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

Phase 2

Active, not recruiting

• Conditions: Bronchiectasis
• Interventions: Drug: Itepekimab (SAR440340); 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

Study Timeline

• Study Start: 2024-02-20
• Study First Submitted: 2024-02-20
• Study First Submitted QC: 2024-02-20
• Study First Posted: 2024-02-28
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-27
• Last Update Posted: 2025-04-29
• Primary Completion: 2026-03-24
• Study Completion: 2026-08-11

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 300

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 & 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.
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
Percentage of participants who are severe PE free over the treatment period	Baseline up to End of Treatment (EOT) (24-52 weeks)

Trial Locations

Locations (138)

University of Alabama at Birmingham- Site Number : 8400040; 🇺🇸 Birmingham, Alabama, United States

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

Scroll for more (128 remaining)