Dupilumab for Severe Eosinophilic Chronic Sinusitis

Overseen By Thanh Q Tran, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of South Florida

Must be taking: Intranasal corticosteroids

Must not be taking: Biologics, Immunosuppressants, Monoclonal antibodies, others

Disqualifiers: Asthma, Cancer, Immunodeficiency, others

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: Unknown

Duration: 24 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

The investigators will investigate the efficacy of dupilumab in patients with severe eosinophilic CRSsNP who are resistant to the conventional treatment with intranasal corticosteroids and have significantly extensive disease involving more than 2 sinuses bilaterally in sinus CT scan and Lund-Mackay sinus (LMK) CT score \>=10 at baseline.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before joining. For example, you must not have taken biologic therapy or systemic immunosuppressants within 2 months before screening, and you must have been on a continuous treatment with leukotriene antagonists for at least 30 days prior to screening. Please check with the trial team for specific guidance on your current medications.

What data supports the effectiveness of the drug Dupilumab for severe eosinophilic chronic sinusitis?

Research shows that Dupilumab is effective in treating chronic rhinosinusitis with nasal polyps, reducing symptoms and improving patients' quality of life. It works by blocking certain proteins involved in inflammation, and patients report significant improvements in their condition. ^{1 2 3 4 5}

Is dupilumab safe for humans?

Dupilumab is generally considered safe for humans, with some patients experiencing mild side effects like injection site reactions and temporary increases in eosinophils (a type of white blood cell). It has been used safely in conditions like asthma, atopic dermatitis, and chronic rhinosinusitis with nasal polyps. ^{1 2 6 7 8}

How does the drug Dupilumab differ from other treatments for severe eosinophilic chronic sinusitis?

Dupilumab is unique because it targets specific proteins involved in the inflammatory process, helping to reduce inflammation in the sinuses. It is administered as an injection, which can be more effective for some patients compared to traditional oral medications or nasal sprays. ^{9 10 11 12 13}

Research Team

Seong Cho, MD

Principal Investigator

University of South Florida

Eligibility Criteria

Adults with severe eosinophilic chronic sinusitis without nasal polyps, who haven't improved after at least 8 weeks of standard nasal corticosteroid treatment. Participants must have a high Lund-Mackay CT score (≥10), significant blood eosinophils (≥200), and experience symptoms like nasal blockage or loss of smell. Excluded are those with certain other conditions, recent infections requiring antibiotics, immunodeficiencies, cancer history within 5 years, drug abuse in the past year, pregnancy, breastfeeding or participation in another clinical trial.

Inclusion Criteria

LMK-CT score ≥ 10 (out of maximum of 24) at screening

Age 18 or older

The person has bilateral sinusitis, meaning that they have infection in both of their sinuses, and it has not been cured by using a corticosteroid treatment for at least 8 weeks.

Exclusion Criteria

Patients with conditions/concomitant diseases making them non-evaluable at screening or for the primary efficacy endpoint such as: Antrochoanal polyps, Nasal septal deviation that would occlude at least one nostril, Acute sinusitis, nasal infection or upper respiratory infection at screening, Ongoing rhinitis medicamentosa, Allergic granulomatous angiitis (Churg-Strauss syndrome), granulomatosis with polyangiitis (Wegener's granulomatosis), Young's syndrome, Kartagener's syndrome or other dyskinetic ciliary syndromes, concomitant cystic fibrosis, Radiologic suspicion, or confirmed invasive or expansive fungal rhinosinusitis, With co-morbid asthma are excluded if forced expiratory volume (FEV1) is 50% (of predicted normal) or less, With known active bacterial, viral, fungal, mycobacterial infection, or other infection or any major episode of infection that required hospitalization or treatment with IV antibiotics within 30 days of screening or during screening or oral antibiotics within 14 days prior to screening. Fungal infection of nail beds is allowed, Have human immunodeficiency virus/acquired immune deficiency syndrome, Have acute or chronic hepatitis B/hepatitis C infection, History of an opportunistic infection (eg, pneumocystis carinii, cryptococcal meningitis, progressive multifocal leukoencephalopathy) or serious bacterial, viral, or fungal infections (eg, disseminated herpes simplex, disseminated herpes zoster) and requiring IV medication(s) ≤ 3 weeks prior to randomization, History of or currently active primary or secondary immunodeficiency, History of cancer within the last 5 years, including solid tumors and hematological malignancies (except basal cell and in situ squamous cell carcinomas of the skin that have been excised and resolved) or colonic mucosal dysplasia, History of lymphoproliferative disorder, lymphoma, leukemia, myeloproliferative disorder, or multiple myeloma, History of alcohol or drug abuse within 1 year prior to randomization, Receipt of live vaccine within 4 weeks prior to randomization, Pregnant or breastfeeding, Participation in another clinical study or treatment with an investigational drug or device, Serious or active medical or psychiatric condition which, in the opinion of the Investigator, may interfere with treatment, assessment, or compliance with the protocol

You have received an experimental monoclonal antibody within the past 6 months or within five times its half-life if its duration is unknown.

You have previously participated in a clinical trial for a medication called dupilumab.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Dupilumab 300 mg every other week for 24 weeks

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Dupilumab

Trial Overview The study is testing Dupilumab's effectiveness for patients with severe eosinophilic chronic sinusitis who don't respond to usual treatments. It involves comparing Dupilumab injections against a placebo to see if it can reduce disease severity as shown by CT scans and symptom scores.

Participant Groups

Group I: Active drug Active Control 1 Intervention

Dupilumab 300 mg every other week for 24 weeks

Group II: Placebo Placebo Group 1 Intervention

Placebo

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?

University of South Florida

Lead Sponsor

Trials

433

Recruited

198,000+

Findings from Research

In a study of 130 patients treated with dupilumab for severe chronic rhinosinusitis with nasal polyps over 18 months, there was a significant reduction in nasal polyposis and improvement in symptoms and quality of life.

The treatment was associated with a transient increase in blood eosinophils and a gradual decrease in total IgE levels, indicating potential changes in immune response, although IgG and IgA levels remained within normal ranges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dupilumab's Impact on Blood Parameters in Nasal Polyposis: 18-Month Follow-Up in Real Life. Loperfido, A., Ciofalo, A., Cavaliere, C., et al.[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]

In a study involving 724 patients with severe chronic rhinosinusitis with nasal polyps, dupilumab significantly improved symptoms of nasal congestion, loss of smell, and rhinorrhoea compared to placebo, with improvements seen as early as Week 2 and continuing through Week 52.

A higher proportion of patients treated with dupilumab reported a reduction from moderate-to-severe symptoms to no-to-mild symptoms at multiple time points, indicating its efficacy in managing this condition regardless of prior surgery or coexisting asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dupilumab provides early and durable improvement of symptoms in patients with chronic rhinosinusitis with nasal polyps. Gevaert, P., Lee, SE., Settipane, RA., et al.[2023]

Dupilumab significantly improved symptoms of chronic rhinosinusitis with nasal polyps (CRSwNP) in patients regardless of their surgical history, demonstrating its efficacy across different subgroups based on prior surgeries and time since last surgery.

Patients who had undergone surgery more recently (within <3 years) experienced greater improvements in nasal polyp scores and other measures compared to those who had surgery longer ago, while the safety profile of dupilumab remained consistent with previous findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of dupilumab in patients with a history of prior sinus surgery for chronic rhinosinusitis with nasal polyps. Hopkins, C., Wagenmann, M., Bachert, C., et al.[2021]

In a study of 66 patients with chronic rhinosinusitis with nasal polyps (CRSwNP), dupilumab significantly reduced symptoms and nasal polyp scores after 6 and 12 months, indicating its effectiveness as a treatment.

The safety profile of dupilumab was favorable, with only 12.7% of patients experiencing injection site reactions and 11.1% having transient hypereosinophilia, suggesting it is a safe option for managing CRSwNP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and Safety Profile of Dupilumab in Chronic Rhinosinusitis with Nasal Polyps: Real-Life Data in Tertiary Care. Galletti, C., Barbieri, MA., Ciodaro, F., et al.[2023]

Dupilumab significantly improved symptoms and objective measures of chronic rhinosinusitis with nasal polyps (CRSwNP) in patients, regardless of whether they also had allergic rhinitis, based on a pooled analysis of 724 patients from two phase III studies.

The treatment also reduced the need for systemic corticosteroids and sinonasal surgery, demonstrating its efficacy and safety profile, which was consistent across patients with and without allergic rhinitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dupilumab efficacy in patients with chronic rhinosinusitis with nasal polyps with and without allergic rhinitis. Peters, AT., Wagenmann, M., Bernstein, JA., et al.[2023]

Dupilumab, a monoclonal antibody used to treat conditions like asthma and atopic dermatitis, can cause hypereosinophilia (high eosinophil levels) as a potential adverse effect, which poses a challenge for clinicians.

An algorithm has been proposed to help manage dupilumab-induced hypereosinophilia, allowing for proper investigation of related health issues while minimizing unnecessary discontinuation of the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dupilumab-induced hypereosinophilia: review of the literature and algorithm proposal for clinical management. Caminati, M., Olivieri, B., Dama, A., et al.[2022]

References

1. Egypt pubmed.ncbi.nlm.nih.gov

Dupilumab's Impact on Blood Parameters in Nasal Polyposis: 18-Month Follow-Up in Real Life. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Subgroups in the treatment of nasal polyposis with dupilumab: A retrospective study. [2023]

3. Australia pubmed.ncbi.nlm.nih.gov

Dupilumab provides early and durable improvement of symptoms in patients with chronic rhinosinusitis with nasal polyps. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Efficacy of dupilumab in patients with a history of prior sinus surgery for chronic rhinosinusitis with nasal polyps. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Long-Term Efficacy of Dupilumab for Eosinophilic Chronic Rhinosinusitis. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Effectiveness and Safety Profile of Dupilumab in Chronic Rhinosinusitis with Nasal Polyps: Real-Life Data in Tertiary Care. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Dupilumab efficacy in patients with chronic rhinosinusitis with nasal polyps with and without allergic rhinitis. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Dupilumab-induced hypereosinophilia: review of the literature and algorithm proposal for clinical management. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Low frequency of HLA-A*0201 allele in patients with Epstein-Barr virus-positive nasal lymphomas with polymorphic reticulosis morphology. [2016]

10. India pubmed.ncbi.nlm.nih.gov

Expression of C-X-C chemokine receptor type 7 in otorhinolaryngologic neoplasms. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Expression of HLA class I, beta(2)-microglobulin, TAP1 and IL-10 in Epstein-Barr virus-associated nasal NK/T-cell lymphoma: Implications for tumor immune escape mechanism. [2019]

12. United States pubmed.ncbi.nlm.nih.gov

Therapeutic LMP1 polyepitope vaccine for EBV-associated Hodgkin disease and nasopharyngeal carcinoma. [2021]

13. United States pubmed.ncbi.nlm.nih.gov

Identification of a novel EBV-induced membrane glycoprotein of 43 kDa with H667 MAb. [2019]