Assessment of INS1007 in Participants With Non-Cystic Fibrosis Bronchiectasis

Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multi-Center Study to Assess the Efficacy, Safety & Tolerability, and PK of INS1007 Administered Once Daily for 24 Weeks in Subjects With Non-CF Bronchiectasis - The Willow Study

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.

Study Overview

• Status: Completed
• Conditions: Non-Cystic Fibrosis Bronchiectasis
• Intervention / Treatment: Drug: Brensocatib 10 mg; Drug: Brensocatib 25 mg; Drug: Placebo

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).

• Study Type: Interventional
• Enrollment (Actual): 256
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Concord, New South Wales, Australia, 2139
      • Concord Repatriation General Hospital
  • Queensland
    • Brisbane, Queensland, Australia, 4101
      • Mater Misericordia Medical Centre
    • Brisbane, Queensland, Australia, 4120
      • Gallipoli Medical Research Foundation
    • Chermside, Queensland, Australia, 4032
      • Metro North Hospital and Health Service (The Prince Charles Hospital)
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Respiratory Clinical Trials Unit, Royal Adelaide Hospital
    • Kent Town, South Australia, Australia, 5067
      • Respiratory Clinical Trials PTY Ltd
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Box Hill Hospital, Eastern Clinical Research Unit
    • Melbourne, Victoria, Australia, 3004
      • Alfred Hospital
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Institute for Respiratory Health
• Belgium
  • Vlaams Brabant
    • Leuven, Vlaams Brabant, Belgium, 3000
      • UZ Leuven
• Bulgaria
  • Plovdiv, Bulgaria, 4000
    • Medical Center Unimed
  • Sliven, Bulgaria, 8800
    • MHAT "Dr IvanSeliminski"-Sliven
  • Stara Zagora, Bulgaria, 6000
    • CardioArt Medical Center
  • Momina
    • Razgrad, Momina, Bulgaria, 7200
      • Medical Center ReSpiro Ltd (Kiselov)
• Denmark
  • Aarhus, Denmark, 8000
    • Aarhus University Hospital
  • Roskilde, Denmark, 4000
    • Sjællands Universitetshospital, Roskilde
  • Capital Region
    • Hvidovre, Capital Region, Denmark, 2650
      • Hvidovre Hospital
• Germany
  • Berlin, Germany, 10717
    • Research Center for Medical Studies (RCMS)
  • München, Germany, 81925
    • Städt. Klinikum München GmbH, Bogenhausen
  • Bavaria
    • Donaustauf, Bavaria, Germany, 93093
      • Krankenhaus Donaustauf
    • Munich, Bavaria, Germany, 80336
      • Klinikum der Universität München Medizinische Klinik V Pneumologie / Mukoviszidose-Zentrum für Erwachsene
  • Bayern
    • Nuernberg, Bayern, Germany, 90419
      • Klinikum Nuernberg
  • Hessen
    • Frankfurt, Hessen, Germany, 60590
      • Universitätsklinikum Frankfurt
    • Frankfurt, Hessen, Germany, 60596
      • IKF Pneumologie Frankfurt
  • NRW
    • Essen, NRW, Germany, 45239
      • Ruhrlandklinik Essen, University Essen
  • Schleswig-Holstein
    • Borstel, Schleswig-Holstein, Germany, 23845
      • Forschungszentrum Borstel
  • Thuringen
    • Jena, Thuringen, Germany, 7747
      • Universitatsklinikum Jena
• Italy
  • Pavia, Italy, 27100
    • Fondazione IRCCS Policlinico San matteo
  • Telese Terme, Italy, 82037
    • ICS Maugeri spa SB, IRCSS Telese
  • Lombardia
    • Milan, Lombardia, Italy, 20122
      • University of Milan, IRCCS Fondazione Ca' Granda Ospedale Maggiore Policlinico
  • Monza E Brianza
    • Monza, Monza E Brianza, Italy, 20900
      • Ospedale San Gerardo
  • Via Paradisa 2
    • Pisa, Via Paradisa 2, Italy, 56124
      • University Hospital of Pisa
• Korea, Republic of
  • Gwangju, Korea, Republic of, 61469
    • Chonnam National University Hospital
  • Incheon, Korea, Republic of, 21431
    • The Catholic University of Korea Incheon St. Mary's Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05030
    • Konkuk University Medical Center
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06591
    • The Catholic University of Korea, Seoul ST. Mary's Hospital
  • Seoul, Korea, Republic of, 02559
    • The Catholic University of Korea, ST. Paul's Hospital
  • Jung-gu
    • Incheon, Jung-gu, Korea, Republic of, 22332
      • Inha University Hospital
  • Namdong-gu
    • Incheon, Namdong-gu, Korea, Republic of, 21565
      • Gachon University Gil Medical Center
• Netherlands
  • Alkmaar, Netherlands, 1815JD
    • Noordwest Ziekenhuis Group
  • Breda, Netherlands, 4818CK
    • Amphia Longresearch Astma/COPD Uni 52/5e etage
  • Nijmegen, Netherlands, 6525GA
    • RadboudUMC, location Dekkerswald
  • Sittard, Netherlands, 6162BG
    • Zuyderland MC
• New Zealand
  • Auckland, New Zealand, 1051
    • Auckland District Health Board, Greenlane clinical Centre
  • BOP
    • Tauranga, BOP, New Zealand, 3110
      • P3 Research
  • Hawkes Bay
    • Hastings, Hawkes Bay, New Zealand, 4130
      • P3 Research (Hawke's Bay)
  • Otago
    • Dunedin, Otago, New Zealand, 9016
      • Southern District health Board/Dunedin Hospital
  • Waikato
    • Hamilton, Waikato, New Zealand, 3204
