Assessment of INS1007 in Participants With Non-Cystic Fibrosis Bronchiectasis

NCT03218917 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: INS1007-2012017-002533-32
• Study Type: interventional
• Target: 256
• Locations: 14 countries
• Sites: 108

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.

Conditions

Non-Cystic Fibrosis Bronchiectasis

Keywords

P aeruginosa; bronchiectasis; active neutrophil elastase

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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

• 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

• Change From Baseline in Concentration of Active Neutrophil Elastase (NE) in Sputum

  Baseline (Day 1) to Week 24

• Number of Participants Who Experienced a Pulmonary Exacerbation

  Baseline (Day 1) to Week 24

Study Arms (3)

Brensocatib 10 mg

EXPERIMENTAL

Participants received brensocatib 10 mg once daily (QD) before breakfast, for 24 weeks.

Drug: Brensocatib 10 mg

Brensocatib 25 mg

EXPERIMENTAL

Participants received brensocatib 25 mg QD before breakfast, for 24 weeks.

Drug: Brensocatib 25 mg

Placebo

PLACEBO COMPARATOR

Participants received the matching placebo QD before breakfast, for 24 weeks.

Drug: Placebo

Interventions

Brensocatib 10 mg DRUG

Administered once per day for 24 weeks

Brensocatib 10 mg

Brensocatib 25 mg DRUG

Administered once per day for 24 weeks

Brensocatib 25 mg

Placebo DRUG

Administered once per day for 24 weeks

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Insmed Incorporated: lead

Study Sites (108)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Phoenix Medical Group

Peoria, Arizona, 85381, United States

Location

NewportNativeMD

Newport Beach, California, 92663, United States

Location

Palmtree Clinical Research

Palm Springs, California, 92262-4871, United States

Location

UC Davis Medical Center

Sacramento, California, 95817, United States

Location

Stanford University Medical Center

Stanford, California, 94305-5236, United States

Location

National Jewish Heath

Denver, Colorado, 80206, United States

Location

UConn Health Center

Farmington, Connecticut, 06030-1321, United States

Location

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Clinical Research Specialists, LLC

Celebration, Florida, 34747, United States

Location

St. Francis Medical Institute

Clearwater, Florida, 33765, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

San Marcus Research Clinic, Inc.

Miami Lakes, Florida, 33014, United States

Location

Sarasota Memorial Hospital Clinical Research Center

Sarasota, Florida, 34239, United States

Location

The Emory Clinic, Pulmonology

Atlanta, Georgia, 30342-2147, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

LSU Health Sciences Center

New Orleans, Louisiana, 70112, United States

Location

Johns Hopkins University, Division of Pulmonary and Critical Care Medicine

Baltimore, Maryland, 21205, United States

Location

Pulmonary and Critical Care Associates of Baltimore

Towson, Maryland, 21286, United States

Location

Mid Atlantic Pulmonary & Research Center

Westminster, Maryland, 21157, United States

Location

Michigan Medicine

Ann Arbor, Michigan, 48109, United States

Location

NYU Pulmonary & Critical Care Associates

New York, New York, 10016, United States

Location

Columbia University Medical Center/ New York Presbyterian Hospital

New York, New York, 10032, United States

Location

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Novant Health Pulmonary Medicine South

Charlotte, North Carolina, 28215, United States

Location

Southeastern Research Center

Winston-Salem, North Carolina, 27103, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Temple University Hospital

Philadelphia, Pennsylvania, 19140, United States

Location

SMS Clinical Research, LLC

Mesquite, Texas, 75149, United States

Location

The University of Texas Health Science at Tyler

Tyler, Texas, 75708, United States

Location

MultiCare Institute for Research & Innovation

Tacoma, Washington, 98405, United States

Location

Concord Repatriation General Hospital

Concord, New South Wales, 2139, Australia

Location

Mater Misericordia Medical Centre

Brisbane, Queensland, 4101, Australia

Location

Gallipoli Medical Research Foundation

Brisbane, Queensland, 4120, Australia

Location

Metro North Hospital and Health Service (The Prince Charles Hospital)

Chermside, Queensland, 4032, Australia

Location

Respiratory Clinical Trials Unit, Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Respiratory Clinical Trials PTY LTD

Kent Town, South Australia, 5067, Australia

Location

Box Hill Hospital, Eastern Clinical Research Unit

Box Hill, Victoria, 3128, Australia

Location

Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Institute for Respiratory Health

