Dupilumab for Chronic Sinusitis

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}

Research Team

Jody Tversky

Principal Investigator

Johns Hopkins University

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

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Theodore DeWeese

Johns Hopkins University

Chief Executive Officer since 2023

MD from an unspecified institution

Allen Kachalia

Johns Hopkins University

Chief Medical Officer since 2023

MD from an unspecified institution

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

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]

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]

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]

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 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]

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 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]

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 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]

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

Rapid and Continuing Improvements in Nasal Symptoms with Dupilumab in Patients with Severe CRSwNP. [2022]

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. Netherlands pubmed.ncbi.nlm.nih.gov

Dupilumab reduces systemic corticosteroid use and sinonasal surgery rate in CRSwNP. [2022]

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

Dupilumab Adverse Events in Nasal Polyp Treatment: Analysis of FDA Adverse Event Reporting System. [2022]

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]

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

Severe chronic rhinosinusitis treated with dupilumab, a real-life analysis of early effectiveness. [2023]

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

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

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]