Dupilumab for Nasal Polyps

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

60 Participants Needed

Trial Summary

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 data supports the idea that Dupilumab for Nasal Polyps is an effective drug?

The available research does not provide any data on Dupilumab for Nasal Polyps. Instead, it focuses on other drugs like sulindac and rofecoxib for different types of polyps, specifically in familial adenomatous polyposis patients. Therefore, there is no information here to support the effectiveness of Dupilumab for Nasal Polyps. ^{1 2 3 4 5}

What safety data is available for Dupilumab in treating nasal polyps?

The provided research does not contain any safety data for Dupilumab or its other names (Dupixent, REGN 668, SAR 231893) in the treatment of nasal polyps. The studies listed focus on other treatments and conditions, primarily related to familial adenomatous polyposis and do not mention Dupilumab. ^{1 6 7 8 9}

Is the drug Dupilumab a promising treatment for nasal polyps?

Yes, Dupilumab is a promising treatment for nasal polyps. It helps reduce the size of nasal polyps, improves symptoms like nasal congestion and loss of smell, and enhances the quality of life for patients. It also reduces the need for surgery and other medications, making it a valuable option for those with severe nasal polyps. ^{10 11 12 13 14}

What is the purpose of this trial?

This study seeks to explore the mechanism through which dupilumab improves olfactory cleft inflammation in patients with chronic sinusitis with nasal polyps (CRSwNP). The investigators expect this study to provide convincing evidence that dupilumab improves clinical olfaction via direct reduction in olfactory cleft inflammation.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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, 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]

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]

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 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]

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]

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]

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 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 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. United States 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. [2014]

2. Spain pubmed.ncbi.nlm.nih.gov

[Treatment with sulindac of adenomatous polyps in familial polyposis]. [2013]

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

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

4. England 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. [2019]

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

Sulindac causes regression of rectal polyps in familial adenomatous polyposis. [2022]

6. England 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. [2018]

7. Korea (South) 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. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Phase II trial of weekly erlotinib dosing to reduce duodenal polyp burden associated with familial adenomatous polyposis. [2023]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Chemoprevention in familial adenomatous polyposis. [2021]

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

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

11. Egypt pubmed.ncbi.nlm.nih.gov

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

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

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

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

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

14. England pubmed.ncbi.nlm.nih.gov

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