Dupilumab for Nasal Polyps

No longer recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Medical University of South Carolina

Must be taking: Dupilumab

Must not be taking: Biologics, Corticosteroids

Disqualifiers: Pregnancy, Cystic fibrosis, Asthma, 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: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well dupilumab, a medication, can reduce inflammation and improve the sense of smell in people with chronic sinusitis and nasal polyps. Researchers aim to determine if dupilumab can directly reduce inflammation in the area responsible for smell. Participants receive a dupilumab injection every two weeks. This trial may suit those who have had chronic sinusitis with nasal polyps for at least 12 weeks and experience two or more related symptoms, such as blocked nasal passages or a lost sense of smell. As a Phase 4 trial, this study involves an FDA-approved treatment, helping to understand its benefits for more patients.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you've used oral corticosteroids in the last month or certain biologic medications for CRSwNP or asthma in the last 6 months.

What is the safety track record for dupilumab?

Research has shown that dupilumab is generally safe. In studies, people with chronic sinusitis and nasal polyps have tolerated it well. Side effects are usually mild and manageable, with minor skin irritation at the injection site being common.

The FDA has already approved dupilumab for treating asthma and eczema, supporting its safety across different conditions. This approval boosts confidence in its use for nasal polyps. Overall, dupilumab appears to be a safe choice for those considering this treatment. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Dupilumab is unique because it targets the inflammatory pathways involved in the formation of nasal polyps, specifically blocking the IL-4 and IL-13 signaling. Unlike traditional treatments like corticosteroids which broadly suppress inflammation, dupilumab offers a more targeted approach, potentially reducing side effects and improving efficacy. Researchers are excited about this treatment because it represents a new class of biologics that could offer relief for patients who don't respond well to existing therapies. Plus, its bi-weekly subcutaneous injection allows for consistent, manageable dosing at home after the initial clinic visit.

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

Research has shown that dupilumab effectively treats chronic sinusitis with nasal polyps (CRSwNP). In one study, patients experienced a 54% improvement in stuffy nose symptoms after a year of treatment. Another study found that dupilumab reduced the size of nasal polyps and helped people regain their sense of smell. Patients also reported overall improvement, with fewer symptoms and better sinus health. These findings suggest that dupilumab could be a promising treatment for individuals with CRSwNP. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with chronic sinusitis and nasal polyps, who have had symptoms for at least 12 weeks and are candidates for dupilumab treatment. They must not have had recent nasal surgery or used oral steroids in the last month, and should not be pregnant or breastfeeding.

Inclusion Criteria

I have been diagnosed with severe nasal polyps.

You have a score of 1 or higher on a smell test rated from 0 to 3.

I am a candidate for dupilumab treatment for my sinus condition.

Exclusion Criteria

My asthma is not well-managed.

I have not had nasal or sinus surgery in the last 3 months.

I have taken oral corticosteroids in the last month.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dupilumab 300 mg subcutaneously every 2 weeks for 3 months

12 weeks

Initial in-clinic visit, followed by bi-weekly self-administration

Follow-up

Participants are monitored for changes in olfactory cleft inflammation and olfaction

3 months

Regular follow-up visits for endoscopy and testing

What Are the Treatments Tested in This Trial?

Interventions

• Dupilumab

Trial Overview

The study tests how dupilumab improves smell by reducing inflammation in the olfactory cleft of patients with chronic sinusitis and nasal polyps. It aims to provide evidence that this drug directly affects the sense of smell through anti-inflammatory action.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 1 Intervention

The treatment group will receive dupilumab at 300mg SC Q2weeks. The first dose will be administered via subcutaneous injection in clinic at baseline. Subjects will self-administer study drug (dupilumab 300 mg) subcutaneous every 2 weeks after initial dosing at visit 2.

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?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

Published Research Related to This Trial

A clinical trial showed that a combination of low-dose eflornithine (DFMO) and sulindac reduced the incidence of high-risk adenomas by over 90% in patients at risk for colorectal cancer, suggesting a promising preventive strategy.

The ongoing Phase III trial (CPP FAP-310) is evaluating the safety and efficacy of DFMO and sulindac in preventing progression of Familial Adenomatous Polyposis (FAP), with 138 participants randomized across three treatment groups to assess polyp burden over 24 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of eflornithine (CPP-1X)/sulindac combination therapy versus each as monotherapy in patients with familial adenomatous polyposis (FAP): design and rationale of a randomized, double-blind, Phase III trial. Burke, CA., Dekker, E., Samadder, NJ., et al.[2018]

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 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]

In a trial with 46 participants suffering from familial adenomatous polyposis (FAP), a once-weekly dose of erlotinib significantly reduced duodenal polyp burden by an average of 29.6% after 6 months, indicating its efficacy as a treatment.

Although 71.7% of participants reported adverse events, most were of lower grade, suggesting that the weekly dosing schedule may improve tolerability while still providing effective cancer prevention for patients with FAP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of weekly erlotinib dosing to reduce duodenal polyp burden associated with familial adenomatous polyposis. Samadder, NJ., Foster, N., McMurray, RP., et al.[2023]

A combination of sulindac and erlotinib significantly reduced the number of duodenal polyps in patients with familial adenomatous polyposis (FAP), addressing a previously unmet need since sulindac alone was ineffective.

