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.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
30
300 mg every other week for 24 weeks
No active drug
University of South Florida Asthma, Allergy and Immunology
Tampa, Florida, United States
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.
Time frame: 24 weeks
Change in participant-reported symptoms scores of sinusitis
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.
Time frame: 24 weeks
Change in visual analogue scale score for sinusitis
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.
Time frame: 24 weeks
Change in nasal peak inspiratory flow
Change in nasal peak inspiratory flow in dupilumab group compared to placebo group.
Time frame: 24 weeks
Change in University of Pennsylvania smell identification test (UPSIT) scores
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.
Time frame: 24 weeks
Time to first response in LMK-CT score
50 percent improvement in LMK-CT score in dupilumab group compared to placebo group
Time frame: 24 weeks
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Change in sinonasal outcome test (SNOT-22) score
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.
Time frame: 24 weeks
Change in biomarkers concentrations in nasal secretion measured by enzyme-linked immunosorbent assay (ELISA)
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
Time frame: 24 weeks