A randomized, double-blind, placebo-controlled, parallel-group, 52-week Phase 3 trial to investigate the efficacy, safety, and tolerability of itepekimab in adult participants with inadequately-controlled chronic rhinosinusitis with nasal polyps
A Phase 3 study to assess the efficacy, safety, and tolerability of itepekimab (anti-Interleukin [IL]-33 monoclonal antibody [mAb]) in participants with inadequately-controlled chronic rhinosinusitis with nasal polyps (CEREN1 )
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
Pending
May. 16, 2025
210
Interventional
randomized controlled trial
double blind
placebo control
parallel assignment
treatment purpose
Participants are eligible to be included in the study only if all of the following criteria apply:
- Participants must be 18 years of age or older
- Participants with a history of chronic rhinosinusitis with nasal polyps (CRSwNP) for at 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 with systemic corticosteroid(s) (SCS) within the prior 2 years before screening (Visit 1)
- - Worsening symptoms of CRS in the past 2 years which would have required treatment with SCS, however participant is intolerant or has a contraindication to SCS
- 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) at screening and randomization
- Ongoing symptoms (for at least 12 weeks before Visit 1) of:
- - Nasal congestion/blockade/obstruction with moderate or severe (symptom severity score 2 or 3) at Visit 1 and a weekly average severity of greater than 1 in the week 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 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 [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 prior to Screening (Visit 1). Nicotine replacement therapy and/or noninhaled tobacco product use are not considered 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 with uncontrolled 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 more exacerbations, requiring SCS or 1 hospitalization requiring SCS in the past year
- History of concomitant lung disease (other than asthma, eg, chronic obstructive pulmonary disease [COPD], interstitial lung disease) which in the opinion of the Investigator could interfere with performance and interpretation of spirometry
- Participants treated with intranasal corticosteroid(s) (INCS) (MFNS is permitted), intranasal emitting devices/stents, nasal spray using exhalation delivery system such as Xhance during the screening period. In Japan and China INCS other than MFNS 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 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) injection
Drug: Placebo matching Itepekimab
Pharmaceutical form: Solution for injection in prefilled syringe.
Route of administration: SC injection
Drug: MFNS
Pharmaceutical form: Solution for administration via spray pump
Route of administration: Intranasal spray
Study Arms:
- Experimental: Itepekimab high dose
SC administration of itepekimab high dose for 52 weeks.
Interventions: Itepekimab, MFNS
- Experimental: Itepekimab low dose
SC administration of itepekimab low dose for 52 weeks.
Interventions: Itepekimab, Placebo, MFNS
- Placebo Comparator: Placebo
SC administration of matching placebo for 52 weeks.
Interventions: Placebo, MFNS
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. NP 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).
2. 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 electronic diary (eDiary).
1. Change from baseline in endoscopic NPS
[Time Frame: Baseline to Week 52]
The NPS is the sum of the right and left nostril scores, as evaluated by means of nasal endoscopy. NP 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).
2. Change from baseline in NCS
[Time Frame: Baseline to Week 52]
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.
3. Change from baseline in opacification of sinuses assessed by Computed Tomography (CT) scan using the Lund Mackay (LMK) score
[Time Frame: Baseline to Week 24]
The LMK system is based on localization with points given for degree of opacification: 0 = normal, 1 = partial opacification, 2 = total opacification. These points are then applied to the maxillary, anterior ethmoid, posterior ethmoid, sphenoid, frontal sinus on each side. The osteomeatal complex is graded as 0 = not occluded, or 2 = occluded, deriving a maximum score of 12 per side. The total score is the sum of scores from each side and ranges from 0 (normal) to 24 (total opacification).
4. 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.
5. Change from baseline in loss of smell severity score using the daily CRSwNP sinonasal symptom eDiary, and University of Pennsylvania Smell Identification Test (UPSIT) score
[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.
The UPSIT is a rapid and easy-to-administer method to quantitatively assess human olfactory function. The total score ranges from 0 (anosmia) to 40 (normosmia).
6. Change from baseline in Sino-Nasal Outcome Test-22-Items (SNOT-22) total score
[Time Frame: Baseline to Weeks 24 and 52]
The SNOT-22 is a patient-reported outcome questionnaire designed to assess the impact of CRS on patient's Health-Related Quality of Life (HRQoL). It has 22 items covering five domains: Nasal, Ear/Facial, Sleep, Function, and Emotion. A global score ranging from 0 to 110 with higher score indicating greater rhinosinusitis related health burden.
7. Change from baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance-Short Form-8b (SD-SF-8b) scores
[Time Frame: Baseline to Weeks 24 and 52]
The PROMIS SD-SF-8b is a generic 8-item sleep disturbance assessment that evaluates difficulties with falling asleep, staying asleep, and getting enough sleep; and perceptions on the quality and satisfaction of sleep. Scores are calculated with a conversion of the raw score (score range 8 to 40) into a standardized T-score with the mean of the 50 and standard deviation (SD) of 10, where higher scores indicate more disturbed sleep.
8. Proportion of participants with CRSwNP requiring SCS or surgery for CRS
[Time Frame: Baseline up to Week 52]
9. Annualized rate of SCS course or surgery for CRS
[Time Frame: Baseline up to Week 52]
10. Time to first either SCS or surgery for CRS
[Time Frame: Baseline through Week 52]
11. Change from baseline in pre-bronchodilator forced expiratory volume in 1 second (FEV1) (in mL) in participants with co-morbid asthma
[Time Frame: Baseline to Weeks 24 and 52]
12. Change from baseline in Asthma Control Questionnaire-5 (ACQ-5) score in participants with co-morbid asthma
[Time Frame: Baseline to Weeks 24 and 52]
The ACQ is a questionnaire that measures the adequacy of asthma control and any changes in asthma control that may occur spontaneously or as a result of treatment. The ACQ-5 has 5 questions on the asthma symptoms. The global score is the mean of the item responses and ranges from 0 and 6 with higher score indicating lower asthma control.
13. Change from the baseline in NPS and NCS in the subgroup of patients with AERD
[Time Frame: Baseline to Weeks 24 and 52]
14. Proportion of participants with AERD requiring SCS or surgery for CRS
[Time Frame: Baseline up to Week 52]
15. Annualized rate of SCS course or surgery for CRS in participants with AERD
[Time Frame: Baseline up to Week 52]
16. Time to first either SCS or surgery for CRS in participants with AERD
[Time Frame: Baseline through Week 52]
17. Change from baseline in pre-bronchodilator FEV1 (in mL) in participants with AERD
[Time Frame: Baseline to Weeks 24 and 52]
18. Proportion of NPS responders (defined as participants with improvement by at least 1 point in NPS)
[Time Frame: Weeks 24 and 52]
19. Proportion of NPS responders (defined as participants with improvement by at least 2 points in NPS)
[Time Frame: Weeks 24 and 52]
20. 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)]
21. Itepekimab concentration in serum
[Time Frame: Baseline to EOS (Week 72)]
22. Incidence of treatment-emergent anti-itepekimab antibody (ADA) responses
[Time Frame: Baseline to EOS (Week 72)]
Sanofi K.K.
After approval
After approval, 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
NCT06834347
ClinicalTrials.gov
2024-516814-39
CTIS
United Kingdom/United States/Canada/Chile/Republic of Korea
