Dupilumab Severe Eosinophilic Chronic Sinusitis Without Nasal Polyposis

November 14, 2022 updated by: University of South Florida

An Evaluation of Dupilumab in Patients With Severe Eosinophilic Chronic Sinusitis Without Nasal Polyposis

The investigators will investigate the efficacy of dupilumab in patients with severe eosinophilic CRSsNP who are resistant to the conventional treatment with intranasal corticosteroids and have significantly extensive disease involving more than 2 sinuses bilaterally in sinus CT scan and Lund-Mackay sinus (LMK) CT score >=10 at baseline.

Study Overview

Detailed Description

The investigators will use high blood eosinophils (>=200) as a biomarker for eosinophilic CRSsNP and investigate the efficacy of dupilumab in patients with severe eosinophilic CRSsNP who are resistant to the conventional treatment with intranasal corticosteroids and have significantly extensive disease involving more than 2 sinuses bilaterally in sinus CT scan and Lund-Mackay sinus (LMK) CT score >=10 at baseline. In addition, the investigators will have a prespecified enrollment goal of at least 50% of patients with type 2 inflammatory diseases such as asthma, allergic rhinitis, and/or atopic dermatitis on the basis of patient-reported history and will stratify subject numbers between dupilumab treatment and placebo group.

Study Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 2

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

  • Name: Thanh Q Tran, MPH
  • Phone Number: 813-844-8544
  • Email: tqtran@usf.edu

Study Contact Backup

Study Locations

    • Florida
      • Tampa, Florida, United States, 33613
        • Recruiting
        • University of South Florida Asthma, Allergy and Immunology
        • Contact:
        • Contact:
        • Principal Investigator:
          • Seong Cho, MD
        • Sub-Investigator:
          • Richard F Lockey, MD
        • Sub-Investigator:
          • Thomas B Casale, MD
        • Sub-Investigator:
          • Amber N Pepper, MD
        • Sub-Investigator:
          • Nicholas Kolinsky, DO
        • Sub-Investigator:
          • David Gubernick, MD
        • Sub-Investigator:
          • Stephanie Hudey, MD
        • Sub-Investigator:
          • Natalie Diaz-Cabrera, MD
        • Sub-Investigator:
          • Donya Imanirad, MD
        • Sub-Investigator:
          • Walaa Hamadi, MD
        • Sub-Investigator:
          • Leah Ishmael, DO
        • Sub-Investigator:
          • Silpa Taunk, MD
        • Sub-Investigator:
          • Sonia Mathew, MD

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age 18 or older
  • LMK-CT score ≥ 10 (out of maximum of 24) at screening.
  • Bilateral sinusitis with at least more than 2 sinus involvement despite completion of a prior intranasal corticosteroid (INCS) treatment for at least 8 weeks prior to screening
  • Presence of at least two of the following symptoms prior to screening:
  • Nasal blockage/obstruction/congestion
  • Nasal discharge (anterior/posterior nasal drip)
  • Facial pain/pressure
  • Reduction or loss of smell
  • Must have Eosinophilic CRSsNP (blood eos ≥ 200) within 6 months prior to screening
  • Able and willing to undergo regular intervention as well as evaluation per study protocol
  • Must agree not to participate in a clinical study involving another investigational drug or device throughout the duration of this study
  • Must be competent to understand the information given in IRB approved ICF and must sign the form prior to the initiation of any study procedure

Exclusion Criteria:

  • Age < 18
  • With CRS with nasal polyps
  • Treated in any clinical trial of dupilumab
  • Has taken:

    1. Biologic therapy/systemic immunosuppressant to treat inflammatory disease or autoimmune disease (eg, rheumatoid arthritis, inflammatory bowel disease, primary biliary cirrhosis, systemic lupus erythematosus, multiple sclerosis, etc) within 2 months before screening or 5 half-lives, whichever is longer
    2. An experimental monoclonal antibody within five half-lives or within 6 months before screening if the half-life is unknown
    3. Anti-immunoglobulin E (IgE) therapy (omalizumab) within 130 days prior to screening
    4. Leukotriene antagonists/modifiers unless patient is on a continuous treatment for at least 30 days prior to screening
    5. Initiation of allergen immunotherapy within 3 months prior to screening or a plan to begin therapy or change its dose during the run-in period or the randomized treatment period
  • Have had a sino-nasal surgery changing the lateral wall structure of the nose making impossible the evaluation of NPS
  • Patients with conditions/concomitant diseases making them non-evaluable at screening or for the primary efficacy endpoint such as:

