Tezepelumab for Allergic Rhinitis and Asthma

(TEZARS Trial)

Overseen By Sarah Garvey, RPN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dr. Anne Ellis

Must be taking: Inhaled corticosteroids

Disqualifiers: Immunological disorders, Cardiovascular, Hepatitis, others

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

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: 17

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a drug called tezepelumab for individuals with both allergic asthma and hay fever. Researchers aim to determine if this drug can reduce nasal symptoms and certain chemicals involved in allergic reactions after allergen exposure. Participants with allergies will receive the drug, while those without allergies will not. This study suits individuals who have had both asthma and hay fever for at least two years and currently manage their asthma with medication. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that you cannot participate if you are using any prohibited medications listed in Section 7.7, so it's best to discuss your current medications with the study team.

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

Research has shown that tezepelumab is generally safe for people. In studies on severe asthma, it greatly reduced asthma attacks, indicating effectiveness without major safety issues.

Tezepelumab has been tested on many patients, and serious side effects are rare. Some individuals might experience mild reactions, such as redness or swelling at the injection site, but these are usually not serious.

Tezepelumab is already approved for treating severe asthma in Canada, indicating that its safety has been carefully evaluated for that condition. Although this study focuses on allergic asthma and hay fever, the existing safety data for tezepelumab in asthma provides reassurance for those considering participation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for allergic rhinitis and asthma?

Tezepelumab is unique because it targets a specific molecule in the immune system called thymic stromal lymphopoietin (TSLP), which plays a key role in allergic inflammation. This is different from most current treatments for allergic rhinitis and asthma, such as antihistamines and corticosteroids, which primarily focus on managing symptoms rather than preventing them at the source. Researchers are excited about Tezepelumab because it has the potential to reduce the frequency and severity of allergic reactions by addressing the underlying immune response, which could lead to longer-lasting relief for patients. Additionally, targeting TSLP may offer benefits for patients who do not respond well to existing therapies.

What evidence suggests that tezepelumab might be an effective treatment for allergic rhinitis and asthma?

Research has shown that tezepelumab effectively treats severe asthma. In studies, it significantly reduced asthma attacks and improved lung function compared to a placebo. Tezepelumab blocks a specific protein in the body that plays a key role in asthma and allergic reactions. This trial will assess tezepelumab's potential benefits for both allergic and non-allergic participants. Although it is still under study for hay fever, its success in asthma offers hope for similar outcomes. The drug is already approved for treating severe asthma, indicating it has passed thorough testing for that condition. ^{1 2 3 6 7}

Who Is on the Research Team?

Anne K Ellis, MD

Principal Investigator

Queen's University

Are You a Good Fit for This Trial?

The TEZARS trial is for people with both severe asthma and allergic rhinitis (hayfever). Participants must be able to visit the clinic multiple times. Non-allergic individuals will also participate but won't receive the drug; instead, they'll help compare results.

Inclusion Criteria

I am not allergic to common airborne allergens as confirmed by tests.

Allergic participants: A minimum 2-year documented history of rhinoconjunctivitis symptoms to a relevant aeroallergen, Positive skin prick test to a relevant aeroallergen at screening with a wheal diameter at least 5 mm larger than that produced by the negative control, A minimum 2-year documented history of asthma, controlled with either moderate or high dose inhaled corticosteroids with or without another controller medication, Positive screening Nasal Allergen Challenge, defined by a TNSS response of ≥ 7 (on a 12-point scale) and a decrease in PNIF of ≥ 50% after 10 minutes in response to a nasal application of a relevant aeroallergen extract

Must be able and willing to provide written informed consent

Exclusion Criteria

I have a history of immune disorders but no recent serious skin cancer.

Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site)

I can follow the study's requirements and communicate with the investigator.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 visit

1 visit (in-person)

Baseline Nasal Allergen Challenge

Participants undergo a baseline Nasal Allergen Challenge to assess initial response to allergens

1 visit

1 visit (in-person)

Treatment

Allergic participants receive one dose of tezepelumab every 1 month for 12 months

12 months

12 visits (in-person)

6-Month Follow-up Nasal Allergen Challenge

Participants undergo a Nasal Allergen Challenge to assess response after 6 months of treatment

1 visit

1 visit (in-person)

12-Month Follow-up Nasal Allergen Challenge

Participants undergo a Nasal Allergen Challenge to assess response after 12 months of treatment

1 visit

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 month

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Tezepelumab

Trial Overview

This study tests Tezepelumab's effectiveness in reducing nasal symptoms and certain chemicals in the nose after allergen exposure. Allergic participants get monthly injections for a year, while non-allergic ones only undergo allergen challenges.

How Is the Trial Designed?

Group I: Allergic Participants Experimental Treatment 1 Intervention

Group II: Non-allergic Participants Active Control 1 Intervention

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?

Dr. Anne Ellis

Lead Sponsor

Trials

2

Recruited

120+

Dr. Anne Ellis

Lead Sponsor

Trials

2

Recruited

120+

Published Research Related to This Trial

Tezepelumab significantly reduced airway eosinophil counts in patients with uncontrolled asthma, indicating its efficacy in lowering eosinophilic airway inflammation, which is a key factor in asthma exacerbations.

