Dupilumab Severe Eosinophilic Chronic Sinusitis Without Nasal Polyposis

NCT04430179 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: STUDY000808
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Severe Eosinophilic Chronic Sinusitis Without Nasal Polyposis

Outcome Measures

Primary Outcomes (1)

• Change in Lund-Mackay sinus computed tomography (LMK-CT) score

  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 Outcomes (7)

• Change in participant-reported symptoms scores of sinusitis

  24 weeks

• Change in visual analogue scale score for sinusitis

  24 weeks

• Change in nasal peak inspiratory flow

  24 weeks

• Change in University of Pennsylvania smell identification test (UPSIT) scores

  24 weeks

• Time to first response in LMK-CT score

  24 weeks

Study Arms (2)

Active drug

ACTIVE COMPARATOR

Dupilumab 300 mg every other week for 24 weeks

Drug: Dupilumab 300 MG/2 ML Subcutaneous Solution [DUPIXENT]

Placebo

PLACEBO COMPARATOR

Placebo

Other: Placebo

Interventions

Dupilumab 300 MG/2 ML Subcutaneous Solution [DUPIXENT] DRUG

300 mg every other week for 24 weeks

Active drug

Placebo OTHER

No active drug

Placebo

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• Age \< 18
• With CRS with nasal polyps
• Treated in any clinical trial of dupilumab
• Has taken:
• 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
• An experimental monoclonal antibody within five half-lives or within 6 months before screening if the half-life is unknown
• Anti-immunoglobulin E (IgE) therapy (omalizumab) within 130 days prior to screening
• Leukotriene antagonists/modifiers unless patient is on a continuous treatment for at least 30 days prior to screening
• 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:
• Antrochoanal polyps
• Nasal septal deviation that would occlude at least one nostril
• Acute sinusitis, nasal infection or upper respiratory infection at screening
• Ongoing rhinitis medicamentosa

Sponsors & Collaborators

• University of South Florida: lead

Study Sites (1)

University of South Florida Asthma, Allergy and Immunology

Tampa, Florida, 33613, United States

Location

Related Publications (13)

• Kim DY, Lee SH, Carter RG, Kato A, Schleimer RP, Cho SH. A Recently Established Murine Model of Nasal Polyps Demonstrates Activation of B Cells, as Occurs in Human Nasal Polyps. Am J Respir Cell Mol Biol. 2016 Aug;55(2):170-5. doi: 10.1165/rcmb.2016-0002RC.

  PMID: 27163839 BACKGROUND

• Tokunaga T, Sakashita M, Haruna T, Asaka D, Takeno S, Ikeda H, Nakayama T, Seki N, Ito S, Murata J, Sakuma Y, Yoshida N, Terada T, Morikura I, Sakaida H, Kondo K, Teraguchi K, Okano M, Otori N, Yoshikawa M, Hirakawa K, Haruna S, Himi T, Ikeda K, Ishitoya J, Iino Y, Kawata R, Kawauchi H, Kobayashi M, Yamasoba T, Miwa T, Urashima M, Tamari M, Noguchi E, Ninomiya T, Imoto Y, Morikawa T, Tomita K, Takabayashi T, Fujieda S. Novel scoring system and algorithm for classifying chronic rhinosinusitis: the JESREC Study. Allergy. 2015 Aug;70(8):995-1003. doi: 10.1111/all.12644. Epub 2015 May 26.

  PMID: 25945591 BACKGROUND

• Hu Y, Cao PP, Liang GT, Cui YH, Liu Z. Diagnostic significance of blood eosinophil count in eosinophilic chronic rhinosinusitis with nasal polyps in Chinese adults. Laryngoscope. 2012 Mar;122(3):498-503. doi: 10.1002/lary.22507. Epub 2012 Jan 17.

  PMID: 22252861 BACKGROUND

• Ho J, Hamizan AW, Alvarado R, Rimmer J, Sewell WA, Harvey RJ. Systemic Predictors of Eosinophilic Chronic Rhinosinusitis. Am J Rhinol Allergy. 2018 Jul;32(4):252-257. doi: 10.1177/1945892418779451. Epub 2018 Jun 4.

  PMID: 29862828 BACKGROUND

• Thwaites RS, Gunawardana NC, Broich V, Mann EH, Ahnstrom J, Campbell GA, Lindsley S, Singh N, Tunstall T, Lane DA, Openshaw PJ, Hawrylowicz CM, Hansel TT. Biphasic activation of complement and fibrinolysis during the human nasal allergic response. J Allergy Clin Immunol. 2018 May;141(5):1892-1895.e6. doi: 10.1016/j.jaci.2018.01.022. Epub 2018 Feb 7. No abstract available.

