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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06834360




Registration number
NCT06834360
Ethics application status
Date submitted
14/02/2025
Date registered
19/02/2025

Titles & IDs
Public title
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
Scientific title
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
Secondary ID [1] 0 0
2024-516815-26
Secondary ID [2] 0 0
EFC18419
Universal Trial Number (UTN)
Trial acronym
CEREN2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Rhinosinusitis With Nasal Polyps 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Itepekimab (SAR440340)
Treatment: Drugs - Placebo
Treatment: Drugs - Mometasone furoate nasal spray (MFNS)

Experimental: Itepekimab high dose - Subcutaneous (SC) administration of Itepekimab high dose for 52 weeks

Experimental: Itepekimab low dose - SC administration of Itepekimab low dose for 52 weeks

Placebo comparator: Placebo - SC administration of matching placebo for 52 weeks


Treatment: Drugs: Itepekimab (SAR440340)
Pharmaceutical form: Solution for injection in prefilled syringe. Route of administration: Subcutaneous

Treatment: Drugs: Placebo
Pharmaceutical form: Solution for injection in prefilled syringe. Route of administration: Subcutaneous

Treatment: Drugs: Mometasone furoate nasal spray (MFNS)
Pharmaceutical form: Solution for administration via spray pump. Route of administration: Intranasal spray
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change from baseline in the endoscopic NPS
Assessment method [1] 0 0
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).
Timepoint [1] 0 0
Baseline to Week 24
Primary outcome [2] 0 0
Change from baseline in the NCS
Assessment method [2] 0 0
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.
Timepoint [2] 0 0
Baseline to Week 24
Secondary outcome [1] 0 0
Change from baseline in endoscopic NPS
Assessment method [1] 0 0
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).
Timepoint [1] 0 0
Baseline to Week 52
Secondary outcome [2] 0 0
Change from baseline in NCS
Assessment method [2] 0 0
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.
Timepoint [2] 0 0
Baseline to Week 52
Secondary outcome [3] 0 0
Change from baseline in opacification of sinuses assessed by Computed Tomography (CT) scan using the LMK score
Assessment method [3] 0 0
The Lund-Mackay (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).
Timepoint [3] 0 0
Baseline to Week 24
Secondary outcome [4] 0 0
Change from baseline in the TSS (nasal congestion/obstruction, anterior/posterior rhinorrhea, and loss of sense of smell)
Assessment method [4] 0 0
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.
Timepoint [4] 0 0
Baseline to Weeks 24 and 52
Secondary outcome [5] 0 0
Change from baseline in loss of smell severity score using the daily CRSwNP sinonasal symptom eDiary, and UPSIT score
Assessment method [5] 0 0
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. The University of Pennsylvania Smell Identification Test (UPSIT) test is a rapid and easy-to-administer method to quantitatively assess human olfactory function. The total score ranges from 0 (anosmia) to 40 (normosmia).
Timepoint [5] 0 0
Baseline to Weeks 24 and 52
Secondary outcome [6] 0 0
Change from baseline in SNOT-22 total score
Assessment method [6] 0 0
The Sino-Nasal Outcome Test-22-Items (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.
Timepoint [6] 0 0
Baseline to Weeks 24 and 52
Secondary outcome [7] 0 0
Change from baseline in PROMIS SD-SF-8b scores
Assessment method [7] 0 0
The Patient Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance - Short Form 8b (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 SD of 10, where higher scores indicate more disturbed sleep.
Timepoint [7] 0 0
Baseline to Weeks 24 and 52
Secondary outcome [8] 0 0
Proportion of participants with CRSwNP requiring systemic corticosteroid(s) (SCS) or surgery for CRS
Assessment method [8] 0 0
Timepoint [8] 0 0
Baseline up to Week 52
Secondary outcome [9] 0 0
Annualized rate of SCS course or surgery for CRS
Assessment method [9] 0 0
Timepoint [9] 0 0
Baseline up to Week 52
Secondary outcome [10] 0 0
Time to first either SCS or surgery for CRS
Assessment method [10] 0 0
Timepoint [10] 0 0
Baseline through Week 52
Secondary outcome [11] 0 0
Change from baseline in pre-BD FEV1 (in mL) in participants with co-morbid asthma
Assessment method [11] 0 0
Pre-BD FEV1: pre-bronchodilator forced expiratory volume in 1 second
Timepoint [11] 0 0
Baseline to Weeks 24 and 52
Secondary outcome [12] 0 0
Change from baseline in ACQ-5 score in participants with co-morbid asthma
Assessment method [12] 0 0
The Asthma Control Questionnaire (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.
Timepoint [12] 0 0
Baseline to Weeks 24 and 52
Secondary outcome [13] 0 0
Change from the baseline in NPS and NCS in the subgroup of patients with aspirin-exacerbated respiratory disease (AERD)
Assessment method [13] 0 0
Timepoint [13] 0 0
Baseline to Weeks 24 and 52
Secondary outcome [14] 0 0
Proportion of participants with AERD requiring SCS or surgery for CRS
Assessment method [14] 0 0
Timepoint [14] 0 0
Baseline up to Week 52
Secondary outcome [15] 0 0
Annualized rate of SCS course or surgery for CRS in participants with AERD
Assessment method [15] 0 0
Timepoint [15] 0 0
Baseline up to Week 52
Secondary outcome [16] 0 0
Time to first either SCS or surgery for CRS in participants with AERD
Assessment method [16] 0 0
Timepoint [16] 0 0
Baseline through Week 52
Secondary outcome [17] 0 0
Change from baseline in pre-BD FEV1 (in ml) in participants with AERD
Assessment method [17] 0 0
Pre-BD FEV1: pre-bronchodilator forced expiratory volume in 1 second
Timepoint [17] 0 0
Baseline to Weeks 24 and 52
Secondary outcome [18] 0 0
Proportion of NPS responders (defined as participants with improvement by at least 1 point in NPS)
Assessment method [18] 0 0
Timepoint [18] 0 0
Weeks 24 and 52
Secondary outcome [19] 0 0
Proportion of NPS responders (defined as participants with improvement by at least 2 points in NPS)
Assessment method [19] 0 0
Timepoint [19] 0 0
Weeks 24 and 52
Secondary outcome [20] 0 0
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
Assessment method [20] 0 0
Timepoint [20] 0 0
Baseline to End of Study (EOS) (Week 72)
Secondary outcome [21] 0 0
Itepekimab concentration in serum
Assessment method [21] 0 0
Timepoint [21] 0 0
Baseline to EOS (Week 72)
Secondary outcome [22] 0 0
Incidence of treatment-emergent anti-itepekimab antibody (ADA) responses
Assessment method [22] 0 0
Timepoint [22] 0 0
Baseline to EOS (Week 72)

