Efficacy and Safety Evaluation of Subcutaneous Mepolizumab in Pediatric Patients with Hypereosinophilic Syndrome: A 52-Week, Phase 3, Open-Label, Single-Arm Study

The primary objective of this study is to evaluate the **efficacy** of mepolizumab, administered subcutaneously every four weeks, in participants aged 6 to 17 years with **hypereosinophilic syndrome (HES)**. This is clinically relevant as it aims to determine the therapeutic potential of mepolizumab in managing HES, a condition characterized by elevated eosinophil levels that can lead to organ damage.

Secondary objectives include:

• Assessing the effect of mepolizumab on the change in oral corticosteroid (OCS) dose in participants taking OCS at baseline.
• Evaluating the change in OCS dose in participants with HES.
• Assessing the efficacy of mepolizumab on fatigue in participants aged 12 to 17 years.
• Evaluating the immunogenicity of mepolizumab.
• Assessing the effect of long-term use of mepolizumab on a pharmacodynamic (PD) marker.
• Assessing the pharmacokinetics (PK) of mepolizumab.

The clinical trial involves a total of **17 participants** diagnosed with **Hypereosinophilic syndrome (HES)**, aged between 6 to 17 years. Both male and female subjects are included in the study population. Participants were selected based on their diagnosis of HES for at least six months prior to enrollment and a history of two or more HES flares within the past 12 months. Additionally, participants must have a blood eosinophil count of at least 1000 cells/μL at screening and be on a stable dose of HES therapy for the four weeks preceding the first dose of mepolizumab. The trial population includes a vulnerable group, as it involves pediatric participants. Lifestyle considerations such as diet and physical activity are not specified. The study requires that female participants of childbearing potential use an acceptable method of contraception and undergo pregnancy testing as appropriate. The trial ensures that a legal guardian or primary caregiver is available to assist with follow-up and support the participant throughout the study.

The clinical trial is a **Phase 3**, 52-week, open-label, single-arm study designed to evaluate the efficacy and safety of **mepolizumab** administered subcutaneously in participants aged 6 to 17 years with **hypereosinophilic syndrome (HES)**. The primary objective is to assess the frequency of HES flares over the treatment period, while secondary endpoints include changes in oral corticosteroid (OCS) doses, fatigue severity, and blood eosinophil counts. The trial will also monitor the occurrence of anti-drug antibodies (ADA) and neutralizing antibodies (NAb), as well as measure mepolizumab plasma concentrations at specified intervals.

Participants will be involved in the study for a total duration of 52 weeks, with the trial estimated to conclude by September 30, 2024. The study begins with a screening visit to confirm eligibility, which includes criteria such as age, a history of HES, and stable HES therapy. Following the screening, eligible participants will proceed to the enrollment visit, where they will receive their first dose of the investigational product. Subsequent study visits will occur every four weeks to administer the treatment and assess the participants' health status and response to therapy.

The end-of-study visit will mark the conclusion of the participant's involvement, where final assessments will be conducted to evaluate the overall impact of the treatment. Participants may be withdrawn from the study early if they experience significant adverse events, fail to comply with the study protocol, or if the investigator deems it necessary for their safety. The investigational product, mepolizumab, is provided in a pre-filled syringe for single-use subcutaneous administration, ensuring ease of use and consistency in dosing throughout the trial.

The clinical trial involves the administration of **mepolizumab**, an investigational medication, to evaluate its efficacy and safety in participants aged 6 to 17 years with hypereosinophilic syndrome (HES). **Mepolizumab** is provided in the form of a **solution for injection** and is administered via **subcutaneous use**. The investigational product is delivered using a fixed-dose, fully disposable prefilled syringe, specifically the Nucala 100 mg solution for injection in a prefilled safety syringe device. This device is intended for single use only. The dosing schedule for **mepolizumab** involves administration every four weeks over a maximum treatment period of 52 weeks. The investigational product has been repackaged and relabelled for clinical trial use.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The trial is designed as a single-arm study, focusing solely on the administration of **mepolizumab**. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the treatment regimen. The investigational product does not have a maximum daily dose or total dose amount specified, as the administration is based on a fixed schedule of every four weeks.

The efficacy of **mepolizumab** in the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint is the frequency of **hypereosinophilic syndrome (HES)** flares over the 52-week study treatment period. Secondary endpoints include changes in the mean daily oral corticosteroid (OCS) dose, specifically prednisone or prednisolone, from Weeks 0 to 4 compared to Weeks 48 to 52, and achieving a mean daily OCS dose of ≤7.5 mg during Weeks 48 to 52. Additionally, the trial will evaluate the change from baseline in fatigue severity using the Brief Fatigue Inventory (BFI) item 3 score at Week 52, the occurrence of anti-drug antibodies (ADA) and neutralizing antibodies (NAb), the ratio to baseline in absolute blood eosinophil count at discrete time points, and the plasma concentration of mepolizumab at discrete time points during the 52-week study period.