A Proof-of-Concept Study to Assess the Efficacy, Safety and Tolerability of Itepekimab (Anti--IL-33 mAb) in Participants With Chronic Rhinosinusitis Without Nasal Polyps

Sanofi

Status and phase: Enrolling; Phase 2

Conditions: Chronic Rhinosinusitis Without Nasal Polyps

Treatments: Drug: Placebo; Drug: Itepekimab (SAR440340); Drug: Mometasone furoate nasal spray (MFNS)

Study type: Interventional

Funder types: Industry

Identifiers

NCT06691113

U1111-1306-6643 (Registry Identifier)

ACT18421

2024-515576-12 (Registry Identifier)

Details and patient eligibility

About

ACT18421 is a multinational, randomized, double-blind, placebo-controlled, parallel-group, Phase 2 study with 3 treatment groups. The purpose of the study is to evaluate the efficacy, safety and tolerability of 2 dosing regimens of itepekimab compared to placebo in male and female participants with chronic rhinosinusitis without nasal polyps (CRSsNP) aged 18 years of age and older.

Study details include:

• The study duration (4-week screening, 24--week intervention, 20--week safety followup) will be 48 weeks.
• The intervention duration will be 24 weeks.
• The number of visits will be 7 site visits and 8 phone/remote visits.

Enrollment: 60 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participant must be 18 years of age or older.

• 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).

• 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).

• 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.

• 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.

• Participants must have a Sino-Nasal Outcome Test-22-Items (SNOT-22) score of ≥20 at Visit 1 and Visit 2.

• Participants who have received a stable dose of mometasone furoate nasal spray (MFNS) for at least 3 weeks before Visit 2.

• 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

Participants are excluded from the study if any of the following criteria apply:

• 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).
• Radiological suspicion or confirmed invasive or expansive fungal rhinosinusitis.
• 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.
• Sinus surgery within 6 months before Screening (Visit 1)
• Participants who received SCS 1 month prior to Screening (Visit 1) or during the screening period (between Visit 1 and Visit 2).
• 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.
• Participants with a history of severe systemic hypersensitivity reaction to mAb.
• 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.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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60 participants in 3 patient groups, including a placebo group

Itepekimab high dose

Experimental group

Description:

Subcutaneous (SC) administration of Itepekimab high dose for 24 weeks

Treatment:

Drug: Mometasone furoate nasal spray (MFNS)

Drug: Itepekimab (SAR440340)

Itepekimab low dose

Experimental group

Description:

SC administration of Itepekimab low dose for 24 weeks

Treatment:

Drug: Mometasone furoate nasal spray (MFNS)

Drug: Itepekimab (SAR440340)

Drug: Placebo

Placebo

Placebo Comparator group

Description:

SC administration of matching placebo for 24 weeks

Treatment:

Drug: Mometasone furoate nasal spray (MFNS)

Drug: Placebo