A Phase 3 Study to Evaluate the Efficacy and Safety of Benralizumab in Patients With Hypereosinophilic Syndrome (HES) (NATRON)
- Conditions
- Health Condition 1: J989- Respiratory disorder, unspecified
- Registration Number
- CTRI/2023/11/060194
- Lead Sponsor
- abcorp Drug Development India Private Limite
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Yet Recruiting
- Sex
- Not specified
- Target Recruitment
- 0
Provision of the signed and dated written informed consent of the patient or the patients legally authorised representative, and informed assent from the patient prior to any mandatory study-specific procedures, sampling, and analyses.
Males and females 12 years of age and older at the time of signing the ICF.
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).
Documented negative testing for the FIP1L1-PDGFRA fusion tyrosine kinase gene translocation.
Stable HES treatment dose(s) and regimen for =4 weeks at the time of Visit 1
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.
- 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.
AEC =1000 cells/µL at Visit 1 (assessed by local laboratory).
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).
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.
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, 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 Investigators judgment participation in the study will not put the patient at risk
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.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 patients 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.
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 Investigators 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 fun
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method An HES worsening or flare is defined as HES clinical manifestations or lab abnormalities that result in an increase/burst of OCS =10 mg/day for at least 2 days, OR in increase or addition of new cytotoxic and/or immunosuppressive therapy, OR hospitalisationTimepoint: Time to first HES worsening/flare [ Time Frame: Up to 24 weeks]
- Secondary Outcome Measures
Name Time Method