A Proof of Concept study to assess the efficacy, safety and tolerability of itepekimab (anti­IL­33 mAb) in participants with chronic rhinosinusitis without 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

20 Mar 2025 → ongoing

Decision date (initial)

2025-02-11

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Sanofi-Aventis Recherche & Developpement

External identifiers

EU CT number

2024-515576-12-00

WHO UTN

U1111-1306-6643

ClinicalTrials.gov

NCT06691113

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

To evaluate the efficacy of itepekimab compared with placebo on sinus opacification.

Secondary objectives 7

1. To evaluate the efficacy of itepekimab compared with placebo on sinus symptoms.
2. To evaluate the efficacy of itepekimab compared to placebo on symptoms of chronic rhinosinusitis without nasal polyps (CRSsNP).
3. To evaluate the efficacy of itepekimab compared to placebo on Health Related Quality of Life (HRQoL).
4. To evaluate the efficacy of itepekimab compared to placebo on additional measures of sinus opacification.
5. To evaluate the safety and tolerability of itepekimab compared to placebo in participants with CRSsNP.
6. To evaluate the PK of itepekimab.
7. Assessment of immunogenicity to itepekimab.

Conditions and MedDRA coding

Respiratory tract diseases

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Participant must be 18 years of age or older.
2. Participants must have ongoing symptoms of nasal congestion/obstruction at least 12 consecutive weeks before Visit 1 and a Nasal Congestion Score (NCS) ≥2 at Visit 1 (day score) and Visit 2 (weekly average score).
3. Participants must have sinus Total Symptom Score (sTSS) (NC, rhinorrhea, facial pain/pressure) ≥5 at Visit 1 (day score) and Visit 2 (weekly average score).
4. Participants must have at least one of the following features: -Prior sinonasal surgery (as protocol defined) for chronic rhinosinusitis (CRS). -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.
5. Participants must have bilateral inflammation of paranasal sinuses with bilateral ethmoid and maxillary opacification on screening CT scan. Participants must have ≥25% opacification of the ethmoid sinuses and ≥25% opacification of at least 1 maxillary sinus by central reading of CT scan.
6. Participants must have a Sino-Nasal Outcome Test-22-Items (SNOT­22) score of ≥20 at Visit 1 and Visit 2.
7. Participants who have received a stable dose of mometasone furoate nasal spray (MFNS) for at least 3 weeks before Visit 2.
8. 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 9

1. Participants with conditions/concomitant diseases making them non-evaluable at Visit 1 or for the primary efficacy endpoint.
2. Participants with nasal cavity malignant tumor and benign tumors (eg, papilloma, blood boil).
3. Radiological suspicion or confirmed invasive or expansive fungal rhinosinusitis.
4. Have any clinically significant diseases or disorders (eg, cardiovascular, pulmonary, gastrointestinal, liver, kidney, neurological, musculoskeletal, endocrine, metabolic, psychiatric, physical impairment,) that, in the opinion of the Investigator, may put the subject at risk by participating in the study, or interfere with the subject’s intervention, assessment, or influence the results of the study, or have compliance issues with the study.
5. Sinus surgery within 6 months before Screening (Visit 1)
6. Participants who received SCS 1 month prior to Screening (Visit 1) or during the screening period (between Visit 1 and Visit 2).
7. Participants treated with other intranasal corticosteroid(s) (INCS) (only study provided AxMP [MFNS] is permitted), intranasal emitting devices/stents, nasal spray using exhalation delivery system such as Xhance™ during the screening period.
8. Participants with a history of severe systemic hypersensitivity reaction to mAb.
9. Known allergy to itepekimab or to its excipients. Any drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in sinus (maxillary, ethmoid) percent opacification volume assessed by CT scan

Secondary endpoints 7

1. Change from baseline in the sTSS
2. Change from baseline in nasal congestion (NC) severity score, Anterior/posterior rhinorrhea severity score, Facial pain/pressure severity score, and Loss of smell severity score using the CRSsNP daily e diary
3. Change from baseline in SNOT­22 total score
4. Change from baseline in sinus opacification as measured by the Lund-Mackay (LMK) score and the modified LMK score
5. Incidence of (treatment-emergent adverse events (TEAEs), treatment-emergent adverse events of special interest (TEAESIs), treatment emergent serious adverse events (TESAEs), and treatment-emergent adverse events (TEAEs) leading to intervention discontinuation
6. Itepekimab concentration in serum
7. Incidence of treatment-emergent (TE) anti-itepekimab antibodies 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 19

Locations

7 EU/EEA countries · 26 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 150 files

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

Application history

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