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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests dupilumab for individuals with nasal polyps and staphylococcus aureus in their sinuses. The goal is to determine if dupilumab can reduce this bacteria and increase the variety of other, beneficial bacteria, thereby improving overall sinus health. Individuals with chronic rhinosinusitis with nasal polyps (CRSwNP) who have tested positive for staph in their sinuses may be suitable candidates. Participants should already use nasal saline irrigation and maintain stable doses of topical corticosteroids. As a Phase 4 trial, this research aims to understand how the already FDA-approved and effective treatment benefits a broader range of patients.

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 is the safety track record for dupilumab?

Research has shown that dupilumab is generally safe for patients. Studies on individuals with chronic sinusitis and nasal polyps have demonstrated a strong safety record for this treatment. For instance, one study found that dupilumab effectively managed symptoms without causing serious side effects.

Common side effects were mild, such as injection site reactions and temporary eye issues. These side effects were typically manageable and did not lead to serious problems. The FDA has already approved dupilumab for several conditions, supporting its safety.

Overall, evidence suggests that dupilumab is a safe choice for those considering this treatment for nasal polyps. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Most treatments for nasal polyps focus on reducing inflammation using corticosteroids or require surgical intervention. However, dupilumab is unique because it targets the underlying cause of nasal polyps by blocking the IL-4 and IL-13 signaling pathways, which are key drivers of inflammation and polyp formation. Researchers are excited about dupilumab because it not only reduces polyp size but also improves microbial diversity in the nasal passages, addressing a broader range of symptoms and potentially reducing the recurrence of polyps. This dual action offers a promising alternative to traditional treatments, providing a more comprehensive approach to managing this condition.

What is the effectiveness track record for dupilumab in treating nasal polyps?

Research has shown that dupilumab, which participants in this trial will receive, effectively treats chronic rhinosinusitis with nasal polyps (CRSwNP). In one study, patients experienced a 54% improvement in stuffy nose symptoms after a year. Another study found that nasal polyps decreased in size and the sense of smell improved. Patients also reported a better quality of life and fewer symptoms. These findings suggest that dupilumab not only reduces nasal polyps but also enhances overall sinus health and related symptoms. ^{6 7 8 9 10}

Who Is on the Research Team?

Larry C Borish, MD

Principal Investigator

University of Virginia

Are You a Good Fit for This Trial?

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

My asthma is under control.

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

If you have eczema, it should be well managed.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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 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 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]

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]

Citations

1. dupixenthcp.com dupixenthcp.com/crswnp/efficacy/nasal-polyp-and-congestion-score

nasal congestion and polyp score data in adults DUPIXENT (dupilumab) clinical trials showed a 54% improvement in nasal congestion score at week 52 in chronic rhinosinusitis with nasal polyposis patients.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40628428/

Effectiveness of dupilumab in chronic rhinosinusitis with ... Results: Significant improvements were noted post-treatment. Lund-Mackay CT scores decreased from 12.5 to 5.5 (p<0.001), and VAS smell scores dropped from 10.0 ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S193945512400156X

Long-term effects of dupilumab on chronic rhinosinusitis ... Dupilumab significantly improved CRSwNP outcomes in both groups, including SNOT-22 scores, nasal polyp size (LMS), and anosmia/hyposmia. Comorbid asthma was ...

4. explorationpub.com explorationpub.com/Journals/eaa/Article/100951

Dupilumab improved objective and patient-reported ... Dupilumab treatment resulted in clinically significant improvements in NPS, LMK-CT, PNIF, symptoms, and health-related quality of life.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04362501

Study Details | NCT04362501 | Efficacy of Dupilumab for ... Recent phase 3 clinical trials found that dupilumab, an anti-IL4α receptor monoclonal antibody, reduces symptoms and polyp size in individuals with CRS with ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02912468

NCT02912468 | A Controlled Clinical Study of Dupilumab ... Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results ...

7. dupixenthcp.com dupixenthcp.com/crswnp/efficacy/safety-data-and-design

safety data and study designs in adults Review DUPIXENT® (dupilumab) demonstrated safety profile and clinical trial information for inadequately controlled chronic rhinosinusitis with nasal polyps ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5589101/

Dupilumab in the management of moderate-to-severe ... Treatment with dupilumab is potentially useful in patients with severe asthma and associated comorbidities (AD, chronic sinusitis, and nasal polyposis)

9. clinicaltrials.gov clinicaltrials.gov/study/NCT01920893

NCT01920893 | An Evaluation of Dupilumab in Patients ... To evaluate the efficacy of dupilumab (SAR231893/REGN668) in the treatment of bilateral Nasal Polyposis (NP) by assessment of the endoscopic nasal polyp score ( ...

10. 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) ...