A Phase 3, 52-week, open-label, single arm study to investigate the efficacy and safety of mepolizumab SC in participants aged 6 to 17 years with hypereosinophilic syndrome.

Age:
1. Participant must be aged 6 to 17 years inclusive, at Screening (Visit 1);

Type of Participant and Disease Characteristics:
2. Participants who have been diagnosed with HES for at least 6 months prior to
enrolment (Visit 2);
3. A history of 2 or more HES flares within the past 12 months prior to
Screening (Visit 1);
4. Participants must have blood eosinophil count >=1000 cells/µL present at
Screening;
5. Participants must be on a stable dose of HES therapy for the 4 weeks prior
to the first dose of mepolizumab (Visit 2);

Sex and Contraceptive/Barrier Requirements:
6. Male and/or female [(according to their reproductive organs and functions
assigned by chromosomal complement)] [FDA, 2016].
• Contraception and barriers as well as pregnancy testing is required as
appropriate for the age and sexual activity of paediatric participants and as
required by local regulations.
A female participant is eligible to participate if she is either:
• Premenarcheal or
• Not pregnant as confirmed by a negative urine (or serum if required by local
regulations) human chorionic gonadotrophin [hCG] test if of reproductive
potential.
Females of childbearing potential must commit to consistent and correct use of
an acceptable method of contraception (see Section 10.4, Appendix 4 of the
study protocol) for the duration of the trial and 16weeks after the last dose
of investigational product. A urine pregnancy test is required of females of
childbearing potential.

Informed Consent and Assent
7. The investigator, or a person designated by the investigator, will obtain
written informed consent from each study participant's (legal guardian as
defined in Section 10.1.3 of the study protoocol) and the participant's assent,
when applicable, before any study-specific activity is performed (unless a
waiver of informed consent has been granted by an Institutional Review Board
[IRB]/Ethics Committee [EC]). All legal guardians should be fully informed, and
participants should be informed to the fullest extent possible, about the study
in language and terms they are able to understand.
8. The participant capable of providing signed and dated written assent signs
and dates a written assent form (age appropriate) and the parent/guardian signs
and dates a written informed consent form (ICF) for study participation prior
to the initiation of any study-related activities.

Other
9. A legal guardian or primary caregiver must be available to help the
study-site personnel ensure follow-up; support the participant to attended
assessment days according to the SoA (e.g., able to comply with scheduled
visits, treatment plan, laboratory tests, and other study procedures);
consistently and consecutively be available to provide information on the
participant using the rating scales during the scheduled study visits;
accurately and reliably dispense study intervention as directed.

Medical Conditions:
1. Life-threatening HES or life-threatening HES co-morbidities:
Imminently life threatening HES disease severity such that (a) likelihood of
death is high unless the course of the disease is interrupted within 12 weeks
prior to Visit 2 (b) likelihood of severe deterioration of HES is high unless
immediate therapeutic intervention is provided.
2. Other concurrent medical conditions that may affect the participant's safety:
Participants who have known, pre-existing, clinically significant endocrine,
autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic,
haematological, respiratory, or any other system abnormalities that are not
associated with HES and are uncontrolled with standard
treatment.
3. Eosinophilia of unknown significance
4. FIP1L1-PDGFRα (F/P) Status: Participants who test positive for F/P
5. Clinical diagnosis of EGPA
6. Infection:
• 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).
7. Participants with a known immunodeficiency (e.g., HIV), other than that
explained by the use of OCS or other therapy taken for HES.
8. 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.
9. Malignancy:
• 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 that had localised carcinoma (i.e., basal or squamous cell) of the
skin that was resected for cure will not be excluded.
10. Participants who are not responsive to OCS based on clinical response or
blood eosinophil counts.

Prior/Concomitant Therapy:
11. Participants who have previously received mepolizumab in the 4 months prior
to enrolment (Visit 2).
12. Participants receiving any of the following:
• IV or SC corticosteroids in the 4-week period prior to enrolment (Visit 2).
• Any other monoclonal antibodies within 30 days or 5 half-lives, whichever is
longer, of enrolment (Visit 2).

Other investigational product/clinical study:
13. 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). The term "investigational"
applies to any drug not approved for sale in the country in which it is being
used or investigational formulations of marketed products
14. Use of candidate COVID-19 vaccines that have not received limited,
accelerated, or full authorisation/approval, and are only in use as part of a
clinical trial
15. Participants who are currently participating in any other interventional
clinical study

Contraindications:
16. Participants with any history of hypersensitivity to any monoclonal
antibody (including mepolizumab)

Other Exclusions:
17. 12-lead ECG finding:
For all participants:
• An abnormal ECG finding from the 12-lead ECG conducted at Visit 1 if
considered to be clinically significant and would impact the participant's
participation during the study based on the evaluation of the investigator.
For participants aged 6 to 11 years:
• QT interval corrected using Fridericia's formula (QTcF) > 450 msec.
• Left bundle branch block
For participant aged 12 to 17 years:
• QTcF > 450 msec or QT interval corrected for heart rate (QTc) > 480 msec in
participants with bundle branch block
18. Liver abnormality/disease
19. Other laboratory abnormalities