Bronchiectasis Chronic inflammatory lung disease
Conditions
Interventions
Approximately 1,660 subjects will be randomly assigned to receive brensocatib 
10 mg QD, brensocatib 25 mg QD, or placebo QD for 52 weeks.
Sponsors
Insmed Incorporated
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: For Adults subjects : 1. Provide their signed study informed consent to participate. 2. Male or female >=18 years and <=85 years of age (inclusive) at screening. 3. BMI >=18.5 at screening. 4. Clinical history consistent with NCFBE (cough, chronic sputum production and/or recurrent respiratory infections) that is confirmed by chest CT demonstrating bronchiectasis affecting one or more lobes (confirmation may be based on prior chest CT). a. For each subject, the most recent chest CT scan (but not older than 5 years before the Screening date) will be selected for transfer to the central reading facility for confirmation of the diagnosis of NCFBE. b. If the CT scan cannot be read by the reviewers due to quality issues, a new high-resolution CT scan will be performed. c. In case a chest CT Scan in the last 5 years is not available, a new chest CT scan must be obtained for confirmation of the diagnosis of NCFBE by the central reading facility. 5. Postbronchodilator FEV1 at the Screening Visit >=30% of predicted normal value, calculated using National Health and Nutrition Examination Survey reference equations and must have an absolute value >=750 mL. 6. Current sputum producer with a history of chronic expectoration of at least 3 months in the past 12 months, and able to provide sputum sample during screening (Visit 1). If a subject is unable to produce sputum spontaneously during screening, the subject will be considered a screen failure. The subject should not undergo a sputum induction procedure during screening to meet inclusion criterion. 7. Mucopurulent or purulent sputum color assessed at the Screening Visit by color chart developed by MP Murray (Murray et al., 2009). 8. At least 2 pulmonary exacerbations defined by need for antibiotic prescription by a physician for the signs and symptoms of respiratory infections in the past 12 months before the Screening Visit. 9. Women must be post-menopausal (defined as no menses for 12 months without an alternative medical cause), surgically sterile, or using highly effective double barrier contraception (ie, methods that in combination achieve <1% unintended pregnancy rates per year) from Day 1 to at least 90 days after the last dose. Such methods include true abstinence (refraining from heterosexual intercourse during the study); combined (estrogen and progestogen containing) or progestogen-only hormonal contraception associated with inhibition of ovulation and supplemented with a double barrier (preferably male condom); intrauterine devices; intrauterine hormone-releasing systems; or vasectomized partner. For women <=45 years of childbearing potential, an additional confirmatory testing of FSH level with a threshold of >40 mIU/mL should be performed to be considered infertile. Note: Abstinence is only considered to be a highly effective method of contraception when this is the preferred and usual lifestyle of a subject. Periodic abstinence (calendar, symptothermal, postovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method are not acceptable methods of contraception. 10. M
Exclusion criteria
Exclusion criteria: 1. A primary diagnosis of COPD or asthma as judged by the Investigator. Patients with comorbid COPD and/or asthma can be enrolled if bronchiectasis is their primary diagnosis 2. Subjects receiving supplemental oxygen >12 hours per day. 3. Bronchiectasis due to cystic fibrosis. 4. Current smokers as defined per CDC. 5. No evidence of bronchiectasis according to the BE-CT scoring system. 6. Known or suspected immunodeficiency disorder, including history of invasive opportunistic infections (eg, TB, 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. 7. Known history of HIV infection. 8. Established diagnosis of hepatitis B viral infection at the time of screening, or positive for HBsAg at the time of screening. Subjects who have gained immunity for hepatitis B virus infection after vaccination (subjects who are HBsAg-negative, HBsAb-positive, and HBcAb-negative are eligible for the study). Subjects with positive HBcAb are eligible for the study only if hepatitis B virus DNA level is undetectable. 9. Established diagnosis of HCV infection at the time of Screening. Subjects positive for hepatitis C antibody are eligible for the study only if HCV RNA is negative. 10. Currently being treated for NTM lung infection, allergic bronchopulmonary aspergillosis, or TB. 11. Active and current symptomatic infection by COVID-19. 12. Unable to perform technically acceptable spirometry that meet the ATS/ERS acceptability criteria with at least 3 acceptable flow-volume curves, at least 2 of which meet the ATS/ERS repeatability criteria for FEV1 during Screening. 13. Inability to follow the procedures of the study (eg, due to language problems or psychological disorders). 14. Receiving medications or therapy that are prohibited as concomitant medications (see Section 5.3 for prohibited concomitant medications) 15. Started oral or inhaled antibiotics as chronic treatment for NCFBE for <3 months prior to the Screening visit. a. Subjects on antibiotics as chronic treatment should be on such treatment for at least 3 months prior to enrollment while meeting all other inclusion criteria and none of the exclusion criteria. 16. Chronic treatment with oral steroids (irrespective of the indication), is prohibited 17. Subjects who have adjustments to their baseline medications within 1 month before Screening; they can be rescreened a month after the new treatment has been initiated. 18. Abnormal renal function test result eGRF <30 mL/min by Chronic Kidney Disease - Epidemiology Collaboration equation formula) at Screening. 19. Active liver disease or hepatic dysfunction manifested as follows: a. Elevated liver function test results (ALT or AST >3 × ULN). b. Total Bilirubin >2 × ULN (isolated bilirubin >2 × ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). c. Known hepatic or biliary abnormalities, not including Gilbert's syndrome or asymptomatic gallstones. d. Child-Pugh class C
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Rate of adjudicated pulmonary exacerbations over the 52 week treatment period | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Time to first adjudicated PE over the 52-week treatment period 2. Proportion of subjects who are exacerbation free over the 52-week treatment period 3. Change from Baseline in postbronchodilator forced expiratory volume in 1 second (FEV1) at Week 52. 4. Rate of severe adjudicated PEs over the 52-week treatment period. 5. Change in QOL-B, Respiratory Symptoms Domain Score from Baseline to Week 52 in adult subjects. 6. Incidence and severity of treatment-emergent adverse events and other safety variables (eg, clinical laboratory test results, vital signs and ECG. | — |
Countries
Netherlands
Outcome results
None listed