Dupilumab for Chronic Sinusitis

Recruiting in Palo Alto (17 mi)

Overseen by Jody Tversky

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Johns Hopkins University

Must not be taking: Anti-interleukin, Immunosuppressives, Biologics, others

Disqualifiers: Nasal polyps, Uncontrolled asthma, Immunodeficiency, others

Prior Safety Data

Breakthrough Therapy

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial aims to test the effectiveness of dupilumab, a medication that targets specific immune responses, in treating chronic sinus disease without nasal polyps. The study focuses on patients who have limited treatment options and suffer from long-term sinus issues. Dupilumab works by blocking proteins that cause inflammation, potentially offering a new solution for these patients. Dupilumab is a novel monoclonal antibody that recently received approval for the treatment of chronic rhinosinusitis with nasal polyps.

Will I have to stop taking my current medications?

The trial requires stopping certain medications, such as anti-interleukin therapies, immunosuppressive medications, and high-dose aspirin. If you're on these or similar medications, you may need to stop them before joining the trial.

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

Research shows that Dupilumab significantly improves nasal symptoms and reduces the need for surgery and corticosteroids in patients with chronic sinusitis with nasal polyps. It works by blocking certain proteins (interleukin-4 and interleukin-13) that cause inflammation, leading to better symptom control and quality of life. ^{1 2 3 4 5}

Is dupilumab safe for treating chronic sinusitis?

Dupilumab has been shown to be generally safe for treating chronic sinusitis with nasal polyps, with some patients experiencing mild reactions like injection site reactions and temporary increases in certain blood cells. Overall, the treatment is considered safe, but further studies are needed to understand long-term effects. ^{1 6 7 8 9}

How is the drug Dupilumab different from other treatments for chronic sinusitis?

Dupilumab is unique because it is the first approved biological treatment specifically for severe chronic rhinosinusitis with nasal polyps (CRSwNP), and it works by blocking the receptors for interleukin 4 (IL-4) and IL-13, which are key drivers of the inflammation in this condition. ^{1 2 3 4 10}

Eligibility Criteria

This trial is for adults aged 18-75 with chronic sinusitis without nasal polyps, a certain level of sinus infection severity, and specific blood or allergy test results. Participants must agree to use effective contraception if applicable and can't be on certain medications or have conditions like uncontrolled asthma, immune deficiencies, recent biologic medication use, or serious illnesses.

Inclusion Criteria

You have a CT score of 4 or more on both sides of your sinuses, or an endoscopy score of 4 or more.

I agree to use contraception if I'm sexually active.

You have a high blood eosinophil count or have tested positive for allergies to at least 5 out of 30 allergens, or you have a low blood eosinophil count and have tested negative for allergies (low Th2 group).

Exclusion Criteria

I haven't taken any biologic medication in the past 5 months or longer.

My previous cancer has been in remission for at least 5 years.

I am not currently taking any excluded medications.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive either dupilumab or placebo for chronic rhinosinusitis without nasal polyps

6 months

Every two weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Continuous monitoring

Treatment Details

Interventions

• Dupilumab (Monoclonal Antibodies)

Trial Overview The study tests the effectiveness of Dupilumab in treating chronic rhinosinusitis without nasal polyps compared to a placebo. It aims to understand how well Dupilumab works for different underlying causes of this condition by also looking at secondary outcomes.

Participant Groups

Group I: dupilumab treatment group Experimental Treatment 1 Intervention

dupilumab treatment group

Group II: placebo group Placebo Group 1 Intervention

placebo group

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Johns Hopkins University School of Medicine Baltimore, MD

Who Is Running the Clinical Trial?

Johns Hopkins University Lead Sponsor

Regeneron Pharmaceuticals Industry Sponsor

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] Dupilumab represents the first approved biological for severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP).

2. New Zealand pubmed.ncbi.nlm.nih.gov

Rapid and Continuing Improvements in Nasal Symptoms with Dupilumab in Patients with Severe CRSwNP. [2022] In the phase 3 SINUS-24 (NCT02912468) and SINUS-52 (NCT02898454) studies in adults with severe chronic rhinosinusitis with nasal polyps (CRSwNP), dupilumab significantly improved the co-primary endpoints of change from baseline to Week 24 in nasal polyp score (NPS) and nasal congestion/obstruction (NC) vs placebo on background intranasal corticosteroids (standard of care [SOC]). This post hoc analysis of SINUS-24/-52 investigated the direction and magnitude of within-patient change in these endpoints over time.

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

Dupilumab provides early and durable improvement of symptoms in patients with chronic rhinosinusitis with nasal polyps. [2023] To evaluate within-patient symptom improvement in the dupilumab SINUS-24/-52 studies in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) (NCT02912468/NCT02898454).

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] Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease treated with sinus surgery when refractory to medical intervention. However, recurrence postsurgery is common. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor for interleukin 4 (IL-4) and IL-13, key and central drivers of type 2 inflammation. We report the efficacy of dupilumab in patients with CRSwNP from the SINUS-24/SINUS-52 trials (NCT02912468/NCT02898454), by number of prior surgeries and time since last surgery.

