Study in Pediatrics With HypEREosinophilic Syndrome (SPHERE)

Study Overview
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Brief Summary
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The purpose of this study is to investigate the efficacy and safety of mepolizumab in children and adolescents with hypereosinophilic syndrome (HES) who are receiving standard of care (SoC) therapy.

Official Title
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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

Conditions
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Hypereosinophilic Syndrome

Intervention / Treatment
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* Drug: Mepolizumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This is a single arm study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Participants receiving mepolizumab<br> | Drug: Mepolizumab<br>* Mepolizumab will be provided in pre-filled safety syringe<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of HES flares experienced by participants per year | The annualized rate of HES flares will be measured. | Up to Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in mean daily oral corticosteroids (OCS) dose (prednisone/prednisolone or equivalent) from Weeks 0 to 4 to Weeks 48 to 52 | Change in mean daily OCS dose (prednisone/prednisolone or equivalent) will be assessed. | Weeks 0 to 4 and Weeks 48 to 52 | 
| Number of participants with >=50 percent (%) reduction in mean daily OCS dose (prednisone/prednisolone or equivalent) from Weeks 0 to 4 compared with Weeks 48 to 52 | Number of participants with >=50% reduction in mean daily OCS dose (prednisone/prednisolone or equivalent) will be assessed. | Weeks 0 to 4 and Weeks 48 to 52 | 
| Number of participants achieving a mean daily OCS dose (prednisone/prednisolone or equivalent) of <=7.5 milligrams (mg) during Weeks 48 to 52 in participants that are taking OCS at Baseline | Number of participants achieving a mean daily OCS dose (prednisone/prednisolone or equivalent) of <=7.5 mg will be assessed. | Weeks 48 to 52 | 
| Number of participants achieving a mean daily OCS dose (prednisone/prednisolone or equivalent) of <=7.5 mg during Weeks 48 to 52 | Participants achieving mean daily OCS dose (prednisone/prednisolone or equivalent) of <=7.5 mg will be evaluated. | Weeks 48 to 52 | 
| Change from Baseline in fatigue severity based on Brief Fatigue Inventory (BFI) Item 3 (worst level of fatigue during past 24 hours) for Week 52 | Item 3 of the BFI is a 11-point scale that measures fatigue (weariness, tiredness) ranging from 0 no fatigue to 10 as bad as you can imagine. | Baseline and up to Week 52 | 
| Number of participants with Anti-drug antibodies (ADA) and neutralizing antibodies (NAb) | Participants with ADA and NAb will be evaluated. | Up to Week 52 | 
| Ratio to Baseline in absolute blood eosinophil count | Blood samples will be collected. | Baseline and up to Week 52 | 
| Mepolizumab plasma concentrations | Blood samples will be collected for determination of mepolizumab plasma concentration. | Week 4 and up to Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypereosinophilic Syndrome, Mepolizumab, Safety, Efficacy, Pediatric, Adolescent