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
Itepekimab (SAR440340): Pharmaceutical form: Solution for injection in prefilled syringe. Route of administration: Subcutaneous
Placebo: Pharmaceutical form: Solution for injection in prefilled syringe. Route of administration: Subcutaneous
Mometasone furoate nasal spray (MFNS): Pharmaceutical form: Solution for administration via spray pump. Route of administration: Intranasal spray
Study 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
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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 outcome measure(s)
Change from baseline in the endoscopic NPS — Baseline to Week 24 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).
Change from baseline in the NCS — Baseline to Week 24 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.
Trial sites (111)
Facility
City
Region
Status
Excel ENT of Alabama- Site Number : 8400052
Birmingham
Alabama
Velocity Clinical Research - San Diego- Site Number : 8400041
La Mesa
California
Cedars-Sinai Medical Center- Site Number : 8400030
Los Angeles
California
One Of A Kind Clinical Research Center- Site Number : 8400034
Napa
California
University of Florida - Jacksonville- Site Number : 8400053
Jacksonville
Florida
Advanced Research Institute - New Port Richey- Site Number : 8400014
New Port Richey
Florida
University of Illinois at Chicago- Site Number : 8400003
Chicago
Illinois
Advanced ENT & Allergy - Louisville- Site Number : 8400007
Louisville
Kentucky
Velocity Clinical Research - Lafayette- Site Number : 8400026
Lafayette
Louisiana
Johns Hopkins Hospital- Site Number : 8400017
Baltimore
Maryland
University of Cincinnati Medical Center- Site Number : 8400022
Cincinnati
Ohio
Allergy, Asthma and Clinical Research- Site Number : 8400002
Oklahoma City
Oklahoma
Thomas Jefferson University Hospital- Site Number : 8400044
Philadelphia
Pennsylvania
Spartanburg-Greer ENT & Allergy- Site Number : 8400039
Greer
South Carolina
Ear and Sinus Institute- Site Number : 8400048
Fort Worth
Texas
Investigational Site Number : 0320005
San Miguel de Tucumán
Tucumán Province
Investigational Site Number : 0320002
Buenos Aires
Argentina
Investigational Site Number : 0320001
Buenos Aires
Argentina
Investigational Site Number : 0320004
Corrientes
Argentina
Investigational Site Number : 0320003
Mendoza
Argentina
Investigational Site Number : 0360003
Bella Vista
New South Wales
Investigational Site Number : 0360002
Brisbane
Queensland
Investigational Site Number : 0360001
Spearwood
Western Australia
Investigational Site Number : 0560004
Gesves
Namur
Investigational Site Number : 0560006
Alken
Belgium
Investigational Site Number : 0560002
Ghent
Belgium
Investigational Site Number : 0560001
Leuven
Belgium
Private Practice - Dr. Nelson Rosário- Site Number : 0760001
Curitiba
Paraná
Centro de Pesquisa Clínica de Marília - CPCLIM- Site Number : 0760002
Marília
São Paulo
Fundação Faculdade Regional de Medicina de São José do Rio Preto- Site Number : 0760005
São José do Rio Preto
São Paulo
Clinica de Alergia Martti Antila- Site Number : 0760003
Sorocaba
São Paulo
Investigational Site Number : 1240017
Vancouver
British Columbia
Investigational Site Number : 1240019
Burlington
Ontario
Investigational Site Number : 1240015
Cambridge
Ontario
Investigational Site Number : 1240014
Ottawa
Ontario
Investigational Site Number : 1240003
Québec
Quebec
Investigational Site Number : 1240012
Québec
Quebec
Investigational Site Number : 1520001
Concepción
Biobio
Investigational Site Number : 1520004
Talcahuano
Biobio
Investigational Site Number : 1520003
Santiago
Reg Metropolitana de Santiago
+ 71 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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