A Phase 3 study to assess the efficacy, safety, and tolerability of itepekimab (anti­IL­33 mAb) in participants with inadequately-controlled chronic rhinosinusitis with nasal polyps

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sanofi-Aventis Recherche & Developpement

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

30 May 2025 → ongoing

Decision date (initial)

2025-04-01

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Sanofi-Aventis Recherche & Developpement

External identifiers

EU CT number

2024-516815-26-00

WHO UTN

U1111-1306-6544

ClinicalTrials.gov

NCT06834360

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Therapy, Pharmacoeconomic, Safety, Pharmacogenetic, Pharmacodynamic, Efficacy, Pharmacogenomic

To evaluate the efficacy of itepekimab compared with placebo on nasal polyps (NP) size and nasal congestion.

Secondary objectives 14

1. To evaluate the long term efficacy of itepekimab compared with placebo on NP size.
2. To evaluate the long term efficacy of itepekimab compared to placebo on nasal congestion.
3. To evaluate the efficacy of itepekimab compared with placebo on sinus opacification.
4. To evaluate the efficacy of itepekimab compared to placebo on symptoms of chronic rhinosinusitis with nasal polyps (CRSwNP).
5. To evaluate the efficacy of itepekimab compared to placebo on sense of smell.
6. To evaluate the efficacy of itepekimab compared to placebo on health related quality of life.
7. To evaluate the efficacy of itepekimab compared to placebo on sleep disturbance.
8. To evaluate the ability of itepekimab compared to placebo to reduce the risk of worsening/acute sinusitis requiring treatment with systemic corticosteroid(s) (SCS) or sinus surgery.
9. To evaluate the effect of itepekimab compared to placebo on asthma in the subgroup of participants with comorbid asthma.
10. To evaluate the effect of itepekimab compared to placebo in the subgroup of participants with aspirin-exacerbated respiratory disease (AERD).
11. To evaluate the efficacy of itepekimab compared to placebo.
12. To evaluate the safety and tolerability of itepekimab compared to placebo in participants with CRSwNP.
13. To evaluate the pharmacokinetics (PK) of itepekimab.
14. Assessment of immunogenicity to itepekimab over time compared to placebo.

Conditions and MedDRA coding

Chronic rhinosinusitis with nasal polyps

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share 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​

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Participants must be 18 years of age or older.
2. Participants with a history of chronic rhinosinusitis with nasal polyps (CRSwNP) for at least 1 year prior to screening
3. Participants must have at least one of the following features: o Prior sinonasal surgery for nasal polyps (NP). o Worsening symptoms of chronic rhinosinusitis (CRS) requiring treatment with systemic corticosteroid(s) (SCS) within the prior 1 year before screening (Visit 1).
4. 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.
5. Ongoing symptoms (for at least 12 weeks before Visit 1) of: o 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).
6. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least 1 of the following conditions applies: o Is not a women of childbearing potential (WOCBP), OR o 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 12

1. 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.
2. 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.
3. 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.
4. Participants with a history of a severe systemic hypersensitivity reaction to a mAb.
5. Participants with conditions/concomitant diseases making them non­evaluable at Visit 1 or for the primary efficacy endpoint.
6. Participants with nasal cavity malignant tumor and benign tumors (eg, papilloma, blood boil etc).
7. Participants with severe uncontrolled asthma with history of 2 and/or more exacerbations, requiring SCS or 1 hospitalization requiring SCS in the past year.
8. 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.
9. 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.
10. Participants who have undergone any sinus intranasal surgery (including polypectomy) within 6 months before Visit 1.
11. Participants who received SCS 1 month prior to Screening (Visit 1) or during the screening period (between Visit 1 and Visit 2).
12. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Change from baseline in the endoscopic NPS
2. Change from baseline in the NCS

Secondary endpoints 22

1. Change from baseline in endoscopic NPS
2. Change from baseline in NCS
3. Change from baseline in opacification of sinuses assessed by Computed Tomography (CT) scan using the LMK score
4. Change from baseline in the TSS (nasal congestion/obstruction, anterior/posterior rhinorrhea, and loss of sense of smell)
5. Change from baseline in loss of smell severity score using the daily CRSwNP sinonasal symptom eDiary, and UPSIT score
6. Change from baseline in SNOT­22 total score
7. Change from baseline in PROMIS SD­SF­8b scores
8. Proportion of participants with CRSwNP requiring systemic corticosteroid(s) (SCS) or surgery for CRS
9. Annualized rate of SCS course or surgery for CRS
10. Time to first either SCS or surgery for CRS
11. Change from baseline in pre BD FEV1 (in mL) in participants with co-morbid asthma
12. Change from baseline in ACQ 5 score in participants with co-morbid asthma
13. Change from the baseline in NPS and NCS in the subgroup of patients with aspirin-exacerbated respiratory disease (AERD)
14. Proportion of participants with AERD requiring SCS or surgery for CRS
15. Annualized rate of SCS course or surgery for CRS in participants with AERD
16. Time to first either SCS or surgery for CRS in participants with AERD
17. Change from baseline in pre BD FEV1 (in ml) in participants with AERD
18. Proportion of NPS responders (defined as participants with improvement by at least 1 point in NPS)
19. Proportion of NPS responders (defined as participants with improvement by at least 2 points in NPS)
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
21. Itepekimab concentration in serum
22. Incidence of treatment emergent anti itepekimab antibody (ADA) responses

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sanofi-Aventis Recherche & Developpement

Sponsor organisation

Sanofi-Aventis Recherche & Developpement

Address

82 Avenue Raspail

City

Gentilly

Postcode

94250

Country

France

Scientific contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Third parties 15

Locations

11 EU/EEA countries · 47 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 218 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

27 submissions — initial application plus substantial / non-substantial modifications