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
- Conditions
- Bronchiectasis
- Interventions
- Drug: Placebo
- Registration Number
- NCT06280391
- Lead Sponsor
- Sanofi
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 300
- 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.
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Itepekimab Q2W Itepekimab (SAR440340) Subcutaneous (SC) administration of Itepekimab every 2 weeks (Q2W) for up to 52 weeks Itepekimab Q4W Itepekimab (SAR440340) 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 Itepekimab Q4W Placebo 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 Placebo Placebo SC administration of matching placebo Q2W for up to 52 weeks
- Primary Outcome Measures
Name Time Method Annualized rate of moderate or severe Pulmonary exacerbations (PEs) over the treatment period Baseline up to End of Treatment (EOT) (24-52 weeks) Annualized rate of moderate or severe PEs over the placebo-controlled treatment period
- Secondary Outcome Measures
Name Time Method Time to first severe PE over the treatment period 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 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.
Percentage of participants with a decrease from baseline of at least 4 points in SGRQ total score at Week 24 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.
Percentage of participants who are severe PE free over the treatment period Baseline up to End of Treatment (EOT) (24-52 weeks) Change from baseline in SGRQ total score at Week 24 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.
Serum concentrations of itepekimab from baseline to end of study Baseline up to End of Study (EOS) (44 to 72 weeks) Annualized rate of severe PEs over the treatment period Baseline up to End of Treatment (EOT) (24-52 weeks) Incidence of treatment-emergent anti-itepekimab antibodies (ADA) responses throughout the study Baseline up to End of Study (EOS) (44 to 72 weeks) Time to first moderate or severe PE over the treatment period Baseline up to End of Treatment (EOT) (24-52 weeks) 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) 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) Percentage of participants who are PE free 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 Week 8 and Week 24 FEV1 is force expiratory volume in 1 second
Trial Locations
- Locations (138)
Investigational Site Number : 3760009
🇮🇱Ramat Gan, Israel
Investigational Site Number : 3760004
🇮🇱Rehovot, Israel
Investigational Site Number : 3760007
🇮🇱Tel Aviv, Israel
Investigational Site Number : 3760010
🇮🇱Tel Aviv, Israel
Investigational Site Number : 3800001
🇮🇹Milan, Lombardia, Italy
Investigational Site Number : 3800002
🇮🇹Rozzano, Milano, Italy
Investigational Site Number : 3800004
🇮🇹Palermo, Italy
Investigational Site Number : 3800003
🇮🇹Pavia, Italy
Investigational Site Number : 3800006
🇮🇹Reggio Emilia, Italy
Investigational Site Number : 3920002
🇯🇵Kamogawa, Chiba, Japan
Investigational Site Number : 3920004
🇯🇵Himeji, Hyogo, Japan
Investigational Site Number : 3920005
🇯🇵Kiyose, Tokyo, Japan
Investigational Site Number : 3920001
🇯🇵Tokyo, Japan
Investigational Site Number : 3920003
🇯🇵Tokyo, Japan
Investigational Site Number : 5280002
🇳🇱Alkmaar, Netherlands
Investigational Site Number : 5280005
🇳🇱Amsterdam, Netherlands
Investigational Site Number : 5280004
🇳🇱Breda, Netherlands
Investigational Site Number : 5280001
🇳🇱Rotterdam, Netherlands
Investigational Site Number : 5280003
🇳🇱The Hague, Netherlands
Investigational Site Number : 6160005
🇵🇱Lodz, Lódzkie, Poland
Investigational Site Number : 6160001
🇵🇱Bialystok, Podlaskie, Poland
Investigational Site Number : 1560008
🇨🇳Changchun, China
Investigational Site Number : 1560004
🇨🇳Chengdu, China
Investigational Site Number : 1560006
🇨🇳Shanghai, China
Investigational Site Number : 1560001
🇨🇳Guangzhou, China
Investigational Site Number : 1560003
🇨🇳Xuzhou, China
Investigational Site Number : 2080002
🇩🇰Aalborg, Denmark
Investigational Site Number : 2080005
🇩🇰Aarhus, Denmark
Investigational Site Number : 2080004
🇩🇰Odense, Denmark
Investigational Site Number : 2080001
🇩🇰Vejle, Denmark
Investigational Site Number : 2500005
🇫🇷Brest, France
Investigational Site Number : 2500001
🇫🇷Lyon, France
Investigational Site Number : 2500002
🇫🇷Montpellier, France
Investigational Site Number : 2760001
🇩🇪Ahrensburg, Germany
Investigational Site Number : 2760005
🇩🇪Bendorf, Germany
Investigational Site Number : 2760010
🇩🇪Berlin, Germany
Investigational Site Number : 2760009
🇩🇪Cottbus, Germany
Investigational Site Number : 2760007
🇩🇪Essen, Germany
Investigational Site Number : 2760003
🇩🇪Frankfurt, Germany
Investigational Site Number : 2760004
🇩🇪Lübeck, Germany
Investigational Site Number : 2760002
🇩🇪Mainz, Germany
Investigational Site Number : 2760011
🇩🇪Munich, Germany
Investigational Site Number : 3000001
🇬🇷Ioannina, Greece
Investigational Site Number : 3000003
🇬🇷Thessaloniki, Greece
Investigational Site Number : 3760008
🇮🇱Ashkelon, Israel
Investigational Site Number : 3760006
🇮🇱Haifa, Israel
Investigational Site Number : 3760003
🇮🇱Jerusalem, Israel
Investigational Site Number : 3760001
🇮🇱Jerusalem, Israel
Investigational Site Number : 3760002
🇮🇱Petah Tikva, Israel
Investigational Site Number : 1560007
🇨🇳Shenyang, China
Investigational Site Number : 2500004
🇫🇷Nice, France
Investigational Site Number : 2500003
🇫🇷Paris, France
Investigational Site Number : 2500006
🇫🇷Saint-herblain, France
Investigational Site Number : 6160002
🇵🇱Ostrowiec Swietokrzyski, Swietokrzyskie, Poland
Investigational Site Number : 6160003
🇵🇱Lodz, Poland
Investigational Site Number : 6160006
🇵🇱Wejherowo, Poland
Investigational Site Number : 7240007
🇪🇸Barcelona, Barcelona [Barcelona], Spain
Investigational Site Number : 1560005
🇨🇳Beijing, China
Investigational Site Number : 1560002
🇨🇳Shanghai, China
My Community Research Center- Site Number : 8400023
🇺🇸Miami, Florida, United States
University of Alabama at Birmingham- Site Number : 8400040
🇺🇸Birmingham, Alabama, United States
Investigational Site Number : 1240003
🇨🇦Guelph, Ontario, Canada
Pulmonary Associates - Phoenix - East McDowell Road- Site Number : 8400012
🇺🇸Phoenix, Arizona, United States
Southern California Institute for Respiratory Diseases- Site Number : 8400002
🇺🇸Los Angeles, California, United States
Institute Healthcare Assessment- Site Number : 8400037
🇺🇸San Diego, California, United States
Allianz Research Institute- Site Number : 8400013
🇺🇸Westminster, California, United States
Allianz Research Institute CO- Site Number : 8400038
🇺🇸Aurora, Colorado, United States
University of Connecticut Health Center- Site Number : 8400020
🇺🇸Farmington, Connecticut, United States
Yale New Haven Hospital- Site Number : 8400065
🇺🇸New Haven, Connecticut, United States
Advanced Pulmonary Research Institute- Site Number : 8400007
🇺🇸Loxahatchee Groves, Florida, United States
Clever Medical Research- Site Number : 8400001
🇺🇸Miami, Florida, United States
High Quality Research- Site Number : 8400047
🇺🇸Miami, Florida, United States
Private Practice - Dr. Frank Hull - Plantation- Site Number : 8400010
🇺🇸Plantation, Florida, United States
Northwestern Memorial Hospital- Site Number : 8400043
🇺🇸Chicago, Illinois, United States
Destiny Research Center- Site Number : 8400049
🇺🇸Palmetto Bay, Florida, United States
Avanza Medical Research Center- Site Number : 8400018
🇺🇸Pensacola, Florida, United States
University of Kansas Medical Center- Site Number : 8400045
🇺🇸Kansas City, Kansas, United States
University of Michigan Health System - Ann Arbor- Site Number : 8400055
🇺🇸Ann Arbor, Michigan, United States
Pulmonary and Medicine Associates- Site Number : 8400057
🇺🇸Warren, Michigan, United States
Washington University- Site Number : 8400046
🇺🇸Saint Louis, Missouri, United States
NYU Langone Medical Center- Site Number : 8400032
🇺🇸New York, New York, United States
American Health Research - Charlotte- Site Number : 8400017
🇺🇸Charlotte, North Carolina, United States
Advanced Respiratory and Sleep Medicine - Huntersville- Site Number : 8400009
🇺🇸Huntersville, North Carolina, United States
Southeastern Research Center- Site Number : 8400008
🇺🇸Winston-Salem, North Carolina, United States
