Early-onset Dupilumab Effects in CRSwNP

NCT06188871 | Withdrawn Phase 4 FDA Drug

• 1 other identifier: STUDY00008670
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Chronic Rhinosinusitis With Nasal Polyps

Outcome Measures

Primary Outcomes (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.

  3 weeks post baseline

Secondary Outcomes (4)

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

  3 weeks post baseline

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

  3 weeks post baseline

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

  3 weeks post baseline

• Mean change in active Staph Aureus collected via nasal swabs

  3 weeks

Other Outcomes (5)

• Mean change in SNOT-22 score

  3 weeks

• Mean change in UPSIT score

  3 weeks

• Mean change in oscillometry data R5-R20 (frequency-dependent resistance heterogeneity between 5 and 20 Hz)

  3 weeks

Study Arms (1)

Dupilumab

EXPERIMENTAL

Two injections of 300mg dupilumab, subcutaneous 14 days apart

Drug: Dupilumab

Interventions

Dupilumab DRUG

Two injections of 300mg dupilumab, subcutaneous 14 days apart

Also known as: Dupixent

Dupilumab

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• \> 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.

Sponsors & Collaborators

• University of Rochester: lead

Study Sites (1)

University of Rochester Department of Otolaryngology Head and Neck Surgery

Rochester, New York, 14642, United States

Location

Related Publications (7)

• 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.

  PMID: 31543428 BACKGROUND

• 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.

  PMID: 35259535 BACKGROUND

• 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.

  PMID: 33724109 BACKGROUND

• 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.

  PMID: 30488542 BACKGROUND

• 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.

  PMID: 36553635 BACKGROUND

• 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

  BACKGROUND

• 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.

  PMID: 14551791 BACKGROUND

MeSH Terms

Interventions

dupilumab

Study Officials

• Li-Xing Man, MSc, MD, MPA

  University of Rochester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: December 18, 2023
• First Posted: January 3, 2024
• Study Start: June 1, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: May 9, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: Six months after publication of the study data
• Access Criteria: Resources will be shard via Open Science Framework. Access will be open

Locations

US (1)