The purpose of the study is to evaluate if INS1007 can reduce pulmonary exacerbations over a 24-week treatment period in participants with non-cystic fibrosis bronchiectasis.
Phase 2 randomized, double-blind, placebo-controlled, parallel-group, multicenter, multi-national study to assess the efficacy, safety and tolerability, and pharmacokinetics (PK) of INS1007 administered once daily for 24 weeks in participants with non-cystic fibrosis bronchiectasis (NCFBE).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
256
Administered once per day for 24 weeks
Administered once per day for 24 weeks
Administered once per day for 24 weeks
Time to the First Pulmonary Exacerbation Over 24-Week Treatment Period
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
Change From Baseline in Quality of Life Questionnaire - Bronchiectasis (QOL-B) Respiratory Symptoms Domain Score Over 24 Week Treatment Period
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
Change From Screening in Post-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Over 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.
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University of Alabama at Birmingham
Birmingham, Alabama, United States
Phoenix Medical Group
Peoria, Arizona, United States
NewportNativeMD
Newport Beach, California, United States
Palmtree Clinical Research
Palm Springs, California, United States
UC Davis Medical Center
Sacramento, California, United States
Stanford University Medical Center
Stanford, California, United States
National Jewish Heath
Denver, Colorado, United States
UConn Health Center
Farmington, Connecticut, United States
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, United States
Clinical Research Specialists, LLC
Celebration, Florida, United States
...and 98 more locations
Time frame: Screening (Days -42 to -1) to Week 24
Change From Baseline in Concentration of Active Neutrophil Elastase (NE) in Sputum
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
Number of Participants Who Experienced a Pulmonary 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.
Time frame: Baseline (Day 1) to Week 24