Mechanisms of Smell Improvement With Dupilumab.

NCT05964465 | Completed Phase 4 FDA Drug

• 1 other identifier: Pro00125142
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

Brief Summary

This study seeks to explore the mechanism through which dupilumab improves olfactory cleft inflammation in patients with chronic sinusitis with nasal polyps (CRSwNP). The investigators expect this study to provide convincing evidence that dupilumab improves clinical olfaction via direct reduction in olfactory cleft inflammation.

Conditions

Chronic Rhinosinusitis With Nasal Polyps

Keywords

Chronic Rhinosinusitis; Nasal Polyps; dupilumab

Outcome Measures

Primary Outcomes (5)

• Change in volumetric olfactory cleft opacification based on CT.

  Non-contrast sinus computed tomography (CT) scans will be obtained at baseline and 3 month follow-up to provide 1mm cuts that can be formatted in coronal, sagittal, and axial planes. Volumetric analysis of the OC will be performed utilizing equally spaced coronal CT images per our previously described protocols. Total volume of the segmented 3-D olfactory cleft space will be calculated, as well as the volume of air within that space. The percent opacification will be defined as \[1-(total volume of air/total volume of olfactory cleft)\] multiplied by 100. Sinus opacification will be quantified using the Lund-Mackay CT scale.

  3 months post-treatment

• Change in olfactory cleft endoscopy score based on nasalendoscopy.

  Subjects will have sinonasal endoscopy at baseline and every follow up visit. This procedure allows visual inspection of the sinus mucosal lining and grading of polyps, including the olfactory cleft. Results for each side will be recorded separately and combined for a final Olfactory Cleft Endoscopy Scale (OCES) that ranges from 0-20, with higher scores representing increased disease severity.

  3 months post-treatment

• Change in olfactory cleft mucus cytokine levels

  Under endoscopic guidance, a 1 × 2-cm Leukosorb filter paper (Pall Scientific, Port Washington, NY) strip will be placed into the olfactory cleft of each side, and kept in place for 3 minutes, as described in earlier studies. This will be done at baseline, 2 weeks, and 3 months. Olfactory cleft mucus inflammatory cytokine levels will be detected using commercially available LegendPlex Th2 Cytometric Bead Array (BioLegend, San Diego, CA) following the manufacturer's recommended protocol. This panel will include IL4, IL13, IL5 cytokines (among others). The assay will be carried out according to manufacturers' instructions and as previously described. The samples will be read on a Guava easyCyte 8HT flow cytometer (EMD Millipore) and analysis performed with LegendPlex software. Total IgE will be quantified via ELISA (GenWay Biotech. Inc, San Diego, CA).

  3 months post-treatment

• Change in Lund-Kennedy endoscopy score.

  Subjects will have sinonasal endoscopy at baseline and every follow up visit. This procedure allows visual inspection of the sinus mucosal lining and grading of polyps, including the olfactory cleft. Results for each side will be recorded separately and combined for a final Lund-Kennedy endoscopy score (LKES) that ranges from 0-20, with higher scores representing increased disease severity.

  3 months post-treatment

• Change in overall polyp score from sinonasal endoscopy

  Overall polyp score on a 0-4 scale for each nostril (summed 0-8).

  3 months post-treatment.

Secondary Outcomes (2)

• Correlation between change in olfactory cleft mucus IL13 level and Sniffin Sticks TDI

  3 months post-treatment

• Correlation between change in IL13 level and QOD-NS score

  3 months post-treatment

Study Arms (1)

Treatment

EXPERIMENTAL

The treatment group will receive dupilumab at 300mg SC Q2weeks. The first dose will be administered via subcutaneous injection in clinic at baseline. Subjects will self-administer study drug (dupilumab 300 mg) subcutaneous every 2 weeks after initial dosing at visit 2.

Drug: Dupilumab

Interventions

Dupilumab DRUG

Monoclonal antibody blocking interleukin 4 and interleukin 13

Treatment

Eligibility Criteria

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

You may qualify if:

• Adults ≥18 years of age
• Meet criteria for CRSwNP as defined by ICAR-21
• out of 4 cardinal symptoms for ≥12 weeks
• Visible evidence of inflammation on endoscopy or imaging
• Bilateral visible nasal polyps ≥1 in each nasal cavity (0-4 scale each side)
• Olfaction score ≥1 (0-3 scale)
• Candidate for treatment with dupilumab for CRSwNP
• Elected to proceed with dupilumab for treatment of CRSwNP

You may not qualify if:

• Prior use of dupilumab
• Previous treatment with another biologic medication for CRSwNP or asthma within 6 months
• Any nasal or sinus surgery within the last 3 months
• Oral corticosteroid use within the last 1 month
• Current pregnancy, breast-feeding, or plan to become pregnant during next 3 months
• Presence of antrochoanal nasal polyps; acute rhinosinusitis; upper respiratory infection;
• Allergic granulomatous angiitis/eosinophilic granulomatosis with polyangiitis;
• Granulomatosis with polyangiitis; cystic fibrosis; Young syndrome;
• Kartagener syndrome; or dyskinetic cilia syndrome
• Poorly controlled asthma

Sponsors & Collaborators

• Medical University of South Carolina: lead

Study Sites (2)

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

University of Virginia

Charlottesville, Virginia, 22904, United States

Location

MeSH Terms

Conditions

Nasal Polyps

Interventions

dupilumab

Condition Hierarchy (Ancestors)

Nose Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Polyps; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Director of Clinical Research

Study Record Dates

• First Submitted: February 15, 2023
• First Posted: July 28, 2023
• Study Start: August 10, 2023
• Primary Completion: January 30, 2025
• Study Completion: January 30, 2025
• Last Updated: February 17, 2026

Record last verified: 2026-02

Locations

US (2)