The main purpose of study is to assess the safety, tolerability, pharmacokinetics (PK), and efficacy of benralizumab.
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. Paediatric participants with hypereosinophilic syndrome (HES) will be enrolled in the second 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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
4
Benralizumab will be administered as SC injection on Q4W.
Research Site
Aurora, Colorado, United States
RECRUITINGResearch Site
São Paulo, Brazil
RECRUITINGResearch Site
Toronto, Ontario, Canada
RECRUITINGNumber of Participants with Adverse Events (AEs)
The safety and tolerability of benralizumab will be evaluated.
Time frame: From screening (Week -4 to -1) until Week 52
Serum Concentrations of Benralizumab
The PK of benralizumab will be evaluated.
Time frame: Weeks 0, 12, 24, 25, 36, and 52
EGPA Cohort: Percentage of Participants with Remission 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.
Time frame: At Week 24
Number of Participants with Positive Antidrug Antibody (ADA)
The immunogenicity of benralizumab will be evaluated.
Time frame: Weeks 0, 12, 24, 36, 48, and 52
Change From Baseline in Peripheral Blood Eosinophil Count
The PD effect of benralizumab on peripheral blood eosinophil count will be evaluated.
Time frame: From Baseline to Weeks 0, 12, 24, 36, 52
EGPA Cohort: Time to First EGPA Relapse
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.
AstraZeneca Clinical Study Information Center
CONTACT
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Research Site
Guadalajara, Mexico
RECRUITINGResearch Site
Altındağ, Turkey (Türkiye)
RECRUITINGResearch Site
Istanbul, Turkey (Türkiye)
RECRUITINGTime frame: Up to 52 weeks
HES Cohort: Time to first HES worsening/flare
The effect of benralizumab on HES worsening/flares will be evaluated.
Time frame: Up to 52 weeks
HES Cohort: Percentage of participants who experience a HES worsening/flare
The effect of benralizumab on HES worsening/flares will be evaluated.
Time frame: Up to 52 weeks
HES Cohort: Number of HES worsening/flares (annualised rate/year)
The effect of benralizumab on HES worsening/flares will be evaluated. The annualised HES worsening/flare rate will be calculated as follows: The total number of flares \*365.25 / total duration of follow-up in the treatment period (days).
Time frame: Up to 52 weeks
HES Cohort: Percentage of Participants requiring an increase in corticosteroid dose
The effect of benralizumab on corticosteroid use will be evaluated.
Time frame: Up to 52 weeks
HES Cohort: Time to first haematologic relapse
The time to first haematologic relapse will be defined as the time from first dose of IP to the first post baseline visit with Absolute eosinophil count \[AEC\] ≥ 1000 cells/uL.
Time frame: Up to 52 weeks
HES Cohort: Percentage of Participants with haematologic relapse
The effect of benralizumab on haematologic measures of disease activity will be evaluated.
Time frame: Up to 52 weeks
HES Cohort: Percentage of Participants who have AEC < 500 cells/μL for 24 weeks
The effect of benralizumab on haematologic measures of disease activity will be evaluated.
Time frame: Up to 52 weeks
HES Cohort: Patient Global Impression of Change (PGI-C) Score
The effect of benralizumab on participant/caregiver reported measures of disease severity and health status will be assessed. The PGI-C instrument captures the participant's overall evaluation of response to treatment, and rated on a 7-point PGI-C scale ranging from 1 ('much better') to 7 ('much worse').
Time frame: Weeks 12, 24, 36 and 48