dupilumab in crssnp

Conditions: Chronic Rhinosinusitis Without Nasal Polyps; Sinusitis; Chronic Sinusitis; Sinus Disorder; Respiratory Disorder

Summary: primary objective: to evaluate the efficacy of dupilumab as assessed by the reduction at week 24 in sinus opacification on computerized tomography (ct) scan in the dupilumab group only secondary objectives: * to evaluate the efficacy of dupilumab as assessed by the reduction at week 24 in sinus opacification on ct scan and sinus total symptom score (stss) compared to placebo * to evaluate the safety and tolerability of dupilumab in crssnp patients compared to placebo * to evaluate the pharmacokinetics (pk) of dupilumab in crssnp patients compared to placebo * assessment of immunogenicity to dupilumab over time compared to placebo

the duration of study for each participant will include 2-4 weeks of screening period, 24-52 weeks randomized investigational medicinal product (imp) intervention period and 12 weeks of follow-up period.

Eligibility criteria:
inclusion criteria: * participant must be at least 18 years of age at the time of signing the informed consent form (icf). * participants must have bilateral inflammation of paranasal sinuses in ct scan with lmk ≥8 and bilateral ethmoid opacification before randomization. * participants must have ongoing symptoms of loss of smell and rhinorrhea (anterior/posterior) of any severity, with or without facial pain/pressure for at least 12 consecutive weeks by visit 1. * participants must have ongoing symptoms of nasal congestion (nc)/obstruction at least 12 consecutive weeks before visit 1 and a nc score of ≥ 2 at visit 1 (day score) and visit 2 (weekly average score). * participants must have stss (nc, rhinorrhea, facial pain/pressure) ≥5 at visit 1 (day score) and visit 2 (weekly average score). * participants must have one of the 2 following features: * prior sinonasal surgery (see note at end of section 5.2 for definitions of sinonasal surgery) for crs, * treatment with systemic corticosteroids (scs) therapy for crs as defined by any dose and duration within the prior 2 years before screening (visit 1) or intolerance/contraindication to scs. exclusion criteria: * participants with nasal conditions/concomitant nasal diseases such as nasal polyposis in endoscopy at visit 1 or with history of nasal polyposis etc., making them non-evaluable at visit 1 or for the primary efficacy * nasal cavity malignant tumor and benign tumors. * forced expiratory volume (fev1) ≤50% of predicted normal at visit 1. * radiologic suspicion or confirmed invasive or expansive fungal rhinosinusitis. * severe concomitant illness(es) that, in the investigator's judgment, would adversely affect participation in the study * active tuberculosis or non-tuberculous mycobacterial infection, or a history of incompletely treated tuberculosis unless documented adequately treated. * diagnosed active endoparasitic infections; suspected or high risk of endoparasitic infection * known or suspected immunodeficiency * history of malignancy within 5 years before visit 1, except completely treated in situ carcinoma of the cervix, and completely treated and resolved nonmetastatic squamous or basal cell carcinoma of the skin. * active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, or antifungals within 2 weeks before the screening visit 1 or during the screening period. * history of systemic hypersensitivity or anaphylaxis to dupilumab or any of its excipients. * participants in prior dupilumab clinical trial or have been treated with commercially available dupilumab within 12 months or who discontinued dupilumab use due to adverse event. * participants who are treated with intranasal corticosteroid drops; intranasal steroid emitting devices/stents; nasal spray using exhalation delivery system, such as xhance™, during screening period. * participants on unstable dose of intranasal corticosteroids (incs) spray 4 weeks prior to screening visit (visit1) and during screening period. * participants who have undergone sinus intranasal surgery (including polypectomy) within 6 months prior to visit 1. * participants who have taken: * biologic therapy/systemic immunosuppressant to treat inflammatory disease or autoimmune disease within 5 half-lives prior to visit 1 * any investigational mab within 5 half-lives prior to visit 1 * anti-ige therapy (omalizumab) within 4 months prior to visit 1. * treatment with a live (attenuated) vaccine within 4 weeks prior to visit 1 * leukotriene antagonists/modifiers unless participant is on a continuous treatment for at least 30 days prior to visit 1. * initiation of allergen immunotherapy within 3 months prior to visit 1 or a plan to begin therapy or change its dose during the screening or treatment period. * participants received scs during screening period (between visit 1 and visit 2). * either intravenous immunoglobulin therapy and/or plasmapheresis within 30 days prior to screening visit (visit 1). the above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.