A Phase 3 Study to Assess the Efficacy, Safety, and Tolerability of Itepekimab (Anti-IL-33 mAb) in Participants With Inadequately-controlled Chronic Rhinosinusitis With Nasal Polyps

Inclusion Criteria:

• Participants must be 18 years of age or older.

• Participants with a history of chronic rhinosinusitis with nasal polyps (CRSwNP) forat least 1 year prior to screening

• Participants must have at least one of the following features:

• Prior sinonasal surgery for nasal polyps (NP).

• Worsening symptoms of chronic rhinosinusitis (CRS) requiring treatment withsystemic corticosteroid(s) (SCS) within the prior 1 year before screening (Visit 1).

• An endoscopic bilateral Nasal Polyp Score (NPS) of at least 5 out of maximum scoreof 8 (with a minimum score of 2 in each nasal cavity) at screening andrandomization.

• Ongoing symptoms (for at least 12 weeks before Visit 1) of:

• Nasal congestion/blockade/obstruction with moderate or severe (symptom severityscore 2 or 3) at Visit 1 and a weekly average severity of greater than 1 in theweek before randomization (Visit 2), AND

• At least one of the following two symptoms: loss of smell or rhinorrhea (anterior/posterior).

• 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 a history of clinically significant renal, hepatic, metabolic,neurologic, hematologic, ophthalmologic, respiratory (excluding those with asthmaand aspirin-exacerbated respiratory disease (AERD) which may be included in thestudy), gastrointestinal, cardiovascular, cerebrovascular, or other significantmedical illness or disorder, which, in the judgment of the Investigator, couldinterfere with the study or require treatment that might interfere with the study.

• Participants who are currently smoking tobacco and/or vaping, or participants inwhom smoking/vaping cessation has occurred <6 months prior to Screening (Visit 1).Nicotine replacement therapy and/or noninhaled tobacco product use are notconsidered current smoking of tobacco.

• Participants meet any contraindications for mometasone furoate nasal spray (MFNS)such as hypersensitivity to MFNS or any of its components; or participants withuncontrolled opportunistic infections.

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

• 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 etc).

• Participants with severe uncontrolled asthma with history of 2 and/or moreexacerbations, requiring SCS or 1 hospitalization requiring SCS in the past year.

• History of concomitant lung disease (other than asthma, eg, COPD, interstitial lungdisease) which in the opinion of the Investigator could interfere with performanceand interpretation of spirometry.

• Participants treated with intranasal corticosteroid(s) (INCS) (MFNS is permitted),intranasal emitting devices/stents, nasal spray using exhalation delivery systemsuch as XhanceTM during the screening period. In Japan and China INCS other thanMFNS are permitted.

• Participants who have undergone any sinus intranasal surgery (including polypectomy)within 6 months before Visit 1.

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

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

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