Effect of Dupilumab on Nasal Epithelial Barrier Function in Patients With CRSwNP (EpiBar)

Effect of Dupilumab on Nasal Epithelial Barrier Function in Patients With Chronic Rhinosinusitis With Nasal Polyps (CRSwNP) - an Exploratory Pilot Study

The investigators aim to investigate two major so far unresolved topics in CRSwNP research: (1) Thorough functional and molecular characterisation of barrier function in patients suffering from CRSsNP and CRSwNP and (2) effect of dupilumab treatment on barrier function in polyp patients. This will be achieved in patient-derived samples by employing measurement of barrier function in primary cell cultures in combination with a mass cytometry based imaging approach, transcriptomic analysis as well as cytokine and microbiome data of individual patients.

Study Overview

• Status: Recruiting
• Conditions: Chronic Rhinosinusitis With Nasal Polyps; Chronic Rhinosinusitis Without Nasal Polyps
• Intervention / Treatment: Drug: Dupilumab 300 MG/2 ML Subcutaneous Solution [DUPIXENT]

Detailed Description

Primary objective 1: Characterization of differences in barrier function of the nasal epithelium in patients suffering from CRSsNP, CRSwNP with and without asthma or N-ERD (in absence of therapy with monoclonal antibodies). T Primary objective 2: Effect of dupilumab treatment on barrier function of the nasal epithelium in patients suffering from CRSwNP with and without asthma or N-ERD.

• Study Type: Observational
• Enrollment (Estimated): 80

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, A-1090
    • Recruiting
    • Medical University of Vienna
    • Principal Investigator: Sven Schneider, MD
    • Sub-Investigator: Julia Eckl-Dorna, MD, PhD
    • Sub-Investigator: Nicholas Campion, MD
    • Sub-Investigator: Tina Bartosik, MD
    • Contact: Victoria Stanek, MA; Email: victoria.stanek@meduniwien.ac.at
    • Sub-Investigator: Victoria Stanek, MA
    • Sub-Investigator: Aldine Tu, MA
    • Sub-Investigator: Fana Kidane, PhD
    • Sub-Investigator: Mohammed Zghaebi, MA
    • Sub-Investigator: Christoph Krall, PhD
    • Contact: Julia Eckl-Dorna, MD, PhD; Phone Number: 004314040034380; Email: julia.eckl-dorna@meduniwien.ac.at

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with chronic rhinosinusitis with and without nasal polyps

Description

Inclusion Criteria:

• 18-99 years of age
• Willingness to participate in the study
• Suffer from chronic rhinosinusitis defined as in EPOS 2020 criteria, see main text
• Group 1 (n=20, CRSsNP): Absence of nasal polyps
• Group 2 (N=60, CRSwNP): Presence of nasal polyps as confirmed by endoscopy or CT and planned therapy with dupilumab
• Presence or absence of non-steroidal anti-inflammatory drug (NSAID)-Exacerbated Respiratory Disease (N-ERD)
• Patients with a history of treatment with monoclonal antibodies will only be included if at least a washout period of 6 months has passed

Exclusion Criteria:

• Pregnancy (as determined by ß-HCG test) or breast feeding
• Patients with severe anatomic variations or deviations that do not allow access to all areas in the nasal cavity
• Patients with cystic fibrosis or primary ciliary dyskinesia
• Patients with permanent immunosuppression
• A mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study
• Patients with clinically meaningful comorbidity as determined by the evaluating committee
• Patients with a history of exacerbation of chronic rhinosinusitis 4 weeks prior to the screening visit
• Intake of a burst of systemic corticosteroids for the treatment of CRS 4 weeks prior to the screening visit

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
CRSsNP
CRSwNP; Dupilumab	Drug: Dupilumab 300 MG/2 ML Subcutaneous Solution [DUPIXENT]; 300mg/2 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Barrier function in CRSsNP and CRSwNP	Cell index (xCELLigence)	1 Visit (baseline)
Barrier function in CRSwNP with Dupilumab	Cell index (xCELLigence)	3 Visits (baseline, 3 months, 6 months)

Collaborators and Investigators

• Sponsor: Medical University of Vienna

Publications and helpful links

General Publications

• Bachert C, Han JK, Desrosiers M, Hellings PW, Amin N, Lee SE, Mullol J, Greos LS, Bosso JV, Laidlaw TM, Cervin AU, Maspero JF, Hopkins C, Olze H, Canonica GW, Paggiaro P, Cho SH, Fokkens WJ, Fujieda S, Zhang M, Lu X, Fan C, Draikiwicz S, Kamat SA, Khan A, Pirozzi G, Patel N, Graham NMH, Ruddy M, Staudinger H, Weinreich D, Stahl N, Yancopoulos GD, Mannent LP. Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials. Lancet. 2019 Nov 2;394(10209):1638-1650. doi: 10.1016/S0140-6736(19)31881-1. Epub 2019 Sep 19.
• Schneider S, Poglitsch K, Morgenstern C, Quint T, Gangl K, Sinz C, Bartosik T, Campion NJ, Liu DT, Landegger LD, Tu A, Stanek V, Rocha-Hasler M, Bangert C, Eckl-Dorna J. Dupilumab increases aspirin tolerance in NSAID-exacerbated respiratory disease. Eur Respir J. 2023 Mar 16;61(3):2201335. doi: 10.1183/13993003.01335-2022. Print 2023 Mar.

Study record dates

Study Major Dates

• Study Start (Actual): June 6, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: April 25, 2024
• First Submitted That Met QC Criteria: April 30, 2024
• First Posted (Actual): May 3, 2024

Study Record Updates

• Last Update Posted (Actual): May 7, 2025
• Last Update Submitted That Met QC Criteria: May 6, 2025
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Nose Diseases; Otorhinolaryngologic Diseases; Rhinitis; Paranasal Sinus Diseases; Rhinosinusitis; Polyps; Nasal Polyps; Sinusitis; Immunologic Factors; Physiological Effects of Drugs; Antibodies, Monoclonal
• Other Study ID Numbers: EpiBar

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD will be shared upon reasonable request

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No