Background:
Hypereosinophilic syndrome (HES) is a blood disorder that causes high levels of white blood cells called eosinophils. HES can damage the lungs and airways, intestines, skin, and other organs. The current primary treatment for HES can cause serious side effects. Secondary treatments do not work in all people.
Objective:
To test an approved drug (dupilumab), combined with other drugs, in people with HES.
Eligibility:
People aged 18 years and older who take drugs (mepolizumab, reslizumab, or benralizumab) to treat HES.
Design:
Participants will have up to 6 clinic visits and 7 remote visits in up to 48 weeks.
Participants will be screened. They will have blood and urine tests. They will have a test of their heart function. They will take surveys about how HES affects their daily life. Some participants may have a bone marrow biopsy: A sample of tissue and fluid from inside a bone will be removed with a large needle.
Participants will have other tests specific to their symptoms. For example, those with symptoms affecting their lungs will have breathing tests. Others may have tests that target symptoms in their sinuses, gastrointestinal tract, or skin.
Dupilumab is injected under the skin once every 1 or 2 weeks. Dose and timing will vary among participants. They will be taught how to inject themselves at home between clinic visits. They will take dupilumab plus their current medications for 24 weeks. If the drug is helping them, they will continue taking it for another 24 weeks.
Participants will have a final visit 12 weeks after their last dose.
Age >=18 years
Documented diagnosis of HES with historic AEC>1.5x10^9/L on two occasions, no secondary etiology for the eosinophilia despite careful clinical evaluation, and evidence of end organ damage (histologic evidence of tissue infiltration by eosinophils and/or objective evidence of clinical pathology in any organ system that is temporally associated with eosinophilia and not clearly attributable to another cause)
Currently receiving treatment with an eosinophil-lowering biologic (mepolizumab, reslizumab, or benralizumab) for a minimum of 24 weeks
AEC<0.5x10^9/L
Pregnancy or lactation
Known allergic reaction to dupilumab or any of the excipients in Dupixent(TM)
Febrile illness within 7 days of enrollment
Treatment with an investigational drug or other intervention other than mepolizumab, reslizumab, or benralizumab within 12 weeks or 4 half-lives of the investigational agent (whichever is longer).
Parallel
dupilumab
Biological/VaccineDupilumab is an interleukin-4 receptor alpha antagonist. Dosing for an individual will be determined based on the nature of their residual symptoms and the FDA-approved dosing for that indication.
Clinical improvement on dupilumab therapy as assessed by HES-MBS (HES-most bothersome symptom) and HES-SI (HES-Symptom Inventory).
To assess the efficacy of add-on dupilumab therapy in reducing residual asthma, skin, esophageal, and sinus symptoms in patients with HES in complete hematologic and partial clinical remission on eosinophil-lowering biologics.
Incidence of new or worsening symptoms or signs attributable to eosinophilia requiring therapeutic intervention.
To determine the effect of eosinophil-lowering therapy on dupilumab-induced blood eosinophilia and eosinophil-associated AEs.
Peripheral blood absolute eosinophil counts.
To determine the effect of eosinophil-lowering therapy on dupilumab-induced blood eosinophilia and eosinophil-associated AEs.
Proportion of patients who maintain an eosinophil count below 0.5 x 10^9/L.
To determine the effect of eosinophil-lowering therapy on dupilumab-induced blood eosinophilia and eosinophil-associated AEs.
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