A Proof-of-Concept Study to Assess the Efficacy, Safety and Tolerability of Itepekimab (Anti-IL-33 mAb) in Participants With Non-cystic Fibrosis Bronchiectasis

A Randomized, Double-blind, Placebo-controlled, Parallel-group, Proof-of-Concept (PoC) Study to Assess the Efficacy, Safety and Tolerability of Itepekimab, in Participants With Non-cystic Fibrosis Bronchiectasis

ACT18018 is a multinational, randomized, double-blind, placebo-controlled, parallel-group, Phase 2 study with 3 treatment groups. The purpose of this study is to evaluate efficacy, safety and tolerability with 2 dosing regimens of itepekimab compared with placebo in male and/or female participants with NCFB aged 18 years of age up to 85 years of age (inclusive).

Study details include:

• The study duration (screening, 24-52-week treatment, 20-week safety follow-up) will be up to 47-77 weeks.
• The treatment duration will be up to 24-52 weeks.
• The follow-up duration will be 20 weeks.
• Site/phone visits are at a monthly interval.

Study Overview

• Status: Completed
• Conditions: Bronchiectasis
• Intervention / Treatment: Drug: Itepekimab (SAR440340); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 312
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1121
    • Investigational Site Number : 0320003
  • Buenos Aires, Argentina, 1280
    • Investigational Site Number : 0320008
  • Buenos Aires, Argentina, 1414
    • Investigational Site Number : 0320001
  • Buenos Aires, Argentina, 1427
    • Investigational Site Number : 0320004
  • Córdoba, Argentina, 5003
    • Investigational Site Number : 0320007
  • Mendoza, Argentina, 5500
    • Investigational Site Number : 0320006
  • San Miguel de Tucumán, Argentina, 4000
    • Investigational Site Number : 0320005
  • Buenos Aires
    • La Plata, Buenos Aires, Argentina, 1900
      • Investigational Site Number : 0320002
• Brazil
  • São Paulo, Brazil, 05403-900
    • Incor - Instituto do Coracao- Site Number : 0760002
  • Minas Gerais
    • Uberlândia, Minas Gerais, Brazil, 38411-186
      • Oncoclínicas UMC- Site Number : 0760007
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90020-090
      • Irmandade da Santa Casa de Misericórdia de Porto Alegre- Site Number : 0760005
    • Porto Alegre, Rio Grande do Sul, Brazil, 90610-000
      • Hospital São Lucas da PUCRS - Porto Alegre - Avenida Ipiranga- Site Number : 0760001
    • Porto Alegre, Rio Grande do Sul, Brazil, 91010-006
      • WM Pesquisas Clínicas em Doenças Respiratórias- Site Number : 0760004
• Canada
  • Ontario
    • Guelph, Ontario, Canada, N1H 6J2
      • Investigational Site Number : 1240003
  • Quebec
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Investigational Site Number : 1240005
    • Trois-Rivières, Quebec, Canada, G8T 7A1
      • Investigational Site Number : 1240001
• Chile
  • Maule Region
    • Talca, Maule Region, Chile, 3465584
      • Investigational Site Number : 1520001
  • Reg Metropolitana de Santiago
    • Santiago, Reg Metropolitana de Santiago, Chile, 7500587
      • Investigational Site Number : 1520003
    • Santiago, Reg Metropolitana de Santiago, Chile, 7500692
      • Investigational Site Number : 1520002
  • Región de Valparaíso
    • Quillota, Región de Valparaíso, Chile, 2260877
      • Investigational Site Number : 1520004
• China
  • Beijing, China, 100020
    • Investigational Site Number : 1560005
  • Changchun, China, 130021
    • Investigational Site Number : 1560008
  • Chengdu, China, 610041
    • Investigational Site Number : 1560004
