Dupilumab for Hypereosinophilic Syndrome

Overseen By Amy D Klion, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must be taking: Mepolizumab, Reslizumab, Benralizumab

Must not be taking: Investigational drugs

Disqualifiers: Pregnancy, Immunodeficiency, Malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 24 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests dupilumab, a medication approved for other uses, to determine its effectiveness for hypereosinophilic syndrome (HES). HES is a blood disorder that causes high levels of eosinophils, leading to damage in organs like the lungs, skin, and intestines. The trial aims to assess whether dupilumab, combined with other medications, can improve symptoms in individuals who haven't fully responded to their current treatment. It seeks participants with HES who are already using drugs like mepolizumab, reslizumab, or benralizumab but still experience daily symptoms such as asthma, skin issues, or sinus problems. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

No, you will not have to stop taking your current medications. The trial allows participants to continue their existing treatment with mepolizumab, reslizumab, or benralizumab while adding dupilumab.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that dupilumab is generally well-tolerated by people with various conditions. For instance, those with persistent asthma who used dupilumab experienced fewer asthma attacks compared to those who took a placebo. This suggests that the treatment is safe for individuals with high levels of eosinophils, similar to those found in hypereosinophilic syndrome (HES).

Moreover, dupilumab's safety remains consistent across different conditions like eczema and asthma, indicating that side effects are similar and manageable. Common side effects may include reactions at the injection site or mild infections, while serious side effects are rare.

The FDA has already approved dupilumab for other conditions, supporting its safety profile. This trial aims to determine if it can also help people with HES without causing major side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for hypereosinophilic syndrome?

Unlike the standard treatments for hypereosinophilic syndrome, which typically involve corticosteroids and immunosuppressants, Dupilumab acts differently by targeting the IL-4 and IL-13 pathways. These pathways play a crucial role in the inflammatory processes associated with this condition. Researchers are excited about Dupilumab because it offers a more targeted approach that could potentially reduce inflammation more effectively, with fewer side effects. Additionally, it is administered via subcutaneous injection, which can be more convenient for patients compared to intravenous treatments.

What evidence suggests that dupilumab might be an effective treatment for hypereosinophilic syndrome?

This trial will evaluate the effectiveness of dupilumab for hypereosinophilic syndrome (HES) when used alongside mepolizumab, reslizumab, or benralizumab. Studies have shown that dupilumab can be effective for individuals with HES. Research indicates that dupilumab reduces symptoms in HES patients by targeting and lowering eosinophils, the problematic white blood cells. In individuals with asthma and high levels of these cells, dupilumab reduced flare-ups by 87% compared to a placebo. Another study found it improved lung function and asthma control by reducing certain signs of inflammation. These findings suggest that dupilumab could be a promising treatment option for managing symptoms in people with HES. ^{3 4 6 7 8}

Who Is on the Research Team?

Amy D Klion, M.D.

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

Are You a Good Fit for This Trial?

Adults over 18 with Hypereosinophilic Syndrome (HES) who are partially responding to current eosinophil-depleting drugs like mepolizumab, reslizumab, or benralizumab. Participants will undergo various tests and must be willing to self-inject dupilumab regularly.

Inclusion Criteria

AEC<0.5x10^9/L

For participants who can become pregnant: sexual abstinence or use of highly effective contraception 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)

Exclusion Criteria

Pregnancy or lactation

Known allergic reaction to dupilumab or any of the excipients in Dupixent(TM)

Any condition that, in the investigator's opinion, places the patient at undue risk by participating in the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive dupilumab in addition to their current eosinophil-lowering biologic therapy for 24 weeks. Dosing varies based on residual symptoms.

24 weeks

6 visits (in-person), 7 visits (remote)

Extended Treatment

Participants who respond well to treatment continue dupilumab for an additional 24 weeks with tapering of background therapy.

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

12 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Dupilumab

Trial Overview The trial is testing the effectiveness of adding dupilumab to existing treatments for HES. Over a period of up to 48 weeks, participants will receive injections alongside their standard medication and attend clinic and remote visits.

How Is the Trial Designed?

Group I: Dupilumab in addition to mepolizumab, reslizumab, or benralizumab (at least 24 but up to 48 weeks) Experimental Treatment 1 Intervention

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.

Dupilumab is already approved in United States, European Union for the following indications:

Approved in United States as Dupixent for:

• Atopic dermatitis
• Asthma
• Chronic rhinosinusitis with nasal polyps
• Eosinophilic esophagitis

Approved in European Union as Dupixent for:

• Atopic dermatitis
• Asthma
• Chronic rhinosinusitis with nasal polyps
• Eosinophilic esophagitis

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

In a study of 21 patients with chronic rhinosinusitis with nasal polyps (CRSwNP) undergoing dupilumab therapy, 19% developed hypereosinophilia (HE), but no cases of hypereosinophilic syndrome were reported, indicating that HE is generally benign in this context.

The study proposes a management flowchart for HE during dupilumab treatment, suggesting that HE levels below 3 × 10^9/L can be monitored without intervention, while levels above this threshold may require short-term corticosteroid therapy to prevent potential organ involvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypereosinophilia management in patients with type 2 chronic rhinosinusitis treated with dupilumab: preliminary results. Vinciguerra, A., Rampi, A., Yacoub, MR., et al.[2022]

In some patients, treatment with dupilumab can lead to a persistent increase in eosinophil levels, known as hypereosinophilia.

