A Phase 3 Study to Assess the Efficacy, Safety, and Tolerability of Itepekimab (Anti-IL-33 mAb) in Adult Japanese Participants With Inadequately-controlled Chronic Rhinosinusitis With Nasal Polyps (CEREN-4)

A Randomized, Double-blind, Parallel-group, 52-week Trial to Investigate the Efficacy, Safety, and Tolerability of Itepekimab in Adult Japanese Participants With Inadequately-controlled Chronic Rhinosinusitis With Nasal Polyps

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

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Rhinosinusitis With Nasal Polyps
• Intervention / Treatment: Drug: Itepekimab (SAR440340); Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Trial Transparency email recommended (Toll free for US & Canada); Phone Number: option 6 800-633-1610; Email: contact-us@sanofi.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Itepekimab high dose; Subcutaneous (SC) administration of Itepekimab high dose for 52 weeks	Drug: Itepekimab (SAR440340); Pharmaceutical form: Solution for injection in prefilled syringe. Route of administration: Subcutaneous; Other Names: REGN3500
Experimental: Itepekimab low dose; SC administration of Itepekimab low dose for 52 weeks	Drug: Itepekimab (SAR440340); Pharmaceutical form: Solution for injection in prefilled syringe. Route of administration: Subcutaneous; Other Names: REGN3500; Drug: Placebo; Pharmaceutical form: Solution for injection in prefilled syringe. Route of administration: Subcutaneous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in the endoscopic NPS	The Nasal Polyp Score (NPS) is the sum of the right and left nostril scores, as evaluated by means of nasal endoscopy. Nasal polyp is graded based on polyp size from 0 to 4 with higher scores indicating larger polyps. The sum of right and left nostril scores ranges from 0 (no polyps) to 8 (large polyps).	Baseline to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in endoscopic NPS	The NPS is the sum of the right and left nostril scores, as evaluated by means of nasal endoscopy. Nasal polyp is graded based on polyp size from 0 to 4 with higher scores indicating larger polyps. The sum of right and left nostril scores ranges from 0 (no polyps) to 8 (large polyps).	Baseline to Week 52
Itepekimab concentration in serum		Baseline to EOS (Week 72)
Change from baseline in the NCS	The Nasal Congestion Score (NCS) is scored using a 0-3 categorical scale where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms. Outcome value is defined as the preceding 28-day average of morning scores recorded in eDiary.	Baseline to Week 24
Proportion of NPS responders (defined as participants with improvement by at least 1 points in NPS)		Week 24 and Week 52
Change from baseline in NCS	The NCS is scored using a 0-3 categorical scale where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms. Outcome value is defined as the preceding 28-day average of morning scores recorded in eDiary.	Baseline to Week 52
Change from baseline in the TSS (nasal congestion/obstruction, anterior/posterior rhinorrhea, and loss of sense of smell)	The CRSwNP Total Symptom Score (TSS) is a composite score derived from nasal congestion (NC)/obstruction, anterior/posterior rhinorrhea,and loss of smell. The total score ranges from 0 to 9 with higher scores on TSS indicating greater overall symptom severity.	Baseline to Weeks 24 and 52
Change from baseline in loss of smell severity score using the daily CRSwNP sinonasal symptom eDiary	The CRSwNP sinonasal symptom diary is designed to assess the severity of chronic rhinosinusitis (CRS) sinonasal symptoms on daily basis. These symptoms include NC/obstruction, anterior rhinorrhea and posterior rhinorrhea, facial pain/pressure, loss of smell, and headache. Each of the individual items of the diary are scored from 0 ("No symptoms") to 3 ("Severe symptoms - symptoms that are hard to tolerate, cause interference with activities or daily living"). Higher scores on the items of the individual symptoms denote greater symptom severity.	Baseline to Weeks 24 and 52
Incidence of TEAEs, TESAEs, TEAESIs and TEAEs leading to treatment discontinuation	Treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), treatment-emergent adverse events of special interest (TEAESIs)	Baseline to End of Study (EOS) (Week 72)
Incidence of treatment-emergent antidrug antibody (ADA) responses		Baseline to EOS (Week 72)

Collaborators and Investigators

• Sponsor: Sanofi
• Collaborators: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Study record dates

Study Major Dates

• Study Start (Estimated): May 8, 2026
• Primary Completion (Estimated): October 20, 2027
• Study Completion (Estimated): October 10, 2028

Study Registration Dates

• First Submitted: March 16, 2026
• First Submitted That Met QC Criteria: March 16, 2026
• First Posted (Actual): March 20, 2026

Study Record Updates

• Last Update Posted (Actual): March 20, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: itepekimab
• Other Study ID Numbers: EFC21029; U1111-1322-6073 (Registry Identifier: ICTRP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes