A Proof-of-Concept Study to Assess the Efficacy, Safety and Tolerability of Itepekimab (Anti--IL-33 mAb) in Participants With Chronic Rhinosinusitis Without Nasal Polyps

ACT18421 is a multinational, randomized, double-blind, placebo-controlled, parallel-group, Phase 2 study with 3 treatment groups. The purpose of the study is to evaluate the efficacy, safety and tolerability of 2 dosing regimens of itepekimab compared to placebo in male and female participants with chronic rhinosinusitis without nasal polyps (CRSsNP) aged 18 years of age and older. Study details include: * The study duration (4-week screening, 24--week intervention, 20--week safety followup) will be 48 weeks. * The intervention duration will be 24 weeks. * The number of visits will be 7 site visits and 8 phone/remote visits.

Inclusion Criteria: * Participant must be 18 years of age or older. * Participants must have ongoing symptoms of nasal congestion/obstruction at least 12 consecutive weeks before Visit 1 and a Nasal Congestion Score (NCS) ≥2 at Visit 1 (day score) and Visit 2 (weekly average score). * Participants must have sinus Total Symptom Score (sTSS) (NC, rhinorrhea, facial pain/pressure) ≥5 at Visit 1 (day score) and Visit 2 (weekly average score). * Participants must have at least one of the following features: * Prior sinonasal surgery (as protocol defined) for chronic rhinosinusitis (CRS). * Treatment with systemic corticosteroid(s) (SCS) within the prior 2 years before Screening (Visit 1) * Worsening symptoms of CRS in the past 2 years which would have required treatment with SCS, however participant is intolerant or has a contraindication to SCS. * Participants must have bilateral inflammation of paranasal sinuses with bilateral ethmoid and maxillary opacification on screening CT scan. Participants must have ≥25% opacification of the ethmoid sinuses and ≥25% opacification of at least 1 maxillary sinus by central reading of CT scan. * Participants must have a Sino-Nasal Outcome Test-22-Items (SNOT-22) score of ≥20 at Visit 1 and Visit 2. * Participants who have received a stable dose of mometasone furoate nasal spray (MFNS) for at least 3 weeks before Visit 2. * A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least 1 of the following conditions applies: * Is not a women of childbearing potential (WOCBP). OR * Is a WOCBP and agrees to use a contraceptive method that is highly effective, with a failure rate of \