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

Inclusion Criteria:

• Participant must be 18 years of age or older.

• Participants must have ongoing symptoms of nasal congestion/obstruction at least 12consecutive 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, facialpain/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 beforeScreening (Visit 1)

• Worsening symptoms of CRS in the past 2 years which would have requiredtreatment with SCS, however participant is intolerant or has a contraindicationto SCS.

• Participants must have bilateral inflammation of paranasal sinuses with bilateralethmoid and maxillary opacification on screening CT scan. Participants must have ≥25% opacification of the ethmoid sinuses and ≥25% opacification of at least 1maxillary sinus by central reading of CT scan.

• Participants must have a Sino-Nasal Outcome Test-22-Items (SNOT-22) score of ≥20 atVisit 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 orbreastfeeding, 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 <1% during the study (at a minimum until 20 weeks afterthe last dose of study intervention).

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

• Participants with conditions/concomitant diseases making them non-evaluable at Visit 1 or for the primary efficacy endpoint.

• Participants with nasal cavity malignant tumor and benign tumors (eg, papilloma,blood boil).

• Radiological suspicion or confirmed invasive or expansive fungal rhinosinusitis.

• Have any clinically significant diseases or disorders (eg, cardiovascular,pulmonary, gastrointestinal, liver, kidney, neurological, musculoskeletal,endocrine, metabolic, psychiatric, physical impairment) that, in the opinion of theInvestigator, may put the subject at risk by participating in the study, orinterfere with the subject's intervention, assessment, or influence the results ofthe study, or have compliance issues with the study.

• Sinus surgery within 6 months before Screening (Visit 1)

• Participants who received SCS 1 month prior to Screening (Visit 1) or during thescreening period (between Visit 1 and Visit 2).

• Participants treated with other intranasal corticosteroid(s) (INCS) (only studyprovided AxMP [MFNS] is permitted), intranasal emitting devices/stents, nasal sprayusing exhalation delivery system such as Xhance™ during the screening period.

• Participants with a history of severe systemic hypersensitivity reaction to mAb.

• Known allergy to itepekimab or to its excipients. Any drug or other allergy that, inthe opinion of the Investigator, contraindicates participation in the study.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.