Study in Pediatrics With HypEREosinophilic Syndrome (SPHERE)

Inclusion Criteria: * Participant must be aged 6 to 17 years inclusive, at Screening (Visit 1). * Participants who have been diagnosed with HES for at least 6 months prior to enrolment (Visit 2). * A history of 2 or more HES flares within the past 12 months prior to Screening (Visit 1). * Participants must have blood eosinophil count \>=1000 cells per microliter (/mcL) present at Screening. * Participants must be on a stable dose of HES therapy for the 4 weeks prior to the first dose of mepolizumab (Visit 2) * Male and/or female * Signed written informed consent Exclusion Criteria: * Life-threatening HES or life-threatening HES co-morbidities * Other concurrent medical conditions that may affect the participant's safety * Eosinophilia of unknown significance * Fusion tyrosine kinase gene translocation \[FIP1L1- Platelet-derived Growth Factor Receptor (PDGFRα) (F/P)\] positivity * Clinical diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA) * Participants with chronic or ongoing active infections requiring systemic treatment, as well as participants who have experienced clinically significant infections due to viruses, bacteria, and fungi within 4 weeks prior to enrolment (Visit 2) * Participants with a pre-existing parasitic infestation within 6 months prior to enrolment (Visit 2) * Participants with a known immunodeficiency (e.g. Human immunodeficiency virus \[HIV\]), other than that explained by the use of OCS or other therapy taken for HES * Participants with documented history of any clinically significant cardiac damage prior to Screening (Visit 1) that, in the opinion of the investigator, would impact the participant's participation during the study * Participants with a history of or current lymphoma, Participants with current malignancy or previous history of cancer in remission for less than 12 months prior to Screening (Visit 1) * Participants who are not responsive to OCS based on clinical response or blood eosinophil counts. * Participants who have previously received mepolizumab in the 4 months prior to enrolment (Visit 2) * Participants receiving non-oral systemic corticosteroids in the 4-week period prior to enrolment (Visit 2). * Participants who have received any other monoclonal antibodies within 30 days or 5 half-lives, whichever is longer, of enrolment (Visit 2). * Participants who have received treatment with an investigational agent (biologic or non-biologic) within the past 30 days or 5 drug half-lives, whichever is longer, prior to enrolment (Visit 2). * Use of candidate Coronavirus disease 2019 (COVID-19) vaccines that have not received limited, accelerated, or full authorization/approval, and are only in use as part of a clinical trial. * Participants who are currently participating in any other interventional clinical study * Participants with any history of hypersensitivity to any monoclonal antibody (including mepolizumab). * Evidence of clinically significant abnormality in the hematological, biochemical, or urinalysis screen from the sample collected at Screening (Visit 1), that could put the participant's safety at risk by participating in the study, as judged by the investigator