Nedlands, Western Australia, 6009, Australia

Location

UZ Leuven

Leuven, Vlaams Brabant, 3000, Belgium

Location

Medical Center ReSpiro Ltd (Kiselov)

Razgrad, Momina, 7200, Bulgaria

Location

Medical Center UNIMED

Plovdiv, 4000, Bulgaria

Location

MHAT "Dr IvanSeliminski"-Sliven

Sliven, 8800, Bulgaria

Location

Cardioart Medical Center

Stara Zagora, 6000, Bulgaria

Location

Hvidovre Hospital

Hvidovre, Capital Region, 2650, Denmark

Location

Aarhus University Hospital

Aarhus, 8000, Denmark

Location

Sjællands Universitetshospital, Roskilde

Roskilde, 4000, Denmark

Location

Krankenhaus Donaustauf

Donaustauf, Bavaria, 93093, Germany

Location

Klinikum der Universität München Medizinische Klinik V Pneumologie / Mukoviszidose-Zentrum für Erwachsene

Munich, Bavaria, 80336, Germany

Location

Klinikum Nuernberg

Nuremberg, Bavaria, 90419, Germany

Location

Universitätsklinikum Frankfurt

Frankfurt am Main, Hesse, 60590, Germany

Location

IKF Pneumologie Frankfurt

Frankfurt am Main, Hesse, 60596, Germany

Location

Ruhrlandklinik Essen, University Essen

Essen, North Rhine-Westphalia, 45239, Germany

Location

Forschungszentrum Borstel

Borstel, Schleswig-Holstein, 23845, Germany

Location

Universitätsklinikum Jena

Jena, Thuringia, 7747, Germany

Location

Research Center for Medical Studies (RCMS)

Berlin, 10717, Germany

Location

Städt. Klinikum München GmbH, Bogenhausen

München, 81925, Germany

Location

University of Milan, IRCCS Fondazione Ca' Granda Ospedale Maggiore Policlinico

Milan, Lombardy, 20122, Italy

Location

Ospedale San Gerardo

Monza, Monza E Brianza, 20900, Italy

Location

University Hospital of Pisa

Pisa, Via Paradisa 2, 56124, Italy

Location

Fondazione IRCCS Policlinico San Matteo

Pavia, 27100, Italy

Location

ICS Maugeri spa SB, IRCSS Telese

Telese Terme, 82037, Italy

Location

Noordwest Ziekenhuis Group

Alkmaar, 1815JD, Netherlands

Location

Amphia Longresearch Astma/COPD Uni 52/5e etage

Breda, 4818CK, Netherlands

Location

RadboudUMC, location Dekkerswald

Nijmegen, 6525GA, Netherlands

Location

Zuyderland MC

Sittard, 6162BG, Netherlands

Location

P3 Research

Tauranga, BOP, 3110, New Zealand

Location

P3 Research (Hawke's Bay)

Hastings, Hawkes Bay, 4130, New Zealand

Location

Southern District health Board/Dunedin Hospital

Dunedin, Otago, 9016, New Zealand

Location

Waikato District Health Board

Hamilton, Waikato Region, 3204, New Zealand

Location

Auckland District Health Board, Greenlane clinical Centre

Auckland, 1051, New Zealand

Location

Centrum Badan Klinicznych, Piotr Napora Lekarze i Spolka Partnerska, Osrodek Badan Wczesnej Fazy

Wroclaw, Lower Silesian Voivodeship, 51-162, Poland

Location

Grażyna Jasieniak Pinis Niepubliczny Zakład Opieki Zdrowotnej Atopia

Krakow, 31-159, Poland

Location

NZOZ Krak-Medyk Sp. z o.o

Krakow, 31-455, Poland

Location

Medical University of Lodz Poland

Lodz, 90-153, Poland

Location

Gabinet Lekarski Pediatryczno-Alergologiczny Zenon Bukowczan

Sucha Beskidzka, 34-200, Poland

Location

Singapore General Hospital

Singapore, 169856, Singapore

Location

Changi General Hospital

Singapore, 529889, Singapore

Location

Inha University Hospital

Incheon, Jung-gu, 22332, South Korea

Location

Gachon University Gil Medical Center

Incheon, Namdong-gu, 21565, South Korea

Location

Chonnam National University Hospital

Gwangju, 61469, South Korea

Location

The Catholic University of Korea Incheon St. Mary's Hospital

Incheon, 21431, South Korea

Location

The Catholic University of Korea, St. Paul's Hospital

Seoul, 02559, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Konkuk University Medical Center

