A Trial to Investigate Benralizumab in Children With Eosinophilic Diseases

Phase 3

Not yet recruiting

Brief Summary: The main purpose of study is to assess the safety, tolerability, and pharmacokinetic (PK) of benralizumab.

Detailed Description: This study is open-label, multicentre, basket study to evaluate the safety, PK, pharmacodynamic (PD), efficacy, and immunogenicity of repeat dosing of benralizumab subcutaneous (SC) every 4 weeks (Q4W) in male and female children with rare eosinophilic diseases.

Paediatric participants with eosinophilic granulomatosis with polyangiitis (EGPA) will be enrolled in the first cohort. Additional cohorts in other eosinophilic diseases may be added in future protocol amendments.

The study consists of 3 periods:

1. Screening period: 1 to 4 weeks

2. Open-label treatment period: 52 weeks

3. Open-label extension period: at least 52 weeks (plus safety follow-up \[SFU\] weeks after last investigational product \[IP\] administration)

All eligible participants will receive benralizumab SC Q4W during the 52-week open-label treatment period.

All participants who complete the 52-week open-label treatment period on IP will be offered the opportunity to continue into an extension period. The extension period is intended to allow each participant at least an additional one year of treatment with benralizumab.

Recruitment & Eligibility

Inclusion Criteria

All Cohorts:

Male or female patients must be aged 6 to < 18 years of age at the time of signing the assent form and their caregiver signing the informed consent form.
Body weight greater than (>=) 15 kilograms (kg).

EGPA Cohort:

Therapy with corticosteroids: The prescribed dose of oral corticosteroids (OCS) (greater than [>] 0.1 milligrams per kilogram per day (mg/kg/day), max dose of 50 milligrams per day (mg/day) must be stable (that is, no adjustment of the dose) for at least 4 weeks prior to baseline (Visit 2).
Immunosuppressive therapy: If receiving immunosuppressive therapy, the dosage must be stable for at least 4 weeks prior to baseline (Visit 2).

Exclusion Criteria

All Cohorts:

Any current malignancy or history of malignancy.
History of anaphylaxis to any biologic therapy or vaccine.
Known, pre-existing, clinically significant endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, haematological, respiratory, or any other system abnormalities.
Previous receipt of benralizumab in an interventional clinical study.

EGPA Cohort:

Diagnosed with granulomatosis with polyangiitis (previously known as Wegener'granulomatosis) or microscopic polyangiitis.
EGPA relapse: any deterioration in EGPA and/or organ-threatening EGPA that per Investigator judgement renders patients unstable in their EGPA within 3 months prior to screening (Visit 1) and through first administration of IP at baseline (Visit 2).
Life-threatening EGPA: imminently life-threatening EGPA disease within 3 months prior to screening (Visit 1) and through first administration of IP at baseline (Visit 2), as per Investigator judgement.

Arm && Interventions

Group	Intervention	Description
EGPA Cohort: Benralizumab	Benralizumab	Participants with greater than or equal to (\>=) 35 kg weight will receive benralizumab dose-1 and participants with less than (\<) 35 kg weight will receive benralizumab dose-2 as SC injection Q4W during the 52-week treatment period. All participants, who complete the 52-week treatment period, will be offered the opportunity to continue into an extension period.

Primary Outcome Measures

Name	Time	Method
Serum Concentrations of Benralizumab	Weeks 0, 12, 24, 25, 36, and 52	The PK of benralizumab will be evaluated.
Number of Participants with Adverse Events (AEs)	From screening (Week -4 to -1) until Week 52	The safety and tolerability of benralizumab will be evaluated.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Peripheral Blood Eosinophil Count	From Baseline to Weeks 0, 12, 24, 36, 52	The PD effect of benralizumab on peripheral blood eosinophil count will be evaluated.
EGPA Cohort: Time to First EGPA Relapse	Up to 52 weeks	The efficacy of benralizumab on time to first relapse will be assessed. EGPA relapse will be defined as worsening or persistence of active disease since the last visit characterized by: a) Active vasculitis (PVAS \> 0); OR b) Worsening of asthma symptoms (based on Asthma Control Questionnaire - Interviewer Administered \[ACQ-IA\]); OR c) Active nasal and/or sinus disease with worsening in at least one sino-nasal symptom question warranting any of the following: 1) Increase OCS; OR 2) Increase/addition of immunosuppressive medication; OR 3) Hospitalisation related to EGPA worsening.
EGPA Cohort: Percentage of Participants with Remission at Week 24	At Week 24	Remission defined as Paediatric Vasculitis Activity Score (PVAS) = 0 and oral corticosteroid (OCS) intake less than or equal to (\<=) 0.1 mg/kg/day.
Number of Participants with Positive Antidrug Antibody (ADA)	Weeks 0, 12, 24, 36, 48, and 52	The immunogenicity of benralizumab will be evaluated.