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

19 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Tezepelumab for allergic rhinitis and asthma?

Research shows that Tezepelumab significantly reduced asthma attacks and improved lung function in patients with severe, uncontrolled asthma, regardless of their specific type of inflammation. This suggests it may be effective for related conditions like allergic rhinitis. ^{1 2 3 4 5}

Is Tezepelumab safe for humans?

Tezepelumab has been shown to be generally safe in humans, with studies indicating that it does not cause more adverse reactions than a placebo in patients with severe asthma. It was well tolerated in both healthy individuals and those with atopic dermatitis, with no evidence of causing immune system reactions. ^{2 6 7 8 9}

How is the drug Tezepelumab different from other treatments for allergic rhinitis and asthma?

Tezepelumab is unique because it is a monoclonal antibody that blocks thymic stromal lymphopoietin (TSLP), a protein involved in airway inflammation, offering broader effects on inflammation compared to other treatments. It has shown significant reductions in asthma exacerbations, even in patients with different types of inflammation, which is not always the case with other asthma medications. ^{1 2 3 4 10}

What is the purpose of this trial?

The goal of this clinical trial is to learn about how well tezepelumab (pronounced TEZ e PEL ue mab), a Health Canada-approved drug for severe asthma, works in participants with coexisting allergic asthma and allergic rhinitis (hayfever). The main questions it aims to answer are: * How well does the study drug work to reduce nasal symptoms following exposure to an allergen after 6 doses, and after 12 doses? * Does the study drug reduce chemicals found in the nose known to be involved in the allergic rhinitis response? Both allergic and non-allergic participants will be enrolled in the study. Non-allergic participants will: * Not be receiving the study drug. * Be exposed to allergen via the Nasal Allergen Challenge, which involves the administration of allergen extract directly to the nose. * Complete nasal symptom and quality of life questionnaires * Have nasal fluid and blood samples collected at various time points up to 24 hours following allergen exposure. * Visit the clinic 3 separate times: * At a screening visit to determine their eligibility to participate in the study * At the baseline Nasal Allergen Challenge visit * At the 24-hour post-Nasal Allergen Challenge follow-up visit Allergic participants will: * Receive one dose of tezepelumab every 1 month for 12 months. Tezepelumab will be administered as an injection into the fatty layer just beneath the skin on the stomach, arm, or thigh. * Be exposed to allergen via the Nasal Allergen Challenge, which involves the administration of allergen extract directly to the nose. * Complete nasal symptom and quality of life questionnaires * Have nasal fluid and blood samples collected at various time points up to 24 hours following allergen exposure. * Visit the clinic 17 separate times: * At a screening visit to determine their eligibility to participate in the study * At the baseline, 6-month, and 12-month Nasal Allergen Challenge visits * At each 24-hour post-Nasal Allergen Challenge follow-up visit * For each dose of the study drug The investigator will compare changes in nasal symptoms and allergic chemicals measured from nasal fluid and blood samples between non-allergic participants and allergic participants at baseline and at 6- and 12-months following the use of the study drug.

Research Team

Anne K Ellis, MD

Principal Investigator

Queen's University

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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, 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 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]

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, 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, 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 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 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]

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]

References

1. 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]

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

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

3. England 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. [2020]

4. England 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. [2022]

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

Tezepelumab in Adults with Uncontrolled Asthma. [2022]

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

Pharmacokinetics, Safety, and Tolerability of Tezepelumab (AMG 157) in Healthy and Atopic Dermatitis Adult Subjects. [2022]

7. Spain pubmed.ncbi.nlm.nih.gov

Tezepelumab for asthma. [2023]

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

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

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

Efficacy of Tezepelumab in Severe, Uncontrolled Asthma: Pooled Analysis of the PATHWAY and NAVIGATOR Clinical Trials. [2023]

10. England 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. [2021]