Tezepelumab for Sinusitis with Nasal Polyps

(ESSENCE Trial)

Recruiting at 50 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: Intranasal corticosteroids

Must not be taking: Systemic immunosuppressants

Disqualifiers: Allergic fungal rhinosinusitis, Pulmonary disease, Cancer, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 24 weeks

180 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called tezepelumab, an experimental drug for people with chronic sinusitis and nasal polyps. The goal is to determine if this treatment can help those who might need surgery for their condition, regardless of asthma status. Participants should have ongoing issues such as a runny nose, loss of smell, or poor sleep due to nasal polyps. The trial includes regular check-ups every four weeks over a 40-week period, with treatment lasting up to 24 weeks. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

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

The trial requires participants to be stable on their current intranasal corticosteroids for at least 30 days before starting and throughout the study. Other medications, especially systemic immunosuppressive drugs, must be stopped 12 weeks before the trial. Check with the study team for specific guidance on your medications.

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

Research has shown that tezepelumab is generally safe for people with nasal polyps. In a study involving over 200 patients, the number of negative side effects was similar to those in the placebo group (a treatment with no active ingredients), indicating that most side effects are mild. Additionally, the FDA approved tezepelumab for treating chronic rhinosinusitis with nasal polyps, based on strong evidence of its safety and effectiveness. For those considering participation in a clinical trial with tezepelumab, this information suggests that many patients have found its safety acceptable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for sinusitis with nasal polyps?

Tezepelumab is unique for treating sinusitis with nasal polyps because it targets the thymic stromal lymphopoietin (TSLP), a key player in driving inflammation. Unlike standard treatments such as corticosteroids and surgery, which primarily address symptoms or remove polyps, Tezepelumab works at the source of the problem by modulating the immune response. Researchers are excited about this treatment because it offers a novel approach that could provide more effective and lasting relief for patients suffering from this chronic condition.

What evidence suggests that tezepelumab might be an effective treatment for sinusitis with nasal polyps?

Research has shown that tezepelumab, which participants in this trial will receive, offers promising results for treating chronic rhinosinusitis with nasal polyps (CRSwNP). The U.S. has approved it because it effectively reduces the size of nasal polyps. Studies have also found that it helps relieve nasal congestion and improves the sense of smell. Additionally, patients reported a better quality of life while using tezepelumab. These findings suggest that tezepelumab can be an effective treatment option for those suffering from CRSwNP. ^{4 5 6 7 8}

Who Is on the Research Team?

Tanya M Laidlaw, MD

Principal Investigator

Director of Translational Research in Allergy and Director of the Aspirin-Exacerbated Respiratory Disease (AERD) Centre at the Brigham and Women's Hospital.

Enrico Heffler, MD, PhD

Principal Investigator

Associate Professor of Internal Medicine and Consultant at the Personalized Medicine, Asthma and Allergy Unit at IRCCS Humanitas Research Hospital

Are You a Good Fit for This Trial?

This trial is for adults with chronic rhinosinusitis and nasal polyps who are eligible for surgery, including those with asthma. Participants must be able to attend visits every four weeks for up to 40 weeks.

Inclusion Criteria

I am following the required contraceptive guidelines.

I weigh at least 40 kg.

I have had severe sinus issues for over a year, needing surgery.

Exclusion Criteria

I have a documented allergy to fungi affecting my sinuses or central part of my nose.

I do not have significant lung issues other than asthma.

I haven't had uncontrollable nosebleeds in the last 2 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

up to 4 weeks

Treatment

Participants receive tezepelumab treatment to assess changes in symptoms of chronic rhinosinusitis with nasal polyposis

24 weeks

Visits every 4 weeks

Safety Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Tezepelumab

Trial Overview

The study tests Tezepelumab's effectiveness in reducing symptoms of chronic rhinosinusitis with nasal polyps over a treatment period of up to 24 weeks, with follow-up visits every four weeks.

How Is the Trial Designed?

Group I: Tezepelumab Experimental Treatment 1 Intervention

Tezepelumab: Tezepelumab single dose subcutaneously injection.

Tezepelumab is already approved in United States, European Union for the following indications:

Approved in United States as Tezspire for:

• Severe asthma

Approved in European Union as Tezspire for:

• Severe asthma

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Fortrea

Industry Sponsor

Trials

22

Recruited

5,800+

Published Research Related to This Trial

Biologics like anti-IgE (omalizumab) and IL-5 blockers (mepolizumab, reslizumab, benralizumab) have shown effectiveness in treating allergic rhinitis and nasal polyposis, which are linked to type 2 inflammation.

While these treatments are effective, they are also expensive, highlighting the need for future studies to assess their cost-effectiveness compared to traditional medical and surgical options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biologics for the Treatment of Allergic Rhinitis, Chronic Rhinosinusitis, and Nasal Polyposis. Eschenbacher, W., Straesser, M., Knoeddler, A., et al.[2021]

Tezepelumab, a monoclonal antibody approved for severe uncontrolled asthma, significantly improved forced expiratory volume (FEV1) by 0.15 L and reduced asthma exacerbation rates by 0.60 per year compared to placebo, based on a meta-analysis of six trials with 2667 patients.

The treatment was found to have an acceptable safety profile, with no higher incidence of adverse drug reactions compared to placebo, indicating it is a safe option for patients with severe asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tezepelumab for Patients with Severe Uncontrolled Asthma: A Systematic Review and Meta-Analysis. Zoumot, Z., Al Busaidi, N., Tashkandi, W., et al.[2022]

Tezepelumab, a monoclonal antibody targeting thymic stromal lymphopoietin, significantly reduced annualized asthma exacerbation rates (AAERs) by 75% in patients with nasal polyposis and 73% in those without, demonstrating its efficacy in severe asthma regardless of nasal polyposis status.

The treatment also led to greater reductions in inflammatory biomarkers such as blood eosinophil counts and levels of FeNO, IL-5, and IL-13, indicating its effectiveness in lowering type 2 inflammation associated with asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Tezepelumab in Patients with Severe, Uncontrolled Asthma with and without Nasal Polyposis: A Post Hoc Analysis of the Phase 2b PATHWAY Study. Emson, C., Corren, J., Sałapa, K., et al.[2022]

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 a real-world study involving 950 patients with severe asthma and chronic rhinosinusitis (CRS), mepolizumab significantly reduced asthma exacerbations by 28% to 44%, with the greatest improvement seen in patients who had both CRS and sinus surgery.

After starting mepolizumab, patients experienced lower use of systemic corticosteroids and reduced healthcare costs, indicating its efficacy in managing severe asthma and CRS in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world effectiveness of mepolizumab in severe asthma and chronic rhinosinusitis in the United States: impact of comorbidity and sinus surgery. Silver, J., Deb, A., Laliberté, F., 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]

Biologics targeting type 2 inflammatory cytokines (like IL4, IL5, and IL13) show significant efficacy in reducing nasal polyp scores and improving health status in patients with severe chronic rhinosinusitis with nasal polyps, with dupilumab demonstrating the highest reduction in symptoms (35% in nasal polyp score).

All biologics studied not only improved nasal airway blockage but also decreased the need for additional medical or surgical interventions, highlighting their potential as effective treatments for managing this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Choice of Biologics in Patients with Severe Chronic Rhinosinusitis with Nasal Polyps. Lipworth, BJ., Chan, R.[2021]

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

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