Effect of Dupilumab on nasal epithelial barrier function in patients with Chronic Rhinosinusitis with nasal polyps (CRSwNP) – an exploratory pilot study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medical University Of Vienna

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Otorhinolaryngologic Diseases [C09]

Trial duration

15 May 2024 → 22 May 2026

Decision date (initial)

2024-05-06

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

• To characterize differences in barrier function of the nasal epithelium in patients suffering from CRSsNP or CRSwNP (in absence of therapy with monoclonal antibodies) and disease controls in response to challenges with various harmful substances in cultured primary nasal- and polyp-derived epithelial cells.
• Effect of dupilumab treatment on barrier function of the nasal epithelium in patients suffering from CRSwNP.

Secondary objectives 6

1. To characterize differences in barrier function of the nasal epithelium in patients suffering from CRSsNP or CRSwNP (in absence of therapy with monoclonal antibodies) as compared to disease controls in response to challenges with various harmful substances in cultured primary nasal- and polyp-derived epithelial cells (samples of disease controls already available).
2. Analysis of epithelial integrity by staining for tight junction proteins (mass cytometry/confocal imaging) in biopsies of polyps and/or nasal mucosa of patients suffering from (A) CRSsNP or CRSwNP patients in absence of monoclonal antibody therapy and (B) from CRSwNP before as well as after 3 and 6 months of dupilumab therapy and (C) compared to disease controls (samples already available)
3. Analysis of cytokine profiles (e.g., MSD platform, NULISA or OLINK) in selected nasal secretions in patients’ cohorts as mentioned above (=CRSsNP or CRSwNP (in absence of therapy with monoclonal antibodies) as compared to disease controls)
4. Analysis of transcriptome (RNA sequencing) and cytokine profile in selected cultured cells derived from patient cohorts as mentioned above
5. Analysis of nasal microbiome composition in patient cohorts as mentioned above
6. Association of experimental (change in barrier function, transcriptome, etc.) with clinical data (TPS, SNOT-22, etc.)

Conditions and MedDRA coding

Chronic rhinosinusitis with nasal polyps

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 18-99 years of age
2. Willingness to participate in the study
3. Suffer from chronic rhinosinusitis defined as in EPOS 2020 criteria, see main text
4. Group 1 (n=20, CRSsNP): Absence of nasal polyps
5. Group 2 (N=60, CRSwNP): Presence of nasal polyps as confirmed by endoscopy or CT and planned therapy with dupilumab
6. Presence or absence of non-steroidal anti-inflammatory drug (NSAID)-Exacerbated Respiratory Disease (N-ERD)
7. 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 8

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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).

Secondary endpoints 8

1. Change in barrier sensitivity as described in primary endpoint in patients over time (0, 3 and 6 months)
2. 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
3. Cytokine levels (pg/ml) in nasal mucosal lining fluids of diseased patients and compared to disease controls
4. Association of barrier sensitivity and cytokine levels
5. Microbiome (Diversity, Shannon index) in diseased patients and compared to disease controls
6. Association of barrier sensitivity and microbiome composition
7. 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
8. Association of experimental (change in barrier function, transcriptome, etc.) with clinical data (TPS, SNOT-22, etc.)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medical University Of Vienna

Sponsor organisation

Medical University Of Vienna

Address

Spitalgasse 23, Alsergrund Alsergrund

City

Vienna

Postcode

1090

Country

Austria

Scientific contact point

Organisation

Medical University Of Vienna

Contact name

Department of Ear, Nose and Throat Disease

Public contact point

Organisation

Medical University Of Vienna

Contact name

Department of Ear, Nose and Throat Disease

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

1 submissions — initial application plus substantial / non-substantial modifications