Tezepelumab for Chronic Rhinosinusitis with Nasal Polyps

(WAYPOINT Trial)

Recruiting at 105 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

416 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Tezepelumab for treating chronic rhinosinusitis with nasal polyps?

Tezepelumab has shown effectiveness in reducing asthma symptoms, which is relevant because similar drugs targeting type 2 inflammation have improved nasal polyp scores and health status in patients with chronic rhinosinusitis with nasal polyps. This suggests Tezepelumab might also be beneficial for this condition. ^{1 2 3 4 5}

Is Tezepelumab safe for humans?

Tezepelumab has been studied in patients with severe uncontrolled asthma, and the research shows it has an acceptable safety profile, meaning it did not cause more side effects than a placebo (a harmless pill used for comparison). ^{1 3 4 6 7}

How is the drug Tezepelumab different from other treatments for chronic rhinosinusitis with nasal polyps?

Tezepelumab is unique because it is a monoclonal antibody that blocks thymic stromal lymphopoietin, a protein involved in inflammation, which is different from other treatments like mepolizumab that target interleukin-5. This mechanism may offer a new approach for patients with chronic rhinosinusitis with nasal polyps, especially those who also have severe asthma. ^{2 3 4 8 9}

What is the purpose of this trial?

This trial is testing an injectable medication called tezepelumab in adults with severe sinus inflammation and nasal polyps. The medication aims to reduce swelling and polyp growth by calming the immune system. Tezepelumab has been previously studied and shown to improve outcomes in patients with severe, uncontrolled asthma.

Research Team

Brian Lipworth, MD

Principal Investigator

University of Dundee

Joseph K Han, MD

Principal Investigator

Eastern Virginia Medical School

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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 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]

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]

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]

References

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

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

2. England pubmed.ncbi.nlm.nih.gov

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

3. 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]

4. 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]

5. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

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

7. England pubmed.ncbi.nlm.nih.gov

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

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

Efficacy of Tezepelumab in Patients with Severe, Uncontrolled Asthma and Perennial Allergy. [2021]

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

Tezepelumab Efficacy in Patients with Severe, Uncontrolled Asthma with Comorbid Nasal Polyps in NAVIGATOR. [2023]