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

• ClinicalTrials.gov Identifier: NCT04594369
• Recruitment Status: Recruiting
• First Posted: October 20, 2020
• Last Update Posted: August 2, 2022
• Sponsor: Insmed Incorporated
• Information provided by (Responsible Party): Insmed Incorporated

Tracking Information

• First Submitted Date: October 14, 2020
• First Posted Date: October 20, 2020
• Last Update Posted Date: August 2, 2022
• Actual Study Start Date: December 1, 2020
• Estimated Primary Completion Date: March 22, 2024 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: April 22, 2022): Rate of Adjudicated Pulmonary Exacerbations (PEs) [ Time Frame: 52 Weeks ]
• Original Primary Outcome Measures (submitted: October 14, 2020): Rate of Pulmonary Exacerbations (PEs) [ Time Frame: 52 Weeks ]

Current Secondary Outcome Measures (submitted: April 22, 2022)

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

Original Secondary Outcome Measures (submitted: October 14, 2020)

• Time to First Pulmonary Exacerbation (PE) [ Time Frame: 52 Weeks ]
• Percentage of Participants who are Pulmonary Exacerbation (PE) Free [ Time Frame: 52 Weeks ]
• Change from Baseline in Postbronchodilator Forced Expiratory Volume in 1 second (FEV1) Measurements [ Time Frame: Baseline to Week 52 ]
• Rate of Severe Pulmonary Exacerbations (PEs) [ Time Frame: 52 Weeks ]
• Change from Baseline to Week 52 in Quality of Life Questionnaire - Bronchiectasis (QOL-B) Respiratory Symptoms Domain Score [ Time Frame: Baseline to Week 52 ]
• Incidence and severity of treatment-emergent adverse events [ Time Frame: Up to Week 56 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Assess the Efficacy, Safety, and Tolerability of Brensocatib in Participants With Non-Cystic Fibrosis Bronchiectasis
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Non-Cystic Fibrosis Bronchiectasis

Intervention

• Drug: Brensocatib 10 mg
  Oral tablet.
  Other Name: INS1007
• Drug: Brensocatib 25 mg
  Oral tablet.
  Other Name: INS1007
• Drug: Placebo
  Brensocatib-matching oral tablet.

Study Arms

• Experimental: Brensocatib 10 mg
  Participants will receive brensocatib 10 mg, tablets orally, once daily, for 52 weeks.
  Intervention: Drug: Brensocatib 10 mg
• Experimental: Brensocatib 25 mg
  Participants will receive brensocatib 25 mg, tablets orally, once daily, for 52 weeks.
  Intervention: Drug: Brensocatib 25 mg
• Placebo Comparator: Placebo
  Participants will receive a brensocatib-matching placebo, tablets orally, once daily, for 52 weeks.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 14, 2020): 1620
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 22, 2024
• Estimated Primary Completion Date: March 22, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years to 85 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Insmed Medical Information; 1-844-446-7633; medicalinformation@insmed.com

• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, Colombia, Denmark, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Latvia, Malaysia, Mexico, Netherlands, New Zealand, Peru, Poland, Portugal, Serbia, Slovakia, Spain, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States
• Removed Location Countries: Estonia, Lithuania

Administrative Information

• NCT Number: NCT04594369
• Other Study ID Numbers: INS1007-301; 2020-003688-25 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Insmed Incorporated
• Original Responsible Party: Same as current
• Current Study Sponsor: Insmed Incorporated
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Insmed Incorporated
• Verification Date: August 2022