Inclusion Criteria

• At least 12 years of age
  • For those countries where local regulations permit enrollment of adults only, participant recruitment will be restricted to those who are ≥18 years of age
• Signed informed consent/assent
• A well-documented requirement for regular treatment with high dose inhaled corticosteroid in the 12 months prior to visit 1 with or without maintenance oral corticosteroids
  • For participants ≥18 years old ICS dose must be ≥ 880 mcg/day fluticasone propionate (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
• 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)
• Prior documentation of eosinophilic asthma or high likelihood of eosinophilic asthma as per randomization criteria
• For participants ≥18 years of age at visit 1 persistent airflow obstruction as indicated by 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
• Previously confirmed history of two or more exacerbations requiring treatment with systemic corticosteroid (intramuscular, intravenous, or oral) in the 12 months prior to visit 1, despite the use of high-dose inhaled corticosteroids
  • For participants receiving maintenance corticosteroid, the corticosteroid treatment for the exacerbations must have been a two-fold dose increase or greater
• Male or Eligible Female
  • To be eligible 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
• 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
• 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

• 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
• 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
• 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
• 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
• Participants who have severe or clinically significant cardiovascular disease uncontrolled with standard treatment including but not limited to 
  • Known ejection fraction of <30% 
  • Severe heart failure meeting New York Heart Association Class IV classification 
  • Hospitalized in the 12 months prior to visit 1 for severe heart failure meeting New York Heart Association Class III 
  • Angina diagnosed less than 3 months prior to or at visit 1
• Participants who have a known, pre-existing, clinically significant endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, hematological or any other system abnormality that is uncontrolled with standard treatment
• Participants with other conditions that could lead to elevated eosinophils such as Hypereosinophilic Syndromes, including Churg-Strauss Syndrome (Eosinophilic Granulomatosis with Polyangiitis), or Eosinophilic Esophagitis
• Participants with a known, pre-existing parasitic infestation within 6 months prior to visit 1
• 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
• A history or suspected history of alcohol misuse or substance abuse within 2 years prior to visit 1
• A known immunodeficiency (e.g. human immunodeficiency virus [HIV]), other than that explained by the use of corticosteroids taken as therapy for asthma
• Participants who have received omalizumab (Xolair) within 130 days of visit 1
• Participants who have received any monoclonal antibody (other than Xolair) to treat inflammatory disease within 5 half-lives of visit 1
• 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)
• Participants with allergy/intolerance to a monoclonal antibody or biologic
• 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 the protocol
• Participants 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)