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

NCT06834360 | Active Not Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: EFC184192024-516815-26U1111-1306-6544
• Study Type: interventional
• Target: 216
• Locations: 23 countries
• Sites: 111

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.

Conditions

Chronic Rhinosinusitis With Nasal Polyps

Outcome Measures

Primary Outcomes (2)

• Change from baseline in the endoscopic NPS

  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).

  Baseline to Week 24

• Change from baseline in the NCS

  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.

  Baseline to Week 24

Secondary Outcomes (22)

• Change from baseline in endoscopic NPS

  Baseline to Week 52

• Change from baseline in NCS

  Baseline to Week 52

• Change from baseline in opacification of sinuses assessed by Computed Tomography (CT) scan using the LMK score

  Baseline to Week 24

• Change from baseline in the TSS (nasal congestion/obstruction, anterior/posterior rhinorrhea, and loss of sense of smell)

  Baseline to Weeks 24 and 52

• Change from baseline in loss of smell severity score using the daily CRSwNP sinonasal symptom eDiary, and UPSIT score

  Baseline to Weeks 24 and 52

Study Arms (3)

Itepekimab high dose

EXPERIMENTAL

Subcutaneous (SC) administration of Itepekimab high dose for 52 weeks

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

Itepekimab low dose

EXPERIMENTAL

SC administration of Itepekimab low dose for 52 weeks

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

Placebo

PLACEBO COMPARATOR

SC administration of matching placebo for 52 weeks

Drug: Placebo; Drug: Mometasone furoate nasal spray (MFNS)

Interventions

Itepekimab (SAR440340) DRUG

Pharmaceutical form: Solution for injection in prefilled syringe. Route of administration: Subcutaneous

Also known as: REGN3500

Itepekimab high dose; Itepekimab low dose

Placebo DRUG

Pharmaceutical form: Solution for injection in prefilled syringe. Route of administration: Subcutaneous

Itepekimab low dose; Placebo

Mometasone furoate nasal spray (MFNS) DRUG

Pharmaceutical form: Solution for administration via spray pump. Route of administration: Intranasal spray

Itepekimab high dose; Itepekimab low dose; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (111)

