Assessment of INS1007 in Participants With Non-Cystic Fibrosis Bronchiectasis
- Conditions
- Non-Cystic Fibrosis Bronchiectasis
- Interventions
- Registration Number
- NCT03218917
- Lead Sponsor
- Insmed Incorporated
- Brief Summary
The purpose of the study is to evaluate if INS1007 can reduce pulmonary exacerbations over a 24-week treatment period in participants with non-cystic fibrosis bronchiectasis.
- Detailed Description
Phase 2 randomized, double-blind, placebo-controlled, parallel-group, multicenter, multi-national study to assess the efficacy, safety and tolerability, and pharmacokinetics (PK) of INS1007 administered once daily for 24 weeks in participants with non-cystic fibrosis bronchiectasis (NCFBE).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 256
- Clinical history consistent with NCFBE (cough, chronic sputum production and/or recurrent respiratory infections)
- Are current sputum producers with a history of chronic expectoration and able to provide a sputum sample during Screening
- Have at least 2 documented pulmonary exacerbations in the past 12 months before Screening
- Have a primary diagnosis of chronic obstructive pulmonary disease (COPD) or asthma
- Have bronchiectasis due to cystic fibrosis (CF), hypogammaglobulinemia, common variable immunodeficiency, or alpha1-antitrypsin deficiency
- Are current smokers
- Are currently being treated for a nontuberculous mycobacterial lung infection, allergic bronchopulmonary aspergillosis, or tuberculosis
- Have any acute infections, (including respiratory infections)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Brensocatib 25 mg Brensocatib 25 mg Participants received brensocatib 25 mg QD before breakfast, for 24 weeks. Placebo Placebo Participants received the matching placebo QD before breakfast, for 24 weeks. Brensocatib 10 mg Brensocatib 10 mg Participants received brensocatib 10 mg once daily (QD) before breakfast, for 24 weeks.
- Primary Outcome Measures
Name Time Method Time to the First Pulmonary Exacerbation Over 24-Week Treatment Period Baseline (Day 1) to Week 24 Time to first pulmonary exacerbation was calculated as the number of days from the date of randomization to the date of first documentation of an exacerbation. 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 4 weeks must have occurred between one exacerbation onset and the next. Any exacerbation that occurred less than 4 weeks from the prior exacerbation was not considered a new exacerbation. The analysis was performed using the stratified log rank test and using Kaplan Meier (KM) curves.
- Secondary Outcome Measures
Name Time Method Change From Screening in Post-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Over 24-Week Treatment Period Screening (Days -42 to -1) to Week 24 FEV1 was used to assess lung function and is the maximum amount of air that can be forced out in one second after taking a deep breath. The percent predicted FEV1 was calculated by converting the spirometer reading to a percentage of what would be predicted as normal FEV1 based on a several personal factors (e.g. sex, age, etc.). Change from screening in percent predicted FEV1 to Week 24 was calculated as: percent predicted FEV1 value at Week 24 and percent predicted FEV1 value at screening. A positive percent change from screening indicates an improvement in lung function. The analysis was done using analysis of covariance (ANCOVA) with Pa colonization status and maintenance macrolide antibiotic use at Baseline as covariates.
Change From Baseline in Quality of Life Questionnaire - Bronchiectasis (QOL-B) Respiratory Symptoms Domain Score Over 24 Week Treatment Period Baseline (Day 1) to Week 24 The QOL-B is a validated, self-administered patient reported outcome (PRO) that assesses symptoms, functioning, and health-related (HR) QOL for participants with non-cystic fibrosis bronchiectasis (NCFBE). The QOL-B contains 37 items in 8 domains (Respiratory Symptoms, Physical Functioning, Role Functioning, Emotional Functioning, Social Functioning, Vitality, Health Perceptions and Treatment Burden). Each of the 37 items is scored from 1 to 4, and each of the 8 domains scale scores is standardized on a 0-100 point scale, with higher scores representing fewer symptoms or better functioning and HR QoL. A positive change from Baseline indicates improvement in symptoms. For this outcome measure, change in the respiratory symptoms domain score from Baseline was reported. The analysis was based on mixed model for repeated measures (MMRM) approach.
Change From Baseline in Concentration of Active Neutrophil Elastase (NE) in Sputum Baseline (Day 1) to Week 24 The concentration of active NE in sputum, was measured by the difference between the pre-treatment concentration and on-treatment concentration. In bronchiectasis, activation of neutrophils in the airway leads to release of NE which leads to damaged airway walls, mucus hypersecretion, exacerbated inflammation, which in turn affects neutrophil and macrophage functions, increasing the risk of infection. Negative change from Baseline indicates improvement.
