Study in Pediatrics With HypEREosinophilic Syndrome (SPHERE)

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04965636

Collaborator

(none)

Enrollment

Locations

Arm

26.6

Anticipated Duration (Months)

2.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Hypereosinophilic Syndrome	Drug: Mepolizumab	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

25 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

This is a single arm studyThis is a single arm study

Masking:

None (Open Label)

Masking Description:

This is an open-label study

Primary Purpose:

Treatment

Official Title:

A 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

Actual Study Start Date :

Jul 14, 2022

Anticipated Primary Completion Date :

Sep 30, 2024

Anticipated Study Completion Date :

Sep 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Participants receiving mepolizumab	Drug: Mepolizumab Mepolizumab will be provided in pre-filled safety syringe

Arm

Intervention/Treatment

Experimental: Participants receiving mepolizumab

Drug: Mepolizumab

Mepolizumab will be provided in pre-filled safety syringe

Outcome Measures

Primary Outcome Measures

Number of HES flares experienced by participants per year [Up to Week 52]
The annualized rate of HES flares will be measured.

Secondary Outcome Measures

Change in mean daily oral corticosteroids (OCS) dose (prednisone/prednisolone or equivalent) from Weeks 0 to 4 to Weeks 48 to 52 [Weeks 0 to 4 and Weeks 48 to 52]
Change in mean daily OCS dose (prednisone/prednisolone or equivalent) will be assessed.
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 [Weeks 0 to 4 and Weeks 48 to 52]
Number of participants with >=50% reduction in mean daily OCS dose (prednisone/prednisolone or equivalent) will be assessed.
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 [Weeks 48 to 52]
Number of participants achieving a mean daily OCS dose (prednisone/prednisolone or equivalent) of <=7.5 mg will be assessed.
Number of participants achieving a mean daily OCS dose (prednisone/prednisolone or equivalent) of <=7.5 mg during Weeks 48 to 52 [Weeks 48 to 52]
Participants achieving mean daily OCS dose (prednisone/prednisolone or equivalent) of <=7.5 mg will be evaluated.
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 [Baseline and up to 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".
Number of participants with Anti-drug antibodies (ADA) and neutralizing antibodies (NAb) [Up to Week 52]
Participants with ADA and NAb will be evaluated.
Ratio to Baseline in absolute blood eosinophil count [Baseline and up to Week 52]
Blood samples will be collected.
Mepolizumab plasma concentrations [Week 4 and up to Week 52]
Blood samples will be collected for determination of mepolizumab plasma concentration.

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Rochester	Minnesota	United States	55905
2	GSK Investigational Site	Cincinnati	Ohio	United States	45229
3	GSK Investigational Site	Cleveland	Ohio	United States	44106
4	GSK Investigational Site	Charleston	South Carolina	United States	29425
5	GSK Investigational Site	Caba	Buenos Aires	Argentina	C1028AAP
6	GSK Investigational Site	Florencio Varela	Buenos Aires	Argentina	1888
7	GSK Investigational Site	Florida	Buenos Aires	Argentina	1602
8	GSK Investigational Site	Quilmes	Buenos Aires	Argentina	1878
9	GSK Investigational Site	Madrid		Spain	28009