  • Guangzhou, China, 510120
    • Investigational Site Number : 1560001
  • Shanghai, China, 200025
    • Investigational Site Number : 1560006
  • Shanghai, China, 200433
    • Investigational Site Number : 1560002
  • Shenyang, China, 110004
    • Investigational Site Number : 1560007
  • Xuzhou, China, 221006
    • Investigational Site Number : 1560003
• Czechia
  • Jindřichův Hradec, Czechia, 377 01
    • Investigational Site Number : 2030002
  • Kralupy nad Vltavou, Czechia, 278 01
    • Investigational Site Number : 2030004
  • Pilsen, Czechia, 305 99
    • Investigational Site Number : 2030003
  • Prague, Czechia, 190 00
    • Investigational Site Number : 2030005
  • Český Krumlov, Czechia, 381 01
    • Investigational Site Number : 2030006
• Denmark
  • Aalborg, Denmark, 9000
    • Investigational Site Number : 2080002
  • Aarhus, Denmark, 8200
    • Investigational Site Number : 2080005
  • Odense, Denmark, 5000
    • Investigational Site Number : 2080004
  • Vejle, Denmark, 7100
    • Investigational Site Number : 2080001
• France
  • Brest, France, 29200
    • Investigational Site Number : 2500005
  • Lyon, France, 69004
    • Investigational Site Number : 2500001
  • Montpellier, France, 34090
    • Investigational Site Number : 2500002
  • Nice, France, 06001
    • Investigational Site Number : 2500004
  • Paris, France, 75679
    • Investigational Site Number : 2500003
  • Saint-Herblain, France, 44800
    • Investigational Site Number : 2500006
• Germany
  • Ahrensburg, Germany, 22926
    • Investigational Site Number : 2760001
  • Bendorf, Germany, 56170
    • Investigational Site Number : 2760005
  • Berlin, Germany, 12159
    • Investigational Site Number : 2760010
  • Cottbus, Germany, 03050
    • Investigational Site Number : 2760009
  • Essen, Germany, 45239
    • Investigational Site Number : 2760007
  • Frankfurt, Germany, 60596
    • Investigational Site Number : 2760003
  • Lübeck, Germany, 23552
    • Investigational Site Number : 2760004
  • Mainz, Germany, 55128
    • Investigational Site Number : 2760002
  • Munich, Germany, 80337
    • Investigational Site Number : 2760011
• Greece
  • Ioannina, Greece, 455 00
    • Investigational Site Number : 3000001
  • Thessaloniki, Greece, 570 10
    • Investigational Site Number : 3000003
• Israel
  • Ashkelon, Israel, 7830604
    • Investigational Site Number : 3760008
  • Haifa, Israel, 3436212
    • Investigational Site Number : 3760006
  • Jerusalem, Israel, 9103102
    • Investigational Site Number : 3760003
  • Jerusalem, Israel, 9112001
    • Investigational Site Number : 3760001
  • Petah Tikva, Israel, 4941492
    • Investigational Site Number : 3760002
  • Ramat Gan, Israel, 5262100
    • Investigational Site Number : 3760009
  • Rehovot, Israel, 7610001
    • Investigational Site Number : 3760004
  • Tel Aviv, Israel, 6423906
    • Investigational Site Number : 3760007
  • Tel Aviv, Israel, 6789140
    • Investigational Site Number : 3760010
• Italy
  • Palermo, Italy, 90127
    • Investigational Site Number : 3800004
  • Pavia, Italy, 27100
    • Investigational Site Number : 3800003
  • Reggio Emilia, Italy, 42123
    • Investigational Site Number : 3800006
  • Lombardy
    • Milan, Lombardy, Italy, 20122
      • Investigational Site Number : 3800001
  • Milano
    • Rozzano, Milano, Italy, 20089
      • Investigational Site Number : 3800002
• Japan
  • Tokyo, Japan, 140-8522
    • Investigational Site Number : 3920001
  • Tokyo, Japan, 162-8655
