Clinical trial NCT04965636: Study in Pediatrics With HypEREosinophilic Syndrome (SPHERE)
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Hypereosinophilic Syndrome
Keywords: Hypereosinophilic Syndrome
Mepolizumab
Safety
Efficacy
Pediatric
Adolescent
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2021-07-16
Enrollment: 16
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a single arm study
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of HES flares experienced by participants per year
timeFrame: Up to Week 52
Secondary outcomes:
measure: Change in mean daily oral corticosteroids (OCS) dose (prednisone/prednisolone or equivalent) from Weeks 0 to 4 to Weeks 48 to 52
timeFrame: Weeks 0 to 4 and Weeks 48 to 52
measure: 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
timeFrame: Weeks 0 to 4 and Weeks 48 to 52
measure: 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
timeFrame: Weeks 48 to 52
measure: Number of participants achieving a mean daily OCS dose (prednisone/prednisolone or equivalent) of <=7.5 mg during Weeks 48 to 52
timeFrame: Weeks 48 to 52
measure: 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
timeFrame: Baseline and up to Week 52
measure: Number of participants with Anti-drug antibodies (ADA) and neutralizing antibodies (NAb)
timeFrame: Up to Week 52
measure: Ratio to Baseline in absolute blood eosinophil count
timeFrame: Baseline and up to Week 52
measure: Mepolizumab plasma concentrations
timeFrame: Week 4 and up to Week 52
Other outcomes:
Locations:
city: Rochester
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Cincinnati
country: United States
facility: GSK Investigational Site
state: Ohio
city: Cleveland
country: United States
facility: GSK Investigational Site
state: Ohio
city: Charleston
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Quilmes
country: Argentina
facility: GSK Investigational Site
city: Sao Paulo
country: Brazil
facility: GSK Investigational Site
city: Sorocaba
country: Brazil
facility: GSK Investigational Site
city: Petach Tikva
country: Israel
facility: GSK Investigational Site
city: Rotterdam
country: Netherlands
facility: GSK Investigational Site
city: Ankara
country: Turkey
facility: GSK Investigational Site
city: Izmir
country: Turkey
facility: GSK Investigational Site
city: Kayseri
country: Turkey
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: