Mepolizumab for Chronic Sinusitis

Recruiting at 1 trial location

Overseen By Jean Kim, MD PhD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Johns Hopkins University

Must not be taking: Glucocorticoids, Biologics

Disqualifiers: Under 18, Pregnant, Prisoners, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

8 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this laboratory study is the examine the effect of mepolizumab drug on the health and function of the cells lining the human nasal airways in vitro cell culture derived from patients with chronic rhinosinusitis with nasal polyposis. The main questions the study aims to study are: 1. To see what mepolizumab does to suppress inflammation of the human cells. 2. To see what mepolizumab does to maintain barrier integrity of epithelial cells

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, specifically oral or systemic IV glucocorticoids (a type of steroid) within 2 weeks of surgery and any immunomodulatory biologics (drugs that modify the immune system) like omalizumab, dupilumab, mepolizumab, benralizumab, reslizumab, or rituximab.

What data supports the effectiveness of the drug Mepolizumab for treating chronic sinusitis?

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 sinus surgeries and the use of corticosteroids, which are medications that reduce inflammation. ^{1 2 3 4 5}

Is Mepolizumab safe for humans?

There is a case report of a patient with chronic rhinosinusitis with nasal polyps who recovered their sense of smell after treatment with Mepolizumab, but the report does not mention any safety concerns or side effects. ^{6 7 8 9 10}

How does the drug mepolizumab differ from other treatments for chronic sinusitis?

Mepolizumab is unique because it targets interleukin-5 (IL-5), a protein involved in inflammation, which helps reduce nasal polyp size and nasal obstruction in chronic sinusitis with nasal polyps. Unlike standard treatments, it is administered as a subcutaneous injection every 4 weeks and has shown to decrease the need for corticosteroids and sinus surgeries. ^{1 2 4 11 12}

Research Team

Jean Kim, MD PhD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for adults with chronic sinusitis and nasal polyps, confirmed by CT or endoscopy, experiencing symptoms like nasal blockage or reduced smell for over 12 weeks. It's not suitable for children under 18, pregnant/lactating women, prisoners, mentally disabled individuals who can't consent, or those recently on steroids/biologics.

Inclusion Criteria

I have had sinus inflammation for over 12 weeks with at least two symptoms like blocked nose, runny nose, facial pain, or loss of smell.

My CT scan or endoscopic exam shows sinus inflammation or infection.

You have nasal polyps found during a nose exam or sinus CT scan.

Exclusion Criteria

Prisoners

Mentally disabled persons

I am unable to understand and give consent for treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

In Vitro Treatment

Nasal epithelial cells are exposed to mepolizumab in vitro to assess its effects on inflammation and epithelial cell integrity

0 to 48 hours

Control

Nasal epithelial cells are exposed to media without mepolizumab in vitro to serve as a control

0 to 48 hours

Follow-up

Analysis of inflammatory markers and epithelial integrity post-treatment

1 week

Treatment Details

Interventions

• Mepolizumab

Trial Overview The study tests Mepolizumab's effects on human nasal airway cells from chronic rhinosinusitis patients in a lab setting. It aims to determine how the drug reduces inflammation and maintains the integrity of the cell lining in these patients.

Participant Groups

Group I: Mepolizumab treatment arm Experimental Treatment 1 Intervention

Nasal epithelial cells will be exposed in vitro to mepolizumab in culture.

Group II: Control arm Active Control 1 Intervention

Nasal epithelial cells will be exposed in vitro to media without mepolizumab in culture

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

GlaxoSmithKline

Industry Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

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 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 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 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 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]

A 62-year-old female patient with chronic rhinosinusitis with nasal polyps (CRSwNP) and severe asthma experienced complete recovery of her sense of smell after 4 months of treatment with mepolizumab, a medication typically used for severe asthma.

Mepolizumab treatment led to good control of both asthma and CRSwNP symptoms, suggesting that it may effectively reduce nasal obstruction caused by polyps, thereby improving olfactory function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recovery of smell sense loss by mepolizumab in a patient allergic to Dermatophagoides and affected by chronic rhinosinusitis with nasal polyps. Cavaliere, C., Incorvaia, C., Frati, F., et al.[2022]

In a study of 77 surgical patients at high risk for postoperative nausea and vomiting (PONV), prophylactic meclizine significantly reduced the severity of nausea compared to placebo, particularly at 15 and 45 minutes after treatment.

