Early-onset Dupilumab Effects in CRSwNP

April 2, 2024 updated by: Li-Xing Man, University of Rochester

Early Changes in Type 2 Inflammatory Cytokines, Respiratory Oscillometry, and Sinonasal Microbiome With Dupilumab Treatment for Chronic Rhinosinusitis With Nasal Polyps

While it is known that Dupilumab has profound effects in patients with CRSwNP, these are often seen months later after treatment initiation; however, in practice, patients often endorse feeling significantly better within days of their first injection. No studies have investigated the molecular basis for such an acute change. This study proposes that specific cytokine changes in phenotype in addition to microbiome and oscillometry effects play a synergistic role in producing this effect.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a single center, prospective, controlled pilot study investigating the acute-onset changes across multiple parameters from immunology to microbiome and pulmonary physiology in patients with CRSwNP after receiving initial doses of dupilumab therapy. In total, eligible participants will be enrolled in the study for a total of 3 weeks, during which they will receive two injections of 300 mg of dupilumab. There will be a total of 8 study visits with the 1st visit being a 1-month pre-intervention baseline allowing each patient to serve as independent controls. The next seven visits will be at the following time points: Day of the 1st injection, 24-hrs after the first injection, 48 hrs after the first injection, one week after the first injection, two weeks after the first injection prior to receiving the second injection, 24hrs after receiving the 2nd injection and the 3-week timepoint (1 week after the second injection). At each visit, patients will be screened for side effects and nasal endoscopy will be performed as well as collection of nasal secretions via sinus packings that are placed in both nares for five minutes. The packings will subsequently be removed and per the collection protocol will undergo centrifugation, aliquoting and storage in a -80 freezer for future cytokine analysis via ELISA assays for various cytokine markers of type 2 inflammation, neutrophil activity, and mucin type. At specific visits, additional measures will be collected including Staph Aureus swabs for qPCR and cell culture, SNOT-22 surveys and smell testing, and oscillometry.

Study Type

Interventional

Enrollment (Estimated)

5

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Li-Xing Man, MSc, MD, MPA

Study Locations

  • United States
    • New York
      • Rochester, New York, United States, 14642
        • University of Rochester Department of Otolaryngology Head and Neck Surgery

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients age 18+
  • who in normal clinical practice would be a candidate for dupilumab.
  • with a diagnosis of CRSwNP including

  • at least 2 of the following symptoms on screening:

    • nasal blockade/obstruction/congestion or nasal discharge;
    • facial pain/pressure;
    • reduction or loss of smell

Exclusion Criteria:

  • > 80 years of age
  • prior history of immunotherapy use (including prior participation in dupilumab or other clinical trials)
  • Treatment with systemic corticosteroids, monoclonal antibodies, immunosuppressive treatments or anti-IgE therapy during the past two months prior to trial participation.
  • CRS without polyps or another non-nasal polyposis condition
  • Patients with conditions/concomitant diseases making them ineligible for evaluation of the primary efficacy endpoint such as: acute sinusitis/nasal infection or upper respiratory infection at day of screening or in the two weeks prior to screening, Churg-Strauss syndrome, Young's syndrome, Kartagener's syndrome or dyskinetic ciliary syndromes, concomitant cystic fibrosis, CT scan suggestive of allergic fungal rhinosinusitis
  • Patients with comorbid asthma if they had a recent asthma exacerbation requiring systemic (oral and/or parenteral) steroid treatment or hospitalization for >24h for treatment of asthma, within 3 months prior to screening or are on a dose of greater than 1000 ug fluticasone or an equivalent inhaled corticosteroid.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dupilumab
Two injections of 300mg dupilumab, subcutaneous 14 days apart
Drug: Dupilumab
Two injections of 300mg dupilumab, subcutaneous 14 days apart
Other Names:
  • Dupixent

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean change in concentration of IgE (IU/mL)
Time Frame: 3 weeks post baseline
Determined by output from ELISA assays using antibody against IgE measured as mean change from baseline (IU/mL). Analysis will be performed as mean change from baseline.
3 weeks post baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean change in concentration of type II inflammatory markers contributing to sinonasal inflammation (ng/mL)
Time Frame: 3 weeks post baseline
Determined by output from ELISA assays using antibody against downstream markers of the IL-4/IL-13 cascade, as well as antibodies against markers of neutrophil activity and mucin types that may be altered with dupilumab treatment. Reported as mean change from baseline (pg/ml or ng/ml)
3 weeks post baseline
Mean change in concentration of markers of neutrophil activity contributing to sinonasal inflammation (ng/mL)
Time Frame: 3 weeks post baseline
Determined by output from ELISA assays using antibody against downstream markers of the IL-4/IL-13 cascade, as well as antibodies against markers of neutrophil activity and mucin types that may be altered with dupilumab treatment. Reported as mean change from baseline (pg/ml or ng/ml)
3 weeks post baseline
Mean change in concentration of markers of mucin type contributing to sinonasal inflammation (ng/mL)
Time Frame: 3 weeks post baseline
Determined by output from ELISA assays using antibody against downstream markers of the IL-4/IL-13 cascade, as well as antibodies against markers of neutrophil activity and mucin types that may be altered with dupilumab treatment. Reported as mean change from baseline (pg/ml or ng/ml)
3 weeks post baseline
Mean change in active Staph Aureus collected via nasal swabs
Time Frame: 3 weeks
Determined objectively by mean change in log output from qPCR assays as changes in rCFU/cm2
3 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean change in SNOT-22 score
Time Frame: 3 weeks
Determined by patient reported results on SNOT-22 surveys at each visit.
3 weeks
Mean change in UPSIT score
Time Frame: 3 weeks
Determined by smell testing conducted 1 week after 1st injection and at the final visit (1 week after the 2nd injection).
3 weeks
Mean change in oscillometry X5 (reactance at 5 Hz)
Time Frame: 3 weeks
Data from oscillometry software will be used to demonstrate change in median values for the above variables at the four specified visits when oscillometry data is collected. Related samples Wilcoxon signed-rank tests will be used to analyze median differences in oscillometry.
3 weeks
Mean change in oscillometry AX (area under the reactance curve)
Time Frame: 3 weeks
Data from oscillometry software will be used to demonstrate change in median values for the above variables at the four specified visits when oscillometry data is collected. Related samples Wilcoxon signed-rank tests will be used to analyze median differences in oscillometry.
3 weeks
Mean change in oscillometry data R5-R20 (frequency-dependent resistance heterogeneity between 5 and 20 Hz)
Time Frame: 3 weeks
Data from oscillometry software will be used to demonstrate change in median values for the above variables at the four specified visits when oscillometry data is collected. Related samples Wilcoxon signed-rank tests will be used to analyze median differences in oscillometry.
3 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Rochester

Investigators

  • Principal Investigator: Li-Xing Man, MSc, MD, MPA, University of Rochester

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

April 1, 2024

Primary Completion (Estimated)

December 31, 2025

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

December 18, 2023

First Submitted That Met QC Criteria

December 18, 2023

First Posted (Actual)

January 3, 2024

Study Record Updates

Last Update Posted (Actual)

April 4, 2024

Last Update Submitted That Met QC Criteria

April 2, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY00008670

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Resources will be shard via Open Science Framework

IPD Sharing Time Frame

Six months after publication of the study data

IPD Sharing Access Criteria

Resources will be shard via Open Science Framework. Access will be open

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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