Clinical trial NCT06834360: 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
Official 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Chronic Rhinosinusitis With Nasal Polyps
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2025-02-19
Enrollment: 210
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: EFC18419 is a multinational, randomized, double-blind, placebo-controlled, parallel-group, Phase 3 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 as add-on therapy to intranasal corticosteroids (INCS) in male and female participants with chronic rhinosinusitis with nasal polyps (CRSwNP) aged 18 years of age and older.

Study details include:

* The study duration per participant (4-week screening, 52-week treatment, 20-week safety follow-up) will be up to 76 weeks. For participants transitioning to the LTS18420 study, the study duration will be 56 weeks.
* The treatment duration will be up to 52 weeks.
* The number of visits will be 9 site visits and 20 phone/home visits.


Eligibility criteria: 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 1 year before screening (Visit 1).
* 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).

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.

Primary outcomes:
measure: Change from baseline in the endoscopic NPS
timeFrame: Baseline to Week 24
measure: Change from baseline in the NCS
timeFrame: Baseline to Week 24
Secondary outcomes:
measure: Change from baseline in endoscopic NPS
timeFrame: Baseline to Week 52
measure: Change from baseline in NCS
timeFrame: Baseline to Week 52
measure: Change from baseline in opacification of sinuses assessed by Computed Tomography (CT) scan using the LMK score
timeFrame: Baseline to Week 24
measure: Change from baseline in the TSS (nasal congestion/obstruction, anterior/posterior rhinorrhea, and loss of sense of smell)
timeFrame: Baseline to Weeks 24 and 52
measure: Change from baseline in loss of smell severity score using the daily CRSwNP sinonasal symptom eDiary, and UPSIT score
timeFrame: Baseline to Weeks 24 and 52
measure: Change from baseline in SNOT-22 total score
timeFrame: Baseline to Weeks 24 and 52
measure: Change from baseline in PROMIS SD-SF-8b scores
timeFrame: Baseline to Weeks 24 and 52
measure: Proportion of participants with CRSwNP requiring systemic corticosteroid(s) (SCS) or surgery for CRS
timeFrame: Baseline up to Week 52
measure: Annualized rate of SCS course or surgery for CRS
timeFrame: Baseline up to Week 52
measure: Time to first either SCS or surgery for CRS
timeFrame: Baseline through Week 52
measure: Change from baseline in pre-BD FEV1 (in mL) in participants with co-morbid asthma
timeFrame: Baseline to Weeks 24 and 52
measure: Change from baseline in ACQ-5 score in participants with co-morbid asthma
timeFrame: Baseline to Weeks 24 and 52
measure: Change from the baseline in NPS and NCS in the subgroup of patients with aspirin-exacerbated respiratory disease (AERD)
timeFrame: Baseline to Weeks 24 and 52
measure: Proportion of participants with AERD requiring SCS or surgery for CRS
timeFrame: Baseline up to Week 52
measure: Annualized rate of SCS course or surgery for CRS in participants with AERD
timeFrame: Baseline up to Week 52
measure: Time to first either SCS or surgery for CRS in participants with AERD
timeFrame: Baseline through Week 52
measure: Change from baseline in pre-BD FEV1 (in ml) in participants with AERD
timeFrame: Baseline to Weeks 24 and 52
measure: Proportion of NPS responders (defined as participants with improvement by at least 1 point in NPS)
timeFrame: Weeks 24 and 52
measure: Proportion of NPS responders (defined as participants with improvement by at least 2 points in NPS)
timeFrame: Weeks 24 and 52
measure: 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
timeFrame: Baseline to End of Study (EOS) (Week 72)
measure: Itepekimab concentration in serum
timeFrame: Baseline to EOS (Week 72)
measure: Incidence of treatment-emergent anti-itepekimab antibody (ADA) responses
timeFrame: Baseline to EOS (Week 72)
Other outcomes:
Locations:
city: San Diego
country: United States
facility: San Diego Clinical Research Center- Site Number : 8400041
state: California
city: Louisville
country: United States
facility: Advanced ENT & Allergy - Louisville- Site Number : 8400007
state: Kentucky
city: Oklahoma City
country: United States
facility: Allergy, Asthma and Clinical Research- Site Number : 8400002
state: Oklahoma
city: Fort Worth
country: United States
facility: Ear and Sinus Institute- Site Number : 8400048
state: Texas
city: Brisbane
country: Australia
facility: Investigational Site Number : 0360002
state: Queensland
city: Spearwood
country: Australia
facility: Investigational Site Number : 0360001
state: Western Australia
city: Québec City
country: Canada
facility: Investigational Site Number : 1240003
state: Quebec
city: Québec City
country: Canada
facility: Investigational Site Number : 1240012
state: Quebec
city: Concepción
country: Chile
facility: Investigational Site Number : 1520001
state: Biobío
city: Santiago
country: Chile
facility: Investigational Site Number : 1520003
state: Reg Metropolitana De Santiago
city: Baotou
country: China
facility: Investigational Site Number : 1560020
city: Beijing
country: China
facility: Investigational Site Number : 1560001
city: Chengdu
country: China
facility: Investigational Site Number : 1560004
city: Jinan
country: China
facility: Investigational Site Number : 1560002
city: Jingzhou
country: China
facility: Investigational Site Number : 1560012
city: Nanning
country: China
facility: Investigational Site Number : 1560021
city: Shenyang
country: China
facility: Investigational Site Number : 1560006
city: Suzhou
country: China
facility: Investigational Site Number : 1560024
city: Taiyuan
country: China
facility: Investigational Site Number : 1560017
city: Yantai
country: China
facility: Investigational Site Number : 1560003
city: Zibo
country: China
facility: Investigational Site Number : 1560009
city: Budapest
country: Hungary
facility: Investigational Site Number : 3480005
city: Jerusalem
country: Israel
facility: Investigational Site Number : 3760004
city: Lodz
country: Poland
facility: Investigational Site Number : 6160002
state: Lódzkie
city: Bielsko-Biala
country: Poland
facility: Investigational Site Number : 6160001
city: Poznan
country: Poland
facility: Investigational Site Number : 6160004
city: Wigan
country: United Kingdom
facility: Investigational Site Number : 8260002
state: Lancashire
city: London
country: United Kingdom
facility: Investigational Site Number : 8260001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: