DUPILUMAB for Chronic rhinosinusitis with nasal polyps | Chronic rhinosinusitis without nasal polyps

Inclusion criteria

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

Exclusion criteria

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

Primary endpoints

• {"endpoint_text":"- Primary endpoint is the change in barrier sensitivity (Cell index) (1) at visit 1 (baseline) in stimulated versus unstimulated cells of patients suffering from CRSsNP or CRSwNP as compared to disease controls as well as in (2) CRSwNP patients at V1 and after 6 months of dupilumab treatment (V3).","definition_or_measurement_approach":"Change in barrier sensitivity measured as Cell index in cultured primary nasal- and polyp-derived epithelial cells after challenge with various harmful substances; comparison of stimulated versus unstimulated cells at baseline and comparison of CRSwNP patients at baseline and after 6 months of dupilumab therapy."}

Secondary endpoints

• {"endpoint_text":"- Change in barrier sensitivity as described in primary endpoint in patients over time (0, 3 and 6 months)","definition_or_measurement_approach":"Serial measurement of barrier sensitivity (Cell index) at 0, 3 and 6 months in cultured cells as per primary endpoint methodology."}
• {"endpoint_text":"- Expression levels of tight junction proteins (by mass cytometry imaging – percentage of positive cells and intensity of staining) in selected biopsies and fixed cultured primary cells in diseased patients and compared to disease controls","definition_or_measurement_approach":"Assessment of tight junction protein expression using mass cytometry/confocal imaging; reported as percentage of positive cells and staining intensity in biopsies and cultured cells."}
• {"endpoint_text":"- Cytokine levels (pg/ml) in nasal mucosal lining fluids of diseased patients and compared to disease controls","definition_or_measurement_approach":"Quantification of cytokine concentrations (pg/ml) in nasal mucosal lining fluids using platforms such as MSD, NULISA or OLINK."}
• {"endpoint_text":"- Association of barrier sensitivity and cytokine levels","definition_or_measurement_approach":"Correlation analyses between measured barrier sensitivity (Cell index) and cytokine concentration data."}
• {"endpoint_text":"- Microbiome (Diversity, Shannon index) in diseased patients and compared to disease controls","definition_or_measurement_approach":"Microbiome composition analysis reporting diversity metrics such as Shannon index from nasal samples."}
• {"endpoint_text":"- Association of barrier sensitivity and microbiome composition","definition_or_measurement_approach":"Statistical association analyses between barrier sensitivity measures and microbiome composition/diversity metrics."}
• {"endpoint_text":"- Transcriptome (differentially expressed genes and pathway analysis) and cytokine levels (pg/ml) in selected cultured cells derived from diseased patients and compared to disease controls","definition_or_measurement_approach":"RNA sequencing for transcriptome analysis (differential expression and pathway analysis) in cultured cells, together with cytokine quantification (pg/ml)."}
• {"endpoint_text":"- Association of experimental (change in barrier function, transcriptome, etc.) with clinical data (TPS, SNOT-22, etc.)","definition_or_measurement_approach":"Integrative analyses associating experimental readouts (barrier function, transcriptome, cytokines) with clinical scores such as TPS and SNOT-22."}

Austria

Earliest CTIS Part Ii Submission Date

25-03-2024

Latest Decision Or Authorization Date

06-05-2024

Processing Time Days

42

Number Of Sites

1

Number Of Participants

80

Primary sponsor

Full Name

Medical University Of Vienna

Organisation Type

Educational Institution

Country Of Registered Address

Austria