Mepolizumab for Chronic Sinusitis with Nasal Polyps

Overseen By Atenea Pascual, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: St. Paul's Sinus Centre

Disqualifiers: Tumours, Immunodeficiency, Autoimmune, Smoking, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 8

Duration: 24 weeks

90 Participants Needed

Trial Summary

What is the purpose of this trial?

This study aims to analyze the immune profiles of patients with Chronic Rhinosinusitis with Nasal polyps (CRSwNP) with and without asthma before and after Mepolizumab. A group of participants with CRS without nasal polyps (CRSsNP) with asthma will be included to compare their immune profiles to CRSwNP.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug mepolizumab for chronic sinusitis with nasal polyps?

Research shows that mepolizumab can reduce the size of nasal polyps and improve symptoms like nasal blockage in people with chronic sinusitis with nasal polyps. It also helps decrease the need for corticosteroids and sinus surgeries, leading to a better quality of life. ^{1 2 3 4 5}

Is Mepolizumab safe for humans?

Mepolizumab has been shown to be safe in studies for chronic rhinosinusitis with nasal polyps and other inflammatory airway diseases, with no major safety concerns reported. ^{1 2 3 5 6}

How is the drug mepolizumab unique for treating chronic sinusitis with nasal polyps?

Mepolizumab is unique because it targets and reduces blood eosinophils (a type of white blood cell involved in inflammation), which helps decrease nasal polyp size and nasal obstruction, reducing the need for sinus surgery and systemic corticosteroids, which can have adverse effects. ^{1 2 3 5 7}

Eligibility Criteria

This trial is for adults over 19 with Chronic Rhinosinusitis and nasal polyps, with or without asthma. Participants must not be smokers, have a history of lung transplants, sinus or bronchial tumors, certain infections, autoimmune diseases, immunodeficiency or allergies to biologics. Women must use birth control and have negative pregnancy tests during the study.

Inclusion Criteria

I am over 19 years old.

I have chronic sinusitis with nasal polyps, with or without asthma, confirmed by tests.

I am using birth control and have a negative pregnancy test.

Exclusion Criteria

I have a parasitic worm infection.

I am not pregnant or breastfeeding.

You currently smoke or used to smoke.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline

Eligibility confirmed and baseline measurements taken, including nasal sample collection for cytokine analysis

1 week

1 visit (in-person)

Treatment

Participants receive Mepolizumab or placebo every 4 weeks for 24 weeks, with nasal sample collection and questionnaires administered

24 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Mepolizumab

Trial Overview The study compares immune responses in patients treated with Mepolizumab versus those given a placebo. It includes chronic rhinosinusitis sufferers both with and without nasal polyps but excludes individuals who've recently taken antibiotics or have specific health exclusions.

Participant Groups

Group I: Mepolizumab Experimental Treatment 1 Intervention

Mepolizumab (100 mg) subcutaneously every 4 weeks

Group II: Placebo Placebo Group 1 Intervention

Placebo 100 mg subcutaneously every 4 weeks

Who Is Running the Clinical Trial?

St. Paul's Sinus Centre

Lead Sponsor

Trials

4

Recruited

170+

Findings from Research

In the phase III SYNAPSE study involving 407 patients, mepolizumab significantly reduced nasal polyp size and nasal obstruction in chronic rhinosinusitis with nasal polyps, showing efficacy across various subgroups including those with asthma and aspirin-exacerbated respiratory disease (AERD).

Patients receiving mepolizumab demonstrated a higher rate of improvement in nasal polyp scores and nasal obstruction compared to those on placebo, indicating that mepolizumab is effective regardless of baseline blood eosinophil counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mepolizumab for chronic rhinosinusitis with nasal polyps: Treatment efficacy by comorbidity and blood eosinophil count. Bachert, C., Sousa, AR., Han, JK., et al.[2022]

In a study of 55 patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) treated with mepolizumab, significant improvements were observed in nasal symptoms and polyp scores after 6 months, particularly in patients with aspirin-exacerbated respiratory disease (AERD).

