Tezepelumab for Sinusitis with Nasal Polyps

(ESSENCE Trial)

Recruiting at 41 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

Trial Summary

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 Tezepelumab safe for humans?

Tezepelumab has been studied in patients with severe uncontrolled asthma and was found to have an acceptable safety profile, with no higher incidence of adverse reactions compared to a placebo. ^{1 2 3 4 5}

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

Tezepelumab is unique because it targets a different part of the immune system compared to other treatments, focusing on a protein called thymic stromal lymphopoietin (TSLP), which plays a key role in the inflammation process. This makes it potentially effective for patients who do not respond well to existing treatments that target other inflammatory pathways. ^{2 3 6 7 8}

What is the purpose of this trial?

The main objective of this study is to evaluate treatment outcomes of tezepelumab among participants with physician-determined surgery-eligible CRSwNP, with or without asthma. Study details include: 1. The study duration will be up to 40 weeks. 2. The treatment duration will be up to 24 weeks. 3. The visit frequency will be once every 4 weeks (Q4W).

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

References

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

Tezepelumab for Patients with Severe Uncontrolled Asthma: A Systematic Review and Meta-Analysis. [2022]

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

The Choice of Biologics in Patients with Severe Chronic Rhinosinusitis with Nasal Polyps. [2021]

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

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

4. New Zealand 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. [2022]

5. England pubmed.ncbi.nlm.nih.gov

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

6. United States 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. [2023]

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

Biologics for the Treatment of Allergic Rhinitis, Chronic Rhinosinusitis, and Nasal Polyposis. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

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