      • Waikato District Health Board
• Poland
  • Kraków, Poland, 31-159
    • Grażyna Jasieniak Pinis Niepubliczny Zakład Opieki Zdrowotnej Atopia
  • Kraków, Poland, 31-455
    • NZOZ Krak-Medyk Sp. z o.o
  • Sucha Beskidzka, Poland, 34-200
    • Gabinet Lekarski Pediatryczno-Alergologiczny Zenon Bukowczan
  • Łódź, Poland, 90-153
    • Medical University of Lodz Poland
  • Dolnośląskie
    • Wrocław, Dolnośląskie, Poland, 51-162
      • Centrum Badan Klinicznych, Piotr Napora Lekarze i Spolka Partnerska, Osrodek Badan Wczesnej Fazy
• Singapore
  • Singapore, Singapore, 529889
    • Changi General Hospital
  • Singapore, Singapore, 169856
    • Singapore General Hospital
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clínic de Barcelona
  • Barcelona, Spain, 08041
    • Hospital de la Santa Creu i Sant Pau
  • Barcelona, Spain, 08907
    • Hospital Universitari de Bellvitge
  • Girona, Spain, 17007
    • Hospital Universitari de Girona Dr. Josep Trueta
  • Valencia, Spain, 46026
    • Hospital Universiatrio y politecnico La Fe
• United Kingdom
  • London, United Kingdom, SW3 6HP
    • Royal Brompton & Harefield NHS Foundation Trust
  • Manchester, United Kingdom, M8 5RB
    • Pennine Acute Hospitals NHS Trust
  • Southampton, United Kingdom, SO16 6YD
    • University Hospital Southampton NHS Foundation Trust
  • Angus
    • Dundee, Angus, United Kingdom, DD1 9SY
      • NHS Tayside
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB23 3RE
      • Papworth Hospital NHS Foundation Trust
  • Lancashire
    • Blackpool, Lancashire, United Kingdom, FY38NR
      • Blackpool Teaching Hospitals NHS Foundation Trust
  • Merseyside
    • Liverpool, Merseyside, United Kingdom, L14 3PE
      • Liverpool Heart and Chest Hospital NHS Foundation Trust
  • Scotland
    • Edinburgh, Scotland, United Kingdom, EH16 4SA
      • NHS Lothian
  • Surrey
    • Chertsey, Surrey, United Kingdom, KT16 0PZ
      • Ashford and St Peter's Hospitals NHS Foundation Trust
  • West Midlands
    • Wolverhampton, West Midlands, United Kingdom, WV10 0QP
      • The Royal Wolverhampton NHS Trust
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • Arizona
    • Peoria, Arizona, United States, 85381
      • Phoenix Medical Group
  • California
    • Newport Beach, California, United States, 92663
      • NewportNativeMD
    • Palm Springs, California, United States, 92262-4871
      • Palmtree Clinical Research
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center
    • Stanford, California, United States, 94305-5236
      • Stanford University Medical Center
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Heath
  • Connecticut
    • Farmington, Connecticut, United States, 06030-1321
      • UConn Health Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • MedStar Georgetown University Hospital
  • Florida
    • Celebration, Florida, United States, 34747
      • Clinical Research Specialists, LLC
    • Clearwater, Florida, United States, 33765
      • St. Francis Medical Institute
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine
    • Miami Lakes, Florida, United States, 33014
      • San Marcus Research Clinic, Inc.
    • Sarasota, Florida, United States, 34239
      • Sarasota Memorial Hospital Clinical Research Center
  • Georgia
    • Atlanta, Georgia, United States, 30342-2147
      • The Emory Clinic, Pulmonology
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • LSU Health Sciences Center
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University, Division of Pulmonary and Critical Care Medicine
    • Towson, Maryland, United States, 21286
      • Pulmonary and Critical Care Associates of Baltimore
    • Westminster, Maryland, United States, 21157
      • Mid Atlantic Pulmonary & Research Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Michigan Medicine
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center/ New York Presbyterian Hospital
    • New York, New York, United States, 10016
      • NYU Pulmonary & Critical Care Associates
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • The University of North Carolina at Chapel Hill
    • Charlotte, North Carolina, United States, 28215
      • Novant Health Pulmonary Medicine South
    • Winston-Salem, North Carolina, United States, 27103
      • Southeastern Research Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
  • Texas
    • Mesquite, Texas, United States, 75149
      • SMS Clinical Research, LLC
    • Tyler, Texas, United States, 75708
      • The University of Texas Health Science at Tyler
  • Washington
    • Tacoma, Washington, United States, 98405
      • MultiCare Institute for Research & Innovation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Clinical history consistent with NCFBE (cough, chronic sputum production and/or recurrent respiratory infections)
2. Are current sputum producers with a history of chronic expectoration and able to provide a sputum sample during Screening
3. Have at least 2 documented pulmonary exacerbations in the past 12 months before Screening

