Tezepelumab for Severe asthma | Chronic rhinosinusitis with nasal polyps

Inclusion criteria

• {"criterion_text":"-Provision of informed consent prior to any study specific procedures\n-Age 18-99 years and willing to participate in the study\n-Have a recorded clinical diagnosis of asthma (ICD-10 Code: J45)\n-Undergo severe asthma treatment according to GINA/DAL treatment step 4 or 5\n-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: •\tACT <20, ACQ>0.75 •\tDuring the last 12 months 2 courses of OCS for at least 3 days due to severe asthma symptoms •\tDuring last 12 months one exacerbation requiring hospitalization •\tLung 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\n-mucus score of ≥ 1\n-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)"}

Exclusion criteria

• {"criterion_text":"-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\n-Immunosuppressive treatment (e.g. cyclosporine)\n-Drug and alcohol abuse\n-Current smoker and former smokers if stopped smoking <6 months\n-Pregnancy (as determined by urine pregnancy test)\n-Patients with severe anatomic variations or deviations that do not allow access to all areas in the nasal cavity or to perform bronchoscopy\n-Patients with any other confounding underlying lung disorder including but not limited to: o Bronchiectasis, pulmonary fibrosis, emphysema, primary ciliary dyskinesia o Cystic fibrosis, any known parasitic infections and lung cancer\n-Patients with other causes of nasal polyps than Type 2 CRS inflammation\n-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\n-Contraindications for endobronchial and/or transbronchial biopsy\n-A mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study\n-Patients with clinically meaningful comorbidity as determined by the evaluating committee"}

Primary endpoints

• {"endpoint_text":"-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.","definition_or_measurement_approach":"Measured as changes in normalized cell index in cultured primary epithelial cells using the xCELLigence system for continuous monitoring of barrier function following challenge with barrier-damaging substances."}

Secondary endpoints

• {"endpoint_text":"-Mucus plugging: CT scan\n-Cellular composition: percentage of populations and mean metal intensity (marker expression)\n-Inflammatory mediator expression: Levels (e.g. ng/mL)\n-Microbiome: Composition, Diversity Indices\n-Tight junction protein staining: mean fluorescence intensity\n-Association: Pearson or Spearman-rank correlation coefficient depending on data distribution","definition_or_measurement_approach":"Mucus plugging assessed by CT scan; Cellular composition measured as percentage of populations and mean metal intensity (marker expression); Inflammatory mediator expression measured as levels (e.g. ng/mL); Microbiome assessed by composition and diversity indices; Tight junction protein staining measured by mean fluorescence intensity; Associations assessed using Pearson or Spearman-rank correlation coefficients depending on data distribution."}

Austria

Earliest CTIS Part Ii Submission Date

11-02-2025

Latest Decision Or Authorization Date

03-03-2025

Processing Time Days

20

Number Of Sites

1

Number Of Participants

20

Primary sponsor

Full Name

Medical University Of Vienna

Organisation Type

Educational Institution

Country Of Registered Address

Austria