Eosinophilic Granulomatosis With Polyangiitis (EGPA), Hypereosinophilia Syndrome (HES)
Conditions
Brief summary
The main purpose of study is to assess the safety, tolerability, pharmacokinetics (PK), and efficacy 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. 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.
Interventions
DRUGBenralizumab
Benralizumab will be administered as SC injection on Q4W.
Sponsors
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
All Cohorts: * Male or female participants 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). HES Cohort: * Documented HES diagnosis, defined as history of persistent eosinophilia \>1500 cells/µL without secondary cause on 2 examinations ≥1 month apart and evidence of eosinophil-mediated organ involvement. * Symptomatic active HES, or history of a prior flare, or considered eligible based on disease severity per investigator judgement. * AEC ≥1000 cells/µL at screening (Visit 1). * Documented negative testing for Fip1-like 1 gene fused with the platelet-derived growth factor receptor alpha gene (FIP1L1-PDGFR) fusion tyrosine kinase gene translocation.
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 participants 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. HES Cohort: * Life-threatening HES or HES complications, as judged by the investigator. * Hypereosinophilia of unknown significance (HE-US). * Diagnosis of systemic mastocytosis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Serum Concentrations of Benralizumab | Weeks 0, 12, 24, 25, 36, and 52 | The PK of benralizumab will be evaluated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| HES Cohort: Time to first HES worsening/flare | Up to 52 weeks | The effect of benralizumab on HES worsening/flares will be evaluated. |
| HES Cohort: Percentage of participants who experience a HES worsening/flare | Up to 52 weeks | The effect of benralizumab on HES worsening/flares will be evaluated. |
| HES Cohort: Number of HES worsening/flares (annualised rate/year) | Up to 52 weeks | 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). |
| HES Cohort: Percentage of Participants requiring an increase in corticosteroid dose | Up to 52 weeks | The effect of benralizumab on corticosteroid use will be evaluated. |
| HES Cohort: Time to first haematologic relapse | Up to 52 weeks | 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. |
| HES Cohort: Percentage of Participants with haematologic relapse | Up to 52 weeks | The effect of benralizumab on haematologic measures of disease activity will be evaluated. |
| HES Cohort: Percentage of Participants who have AEC < 500 cells/μL for 24 weeks | Up to 52 weeks | The effect of benralizumab on haematologic measures of disease activity will be evaluated. |
| HES Cohort: Patient Global Impression of Change (PGI-C) Score | Weeks 12, 24, 36 and 48 | 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'). |
Countries
Brazil, Canada, France, India, Israel, Mexico, Netherlands, Poland, Turkey (Türkiye), United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed