Assessment of INS1007 in Participants With Non-Cystic Fibrosis Bronchiectasis

Time to first pulmonary exacerbation was calculated as the number of days from the date of randomization to the date of first documentation of an exacerbation. Pulmonary exacerbation was defined as having 3 or more of the following symptoms for at least 48 hours resulting in a physician's decision to prescribe antibiotics: 1. Increased cough 2. Increased sputum volume or change in sputum consistency 3. Increased sputum purulence 4. Increased breathlessness and/or decreased exercise tolerance 5. Fatigue and/or malaise 6. Hemoptysis A minimum of 4 weeks must have occurred between one exacerbation onset and the next. Any exacerbation that occurred less than 4 weeks from the prior exacerbation was not considered a new exacerbation. The analysis was performed using the stratified log rank test and using Kaplan Meier (KM) curves.

Time frame: Baseline (Day 1) to Week 24

Population: ITT population included all participants who were randomized. Overall number of participants analyzed are number of participants with at least one exacerbation over 24-week treatment period.

The concentration of active NE in sputum, was measured by the difference between the pre-treatment concentration and on-treatment concentration. In bronchiectasis, activation of neutrophils in the airway leads to release of NE which leads to damaged airway walls, mucus hypersecretion, exacerbated inflammation, which in turn affects neutrophil and macrophage functions, increasing the risk of infection. Negative change from Baseline indicates improvement.

Time frame: Baseline (Day 1) to Week 24

Population: Pharmacodynamic population included participants who received at least 1 dose of the study drugs, have at least 1 pre-dose and 1 post-dose measurement for NE, or proteinase 3, or cathepsin G, or other biomarkers, and have no major protocol deviations that considered to impact on the analysis of the PD data.

The QOL-B is a validated, self-administered patient reported outcome (PRO) that assesses symptoms, functioning, and health-related (HR) QOL for participants with non-cystic fibrosis bronchiectasis (NCFBE). The QOL-B contains 37 items in 8 domains (Respiratory Symptoms, Physical Functioning, Role Functioning, Emotional Functioning, Social Functioning, Vitality, Health Perceptions and Treatment Burden). Each of the 37 items is scored from 1 to 4, and each of the 8 domains scale scores is standardized on a 0-100 point scale, with higher scores representing fewer symptoms or better functioning and HR QoL. A positive change from Baseline indicates improvement in symptoms. For this outcome measure, change in the respiratory symptoms domain score from Baseline was reported. The analysis was based on mixed model for repeated measures (MMRM) approach.

Time frame: Baseline (Day 1) to Week 24

Population: ITT population included all participants who were randomized. Overall number of participants analyzed are the number of participants with data available for analyses at the latest assessment visit over the 24-week treatment period.

FEV1 was used to assess lung function and is the maximum amount of air that can be forced out in one second after taking a deep breath. The percent predicted FEV1 was calculated by converting the spirometer reading to a percentage of what would be predicted as normal FEV1 based on a several personal factors (e.g. sex, age, etc.). Change from screening in percent predicted FEV1 to Week 24 was calculated as: percent predicted FEV1 value at Week 24 and percent predicted FEV1 value at screening. A positive percent change from screening indicates an improvement in lung function. The analysis was done using analysis of covariance (ANCOVA) with Pa colonization status and maintenance macrolide antibiotic use at Baseline as covariates.

Time frame: Screening (Days -42 to -1) to Week 24

Population: ITT population included all participants who were randomized. Overall number of participants analyzed are the number of participants with data available for analyses over the 24-week treatment period.

Pulmonary exacerbation was defined as having 3 or more of the following symptoms for at least 48 hours resulting in a physician's decision to prescribe antibiotics. 1. Increased cough 2. Increased sputum volume or change in sputum consistency 3. Increased sputum purulence 4. Increased breathlessness and/or decreased exercise tolerance 5. Fatigue and/or malaise 6. Hemoptysis A minimum of 4 weeks must have occurred between one exacerbation onset and the next. Any exacerbation that occurred less than 4 weeks from the prior exacerbation was not considered a new exacerbation.

Time frame: Baseline (Day 1) to Week 24

Population: ITT population included all participants who were randomized.