Excel ENT of Alabama- Site Number : 8400052

Birmingham, Alabama, 35244, United States

Location

Velocity Clinical Research - San Diego- Site Number : 8400041

La Mesa, California, 91942, United States

Location

Cedars-Sinai Medical Center- Site Number : 8400030

Los Angeles, California, 90048, United States

Location

One Of A Kind Clinical Research Center- Site Number : 8400034

Napa, California, 94558, United States

Location

University of Florida - Jacksonville- Site Number : 8400053

Jacksonville, Florida, 32209, United States

Location

Advanced Research Institute - New Port Richey- Site Number : 8400014

New Port Richey, Florida, 34653, United States

Location

University of Illinois at Chicago- Site Number : 8400003

Chicago, Illinois, 60607, United States

Location

Advanced ENT & Allergy - Louisville- Site Number : 8400007

Louisville, Kentucky, 40220, United States

Location

Velocity Clinical Research - Lafayette- Site Number : 8400026

Lafayette, Louisiana, 70508, United States

Location

Johns Hopkins Hospital- Site Number : 8400017

Baltimore, Maryland, 21287, United States

Location

University of Cincinnati Medical Center- Site Number : 8400022

Cincinnati, Ohio, 45219, United States

Location

Allergy, Asthma and Clinical Research- Site Number : 8400002

Oklahoma City, Oklahoma, 73120, United States

Location

Thomas Jefferson University Hospital- Site Number : 8400044

Philadelphia, Pennsylvania, 19107, United States

Location

Spartanburg-Greer ENT & Allergy- Site Number : 8400039

Greer, South Carolina, 29650, United States

Location

Ear and Sinus Institute- Site Number : 8400048

Fort Worth, Texas, 76104, United States

Location

Investigational Site Number : 0320005

San Miguel de Tucumán, Tucumán Province, 4000, Argentina

Location

Investigational Site Number : 0320002

Buenos Aires, 1121, Argentina

Location

Investigational Site Number : 0320001

Buenos Aires, 1414, Argentina

Location

Investigational Site Number : 0320004

Corrientes, 3400, Argentina

Location

Investigational Site Number : 0320003

Mendoza, 5500, Argentina

Location

Investigational Site Number : 0360003

Bella Vista, New South Wales, 2153, Australia

Location

Investigational Site Number : 0360002

Brisbane, Queensland, 4029, Australia

Location

Investigational Site Number : 0360001

Spearwood, Western Australia, 6163, Australia

Location

Investigational Site Number : 0560004

Gesves, Namur, 5340, Belgium

Location

Investigational Site Number : 0560006

Alken, 3570, Belgium

Location

Investigational Site Number : 0560002

Ghent, 9000, Belgium

Location

Investigational Site Number : 0560001

Leuven, 3000, Belgium

Location

Private Practice - Dr. Nelson Rosário- Site Number : 0760001

Curitiba, Paraná, 80810-100, Brazil

Location

Centro de Pesquisa Clínica de Marília - CPCLIM- Site Number : 0760002

Marília, São Paulo, 17504-072, Brazil

Location

Fundação Faculdade Regional de Medicina de São José do Rio Preto- Site Number : 0760005

