This is a randomized, multicenter, double-blind, Phase 3 study with 2 parallel groups. The purpose of this study is to evaluate the efficacy, safety, and tolerability of 2 different dosing regimens of itepekimab monotherapy in Japanese participants aged 18 years or older with chronic rhinosinusitis with nasal polyp(s) (CRSwNP) who are not adequately controlled despite previous surgery and/or treatment with systemic corticosteroid(s) (SCS).

The total study duration par participant is approximately 76 week, including:

• A screening period for up to 4 weeks.
• A randomized study intervention period for up to 52 weeks
• A post-intervention safety follow-up for up to 20 weeks
• The number of visits will be 9 site visits and 20 phone/home visits

Inclusion Criteria:

• Participants must be 18 years of age or older.

• Participants with a history of CRSwNP for at least 1 year.

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

  • Prior sinonasal surgery for NP.
  • Worsening symptoms of CRS requiring treatment with SCS within the prior 1 year.

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

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

  • Nasal congestion/blockade/obstruction with moderate or severe symptom (score of 2 or 3), AND
  • At least one of the following two symptoms: loss of smell or rhinorrhea (anterior/posterior).

• Not currently on and have not been receiving INCS for at least one month.

• 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 <1% during the study (at a minimum until 20 weeks after the 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 asthma and AERD which may be included in the study), gastrointestinal, cardiovascular, cerebrovascular, or other significant medical illness or disorder, which, in the judgment of the Investigator, could interfere with the study or require treatment that might interfere with the study.
• Participants who are currently smoking tobacco and/or vaping, or participants in whom smoking/vaping cessation has occurred <6 months. Nicotine replacement therapy and/or noninhaled tobacco product use are not considered current smoking of tobacco.
• Participants with a history of a severe systemic hypersensitivity reaction to a mAb.
• Participants with conditions/concomitant diseases making them non-evaluable 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 more exacerbations, requiring SCS or 1 hospitalization requiring SCS in the past year.
• Participants treated with intranasal corticosteroid(s) (INCS), intranasal emitting devices/stents, nasal spray using exhalation delivery system such as XhanceTM one month prior during the screening period.
• 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 the screening period (between Visit 1 and Visit 2).
• Known allergy to itepekimab or its excipients, or any drug or other allergy that, in the 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.

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org