Dupilumab Treatment Effects in an Ethnically Diverse Population With Chronic Rhinosinusitis With Nasal Polyposis

Official title

Dupilumab Treatment Effects in an Ethnically Diverse Population With Chronic Rhinosinusitis With Nasal Polyposis (CRSwNP)

Overview

The central hypothesis of this study is that the addition of dupilumab treatment onto standard-of-care intranasal corticosteroids will improve patient-reported measures of disease activity and sense of smell in a cohort of mostly ethnical and racial minority patients with CRSwNP

Detailed description

First, it will confirm the effectiveness of dupilumab in the treatment of CRSwNP in ethnic and racial minority patients who have traditionally been underrepresented in existing clinical trials of biologics in CRSwNP Second, this research will establish a biomarker of therapeutic response to dupilumab identifying the biological effect of dupilumab in CRSwNP patients and its association with symptom improvement.

Finally, the investigators will measure the effect of dupilumab on asthma symptoms and lung function in patients with CRSwNP and comorbid asthma.

There will be a screening visit, followed by a baseline visit where the medication will be given. Follow-up visits will be scheduled at 2 weeks and then 16 weeks from baseline. Long-term visits will take place in 36 and 52 weeks.

Interventions

• Biological Dupilumab
  Standard of care treatment with dupilumab

Primary outcome measures

• Change in Sinonasal outcome test (SNOT-22) score, scale 0-110, higher is worse outcome [Time frame: at 2, 16, 36, and 52 weeks of treatment]
• Change in University of Pennsylvania Smell Identification Test (UPSIT) scores, scale 0-40, lower is worse outcome values [Time frame: at 2, 16, 36, and 52 weeks of treatment]
• Change in nasal peak flow (NPF) value (L/min) [Time frame: at 2, 16, 36, and 52 weeks of treatment]

Secondary outcome measures (3)

• Change in urinary levels of Leukotriene E4 (uLTE4) levels in ug/L [Time frame: at 2, 16, 36, and 52 weeks of treatment]
• Change in peripheral blood eosinophil counts in k/uL [Time frame: at 2, 16, 36, and 52 weeks of treatment]
• Change in Immunoglobulin E (IgE) level in IU/mL [Time frame: at 2, 16, 36, and 52 weeks of treatment]

Eligibility criteria

Inclusion criteria

• Patients with physician-diagnosed CRSwNP, with or without comorbid asthma that meet indication criteria for FDA-approved use of Dupilumab.
• Patients aged 18 years and older.
• Patient willing to provide consent to be a participant in the study.
• Patients with insurance that allows Dupilumab coverage or Dupilumab coverage obtained through "Dupixent MyWay Program"

Exclusion criteria

• Age under 18
• Suspected or diagnosed allergic fungal rhinosinusitis.
• Suspected or diagnosed cystic fibrosis.
• Dupilumab coverage denied through insurance or "Dupixent MyWay Program"
• Patients who required a steroid taper in the preceding 30 days. However, patients on chronic steroids less or equal to 20 mg of prednisone daily, are eligible.
• Patients who were on a different biologic medication in the preceding 3 months.
• Patients with a diagnosis of EGPA/Churg-Strauss Syndrome
• Pregnant patients
• Patients with inverted papilloma growth

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Case-control

Study locations

United States · 1 center

• Montefiore Medical Center — The Bronx

Publications

• Fokkens W, Desrosiers M, Harvey R, Hopkins C, Mullol J, Philpott C, Alobid I, Anselmo-Lima WT, Bachert C, Baroody F, Bernal-Sprekelsen M, von Buchwald C, Cervin A, Cohen N, Constantinidis J, De Gabory L, Douglas R, Gevaert P, Hafner A, Hellings P, Joos G, Kalogjera L, Kern R, Knill A, Kocks J, Landis BN, Limpens J, Lebeer S, Lourenco O, Matricardi PM, Meco C, O Mahony L, Reitsma S, Ryan D, Schloss PMID 30810118
• Orlandi RR, Kingdom TT, Hwang PH, Smith TL, Alt JA, Baroody FM, Batra PS, Bernal-Sprekelsen M, Bhattacharyya N, Chandra RK, Chiu A, Citardi MJ, Cohen NA, DelGaudio J, Desrosiers M, Dhong HJ, Douglas R, Ferguson B, Fokkens WJ, Georgalas C, Goldberg A, Gosepath J, Hamilos DL, Han JK, Harvey R, Hellings P, Hopkins C, Jankowski R, Javer AR, Kern R, Kountakis S, Kowalski ML, Lane A, Lanza DC, Lebowitz PMID 26889651
• Bachert C, Mannent L, Naclerio RM, Mullol J, Ferguson BJ, Gevaert P, Hellings P, Jiao L, Wang L, Evans RR, Pirozzi G, Graham NM, Swanson B, Hamilton JD, Radin A, Gandhi NA, Stahl N, Yancopoulos GD, Sutherland ER. Effect of Subcutaneous Dupilumab on Nasal Polyp Burden in Patients With Chronic Sinusitis and Nasal Polyposis: A Randomized Clinical Trial. JAMA. 2016 Feb 2;315(5):469-79. doi: 10.1001/ja PMID 26836729
• Gevaert P, Omachi TA, Corren J, Mullol J, Han J, Lee SE, Kaufman D, Ligueros-Saylan M, Howard M, Zhu R, Owen R, Wong K, Islam L, Bachert C. Efficacy and safety of omalizumab in nasal polyposis: 2 randomized phase 3 trials. J Allergy Clin Immunol. 2020 Sep;146(3):595-605. doi: 10.1016/j.jaci.2020.05.032. Epub 2020 Jun 7. PMID 32524991
• 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 pat PMID 31543428
• Bachert C, Hellings PW, Mullol J, Naclerio RM, Chao J, Amin N, Grabher A, Swanson BN, Hamilton JD, Guillonneau S, Taniou C, Zhang D, Pirozzi G, Graham NMH, Staudinger H, Mannent LP, Khan A. Dupilumab improves patient-reported outcomes in patients with chronic rhinosinusitis with nasal polyps and comorbid asthma. J Allergy Clin Immunol Pract. 2019 Sep-Oct;7(7):2447-2449.e2. doi: 10.1016/j.jaip.2019 PMID 30928658
• Maspero JF, Katelaris CH, Busse WW, Castro M, Corren J, Chipps BE, Peters AT, Pavord ID, Ford LB, Sher L, Rabe KF, Rice MS, Rowe P, Lu Y, Harel S, Jagerschmidt A, Khan AH, Kamat S, Pirozzi G, Amin N, Ruddy M, Graham NMH, Mannent LP, Teper A. Dupilumab Efficacy in Uncontrolled, Moderate-to-Severe Asthma with Self-Reported Chronic Rhinosinusitis. J Allergy Clin Immunol Pract. 2020 Feb;8(2):527-539.e PMID 31351189
• Cardell LO, Stjarne P, Jonstam K, Bachert C. Endotypes of chronic rhinosinusitis: Impact on management. J Allergy Clin Immunol. 2020 Mar;145(3):752-756. doi: 10.1016/j.jaci.2020.01.019. Epub 2020 Jan 28. PMID 32001254

Identifiers

NCT: NCT05246267 · 2021-13161

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