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

NCT06834347 | Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: EFC184182024-516814-39U1111-1306-4858
• Study Type: interventional
• Target: 210
• Locations: 21 countries
• Sites: 121

Brief Summary

EFC18418 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 (121)

University of Southern California (USC) / Keck Medicine of USC- Site Number : 8400037

Arcadia, California, 91006, United States

RECRUITING

Sensa Health- Site Number : 8400038

Los Angeles, California, 90006, United States

RECRUITING

Newport Native MD- Site Number : 8400031

Newport Beach, California, 92663, United States

RECRUITING

Sacramento Ear Nose & Throat - Roseville- Site Number : 8400064

Roseville, California, 95661, United States

RECRUITING

Breathe Clear Institute of Sinus and Allergy Relief- Site Number : 8400040

Torrance, California, 90503, United States

RECRUITING

Orso Health - Torrance - Hawthorne Boulevard- Site Number : 8400035

Torrance, California, 90505, United States

RECRUITING

Advanced Research Associates (ARA) Professionals- Site Number : 8400011

Miami, Florida, 33176, United States

RECRUITING

Paradisus Med Research - Miami- Site Number : 8400009

Miami, Florida, 33185, United States

RECRUITING

Orlando ENT Associates - Orlando- Site Number : 8400008

Orlando, Florida, 32807, United States

RECRUITING

Emory University School of Medicine- Grady Campus- Site Number : 8400047

Atlanta, Georgia, 30303, United States

RECRUITING

Treasure Valley Medical Research- Site Number : 8400063

Boise, Idaho, 83706, United States

RECRUITING

University of Chicago Medical Center- Site Number : 8400018

Chicago, Illinois, 60637, United States

RECRUITING

Deaconess Clinic Allergy East- Site Number : 8400056

Evansville, Indiana, 47715, United States

RECRUITING

SSM Health Saint Louis University Hospital- Site Number : 8400005

St Louis, Missouri, 63104, United States

RECRUITING

Northwell Health Physician Partners Rheumatology at Great Neck- Site Number : 8400028