    • Investigational Site Number : 3920003
  • Chiba
    • Kamogawa, Chiba, Japan, 296-0041
      • Investigational Site Number : 3920002
  • Hyōgo
    • Himeji, Hyōgo, Japan, 670-0849
      • Investigational Site Number : 3920004
  • Tokyo
    • Kiyose, Tokyo, Japan, 204-8522
      • Investigational Site Number : 3920005
• Netherlands
  • Alkmaar, Netherlands, 1815 JD
    • Investigational Site Number : 5280002
  • Amsterdam, Netherlands, 1105 AZ
    • Investigational Site Number : 5280005
  • Breda, Netherlands, 4818 CK
    • Investigational Site Number : 5280004
  • Rotterdam, Netherlands, 3015 CE
    • Investigational Site Number : 5280001
  • The Hague, Netherlands, 2545 CH
    • Investigational Site Number : 5280003
• Poland
  • Lodz, Poland, 90-302
    • Investigational Site Number : 6160003
  • Wejherowo, Poland, 84-200
    • Investigational Site Number : 6160006
  • Lódzkie
    • Lodz, Lódzkie, Poland, 90-153
      • Investigational Site Number : 6160005
  • Podlaskie Voivodeship
    • Bialystok, Podlaskie Voivodeship, Poland, 15-044
      • Investigational Site Number : 6160001
  • Świętokrzyskie Voivodeship
    • Ostrowiec Świętokrzyski, Świętokrzyskie Voivodeship, Poland, 27-400
      • Investigational Site Number : 6160002
• Spain
  • Barcelona [Barcelona]
    • Barcelona, Barcelona [Barcelona], Spain, 08036
      • Investigational Site Number : 7240006
    • Barcelona, Barcelona [Barcelona], Spain, 08035
      • Investigational Site Number : 7240003
    • Barcelona, Barcelona [Barcelona], Spain, 08017
      • Investigational Site Number : 7240007
    • L'Hospitalet de Llobregat, Barcelona [Barcelona], Spain, 08907
      • Investigational Site Number : 7240001
  • Girona [Gerona]
    • Girona, Girona [Gerona], Spain, 17005
      • Investigational Site Number : 7240012
  • Madrid, Comunidad de
    • Madrid, Madrid, Comunidad de, Spain, 28007
      • Investigational Site Number : 7240002
• Taiwan
  • Kaohsiung City, Taiwan, 807
    • Investigational Site Number : 1580005
  • New Taipei City, Taiwan, 220
    • Investigational Site Number : 1580002
  • Taichung, Taiwan, 404
    • Investigational Site Number : 1580006
  • Taipei, Taiwan, 100
    • Investigational Site Number : 1580004
  • Taipei, Taiwan, 110
    • Investigational Site Number : 1580003
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01330
    • Investigational Site Number : 7920003
  • Akdeniz, Turkey (Türkiye), 33070
    • Investigational Site Number : 7920002
  • Ankara, Turkey (Türkiye), 06620
    • Investigational Site Number : 7920005
  • Istanbul, Turkey (Türkiye), 34093
    • Investigational Site Number : 7920001
  • Samsun, Turkey (Türkiye), 55139
    • Investigational Site Number : 7920006
  • İzmit, Turkey (Türkiye), 41001
    • Investigational Site Number : 7920004
• United Kingdom
  • Lancaster, United Kingdom, LA1 4RP
    • Investigational Site Number : 8260004
  • Newcastle upon Tyne, United Kingdom, NE7 7DN
    • Investigational Site Number : 8260001
  • Reading, United Kingdom, RG1 5AN
    • Investigational Site Number : 8260005
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB23 3RE
      • Investigational Site Number : 8260009
  • Norfolk
    • Norwich, Norfolk, United Kingdom, NR4 7UY
      • Investigational Site Number : 8260008
  • North Tyneside
    • North Shields, North Tyneside, United Kingdom, NE29 8NH
      • Investigational Site Number : 8260003
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham- Site Number : 8400040
