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
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- GlaxoSmithKline
- Enrollment
- 16
- Locations
- 15
- Primary Endpoint
- Number of HES flares experienced by participants per year
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Masking Description
This is an open-label study
Eligibility Criteria
- Ages
- 6 Years to 17 Years (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Mepolizumab 300 mg SC
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.
Intervention: Mepolizumab (Drug)
Mepolizumab 200/300 mg SC
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.
Intervention: Mepolizumab (Drug)
Mepolizumab 100 mg SC
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.
Intervention: Mepolizumab (Drug)
Mepolizumab 200/100 mg SC
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.
Intervention: Mepolizumab (Drug)
Outcomes
Primary Outcomes
Number of HES flares experienced by participants per year
Time Frame: Up to Week 52
The annualized rate of HES flares will be measured.
Number of Participants Who Experienced HES Flares Over the 52-Week Study Treatment Period
Time Frame: Up to Week 52
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.
Secondary Outcomes
- 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 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)
- 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)
- Number of participants with Anti-drug antibodies (ADA) and neutralizing antibodies (NAb)(Up to Week 52)
- Ratio to Baseline in absolute blood eosinophil count(Baseline and up to Week 52)
- Mepolizumab plasma concentrations(Week 4 and up to Week 52)
- 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)
- 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)
- 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)
- Number of Participants With Any Time Post-Baseline Positive Anti-mepolizumab Antibodies (ADA)(Up to Week 52)
- Number of Participants With Any Time Post-Baseline Positive Neutralizing Antibodies (NAb)(Up to Week 52)
- Ratio to Baseline in Blood Eosinophil Count(Baseline (Week 0), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52)
- Plasma Concentrations of Mepolizumab(Pre-dose at Weeks 4 and 24; Week 52)