Tezepelumab for Asthma

(TERAA Trial)

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

100 Participants Needed

Trial Summary

What is the purpose of this trial?

Adults with severe asthma may have sudden worsening shortness of breath that results in their going to Emergency Department for urgent care. Emergency Room visits for asthma management across Alberta have been reviewed and it has been found that adults frequently need to return for repeated worsening. This is a large drain on health care resources as well as being very distressing for individuals with asthma. Occasionally this results in admission to hospital and rarely may lead to death. People are often treated with steroids to try to prevent the need for Emergency Room visits even though steroid medications have many long term bad side effects. A new medication for patients considered to have severe asthma has been recently approved by Health Canada. This medication, Tezepelumab, is a monthly injection and it helps control asthma in adults regardless of the underlying cause. The study will examine if starting Tezepelumab, compared with a placebo, in the Emergency Room will help settle symptoms of asthma and prevent future worsening requiring repeated Emergency Room visits or the need for courses of outpatient steroid medications.

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 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 no higher incidence of adverse reactions compared to a placebo. ^{2 5 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 improve asthma control, making it effective for patients with severe, uncontrolled asthma. ^{1 2 4 5 9}

Research Team

Irvin Mayers, MD

Principal Investigator

University of Alberta

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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

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 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]

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]

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 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 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. 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]

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

Tezspire Approved for Severe Asthma. [2023]

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

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

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

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

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]