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Pulmonary Associates - Phoenix - East McDowell Road- Site Number : 8400012
  • California
    • Los Angeles, California, United States, 90048
      • Southern California Institute for Respiratory Diseases- Site Number : 8400002
    • San Diego, California, United States, 92120
      • Institute Healthcare Assessment- Site Number : 8400037
    • Westminster, California, United States, 92683
      • Allianz Research Institute- Site Number : 8400013
  • Colorado
    • Aurora, Colorado, United States, 80014
      • Allianz Research Institute CO- Site Number : 8400038
  • Connecticut
    • Farmington, Connecticut, United States, 06032
      • University of Connecticut Health Center- Site Number : 8400020
    • New Haven, Connecticut, United States, 06510
      • Yale New Haven Hospital- Site Number : 8400065
  • Florida
    • Loxahatchee Groves, Florida, United States, 33470
      • Advanced Pulmonary Research Institute- Site Number : 8400007
    • Miami, Florida, United States, 33126
      • Clever Medical Research- Site Number : 8400001
    • Miami, Florida, United States, 33155
      • My Community Research Center- Site Number : 8400023
    • Miami, Florida, United States, 33184
      • High Quality Research- Site Number : 8400047
    • Palmetto Bay, Florida, United States, 33157
      • Destiny Research Center- Site Number : 8400049
    • Pensacola, Florida, United States, 32503
      • Avanza Medical Research Center- Site Number : 8400018
    • Plantation, Florida, United States, 33324
      • Private Practice - Dr. Frank Hull - Plantation- Site Number : 8400010
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital- Site Number : 8400043
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center- Site Number : 8400045
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Health System - Ann Arbor- Site Number : 8400055
    • Warren, Michigan, United States, 48088
      • Pulmonary and Medicine Associates- Site Number : 8400057
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University- Site Number : 8400046
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Medical Center- Site Number : 8400032
  • North Carolina
    • Charlotte, North Carolina, United States, 28277
      • American Health Research - Charlotte- Site Number : 8400017
    • Huntersville, North Carolina, United States, 28078
      • Advanced Respiratory and Sleep Medicine - Huntersville- Site Number : 8400009
    • Winston-Salem, North Carolina, United States, 27103
      • Southeastern Research Center- Site Number : 8400008
  • Pennsylvania
    • DuBois, Pennsylvania, United States, 15801
      • Clinical Research Associates of Central PA - Dubois- Site Number : 8400005
    • Philadelphia, Pennsylvania, United States, 19104
      • Penn Medicine: University of Pennsylvania Health System- Site Number : 8400039
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital- Site Number : 8400015
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina - Charleston - Jonathan Lucas Street- Site Number : 8400027
  • Texas
    • McKinney, Texas, United States, 75069
      • Metroplex Pulmonary and Sleep Center- Site Number : 8400014
    • Plano, Texas, United States, 75024
      • Plano Primary Care Clinic- Site Number : 8400019
    • Sugar Land, Texas, United States, 77479
      • Pioneer Research Solutions, Inc.- Site Number : 8400048
    • Tyler, Texas, United States, 75708
      • The University of Texas Health Center at Tyler- Site Number : 8400053

