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

NCT06477653 | Recruiting Phase 2

• 2 other identifiers: 10001979001979-I
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hypereosinophilic Syndrome

Keywords

Hypereosinophilic Syndrome; Eosinophil; Monoclonal Antibody; Clinical Trial; Treatment

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline through week 24

Secondary Outcomes (3)

• Incidence of new or worsening symptoms or signs attributable to eosinophilia requiring therapeutic intervention.

  During the first 24 weeks of study.

• Peripheral blood absolute eosinophil counts.

  At 4, 12 and 24 weeks.

• Proportion of patients who maintain an eosinophil count below 0.5 x 10^9/L.

  At 4, 12 and 24 weeks.

Study Arms (1)

Dupilumab in addition to mepolizumab, reslizumab, or benralizumab (at least 24 but up to 48 weeks)

EXPERIMENTAL

Dosing for an individual will be determined based on the nature of their residual symptoms and the FDA-approved dosing for that indication. Patients will self-administer using pre-filled syringes with needle shield or pre-filled pens. Patients with asthma and/or atopic dermatitis will receive a loading dose of 600 mg subcutaneously (followed by 300 mg SC every 2 weeks. Patients with Chronic Rhinosinusitis with Nasal Polyposis will not receive a loading dose and will be treated with 300 mg subcutaneously every 2 weeks. Patients with Eosinophilic Esophagitis will not receive a loading dose of 600 mg subcutaneously and will be treated with 300 mg subcutaneously weekly. Patients who meet criteria for more than one indication will be treated with the higher dose.

Biological: dupilumab

Interventions

dupilumab BIOLOGICAL

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.

Dupilumab in addition to mepolizumab, reslizumab, or benralizumab (at least 24 but up to 48 weeks)

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To be eligible to participate in this study, an individual must meet all the following criteria:
• 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
• Residual symptoms after a minimum of 24 weeks of eosinophil-lowering biologic therapy with at least 1 most bothersome symptom of moderate severity (HES-SI score \>=2) consistent with \>=1 of the following diagnoses:
• a. asthma, defined as physician-documented asthma requiring medium to high dose inhaled corticosteroids + long-acting beta agonist b. atopic dermatitis, defined as physician-documented chronic or recurrent inflammatory skin disease
• c. CRSwNP, defined as evidence of rhinosinusitis and nasal polyposis on physical examination or imaging
• d. EoE, defined as biopsy-proven esophageal eosinophilia \>15 eosinophils/high power field
• For participants who can become pregnant: sexual abstinence or use of highly effective contraception (i.e., partner vasectomy, bilateral tubal ligation, IUD, progestin implants, and other hormonal methods) starting 4 weeks prior to study drug initiation and agreement to use such a method during study participation and for an additional 12 weeks after the end of study drug administration
• Participation in NIH protocol 94-I-0079 (Activation and function of eosinophils in conditions with blood or tissue eosinophilia)
• Ability of subject to understand and the willingness to sign a written informed consent document

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• 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).
• Known or suspected acquired or inborn immunodeficiency disorder, including HIV infection
• Known diagnosis of eosinophilic granulomatosis with polyangiitis
• Change in eosinophil-active therapy within the past 6 weeks, including but not limited to topical corticosteroids, leukotriene inhibitors, initiation or change of a food-elimination diet regimen or re-introduction of a previously eliminated food (in patients with gastrointestinal involvement), and proton pump inhibitors (in patients with gastrointestinal involvement)
• Planned or anticipated major surgical procedure during the study
• Active parasitic infection
• History of malignancy within 5 years, excluding completely treated in situ carcinoma of the cervix, or squamous or basal cell carcinoma of the skin
• Any condition that, in the investigator s opinion, places the patient at undue risk by participating in the study
• For patients with eosinophilic gastrointestinal disease only:
• Active infection with Helicobacter pylori
• History of achalasia, Crohn s disease, ulcerative colitis, celiac disease, or prior esophageal surgery

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Hypereosinophilic Syndrome

Interventions

dupilumab

Condition Hierarchy (Ancestors)

Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Amy D Klion, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amy D Klion, M.D.

CONTACT

(240) 381-6073; amy.klion@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2024
• First Posted: June 27, 2024
• Study Start: February 5, 2025
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): March 30, 2027
• Last Updated: May 4, 2026

Record last verified: 2026-04-30

Locations

US (1)