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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sanofi-Aventis Recherche & Developpement

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Decision date (initial)

2026-06-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Sanofi-Aventis Recherche et Développement

External identifiers

EU CT number

2025-523403-29-00

WHO UTN

U1111-1322-6304

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic, Pharmacodynamic

To assess the activity of SAR445399 compared to placebo on mucus plug score (MPS) reduction in participants with non-cystic fibrosis bronchiectasis (NCFB)

Secondary objectives 6

1. To evaluate the effect of SAR445399 compared to placebo on pulmonary function in participants with non-cystic fibrosis bronchiectasis (NCFB)
2. To evaluate the effect of SAR445399 compared to placebo on occurrence of pulmonary exacerbations (PEx) in participants with non-cystic fibrosis bronchiectasis (NCFB)
3. To evaluate the effect of SAR445399 compared to placebo on occurrence of severe pulmonary exacerbation (PEx) in participants with non-cystic fibrosis bronchiectasis (NCFB)
4. To evaluate the safety and tolerability of SAR445399 in participants with non-cystic fibrosis bronchiectasis (NCFB)
5. To assess the pharmacokinetics (PK) profile of SAR445399 in participants with non-cystic fibrosis bronchiectasis (NCFB)
6. To assess the immunogenicity of SAR445399 in participants with non-cystic fibrosis bronchiectasis (NCFB)

Conditions and MedDRA coding

Non-cystic fibrosis bronchiectasis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Participants must be 18 to 80 years of age inclusive, at the time of signing the informed consent
2. Clinical history consistent with NCFB, such as chronic productive cough and/or recurrent respiratory infections
3. 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
4. Radiologic evidence of bronchiectasis, confirmed by a chest HRCT
5. A minimum MPS of 4 (out of maximum 18) on chest HRCT performed before Baseline Visit
6. Current sputum production with a documented history of chronic expectoration lasting ≥3 months within the previous 12 months
7. Participants must have a post-bronchodilator FEV1 ≥30% of predicted normal value

Exclusion criteria 8

1. 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
2. Diagnosis of ABPA or any of the allergic bronchopulmonary mycoses
3. Active NTM pulmonary disease currently requiring or receiving antimycobacterial treatment, or history of NTM pulmonary disease with incomplete treatment. Participants with NTM identified at Screening in association with symptoms or radiological findings warranting therapeutic evaluation according to ATS/IDSA criteria are also excluded
4. Bronchiectasis due to any of the following: CF, CVID, AAT or PCD
5. History of significant hemoptysis (requiring medical intervention and/or requiring blood transfusion)
6. Current tobacco smokers
7. 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
8. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline to Week 24 in mucus plug score (MPS) derived from chest high-resolution computerized tomography (HRCT)

Secondary endpoints 16

1. Change from baseline to Week 24 in post-bronchodilator forced expiratory volume in 1 second (FEV1)
2. Change from baseline to Week 52 in post-bronchodilator forced expiratory volume in 1 second (FEV1)
3. Change from baseline to Week 24 in pre-bronchodilator forced expiratory volume in 1 second (FEV1)
4. Change from baseline to Week 52 in pre-bronchodilator forced expiratory volume in 1 second (FEV1)
5. Annualized rate of pulmonary exacerbation (PEx) from baseline up to Week 24
6. Annualized rate of pulmonary exacerbation (PEx) from baseline up to Week 52
7. Responder status for being exacerbation-free over the 24-week study period
8. Responder status for being exacerbation-free over the 52-week study period
9. Annualized rate of severe pulmonary exacerbation (PEx) from baseline up to Week 24
10. Annualized rate of severe pulmonary exacerbation (PEx) from baseline up to Week 52
11. Responder status for being severe exacerbation-free over the 24-week study period
12. Responder status for being severe exacerbation-free over the 52-week study period
13. 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
14. Incidence of potentially clinically significant abnormalities in laboratory tests, vital signs, and 12-lead electrocardiograms (ECGs) throughout the study
15. Plasma concentration of SAR445399 at prespecified timepoints throughout the study
16. Incidence of anti-drug antibodies (ADAs) against SAR445399 throughout the study

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sanofi-Aventis Recherche & Developpement

Sponsor organisation

Sanofi-Aventis Recherche & Developpement

Address

82 Avenue Raspail

City

Gentilly

Postcode

94250

Country

France

Scientific contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Third parties 9

Locations

3 EU/EEA countries · 9 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 27 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications