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

Bronchiectasis Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06280391
• Other study ID #: ACT18018
• Secondary ID: U1111-1295-32372
• Status: Recruiting
• Phase: Phase 2
• Start date: February 20, 2024
• Est. completion date: August 11, 2026

Study information

• Verified date: May 2024
• Source: Sanofi
• Contact: Trial Transparency email recommended (Toll free for US & Canada)
• Phone: 800-633-1610
• Email: Contact-US[@]sanofi.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: August 11, 2026
• Est. primary completion date: March 24, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Bronchiectasis

Intervention

Drug:
• Itepekimab (SAR440340)
Pharmaceutical form: solution for injection in pre-filled syringe. Route of administration: subcutaneous
• Placebo
Pharmaceutical form: solution for injection in pre-filled syringe. Route of administration: subcutaneous

Locations

Country	Name	City	State
Israel	Investigational Site Number : 3760006	Haifa
United Kingdom	Investigational Site Number : 8260001	Newcastle upon Tyne
United Kingdom	Investigational Site Number : 8260008	Norwich	Norfolk
United Kingdom	Investigational Site Number : 8260005	Reading
United Kingdom	Investigational Site Number : 8260003	Tyne And Wear	North Tyneside
United States	American Health Research Site Number : 8400017	Charlotte	North Carolina
United States	Avanza Medical Research Center Site Number : 8400018	Pensacola	Florida
United States	Allianz Research Institute Site Number : 8400013	Westminster	California
United States	Southeastern Research Center Site Number : 8400008	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Israel,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Time to first moderate or severe PE over the treatment period		Baseline up to End of Treatment (EOT) (24-52 weeks)
Secondary	Percentage of participants who are PE free over the treatment period		Baseline up to End of Treatment (EOT) (24-52 weeks)
Secondary	Annualized rate of severe PEs over the treatment period		Baseline up to End of Treatment (EOT) (24-52 weeks)
Secondary	Percentage of participants who are severe PE free over the treatment period		Baseline up to End of Treatment (EOT) (24-52 weeks)
Secondary	Time to first severe PE over the treatment period		Baseline up to End of Treatment (EOT) (24-52 weeks)
Secondary	Change From Baseline in FEV1 at Week 8 and Week 24	FEV1 is force expiratory volume in 1 second	Week 8 and Week 24
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	Serum concentrations of itepekimab from baseline to end of study		Baseline up to End of Study (EOS) (44 to 72 weeks)
Secondary	Incidence of treatment-emergent anti-itepekimab antibodies (ADA) responses throughout the study		Baseline up to End of Study (EOS) (44 to 72 weeks)