Study in Pediatrics With HypEREosinophilic Syndrome (SPHERE)

NCT04965636 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: 215360
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypereosinophilic Syndrome

Keywords

Hypereosinophilic Syndrome; Mepolizumab; Safety; Efficacy; Pediatric; Adolescent

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Experienced HES Flares Over the 52-Week Study Treatment Period

  A HES flare is defined as a HES related clinical manifestation based on a physician-documented change in clinical signs or symptoms (worsening symptoms and/or elevated blood eosinophil level) which resulted in need for either: an increase from the most recent dose in the maintenance Oral Corticosteroid (OCS) dose (prednisone/prednisolone equivalent) by at least 10 mg per day for 5 days or an increase in or addition of any immunosuppressive and/or cytotoxic HES therapy from/to the most recent dose of HES therapy. Data is presented by the number of HES flares (0, 1, 2, 3 ,4 and \>=5) in the participants.

  Up to Week 52

Secondary Outcomes (9)

• Change in Mean Daily Oral Corticosteroids (OCS) Dose (Prednisone/Prednisolone or Equivalent) for Each 4-week Period From Weeks 0-4 to Weeks 48-52

  Baseline (Weeks 0-4), Weeks 4-8, Weeks 8-12, Weeks 12-16, Weeks 16-20, Weeks 20-24, Weeks 24-28, Weeks 28-32, Weeks 32-36, Weeks 36-40, Weeks 40-44, Weeks 44-48 and Weeks 48-52

• Number of Participants With Reduction of >=50 Percentage (%) in Mean Daily OCS Dose (Prednisone/Prednisolone or Equivalent) for Each 4-week Period From Weeks 0-4 to Weeks 48-52

  Baseline (Weeks 0-4), Weeks 4-8, Weeks 8-12, Weeks 12-16, Weeks 16-20, Weeks 20-24, Weeks 24-28, Weeks 28-32, Weeks 32-36, Weeks 36-40, Weeks 40-44, Weeks 44-48 and Weeks 48-52

• Number of Participants With a Mean Daily OCS Dose (Prednisone/Prednisolone or Equivalent) of Less Than or Equal to (<=) 7.5 Milligrams (mg) During Weeks 48-52 in Subpopulation of Participants That Were Taking OCS at Baseline

  Weeks 48-52

• Number of Participants With a Mean Daily OCS Dose (Prednisone/Prednisolone or Equivalent) of <=7.5 mg During Weeks 48-52 in Overall Population

  Weeks 48-52

• Change From Baseline in Fatigue Severity Based on Weekly Average Score of Brief Fatigue Inventory (BFI) Item 3 (Worst Level of Fatigue During Past 24 Hours) for Week 52 for Participants in the Age Group of 12 to 17 Years

  Baseline (Week 0) and Week 52

Study Arms (4)

Mepolizumab 100 mg SC

EXPERIMENTAL

Participants in the age group of 6 to 11 years with body weight less than (\<) 40 kilogram (kg) received Mepolizumab 100 milligram (mg) subcutaneous (SC) injection every 4 weeks over a treatment period of 52 weeks.

Drug: Mepolizumab

Mepolizumab 300 mg SC

EXPERIMENTAL

Participants in the age group of 12 to 17 years received Mepolizumab 300 mg SC injection every 4 weeks over a treatment period of 52 weeks.

Drug: Mepolizumab

Mepolizumab 200/100 mg SC

EXPERIMENTAL

A participant in the age group of 6 to 11 years with body weight greater than or equal to (\>=) 40 kg received mepolizumab 200 mg SC injections every 4 weeks. During the conduct of the study, the mepolizumab dose was reduced to 100 mg SC injection every 4 weeks as body weight of the participant reduced to less than (\<) 40 kg over a treatment period of 52 weeks.

Drug: Mepolizumab

Mepolizumab 200/300 mg SC

EXPERIMENTAL

A participant in the age group of 6 to 11 years with body weight \>=40 kg received mepolizumab 200 mg SC injections every 4 weeks. During the conduct of the study, the mepolizumab dose was increased to 300 mg SC injection every 4 weeks as age of the participant increased to the age group of 12 to 17 years over a treatment period of 52 weeks.

Drug: Mepolizumab

Interventions

Mepolizumab DRUG

Mepolizumab was provided in pre-filled safety syringe

Mepolizumab 100 mg SC; Mepolizumab 200/100 mg SC; Mepolizumab 200/300 mg SC; Mepolizumab 300 mg SC

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Buenos Aires, C1028AAP, Argentina

Location

MeSH Terms

Conditions

Hypereosinophilic Syndrome

Interventions

mepolizumab

Condition Hierarchy (Ancestors)

Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: This is an open-label study
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: July 7, 2021
• First Posted: July 16, 2021
• Study Start: July 14, 2022
• Primary Completion: October 28, 2025
• Study Completion: October 28, 2025
• Last Updated: May 4, 2026
• Results First Posted: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or asset(s) with development terminated across all indications.
• Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.

Locations

AR (1)