Dupilumab as Add-On Therapy for Hypereosinophilic Syndrome With Partial Clinical Response to Eosinophil-Depleting Biologic Agents

Study Description: The purpose of this study is to evaluate the efficacy and tolerability of dupilumab in reducing clinical manifestations in patients with hypereosinophilic syndrome (HES) and persistent eosinophil-related pulmonary, skin, gastrointestinal, or sinus symptoms despite eosinophil reduction in response to eosinophil-lowering biologic therapy. Patients who meet criteria for HES and are currently receiving mepolizumab, reslizumab or benralizumab with persistent symptoms (as above) despite absolute eosinophil count (AEC)\<0.5x10\^9/L will be eligible to enroll. Participants will be treated with dupilumab at the US Food and Drug Administration (FDA)-approved doses for asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyposis (CRSwNP), or eosinophilic esophagitis (EoE) depending on their residual symptoms Participants will have clinical evaluations and AEC measured every 4 weeks for 24 weeks. Participants who remain in clinical remission and have an AEC\<0.5x10\^9/L will be eligible to continue dupilumab therapy for an additional 24 weeks with tapering of background therapy (other than the eosinophil-lowering biologic) as clinically tolerated. Objectives: Primary Objective: To assess the efficacy of add-on dupilumab therapy in reducing residual pulmonary, skin, esophageal, and sinus symptoms in patients with HES in complete hematologic and partial clinical remission on eosinophil-lowering biologics Secondary Objective: To determine the effect of eosinophil-lowering therapy on dupilumab-induced blood eosinophilia and eosinophil-associated AEs Endpoints: Primary Endpoint: Clinical improvement on dupilumab therapy at 24 weeks, as assessed by HES-Most Bothersome Symptom (HES-MBS) and HES-Symptom Inventory (HES-SI) Secondary Endpoints: 1. Incidence of new or worsening symptoms or signs attributable to eosinophilia requiring therapeutic intervention through week 24 2. Peripheral blood AEC at 4, 12, and 24 weeks. 3. Proportion of patients who maintain an eosinophil count below 0.5x10\^9/L at 4, 12 and 24 weeks.