Great Neck, New York, 11021, United States

RECRUITING

Essential Medical Research- Site Number : 8400066

Tulsa, Oklahoma, 74137, United States

RECRUITING

TEN20 Clinical Research - Dallas- Site Number : 8400015

Dallas, Texas, 75244, United States

RECRUITING

Houston Methodist Hospital- Site Number : 8400054

Houston, Texas, 77030, United States

RECRUITING

ENT Associates of Texas - McKinne- Site Number : 8400062

McKinney, Texas, 75070, United States

RECRUITING

Alamo ENT Associates- Site Number : 8400065

San Antonio, Texas, 78258, United States

RECRUITING

Eastern Virginia Medical School (EVMS) Medical Group- Site Number : 8400046

Norfolk, Virginia, 23510, United States

RECRUITING

Investigational Site Number : 0320002

La Plata, Buenos Aires, 1900, Argentina

RECRUITING

Investigational Site Number : 0320004

Rosario, Santa Fe Province, 2000, Argentina

RECRUITING

Investigational Site Number : 0320001

Buenos Aires, 1425, Argentina

RECRUITING

Investigational Site Number : 0320005

Buenos Aires, 1638, Argentina

RECRUITING

Investigational Site Number : 0320003

Mendoza, 5500, Argentina

RECRUITING

Investigational Site Number : 0400005

Graz, 8036, Austria

RECRUITING

Investigational Site Number : 0400002

Linz, 4010, Austria

RECRUITING

Investigational Site Number : 0400001

Vienna, 1090, Austria

RECRUITING

Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto- Site Number : 0760002

Ribeirão Preto, São Paulo, 14049-900, Brazil

RECRUITING

Centro Internacional de Pesquisa Clínica (CIPES)- Site Number : 0760005

São José dos Campos, São Paulo, 12230-001, Brazil

RECRUITING

Hospital Israelita Albert Einstein- Site Number : 0760001

São Paulo, 05651-901, Brazil

RECRUITING

Investigational Site Number : 1240005

London, Ontario, N6A 4V2, Canada

RECRUITING

Investigational Site Number : 1240002

Montreal, Quebec, H4a 3j1, Canada

RECRUITING

Investigational Site Number : 1240001

Québec, Quebec, G1V 4G5, Canada

RECRUITING

Investigational Site Number : 1520006

Valdivia, Los Ríos Region, 5110683, Chile

RECRUITING

Investigational Site Number : 1520003

Talca, Maule Region, 3465584, Chile

RECRUITING

Investigational Site Number : 1520004

Lo Barnechea, Reg Metropolitana de Santiago, 7691236, Chile

RECRUITING

Investigational Site Number : 1520002

Santiago, Reg Metropolitana de Santiago, 7500692, Chile

RECRUITING

Investigational Site Number : 1520001

Santiago, Reg Metropolitana de Santiago, 8207257, Chile

RECRUITING

Investigational Site Number : 1520005

Viña del Mar, Valparaiso, 2540364, Chile

RECRUITING

Investigational Site Number : 2460004

Helsinki, 00029, Finland

RECRUITING

Investigational Site Number : 2460003

Helsinki, 00130, Finland

RECRUITING

Investigational Site Number : 2460002

Kuopio, 70210, Finland

RECRUITING

Investigational Site Number : 2760004

Berlin, 10117, Germany

RECRUITING

Investigational Site Number : 2760007

Frankfurt, 60318, Germany

RECRUITING

Investigational Site Number : 2760008

Hamburg, 22523, Germany

RECRUITING

Investigational Site Number : 2760009

Landsberg, 06188, Germany

RECRUITING

Investigational Site Number : 2760002

Münster, 48149, Germany

RECRUITING

Investigational Site Number : 2760001

Tübingen, 72076, Germany

RECRUITING

Investigational Site Number : 2760005

Wiesbaden, 65205, Germany

RECRUITING

Investigational Site Number : 2760003

Würzburg, 97080, Germany

RECRUITING

Investigational Site Number : 3480002

Budapest, 1046, Hungary

RECRUITING

Investigational Site Number : 3480004

Debrecen, 4032, Hungary

RECRUITING

Investigational Site Number : 3480003

Nyíregyháza, 4400, Hungary

ACTIVE NOT RECRUITING

Investigational Site Number : 3480001

Pécs, 7621, Hungary

RECRUITING

Investigational Site Number : 3760007

Haifa, 3436212, Israel

RECRUITING

Investigational Site Number : 3760004

Kefar Sava, 4428164, Israel

RECRUITING

Investigational Site Number : 3760005

Petah Tikva, 4941492, Israel

RECRUITING

Investigational Site Number : 3760009

Tel Aviv, 6423906, Israel

RECRUITING

Azienda Ospedaliero-Universitaria di Ferrara-Site Number: 3800004

Cona, Ferrara, 44124, Italy

RECRUITING

Azienda Ospedaliera Universitaria Careggi-Site Number : 3800011

Florence, Firenze, 50134, Italy

RECRUITING

IRCCS Ospedale Policlinico San Martino-Site Number : 3800013

Genoa, Genova, 16132, Italy

RECRUITING

ASST Santi Paolo e Carlo-Presidio Ospedale San Paolo-Site Number : 3800006

Milan, Milano, 20142, Italy

RECRUITING

Azienda Ospedale - Università Padova-Site Number : 3800008

Padua, Padova, 35128, Italy

RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli IRCCS-Site Number: 3800002

