A Study to Access Activity and Safety With SAR445399 Compared With Placebo in Participants Aged 18 to 80 Years of Age With Non-Cystic Fibrosis Bronchiectasis

A Randomized, Double-blinded, Placebo-controlled, Parallel Group, Phase 2a Study to Assess the Activity, Safety, and Tolerability of SAR445399 in Adult Participants With Non-Cystic Fibrosis Bronchiectasis (NCFB)

This is a randomized, double-blind, placebo-controlled study to measure the reduction in mucus plug score at 24 weeks of treatment with SAR445399 compared with placebo in adult participants aged 18 to 80 years with non-cystic fibrosis bronchiectasis (NCFB).

Study Overview

• Status: Recruiting
• Conditions: Non-cystic Fibrosis Bronchiectasis
• Intervention / Treatment: Biological: SAR445399; Biological: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Trial Transparency email recommended (Toll free for US & Canada); Phone Number: option 6 800-633-1610; Email: Contact-US@sanofi.com

Study Locations

• United States
  • Florida
    • Loxahatchee Groves, Florida, United States, 33470
      • Recruiting
      • Advanced Pulmonary Research Institute- Site Number : 8400001
    • Plantation, Florida, United States, 33324
      • Recruiting
      • Hull and Hull Medical Specialists- Site Number : 8400002
  • Pennsylvania
    • DuBois, Pennsylvania, United States, 15801
      • Recruiting
      • Clinical Research Associates of Central Pennsylvania- Site Number : 8400006

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Participants must be 18 to 80 years of age inclusive, at the time of signing the informed consent
• Clinical history consistent with NCFB, such as chronic productive cough and/or recurrent respiratory infections
• Documented evidence of at least 2 PEx defined as episodes requiring a physician-prescribed course of antibiotics (oral and/or IV) for ≥5 days for signs and symptoms of respiratory infection within the 12 months prior to the Screening Visit
• Radiologic evidence of bronchiectasis, confirmed by a chest HRCT
• A minimum MPS of 4 (out of maximum 18) on chest HRCT performed before Baseline Visit
• Current sputum production with a documented history of chronic expectoration lasting ≥3 months within the previous 12 months
• Participants must have a post-bronchodilator FEV1 ≥30% of predicted normal value

Exclusion Criteria:

• A primary diagnosis of smoking-related COPD or asthma as determined by the Investigator. Participants with comorbid smoking-related COPD may be included if bronchiectasis is confirmed as their primary diagnosis and is the predominant cause of their respiratory symptoms
• Diagnosis of ABPA or any of the allergic bronchopulmonary mycoses
• Active NTM lung infection or incomplete NTM treatment course
• Bronchiectasis due to any of the following: CF, CVID, AAT or PCD
• History of significant hemoptysis (requiring medical intervention and/or requiring blood transfusion)
• Current tobacco smokers
• Known or suspected immunosuppression, including history of invasive opportunistic infections (eg., histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis), despite infection resolution, or otherwise recurrent infections of abnormal frequency, or prolonged infections suggesting an immune-compromised status, as judged by the Investigator
• Participants with active autoimmune disease or participants using immunosuppressive therapy for autoimmune disease, including but not limited to connective tissue diseases (eg., systemic lupus erythematosus, scleroderma, polymyositis, dermatomyositis, mixed connective tissue disease), rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, Hashimoto's thyroiditis, Graves' disease, primary biliary cirrhosis, and psoriasis vulgaris

