Hypereosinophilic Syndrome (HES)
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of the signed and dated written informed consent of the patient or the patient’s legally authorised representative, and informed assent from the patient (per local regulations) prior to any mandatory study-specific procedures, sampling, and analyses 2. Males and females 12 years of age and older at the time of signing the ICF 3. Documented diagnosis of HES (history of persistent eosinophilia >1500 cells/µL without secondary cause on 2 examinations [interval =1 month; Valent et al 2012] and evidence of end organ manifestations attributable to the eosinophilia) 4. Documented negative testing for the FIP1L1-PDGFRA fusion tyrosine kinase gene translocation 5. Stable HES treatment dose(s) and regimen for for =4 weeks at the time of Visit 1 6. Signs or symptoms of HES worsening/flare and/or laboratory abnormalities indicative of HES worsening/flare (other than isolated eosinophilia) at Visit 1 7. AEC =1000 cells/µL at Visit 1 (assessed by local laboratory) 8. Corticosteroid responsiveness defined as an AEC =65 years) yes F.1.3.1 Number of subjects for this age range 6
Exclusion criteria
Exclusion criteria: 1. Life-threatening HES and/or HES complication(s) as judged by the Investigator: (a) Medical intervention for HES-related life-threatening event(s) within 12 weeks prior to randomisation OR (b) History of thrombotic complications, stroke, or significant cardiac damage related to HES, OR c) Disease severity that, in the opinion of the Investigator, makes the patient inappropriate for inclusion in the study 2. Presence of FIP1L1-PDGFRA fusion tyrosine kinase gene translocation or other known imatinib-sensitive mutation 3. Clinical diagnosis of eosinophilic granulomatosis with polyangiitis 4. Known, pre-existing, clinically significant endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, haematological, respiratory, or any other system abnormalities that are not associated with HES and are uncontrolled with standard treatment which, in the opinion of the Investigator, may put the patient at risk because of his/her participation in the study, or may influence the results of the study, or the patient’s ability to complete the entire duration of the study 5.Hypereosinophilia of unknown significance 6. Cardiovascular: Documented history of any clinically significant cardiac damage prior to Visit 1 that, in the opinion of the Investigator, would impact the patient’s participation during the study and/or clinically significant echocardiography findings within 12 months prior to Visit 1, if available 7. Known currently active liver disease (a) Chronic stable hepatitis B and C (including positive testing for hepatitis B surface antigen or hepatitis C antibody) or other stable chronic liver disease are acceptable if patient otherwise meets eligibility criteria. Stable chronic liver disease should generally be defined by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, oesophageal or gastric varices, or persistent jaundice, or cirrhosis (b) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level =3× the upper limit of normal (ULN) during the screening period (AST or ALT >5×ULN if documented HES with liver manifestations). Transient increase of AST/ALT level that resolves by the time of randomisation is acceptable if, in the Investigator’s opinion, the patient does not have an active liver disease and meets other eligibility criteria 8. Current malignancy, or history of malignancy, except: (a) Patients who have had basal cell carcinoma, localised squamous cell carcinoma of the skin, or in situ carcinoma of the cervix are eligible provided the patient is in remission and curative therapy was completed at least 12 months prior to the date that informed consent, and assent when applicable, was obtained (b) Patients who have had other malignancies are eligible provided the patient is in remission and curative therapy was completed at least 5 years prior to the date informed consent, and assent when applicable, was obtained 9. Diagnosis of systemic mastocytosis 10. Chronic or ongoing active infections requiring systemic treatment, as well as clinically significant viral, bacterial, or fungal infection within 4 weeks prior to Visit 1 11. A helminth parasitic infection diagnosed within 24 weeks prior to Visit 1 that has not been treated or has failed to respond to standard of care therapy. A confirmation of a complete resolution of any helminth parasitic infection prior to Visit 1 should be available 12. A history of known immunodeficiency disorder other than that explaine
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of benralizumab on the time to first HES worsening/flare;Secondary Objective: For DB period to evaluate the effect of benralizumab on: -time to 1st haematological relapse -proportion of patients (1) who experience HES worsening/flare (2) with haematologic relapse and (3) who maintain absolute eosinophil count (AEC) <500 cells/µL for 24 weeks -corticosteroid use -patient-reported measure of fatigue -health status and related quality of life measures (HRQoL): SF-36v2, PGIS, PGIC And also the safety, tolerability, PK and immunogenicity of benralizumab in patients with HES For OLE extension period to evaluate the effect of benralizumab on: -proportion of patients who experience HES worsening/flare and on the number of HES worsening/flare (a) -patient reported measure of fatigue (b) -HRQoL (a) Applicable to full duration of OLE (b) Applicable to 1st year of OLE only And also the safety, tolerability, PK and immunogenicity of benralizumab in patients with HES (a);Primary end point(s): Time to first HES worsening/flare (HES worsening/flare: HES clinical manifestations or lab abnormalities that result in an increase/burst of oral corticosteroids (OCS) =10 mg/day for at least 2 days OR an increase, or addition of new cytotoxic and/or immunosuppressive therapy, OR hospitalization);Timepoint(s) of evaluation of this end point: Throughout the 24wk double-blind treatment period | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): DB treatment period -Time to first haematologic relapse -Proportion of patients who experience HES worsening/flare -Proportion of patients who have haematologic relapse -Proportion of patients who have AEC<500 cells/µL for 24 weeks -Proportion of patients who require an increase in corticosteroid dose from baseline at any point in the double-blind treatment period -Fatigue questionnaire -Serum benralizumab concentrations, Anti-benralizumab antibodies and neutralising antibodies (nAb) -Safety and tolerability will be evaluated in terms of adverse events (AEs), vital signs, clinical laboratory, and electrocardiogram (ECG) OLE treatment period -Proportion of patients who experience HES worsening/flare -Fatigue questionnaire -Safety and tolerability will be evaluated in terms of AEs, vital signs, clinical laboratory, and ECG -Serum benralizumab concentrations, anti-benralizumab antibodies and nAb -HES symptom questionnaire;Timepoint(s) of evaluation of this end point: Varies depending on the endpoint/objective | — |
Countries
Austria, Belgium, Canada, Denmark, France, Germany, Israel, Italy, Japan, Netherlands, Poland, Spain, Switzerland, United Kingdom, United States
Contacts
Public ContactInformation Center
AstraZeneca AB
Outcome results
None listed