Clinical Research Associates of Central PA - Dubois- Site Number : 8400005
🇺🇸DuBois, Pennsylvania, United States
Penn Medicine: University of Pennsylvania Health System- Site Number : 8400039
🇺🇸Philadelphia, Pennsylvania, United States
Temple University Hospital- Site Number : 8400015
🇺🇸Philadelphia, Pennsylvania, United States
Medical University of South Carolina - Charleston - Jonathan Lucas Street- Site Number : 8400027
🇺🇸Charleston, South Carolina, United States
Metroplex Pulmonary and Sleep Center- Site Number : 8400014
🇺🇸McKinney, Texas, United States
Plano Primary Care Clinic- Site Number : 8400019
🇺🇸Plano, Texas, United States
Pioneer Research Solutions, Inc.- Site Number : 8400048
🇺🇸Sugar Land, Texas, United States
The University of Texas Health Center at Tyler- Site Number : 8400053
🇺🇸Tyler, Texas, United States
Investigational Site Number : 0320002
🇦🇷La Plata, Buenos Aires, Argentina
Investigational Site Number : 0320003
🇦🇷Buenos Aires, Argentina
Investigational Site Number : 0320008
🇦🇷Buenos Aires, Argentina
Investigational Site Number : 0320001
🇦🇷Buenos Aires, Argentina
Investigational Site Number : 0320004
🇦🇷Buenos Aires, Argentina
Investigational Site Number : 0320007
🇦🇷Córdoba, Argentina
Investigational Site Number : 0320006
🇦🇷Mendoza, Argentina
Investigational Site Number : 0320005
🇦🇷San Miguel de Tucumán, Argentina
Oncoclínicas UMC- Site Number : 0760007
🇧🇷Uberlândia, Minas Gerais, Brazil
Irmandade da Santa Casa de Misericórdia de Porto Alegre- Site Number : 0760005
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Hospital São Lucas da PUCRS - Porto Alegre - Avenida Ipiranga- Site Number : 0760001
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Investigational Site Number : 1520001
🇨🇱Talca, Maule, Chile
Investigational Site Number : 1520003
🇨🇱Santiago, Reg Metropolitana De Santiago, Chile
Investigational Site Number : 1520002
🇨🇱Santiago, Reg Metropolitana De Santiago, Chile
Investigational Site Number : 1520004
🇨🇱Quillota, Valparaíso, Chile
WM Pesquisas Clínicas em Doenças Respiratórias- Site Number : 0760004
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Investigational Site Number : 1240005
🇨🇦Sherbrooke, Quebec, Canada
Investigational Site Number : 1240001
🇨🇦Trois-rivières, Quebec, Canada
Incor - Instituto do Coracao- Site Number : 0760002
🇧🇷São Paulo, Brazil
Investigational Site Number : 2030002
🇨🇿Jindřichův Hradec, Czechia
Investigational Site Number : 2030004
🇨🇿Kralupy Nad Vltavou, Czechia
Investigational Site Number : 2030003
🇨🇿Pilsen, Czechia
Investigational Site Number : 2030005
🇨🇿Prague, Czechia
Investigational Site Number : 2030006
🇨🇿Český Krumlov, Czechia
Investigational Site Number : 7240003
🇪🇸Barcelona, Barcelona [Barcelona], Spain
Investigational Site Number : 7240006
🇪🇸Barcelona, Barcelona [Barcelona], Spain
Investigational Site Number : 7240001
🇪🇸L'hospitalet de Llobregat, Barcelona [Barcelona], Spain
Investigational Site Number : 7240012
🇪🇸Girona, Girona [Gerona], Spain
Investigational Site Number : 7240002
🇪🇸Madrid, Madrid, Comunidad De, Spain
Investigational Site Number : 1580005
🇨🇳Kaohsiung City, Taiwan
Investigational Site Number : 1580002
🇨🇳New Taipei City, Taiwan
Investigational Site Number : 1580006
🇨🇳Taichung, Taiwan
Investigational Site Number : 1580004
🇨🇳Taipei City, Taiwan
Investigational Site Number : 1580003
🇨🇳Taipei City, Taiwan
Investigational Site Number : 7920003
🇹🇷Adana, Turkey
Investigational Site Number : 7920002
🇹🇷Akdeniz, Turkey
Investigational Site Number : 7920005
🇹🇷Ankara, Turkey
Investigational Site Number : 7920001
🇹🇷Istanbul, Turkey
Investigational Site Number : 7920004
🇹🇷Izmit, Turkey
Investigational Site Number : 7920006
🇹🇷Samsun, Turkey
Investigational Site Number : 8260009
🇬🇧Cambridge, Cambridgeshire, United Kingdom
Investigational Site Number : 8260008
🇬🇧Norwich, Norfolk, United Kingdom
Investigational Site Number : 8260003
🇬🇧North Shields, North Tyneside, United Kingdom
Investigational Site Number : 8260004
🇬🇧Lancaster, United Kingdom
Investigational Site Number : 8260001
🇬🇧Newcastle Upon Tyne, United Kingdom
Investigational Site Number : 8260005
🇬🇧Reading, United Kingdom