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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how the drug mepolizumab affects cells from the nasal passages of individuals with chronic sinusitis and nasal polyps. Researchers aim to determine if mepolizumab can reduce inflammation and maintain the strength of the cells' barrier. Participants must have experienced sinus inflammation for over 12 weeks, with symptoms such as nasal blockage or facial pain, confirmed by a scan or exam, and have nasal polyps. As an Early Phase 1 trial, this research focuses on understanding how mepolizumab works in people, offering participants the opportunity to be among the first to receive this treatment.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that mepolizumab is generally safe for individuals with chronic sinus issues, such as nasal polyps. In one study, only 15% of participants using mepolizumab reported side effects potentially related to the treatment. This is similar to the 9% who reported side effects while taking a placebo, a harmless pill used for comparison. Another study found that mepolizumab was well-tolerated, indicating that people could use the treatment without major problems. While some might experience mild side effects, mepolizumab appears to be a safe option for managing chronic sinus problems. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for chronic sinusitis focus on reducing symptoms with medications like nasal corticosteroids, saline sprays, or antibiotics. But mepolizumab works differently, targeting a specific part of the immune system. It's a monoclonal antibody that blocks interleukin-5 (IL-5), a protein that causes inflammation. This unique approach could help tackle sinusitis from the root cause, potentially offering relief where other treatments fall short. Researchers are excited because mepolizumab might provide a new, effective option for patients who don't respond well to standard therapies.

What evidence suggests that mepolizumab might be an effective treatment for chronic sinusitis?

Research has shown that mepolizumab can help people with chronic rhinosinusitis with nasal polyps. Studies have found that it eases symptoms like a stuffy nose and improves quality of life. Mepolizumab also helps shrink nasal polyps and reduces the need for surgeries. Patients reported feeling better and had fewer issues with their sense of smell. In this trial, participants in the mepolizumab treatment arm will have nasal epithelial cells exposed to mepolizumab in vitro, while the control arm will not receive this exposure. Overall, evidence suggests that mepolizumab effectively manages symptoms and improves life for those with this condition. ^{1 2 5 6 7}

Who Is on the Research Team?

Jean Kim, MD PhD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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]

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 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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38696895/

Effectiveness and safety profile of mepolizumab in chronic ... A statistically significant reduction in the Sino-Nasal Outcome Tests-22 (SNOT-22) and nasal polyp score (NPS) was shown at the 6th and 12th months compared to ...

2. jacionline.org jacionline.org/article/S0091-6749(24)02320-0/fulltext

Mepolizumab Improves Patient-Reported Outcomes and ... Conclusions. In real-world patients with CRSwNP, mepolizumab substantially improved SNOT-22 scores and treatment burden.

3. sciencedirect.com sciencedirect.com/science/article/pii/S0196070924003831

Mepolizumab in chronic rhinosinusitis with nasal polyps The results are promising in terms of quality of life, symptom severity, reduction in polyp size, and improvement in olfactory function. Finally, our data ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40978169/

Mepolizumab for the management of chronic rhinosinusitis ... In this first retrospective mepolizumab study for patients with CRSwNP without severe asthma, improvements in all outcomes were observed ...

5. jaci-global.org jaci-global.org/article/S2772-8293(25)00150-X/fulltext

Mepolizumab for the management of chronic rhinosinusitis ... Mepolizumab was found to improve nasal symptoms and health-related quality of life and to reduce NP size, number of nasal surgeries, and SCS receipt in patients ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33872587/

Mepolizumab for chronic rhinosinusitis with nasal polyps ... Adverse events considered related to study treatment were reported in 30 (15%) of 206 patients receiving mepolizumab and 19 (9%) of 201 receiving placebo. On- ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04607005?tab=results

Efficacy and Safety of Mepolizumab in Adults With Chronic ... Efficacy and Safety of Mepolizumab in Adults With Chronic Rhinosinusitis With Nasal Polyps (CRSwNP)/​ Eosinophilic Chronic Rhinosinusitis (ECRS) (MERIT).