A two-month follow-up eosinophil count can help predict whether this hypereosinophilia will last over time, which is important for managing patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early increase in eosinophil count may predict long-term hypereosinophilia during dupilumab treatment: a 2-year observational study. Rampi, A., Tanzini, U., Vinciguerra, A., et al.[2023]

Dupilumab (Dupixent) has been associated with a risk of ocular adverse reactions, highlighting the importance of monitoring patients for eye-related side effects during treatment.

Prompt management of any ocular issues is essential for patients receiving dupilumab, ensuring their safety and well-being while benefiting from the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety update: dupilumab and ocular adverse reactions. [2022]

A 76-year-old male patient with hypereosinophilic dermatitis (HED) showed a significant reduction in eosinophil levels from 20.7% to 4.1% after 8 weeks of treatment with dupilumab, along with complete relief from severe itching.

After 6 months of dupilumab treatment, the patient remained relapse-free for 17 months without any reported adverse events, suggesting that dupilumab may be a safe and effective long-term treatment option for HED.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypereosinophilic Dermatitis: Successful Treatment with Dupilumab. Wu, C., Zhang, J., Zhao, Y.[2023]

Dupilumab is an effective treatment for chronic rhinosinusitis with polyposis (CRSwNP), showing significant improvements in patients' subjective disease burden and objective measures, regardless of specific disease characteristics like aspirin exacerbated respiratory disease (AERD) or elevated eosinophil levels.

In a study of 75 patients, dupilumab therapy was reported to be more effective than functional endoscopic sinus surgery (FESS) in certain cases, indicating that some patients may benefit more from dupilumab than from surgical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subgroups in the treatment of nasal polyposis with dupilumab: A retrospective study. Bertlich, M., Freytag, S., Dombrowski, T., et al.[2023]

A 72-year-old man with idiopathic hypereosinophilic syndrome was successfully treated with dupilumab, leading to complete clinical and biochemical resolution of the disease.

Dupilumab treatment resulted in a significant decrease in eosinophil levels from 4.13 to 0.92, and the patient experienced no complications during the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypereosinophilic syndrome with cutaneous manifestations successfully treated with Dupilumab as a sole agent: A case report. Scully, K., Shao, E., Banney, L., et al.[2023]

Dupilumab, a biologic drug for severe asthma, can cause transient hypereosinophilia in 4%-25% of patients, which may lead to serious conditions like eosinophilic granulomatosis with polyangiitis (EGPA) and worsening asthma symptoms, especially when tapering corticosteroids or switching treatments.

When selecting biologic therapies, it's important to monitor eosinophil levels, as anti-IL-5 agents are preferred for patients with high eosinophil counts (>1500/μL), and combining anti-IL-5 and anti-IL-4/IL-13 therapies may provide better control of asthma and prevent complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eosinophilia Induced by Blocking the IL-4/IL-13 Pathway: Potential Mechanisms and Clinical Outcomes. Olaguibel, JM., Sastre, J., Rodríguez, JM., et al.[2022]

Dupilumab is a monoclonal antibody that targets the IL-4 receptor, effectively inhibiting the action of IL-4 and IL-13, which are key players in allergic diseases.

It received its first approval in March 2017 for treating moderate-to-severe atopic dermatitis in adults who do not respond well to topical treatments, and is also being developed for asthma, nasal polyps, and eosinophilic esophagitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dupilumab: First Global Approval. Shirley, M.[2022]

Citations

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NCT02277769 | Study of Dupilumab (REGN668/ ... This is a randomized, double-blind, placebo-controlled, parallel-group study to confirm the efficacy and safety of Dupilumab monotherapy in adults with moderate ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1304048

Dupilumab in Persistent Asthma with Elevated Eosinophil ... Three patients had an asthma exacerbation with dupilumab (6%) versus 23 with placebo (44%), corresponding to an 87% reduction with dupilumab ( ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39515522/

Dupilumab Use in Patients With Hypereosinophilic Syndromes Conclusions: These data suggest that dupilumab is effective in treating residual symptoms in HES patients but that the incidence of eosinophil-related ...

4. news.sanofi.us news.sanofi.us/2023-10-22-Dupixent-R-dupilumab-Phase-3-Results-show-sustained-efficacy-for-up-to-one-year-in-children-1-to-11-years-of-age-with-eosinophilic-esophagitis-EoE

Dupixent® (dupilumab) Phase 3 Results show sustained ... Data from this Phase 3 trial support the potential of dupilumab to treat EoE in children, with sustained efficacy and safety, which is ...

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Dupilumab in persistent asthma with elevated eosinophil ... Significant improvements were observed for most measures of lung function and asthma control. Dupilumab reduced biomarkers associated with Th2- ...

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EoE Safety Data | DUPIXENT® (dupilumab) The safety profile of DUPIXENT was similar in Parts A and B between adults and 72 pediatric subjects aged 12 to 17 years, weighing ≥40 kg.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02277769

NCT02277769 | Study of Dupilumab (REGN668 ... This is a randomized, double-blind, placebo-controlled, parallel-group study to confirm the efficacy and safety of Dupilumab monotherapy in adults with ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2019/761055Orig1s014rev.pdf

Approval Package - accessdata.fda.gov Overall, the safety data are consistent with the existing safety data from the atopic dermatitis and asthma programs and do not raise safety ...