A Study to Assess the Efficacy, Safety, and Tolerability of Brensocatib in Participants With Non-Cystic Fibrosis Bronchiectasis

Insmed Incorporated1,767 enrolled

Overview

The primary objective of this study is to evaluate the effect of brensocatib at 10 mg and 25 mg compared with placebo on the rate of pulmonary exacerbations (PEs) over the 52-week treatment period.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

1,767

Conditions

Non-Cystic Fibrosis Bronchiectasis

Interventions

Brensocatib 10 mgDRUG

Oral tablet.

Brensocatib 25 mgDRUG

Oral tablet.

PlaceboDRUG

Brensocatib-matching oral tablet.

Eligibility

Sex: ALLMin age: 12 YearsMax age: 85 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Provide their signed study informed consent to participate. a. Adolescent participants must have signed study assent form to participate, and the adolescent's parent or legal guardian must have provided signed informed consent for the adolescent to participate. 2. Clinical history consistent with non-cystic fibrosis bronchiectasis (NCFBE) (cough, chronic sputum production and/or recurrent respiratory infections) that is confirmed by chest computerized tomography (CT) scan. 3. At least 2 PEs 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. a. Adolescent participants are required to have at least 1 pulmonary exacerbation in the prior 12 months. 4. Women must be postmenopausal (defined as no menses for 12 months without an alternative medical cause), surgically sterile, or using highly effective 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. 5. Male participants with female partners of childbearing potential must be using effective contraception from Day 1 to at least 90 days after the last dose. 6. Male participants with pregnant or non-pregnant women of child-bearing potential partners must use condoms to avoid potential exposure to the embryo/fetus. Exclusion Criteria: 1. A primary diagnosis of chronic obstructive pulmonary disease (COPD) or asthma as judged by the Investigator. 2. Bronchiectasis due to cystic fibrosis. 3. Current smokers as defined per Centers for Disease Control (CDC). 4. Known or suspected immunodeficiency disorder, including history of invasive opportunistic infections. 5. Known history of human immunodeficiency virus (HIV) infection. 6. Currently being treated for nontuberculous mycobacteria (NTM) lung infection, allergic bronchopulmonary aspergillosis, or tuberculosis (TB). 7. Active and current symptomatic infection by 2019 corona virus disease (COVID-19). 8. Inability to follow the procedures of the study (eg, due to language problems or psychological disorders). 9. Receiving medications or therapy that are prohibited as concomitant medications. 10. Previously participated in a clinical trial for brensocatib. 11. Received any live attenuated vaccine within 4 weeks prior to the first administration of brensocatib. 12. Suffering an exacerbation 4 weeks before Screening or during the Screening period. 13. Adult participants only: Have compliance issues with completion of electronic diary entries during the Screening Period and in the opinion of the Investigator, compliance is unlikely to improve during the study. 14. Participated in any other interventional clinical studies within 3 months before Screening Visit. 15. History of alcohol or drug abuse within 6 months prior to the Screening Visit. 16. Is the Investigator or any Sub-Investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the study. 17. Known history of hypersensitivity to brensocatib or any of its excipients.

Locations (373)

Outcomes

Primary Outcomes

Annualized Rate of Pulmonary Exacerbations (PEs)

PE was defined as having 3 or more of these 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 severe pulmonary exacerbation was that required intravenous (IV) antibacterial drug treatment and/or hospitalization. A minimum of 14 days must have occurred between one exacerbation onset and the next. Any exacerbation that occurred less than 14 days from the prior exacerbation was not considered a new exacerbation. Independent adjudication committee with pulmonary physicians adjudicated reported PE events to see if they fulfil the protocol definition. The rate of PE was analyzed using the negative binomial model.

Time frame: Up to Week 52

Secondary Outcomes

Time to First PE

PE was defined as having 3 or more of following symptoms for at least 48 hours resulting in physician's decision to prescribe antibiotics:1.Increased cough2.Increased sputum volume or change in sputum consistency3.Increased sputum purulence4.Increased breathlessness \&/or decreased exercise tolerance5.Fatigue \&/or malaise6.Hemoptysis.Severe PE were those requiring IV antibacterial drug treatment \&/or hospitalization. Minimum of 14 days must have occurred between one exacerbation onset and next. Any exacerbation that occurred within 14 days of prior exacerbation was not considered a new exacerbation. Time to first PE was calculated from randomization date to onset date of the first exacerbation. Participants who did not have exacerbation at end of 52-week treatment period were considered as censored at date of Week 52 in Cox proportional hazard model. Independent adjudication committee with pulmonary physicians adjudicated reported PE events to see if they fulfil protocol definition.

Time frame: Up to Week 52

Responder Status for Exacerbation-Free Over the 52-Week Treatment Period

Responder status was based on percentage of participants who were exacerbation free over 52-weeks of 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 14 days must have occurred between one exacerbation onset and the next. Any exacerbation that occurred less than 14 days from the prior exacerbation was not considered a new exacerbation. Independent adjudication committee of pulmonary physicians adjudicated reported PE events to see if they fulfill protocol definition. For discontinuation prior to Week 52 without having experienced a confirmed PE, responder status was imputed by multiple imputation.

Data from ClinicalTrials.gov

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