Patients receiving meclizine also experienced a lower incidence of nausea after discharge (10% vs. 29% in the placebo group), suggesting that meclizine is an effective long-acting option for managing PONV in at-risk individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meclizine in combination with ondansetron for prevention of postoperative nausea and vomiting in a high-risk population. Forrester, CM., Benfield, DA., Matern, CE., et al.[2014]

In a study of 337 adult patients, dolasetron mesilate was found to be significantly more effective than placebo in preventing postoperative nausea and vomiting (PONV), with higher complete response rates across all doses tested.

Dolasetron treatment resulted in lower usage of escape antiemetic medications and high satisfaction rates among both patients and physicians, indicating its efficacy and tolerability in managing PONV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous dolasetron mesilate ameliorates postoperative nausea and vomiting. Diemunsch, P., Leeser, J., Feiss, P., et al.[2019]

In a study of 88 patients with non-Hodgkin lymphoma receiving moderately emetogenic chemotherapy, palonosetron demonstrated increasing efficacy, with complete response rates rising from 68.2% in the first cycle to 80.5% in the second cycle, and over 90% of patients remained emesis-free without additional antiemetics.

Palonosetron showed a favorable safety profile, with only 8% of treatment-emergent adverse events related to the drug, indicating it is a safe option for managing chemotherapy-induced nausea and vomiting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter phase IV study of palonosetron in the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with non-Hodgkin lymphomas undergoing repeated cycles of moderately emetogenic chemotherapy. Choi, BS., Borsaru, GP., Ballinari, G., et al.[2021]

Patients receiving palonosetron for chemotherapy-induced nausea and vomiting (CINV) required significantly more hydration (0.9 L) compared to those receiving granisetron extended-release subcutaneous (GERSC) (0.3 L), indicating that palonosetron may lead to higher hydration needs.

Switching from palonosetron to GERSC resulted in lower hydration rates, particularly in patients undergoing highly emetogenic chemotherapy, suggesting that GERSC may be more effective in reducing hydration requirements in CINV management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hydration requirements with emetogenic chemotherapy: granisetron extended-release subcutaneous versus palonosetron. Vacirca, J., Caruana, D., Calcanes, G., et al.[2018]

Mepolizumab, a monoclonal antibody targeting IL-5, has shown potential in reducing asthma exacerbations and improving health-related quality of life (HRQoL) in patients with severe eosinophilic asthma, based on a review of 8 studies involving 1707 participants.

While mepolizumab demonstrated a significant reduction in exacerbation rates in eosinophilic asthma (Risk Ratio 0.52), the overall evidence is limited and inconclusive for broader asthma populations, highlighting the need for further research to determine its efficacy across different asthma subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mepolizumab versus placebo for asthma. Powell, C., Milan, SJ., Dwan, K., et al.[2018]

In a study of 351 patients with severe eosinophilic asthma, initiating treatment with mepolizumab led to a significant reduction in the use of high-dose inhaled corticosteroids (ICS) over a 12-month period, with 49% of patients reducing or discontinuing ICS.

Patients who discontinued ICS after starting mepolizumab experienced lower rates of chronic oral corticosteroid (OCS) use, fewer exacerbations, and reduced reliance on short-acting β2-agonists, indicating improved clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A real-world study of inhaled corticosteroid use in patients with severe eosinophilic asthma treated with mepolizumab. Corren, J., Silver, J., Molfino, NA., et al.[2022]

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. England pubmed.ncbi.nlm.nih.gov

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

3. Netherlands pubmed.ncbi.nlm.nih.gov

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

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. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Recovery of smell sense loss by mepolizumab in a patient allergic to Dermatophagoides and affected by chronic rhinosinusitis with nasal polyps. [2022]

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

Meclizine in combination with ondansetron for prevention of postoperative nausea and vomiting in a high-risk population. [2014]

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

Intravenous dolasetron mesilate ameliorates postoperative nausea and vomiting. [2019]

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

Multicenter phase IV study of palonosetron in the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with non-Hodgkin lymphomas undergoing repeated cycles of moderately emetogenic chemotherapy. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Hydration requirements with emetogenic chemotherapy: granisetron extended-release subcutaneous versus palonosetron. [2018]

11. England pubmed.ncbi.nlm.nih.gov

Mepolizumab versus placebo for asthma. [2018]

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

A real-world study of inhaled corticosteroid use in patients with severe eosinophilic asthma treated with mepolizumab. [2022]