A Phase 3 Study to Evaluate the Efficacy and Safety of Benralizumab in Patients With Hypereosinophilic Syndrome (HES)

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Brief Title

A Phase 3 Study to Evaluate the Efficacy and Safety of Benralizumab in Patients With Hypereosinophilic Syndrome (HES)

Official Title

A Multicentre, Randomised, Double-blind, Parallel-group, Placebo-controlled, 24-week Phase 3 Study With an Open-label Extension to Evaluate the Efficacy and Safety of Benralizumab in Patients With Hypereosinophilic Syndrome (HES)

Brief Summary

      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.
    


Study Phase

Phase 3

Study Type

Interventional


Primary Outcome

Time to first HES worsening/flare

Secondary Outcome

 Time to first haematologic relapse

Condition

Hypereosinophilic Syndrome

Intervention

Benralizumab

Study Arms / Comparison Groups

 Benralizumab arm
Description:  1x Benralizumab SC injection

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

120

Start Date

January 6, 2020

Completion Date

July 23, 2023

Primary Completion Date

June 26, 2022

Eligibility 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 ≥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 <1000 cells/μL 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 16 weeks (5 half-lives) 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, OR

               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. 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.

               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.
      

Gender

All

Ages

12 Years - 130 Years

Accepts Healthy Volunteers

No

Contacts

, 1-877-240-9479, [email protected]zeneca.com



Administrative Informations


NCT ID

NCT04191304

Organization ID

D3254C00001

Secondary IDs

2019-002039-27

Responsible Party

Sponsor

Study Sponsor

AstraZeneca


Study Sponsor

, , 


Verification Date

December 2019