Dupilumab for Chronic Sinusitis

Overseen By Jeanne Hoddinott

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Johns Hopkins University

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

Disqualifiers: Nasal polyps, Uncontrolled asthma, 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: 1

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of dupilumab, an injectable medication, for individuals with chronic sinusitis (long-term sinus inflammation) without nasal polyps. Researchers seek to identify which types of chronic sinusitis might benefit most from this treatment. Participants will receive either dupilumab or a placebo (a harmless, inactive substance) to compare outcomes. Individuals who have experienced chronic sinusitis without polyps and have previously used oral steroids or antibiotics might be suitable for this study. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that dupilumab is likely to be safe for humans?

Research has shown that dupilumab is generally safe for use. Most individuals experience mild to moderate side effects, such as injection site reactions, eye issues like redness or irritation, and occasional headaches.

In studies involving patients with long-term sinus problems and nasal polyps, dupilumab proved to be safe, with most side effects being mild. Additionally, the FDA has approved dupilumab for other conditions like eczema and asthma, indicating it has passed safety evaluations for those uses.

Overall, while some side effects may occur, dupilumab has been tested extensively and is considered safe for treating certain conditions. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for chronic sinusitis, like nasal corticosteroids and saline rinses, primarily aim to reduce inflammation and manage symptoms. But Dupilumab works differently, targeting the immune system's pathways that contribute to inflammation. Unlike standard treatments, Dupilumab specifically blocks the IL-4 and IL-13 signaling pathways, which are key drivers of the immune response in sinusitis. Researchers are excited about Dupilumab because this targeted approach has the potential to address the root cause of inflammation, potentially offering more effective and longer-lasting relief for patients.

What evidence suggests that dupilumab might be an effective treatment for chronic sinusitis?

Research has shown that dupilumab, which participants in this trial may receive, effectively treats conditions like chronic sinusitis. Studies have found that it improves symptoms and quality of life for people with chronic sinus problems and nasal polyps. In other trials, patients quickly experienced relief and saw improvements in their sinus issues. Dupilumab also improved CT scan results of the sinuses, indicating a noticeable difference in their condition. While most current data focuses on cases with nasal polyps, its success in similar conditions suggests it might also help with other sinus problems. ^{2 4 6 7 8}

Who Is on the Research Team?

Jody Tversky

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

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.

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 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

What Are the Treatments Tested in This Trial?

Interventions

• Dupilumab

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.

How Is the Trial Designed?

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

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Regeneron Pharmaceuticals

Industry Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Published Research Related to This Trial

Dupilumab significantly reduced the need for sinonasal surgery by 82.6% and the requirement for systemic corticosteroids (SCS) by 73.9% in adults with chronic rhinosinusitis with nasal polyps (CRSwNP), based on pooled data from two phase 3 studies involving over 600 participants.

Patients treated with dupilumab showed marked improvements in various symptoms and quality of life measures, including nasal congestion and smell identification, compared to those receiving a placebo, indicating its efficacy in managing severe CRSwNP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dupilumab reduces systemic corticosteroid use and sinonasal surgery rate in CRSwNP. Desrosiers, M., Mannent, LP., Amin, N., et al.[2022]

In the phase 3 SINUS-24 and SINUS-52 studies involving 438 adults with severe chronic rhinosinusitis with nasal polyps, dupilumab significantly improved nasal polyp scores and nasal congestion compared to standard care, with 70% of patients showing improvement by Week 4 and 78.7% by Week 52.

Dupilumab treatment resulted in clinically meaningful improvements in nasal polyp scores for 55.7% of patients at Week 4 and 72.3% at Week 52, while only 5.7% of dupilumab patients experienced worsening symptoms at Week 52, compared to 40.1% in the standard care group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid and Continuing Improvements in Nasal Symptoms with Dupilumab in Patients with Severe CRSwNP. Bachert, C., Khan, AH., Hopkins, C., et al.[2022]

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 analyzing 911 adverse reactions associated with dupilumab for chronic rhinosinusitis with nasal polyps (CRSwNP), it was found that this treatment had fewer individual adverse reactions (iDAR) compared to treatments for asthma and atopic dermatitis, suggesting a favorable safety profile.

However, serious adverse reactions were reported in 13.3% of cases, with a notable risk among men and older adults, indicating that while dupilumab is generally safe, certain populations may experience more severe side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dupilumab Adverse Events in Nasal Polyp Treatment: Analysis of FDA Adverse Event Reporting System. Swisher, AR., Kshirsagar, RS., Adappa, ND., et al.[2022]

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]

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]

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 shows significant long-term therapeutic efficacy in treating chronic rhinosinusitis with nasal polyps (CRSwNP), with improvements in key health measures observed over a 2-year follow-up period involving 228 patients.

The study found that tapering dupilumab treatment was feasible for the majority of patients (over 93% at 48 and 96 weeks), and therapeutic benefits were maintained even as the dosage was reduced, indicating a stable response to the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-year results of tapered dupilumab for CRSwNP demonstrates enduring efficacy established in the first 6 months. van der Lans, RJL., Otten, JJ., Adriaensen, GFJPM., et al.[2023]

Dupilumab was found to be effective in treating severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP), showing significant improvements in nasal polyp scores and quality of life measures after just 15 days, which were sustained over 6 months.

The study involved 23 patients and reported only minor complications (26.1% of patients), indicating that dupilumab is a safe treatment option for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe chronic rhinosinusitis treated with dupilumab, a real-life analysis of early effectiveness. Mocellin, D., Ioppi, A., Gaglio, G., et al.[2023]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02912468

NCT02912468 | A Controlled Clinical Study of Dupilumab ... Primary Objective: To evaluate the efficacy of dupilumab 300 milligram (mg) every 2 weeks (q2w) compared to placebo on a background of mometasone furoate ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01920893

NCT01920893 | An Evaluation of Dupilumab in Patients ... Primary Objective: To evaluate the efficacy of dupilumab (SAR231893/REGN668) in the treatment of bilateral Nasal Polyposis (NP) by assessment of the ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11457478/

Efficacy of dupilumab on chronic rhinosinusitis with nasal ... We observed that dupilumab for CRSwNP leads to a very rapid improvement in polyps, symptoms, and quality of life, regardless of previous ...

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

Approval Package - accessdata.fda.gov the study results demonstrated evidence of efficacy in endpoints specific to chronic rhinosinusitis such as improved CT sinus scores and ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04959448

NCT04959448 | Study Assessing Long-teRm Outcomes of ... Study assessing long-term outcomes of dupilumab (DUPIXENT®) treatment in adult patients with chronic rhinosinusitis with nasal polyposis (CRSwNP)

6. 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 moderate ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2213219824009413

Dupilumab Versus Mepolizumab for Chronic Rhinosinusitis ... The anti-IL-4Rα dupilumab and the anti-IL-5 mepolizumab have shown efficacy and safety data for patients with chronic rhinosinusitis with nasal polyps (CRSwNP) ...

8. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK596600/

Clinical Review - Dupilumab (Dupixent) - NCBI Bookshelf - NIH Dupilumab also received a Health Canada indication for atopic dermatitis and for chronic rhinosinusitis with nasal polyposis. It was also previously reviewed by ...