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
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)
Obara Kentaro
Sanofi K.K.
Tokyo Opera City Tower, 3-20-2, Nishi Shinjuku, Shinjuku-ku, Tokyo 163-1488, Japan
+81-3-6301-3670
clinical-trials-jp@sanofi.com
Clinical Study Unit
Sanofi K.K.
Tokyo Opera City Tower, 3-20-2, Nishi Shinjuku, Shinjuku-ku, Tokyo 163-1488, Japan
+81-3-6301-3670
clinical-trials-jp@sanofi.com
Complete
April. 15, 2026
20
Interventional
randomized controlled trial
double blind
dose comparison control
parallel assignment
treatment purpose
- Participants must be 18 years of age or older.
- Participants with a history of chronic rhinosinusitis with nasal polyp(s) (CRSwNP) for at least 1 year.
- Participants must have at least one of the following features:
- - Prior sinonasal surgery for nasal polyp.
- - Worsening symptoms of chronic rhinosinusitis (CRS) requiring treatment with systemic corticosteroid(s) (SCS) within the prior 1 year.
- An endoscopic bilateral Nasal Polyp Score (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 intranasal corticosteroids (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).
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 aspirin-exacerbated respiratory disease[s] [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 monoclonal antibody (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 INCS, intranasal emitting devices/stents, nasal spray using exhalation delivery system such as Xhance 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.
18age old over
No limit
Both
Chronic rhinosinusitis with nasal polyps
Drug: Itepekimab (SAR440340, REGN3500)
Pharmaceutical form: Solution for injection in prefilled syringe
Route of administration: Subcutaneous (SC)
Drug: Placebo
Pharmaceutical form: Solution for injection in prefilled syringe
Route of administration: SC
Study Arms:
Experimental: Itepekimab high dose
- SC administration of Itepekimab high dose for 52 weeks.
- - Interventions: Itepekimab
Experimental: Itepekimab low dose
- SC administration of Itepekimab low dose for 52 weeks.
- - Interventions: Itepekimab, Placebo
1. Change from baseline in the endoscopic NPS
[Time Frame: Baseline to Week 24]
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).
1. Change from baseline in the Nasal Congestion Score (NCS)
[Time Frame: Baseline to Week 24]
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."
2. Proportion of NPS responders (defined as participants with improvement by at least 1 point in NPS)
[Time Frame: Week 24 and Week 52]
3. Change from baseline in endoscopic NPS
[Time Frame: Baseline to Week 52]
Refer to the primary outcome-1 for "NPS".
4. Change from baseline in NCS
[Time Frame: Baseline to Week 52]
Refer to the secondary outcome-1 for "NCS".
5. Change from baseline in the Total Symptom Score (TSS) (nasal congestion/obstruction, anterior/posterior rhinorrhea, and loss of sense of smell)
[Time Frame: Baseline to Weeks 24 and 52]
The CRSwNP TSS is a composite score derived from nasal congestion/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.
6. Change from baseline in loss of smell severity score using the daily CRSwNP sinonasal symptom eDiary
[Time Frame: Baseline to Weeks 24 and 52]
The CRSwNP sinonasal symptom diary is designed to assess the severity of CRS sinonasal symptoms on daily basis. These symptoms include nasal congestion/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.
7. Incidence of treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), treatment-emergent adverse events of special interest (TEAESIs) and TEAEs leading to treatment discontinuation
[Time Frame: Baseline to End of Study (EOS) (Week 72)]
TEAEs, TESAEs, TEAESIs
8. Itepekimab concentration in serum
[Time Frame: Baseline to EOS (Week 72)]
9. Incidence of treatment-emergent antidrug antibody (ADA) responses
[Time Frame: Baseline to EOS (Week 72)]
Sanofi K.K.
Not applicable due to cancellation
Not applicable due to cancellation, Tokyo
Yes
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