5. Netherlands pubmed.ncbi.nlm.nih.gov

Dupilumab reduces systemic corticosteroid use and sinonasal surgery rate in CRSwNP. [2022] Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease with a high symptom burden and poor quality of life. Treatment options include recurrent surgeries and/or frequent systemic corticosteroids (SCS). Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key drivers of type 2-mediated inflammation. We report results of pooled analyses from 2 randomised, double-blind, placebo-controlled phase 3 studies (SINUS 24 [NCT02912468]; SINUS-52 [NCT02898454]) to evaluate dupilumab effect versus placebo in adults with CRSwNP with/without SCS use and sinonasal surgery.

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

Dupilumab Adverse Events in Nasal Polyp Treatment: Analysis of FDA Adverse Event Reporting System. [2022] Dupilumab was the first biologic approved to treat chronic rhinosinusitis with nasal polyps (CRSwNP). While the risk of adverse events in phase-III clinical trials was low, dupilumab-associated adverse reactions (DAR) with real-world use is unknown and potentially under-reported. We aimed to evaluate DAR for CRSwNP treatment (CRSwNP-tx) using the FDA Adverse Event Reporting System (FAERS).

7. 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] Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by a type 2 pattern of inflammation resulting in the production of some cytokines. Dupilumab radically changes the treatment of CRSwNP, but, considering its recent approval, it may be useful to evaluate its safety profile in a real-world setting. This work aimed to prospectively highlight the effectiveness and safety profile of dupilumab in patients with CRSwNP enrolled in the Otorhinolaryngology Unit of the University Hospital of Messina. An observational cohort study was carried out considering all patients treated with dupilumab. A descriptive analysis was conducted reporting all demographic characteristics, endoscopic evaluations, and symptom conditions. A total of 66 patients were treated with dupilumab, but three patients were excluded due to a lack of adherence during the observational period. A statistically significant reduction in the Sino-Nasal Outcome Test 22 (SNOT-22) and nasal polyps score (NPS) was shown at the 6th and 12th months compared to baseline values (SNOT-22, -37 and -50, p < 0.001 for both comparisons; NPS, -3 and -4, p < 0.001 for both comparisons). During the follow-up, eight patients (12.7%) had a reaction at the site of injection, and seven (11.1%) had transient hypereosinophilia. Given the optimal treatment response and the minimal adverse effects observed, clinicians should consider dupilumab a safe and effective treatment. Further studies are necessary to better understand the long-term effects.

8. Italy pubmed.ncbi.nlm.nih.gov

Severe chronic rhinosinusitis treated with dupilumab, a real-life analysis of early effectiveness. [2023] The present study evaluated the safety and efficacy of dupilumab in severe uncontrolled type 2 chronic rhinosinusitis with nasal polyps (CRSwNP).

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

Dupilumab efficacy in patients with chronic rhinosinusitis with nasal polyps with and without allergic rhinitis. [2023] Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a predominantly type 2 inflammatory disease, which often coexists with allergic rhinitis (AR). Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key and central drivers of type 2 inflammation. Objective: This post hoc analysis investigated the efficacy and safety of dupilumab in patients with severe CRSwNP with or without coexisting AR in the pooled phase III SINUS-24/SINUS-52 studies. Methods: Patients randomized to subcutaneous dupilumab 300 mg (n = 438) or placebo (n = 286) every 2 weeks for 24 (SINUS-24) or 52 weeks (SINUS-52) were analyzed. Pooled data from the first 24 weeks of treatment are presented. Changes from baseline in disease outcome measures and biomarker levels were analyzed by the patient-reported history of AR status. Results: Overall, 338 of 724 patients (46.7%) had AR. Baseline characteristics were generally similar between patients with and those without AR. Dupilumab significantly improved objective and patient-reported measures of CRSwNP, including loss of smell, and reduced systemic and nasal biomarker levels versus placebo at week 24, with no significant treatment difference between patients with and those without AR. Use of systemic corticosteroids and/or sinonasal surgery during treatment was significantly reduced with dupilumab versus placebo, irrespective of AR status (p ≤ 0.0029). The safety profile of dupilumab was similar in patients with and in patients without AR. Conclusion: Dupilumab demonstrated significant improvements in both clinical end points and symptom scores versus placebo in patients with severe CRSwNP, irrespective of comorbid AR status, a common subgroup of patients often associated with poorer CRSwNP outcomes. Clinical trials NCT02912468 (SINUS-24) and NCT02898454 (SINUS-52), <ext-link ext-link-type="uri" xlink:href="http://www. IngetaConnect.com">www.clinicaltrials.gov</ext-link>.

10. Denmark pubmed.ncbi.nlm.nih.gov

Two-year results of tapered dupilumab for CRSwNP demonstrates enduring efficacy established in the first 6 months. [2023] Dupilumab is an anti-T2-inflammatory biological registered for chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), indicated by integrated CRS-care pathways when optimal medico-surgical treatment yields insufficient CRS control. This study aims to evaluate long-term results with focus on established therapeutic efficacy while tapering dupilumab.