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

NCT06691113 | Active Not Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: ACT184212024-515576-12U1111-1306-6643
• Study Type: interventional
• Target: 66
• Locations: 13 countries
• Sites: 57

Brief Summary

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.

Conditions

Chronic Rhinosinusitis Without Nasal Polyps

Outcome Measures

Primary Outcomes (1)

• Change from baseline in sinus (maxillary, ethmoid) percent opacification volume assessed by CT scan

  Change from baseline in sinus inflammation as assessed by Computerized Tomography (CT) scan of the sinuses in the itepekimab-- compared to placebo-- treated study participants on the background of intranasal corticosteroid (INCS).

  Baseline to End of Treatment (EOT) (Week 24)

Secondary Outcomes (10)

• Change from baseline in the sTSS

  Baseline to EOT (Week 24)

• Change from baseline in nasal congestion (NC) severity score using the CRSsNP daily ediary

  Baseline to EOT (Week 24)

• Change from baseline in anterior/posterior rhinorrhea severity score using the CRSsNP daily ediary

  Baseline to EOT (Week 24)

• Change from baseline in facial pain/pressure severity score using the CRSsNP daily ediary

  Baseline to EOT (Week 24)

• Change from baseline in loss of smell severity score using the CRSsNP daily ediary

  Baseline to EOT (Week 24)

Study Arms (3)

Itepekimab high dose

EXPERIMENTAL

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

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

Itepekimab low dose

EXPERIMENTAL

SC administration of Itepekimab low dose for 24 weeks

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

Placebo

PLACEBO COMPARATOR

SC administration of matching placebo for 24 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:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (57)

Allervie Clinical Research - Birmingham- Site Number : 8400006

Birmingham, Alabama, 35209, United States

Location

Modena Allergy + Asthma- Site Number : 8400005

La Jolla, California, 92037, United States

Location

United Medical Doctors - Murrieta- Site Number : 8400001

Murrieta, California, 92563, United States

Location

Sacramento Ear Nose & Throat - Roseville- Site Number : 8400008

Roseville, California, 95661, United States

Location

Western States Clinical Research- Site Number : 8400009

Wheat Ridge, Colorado, 80033, United States

Location

Advanced Research Associates (ARA) Professionals- Site Number : 8400002

Miami, Florida, 33176, United States

Location

Treasure Valley Medical Research- Site Number : 8400022

Boise, Idaho, 83706, United States

Location

ENT Associates of Texas - McKinne- Site Number : 8400013

McKinney, Texas, 75070, United States

Location

Alamo ENT Associates- Site Number : 8400026

San Antonio, Texas, 78258, United States

Location

Eastern Virginia Medical School (EVMS) Medical Group- Site Number : 8400007

Norfolk, Virginia, 23510, United States

Location

Investigational Site Number : 0320003

San Miguel de Tucumán, Tucumán Province, 4000, Argentina

Location

Investigational Site Number : 0320001

Buenos Aires, 1425, Argentina

Location

Investigational Site Number : 0320004

Corrientes, 3400, Argentina

Location

Investigational Site Number : 0560003

Brussels, 1200, Belgium

Location

Investigational Site Number : 0560004

Gesves, 5340, Belgium

Location

Investigational Site Number : 0560002

Ghent, 9000, Belgium

Location

Investigational Site Number : 0560001

Leuven, 3000, Belgium

Location

Investigational Site Number : 1240005

London, Ontario, N6A 4V2, Canada

Location

Investigational Site Number : 1240002

Montreal, Quebec, H4A 3J1, Canada

Location

Investigational Site Number : 1240001

Québec, Quebec, G1V 4G5, 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 : 1240009

Trois-Rivières, Quebec, G8T 7A1, Canada

Location

Investigational Site Number : 1520002

Concepción, Biobio, 4070094, Chile

Location

Investigational Site Number : 1520001

Santiago, Reg Metropolitana de Santiago, 7500505, Chile

Location

Investigational Site Number : 1520003

Santiago, Reg Metropolitana de Santiago, 7500692, Chile

Location

Investigational Site Number : 1560004

Baotou, 014040, China

Location

Investigational Site Number : 1560001

Beijing, 100730, China

Location

Investigational Site Number : 1560002

Shanghai, 200127, China

Location

Investigational Site Number : 1560003

Zibo, 255036, China

Location

Investigational Site Number : 2500012

La Rochelle, 17019, France

Location

Investigational Site Number : 2500004

Marseille, 13005, France

Location

Investigational Site Number : 2500005

Montpellier, 34295, France

Location

Investigational Site Number : 2500010

Poitiers, 86021, France

Location

Fondazione Policlinico Universitario Campus Bio-Medico-Site Number : 3800002

Rome, Roma, 00128, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS-Site Number : 3800001

Rome, Roma, 00168, Italy

Location

Azienda Ospedaliero-Universitaria Pisana-Site Number : 3800003

Pisa, 56124, Italy

Location

Investigational Site Number : 6160002

Poznan, Greater Poland Voivodeship, 60-693, Poland

Location

Investigational Site Number : 6160006

Krakow, Lesser Poland Voivodeship, 31-513, Poland

Location

Investigational Site Number : 6160008

Lodz, Lódzkie, 90-302, Poland

Location

Investigational Site Number : 6160001

Warsaw, Masovian Voivodeship, 00-909, Poland

Location

Investigational Site Number : 6160004

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

Location

Investigational Site Number : 6200001

Guimarães, 4800-055, Portugal

Location

Investigational Site Number : 6200002

Porto, 3814-501, Portugal

Location

Investigational Site Number : 6420001

Brasov, 500283, Romania

Location

Investigational Site Number : 6420002

Bucharest, 022328, Romania

Location

Investigational Site Number : 4100005

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

Location

Investigational Site Number : 4100003

Seoul, Seoul-teukbyeolsi, 03080, South Korea

Location

Investigational Site Number : 4100004

Seoul, Seoul-teukbyeolsi, 03722, South Korea

Location

Investigational Site Number : 4100002

Seoul, Seoul-teukbyeolsi, 06351, South Korea

Location

Investigational Site Number : 4100001

Seoul, Seoul-teukbyeolsi, 07061, South Korea

Location

Investigational Site Number : 7240003

Barcelona, Barcelona [Barcelona], 08003, Spain

Location

Investigational Site Number : 7240002

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

Location

Investigational Site Number : 7240004

Jerez de la Frontera, Cádiz, 11407, Spain

Location

Investigational Site Number : 7240005

Pamplona, Navarre, 31008, Spain

Location

Investigational Site Number : 7240001

Seville, Sevilla, 41009, Spain

Location

Investigational Site Number : 7240006

Madrid, 28040, Spain

Location

Related Links

• ACT18421 Plain Language Results Summary

MeSH Terms

Interventions

itepekimab

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• 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: November 12, 2024
• First Posted: November 15, 2024
• Study Start: December 16, 2024
• Primary Completion: March 31, 2026
• Study Completion (Estimated): August 18, 2026
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

KR (5); ES (6); RO (2); AR (3); FR (4); CL (3); CN (4); IT (3); US (10); PL (5); PT (2); BE (4); CA (6)