  PMID: 29427640 BACKGROUND

• Hopkins C, Browne JP, Slack R, Lund VJ, Topham J, Reeves BC, Copley LP, Brown P, van der Meulen JH. Complications of surgery for nasal polyposis and chronic rhinosinusitis: the results of a national audit in England and Wales. Laryngoscope. 2006 Aug;116(8):1494-9. doi: 10.1097/01.mlg.0000230399.24306.50.

  PMID: 16885760 BACKGROUND

• Gevaert P, Lang-Loidolt D, Lackner A, Stammberger H, Staudinger H, Van Zele T, Holtappels G, Tavernier J, van Cauwenberge P, Bachert C. Nasal IL-5 levels determine the response to anti-IL-5 treatment in patients with nasal polyps. J Allergy Clin Immunol. 2006 Nov;118(5):1133-41. doi: 10.1016/j.jaci.2006.05.031. Epub 2006 Sep 26.

  PMID: 17088140 BACKGROUND

• Gevaert P, Calus L, Van Zele T, Blomme K, De Ruyck N, Bauters W, Hellings P, Brusselle G, De Bacquer D, van Cauwenberge P, Bachert C. Omalizumab is effective in allergic and nonallergic patients with nasal polyps and asthma. J Allergy Clin Immunol. 2013 Jan;131(1):110-6.e1. doi: 10.1016/j.jaci.2012.07.047. Epub 2012 Sep 27.

  PMID: 23021878 BACKGROUND

• Gevaert P, Van Bruaene N, Cattaert T, Van Steen K, Van Zele T, Acke F, De Ruyck N, Blomme K, Sousa AR, Marshall RP, Bachert C. Mepolizumab, a humanized anti-IL-5 mAb, as a treatment option for severe nasal polyposis. J Allergy Clin Immunol. 2011 Nov;128(5):989-95.e1-8. doi: 10.1016/j.jaci.2011.07.056. Epub 2011 Sep 28.

  PMID: 21958585 BACKGROUND

• Benjamin MR, Stevens WW, Li N, Bose S, Grammer LC, Kern RC, Tan BK, Conley DB, Smith SS, Welch KC, Schleimer RP, Peters AT. Clinical Characteristics of Patients with Chronic Rhinosinusitis without Nasal Polyps in an Academic Setting. J Allergy Clin Immunol Pract. 2019 Mar;7(3):1010-1016. doi: 10.1016/j.jaip.2018.10.014. Epub 2018 Oct 25.

  PMID: 30368005 RESULT

• Wang X, Zhang N, Bo M, Holtappels G, Zheng M, Lou H, Wang H, Zhang L, Bachert C. Diversity of TH cytokine profiles in patients with chronic rhinosinusitis: A multicenter study in Europe, Asia, and Oceania. J Allergy Clin Immunol. 2016 Nov;138(5):1344-1353. doi: 10.1016/j.jaci.2016.05.041. Epub 2016 Jul 15.

  PMID: 27544740 RESULT

• Stevens WW, Peters AT, Tan BK, Klingler AI, Poposki JA, Hulse KE, Grammer LC, Welch KC, Smith SS, Conley DB, Kern RC, Schleimer RP, Kato A. Associations Between Inflammatory Endotypes and Clinical Presentations in Chronic Rhinosinusitis. J Allergy Clin Immunol Pract. 2019 Nov-Dec;7(8):2812-2820.e3. doi: 10.1016/j.jaip.2019.05.009. Epub 2019 May 22.

  PMID: 31128376 RESULT

• Han DH, Kim SW, Cho SH, Kim DY, Lee CH, Kim SS, Rhee CS. Predictors of bronchial hyperresponsiveness in chronic rhinosinusitis with nasal polyp. Allergy. 2009 Jan;64(1):118-22. doi: 10.1111/j.1398-9995.2008.01841.x. Epub 2008 Dec 17.

  PMID: 19120071 RESULT

MeSH Terms

Interventions

dupilumab

Study Officials

• Seong Cho, MD

  University of South Florida

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Active drug vs placebo

Study Record Dates

• First Submitted: April 13, 2020
• First Posted: June 12, 2020
• Study Start: December 17, 2020
• Primary Completion: July 1, 2025
• Study Completion: July 1, 2025
• Last Updated: January 24, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)