Eligibility
Key inclusion criteria
* 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).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 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, 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 XhanceTM 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
6/02/2025
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
13/12/2027
Actual
Sample size
Target
210
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,WA
Recruitment hospital [1] 0 0
Investigational Site Number : 0360002 - Brisbane
Recruitment hospital [2] 0 0
Investigational Site Number : 0360001 - Spearwood
Recruitment postcode(s) [1] 0 0
4029 - Brisbane
Recruitment postcode(s) [2] 0 0
6163 - Spearwood
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Kentucky
Country [3] 0 0
United States of America
State/province [3] 0 0
Oklahoma
Country [4] 0 0
Canada
State/province [4] 0 0
Quebec
Country [5] 0 0
Chile
State/province [5] 0 0
Reg Metropolitana De Santiago
Country [6] 0 0
China
State/province [6] 0 0
Beijing
Country [7] 0 0
China
State/province [7] 0 0
Chengdu
Country [8] 0 0
China
State/province [8] 0 0
Jingzhou
Country [9] 0 0
China
State/province [9] 0 0
Shenyang
Country [10] 0 0
United Kingdom
State/province [10] 0 0
Lancashire
Country [11] 0 0
United Kingdom
State/province [11] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Sanofi
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Regeneron Pharmaceuticals
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Sciences & Operations
Address 0 0
Sanofi
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Trial Transparency email recommended (Toll free for US & Canada)
Address 0 0
Country 0 0
Phone 0 0
800-633-1610
Email 0 0
contact-us@sanofi.com
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT06834360