Clinical trial NCT06280391: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Bronchiectasis
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2024-02-28
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

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