The study's transcriptome analyses indicated that this combination therapy works by inhibiting key cancer-related pathways, including Wnt/β-catenin, EGFR, and cyclooxygenase, which are involved in tumor growth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular Predicators of Duodenal Familial Adenomatous Polyposis Chemoprevention: Do Chemopreventive Drugs Hit Their Presumed Molecular Targets? Shureiqi, I.[2018]

Chemopreventive strategies, including the use of NSAIDs like sulindac and COX-2 inhibitors like celecoxib, have been shown to effectively reduce adenomas in patients with familial adenomatous polyposis (FAP) after colectomy, helping to prevent recurrence in the retained rectum.

Emerging studies suggest that combining lower doses of these medications with other agents like ursodeoxycholic acid, statins, and difluoromethylornithine may enhance safety and efficacy, while natural compounds like curcumin and eicosapentaenoic acid also show promise in small clinical trials for FAP chemoprevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemoprevention in familial adenomatous polyposis. Kim, B., Giardiello, FM.[2021]

In a study of seven patients with familial adenomatous polyposis, treatment with sulindac (150 mg twice daily) for 24 months resulted in a significant reduction or complete disappearance of rectal polyps, demonstrating its efficacy in managing this condition.

The treatment was well tolerated by all patients, with no reported side effects, indicating that sulindac is a safe option for inducing regression of polyps in this high-risk population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment with sulindac of adenomatous polyps in familial polyposis]. Cerdán, FJ., Torres-Melero, J., Martínez, S., et al.[2013]

In a randomized, placebo-controlled study involving 10 patients with rectal polyps, sulindac (300 mg/day) led to significant regression of polyps in 9 out of 10 patients, while the placebo resulted in either an increase or no change in polyps for most participants.

Despite the effective regression of polyps with sulindac, the study found no significant changes in the cellular proliferation index (Ki 67) in biopsy specimens, suggesting that the mechanism of action may not involve altering cell proliferation rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sulindac causes regression of rectal polyps in familial adenomatous polyposis. Labayle, D., Fischer, D., Vielh, P., 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 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]

Long-term use of sulindac, a nonsteroidal anti-inflammatory drug, has been shown to effectively reduce the size and number of colonic polyps in a patient with familial adenomatous polyposis (FAP) who had not undergone prophylactic colectomy.

This case highlights the potential of sulindac as a chemopreventive strategy for managing adenomas in FAP patients, suggesting it may delay the progression to colorectal cancer without the need for immediate surgical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regression of Colonic Adenomas After Treatment With Sulindac in Familial Adenomatous Polyposis: A Case With a 2-Year Follow-up Without a Prophylactic Colectomy. Kim, KY., Jeon, SW., Park, JG., et al.[2021]

In a study of 24 patients with familial adenomatous polyposis, sulindac treatment led to a significant reduction in rectal polyp size and a decrease in epithelial cell proliferation, indicating its efficacy in managing rectal polyposis.

The treatment also showed a trend towards regression of duodenal polyps and reduced cell proliferation in the duodenum, suggesting that sulindac may be beneficial for early duodenal polyposis or as an adjunct therapy after duodenal clearance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized controlled trial of the effect of sulindac on duodenal and rectal polyposis and cell proliferation in patients with familial adenomatous polyposis. Nugent, KP., Farmer, KC., Spigelman, AD., et al.[2019]

In a randomized, double-blind study of 21 familial adenomatous polyposis patients, treatment with 25 mg of rofecoxib daily for 9 months significantly reduced the number of rectal polyps by 6.8% compared to a 3.1% increase in the placebo group, demonstrating its efficacy.

Rofecoxib also led to a significant reduction in polyp size (-16.2% vs. 1.5% in the placebo group) without a notable increase in adverse events, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, placebo-controlled trial of the effects of rofecoxib, a selective cyclooxygenase-2 inhibitor, on rectal polyps in familial adenomatous polyposis patients. Higuchi, T., Iwama, T., Yoshinaga, K., et al.[2014]

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.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39907855/

Effect of Dupilumab in CRSwNP Sinonasal Outcomes from ...

Recent findings: Significant improvements were noted, with the average SNOT-22 score reduction being 37.2 points post-dupilumab treatment. The ...

4.

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 ...

5.

explorationpub.com

explorationpub.com/Journals/eaa/Article/100951

Dupilumab improved objective and patient-reported ...

Conclusions: In patients with CRSwNP with complete bilateral nasal obstruction, dupilumab treatment resulted in clinically significant improvements in NPS, LMK- ...

6.

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 ...

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02277769

NCT02277769 | Study of Dupilumab (REGN668/ ...

The Safety Data of Dupilumab for the Treatment of Moderate-to-Severe Atopic Dermatitis in Infants, Children, Adolescents, and Adults. Am J Clin Dermatol ...

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/NCT02912468

NCT02912468 | A Controlled Clinical Study of Dupilumab ...

Drug : Dupilumab SAR231893 (REGN668) ... Efficacy and safety of dupilumab in patients with uncontrolled severe chronic rhinosinusitis with nasal polyps ...

10.

accessdata.fda.gov

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

Approval Package - accessdata.fda.gov

The safety of dupilumab was adequately assessed in the nasal polyp development program. ... Overall, the safety data are consistent with the ...