    1. Antrochoanal polyps
    2. Nasal septal deviation that would occlude at least one nostril
    3. Acute sinusitis, nasal infection or upper respiratory infection at screening
    4. Ongoing rhinitis medicamentosa
    5. Allergic granulomatous angiitis (Churg-Strauss syndrome), granulomatosis with polyangiitis (Wegener's granulomatosis), Young's syndrome, Kartagener's syndrome or other dyskinetic ciliary syndromes, concomitant cystic fibrosis
    6. Radiologic suspicion, or confirmed invasive or expansive fungal rhinosinusitis
  • With co-morbid asthma are excluded if forced expiratory volume (FEV1) is 50% (of predicted normal) or less
  • With known active bacterial, viral, fungal, mycobacterial infection, or other infection or any major episode of infection that required hospitalization or treatment with IV antibiotics within 30 days of screening or during screening or oral antibiotics within 14 days prior to screening. Fungal infection of nail beds is allowed
  • Have human immunodeficiency virus/acquired immune deficiency syndrome
  • Have acute or chronic hepatitis B/hepatitis C infection
  • History of an opportunistic infection (eg, pneumocystis carinii, cryptococcal meningitis, progressive multifocal leukoencephalopathy) or serious bacterial, viral, or fungal infections (eg, disseminated herpes simplex, disseminated herpes zoster) and requiring IV medication(s) ≤ 3 weeks prior to randomization
  • History of or currently active primary or secondary immunodeficiency
  • History of cancer within the last 5 years, including solid tumors and hematological malignancies (except basal cell and in situ squamous cell carcinomas of the skin that have been excised and resolved) or colonic mucosal dysplasia
  • History of lymphoproliferative disorder, lymphoma, leukemia, myeloproliferative disorder, or multiple myeloma
  • History of alcohol or drug abuse within 1 year prior to randomization
  • Receipt of live vaccine within 4 weeks prior to randomization
  • Pregnant or breastfeeding
  • Participation in another clinical study or treatment with an investigational drug or device
  • Serious or active medical or psychiatric condition which, in the opinion of the Investigator, may interfere with treatment, assessment, or compliance with the protocol

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: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
No active drug
Active Comparator: Active drug
Dupilumab 300 mg every other week for 24 weeks
300 mg every other week for 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Lund-Mackay sinus computed tomography (LMK-CT) score
Time Frame: 24 weeks
Change in LMK-CT score in dupilumab group compared to control group. The total score ranges from 0 (normal) - 24 (more opacified): higher score indicates worse status.
24 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in participant-reported symptoms scores of sinusitis
Time Frame: 24 weeks
Change in baseline in participant-reported symptoms scores of sinusitis in dupilumab group compared to control group. Morning symptoms of sinusitis will be assessed using a 0 (no symptoms) - 3 (severe symptoms) categorical scale, where a higher score indicates severe symptoms.
24 weeks
Change in visual analogue scale score for sinusitis
Time Frame: 24 weeks
Change in visual analogue scale score for sinusitis in dupilumab group compared to control group. the severity of sinusitis symptoms will be assessed on a 0 cm (not troublesome) - 10 cm (worst thinkable troublesome) where a higher score indicates worst thinkable troublesome.
24 weeks
Change in nasal peak inspiratory flow
Time Frame: 24 weeks
Change in nasal peak inspiratory flow in dupilumab group compared to placebo group.
24 weeks
Change in University of Pennsylvania smell identification test (UPSIT) scores
Time Frame: 24 weeks
Change in UPSIT scores in dupilumab group compared to placebo group. Total score ranges from 0 (anosmia)-40 (normal sense of smell), a lower score indicates severe smell loss.
24 weeks
Time to first response in LMK-CT score
Time Frame: 24 weeks
50 percent improvement in LMK-CT score in dupilumab group compared to placebo group
24 weeks
Change in sinonasal outcome test (SNOT-22) score
Time Frame: 24 weeks
Change in 22-item SNOT-22 test score in dupilumab group compared to placebo group. The total score may range from 0 (no problem)-110 (worst quality of life), higher scores represent the worst quality of life; minimal clinically important change ≥ 8.90.
24 weeks
Change in biomarkers concentrations in nasal secretion measured by enzyme-linked immunosorbent assay (ELISA)
Time Frame: 24 weeks
Change in biomarkers concentrations in nasal secretion in dupilumab group compared to placebo group. ELISA will be done to measure biomarkers concentrations (pg/mL): ECP, IL-4, IL-5, IL-13, periostin, eotaxin-3, TARC, and IgE
24 weeks

Collaborators and Investigators

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

Investigators

  • Principal Investigator: Seong Cho, MD, University of South Florida

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 (Actual)

December 17, 2020

Primary Completion (Anticipated)

July 1, 2023

Study Completion (Anticipated)

December 1, 2023

Study Registration Dates

First Submitted

April 13, 2020

First Submitted That Met QC Criteria

June 11, 2020

First Posted (Actual)

June 12, 2020

Study Record Updates

Last Update Posted (Actual)

November 15, 2022

Last Update Submitted That Met QC Criteria

November 14, 2022

Last Verified

November 1, 2022

More Information

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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