Dupilumab for Nasal Polyps

Overseen By Kristin W Wavell Shifflett, BS

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Virginia

Must be taking: Dupilumab

Must not be taking: Oral corticosteroids, Asthma biologics

Disqualifiers: Uncontrolled asthma, Recent infection, Smoking, 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: Unknown

Duration: 16 weeks

20 Participants Needed

Trial Summary

What is the purpose of this trial?

Hypothesis: The investigators hypothesize that in patients with CRSwNP who demonstrate sinus colonization with staphylococcus aureus, the administration of dupilumab will be associated with decreased staph colonization and an increase in microbial diversity. Primary Objective will be to demonstrate that dupilumab reduces staphylococcus aureus (phyla firmicutes) abundance while increasing microbial diversity in patients with CRSwNPs who are culture positive for staph aureus at enrollment. Secondary Objectives will be to correlate reduction in Staph aureus abundance and improved bacterial diversity with increased expression of anti-microbial proteins (ß-defensins1-4) and cathelicidin LL-37. In addition, the investigators will correlate improvements in microbial diversity/decreased staph abundance with clinical improvements as assessed via questionnaires and objective/subjective smell function and also as improvements in cellular/immune T2 inflammation as assessed by reduced expression of T2 cytokines/chemokines and eosinophil/eosinophil-derived proteins.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must have stable dosing of topical corticosteroids for more than a month, and you cannot have used oral corticosteroids or antibiotics recently. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Dupilumab for treating nasal polyps?

Dupilumab has been shown to improve nasal polyp size, sinus clarity, and quality of life in patients with chronic rhinosinusitis with nasal polyps. It also reduces symptoms like nasal congestion and the need for surgery, regardless of other conditions like asthma or allergic rhinitis. ^{1 2 3 4 5}

How is the drug Dupilumab unique in treating nasal polyps?

Dupilumab is unique because it is the first biological therapy approved for adults with severe, uncontrolled nasal polyps, working by blocking specific proteins (interleukin-4 and interleukin-13) that drive inflammation. It is administered as a subcutaneous injection every two weeks and has been shown to improve symptoms and reduce the need for surgery and corticosteroids. ^{1 2 3 5 6}

Research Team

Larry C Borish, MD

Principal Investigator

University of Virginia

Eligibility Criteria

Adults aged 18-65 with chronic rhinosinusitis with nasal polyps (CRSwNP) and staph aureus colonization can join. They must meet FDA criteria for Dupilumab use, have well-controlled asthma or atopic dermatitis if present, and a history of sinus surgery. Smokers, pregnant women, those with recent serious illness or medication changes are excluded.

Inclusion Criteria

I am between 18 and 65 years old.

My asthma is under control.

I have a history of severe nasal polyps, including aspirin-exacerbated respiratory disease.

Exclusion Criteria

I had a cold or similar illness in the last 6 weeks.

I have taken oral corticosteroids in the last 60 days.

I have not taken antibiotics in the last 6 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dupilumab to demonstrate decreased staph prevalence and improve microbial diversity

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Dupilumab

Trial Overview The trial tests whether Dupilumab injections reduce staph bacteria in the sinuses and increase microbial diversity in CRSwNP patients. It also examines if these changes improve smell function and decrease inflammation markers related to T2 cytokines/chemokines.

Participant Groups

Group I: Dupilumab treatment Experimental Treatment 1 Intervention

Treatment with dupilumab to demonstrate decreased staph prevalence and improve microbial diversity

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 Virginia

Lead Sponsor

Trials

802

Recruited

1,342,000+

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

Findings from Research

Dupilumab is a monoclonal antibody that effectively targets the IL-4 receptor, significantly improving symptoms and quality of life in adults with inadequately controlled chronic rhinosinusitis with nasal polyps (CRSwNP) over 24 to 52 weeks in phase III studies.

The treatment was well tolerated and led to reductions in nasal polyp size, sinus opacification, and the need for systemic corticosteroids or nasal polyp surgery, showing benefits even in patients with comorbid asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dupilumab: A Review in Chronic Rhinosinusitis with Nasal Polyps. Hoy, SM.[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 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 of 97 patients with chronic rhinosinusitis with nasal polyps (CRSwNP), dupilumab treatment led to significant reductions in polyp size after 6 months, with median total polyp scores dropping from 3 to 0 for small polyps and from 6 to 2 for large polyps.

The effectiveness of dupilumab was consistent regardless of polyp size at the start of treatment, and the use of oral or nasal steroids did not affect the treatment's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The "real life" efficacy of dupilumab is independent of initial polyp size and concomitant steroids in CRSwNP. Campion, NJ., Brugger, J., Tu, A., et al.[2023]

References

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

Dupilumab: A Review in Chronic Rhinosinusitis with Nasal Polyps. [2022]

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

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

3. Egypt pubmed.ncbi.nlm.nih.gov

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

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

Real-world evidence for the effectiveness and safety of dupilumab in patients with CRSwNP after 1 year of therapy. [2023]

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

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

6. England pubmed.ncbi.nlm.nih.gov

The "real life" efficacy of dupilumab is independent of initial polyp size and concomitant steroids in CRSwNP. [2023]