Non-Cystic Fibrosis Bronchiectasis MedDRA version: 23.0 Level: LLT Classification code 10083611 Term: Non-cystic fibrosis bronchiectasis System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Sponsors
Insmed Incorporated
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provide their signed study informed consent to participate. a. Adolescent subjects must have signed study assent form (if required per local requirements) to participate, and the adolescent's parent or legal guardian must have provided signed informed consent for the adolescent to participate 2. Male or female =18 years and =85 years of age (inclusive) at screening. a. Adolescent subjects – male or female =12 to <18 years of age at Screening in participating countries and sites where local regulations, countries, and/or institutional policies allow for subjects <18 years of age to participate 3. Adult subjects must have a BMI =18.5 at screening. a. Adolescent subjects must have a weight of =30 kg 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 high-resolution 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. Adult subjects: 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. a. Adolescent subjects are exempt from the requirement to provide a sputum sample if they are unable to do so and should not undergo a sputum induction procedure during Screening 7. Mucopurulent or purulent sputum color assessed at the Screening Visit by color chart developed by MP Murray. 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 postmenopausal (defined as no menses for 12 months without an alternative medical cause), surgically sterile, or using highly effective double barrier contraception (ie, methods that can achieve a failure rate <1% per year when used consistently and correctly) 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. The Investigator or designee should explain the acceptable methods of birth control to the subject, and instruct the subject to follow the direction. For WOCBP =45 years
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: an adult who has smoked 100 cigarettes in his or her lifetime and who currently smokes cigarettes. 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 immunecompromised 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 15. Started oral or inhaled antibiotics as chronic treatment for NCFBE for 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 20. History of malignancy in the past 5 years, except completely treated in situ carcinoma of the cervix and completely treated non-metastatic squamous or basal cell carcinoma of the skin. 21. Previously participated in a clinical trial for brensocatib. 22. An absolute neutrophil count <1,000/mm3 at the Screening Visit. 23. Received any live attenuated vaccin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of brensocatib at 10 mg and 25 mg compared with placebo on the rate of pulmonary exacerbations (PEs).;Secondary Objective: 1. To evaluate the effect of brensocatib compared with placebo on the time to first PE 2. To evaluate effect of brensocatib compared with placebo on the responder status for exacerbation free 3. To evaluate the effect of brensocatib compared with placebo on the change in postbronchodilator forced expiratory volume in 1 second (FEV1) at Week52 4. To evaluate the effect of brensocatib compared with placebo on the annualized rate of severe PEs 5. To evaluate the effect of brensocatib compared with placebo on the change in quality of life, as assessed by the Quality of Life Questionnaire – Bronchiectasis (QOL-B) Respiratory Symptoms Domain Score at Week 52 in adult subjects 6. To evaluate the effect of brensocatib compared with placebo on adverse events, clinical laboratory parameters, vital signs, and ECG. 7. To evaluate brensocatib exposure in adults and adolescents on Brensocatib plasma concentrations over time ;Primary end point(s): Rate of adjudicated PEs over the 52-week treatment period.;Timepoint(s) of evaluation of this end point: Over the 52-week treatment period. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 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, ECG);Timepoint(s) of evaluation of this end point: over the 52-week treatment period. | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, Colombia, Denmark, Estonia, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Japan, Lithuania, Malaysia, Mexico, Netherlands, Peru, Poland, Portugal, Slovakia, Spain, Taiwan, Thailand, Türkiye, United Kingdom, United States
Contacts
Public ContactRegulatory Affairs EMEA
Insmed Switzerland GmbH
Outcome results
None listed