Tezepelumab for Asthma

(ARRIVAL Trial)

Recruiting at 76 trial locations

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: AstraZeneca

Must be taking: High-dose ICS, LABA

Must not be taking: Biologics, Immunosuppressives

Disqualifiers: Pulmonary disease, Smoking, Alcohol abuse, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

The objective of this study is to assess the potential for tezepelumab-treated patients (subcutaneous administration) to reduce maintenance therapy without loss of asthma control in adolescent and adults with severe asthma.. Study details include: 1. The study duration will be up to 72 weeks. 2. The treatment duration will be up to 68 weeks. 3. The visit frequency will be once every 4 weeks (Q4W).

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop your current medications. However, it mentions that additional asthma controller medications are allowed, and certain medications like systemic immunosuppressive drugs should not have been used recently. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Tezepelumab for asthma?

Research shows that Tezepelumab significantly reduces asthma attacks and improves lung function in people with severe, uncontrolled asthma. It has been shown to decrease asthma exacerbations by up to 71% and improve breathing capacity compared to a placebo. ^{1 2 3 4 5}

Is Tezepelumab safe for humans?

Tezepelumab has been shown to have an acceptable safety profile in clinical trials for severe uncontrolled asthma, with patients experiencing a similar rate of adverse events as those receiving a placebo. ^{2 4 6 7 8}

How is the drug Tezepelumab different from other asthma treatments?

Tezepelumab is unique because it targets thymic stromal lymphopoietin (TSLP), an upstream molecule in the inflammation pathway, which allows it to treat a broader range of asthma types, including those with noneosinophilic inflammation. Unlike other treatments that target specific cytokines, Tezepelumab can reduce various inflammation markers and is effective for patients with severe asthma not controlled by standard medications. ^{1 2 4 5 9}

Eligibility Criteria

This trial is for people aged 12-80 with severe asthma, who've been on high-dose inhalers plus long-acting bronchodilators for at least 6 months. They should have a history of asthma documented for over a year and show certain levels of lung function variability or reversibility.

Inclusion Criteria

I have read and understood the information about the trial.

I have given my written consent to participate in the study.

I am between 12 and 80 years old.

Trial Timeline

Screening/Run-in

Participants are screened for eligibility to participate in the trial

Up to 4 weeks

Treatment Induction

Initial treatment phase to assess response to tezepelumab

4 weeks

1 visit (in-person)

Treatment Continuation

Continued treatment with tezepelumab to maintain asthma control

20 weeks

5 visits (in-person)

Tezepelumab Treatment With or Without ICS Step-down Therapy

Assessment of asthma control with potential step-down of ICS therapy

32 weeks

8 visits (in-person)

Maintenance

Final phase to maintain asthma control and assess long-term outcomes

16 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Tezepelumab (Monoclonal Antibodies)

Trial Overview The study tests if tezepelumab can help patients reduce their regular asthma medications without losing control over their symptoms. It involves subcutaneous injections, lasts up to 72 weeks, with visits every four weeks.

Participant Groups

Group I: Group 3 - No Asthma Control or Low Biomarkers - No Step-down of ICS Experimental Treatment 4 Interventions

No Asthma Control or Low Biomarkers - No Step-down of ICS

Group II: Group 2 - Asthma Control or Low Biomarkers - No Step-down of ICS Experimental Treatment 5 Interventions

Asthma Control or Low Biomarkers - No Step-down of ICS. Only patients with asthma control or low biomarkers at Week 24 will be randomized into Group 1 or 2

Group III: Group 1 - Asthma Control or Low Biomarkers - Step-down of ICS Experimental Treatment 5 Interventions

Asthma Control or Low Biomarkers - Step-down of ICS. Only patients with asthma control or low biomarkers at Week 24 will be randomized into Group 1 or 2

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 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]

In the phase 3 NAVIGATOR study involving patients aged 12-80 with severe asthma, tezepelumab significantly improved various lung function parameters, including pre-bronchodilator FEV1 and forced vital capacity (FVC), compared to placebo over 52 weeks.

Improvements in lung function were observed as early as 1-2 weeks and were particularly pronounced in patients with a shorter disease duration and specific baseline lung function characteristics, indicating tezepelumab's efficacy in managing severe asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Tezepelumab on Lung Function in Patients With Severe, Uncontrolled Asthma in the Phase 3 NAVIGATOR Study. Menzies-Gow, A., Ambrose, CS., Colice, G., et al.[2023]

Tezepelumab-ekko (Tezspire) is FDA-approved as an add-on maintenance therapy for individuals aged 12 and older with severe asthma that is not adequately controlled by existing medications.

The administration of Tezspire requires a healthcare provider to give it subcutaneously, highlighting the importance of professional oversight in its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tezspire Approved for Severe Asthma. Aschenbrenner, DS.[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 annual asthma exacerbations and improved asthma control in 1600 patients across four randomized controlled trials, demonstrating its efficacy in treating uncontrolled asthma.

While tezepelumab was associated with some non-serious adverse events like nasopharyngitis and headache, it showed a lower incidence of serious adverse events compared to placebo, indicating a favorable safety profile overall.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of tezepelumab in the treatment of uncontrolled asthma: A systematic review and meta-analysis of randomized controlled trials. Lin, F., Yu, B., Deng, B., et al.[2023]

Tezepelumab is a novel biologic treatment for severe uncontrolled asthma that targets thymic stromal lymphopoietin (TSLP), a key cytokine involved in asthma inflammation, and has been shown to reduce various inflammatory biomarkers.

The drug significantly decreases the annualized asthma exacerbation rate and improves asthma control, quality of life, and lung function, particularly benefiting patients with high levels of type 2 (T2) inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Positioning of Tezepelumab in severe asthma. Miralles-López, JC., Antolín-Amérigo, D., García-Moguel, I., et al.[2023]

References

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

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

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

Tezepelumab in Adults with Uncontrolled Asthma. [2022]

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

Effect of Tezepelumab on Lung Function in Patients With Severe, Uncontrolled Asthma in the Phase 3 NAVIGATOR Study. [2023]

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

Tezspire Approved for Severe Asthma. [2023]

5. 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]

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

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

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

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

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

The efficacy and safety of tezepelumab in the treatment of uncontrolled asthma: A systematic review and meta-analysis of randomized controlled trials. [2023]

9. Spain pubmed.ncbi.nlm.nih.gov

Positioning of Tezepelumab in severe asthma. [2023]