Non-cystic Fibrosis Bronchiectasis
Conditions
Keywords
Non-Cystic Fibrosis Bronchiectasis, NCFB, Bronchiectasis
Brief summary
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).
Interventions
BIOLOGICALSAR445399
Pharmaceutical form: solution for injection Route of administration: injection
BIOLOGICALPlacebo
Pharmaceutical form: solution for injection Route of administration: injection
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
\[Specify Complex Masking\]
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline to Week 24 in mucus plug score (MPS) derived from chest high-resolution computerized tomography (HRCT) | from baseline up to Week 24 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline to Week 24 in post-bronchodilator forced expiratory volume in 1 second (FEV1) | from baseline up to Week 24 | Post-bronchodilator forced expiratory volume in 1 second |
| Change from baseline to Week 52 in post-bronchodilator forced expiratory volume in 1 second (FEV1) | from baseline up to Week 52 | Post-bronchodilator forced expiratory volume in 1 second |
| Change from baseline to Week 24 in pre-bronchodilator forced expiratory volume in 1 second (FEV1) | from baseline up to Week 24 | Pre-bronchodilator forced expiratory volume in 1 second |
| Change from baseline to Week 52 in pre-bronchodilator forced expiratory volume in 1 second (FEV1) | from baseline up to Week 52 | Pre-bronchodilator forced expiratory volume in 1 second |
| Annualized rate of pulmonary exacerbation (PEx) from baseline up to Week 24 | 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 |
| Annualized rate of pulmonary exacerbation (PEx) from baseline up to Week 52 | 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 |
| Responder status for being exacerbation-free over the 24-week study period | from baseline up to Week 24 | Proportion of patients without a pulmonary exacerbation (PEx) event from baseline up to Week 24 |
| Responder status for being exacerbation-free over the 52-week study period | from baseline up to Week 52 | Proportion of patients without pulmonary exacerbation (PEx) event from baseline up to Week 52 |
| Annualized rate of severe pulmonary exacerbation (PEx) from baseline up to Week 24 | from baseline up to Week 24 | A pulmonary exacerbation is classified as severe when it necessitates either:Intravenous antibacterial treatment, and/or hospital admission |
| Annualized rate of severe pulmonary exacerbation (PEx) from baseline up to Week 52 | from baseline up to Week 52 | A pulmonary exacerbation is classified as severe when it necessitates either:Intravenous antibacterial treatment, and/or hospital admission |
| Responder status for being severe exacerbation-free over the 24-week study period | from baseline up to Week 24 | Proportion of patients without a severe pulmonary exacerbation (PEx) event from baseline up to Week 24 |
| Responder status for being severe exacerbation-free over the 52-week study period | from baseline up to Week 52 | Proportion of patients without a severe pulmonary exacerbation (PEx) event 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 | from baseline up to Week 66 | Incidence of participants with TEAEs, including AESIs, and SAEs |
| 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 | — |
Countries
United States
Contacts
CONTACTTrial Transparency email recommended (Toll free for US & Canada)
Outcome results
None listed