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 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:
(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 Investigator's 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 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.
(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.

Locations

Purpose

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 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:
(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 Investigator's 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 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.
(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.

Locations

Oversight

More Information

The study website.

This is a one-page brochure on Natron study.