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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy, Safety, and Tolerability of Brensocatib Administered Once Daily for 52 Weeks in Subjects With Non-Cystic Fibrosis Bronchiectasis - The ASPEN Study

Conditions
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Non-Cystic Fibrosis Bronchiectasis

Intervention / Treatment
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* Drug: Brensocatib 10 mg
* Drug: Brensocatib 25 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. 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. 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. 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. 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. 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: A primary diagnosis of chronic obstructive pulmonary disease (COPD) or asthma as judged by the Investigator. Bronchiectasis due to cystic fibrosis. Current smokers as defined per Centers for Disease Control (CDC). Known or suspected immunodeficiency disorder, including history of invasive opportunistic infections. Known history of human immunodeficiency virus (HIV) infection. Currently being treated for nontuberculous mycobacteria (NTM) lung infection, allergic bronchopulmonary aspergillosis, or tuberculosis (TB). Active and current symptomatic infection by 2019 corona virus disease (COVID-19). Inability to follow the procedures of the study (eg, due to language problems or psychological disorders). Receiving medications or therapy that are prohibited as concomitant medications. Previously participated in a clinical trial for brensocatib. Received any live attenuated vaccine within 4 weeks prior to the first administration of brensocatib. Suffering an exacerbation 4 weeks before Screening or during the Screening period. 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. Participated in any other interventional clinical studies within 3 months before Screening Visit. History of alcohol or drug abuse within 6 months prior to the Screening Visit. 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. Known history of hypersensitivity to brensocatib or any of its excipients.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brensocatib 10 mg<br>Participants will receive brensocatib 10 mg, tablets orally, once daily, for 52 weeks. | Drug: Brensocatib 10 mg<br>* Oral tablet.<br>* Other names: INS1007;|
| Experimental: Brensocatib 25 mg<br>Participants will receive brensocatib 25 mg, tablets orally, once daily, for 52 weeks. | Drug: Brensocatib 25 mg<br>* Oral tablet.<br>* Other names: INS1007;|
| Placebo Comparator: Placebo<br>Participants will receive a brensocatib-matching placebo, tablets orally, once daily, for 52 weeks. | Drug: Placebo<br>* Brensocatib-matching oral tablet.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Adjudicated Pulmonary Exacerbations (PEs) |  | 52 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Adjudicated Pulmonary Exacerbation (PE) |  | 52 Weeks | 
| Percentage of Participants who are Pulmonary Exacerbation (PE) Free |  | 52 Weeks | 
| Change From Baseline in Postbronchodilator Forced Expiratory Volume in 1 Second (FEV1) |  | Baseline, at Week 52 | 
| Rate of Severe Adjudicated Pulmonary Exacerbations (PEs) |  | 52 Weeks | 
| Change from Baseline to Week 52 in Quality of Life Questionnaire - Bronchiectasis (QOL-B) Respiratory Symptoms Domain Score in Adult Participants |  | Baseline to Week 52 | 
| Number of Participants who Experience at Least one Treatment-Emergent Adverse Events (TEAEs) |  | 56 Weeks | 
| Plasma Concentration of Brensocatib at Select Time Points |  | Pre-dose and post-dose at multiple time points up to Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ASPEN, Brensocatib, INS1007