The above information is not intended to contain all considerations relevant to a participant'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: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; Participants will receive SAR445399	Biological: SAR445399; Pharmaceutical form: solution for injection Route of administration: injection
Placebo Comparator: Arm B; Participants will receive placebo	Biological: Placebo; Pharmaceutical form: solution for injection Route of administration: injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline to Week 24 in mucus plug score (MPS) derived from chest high-resolution computerized tomography (HRCT)	Mucus plug score is determined by counting the number of bronchopulmonary segments that contain at least one mucus plug, defined as a complete occlusion of the airway The total MPS ranges from 0 to 18 with higher scores indicating worse outcome	from baseline up to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline to Week 24 in post-bronchodilator forced expiratory volume in 1 second (FEV1)	Post-bronchodilator forced expiratory volume in 1 second	from baseline up to Week 24
Change from baseline to Week 52 in post-bronchodilator forced expiratory volume in 1 second (FEV1)	Post-bronchodilator forced expiratory volume in 1 second	from baseline up to Week 52
Change from baseline to Week 24 in pre-bronchodilator forced expiratory volume in 1 second (FEV1)	Pre-bronchodilator forced expiratory volume in 1 second	from baseline up to Week 24
Change from baseline to Week 52 in pre-bronchodilator forced expiratory volume in 1 second (FEV1)	Pre-bronchodilator forced expiratory volume in 1 second	from baseline up to Week 52
Annualized rate of pulmonary exacerbation (PEx) from baseline up to Week 24	Pulmonary exacerbations (PEx) were defined as a worsening of 3 or more major symptoms over a 48-hour period, including increased cough, increased sputum volume or changes in sputum consistency, increased sputum purulence, increased breathlessness, decreased exercise tolerance, fatigue and/or malaise, and hemoptysis. These symptoms had to lead to a healthcare provider's decision to prescribe systemic antibiotics	from baseline up to Week 24
Annualized rate of pulmonary exacerbation (PEx) from baseline up to Week 52	Pulmonary exacerbations (PEx) were defined as a worsening of 3 or more major symptoms over a 48-hour period, including increased cough, increased sputum volume or changes in sputum consistency, increased sputum purulence, increased breathlessness, decreased exercise tolerance, fatigue and/or malaise, and hemoptysis. These symptoms had to lead to a healthcare provider's decision to prescribe systemic antibiotics	from baseline up to Week 52
Responder status for being exacerbation-free over the 24-week study period	Proportion of patients without a pulmonary exacerbation (PEx) event from baseline up to Week 24	from baseline up to Week 24
Responder status for being exacerbation-free over the 52-week study period	Proportion of patients without pulmonary exacerbation (PEx) event from baseline up to Week 52	from baseline up to Week 52
Annualized rate of severe pulmonary exacerbation (PEx) from baseline up to Week 24	A pulmonary exacerbation is classified as severe when it necessitates either:Intravenous antibacterial treatment, and/or hospital admission	from baseline up to Week 24
Annualized rate of severe pulmonary exacerbation (PEx) from baseline up to Week 52	A pulmonary exacerbation is classified as severe when it necessitates either:Intravenous antibacterial treatment, and/or hospital admission	from baseline up to Week 52
Responder status for being severe exacerbation-free over the 24-week study period	Proportion of patients without a severe pulmonary exacerbation (PEx) event from baseline up to Week 24	from baseline up to Week 24
Responder status for being severe exacerbation-free over the 52-week study period	Proportion of patients without a severe pulmonary exacerbation (PEx) event from baseline up to Week 52	from baseline up to Week 52
Incidence of treatment-emergent adverse events (TEAEs), adverse event of special interests (AESIs), serious adverse events (SAEs), adverse events (AEs) leading to permanent study treatment discontinuation throughout the study	Incidence of participants with TEAEs, including AESIs, and SAEs	from baseline up to Week 66
Incidence of potentially clinically significant abnormalities in laboratory tests, vital signs, and 12-lead electrocardiograms (ECGs) throughout the study		from baseline up to Week 66
Plasma concentration of SAR445399 at prespecified timepoints throughout the study		from baseline up to Week 66
Incidence of anti-drug antibodies (ADAs) against SAR445399 throughout the study		from baseline up to Week 66

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start (Estimated): June 15, 2026
• Primary Completion (Estimated): October 29, 2027
• Study Completion (Estimated): August 7, 2028

Study Registration Dates

• First Submitted: April 17, 2026
• First Submitted That Met QC Criteria: April 17, 2026
• First Posted (Actual): April 23, 2026

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: June 2, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Bronchiectasis; NCFB; Non-Cystic Fibrosis Bronchiectasis
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Bronchial Diseases; Bronchiectasis
• Other Study ID Numbers: PDY19372; 2025-523403-29 (Registry Identifier: CTIS); U1111-1322-6304 (Registry Identifier: WHO ICTRP)

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