Tezepelumab for Severe Asthma

(PASSAGE Trial)

No longer recruiting at 40 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: Any Age

Sex: Any

Trial Phase: Phase 4

Sponsor: AstraZeneca

Must be taking: ICS, LABA

Must not be taking: Biologics

Disqualifiers: Severe COPD, 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: 13

Duration: 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of tezepelumab, a medicine for people with severe asthma. The goal is to evaluate its efficacy and safety in different groups of people who have not been extensively studied before. Participants will receive a dose of tezepelumab every four weeks for about a year. The trial seeks individuals who have had asthma for at least a year, are on specific asthma medications, and have experienced frequent asthma attacks recently. As a Phase 4 trial, this research aims to understand how the already FDA-approved and effective treatment benefits a broader range of patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it does require that you have been on certain asthma medications for at least 12 months before joining. You should discuss your specific medications with the trial team.

What is the safety track record for tezepelumab?

Research shows that tezepelumab is generally safe for people with severe asthma. Studies have found that it helps reduce asthma flare-ups in individuals with various types of asthma. Earlier research found that patients experienced mild to moderate side effects, such as headaches or sore throats, with no major safety issues reported. Since this treatment is already approved for asthma, it is considered safe to use. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Tezepelumab is unique because it targets a key protein in the body called thymic stromal lymphopoietin (TSLP), which plays a crucial role in the inflammatory process of asthma. Unlike most asthma treatments that focus on controlling symptoms by affecting the airways directly, Tezepelumab works by blocking this upstream driver of inflammation, potentially preventing asthma attacks before they even start. Researchers are excited about this treatment because it offers a new mechanism of action, which could provide relief for patients with severe asthma who do not respond well to existing therapies like inhaled corticosteroids or biologics targeting other pathways.

What is the effectiveness track record for tezepelumab in treating severe asthma?

Research has shown that tezepelumab, the treatment under study in this trial, works well for people with severe asthma. Studies have found it can reduce asthma flare-ups by up to 79%, leading to fewer trips to the emergency room or hospital. Specifically, one study found that people using tezepelumab experienced 62% to 71% fewer flare-ups compared to those not using it. These results suggest that tezepelumab has strong potential to manage severe asthma effectively. ^{1 2 4 5 6}

Who Is on the Research Team?

Njira Lugogo., MD.

Principal Investigator

University of Michigan Health. Michigan, USA

Are You a Good Fit for This Trial?

This trial is for adults and adolescents (12 years or older) with severe asthma who've had at least 2 exacerbations in the past year, are on medium to high dose inhaler steroids plus another controller medication, and are under a specialist's care. They must be eligible for tezepelumab per US guidelines but not have used other biologics recently or be part of another asthma study.

Inclusion Criteria

I have been on a medium to high dose asthma treatment for at least a year.

Currently receiving care from specialist physicians (eg, pulmonologists and/or allergists).

My doctor has approved me for tezepelumab treatment as per US guidelines.

Exclusion Criteria

Participation in an interventional clinical trial for asthma within 12 months prior to enrollment.

Judgment by the Investigator that the participant is unlikely to comply with study procedures, restrictions, and requirements.

I haven't used asthma biologics for 4 months or 5 half-lives before joining.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 210 mg of tezepelumab via subcutaneous injection every 4 weeks from Week 0 to Week 48

48 weeks

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Tezepelumab

Trial Overview The trial is testing the effectiveness and safety of tezepelumab in treating severe asthma. It focuses on diverse populations within the United States that haven't been studied much before.

How Is the Trial Designed?

Group I: Tezepelumab Experimental Treatment 1 Intervention

Participants will be receiving 210 mg of tezepelumab every 4 weeks (Q4W) from Week 0 until Week 48.

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

Parexel

Industry Sponsor

Trials

322

Recruited

137,000+

Peyton Howell

Parexel

Chief Executive Officer

Master of Healthcare Administration from The Ohio State University, Bachelor of Arts in Health Communications from the University of Illinois

Dr. Austin Smith

Parexel

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Published Research Related to This Trial

In a study involving 550 adults with severe, uncontrolled asthma, tezepelumab significantly reduced annualized asthma exacerbation rates by 55-83% compared to placebo, demonstrating its efficacy in managing severe asthma.

Tezepelumab also lowered levels of various type 2 inflammatory biomarkers, indicating a reduction in airway inflammation, regardless of the patients' baseline biomarker profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baseline type 2 biomarker levels and response to tezepelumab in severe asthma. Corren, J., Pham, TH., Garcia Gil, E., 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 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 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 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 is a monoclonal antibody that targets thymic stromal lymphopoietin (TSLP), a key cytokine involved in asthma, and works by blocking TSLP from activating inflammatory cells, which is crucial for managing moderate-to-severe asthma.

Clinical trials have shown that tezepelumab is effective and safe for treating asthma, and ongoing studies are exploring its potential for other medical conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tezepelumab: an anti-thymic stromal lymphopoietin monoclonal antibody for the treatment of asthma. Shinkai, M., Yabuta, T.[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 for severe asthma, demonstrated a lower incidence of adverse events and serious adverse events over 104 weeks compared to placebo, indicating a favorable safety profile.

The treatment significantly reduced asthma exacerbation rates by 58% in participants from the NAVIGATOR study and by 39% in those from the SOURCE study, showing sustained efficacy in managing severe, uncontrolled asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of tezepelumab in people with severe, uncontrolled asthma (DESTINATION): a randomised, placebo-controlled extension study. Menzies-Gow, A., Wechsler, ME., Brightling, CE., 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]

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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa1704064

Tezepelumab in Adults with Uncontrolled Asthma Thus, exacerbation rates in the respective tezepelumab groups were lower by 62%, 71%, and 66% than the rate in the placebo group (P<0.001 for ...

2. 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 ...

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

Is Efficacy of Tezepelumab Independent of Severe Asthma ... Importantly, tezepelumab reduced the annualized rate of severe exacerbations requiring emergency department visit or hospitalization by 79% in the total ...

4. 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)

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

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02054130

NCT02054130 | Study to Evaluate the Efficacy and Safety ... The primary objective of the study is to evaluate the effect of 3 dose levels of MEDI9929 (AMG 157) on asthma exacerbations in adult subjects with inadequately ...