Primary objective of the study is to evaluate whether patients with severe eosinophilic asthma who have received long-term treatment with mepolizumab (at least 3 years) need to maintain treatment with mepolizumab to continue to receive benefit. Subjects who participated in the open-label studies MEA115666 or 201312 with at least 6 months of treatment with mepolizumab prior to Visit 1 and who have no more than 2 consecutive missed doses of mepolizumab treatment will be eligible to participate in this study. This study will be conducted in 4 parts in approximately 300 subjects. Part A will be Variable Open-Label Run-in (for subjects with less than 3 years of mepolizumab treatment). Once the required 3 year exposure is reached, subjects will enter Part B- Fixed Open-Label Run-In (4 weeks to 8 weeks). During Part A and B subjects will be administered Open-label mepolizumab (100 milligram [mg] Subcutaneous [SC]) every 4 weeks. Part C will be the randomized double-blinded part. Upon completion of Part B, eligible subjects will be randomized to mepolizumab (100 mg SC) every 4 weeks or placebo administered SC every 4 weeks for 52 weeks.

Subjects discontinuing investigational product (IP) due to a clinically significant asthma exacerbation will then enter optional Part D of the study. During Part D, subjects receive open-label mepolizumab in addition to their standard of care therapy for the remainder of the study, through Part D up to 52-weeks post-randomization. An Exit Visit will be conducted 52 weeks after randomization in order to assess subject's efficacy parameters, immunogenicity status, and to conduct additional safety assessments. Eligible subjects will participate in the study ranging from 56 to192 weeks, depending on the duration of Part A (0 to 132 weeks) and Part B (4 to 8 weeks).

Inclusion Criteria:

• Informed Consent: Prior to commencing any study related activities, subjects must be able and willing to provide written informed consent, and an assent for subjects under 18 years of age, at Visit 0 (or Visit 1 if these Visits are conducted on the same day).
• MEA115666 or 201312 Study Participation: Participation (through the Follow Up/Exit Visit or Early Withdrawal) in either study with documented evidence of at least 6 months of continuous mepolizumab treatment prior to Visit 1. Continuous treatment with mepolizumab is defined as no more than 2 consecutive missed doses (no treatment gaps of more than 12 weeks [84 days] between any two doses).
• Current Anti-Asthma Therapy: Asthma is currently being treated with a controller medication and the subject has been on a controller medication for the past 12 weeks. Subjects will be expected to continue controller therapy for the duration of the study.
• Male or Eligible Female Subjects: A female is eligible to enter and participate in the study if she is of: Non-child bearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal or surgically sterile). Surgically sterile females are defined as those with a documented hysterectomy and/or bilateral oophorectomy or tubal ligation. Post-menopausal females are defined as being amenorrhoeic for greater than 1 year with an appropriate clinical profile, e.g., age appropriate, > 45 years, in the absence of hormone replacement therapy.

OR Child bearing potential, has a negative pregnancy test at screening, and agrees to acceptable contraceptive methods approved in their local country, when used consistently and correctly (i.e., in accordance with the approved product label and the instructions of the physician) for the duration of the study and for 4 months after the last study drug administration.

A urine pregnancy test is required of all females of child-bearing potential at each scheduled study visit prior to the injection of study treatment, and at the Exit Visit, Early Withdrawal (EW) or Discontinuation of IP Visit.

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

Exclusion Criteria:

• MEA115666 or 201312 IP Discontinuation: Subjects withdrawn from IP or withdrawn from study participation from either MEA115666 or 201312 for safety reasons.
• Health Status: Clinically significant deterioration in health status at the completion of participation or EW from either the MEA115666 or 201312 trials which in the opinion of the investigator would make the subject unsuitable for participation in this study.
• Pregnancy: Subjects who are pregnant or breastfeeding. Subjects should not be enrolled if they plan to become pregnant during the time of study participation.
• Cardiovascular: Subjects who have severe or clinically significant cardiovascular disease uncontrolled with standard treatment. Including but not limited to:

known ejection fraction of <30% OR severe heart failure meeting New York Heart Association Class IV classification OR hospitalised in the 12 months prior to Visit 1 for severe heart failure meeting New York Heart Association Class III OR angina diagnosed less than 3 months prior to Visit 1 or at Visit 1.

• 12-Lead Electrocardiogram (ECG): ECG which has a clinically significant abnormality observed at the Screening Visit as determined by the investigator. Subjects with the following abnormalities are excluded from study participation: QT interval corrected for heart rate by Fridericia's formula (QTcF) > 450 milliseconds (msec), or QTcF >480 msec for subjects with Bundle Branch Block.
• Malignancy: A current malignancy or previous history of cancer in remission for less than 12 months prior to screening (Subjects that had localized carcinoma of the skin which was resected for cure will not be excluded).

Note for South Korea: Korean subjects with a diagnosis of malignancy within 5 years are excluded.

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

XOLAIR is a registered trademark of Genentech USA, Inc. and Novartis Pharmaceuticals Corporation.

• Adherence: Subjects who have known evidence of lack of adherence within studies MEA115666 or 201312 (less than 80%) to controller medications, scheduled study visits and/or ability to follow physician's recommendations.
• Smoking status: Current smokers
• Inability to read: In the opinion of the Investigator, any subject who is unable to read and/or would not be able to complete a questionnaire.

IPD for this study will be made available via the Clinical Study Data Request site.

IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.

Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.