Tezepelumab for Eosinophilic Esophagitis

(CROSSING Trial)

Recruiting at 105 trial locations

Overseen By EoE Trial & You Clinical Trial Navigator

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: PPI, STC

Disqualifiers: Crohn's, Ulcerative colitis, Celiac, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

360 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests an injection treatment for people with a condition that causes swelling in the esophagus. The treatment aims to reduce this swelling by calming the immune system.

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

You may need to stop certain medications for the trial. If you are taking medications for EoE, you should stop them at least 8 weeks before the trial starts. If you are on biologic medications, you need a washout period (time without taking the medication) of 4 months or 5 half-lives, whichever is longer, before the trial begins.

What data supports the effectiveness of the drug Tezepelumab for treating eosinophilic esophagitis?

Tezepelumab has been shown to significantly reduce asthma exacerbations in patients with severe, uncontrolled asthma, suggesting its potential effectiveness in other conditions involving inflammation, like eosinophilic esophagitis. Additionally, similar treatments like mepolizumab have shown efficacy in treating eosinophilic esophagitis, which supports the potential of Tezepelumab for this condition. ^{1 2 3 4 5}

How is the drug Tezepelumab unique for treating eosinophilic esophagitis?

Tezepelumab is unique because it targets thymic stromal lymphopoietin, a molecule involved in the inflammation process, which is different from other treatments that target eosinophils directly. This approach may offer a new way to manage conditions like eosinophilic esophagitis by addressing the underlying inflammation. ^{1 6 7 8 9}

Eligibility Criteria

Adults and adolescents aged 12-80 with a confirmed diagnosis of EoE, weighing at least 40 kg, experiencing swallowing difficulties at least twice weekly. Participants must have been on a stable diet and any acid reflux or allergy medications for 8 weeks before the trial starts.

Inclusion Criteria

I am between 12 and 80 years old.

I have had trouble swallowing food at least twice a week in the last month.

I weigh at least 40 kg.

Exclusion Criteria

I have been diagnosed with EGPA vasculitis.

I do not have significant gastrointestinal issues like Crohn's, ulcerative colitis, or IBS.

I have a narrow esophagus that makes it hard for standard medical scopes to pass.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-8 weeks

Treatment

Participants receive randomized double-blind placebo-controlled treatment with Tezepelumab or placebo

52 weeks

Visits at Weeks 0, 4, 12, 24, and 52

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Extension

Optional active treatment extension period with Tezepelumab

24 weeks

Treatment Details

Interventions

• Tezepelumab

Trial Overview The study is testing Tezepelumab, given by injection using a pre-filled syringe, against a placebo to see if it's effective and safe in treating eosinophilic esophagitis (EoE). It's randomized and double-blind so neither doctors nor patients know who gets the real treatment.

Participant Groups

Group I: Tezepelumab Low Dose Experimental Treatment 1 Intervention

Tezepelumab subcutaneous injections, in accessorised pre-filled syringes

Group II: Tezepelumab High Dose Experimental Treatment 1 Intervention

Tezepelumab subcutaneous injections, in accessorised pre-filled syringes

Group III: Placebo Placebo Group 1 Intervention

Placebo subcutaneous injections, in accessorised pre-filled syringes

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

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

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 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]

Mepolizumab, a monoclonal antibody that neutralizes IL-5, has shown effectiveness in reducing eosinophil levels in patients with eosinophilic diseases, including asthma and hypereosinophilic syndrome.

While initial trials showed limited impact on asthma symptoms, more recent studies indicate that mepolizumab significantly reduces asthma exacerbations and improves quality of life in patients with severe eosinophilic asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mepolizumab and eosinophil-mediated disease. Walsh, GM.[2019]

Tezepelumab, a monoclonal antibody targeting thymic stromal lymphopoietin, demonstrated linear pharmacokinetics and a long half-life of 19.9 to 25.7 days, indicating effective dosing intervals for asthma treatment.

The drug was well tolerated in phase I studies with no signs of immunogenicity, suggesting it is safe for use in healthy individuals and those with atopic dermatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, Safety, and Tolerability of Tezepelumab (AMG 157) in Healthy and Atopic Dermatitis Adult Subjects. Parnes, JR., Sullivan, JT., Chen, L., et al.[2022]

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 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]

Fevipiprant is not expected to be adopted as a treatment for severe asthma, indicating limited efficacy or safety concerns.

Tezepelumab shows promise as a potential treatment for severe asthma, effective for patients regardless of eosinophilic inflammation status, suggesting a broader applicability in asthma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent developments in the management of severe asthma. Meteran, H., Tønnesen, LL., Sivapalan, P., et al.[2022]

Benralizumab, a monoclonal antibody targeting the IL-5 receptor, has been successfully used to treat a young female patient with Eosinophilic Granulomatosis with Polyangiitis (EGPA) and a history of severe eosinophilic asthma.

This case highlights a shift in treatment strategies for EGPA, focusing on targeting eosinophils, which play a significant role in the disease's development, rather than relying solely on traditional corticosteroids and immunosuppressants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case Report: Severe Eosinophilic Asthma Associated With ANCA-Negative EGPA in a Young Adult Successfully Treated With Benralizumab. Ricciardi, L., Soler, DG., Bennici, A., et al.[2022]

In a case series of three patients with Eosinophilic Granulomatosis with Polyangiitis (EGPA), the use of monoclonal antibodies targeting Interleukin-5 (IL-5), specifically mepolizumab and benralizumab, effectively controlled asthma symptoms and reduced the need for corticosteroids.

These treatments were particularly beneficial for patients who experienced frequent asthma exacerbations despite existing corticosteroid therapies or suffered from adverse effects related to corticosteroid use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-IL5 Monoclonal Antibodies Reduce Asthma Exacerbations and Corticosteroids Dose in Three Eosinophilic Granulomatosis with Polyangiitis Case Reports. Skouvaklidou, E., Kipourou, M., Zisopoulos, D., et al.[2023]

References

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

Tezspire Approved for Severe Asthma. [2023]

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

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

3. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Mepolizumab and eosinophil-mediated disease. [2019]

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

Pharmacokinetics, Safety, and Tolerability of Tezepelumab (AMG 157) in Healthy and Atopic Dermatitis Adult Subjects. [2022]

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

Tezepelumab in Adults with Uncontrolled Asthma. [2022]

6. New Zealand 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. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Recent developments in the management of severe asthma. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Case Report: Severe Eosinophilic Asthma Associated With ANCA-Negative EGPA in a Young Adult Successfully Treated With Benralizumab. [2022]

9. Greece pubmed.ncbi.nlm.nih.gov

Anti-IL5 Monoclonal Antibodies Reduce Asthma Exacerbations and Corticosteroids Dose in Three Eosinophilic Granulomatosis with Polyangiitis Case Reports. [2023]