Effect of Tezepelumab on Barrier Function in Severe Asthmatic Patients With and Without Comorbid Chronic Rhinosinusitis With Nasal Polyps

NCT07046117 | Not Yet Recruiting DMC

• 1 other identifier: Tezebarrier2025
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

In this study, we will investigate the effect of tezepelumab on the epithelial barrier function of the upper and lower airways in patients suffering from severe asthma with and without chronic rhinosinusitis with nasal polyps. This will be achieved by analysis of epithelial barrier function upon challenge with various harmful substances (e.g. cigarette smoke extract, allergens) in cultured primary respiratory tract epithelial cells. Furthermore we will assess changes in clinical parameters, cellular composition and inflammatory mediators.

Conditions

Asthma Bronchiale; Chronic Rhinosinusitis With Nasal Polyps (CRSwNP)

Keywords

asthma; chronic rhinosinusitis with nasal polyps; tezepelumab; epithelial barrier; airways

Outcome Measures

Primary Outcomes (1)

• Change in cell index

  Changes in normalized cell index in response to barrier-damaging substances in cultured primary epithelial cells of the different disease entities using the xCELLigence system for continuous monitoring of barrier function.

  6 months

Secondary Outcomes (3)

• Change in mucus plugging

  6 months

• Change in marker expression immune cell subsets

  6 months

• Change in inflammatory mediators

  6 months

Study Arms (2)

Asthma only

ACTIVE COMPARATOR

Patients suffering from asthma in absence of CRSwNP will be administerd tezepelumab every 4 weeks

Drug: Tezepelumab

Asthma with CRSwNP

ACTIVE COMPARATOR

Patients suffering from Asthma with CRSwNP will be administered Tezepelumab every 4 weeks

Drug: Tezepelumab

Interventions

Tezepelumab DRUG

injection with Tezepelumab every 4 weeks

Asthma only; Asthma with CRSwNP

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of informed consent prior to any study specific procedures
• Age 18-99 years and willing to participate in the study
• Have a recorded clinical diagnosis of asthma (ICD-10 Code: J45)
• Undergo severe asthma treatment according to GINA/DAL treatment step 4 or 5
• Meet the requirements for treatment of severe asthma with Tezepelumab defined as:
• severe asthma that remains uncontrolled despite a high dosage of ICS/LABA, or that requires a high dose to prevent it from becoming uncontrolled. One of the following criteria needs to be fulfilled:
• ACT \<20, ACQ\>0.75
• During the last 12 months 2 courses of OCS for at least 3 days due to severe asthma symptoms
• During last 12 months one exacerbation requiring hospitalization
• Lung function: FEV1 \<80% predicted
• FeNO ≥ 20 ppB
• had either ≥250 eosinophils /µl measured in the blood OR measurement of blood eosinophils ≥150 cells during reduction of OCS dosing or high dose ICS and/or one measurement of sputum eosinophils \> 2% or BAL eosinophils \> 2%
• Group with polyps: Presence of nasal polyps as confirmed by endoscopy or CT according to the European Position Paper on Rhinosinusitis and Nasal Polyps Guidelines
• mucus score of ≥ 1
• Patients with a history of treatment with monoclonal antibodies for asthma or polyps will only be included if at least a washout period of 3 half-lives or 3 months have passed (whichever is longer)

You may not qualify if:

• \. Patients with current therapy with biologics as well as therapy with biologics 12 weeks (3 half-lives) before the start of the study or history of therapy with tezepelumab 2. Pregnancy (as determined by urine pregnancy test) 3. Patients with severe anatomic variations or deviations that do not allow access to all areas in the nasal cavity or to perform bronchoscopy 4. Patients with any other confounding underlying lung disorder including but not limited to:
• Bronchiectasis, pulmonary fibrosis, emphysema, primary ciliary dyskinesia
• Cystic fibrosis, any known parasitic infections and lung cancer
• \. Patients with other causes of nasal polyps than Type 2 CRS inflammation 6. Patients with pulmonary conditions with symptoms of asthma and blood eosinophilia including but not limited to: Eosinophilic granulomatosis with polyangiitis (EGPA) allergic bronchopulmonary aspergillus and hypereosinophilic syndrome 7. Contraindications for endobronchial and/or transbronchial biopsy. 8. A mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study 9. Patients with clinically meaningful comorbidity as determined by the evaluating committee 10. Immunosuppressive treatment (e.g. cyclosporine) 11. Drug and alcohol abuse 12. Current smoker and former smokers if stopped smoking \<6 months

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (1)

Medical University of Vienna

Vienna, Austria, A-1090, Austria

Location

MeSH Terms

Conditions

Asthma

Interventions

tezepelumab

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Marco Idzko, MD, PhD

  Medical University of Vienna

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Julia Eckl-Dorna, MD, PhD

CONTACT

+43140400; julia.eckl-dorna@meduniwien.ac.at

Victoria Stanek

CONTACT

Stanek; victoria.stanek@meduniwien.ac.at

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Univ.Prof.Dr.med.

Study Record Dates

• First Submitted: June 5, 2025
• First Posted: July 1, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: July 1, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ANALYTIC CODE
• Time Frame: from Dec 2025 with open end
• Access Criteria: those who are registerd with public databases or who contact the investigators via email

Locations

AU (1)