Seoul, 05030, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, 06591, South Korea

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

Hospital Universitari de Bellvitge

Barcelona, 08907, Spain

Location

Hospital Universitari de Girona Dr. Josep Trueta

Girona, 17007, Spain

Location

Hospital Universiatrio y politecnico La Fe

Valencia, 46026, Spain

Location

NHS Tayside

Dundee, Angus, DD1 9SY, United Kingdom

Location

Papworth Hospital NHS Foundation Trust

Cambridge, Cambridgeshire, CB23 3RE, United Kingdom

Location

Blackpool Teaching Hospitals NHS Foundation Trust

Blackpool, Lancashire, FY38NR, United Kingdom

Location

Liverpool Heart and Chest Hospital NHS Foundation Trust

Liverpool, Merseyside, L14 3PE, United Kingdom

Location

NHS Lothian

Edinburgh, Scotland, EH16 4SA, United Kingdom

Location

Ashford and St Peter's Hospitals NHS Foundation Trust

Chertsey, Surrey, KT16 0PZ, United Kingdom

Location

The Royal Wolverhampton NHS Trust

Wolverhampton, West Midlands, WV10 0QP, United Kingdom

Location

Royal Brompton & Harefield NHS Foundation Trust

London, SW3 6HP, United Kingdom

Location

Pennine Acute Hospitals NHS Trust

Manchester, M8 5RB, United Kingdom

Location

University Hospital Southampton NHS Foundation Trust

Southampton, SO16 6YD, United Kingdom

Location

Related Publications (4)

• Johnson ED, Long MB, Perea L, Shih VH, Fernandez C, Teper A, Cipolla D, McIntosh E, Galloway R, Eke Z, Shuttleworth M, Hull R, Spinou A, De Soyza A, Ringshausen FC, Goeminne P, Lorent N, Haworth C, Loebinger MR, Blasi F, Shteinberg M, Aliberti S, Polverino E, Sibila O, Shoemark A, Mange K, Huang JTJ, Stobo J, Chalmers JD. Broad Immunomodulatory Effects of the Dipeptidyl Peptidase-1 Inhibitor Brensocatib in Bronchiectasis: Data from the Phase 2, Double-Blind, Placebo-controlled WILLOW Trial. Am J Respir Crit Care Med. 2025 May;211(5):770-778. doi: 10.1164/rccm.202408-1545OC.

  PMID: 39938076 DERIVED

• Basso J, Chen KJ, Zhou Y, Mark L, LaSala D, Dorfman A, Atalla M, Chun D, Viramontes V, Chang C, Leifer F, McDonald PP, Cipolla DC. The pharmacokinetic profile of brensocatib and its effect on pharmacodynamic biomarkers including NE, PR3, and CatG in various rodent species. Front Pharmacol. 2023 Jul 19;14:1208780. doi: 10.3389/fphar.2023.1208780. eCollection 2023.

  PMID: 37538173 DERIVED

• Cipolla D, Zhang J, Korkmaz B, Chalmers JD, Basso J, Lasala D, Fernandez C, Teper A, Mange KC, Perkins WR, Sullivan EJ. Dipeptidyl peptidase-1 inhibition with brensocatib reduces the activity of all major neutrophil serine proteases in patients with bronchiectasis: results from the WILLOW trial. Respir Res. 2023 May 17;24(1):133. doi: 10.1186/s12931-023-02444-z.

  PMID: 37198686 DERIVED

• 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.

  PMID: 32897034 DERIVED

MeSH Terms

Conditions

Bronchiectasis

Interventions

brensocatib

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Insmed Medical Information
• Organization: Insmed Incorporated

medicalinformation@Insmed.com

1-844-446-7633

Study Officials

• Carlos Fernandez, MD

  Insmed Incorporated

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2017
• First Posted: July 17, 2017
• Study Start: October 31, 2017
• Primary Completion: December 12, 2019
• Study Completion: December 12, 2019
• Last Updated: March 27, 2023
• Results First Posted: February 8, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

BU (4); NZ (5); DK (3); BE (1); SG (2); GB (10); AU (9); KR (9); US (36); IT (5); ES (5); PL (5); DE (10); NL (4)