Tezepelumab for Chronic Rhinosinusitis with Nasal Polyps

(WAYPOINT Trial)

No longer recruiting at 119 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: Immunosuppressives, Decongestants

Disqualifiers: Sinus surgery, COVID-19 positive, others

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: 3

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new treatment called Tezepelumab, an injection for individuals with severe chronic rhinosinusitis with nasal polyps. This condition causes persistent stuffiness, runny nose, and loss of smell, and might even require surgery. Participants will receive either Tezepelumab or a placebo, a harmless substance resembling the treatment, through an injection. This trial suits individuals who have struggled with these symptoms for over a year and are considering or have needed surgery. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

You may need to stop taking certain medications, like decongestants and immunosuppressive drugs, before joining the trial. It's best to discuss your current medications with the trial team to see if any changes are needed.

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

Research has shown that Tezepelumab is generally safe for individuals with chronic rhinosinusitis with nasal polyps. Studies have found its side effects to be similar to those of a placebo, a non-active substance used in the study. In a study involving over 200 patients, researchers compared the side effects of Tezepelumab to those in the placebo group.

The FDA has approved Tezepelumab for treating this condition, indicating it has passed rigorous safety and effectiveness tests. However, as with any treatment, some individuals might experience mild side effects. Discuss any concerns with a healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for chronic rhinosinusitis?

Tezepelumab is unique because it targets a specific part of the immune system called TSLP (thymic stromal lymphopoietin), which plays a key role in the inflammation that causes nasal polyps in chronic rhinosinusitis. Unlike traditional treatments like corticosteroids or surgery, which can have wider effects and potential side effects, Tezepelumab offers a more targeted approach. Researchers are excited about this treatment because it has the potential to provide relief for patients who don’t respond well to existing therapies, offering a new way to reduce symptoms and improve quality of life.

What evidence suggests that Tezepelumab might be an effective treatment for chronic rhinosinusitis with nasal polyps?

Research has shown that tezepelumab, which participants in this trial may receive, effectively treats severe chronic rhinosinusitis with nasal polyps. In clinical studies, patients who took tezepelumab had smaller nasal polyps and less nasal congestion. These studies also found that patients experienced better overall sinus symptoms and improved quality of life compared to those who took a placebo, which is another arm in this trial. Evidence suggests that this treatment can help reduce the need for surgery or oral steroids. The FDA has approved tezepelumab for treating this condition, recognizing its effectiveness. ^{2 3 4 5 6}

Who Is on the Research Team?

Brian Lipworth, MD

Principal Investigator

University of Dundee

Joseph K Han, MD

Principal Investigator

Eastern Virginia Medical School

Are You a Good Fit for This Trial?

This trial is for people with severe chronic rhinosinusitis and nasal polyps, who've had symptoms like runny nose or loss of smell for over 8 weeks. They should have a history of sinus issues needing steroids or surgery but haven't used certain meds in the last 3 months. Those recently vaccinated for COVID-19 or with other serious lung conditions can't join.

Inclusion Criteria

I have been on a stable treatment for nasal polyps for 30 days.

I've been treated for nasal polyps with steroids or had surgery for it in the last year, but not in the last 3 months.

Your SNOT-22 total score is 30 or higher at the first screening visit.

Exclusion Criteria

I received a COVID-19 vaccine at least 28 days before my treatment starts.

I do not regularly use decongestants, except for endoscopic procedures.

I haven't taken any immunosuppressive drugs in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive tezepelumab or placebo via subcutaneous injection over a 52-week period

52 weeks

Regular visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12-24 weeks

2-3 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Tezepelumab

Trial Overview The study tests Tezepelumab's effectiveness and safety against a placebo in participants with severe sinus issues due to nasal polyps. It's randomized, meaning participants are put into the Tezepelumab or placebo group by chance, and double-blind so neither doctors nor patients know who gets what.

How Is the Trial Designed?

Group I: Tezepelumab Experimental Treatment 1 Intervention

Tezepelumab subcutaneous injection, in an accessorized pre-filled syringe.

Group II: Placebo Placebo Group 1 Intervention

Placebo subcutaneous injection, in an accessorized pre-filled syringe.

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

Amgen

Industry Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

Published Research Related to This Trial

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 significantly reduced annualized asthma exacerbation rates (AAER) by 66% to 78% in patients with perennial allergy and by 67% to 71% in those without, based on a study of 550 adults over 52 weeks.

The treatment also improved lung function (measured by prebronchodilator FEV1) and reduced type 2 biomarkers, demonstrating its efficacy in managing severe, uncontrolled asthma regardless of allergy status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Tezepelumab in Patients with Severe, Uncontrolled Asthma and Perennial Allergy. Corren, J., Ambrose, CS., Sałapa, K., et al.[2021]

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 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 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 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]

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]

Citations

1. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2025/TEZSPIRE-approved-in-the-US-for-chronic-rhinosinusitis-with-nasal-polyps.html

TEZSPIRE approved in the US for chronic rhinosinusitis ... Efficacy and safety of tezepelumab in adults with severe chronic rhinosinusitis with nasal polyps: results from the Phase 3 WAYPOINT Study.

2. tezspirehcp.com tezspirehcp.com/nasal-polyps/clinical-data

Clinical Data | TEZSPIRE® (tezepelumab-ekko) for Nasal Polyps Explore TEZSPIRE vs placebo clinical data about improvements in NPSD symptom score, quality of life, and reduction for SCS use and/or surgery.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40106374/

Tezepelumab in Adults with Severe Chronic Rhinosinusitis ... Tezepelumab therapy led to significantly greater reductions in the size of nasal polyps, the severity of nasal congestion and sinonasal symptoms.

4. tezspire.com tezspire.com/nasal-polyps.html

Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) Treatment TEZSPIRE can help you break away from a cycle of temporary relief. In a one-year clinical trial, TEZSPIRE was proven to help: SHRINK NASAL ...

5. amgen.com amgen.com/newsroom/press-releases/2025/10/fda-approves-tezspire-for-chronic-rhinosinusitis-with-nasal-polyps

FDA APPROVES TEZSPIRE® FOR CHRONIC ... Efficacy and safety of tezepelumab in adults with severe chronic rhinosinusitis with nasal polyps: results from the Phase 3 WAYPOINT Study.

6. tezspirehcp.com tezspirehcp.com/nasal-polyps/safety

Safety Profile | TEZSPIRE® (tezepelumab-ekko) for Nasal ... See TEZSPIRE's established safety profile data shown as adverse reaction incidences vs placebo, evaluated in a study with +200 patients with CRSwNP.