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant must be 18 to 85 years of age inclusive.
• Clinical history consistent with NCFB (cough, chronic sputum production and/or recurrent respiratory infections).
• Participants with a FEV1 % predicted ≥30%.
• Participants with at least 2 moderate or 1 severe Pulmonary exacerbations (PEs) in the past 12 months.

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

• Have bronchiectasis due to CF, hypogammaglobulinemia, common variable immunodeficiency, known active nontuberculous mycobacteria (NTM) lung infection, or pulmonary fibrosis.
• Known or suspected immunodeficiency disorder.
• Pulmonary exacerbation which has not resolved clinically during screening period.
• Have significant haemoptysis.
• Have any clinically significant abnormal laboratory values at Screening or diseases or disorders.
• History of lung transplantation.
• History of malignancy within 5 years before Screening, or during the screening period
• Currently being treated with antimicrobial therapy for tuberculosis (TB).
• Currently on active treatment for allergic bronchopulmonary aspergillosis (ABPA).
• Participants with active autoimmune disease or participants using immunosuppressive therapy for autoimmune disease
• Known allergy to itepekimab or to excipients
• Live-attenuated vaccine(s) within 4 weeks prior to Screening or plans to receive such vaccines during the study
• Unstable ischemic heart disease
• Cardiomyopathy or other relevant cardiovascular disorder
• Clinically significant new abnormal electrocardiogram (ECG) within 6 months prior to, or at Screening
• History of human immunodeficiency virus (HIV) infection or positive HIV 1/2 serology at Screening.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Itepekimab Q2W; Subcutaneous (SC) administration of Itepekimab every 2 weeks (Q2W) for up to 52 weeks	Drug: Itepekimab (SAR440340); Pharmaceutical form: solution for injection in pre-filled syringe. Route of administration: subcutaneous; Other Names: REGN3500
Placebo Comparator: Placebo; SC administration of matching placebo Q2W for up to 52 weeks	Drug: Placebo; Pharmaceutical form: solution for injection in pre-filled syringe. Route of administration: subcutaneous
Experimental: Itepekimab Q4W; SC administration of Itepekimab every 4 weeks (Q4W) with alternating placebo administration at the 2week interval between active IMP as SC injection for up to 52 weeks	Drug: Itepekimab (SAR440340); Pharmaceutical form: solution for injection in pre-filled syringe. Route of administration: subcutaneous; Other Names: REGN3500; Drug: Placebo; Pharmaceutical form: solution for injection in pre-filled syringe. Route of administration: subcutaneous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annualized rate of moderate or severe Pulmonary exacerbations (PEs) over the treatment period	Annualized rate of moderate or severe PEs over the placebo-controlled treatment period	Baseline up to End of Treatment (EOT) (24-52 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first moderate or severe PE over the treatment period		Baseline up to End of Treatment (EOT) (24-52 weeks)
Percentage of participants who are PE free over the treatment period		Baseline up to End of Treatment (EOT) (24-52 weeks)
Annualized rate of severe PEs over the treatment period		Baseline up to End of Treatment (EOT) (24-52 weeks)
Percentage of participants who are severe PE free over the treatment period		Baseline up to End of Treatment (EOT) (24-52 weeks)
Time to first severe PE over the treatment period		Baseline up to End of Treatment (EOT) (24-52 weeks)
Change From Baseline in FEV1 at Week 8 and Week 24	FEV1 is force expiratory volume in 1 second	Week 8 and Week 24
Number of days of new and/or added (in participants with maintenance antibiotic use) antibiotic use		Baseline up to End of Treatment (EOT) (24-52 weeks)
Change from Baseline in QOL-B Respiratory Symptoms Domain Score in Adult Participants at Week 24	The Quality-Of-Life-Bronchiectasis (QOL-B) is a validated, self-administered patient reported outcome (PRO) that assesses symptoms, functioning and health-related QOL for subjects with NCFB.	Week 24
Change from baseline in SGRQ total score at Week 24	The St. George's Respiratory Questionnaire (SGRQ) is a 50-item questionnaire designed to measure and quantify health status in adult participants with chronic airflow limitation.	Week 24
Percentage of participants with a decrease from baseline of at least 4 points in SGRQ total score at Week 24	The St. George's Respiratory Questionnaire (SGRQ) is a 50-item questionnaire designed to measure and quantify health status in adult participants with chronic airflow limitation.	Week 24
Incidence of TEAEs, AESIs, SAEs, and AEs leading to permanent study treatment discontinuation in the treatment-emergent period		Baseline up to End of Study (EOS) (44 to 72 weeks)
Serum concentrations of itepekimab from baseline to end of study		Baseline up to End of Study (EOS) (44 to 72 weeks)
Incidence of treatment-emergent anti-itepekimab antibodies (ADA) responses throughout the study		Baseline up to End of Study (EOS) (44 to 72 weeks)

Collaborators and Investigators

• Sponsor: Sanofi
• Collaborators: Regeneron Pharmaceuticals

Publications and helpful links

Helpful Links

• ACT18018 Plain Language Results Summary

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2024
• Primary Completion (Actual): September 16, 2025
• Study Completion (Actual): February 2, 2026

Study Registration Dates

• First Submitted: February 20, 2024
• First Submitted That Met QC Criteria: February 20, 2024
• First Posted (Actual): February 28, 2024

Study Record Updates

• Last Update Posted (Actual): February 12, 2026
• Last Update Submitted That Met QC Criteria: February 9, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Bronchial Diseases; Bronchiectasis; itepekimab
• Other Study ID Numbers: ACT18018; U1111-1295-3237 (Registry Identifier: ICTRP); 2023-508663-70 (Registry Identifier: CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No