The treatment also improved airway hyperresponsiveness to mannitol, suggesting that blocking TSLP may provide additional benefits in asthma management beyond just reducing type 2 inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of tezepelumab on airway inflammatory cells, remodelling, and hyperresponsiveness in patients with moderate-to-severe uncontrolled asthma (CASCADE): a double-blind, randomised, placebo-controlled, phase 2 trial. Diver, S., Khalfaoui, L., Emson, C., et al.[2022]

Tezepelumab, a monoclonal antibody targeting thymic stromal lymphopoietin, has shown the potential to reduce asthma exacerbations by up to 71% in adults with severe, uncontrolled asthma, regardless of their eosinophilic status, as demonstrated in the PATHWAY phase 2b study.

The ongoing CASCADE phase 2 study is exploring the anti-inflammatory effects of tezepelumab on various airway inflammatory cells and remodeling in patients with moderate-to-severe asthma, aiming to understand its efficacy across different inflammatory profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CASCADE: a phase 2, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the effect of tezepelumab on airway inflammation in patients with uncontrolled asthma. Emson, C., Diver, S., Chachi, L., et al.[2020]

Tezepelumab, a monoclonal antibody targeting thymic stromal lymphopoietin, demonstrated linear pharmacokinetics and a long half-life of 19.9 to 25.7 days, indicating effective dosing intervals for asthma treatment.

The drug was well tolerated in phase I studies with no signs of immunogenicity, suggesting it is safe for use in healthy individuals and those with atopic dermatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, Safety, and Tolerability of Tezepelumab (AMG 157) in Healthy and Atopic Dermatitis Adult Subjects. Parnes, JR., Sullivan, JT., Chen, L., 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]

Tezepelumab significantly reduced asthma exacerbations by 60% compared to placebo in a pooled analysis of 1,334 patients from two major trials, demonstrating its efficacy across various subgroups of severe, uncontrolled asthma.

The treatment not only lowered the rate of exacerbations but also decreased related hospitalizations and emergency visits, with a similar safety profile to placebo, indicating it is a safe and effective option for managing severe asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Tezepelumab in Severe, Uncontrolled Asthma: Pooled Analysis of the PATHWAY and NAVIGATOR Clinical Trials. Corren, J., Menzies-Gow, A., Chupp, G., et al.[2023]

In a phase 2 trial involving 436 patients with uncontrolled moderate-to-severe asthma, tezepelumab significantly reduced the annualized rate of asthma exacerbations by 61% to 71% compared to placebo, demonstrating its efficacy in managing asthma symptoms.

Tezepelumab also improved lung function, as indicated by higher forced expiratory volume in 1 second (FEV1) across all dosing groups, with minimal adverse events leading to discontinuation, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tezepelumab in Adults with Uncontrolled Asthma. Corren, J., Parnes, JR., Wang, L., 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]

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 first-in-class monoclonal antibody targeting TSLP, has demonstrated efficacy and safety in treating severe asthma across different patient profiles, as shown in phase II and III studies.

TSLP plays a crucial role in airway inflammation, making it a promising therapeutic target for asthma treatment, regardless of the patient's specific inflammatory type or baseline biomarkers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tezepelumab for asthma. Nolasco, S., Pelaia, C., Scioscia, G., et al.[2023]

Tezepelumab, a monoclonal antibody targeting thymic stromal lymphopoietin, significantly reduced asthma exacerbations by up to 71% in adults with severe, uncontrolled asthma, as shown in the previous PATHWAY phase 2b study.

The ongoing NAVIGATOR phase 3 study, involving 1061 participants, aims to evaluate tezepelumab's efficacy in reducing exacerbations and improving lung function and quality of life across various asthma phenotypes, including those with low eosinophil counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NAVIGATOR: a phase 3 multicentre, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the efficacy and safety of tezepelumab in adults and adolescents with severe, uncontrolled asthma. Menzies-Gow, A., Colice, G., Griffiths, JM., et al.[2021]

Citations

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pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/37015033/

Efficacy of Tezepelumab in Severe, Uncontrolled Asthma

Tezepelumab reduced exacerbation-related hospitalization or emergency department visits and improved secondary outcomes compared with placebo ...

2.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa1704064

Tezepelumab in Adults with Uncontrolled Asthma

Treatment with tezepelumab resulted in significantly lower annualized rates of asthma exacerbations than the rate with placebo among patients ...

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clinicaltrials.gov

clinicaltrials.gov/study/NCT05329194

Study Details | NCT05329194 | Effectiveness and Safety ...

This is a multicenter, single-arm, open-label, Post-authorization, Phase 4 study to assess the effectiveness of tezepelumab in the United States (US)

4.

sciencedirect.com

sciencedirect.com/science/article/pii/S1323893022001319

Current summary of clinical studies on anti-TSLP antibody, ...

These results suggest that TSLP plays an important role in allergen-induced airway narrowing in asthma and that tezepelumab can effectively prevent asthma ...

5.

tezspirehcp.com

tezspirehcp.com/severe-asthma/clinical-data/additional-data

TEZSPIRE® (tezepelumab-ekko) for Severe Asthma | For HCPs

Look at more TEZSPIRE clinical data related to reductions in exacerbations, and improvements in lung function and overall quality of life.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10870843/

Is Efficacy of Tezepelumab Independent of Severe Asthma ...

Tezepelumab reduced AAER irrespective of allergic status (by 62% and 54% in patients with and without allergy to perennial aeroallergens, respectively), as has ...

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amgen.com

amgen.com/stories/2021/12/-/media/Themes/Global/Global/Global/images/migration/stories/2021/12-17-Severe-Asthma-and-TSLP---Fast-Facts/Tezspire-PDUFA-Discovery-Infographic.pdf

(tezepelumab-ekko)

This trial tested the efficacy and safety of Tezspire™ in adults and adolescents with severe asthma. When added to SOC† patients who received Tezspire™ (n=529).