Rome, Roma, 00168, Italy

RECRUITING

Ospedale Bellaria-Site Number: 3800009

Bologna, 40139, Italy

RECRUITING

Investigational Site Number : 3920010

Ichikawa, Chiba, 272-0143, Japan

RECRUITING

Investigational Site Number : 3920004

Narita, Chiba, 286-8520, Japan

RECRUITING

Investigational Site Number : 3920009

Isehara, Kanagawa, 259-1193, Japan

RECRUITING

Investigational Site Number : 3920002

Odawara, Kanagawa, 250-8558, Japan

ACTIVE NOT RECRUITING

Investigational Site Number : 3920014

Yokohama, Kanagawa, 236-0037, Japan

RECRUITING

Investigational Site Number : 3920005

Suwa, Nagano, 392-0027, Japan

RECRUITING

Investigational Site Number : 3920012

Kusatsu, Shiga, 525-0066, Japan

RECRUITING

Investigational Site Number : 3920006

Fukui, 910-1104, Japan

RECRUITING

Investigational Site Number : 3920001

Fukuoka, 812-0053, Japan

RECRUITING

Investigational Site Number : 3920011

Hiroshima, 734-0004, Japan

RECRUITING

Investigational Site Number : 3920003

Kumamoto, 860-0814, Japan

ACTIVE NOT RECRUITING

Investigational Site Number : 3920013

Niigata, 951-8520, Japan

RECRUITING

Investigational Site Number : 3920008

Tokyo, 153-8515, Japan

RECRUITING

Investigational Site Number : 4840004

Chihuahua City, 31000, Mexico

RECRUITING

Investigational Site Number : 4840003

Durango, 34000, Mexico

RECRUITING

Investigational Site Number : 5280004

Alkmaar, 1815 JD, Netherlands

RECRUITING

Investigational Site Number : 5280002

Leiderdorp, 2353 GA, Netherlands

RECRUITING

Investigational Site Number : 6160006

Krakow, Lesser Poland Voivodeship, 31-513, Poland

RECRUITING

Investigational Site Number : 6160001

Wroclaw, Lower Silesian Voivodeship, 53-149, Poland

RECRUITING

Investigational Site Number : 6160004

Wroclaw, Lower Silesian Voivodeship, 53-301, Poland

RECRUITING

Investigational Site Number : 6160005

Lublin, Lublin Voivodeship, 20-363, Poland

RECRUITING

Investigational Site Number : 6160002

Warsaw, Masovian Voivodeship, 00-909, Poland

RECRUITING

Investigational Site Number : 6160003

Bialystok, Podlaskie Voivodeship, 15-756, Poland

RECRUITING

Investigational Site Number : 6200003

Guimarães, 4800-055, Portugal

RECRUITING

Investigational Site Number : 6200004

Matosinhos Municipality, 4464-513, Portugal

RECRUITING

Investigational Site Number : 6200002

Porto, 3814-501, Portugal

RECRUITING

Investigational Site Number : 6200001

Santa Maria da Feira, 4520-211, Portugal

RECRUITING

Investigational Site Number : 4100005

Cheonan-Si, Chungcheongnam-do, 31116, South Korea

RECRUITING

Investigational Site Number : 4100009

Seongnam-si, Gyeonggi-do, 13620, South Korea

RECRUITING

Investigational Site Number : 4100008

Incheon, Incheon-gwangyeoksi, 21565, South Korea

RECRUITING

Investigational Site Number : 4100003

Seoul, Seoul-teukbyeolsi, 03080, South Korea

RECRUITING

Investigational Site Number : 4100004

Seoul, Seoul-teukbyeolsi, 03722, South Korea

RECRUITING

Investigational Site Number : 4100002

Seoul, Seoul-teukbyeolsi, 06351, South Korea

RECRUITING

Investigational Site Number : 4100001

Seoul, Seoul-teukbyeolsi, 07061, South Korea

RECRUITING

Investigational Site Number : 4100006

Seoul, 02841, South Korea

RECRUITING

Investigational Site Number : 7240007

Santiago de Compostela, A Coruña [La Coruña], 15702, Spain

RECRUITING

Investigational Site Number : 7240003

Santiago de Compostela, A Coruña [La Coruña], 15706, Spain

RECRUITING

Investigational Site Number : 7240008

Barcelona, Barcelona [Barcelona], 08022, Spain

RECRUITING

Investigational Site Number : 7240002

Barcelona, Catalunya [Cataluña], 08036, Spain

RECRUITING

Investigational Site Number : 7240004

Jerez de la Frontera, Cádiz, 11407, Spain

RECRUITING

Investigational Site Number : 7240001

Majadahonda, Madrid, 28222, Spain

RECRUITING

Investigational Site Number : 7240006

Seville, Sevilla, 41009, Spain

RECRUITING

Investigational Site Number : 7240009

Sabadell, 08208, Spain

RECRUITING

Investigational Site Number : 7240005

Zaragoza, 50009, Spain

RECRUITING

Investigational Site Number : 7520002

Lund, 221 85, Sweden

RECRUITING

Investigational Site Number : 7520001

Solna, 171 64, Sweden

RECRUITING

Investigational Site Number : 7520004

Stockholm, 114 86, Sweden

RECRUITING

Investigational Site Number : 7920003

Ankara, 06230, Turkey (Türkiye)

RECRUITING

Investigational Site Number : 7920001

Istanbul, 34093, Turkey (Türkiye)

RECRUITING

Investigational Site Number : 7920002

Istanbul, 34865, Turkey (Türkiye)

RECRUITING

Investigational Site Number : 8260002

London, London, City of, NW1 2BU, United Kingdom

RECRUITING

Investigational Site Number : 8260006

Oxford, Oxfordshire, OX3 9DU, United Kingdom

RECRUITING

Investigational Site Number : 8260004

Bradford, BD9 6RJ, United Kingdom

RECRUITING

Investigational Site Number : 8260001

Newcastle upon Tyne, NE7 7DN, United Kingdom

RECRUITING

Related Links

• EFC18418 Plain Language Results Summary

MeSH Terms

Interventions

itepekimab

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Central Study Contacts

Trial Transparency email recommended (Toll free for US & Canada)

CONTACT

800-633-1610; contact-us@sanofi.com

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 12, 2025
• Primary Completion (Estimated): January 8, 2027
• Study Completion (Estimated): December 13, 2027
• Last Updated: April 28, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

CA (3); HU (4); BR (3); KR (8); SE (3); JP (13); PL (6); ME (2); CL (6); US (21); AU (3); FI (3); DE (8); ES (9); PT (4); IL (4); GB (4); AR (5); TU (3); NL (2); IT (7)