Mepolizumab treatment led to a marked reduction in blood eosinophil levels and decreased reliance on systemic corticosteroids, enhancing the overall quality of life for patients with CRSwNP, regardless of asthma status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-Life Effectiveness of Mepolizumab in Refractory Chronic Rhinosinusitis with Nasal Polyps. Domínguez-Sosa, MS., Cabrera-Ramírez, MS., Marrero-Ramos, MDC., et al.[2023]

In a phase 3 trial involving 414 patients with severe chronic rhinosinusitis and nasal polyps, mepolizumab significantly reduced nasal polyp size and improved nasal obstruction compared to placebo after 52 weeks of treatment.

The safety profile of mepolizumab was similar to placebo, with no new safety concerns identified, suggesting it is a safe and effective add-on therapy for patients who do not respond to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mepolizumab for chronic rhinosinusitis with nasal polyps (SYNAPSE): a randomised, double-blind, placebo-controlled, phase 3 trial. Han, JK., Bachert, C., Fokkens, W., et al.[2022]

In the 52-week Phase III SYNAPSE study, mepolizumab significantly reduced nasal polyp size and improved symptoms in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP), showing sustained benefits even 24 weeks after treatment discontinuation.

Among 134 patients followed up, those who received mepolizumab had better outcomes, such as lower nasal polyp scores and reduced need for sinus surgery, compared to placebo, indicating that the treatment's effects can last beyond the treatment period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sustained efficacy of mepolizumab in patients with severe chronic rhinosinusitis with nasal polyps: SYNAPSE 24-week treatment-free follow-up. Desrosiers, M., Diamant, Z., Castelnuovo, P., et al.[2023]

In the SYNAPSE study involving 407 patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP), mepolizumab significantly reduced nasal polyp size and nasal obstruction compared to placebo, demonstrating its efficacy as a treatment option.

By Weeks 24 and 52, a majority of patients treated with mepolizumab who did not undergo surgery showed sustained improvement across multiple response criteria, highlighting its potential to manage symptoms effectively without the need for surgical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating treatment response to mepolizumab in patients with severe CRSwNP. Hopkins, C., Han, JK., Lund, VJ., et al.[2023]

In a study involving 20 adult patients with eosinophilic chronic rhinosinusitis, treatment with mepolizumab for 24 weeks significantly reduced eosinophil counts in sinonasal tissue, indicating its efficacy in targeting IL-5 to suppress eosinophil trafficking.

Despite the reduction in eosinophils, levels of type-2 cytokines (IL-5, IL-4, IL-13, and GM-CSF) increased in the tissue, suggesting a potential local inflammatory feedback loop that may contribute to incomplete treatment responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mepolizumab decreases tissue eosinophils while increasing type-2 cytokines in eosinophilic chronic rhinosinusitis. Walter, S., Ho, J., Alvarado, R., et al.[2023]

In the SYNAPSE trial involving 407 adults with severe chronic rhinosinusitis with nasal polyps (CRSwNP), mepolizumab significantly reduced the risk of patients being placed on a waiting list for sinus surgery compared to placebo, with a probability estimate of 13.9% versus 28.5% at week 52.

Mepolizumab also lowered the risk of needing sinus surgery regardless of how long it had been since the last surgery or the patients' baseline blood eosinophil counts, indicating its broad efficacy in managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mepolizumab for chronic rhinosinusitis with nasal polyps (SYNAPSE): In-depth sinus surgery analysis. Fokkens, WJ., Mullol, J., Kennedy, D., et al.[2023]

References

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

Mepolizumab for chronic rhinosinusitis with nasal polyps: Treatment efficacy by comorbidity and blood eosinophil count. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Real-Life Effectiveness of Mepolizumab in Refractory Chronic Rhinosinusitis with Nasal Polyps. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Mepolizumab for chronic rhinosinusitis with nasal polyps (SYNAPSE): a randomised, double-blind, placebo-controlled, phase 3 trial. [2022]

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

Sustained efficacy of mepolizumab in patients with severe chronic rhinosinusitis with nasal polyps: SYNAPSE 24-week treatment-free follow-up. [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Evaluating treatment response to mepolizumab in patients with severe CRSwNP. [2023]

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

Mepolizumab decreases tissue eosinophils while increasing type-2 cytokines in eosinophilic chronic rhinosinusitis. [2023]

7. Denmark pubmed.ncbi.nlm.nih.gov

Mepolizumab for chronic rhinosinusitis with nasal polyps (SYNAPSE): In-depth sinus surgery analysis. [2023]