Exclusion Criteria:

1. Have a primary diagnosis of chronic obstructive pulmonary disease (COPD) or asthma
2. Have bronchiectasis due to cystic fibrosis (CF), hypogammaglobulinemia, common variable immunodeficiency, or alpha1-antitrypsin deficiency
3. Are current smokers
4. Are currently being treated for a nontuberculous mycobacterial lung infection, allergic bronchopulmonary aspergillosis, or tuberculosis
5. Have any acute infections, (including respiratory infections)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Brensocatib 10 mg; Participants received brensocatib 10 mg once daily (QD) before breakfast, for 24 weeks.	Drug: Brensocatib 10 mg; Administered once per day for 24 weeks
Experimental: Brensocatib 25 mg; Participants received brensocatib 25 mg QD before breakfast, for 24 weeks.	Drug: Brensocatib 25 mg; Administered once per day for 24 weeks
Placebo Comparator: Placebo; Participants received the matching placebo QD before breakfast, for 24 weeks.	Drug: Placebo; Administered once per day for 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to the First Pulmonary Exacerbation Over 24-Week Treatment Period	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.	Baseline (Day 1) to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Quality of Life Questionnaire - Bronchiectasis (QOL-B) Respiratory Symptoms Domain Score Over 24 Week Treatment Period	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.	Baseline (Day 1) to Week 24
Change From Screening in Post-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Over 24-Week Treatment Period	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.	Screening (Days -42 to -1) to Week 24
Change From Baseline in Concentration of Active Neutrophil Elastase (NE) in Sputum	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.	Baseline (Day 1) to Week 24
Number of Participants Who Experienced a Pulmonary 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.	Baseline (Day 1) to Week 24

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in QOL-B scores (excluding Respiratory Symptoms Domain)	Change from Baseline in score of QOL-B domains (excluding respiratory symptoms domain) at 24-weeks.	24-week treatment period
Change from Baseline in Leicester Cough Questionnaire (LCQ) score	Change from Baseline in LCQ score at 24-weeks.	24-week treatment period
Change from Baseline in St. George's Respiratory Questionnaire (SGRQ) score	Change from Baseline in SGRQ total score at 24- weeks.	24-week treatment period
Change from Screening of forced vital capacity (FVC)	Change from Screening of FVC at Weeks 12 and 24.	At Week 12 and Week 24
Change from Screening of peak expiratory flow rate (PEFR)	Change from Screening of PEFR at Weeks 12 and 24.	At Week 12 and Week 24
Change from Screening of forced exploratory flow 25% to 75% (FEF25-75)	Change from Screening in FEF25-75 at Weeks 12 and 24.	At Week 12 and Week 24

Collaborators and Investigators

• Sponsor: Insmed Incorporated

Publications and helpful links

General Publications

• Chalmers JD, Haworth CS, Metersky ML, Loebinger MR, Blasi F, Sibila O, O'Donnell AE, Sullivan EJ, Mange KC, Fernandez C, Zou J, Daley CL; WILLOW Investigators. Phase 2 Trial of the DPP-1 Inhibitor Brensocatib in Bronchiectasis. N Engl J Med. 2020 Nov 26;383(22):2127-2137. doi: 10.1056/NEJMoa2021713. Epub 2020 Sep 7.

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2017
• Primary Completion (Actual): December 12, 2019
• Study Completion (Actual): December 12, 2019

Study Registration Dates

• First Submitted: July 11, 2017
• First Submitted That Met QC Criteria: July 12, 2017
• First Posted (Actual): July 17, 2017

Study Record Updates

• Last Update Posted (Actual): March 27, 2023
• Last Update Submitted That Met QC Criteria: March 23, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: bronchiectasis; P aeruginosa; active neutrophil elastase
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Bronchial Diseases; Fibrosis; Bronchiectasis
• Other Study ID Numbers: INS1007-201; 2017-002533-32 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No