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/?L 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 ≥ 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 OR a documented history of 2 or more HES worsening/flares within 12 months prior to Visit 1 requiring an escalation in therapy

a. At least one flare within the past 12 months must not be related to a decrease in HES therapy during the 4 weeks prior to the flare
7. AEC ≥ 1000 cells/?L at Visit 1 (assessed by local laboratory)
8. Corticosteroid responsiveness defined as an AEC \< 1000 cells/?L after a 2-day course of OCS (prednisone/prednisolone) 1 mg/kg/day at Visit 2 (assessed by local laboratory). Other OCSs in equivalent doses are permitted
9. WOCBP must agree to use a highly effective method of birth control (confirmed by the investigator) from enrolment, throughout the study duration, and within 12 weeks after last dose of IP and have a negative urine dipstick pregnancy test result on Visit 1. Highly effective methods of birth control (those that can achieve a failure rate of less than 1% per year when used consistently and correctly) include:

1. Combined (oestrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, or transdermal
2. Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, or implantable
3. Intrauterine device
4. Intrauterine hormone-releasing system
5. Bilateral tubal occlusion
6. Sexual abstinence, ie, refraining from heterosexual intercourse (the reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient)
7. Vasectomised sexual partner (provided that partner is the sole sexual partner of the WOCBP study patient and that the vasectomised partner has received medical assessment of the surgical success)

Exclusion Criteria:

1. Life-threatening HES and/or HES complication(s) as judged by the investigator:

1. Medical intervention for HES-related life-threatening event(s) within 12 weeks prior to randomization
2. History of thrombotic complications, stroke, or significant cardiac damage related to HES, if the respective events were life threatening and currently represent a risk of life-threatening disease complications. Events that occurred in the past but considered resolved or stable, can be accepted if, as per investigator's judgment, participation in the study will not put the patient at risk
3. 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. Definitive diagnosis of eosinophilic granulomatosis with polyangiitis
4. Known, preexisting, 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, clinically significant echocardiography (if available) or ECG findings within 12 months prior to Visit 1 or clinically significant ECG findings at screening that in the opinion of the investigator may put the patients at risk
7. Known currently active liver disease

1. 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
2. ALT or AST level ≥ 3 × 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 or history of malignancy within 5 years before the screening visit with the following exceptions:

1. Patients treated for in situ carcinoma of the cervix who have completed curative therapy and are in remission for at least 12 months prior to signing the informed consent and
2. Patients with basal cell or superficial squamous skin cancer
3. Patients who have had other malignancies are eligible provided that the patient is in remission and curative therapy was completed at least 5 years prior to the date informed consent 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

12. A history of known immunodeficiency disorder other than that explained by the use of OCS or other therapy taken for HES. Positive HIV test 14. Evidence of prior benralizumab treatment failure

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 06/11/2024. Questions regarding updates should be directed to the study team contact.