Tezepelumab for Asthma

(ARRIVAL Trial)

Recruiting at 84 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: Any Age

Sex: Any

Trial Phase: Phase 3

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

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: 18

300 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to determine if tezepelumab, an injection for asthma, can help people with severe asthma reduce their reliance on other medications while maintaining symptom control. Participants will receive the treatment through a simple injection and attend check-ups every four weeks. The trial divides participants into groups; some will gradually lower their usual medication, while others will continue as normal. Ideal candidates have had severe asthma for at least a year and have experienced asthma attacks requiring hospital visits or extra medication in the past year. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for severe asthma.

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.

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 with severe asthma. Studies have found that patients taking tezepelumab experienced fewer asthma attacks than those who did not. For instance, one study noted a reduction in hospital visits due to asthma attacks when using tezepelumab.

Another study demonstrated that the treatment reduced asthma attacks over a year, with different doses yielding similar results. Some patients experienced side effects, but these were mostly mild to moderate. Importantly, this treatment is already approved for other conditions, suggesting its safety.

Overall, current evidence supports the safety of tezepelumab, but patients should always discuss potential risks with their doctor. ^{1 2 3 4 5}

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

Tezepelumab is unique because it targets a specific part of the immune system called thymic stromal lymphopoietin (TSLP), which plays a key role in triggering asthma inflammation. This mechanism is different from standard asthma treatments like inhaled corticosteroids (ICS) or long-acting beta-agonists, which focus more on managing symptoms rather than preventing the inflammation at its source. Researchers are excited about Tezepelumab because it has the potential to reduce asthma attacks and improve overall asthma control, even in patients who don't respond well to existing treatments. This innovative approach could offer new hope for those with difficult-to-treat asthma.

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

Research has shown that tezepelumab effectively treats severe asthma. Studies have demonstrated that it can greatly reduce asthma attacks. In individuals with severe, uncontrolled asthma, tezepelumab led to a noticeable decrease in asthma flare-ups compared to those taking a placebo. Specifically, one study found that patients using tezepelumab had 62% fewer hospital visits due to asthma. These findings suggest that tezepelumab may help improve asthma control and reduce the need for emergency care. Participants in this trial will be assigned to different groups based on their asthma control and biomarker levels, with some groups undergoing a step-down of inhaled corticosteroids (ICS) and others not. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Tezepelumab

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.

How Is the Trial Designed?

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

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

Fortrea

Industry Sponsor

Trials

22

Recruited

5,800+

Published Research Related to This Trial

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 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]

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-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 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 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, 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

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

Efficacy of Tezepelumab in Severe, Uncontrolled Asthma Tezepelumab reduced exacerbations in patients with severe, uncontrolled asthma across a range of baseline blood eosinophil counts and fractional exhaled nitric ...

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 ...

3. 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. jaci-inpractice.org jaci-inpractice.org/article/S2213-2198(25)00757-3/fulltext

Efficacy and Safety of Tezepelumab in Adults With Severe, ... Compared with placebo recipients, tezepelumab recipients experienced 62% (95% CI: −5, 86) fewer asthma exacerbations requiring hospitalization ...

5. 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) Tezspire™ (n=137) significantly reduced asthma exacerbations vs placebo (n=138).**. 2018. NAVIGATOR: Phase 3*. This trial tested the efficacy and safety of ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05329194

Study Details | NCT05329194 | Effectiveness and Safety ... To asses effectiveness and safety of tezepelumab in adult and adolescent participants with severe asthma including several under-studied populations in the ...