Hypereosinophilic SyndromePhase 2NCT06477653
Dupilumab as Add-On Therapy for Hypereosinophilic Syndrome With Partial Clinical Response to Eosinophil-Depleting Biologic Agents
A Phase 2 study testing dupilumab in people with Hypereosinophilic Syndrome, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Hypereosinophilic Syndrome
- What is being tested?
- dupilumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Feb 2025to 30 Mar 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
Show all 12Show fewer
- 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
- CRSwNP, defined as evidence of rhinosinusitis and nasal polyposis on physical examination or imaging
- 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
Who cannot join
- 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
Show all 16Show fewer
- 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
- Any esophageal stricture unable to be passed with a standard, diagnostic, 9 to 10 mm upper endoscope
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
NIH Clinical Center Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY dial 711, ccopr@nih.gov
About this study
Official title: 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
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.
Read more
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.
Read the 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:
- Incidence of new or worsening symptoms or signs attributable to eosinophilia requiring therapeutic intervention through week 24
- Peripheral blood AEC at 4, 12, and 24 weeks.
- Proportion of patients who maintain an eosinophil count below 0.5x10^9/L at 4, 12 and 24 weeks.
- Conditions
- Hypereosinophilic Syndrome
- Being tested
- dupilumab
- Keywords
- Hypereosinophilic Syndrome, Eosinophil, Monoclonal Antibody, Clinical Trial, Treatment
- Medical subject headings
- Hypereosinophilic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
dupilumabBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: dupilumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline through week 24
Secondary outcomes (3)
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.
Measured: During the first 24 weeks of study.
Peripheral blood absolute eosinophil counts.
To determine the effect of eosinophil-lowering therapy on dupilumab-induced blood eosinophilia and eosinophil-associated AEs.
Measured: At 4, 12 and 24 weeks.
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.
Measured: At 4, 12 and 24 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2024
- Study start5 Feb 2025
- Primary completion30 Dec 2026 (estimated)
- Study completion30 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hypereosinophilic SyndromeStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Amy D Klion, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06477653
- Sponsor's protocol ID
- 10001979
- Other IDs
- 001979-I
- Status last verified
- 4 Nov 2026
- First submitted
- 26 Jun 2024
- Last updated
- 6 Nov 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06477653
- Acronym / sponsor ID
- 10001979
- Conditions
- Hypereosinophilic Syndrome
- Keywords
- Hypereosinophilic Syndrome, Eosinophil, Monoclonal Antibody, Clinical Trial, Treatment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 5 Feb 2025 (actual)
- Primary completion
- 30 Dec 2026 (estimated)
- Study completion
- 30 Mar 2027 (estimated)
- First posted
- 27 Jun 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Incidence of new or worsening symptoms or signs attributable to eosinophilia requiring therapeutic intervention through week 24
- Peripheral blood AEC at 4, 12, and 24 weeks.
- Proportion of patients who maintain an eosinophil count below 0.5x10^9/L at 4, 12 and 24 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dupilumab in addition to mepolizumab, reslizumab, or benralizumab (at least 24 but up to 48 weeks) | Experimental | Biological: dupilumabDosing 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. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (16 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| dupilumabDupilumab 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. | Biological | Dupilumab in addition to mepolizumab, reslizumab, or benralizumab (at least 24 but up to 48 weeks) |
Primary outcome
Clinical improvement on dupilumab therapy as assessed by HES-MBS (HES-most bothersome symptom) and HES-SI (HES-Symptom Inventory).
Time frame: Baseline through week 24
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.
3 secondary outcomes
Incidence of new or worsening symptoms or signs attributable to eosinophilia requiring therapeutic intervention.
Time frame: During the first 24 weeks of study.
Peripheral blood absolute eosinophil counts.
Time frame: At 4, 12 and 24 weeks.
Proportion of patients who maintain an eosinophil count below 0.5 x 10^9/L.
Time frame: At 4, 12 and 24 weeks.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Amy D Klion, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing dupilumab in people with Hypereosinophilic Syndrome, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Amy D Klion, M.D. ((240) 381-6073, amy.klion@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical improvement on dupilumab therapy as assessed by HES-MBS (HES-most bothersome symptom) and HES-SI (HES-Symptom Inventory). (time frame: Baseline through week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2026.