A Study to Evaluate the Effectiveness and Safety of Benralizumab in Patients with Hypereosinophilic Syndrome (HES)

Overview

About this study

This is a multicentre, randomised, double-blind (DB), parallel-group, placebo-controlled, 24-week Phase 3 study to compare the efficacy and safety of benralizumab versus placebo administered by SC injection Q4W in patients with hypereosinophilic syndrome (HES). This study comprises 2 distinct periods (together defined as the 'main study'): A 24-week, DB treatment period, during which patients will be randomised to receive either benralizumab or placebo, in addition to prior stable HES background therapy, and an open-label (OLE) treatment period, during which all patients will receive benralizumab. The primary database lock (DBL) will occur when at least 47 patients have had their first HES worsening/flare event and all randomised patients have been followed up for the 24-week DB treatment period. The target patient population is male and female patients 12 years of age and older with symptomatic active HES. Approximately 120 eligible patients will be randomised at a 1:1 ratio to receive either benralizumab or matching placebo.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

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.

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 1 mg/kg/day at Visit 2 (assessed by local laboratory).

9. Women of childbearing potential (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

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 randomisation OR

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, 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,
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. 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:

1. 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.

2. 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.

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

Eligibility last updated 11/3/22. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Thanai Pongdee, M.D.

Open for enrollment

Contact information:

Kay Bachman R.N., C.C.R.C.

(507) 284-5689

bachman.kay@mayo.edu

More information

Publications

Publications are currently not available