NCT06477653

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

A Pilot Phase 2 Study of the Safety and Efficacy of Dupilumab as Add-on Therapy for Hypereosinophilic Syndrome With Partial Clinical Response to Eosinophil-Depleting Biologic Agents

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 18 Years – 99 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Hypereosinophilic Syndrome

Interventions

Type	Name	Description
BIOLOGICAL	dupilumab	Dupilumab 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.

Timeline

• Start date: 2025-02-05
• Primary completion: 2026-12-30
• Completion: 2027-03-30
• First posted: 2024-06-27
• Last updated: 2026-04-08

Locations

1 site across 1 country: United States