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Chronic Rhinosinusitis With Nasal PolypsPhase 4NCT06188871

Early-onset Dupilumab Effects in CRSwNP

A Phase 4 study testing Dupilumab in people with Chronic Rhinosinusitis With Nasal Polyps, run by University of Rochester at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Chronic Rhinosinusitis With Nasal Polyps
What is being tested?
Dupilumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
1 Jun 2024to 1 Jun 2027
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • > 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Rochester Department of Otolaryngology Head and Neck Surgery

    Rochester, New York, 14642

Other trials in United States

About this study

Official title: 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.

Read the 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.

Being tested
Dupilumab

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DupilumabDrug

    Also called Dupixent

    Two injections of 300mg dupilumab, subcutaneous 14 days apart

Study groups in NCT06188871
Study groupRoleWhat they receive
DupilumabExperimentalTwo injections of 300mg dupilumab, subcutaneous 14 days apart
Receives: Drug: Dupilumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Mean change in concentration of IgE (IU/mL)

    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.

    Measured: 3 weeks post baseline

Secondary outcomes (4)

  1. Mean change in concentration of type II inflammatory markers contributing to sinonasal inflammation (ng/mL)

    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)

    Measured: 3 weeks post baseline

  2. Mean change in concentration of markers of neutrophil activity contributing to sinonasal inflammation (ng/mL)

    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)

    Measured: 3 weeks post baseline

  3. Mean change in concentration of markers of mucin type contributing to sinonasal inflammation (ng/mL)

    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)

    Measured: 3 weeks post baseline

  4. Mean change in active Staph Aureus collected via nasal swabs

    Determined objectively by mean change in log output from qPCR assays as changes in rCFU/cm2

    Measured: 3 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Jan 2024
  2. Study start1 Jun 2024 (estimated)
  3. Primary completion1 Jun 2026 (estimated)
  4. Study completion1 Jun 2027 (estimated)

Why it stopped: Study is no longer interventional. A new observational protocol was created.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Basic science
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06188871
Sponsor's protocol ID
STUDY00008670
Status last verified
May 2024
First submitted
18 Dec 2023
Last updated
9 May 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Resources will be shard via Open Science Framework

Publications

  • Bachert C, Han JK, Desrosiers M, Hellings PW, Amin N, Lee SE, Mullol J, Greos LS, Bosso JV, Laidlaw TM, Cervin AU, Maspero JF, Hopkins C, Olze H, Canonica GW, Paggiaro P, Cho SH, Fokkens WJ, Fujieda S, Zhang M, Lu X, Fan C, Draikiwicz S, Kamat SA, Khan A, Pirozzi G, Patel N, Graham NMH, Ruddy M, Staudinger H, Weinreich D, Stahl N, Yancopoulos GD, Mannent LP. Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials. Lancet. 2019 Nov 2;394(10209):1638-1650. doi: 10.1016/S0140-6736(19)31881-1. Epub 2019 Sep 19.

    PubMed 31543428

  • Canonica GW, Bourdin A, Peters AT, Desrosiers M, Bachert C, Weidinger S, Simpson EL, Daizadeh N, Chen Z, Kamat S, Khan AH, Chao J, Graham NMH, Laws E, Rossi AB, Ardeleanu M, Mannent LP, Amin N, Ortiz B, Deniz Y, Djandji M, Rowe PJ. Dupilumab Demonstrates Rapid Onset of Response Across Three Type 2 Inflammatory Diseases. J Allergy Clin Immunol Pract. 2022 Jun;10(6):1515-1526. doi: 10.1016/j.jaip.2022.02.026. Epub 2022 Mar 6.

    PubMed 35259535

  • Fokkens W, Van Der Lans R, Reitsma S. Dupilumab for the treatment of chronic rhinosinusitis with nasal polyposis. Expert Opin Biol Ther. 2021 May;21(5):575-585. doi: 10.1080/14712598.2021.1901881. Epub 2021 Apr 1.

    PubMed 33724109

  • Jonstam K, Swanson BN, Mannent LP, Cardell LO, Tian N, Wang Y, Zhang D, Fan C, Holtappels G, Hamilton JD, Grabher A, Graham NMH, Pirozzi G, Bachert C. Dupilumab reduces local type 2 pro-inflammatory biomarkers in chronic rhinosinusitis with nasal polyposis. Allergy. 2019 Apr;74(4):743-752. doi: 10.1111/all.13685. Epub 2019 Jan 21.

    PubMed 30488542

  • Mimmi S, Lombardo N, Maisano D, Piazzetta G, Pelaia C, Pelaia G, Greco M, Foti D, Dattilo V, Iaccino E. Spotlight on a Short-Time Treatment with the IL-4/IL-13 Receptor Blocker in Patients with CRSwNP: microRNAs Modulations and Preliminary Clinical Evidence. Genes (Basel). 2022 Dec 15;13(12):2366. doi: 10.3390/genes13122366.

    PubMed 36553635

  • Beck L, Boguniewicz M, Hata T, Fuxench ZC, Simpson E, De Benedetto A, et al. Effect of Dupilumab on the Host-Microbe Interface in Atopic Dermatitis. Journal of Allergy and Clinical Immunology. 2022;149:AB150. https://doi.org/10.1016/j.jaci.2021.12.503

  • Watelet JB, Gevaert P, Holtappels G, Van Cauwenberge P, Bachert C. Collection of nasal secretions for immunological analysis. Eur Arch Otorhinolaryngol. 2004 May;261(5):242-6. doi: 10.1007/s00405-003-0691-y. Epub 2003 Oct 9.

    PubMed 14551791

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Dupilumab in people with Chronic Rhinosinusitis With Nasal Polyps, run by University of Rochester at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 9 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean change in concentration of IgE (IU/mL) (time frame: 3 weeks post baseline). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06188871, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2024.

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