Tezepelumab for COPD

(EMBARK Trial)

Recruiting at 221 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: ICS, LABA, LAMA

Must not be taking: Macrolides, Immunosuppressives

Disqualifiers: Asthma, Tuberculosis, Malignancies, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 52-76 weeks

990 Participants Needed

Trial Summary

What is the purpose of this trial?

A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group, Phase 3 Study to Evaluate the Efficacy and Safety of Tezepelumab in Adults with Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD)

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it mentions that participants should have been on certain inhaled COPD therapies for at least 3 months before starting. It also lists some medications that might not be allowed, like macrolides and certain immune system medications.

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

Tezepelumab has been shown to significantly improve lung function and reduce asthma attacks in patients with severe, uncontrolled asthma, suggesting it may help with similar lung-related conditions like COPD. ^{1 2 3 4 5}

Is tezepelumab safe for humans?

Tezepelumab has been studied in people with severe asthma, and the research shows it is generally safe. Patients did not experience more side effects with tezepelumab compared to a placebo (a substance with no active drug). ^{5 6 7 8 9}

How is the drug tezepelumab unique for treating COPD?

Tezepelumab is unique because it is a monoclonal antibody that blocks thymic stromal lymphopoietin (TSLP), a protein involved in inflammation, which is different from most COPD treatments that typically target symptoms or airflow obstruction. This mechanism has been shown to reduce inflammation in asthma, suggesting potential benefits for COPD. ^{2 7 10 11 12}

Research Team

Dave Singh, MD

Principal Investigator

Division of Infection, Immunity & Resp Medicine, The University of Manchester, United Kingdom

Eligibility Criteria

This trial is for adults with moderate to very severe COPD, a chronic lung disease that obstructs airflow. Participants should meet specific health criteria but the provided information does not detail these requirements.

Inclusion Criteria

Eosinophils count ≥ 150 cells/μL during screening

CAT score ≥ 15 at screening

I have been diagnosed with COPD for over a year.

Exclusion Criteria

Any unstable disorder that can impact participant's safety or study outcomes

I have a lung condition that is not COPD.

I need more than 4 liters per minute of oxygen or my oxygen levels stay below 89% despite using oxygen.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive monthly subcutaneous injections of tezepelumab or placebo for a duration of 52 to 76 weeks

52-76 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• Tezepelumab

Trial Overview The study tests Tezepelumab's effectiveness and safety against a placebo in improving COPD symptoms. It's a phase 3 trial, meaning it's at an advanced stage of testing with more participants to confirm its efficacy and monitor side effects.

Participant Groups

Group I: Dose 2 of Tezepelumab Experimental Treatment 1 Intervention

Tezepelumab, SC, Q4W

Group II: Dose 1 of Tezepelumab Experimental Treatment 1 Intervention

Tezepelumab, SC, Q4W

Group III: Matching Placebo Placebo Group 1 Intervention

Matching placebo, SC, Q4W

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

Amgen

Industry Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

Findings from Research

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]

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, 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]

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]

In clinical trials, subcutaneous tezepelumab significantly reduced the annualized asthma exacerbation rate by up to 71% compared to placebo, demonstrating its efficacy in treating severe uncontrolled asthma.

Tezepelumab is effective across various asthma phenotypes, including nonallergic and noneosinophilic types, making it a versatile treatment option for patients with severe asthma regardless of their specific characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tezepelumab in the Treatment of Uncontrolled Severe Asthma. Feist, J., Lipari, M., Kale-Pradhan, P.[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]

In a 52-week study involving 65 Japanese patients with severe uncontrolled asthma, tezepelumab was found to be safe and well-tolerated, with most adverse events being mild to moderate, and only one case leading to treatment discontinuation.

Tezepelumab significantly reduced asthma exacerbation rates (0.11 per patient-year) and improved lung function and asthma control, with a 71.4% responder rate at Week 52, indicating its efficacy in managing severe asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

One-year safety and tolerability of tezepelumab in Japanese patients with severe uncontrolled asthma: results of the NOZOMI study. Shinkai, M., Ebisawa, M., Fukushima, Y., et al.[2023]

Tezepelumab significantly reduced airway eosinophil counts in patients with uncontrolled asthma, indicating its efficacy in lowering eosinophilic airway inflammation, which is a key factor in asthma exacerbations.

The treatment also improved airway hyperresponsiveness to mannitol, suggesting that blocking TSLP may provide additional benefits in asthma management beyond just reducing type 2 inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of tezepelumab on airway inflammatory cells, remodelling, and hyperresponsiveness in patients with moderate-to-severe uncontrolled asthma (CASCADE): a double-blind, randomised, placebo-controlled, phase 2 trial. Diver, S., Khalfaoui, L., Emson, C., et al.[2022]

References

1. 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]

2. Denmark pubmed.ncbi.nlm.nih.gov

Baseline type 2 biomarker levels and response to tezepelumab in severe asthma. [2022]

3. 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]

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

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

5. England 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. [2023]

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

Tezepelumab in the Treatment of Uncontrolled Severe Asthma. [2023]

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

Tezepelumab Efficacy in Patients with Severe, Uncontrolled Asthma with Comorbid Nasal Polyps in NAVIGATOR. [2023]

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

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

9. England pubmed.ncbi.nlm.nih.gov

One-year safety and tolerability of tezepelumab in Japanese patients with severe uncontrolled asthma: results of the NOZOMI study. [2023]

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

Tezepelumab in Adults and Adolescents with Severe, Uncontrolled Asthma. [2021]

11. England pubmed.ncbi.nlm.nih.gov

An overview of the preclinical discovery and development of tezepelumab for the treatment of asthma. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Effect of tezepelumab on airway inflammatory cells, remodelling, and hyperresponsiveness in patients with moderate-to-severe uncontrolled asthma (CASCADE): a double-blind, randomised, placebo-controlled, phase 2 trial. [2022]