Number of Participants Who Experienced a Pulmonary Exacerbation Baseline (Day 1) to Week 24 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 4 weeks must have occurred between one exacerbation onset and the next. Any exacerbation that occurred less than 4 weeks from the prior exacerbation was not considered a new exacerbation.
Trial Locations
- Locations (108)
MHAT "Dr IvanSeliminski"-Sliven
🇧🇬Sliven, Bulgaria
Cardioart Medical Center
🇧🇬Stara Zagora, Bulgaria
Sjællands Universitetshospital, Roskilde
🇩🇰Roskilde, Denmark
Klinikum der Universität München Medizinische Klinik V Pneumologie / Mukoviszidose-Zentrum für Erwachsene
🇩🇪Munich, Bavaria, Germany
Krankenhaus Donaustauf
🇩🇪Donaustauf, Bavaria, Germany
Universitätsklinikum Frankfurt
🇩🇪Frankfurt, Hessen, Germany
Klinikum Nuernberg
🇩🇪Nuernberg, Bayern, Germany
IKF Pneumologie Frankfurt
🇩🇪Frankfurt, Hessen, Germany
Ruhrlandklinik Essen, University Essen
🇩🇪Essen, NRW, Germany
Research Center for Medical Studies (RCMS)
🇩🇪Berlin, Germany
Forschungszentrum Borstel
🇩🇪Borstel, Schleswig-Holstein, Germany
Universitätsklinikum Jena
🇩🇪Jena, Thuringen, Germany
Städt. Klinikum München GmbH, Bogenhausen
🇩🇪München, Germany
Ospedale San Gerardo
🇮🇹Monza, Monza E Brianza, Italy
Fondazione IRCCS Policlinico San Matteo
🇮🇹Pavia, Italy
ICS Maugeri spa SB, IRCSS Telese
🇮🇹Telese Terme, Italy
Gachon University Gil Medical Center
🇰🇷Incheon, Namdong-gu, Korea, Republic of
Inha University Hospital
🇰🇷Incheon, Jung-gu, Korea, Republic of
Chonnam National University Hospital
🇰🇷Gwangju, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea, St. Paul's Hospital
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea Incheon St. Mary's Hospital
🇰🇷Incheon, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Konkuk University Medical Center
🇰🇷Seoul, Korea, Republic of
Noordwest Ziekenhuis Group
🇳🇱Alkmaar, Netherlands
The Catholic University of Korea, Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Amphia Longresearch Astma/COPD Uni 52/5e etage
🇳🇱Breda, Netherlands
RadboudUMC, location Dekkerswald
🇳🇱Nijmegen, Netherlands
Zuyderland MC
🇳🇱Sittard, Netherlands
P3 Research
🇳🇿Tauranga, BOP, New Zealand
P3 Research (Hawke's Bay)
🇳🇿Hastings, Hawkes Bay, New Zealand
Southern District health Board/Dunedin Hospital
🇳🇿Dunedin, Otago, New Zealand
Waikato District Health Board
🇳🇿Hamilton, Waikato, New Zealand
Auckland District Health Board, Greenlane clinical Centre
🇳🇿Auckland, New Zealand
Centrum Badan Klinicznych, Piotr Napora Lekarze i Spolka Partnerska, Osrodek Badan Wczesnej Fazy
🇵🇱Wrocław, Dolnośląskie, Poland
Grażyna Jasieniak Pinis Niepubliczny Zakład Opieki Zdrowotnej Atopia
🇵🇱Kraków, Poland
NZOZ Krak-Medyk Sp. z o.o
🇵🇱Kraków, Poland
Gabinet Lekarski Pediatryczno-Alergologiczny Zenon Bukowczan
🇵🇱Sucha Beskidzka, Poland
Medical University of Lodz Poland
🇵🇱Łódź, Poland
Singapore General Hospital
🇸🇬Singapore, Singapore
Changi General Hospital
🇸🇬Singapore, Singapore
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital Universitari de Bellvitge
🇪🇸Barcelona, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Universiatrio y politecnico La Fe
🇪🇸Valencia, Spain
Hospital Universitari de Girona Dr. Josep Trueta
🇪🇸Girona, Spain
NHS Tayside
🇬🇧Dundee, Angus, United Kingdom
Liverpool Heart and Chest Hospital NHS Foundation Trust
🇬🇧Liverpool, Merseyside, United Kingdom
The Royal Wolverhampton NHS Trust
🇬🇧Wolverhampton, West Midlands, United Kingdom
Royal Brompton & Harefield NHS Foundation Trust
🇬🇧London, United Kingdom
Pennine Acute Hospitals NHS Trust
🇬🇧Manchester, United Kingdom
University Hospital Southampton NHS Foundation Trust
🇬🇧Southampton, United Kingdom
Institute for Respiratory Health
🇦🇺Nedlands, Western Australia, Australia
University of Florida
🇺🇸Gainesville, Florida, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
NewportNativeMD
🇺🇸Newport Beach, California, United States
National Jewish Heath
🇺🇸Denver, Colorado, United States
St. Francis Medical Institute
🇺🇸Clearwater, Florida, United States
San Marcus Research Clinic, Inc.
