Phase III Open‑Label Study of Subcutaneous Benralizumab in Children with Eosinophilic Disease: Safety, PK/PD, Efficacy and Immunogenicity

The primary objective is to assess the safety and tolerability of subcutaneous benralizumab and to characterize its pharmacokinetics in pediatric patients with eosinophilic disease, providing essential data for risk‑benefit evaluation and dose optimization.

Secondary objectives include:

• Evaluation of the drug’s immunogenicity.
• Assessment of the pharmacodynamic effect on peripheral blood eosinophil count.
• In the EGPA cohort, determination of the durability of response as the proportion of participants in remission at Week 24.
• In the EGPA cohort, measurement of time to first relapse.
• In the HES cohort, evaluation of the impact on disease worsening or flares.
• In the HES cohort, assessment of changes in corticosteroid use.
• In the HES cohort, analysis of hematologic markers of disease activity.
• In the HES cohort, appraisal of participant‑ or caregiver‑reported disease severity and overall health status.

Seven participants were enrolled, comprising both male and female patients aged 6 to < 18 years and weighing at least 15 kg. All subjects had a diagnosis of Eosinophilic Disease, a rare condition, and satisfied disease‑specific criteria such as documented eosinophilia thresholds, negative FIP1L1‑PDGFRA testing for the hypereosinophilic syndrome cohort, and evidence of organ involvement. Inclusion required stable dosing of oral corticosteroids or immunosuppressive therapy for at least four weeks when applicable, and either active disease manifestations or a history of prior flares. Selection was based on these clinical and laboratory parameters, with no additional lifestyle restrictions reported.

The study is a Phase III open-label trial evaluating the pharmacokinetics, pharmacodynamics, safety, efficacy, and immunogenicity of benralizumab in children aged 6 to < 18 years with Eosinophilic Disease. After a screening visit that confirms age, body weight (≥ 15 kg) and disease‑specific inclusion criteria, eligible participants receive a subcutaneous injection of benralizumab (30 mg) at baseline (Visit 2) and at predefined intervals during a treatment period of up to 24 weeks. Follow‑up visits are scheduled to monitor serum drug concentrations, peripheral eosinophil counts, and safety parameters, culminating in an end‑of‑study visit that collects final efficacy and safety data. Participant involvement therefore spans from screening through the end‑of‑study visit, approximately six months. Primary endpoints are the number of participants experiencing Adverse Events and serum benralizumab concentrations; secondary endpoints include anti‑drug antibody presence, changes in eosinophil counts, and disease‑specific remission or flare outcomes. Early termination may occur if a participant experiences a serious adverse event, withdraws consent, or is unable to comply with required assessments. Recruitment began in May 2026 with planned completion in May 2029.

The experimental medication Benralizumab is supplied as a solution for injection in a 10 mg/mL formulation. It is administered by subcutaneous injection. The dose specified in the protocol is 10 mg per administration, delivered according to the study‑defined schedule.

A second investigational product, Fasenra 30 mg solution for injection in a pre‑filled syringe, contains the same active substance. It is also a solution for injection, provided at a concentration of 30 mg/mL, and is given by subcutaneous injection. Each dose consists of 30 mg, administered in accordance with the protocol‑specified timing.

No placebo, standard‑of‑care therapy, or other comparator treatment is outlined for this trial; the study involves only the investigational benralizumab products.

All injections are performed by qualified personnel at the study site. Dosing intervals follow the protocol‑defined timetable, and adherence is monitored through documented administration logs and periodic review of source records to ensure participant compliance.

Efficacy assessment will focus on secondary endpoints. Change from baseline in Peripheral Blood Eosinophil Count will be measured using standard laboratory assays at baseline and at scheduled study visits. The proportion of participants achieving remission at Week 24 will be determined, with remission defined as a Physician Vasculitis Activity Score (PVAS) of 0 and oral corticosteroid intake ≤ 0.1 mg/kg/day. Time to first EGPA relapse will be recorded; relapse is defined by any of the following: active vasculitis (PVAS > 0), worsening asthma symptoms assessed with the Asthma Control Questionnaire – Interviewer Administered (ACQ-IA), or active nasal/sinus disease with symptom worsening that necessitates an increase in corticosteroids, addition of immunosuppressive therapy, or hospitalization.

In the HES cohort, efficacy will be evaluated by time to first HES worsening/flare, the proportion of participants experiencing a flare, and the annualized flare rate during the treatment period. The need for an increase in corticosteroid dose from baseline will be tracked. Hematologic relapse, defined as an absolute eosinophil count (AEC) ≥ 1000 cells/μL, will be monitored; the proportion of participants with relapse and the number maintaining AEC < 500 cells/μL for 24 weeks will be documented. Patient Global Impression of Change (PGI-C) will be collected throughout the treatment period. All assessments will be performed at predefined study visits, including the Week 24 evaluation.