Tezepelumab for Asthma

(TERAA Trial)

Not yet recruiting at 1 trial location

Overseen By Angela C Johnson, RRT

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Alberta

Must be taking: Inhaled corticosteroids, LABA, LAMA, LTRA

Must not be taking: Torsades de Pointes, CYP3A4 inducers

Disqualifiers: Hepatitis, HIV, Smoking, Arrhythmia, others

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: 8

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of a new asthma treatment, Tezepelumab, for adults with severe asthma. The goal is to determine if this monthly injection can reduce emergency room visits and lessen reliance on steroids, which have unwanted side effects. Participants will receive either Tezepelumab or a placebo to compare outcomes. Those who have experienced asthma attacks despite using high-dose inhalers and other medications might be suitable for this study. As a Phase 4 trial, this research aims to understand how this already FDA-approved and effective treatment can benefit more patients.

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

The trial does not specify if you need to stop your current medications. However, you must have been on high-dose inhaled corticosteroids and at least one other asthma controller for at least 3 months before joining. Some medications that affect heart rhythm or liver enzymes may not be allowed.

What is the safety track record for Tezepelumab?

In earlier studies, Tezepelumab showed promising safety results for treating severe asthma. Research indicates it significantly reduced asthma flare-ups requiring hospital visits. Patients using Tezepelumab experienced 62% fewer severe asthma attacks compared to those receiving a placebo.

The treatment is generally well-tolerated. Common side effects are mild and may include a sore throat and headaches. No serious side effects have been directly linked to the medication itself.

Tezepelumab is already approved in some areas for asthma, suggesting its safety is well-understood. This approval provides extra reassurance about its safety for those considering joining a clinical trial. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard asthma treatments, which often include inhaled corticosteroids or bronchodilators, Tezepelumab works by targeting a molecule called thymic stromal lymphopoietin (TSLP). TSLP plays a key role in the allergic inflammation process that can trigger asthma symptoms. By blocking TSLP, Tezepelumab aims to reduce asthma attacks more effectively and offer relief to patients who may not respond well to existing treatments. Researchers are excited about this treatment because it represents a new way to manage asthma, potentially benefiting patients with severe forms of the condition who have limited options.

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

Studies have shown that Tezepelumab effectively treats severe, uncontrolled asthma, significantly reducing asthma attacks by about 62% compared to a placebo. This reduction means fewer hospital visits for those with severe symptoms. In this trial, participants may receive either Tezepelumab or a placebo. Tezepelumab targets a specific part of the immune system involved in asthma, helping control symptoms regardless of the cause. Its approval for treating severe asthma provides confidence in its potential to make a real difference. ^{1 3 4 5 6}

Who Is on the Research Team?

Irvin Mayers, MD

Principal Investigator

University of Alberta

Are You a Good Fit for This Trial?

This trial is for adults aged 18-55 with severe asthma, using high-dose inhaled steroids and another controller. They must have had an asthma attack in the past year and agree to contraception if applicable. Excluded are those with HIV, recent other trials, Tezepelumab hypersensitivity, hospital admission at screening, drug/alcohol abuse history within a year, certain medication use or health conditions like long QT syndrome.

Inclusion Criteria

Provision of informed consent prior to any study specific procedures

I have been diagnosed with asthma by a doctor.

Negative pregnancy test (urine or serum) for female subjects of childbearing potential

Exclusion Criteria

Known hypersensitivity to Tezepelumab or any of the excipients of the product

Involvement in the planning and/or conduct of the study

Previous enrolment in the present study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants receive Tezepelumab or placebo in the Emergency Department, followed by monthly injections

12 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Open-label extension

Participants receive open-label Tezepelumab from Day 90 to Day 180

12 weeks

3 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Tezepelumab

Trial Overview The TERAA study tests whether Tezepelumab can reduce emergency room visits for severe asthma compared to a placebo. It's given as a monthly injection starting from the ER visit. The goal is to see if it helps control symptoms better than standard treatments without needing repeated steroid courses.

How Is the Trial Designed?

Group I: Tezepelumab Open Label Experimental Treatment 1 Intervention

Open-label extension study from Day 90 to Day 180 with Tezepelumab dosing at Day 90

Group II: Tezepelumab Active Control 1 Intervention

Tezepelumab 210 mg S/Q Q4W

Group III: Placebo Placebo Group 1 Intervention

Matching Placebo S/Q Q4W

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?

University of Alberta

Lead Sponsor

Trials

957

Recruited

437,000+

AstraZeneca

Industry 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

Published Research Related to This Trial

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]

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 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]

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 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, 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 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]

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 ...