Interleukin-4Ralpha Blockade by Dupilumab Decreases Staphylococcus Aureus Colonization and Increases Microbial Diversity in Chronic Rhinosinusitis With Nasal Polyposis (CRSwNP)

HSR210309

Hypothesis: The investigators hypothesize that in patients with CRSwNP who demonstrate sinus colonization with staphylococcus aureus, the administration of dupilumab will be associated with decreased staph colonization and an increase in microbial diversity. Primary Objective will be to demonstrate that dupilumab reduces staphylococcus aureus (phyla firmicutes) abundance while increasing microbial diversity in patients with CRSwNPs who are culture positive for staph aureus at enrollment. Secondary Objectives will be to correlate reduction in Staph aureus abundance and improved bacterial diversity with increased expression of anti-microbial proteins (ß-defensins1-4) and cathelicidin LL-37. In addition, the investigators will correlate improvements in microbial diversity/decreased staph abundance with clinical improvements as assessed via questionnaires and objective/subjective smell function and also as improvements in cellular/immune T2 inflammation as assessed by reduced expression of T2 cytokines/chemokines and eosinophil/eosinophil-derived proteins.

2022-09-01

2024-06-30

2024-12-31

Recruiting

Early phase I

20

Inclusion Criteria: • Adults, ages 18-65 * History of CRSwNP including subjects with AERD * Sinonasal culture demonstrating staph aureus at visit 1 * History of FESS with patent sinus ostia sufficient to obtain culture and tissue samples from the middle meatus * Asthma, if present, should be well controlled * Atopic dermatitis, if present, should be well controlled * Use of nasal saline irrigation and stable dosing (\>1 month) of topical corticosteroids is permitted * Intent of the physicians caring to start dupilumab therapy as part of subject's standard of care * Subject meets FDA approved criteria for the use of dupilumab for nasal polyps Exclusion Criteria: * Concurrent serious medical problem * Uncontrolled asthma (ACT \<20 at screening visit) * Recent (within 60 days) use of oral corticosteroids * Recent (within 60 days) urgent care, ED visit, or hospitalization for asthma * Current smoker or has smoked \>10 pack-years * Biologic therapy including asthma biologic therapy in last 3 months * Recent (within 1 month) change in CRS medical treatment (topical steroids, surfactants, irrigation protocol, etc. including changes in delivery volume or delivery methodology) * Recent (within 6 weeks) upper respiratory infection * Antibiotics within 6 weeks * Pregnant or breast-feeding women * Any contraindication to the use of dupilumab including hypersensitivity on previous administration

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE4'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'interventionModelDescription': 'Open label, single arm', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 20, 'type': 'ESTIMATED'}}

2023-11-30