272 participants per treatment group) into the study.
Inclusion Criteria:

 -  Age: At least 12 years of age at the time of signing the informed consent/assent (For
 those countries where local regulations permit enrolment of adults only, participant
 recruitment will be restricted to those who are >=18 years of age)

 -  Inhaled Corticosteroid: 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). For participants >=18 years old: ICS dose must
 be >=880 micrograms (mcg)/day fluticasone propionate (FP) (exactuator) or equivalent
 daily. For ICS/long-acting beta-2-agonist (LABA) combination preparations, the highest
 approved maintenance dose in the local country will meet this ICS criterion. For
 participants >=12 to <=17 years old: ICS dose must be >=440 mcg/day FP (ex-actuator)
 or equivalent daily. For ICS/LABA combination preparations, the mid-strength approved
 maintenance dose in the local country will meet this ICS criterion

 -  Controller Medication: 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 (e.g. LABA,
 leukotriene receptor antagonist [LTRA], or theophylline)

 -  Eosinophilic asthma: Prior documentation of eosinophilic asthma or high likelihood of
 eosinophilic asthma as per Randomisation Criteria 1 and 2

 -  FEV1: Persistent airflow obstruction as indicated by : For participants >=18 years of
 age at visit 1, a pre-bronchodilator FEV1 <80% predicted (National Health and
 Nutrition Examination Survey [NHANES III]) recorded at Visit 1. For participants 12-17
 years of age at Visit 1: A pre-bronchodilator FEV1 <90% predicted (NHANES III)
 recorded at Visit 1 OR FEV1:FVC ratio <0.8 recorded at Visit 1

 -  Exacerbation history: Previously confirmed history of two or more exacerbations
 requiring treatment with systemic Corticosteroid (CS) (intramuscular, intravenous, or
 oral), in the 12 months prior to visit 1, despite the use of high-dose inhaled
 corticosteroids (ICS). For participants receiving maintenance CS, the CS treatment for
 the exacerbations must have been a two-fold dose increase or greater.

 -  Gender: Male or Eligible Female. To be eligible for entry into the study, females of
 childbearing potential must commit to consistent and correct use of an acceptable
 method of birth control listed in the protocol for the duration of the trial and for 4
 months after the last study drug administration.

 -  Informed Consent/Assent: Able to give written informed consent/assent prior to
 participation in the core study, which will include the ability to comply with the
 requirements and restrictions listed in the consent/assent form and in this protocol.
 Participants must be able to read, comprehend, and write at a level sufficient to
 complete study related materials. Written informed consent must be obtained from ALL
 patients/legally authorized representative(s); for patients 12-17 years old, written
 informed assent must be obtained in addition to the legally authorized
 representative(s)' consent.

 -  French participants: In France, a participant will be eligible for inclusion in this
 study only if either affiliated to or a beneficiary of a social security category.

 Exclusion Criteria:

 -  Smoking history: Current smokers or former smokers with a smoking history of >=10 pack
 years (number of pack years = (number of cigarettes per day/20) x number of years
 smoked). A former smoker is defined as a participant who quit smoking at least 6
 months prior to Visit 1.

 -  Concurrent Respiratory Disease: Presence of a known pre-existing, clinically important
 lung condition other than asthma. This includes current infection, bronchiectasis,
 pulmonary fibrosis, bronchopulmonary aspergillosis, or diagnoses of emphysema or
 chronic bronchitis (chronic obstructive pulmonary disease other than asthma) or a
 history of lung cancer.

 -  Malignancy: A current malignancy or previous history of cancer in remission for less
 than 12 months prior to screening (Participants that had localized carcinoma of the
 skin which was resected for cure will not be excluded).

 -  Liver Disease: Known, pre-existing, unstable liver disease (as defined by the presence
 of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric
 varices or persistent jaundice), cirrhosis, and known biliary abnormalities (with the
 exception of Gilbert's syndrome or asymptomatic gallstones).

 -  Cardiovascular: Participants who have severe or clinically significant cardiovascular
 disease uncontrolled with standard treatment. Including but not limited to: (a) known
 ejection fraction of <30% OR (b) severe heart failure meeting New York Heart
 Association Class IV classification OR (c) hospitalised in the 12 months prior to
 Visit 1 for severe heart failure meeting New York Heart Association Class III OR (d)
 angina diagnosed less than 3 months prior to Visit 1 or at Visit 1.

 -  Other Concurrent Medical Conditions: Participants 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: Participants with other conditions that could lead to elevated
 eosinophils such as Hypereosinophilic Syndromes, including Churg-Strauss Syndrome
 (Eosinophilic Granulomatosis with Polyangiitis [EGPA]), or Eosinophilic Esophagitis.
 Participants with a known, pre-existing parasitic infestation within 6 months prior to
 Visit 1 are also to be excluded.

 -  Electrocardiogram (ECG) Assessment: QT interval corrected for heart rate by
 Fridericia's formula (QTc(F)) >=450 milliseconds (msec) or QTc(F) >=480 msec for
 participants with Bundle Branch Block at Visit 1.

 -  Alcohol/Substance Abuse: A history (or suspected history) of alcohol misuse or
 substance abuse within 2 years prior to Visit 1.

 -  Immunodeficiency: A known immunodeficiency (e.g. human immunodeficiency virus [HIV]),
 other than that explained by the use of corticosteroids taken as therapy for asthma.

 -  Xolair: Participants who have received omalizumab (Xolair) within 130 days of Visit 1.

 -  Other Monoclonal Antibodies: Participants who have received any monoclonal antibody
 (other than Xolair) to treat inflammatory disease within 5 half-lives of Visit 1.

 -  Investigational Medications: Participants 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: Participants with allergy/intolerance to a monoclonal antibody or
 biologic.

 -  Pregnancy: Participants who are pregnant or breastfeeding. Patients should not be
 enrolled if they plan to become pregnant during the time of study participation. A
 urine pregnancy test is required of all women of child bearing potential. This test
 will be performed at the time points specified in the Time and Events Schedule in
 protocol.

 -  Adherence: Participants who have known evidence of lack of adherence to controller
 medications and/or ability to follow physician's recommendations.

 -  Previous participation: Previously participated in any study with mepolizumab and
 received investigational product (including placebo)