🇺🇸Miami Lakes, Florida, United States
The Emory Clinic, Pulmonology
🇺🇸Atlanta, Georgia, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Johns Hopkins University, Division of Pulmonary and Critical Care Medicine
🇺🇸Baltimore, Maryland, United States
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
Temple University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Respiratory Clinical Trials Unit, Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Hvidovre Hospital
🇩🇰Hvidovre, Capital Region, Denmark
Aarhus University Hospital
🇩🇰Aarhus, Denmark
University of Milan, IRCCS Fondazione Ca' Granda Ospedale Maggiore Policlinico
🇮🇹Milan, Lombardia, Italy
University Hospital of Pisa
🇮🇹Pisa, Via Paradisa 2, Italy
Medical Center ReSpiro Ltd (Kiselov)
🇧🇬Razgrad, Momina, Bulgaria
Phoenix Medical Group
🇺🇸Peoria, Arizona, United States
UConn Health Center
🇺🇸Farmington, Connecticut, United States
MedStar Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States
Box Hill Hospital, Eastern Clinical Research Unit
🇦🇺Box Hill, Victoria, Australia
NHS Lothian
🇬🇧Edinburgh, Scotland, United Kingdom
Papworth Hospital NHS Foundation Trust
🇬🇧Cambridge, Cambridgeshire, United Kingdom
Ashford and St Peter's Hospitals NHS Foundation Trust
🇬🇧Chertsey, Surrey, United Kingdom
UC Davis Medical Center
🇺🇸Sacramento, California, United States
Palmtree Clinical Research
🇺🇸Palm Springs, California, United States
Stanford University Medical Center
🇺🇸Stanford, California, United States
Clinical Research Specialists, LLC
🇺🇸Celebration, Florida, United States
University of Miami Miller School of Medicine
🇺🇸Miami, Florida, United States
Sarasota Memorial Hospital Clinical Research Center
🇺🇸Sarasota, Florida, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
LSU Health Sciences Center
🇺🇸New Orleans, Louisiana, United States
Pulmonary and Critical Care Associates of Baltimore
🇺🇸Towson, Maryland, United States
Michigan Medicine
🇺🇸Ann Arbor, Michigan, United States
The University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Columbia University Medical Center/ New York Presbyterian Hospital
🇺🇸New York, New York, United States
Novant Health Pulmonary Medicine South
🇺🇸Charlotte, North Carolina, United States
Mid Atlantic Pulmonary & Research Center
🇺🇸Westminster, Maryland, United States
NYU Pulmonary & Critical Care Associates
🇺🇸New York, New York, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
SMS Clinical Research, LLC
🇺🇸Mesquite, Texas, United States
The University of Texas Health Science at Tyler
🇺🇸Tyler, Texas, United States
MultiCare Institute for Research & Innovation
🇺🇸Tacoma, Washington, United States
Concord Repatriation General Hospital
🇦🇺Concord, New South Wales, Australia
Mater Misericordia Medical Centre
🇦🇺Brisbane, Queensland, Australia
Gallipoli Medical Research Foundation
🇦🇺Brisbane, Queensland, Australia
Metro North Hospital and Health Service (The Prince Charles Hospital)
🇦🇺Chermside, Queensland, Australia
Respiratory Clinical Trials PTY LTD
🇦🇺Kent Town, South Australia, Australia
Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Medical Center UNIMED
🇧🇬Plovdiv, Bulgaria
UZ Leuven
🇧🇪Leuven, Vlaams Brabant, Belgium
Southeastern Research Center
🇺🇸Winston-Salem, North Carolina, United States
Blackpool Teaching Hospitals NHS Foundation Trust
🇬🇧Blackpool, Lancashire, United Kingdom