São José do Rio Preto, São Paulo, 15090-000, Brazil

Location

Clinica de Alergia Martti Antila- Site Number : 0760003

Sorocaba, São Paulo, 18040-425, Brazil

Location

Investigational Site Number : 1240017

Vancouver, British Columbia, V6A 2W1, Canada

Location

Investigational Site Number : 1240019

Burlington, Ontario, L7R 3P9, Canada

Location

Investigational Site Number : 1240015

Cambridge, Ontario, N1R 8L4, Canada

Location

Investigational Site Number : 1240014

Ottawa, Ontario, K1G 6C6, Canada

Location

Investigational Site Number : 1240003

Québec, Quebec, G1V 4W2, Canada

Location

Investigational Site Number : 1240012

Québec, Quebec, G2J 0C4, Canada

Location

Investigational Site Number : 1520001

Concepción, Biobio, 4070094, Chile

Location

Investigational Site Number : 1520004

Talcahuano, Biobio, 2687000, Chile

Location

Investigational Site Number : 1520003

Santiago, Reg Metropolitana de Santiago, 7500505, Chile

Location

Investigational Site Number : 1520002

Quillota, Valparaiso, 2260877, Chile

Location

Investigational Site Number : 1560020

Baotou, 014040, China

Location

Investigational Site Number : 1560001

Beijing, 100730, China

Location

Investigational Site Number : 1560004

Chengdu, 610017, China

Location

Investigational Site Number : 1560025

Chongqing, 400016, China

Location

Investigational Site Number : 1560019

Hangzhou, 310003, China

Location

Investigational Site Number : 1560002

Jinan, 250022, China

Location

Investigational Site Number : 1560012

Jingzhou, 434020, China

Location

Investigational Site Number : 1560021

Nanning, 530021, China

Location

Investigational Site Number : 1560006

Shenyang, 110004, China

Location

Investigational Site Number : 1560024

Suzhou, 215006, China

Location

Investigational Site Number : 1560017

Taiyuan, 030001, China

Location

Investigational Site Number : 1560023

Taiyuan, 030001, China

Location

Investigational Site Number : 1560014

Wuhan, 430060, China

Location

Investigational Site Number : 1560003

Yantai, 264001, China

Location

Investigational Site Number : 1560009

Zibo, 255036, China

Location

Investigational Site Number : 2030002

Hradec Králové, 500 05, Czechia

Location

Investigational Site Number : 2030003

Pardubice, 532 03, Czechia

Location

Investigational Site Number : 2030005

Pilsen, 305 99, Czechia

Location

Investigational Site Number : 2030004

Prague, 100 34, Czechia

Location

Investigational Site Number : 2030001

Prague, 150 06, Czechia

Location

Investigational Site Number : 2080001

Aarhus, 8200, Denmark

Location

Investigational Site Number : 2080004

Copenhagen, 2100, Denmark

Location

Investigational Site Number : 2080002

Køge, 4600, Denmark

Location

Investigational Site Number : 2500011

Bordeaux, 33076, France

Location

Investigational Site Number : 2500004

Marseille, 13005, France

Location

Investigational Site Number : 2500001

Nantes, 44093, France

Location

Investigational Site Number : 2500010

Poitiers, 86021, France

Location

Investigational Site Number : 2500014

Pontoise, 95300, France

Location

Investigational Site Number : 2500007

Toulouse, 31059, France

Location

Investigational Site Number : 2760006

Dresden, 01139, Germany

Location

Investigational Site Number : 2760001

Dresden, 01307, Germany

Location

Investigational Site Number : 2760005

Hamburg, 20246, Germany

Location

Investigational Site Number : 2760002

Leipzig, 04103, Germany

Location

Investigational Site Number : 2760007

Mainz, 55131, Germany

Location

Investigational Site Number : 2760008

Villingen-Schwenningen, 78052, Germany

Location

Investigational Site Number : 3480005

Budapest, 1026, Hungary

Location

Investigational Site Number : 3480001

Szeged, 6720, Hungary

Location

Investigational Site Number : 3760003

Haifa, 3104802, Israel

Location

Investigational Site Number : 3760004

Jerusalem, 9112001, Israel

Location

Investigational Site Number : 3760001

Nahariya, 2210001, Israel

Location

Investigational Site Number : 3760002

Rehovot, 7610001, Israel

Location

Investigational Site Number : 3800001

Milan, Milano, 20132, Italy

Location

Investigational Site Number : 3800005

Naples, Napoli, 80131, Italy

Location

Investigational Site Number : 3800003

Catania, 95123, Italy

Location

Investigational Site Number : 2500005

Toyama, 939-2716, Japan

Location

Investigational Site Number : 4840001

Guadalajara, Jalisco, 44100, Mexico

Location

Investigational Site Number : 4840008

Monterrey, Nuevo León, 64718, Mexico

Location

Investigational Site Number : 4840007

Chihuahua City, 31217, Mexico

Location

Investigational Site Number : 4840002

Veracruz, 91900, Mexico

Location

Investigational Site Number : 5280002

Amsterdam, 1081 HV, Netherlands

Location

Investigational Site Number : 5280001

Utrecht, 3584 CX, Netherlands

Location

Investigational Site Number : 6160004

Poznan, Greater Poland Voivodeship, 60-693, Poland

Location

Investigational Site Number : 6160005

Wroclaw, Lower Silesian Voivodeship, 50-750, Poland

Location

Investigational Site Number : 6160002

Lodz, Lódzkie, 90-302, Poland

Location

Investigational Site Number : 6160001

Bielsko-Biala, Silesian Voivodeship, 43-300, Poland

Location

Investigational Site Number : 6420003

Brasov, 500091, Romania

Location

Investigational Site Number : 6420002

Brasov, 500283, Romania

Location

Investigational Site Number : 6420001

Bucharest, 022328, Romania

Location

Investigational Site Number : 7240006

Barcelona, Barcelona [Barcelona], 08003, Spain

Location

Investigational Site Number : 7240002

Santander, Cantabria, 39008, Spain

Location

Investigational Site Number : 7240004

L'Hospitalet de Llobregat, Catalunya [Cataluña], 08907, Spain

Location

Investigational Site Number : 7240008

Pamplona, Navarre, 31008, Spain

Location

Investigational Site Number : 7240010

Madrid, 28034, Spain

Location

Investigational Site Number : 7240012

Madrid, 28040, Spain

Location

Investigational Site Number : 7920003

Ankara, 06230, Turkey (Türkiye)

Location

Investigational Site Number : 7920001

Bursa, 16059, Turkey (Türkiye)

Location

Investigational Site Number : 7920002

Istanbul, 34360, Turkey (Türkiye)

Location

Investigational Site Number : 8260002

Wigan, Lancashire, Wn6 9ep, United Kingdom

Location

Investigational Site Number : 8260001

London, London, City of, W2 1NY, United Kingdom

Location

Investigational Site Number : 8260003

Taunton, Somerset, TA1 5DA, United Kingdom

Location

Related Links

• EFC18419 Plain Language Results Summary

MeSH Terms

Interventions

itepekimab

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2025
• First Posted: February 19, 2025
• Study Start: February 6, 2025
• Primary Completion (Estimated): November 6, 2026
• Study Completion (Estimated): October 11, 2027
• Last Updated: June 2, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share

Locations

CA (6); HU (2); JP (1); ME (4); AU (3); BR (4); CL (4); CN (15); TU (3); GB (3); DK (3); IT (3); NL (2); IL (4); FR (6); DE (6); RO (3); ES (6); US (15); CZ (5); BE (4); PL (4); AR (5)