Efficacy and Safety Study of Mepolizumab Adjunctive Therapy in Participants With Severe Eosinophilic Asthma on Markers of Asthma Control

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)