Hypereosinophilic Syndrome
Conditions
Keywords
Hypereosinophilic Syndrome, Mepolizumab, Safety, Efficacy, Pediatric, Adolescent
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.
Interventions
DRUGMepolizumab
Mepolizumab was provided in pre-filled safety syringe
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
This is an open-label study
Eligibility
Sex/Gender
ALL
Age
6 Years to 17 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced HES Flares Over the 52-Week Study Treatment Period | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | The mean daily OCS (prednisone or equivalent) dose for each 4-week period from Weeks 0-4 to Weeks 48-52 for each participant were calculated as the sum of the daily doses of OCS during each 4-week period divided by the total number of days. The change in the mean daily OCS dose for each 4-week period from Weeks 0-4 to Weeks 48-52 was calculated for each participant as the mean daily OCS dose for Weeks 48-52 minus the mean daily OCS dose for Weeks 0-4. Baseline value was derived as the sum of the daily doses of OCS during first 4 weeks following the initiation of mepolizumab treatment (Weeks 0-4) divided by total number of days. Change from Baseline was calculated as post-Baseline value minus Baseline Value. |
| 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 | The mean daily OCS (prednisone or equivalent) dose for each 4-week period from Weeks 0-4 to Weeks 48-52 for each participant were calculated as the sum of the daily doses of OCS during each period divided by the total number of days. For each 4-week period, a reduction of 50% or more in mean OCS dose was defined as (mean OCS dose at each 4-week period minus mean OCS dose during Weeks 0-4) divided by (mean OCS dose during Weeks 0-4) multiplied by 100 was \<= -50. Baseline value was derived as the sum of the daily doses of OCS during first 4 weeks following the initiation of mepolizumab treatment (Weeks 0-4) divided by total number of days. |
| 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 | The mean daily OCS (prednisone or equivalent) dose for Weeks 48-52 for each participant were calculated as the sum of the daily doses of OCS during this period divided by the total number of days. Number of participants with a mean daily OCS dose (prednisone/prednisolone or equivalent) of \<=7.5 mg during period of Weeks 48-52 in subpopulation of participants that were taking OCS at Baseline has been presented. |
| 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 | The mean daily OCS (prednisone or equivalent) dose for Weeks 48-52 for each participant were calculated as the sum of the daily doses of OCS during this period divided by the total number of days. Number of participants with a mean daily OCS dose (prednisone/prednisolone or equivalent) of \<=7.5 mg during period of Weeks 48-52 in overall population has been presented. |
| 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 | The BFI is a self-administered questionnaire developed to assess fatigue severity. The BFI has 9 items. BFI- Item 3 assesses the worst level of fatigue during the past 24 hours. Participants report their worst level of fatigue daily, for the previous 24 hours, using a numerical rating scale ranging from 0 (no fatigue) to 10 (as bad as you can imagine). The weekly average score of BFI item 3 was defined as the mean of the observed daily assessments over the 7-day period. The weekly average score of BFI item 3 ranges from 0 to 10, higher score indicates worst outcome. BFI Item 3 was assessed in the participants with the age group of 12 to 17 years at study entry. Baseline was defined as the mean of the 7 daily assessments of BFI item 3 up to but not including the date of first dose of study treatment. Change from Baseline was calculated as post-Baseline value minus Baseline Value. |
| Number of Participants With Any Time Post-Baseline Positive Anti-mepolizumab Antibodies (ADA) | Up to Week 52 | Serum samples were collected for the determination of anti-mepolizumab antibodies (ADA) using a validated electro-chemiluminescent immunoassay. The assay involved screening, confirmation and titration assays. If serum samples tested positive in the screening assay, they were considered 'potentially positive' and were further analyzed for specificity using the confirmation assay. Samples that confirmed positive in the confirmation assay were reported as 'positive'. Confirmed positive ADA samples were further characterized in the titration assay to quasi-quantitate the amount of ADA in the sample and were also further characterized in the Neutralizing antibody (Nab) assay. A participant was considered positive ADA if they had at least one positive any time post-Baseline ADA result. |
| Number of Participants With Any Time Post-Baseline Positive Neutralizing Antibodies (NAb) | Up to Week 52 | Blood samples were collected for the determination of positive neutralizing antibodies. NAb test was to be carried out on samples that were positive in the confirmatory binding antibody assay. A participant was to be considered positive for NAb if they had at least one positive any time post-Baseline neutralizing antibody result. |
| 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 | Blood samples were collected to measure eosinophil count. Ratio to Baseline is defined as post-dose visit value divided by Baseline value. Baseline was defined as the latest blood eosinophil value measured by the central laboratory prior to the first dose of study treatment. |
| Plasma Concentrations of Mepolizumab | Pre-dose at Weeks 4 and 24; Week 52 | Blood samples were collected at the indicated time points for pharmacokinetic analysis of Mepolizumab. |
Countries
Argentina, Brazil, Israel, Netherlands, Turkey (Türkiye), United States
Contacts
STUDY_DIRECTORGSK Clinical Trials
GlaxoSmithKline
Participant flow
Recruitment details
This was a 52-week, open-label, multicenter study to evaluate the efficacy and safety of mepolizumab subcutaneous (SC) injection in children (aged 6 to 11 years) and adolescent (aged 12 to 17 years) participants with hypereosinophilic syndrome (HES) who were receiving standard of care (SoC) therapy.
Pre-assignment details
A total of 16 participants with HES were enrolled in this study. All participants received active treatment with mepolizumab SC injection every 4 weeks over a treatment period of 52 weeks. The initial dose was dependent on age and weight. During the study, the dose was to be adjusted once the participants reached a bodyweight of 40 kg or the age of 12 years.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Customized 12 to 17 Years | 0 Participants |
| Age, Customized 6 to 11 Years | 12 Participants |
| Race/Ethnicity, Customized WHITE | 1 Participants |
| Sex: Female, Male Female | NA Participants |
| Sex: Female, Male Male | NA Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 4 | 0 / 1 | 0 / 1 |
| other Total, other adverse events | 9 / 10 | 1 / 4 | 0 / 1 | 1 / 1 |
| serious Total, serious adverse events | 0 / 10 | 0 / 4 | 0 / 1 | 1 / 1 |
Outcome results
None listed