Assessment of INS1007 in Participants With Non-Cystic Fibrosis Bronchiectasis

Non-Cystic Fibrosis Bronchiectasis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03218917
• Other study ID #: INS1007-201
• Secondary ID: 2017-002533-32
• Status: Completed
• Phase: Phase 2
• Start date: October 31, 2017
• Est. completion date: December 12, 2019

Study information

• Verified date: March 2023
• Source: Insmed Incorporated
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 256
• Est. completion date: December 12, 2019
• Est. primary completion date: December 12, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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)

Related Conditions & MeSH terms

• Bronchiectasis
• Fibrosis
• Non-Cystic Fibrosis Bronchiectasis

Intervention

Drug:
• Brensocatib 10 mg
Administered once per day for 24 weeks
• Brensocatib 25 mg
Administered once per day for 24 weeks
• Placebo
Administered once per day for 24 weeks

Locations

Country	Name	City	State
Australia	Respiratory Clinical Trials Unit, Royal Adelaide Hospital	Adelaide	South Australia
Australia	Box Hill Hospital, Eastern Clinical Research Unit	Box Hill	Victoria
Australia	Gallipoli Medical Research Foundation	Brisbane	Queensland
Australia	Mater Misericordia Medical Centre	Brisbane	Queensland
Australia	Metro North Hospital and Health Service (The Prince Charles Hospital)	Chermside	Queensland
Australia	Concord Repatriation General Hospital	Concord	New South Wales
Australia	Respiratory Clinical Trials PTY LTD	Kent Town	South Australia
Australia	Alfred Hospital	Melbourne	Victoria
Australia	Institute for Respiratory Health	Nedlands	Western Australia
Belgium	UZ Leuven	Leuven	Vlaams Brabant
Bulgaria	Medical Center UNIMED	Plovdiv
Bulgaria	Medical Center ReSpiro Ltd (Kiselov)	Razgrad	Momina
Bulgaria	MHAT "Dr IvanSeliminski"-Sliven	Sliven
Bulgaria	Cardioart Medical Center	Stara Zagora
Denmark	Aarhus University Hospital	Aarhus
Denmark	Hvidovre Hospital	Hvidovre	Capital Region
Denmark	Sjællands Universitetshospital, Roskilde	Roskilde
Germany	Research Center for Medical Studies (RCMS)	Berlin
Germany	Forschungszentrum Borstel	Borstel	Schleswig-Holstein
Germany	Krankenhaus Donaustauf	Donaustauf	Bavaria
Germany	Ruhrlandklinik Essen, University Essen	Essen	NRW
Germany	IKF Pneumologie Frankfurt	Frankfurt	Hessen
Germany	Universitätsklinikum Frankfurt	Frankfurt	Hessen
Germany	Universitätsklinikum Jena	Jena	Thuringen
Germany	Städt. Klinikum München GmbH, Bogenhausen	München
Germany	Klinikum der Universität München Medizinische Klinik V Pneumologie / Mukoviszidose-Zentrum für Erwachsene	Munich	Bavaria
Germany	Klinikum Nuernberg	Nuernberg	Bayern
Italy	University of Milan, IRCCS Fondazione Ca' Granda Ospedale Maggiore Policlinico	Milan	Lombardia
Italy	Ospedale San Gerardo	Monza	Monza E Brianza
Italy	Fondazione IRCCS Policlinico San Matteo	Pavia
Italy	University Hospital of Pisa	Pisa	Via Paradisa 2
Italy	ICS Maugeri spa SB, IRCSS Telese	Telese Terme
Korea, Republic of	Chonnam National University Hospital	Gwangju
Korea, Republic of	Gachon University Gil Medical Center	Incheon	Namdong-gu
Korea, Republic of	Inha University Hospital	Incheon	Jung-gu
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	Seoul National University Hospital	Seoul
Korea, Republic of	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul
Korea, Republic of	The Catholic University of Korea, St. Paul's Hospital	Seoul
Netherlands	Noordwest Ziekenhuis Group	Alkmaar
Netherlands	Amphia Longresearch Astma/COPD Uni 52/5e etage	Breda
Netherlands	RadboudUMC, location Dekkerswald	Nijmegen
Netherlands	Zuyderland MC	Sittard
New Zealand	Auckland District Health Board, Greenlane clinical Centre	Auckland
New Zealand	Southern District health Board/Dunedin Hospital	Dunedin	Otago
New Zealand	Waikato District Health Board	Hamilton	Waikato
New Zealand	P3 Research (Hawke's Bay)	Hastings	Hawkes Bay
New Zealand	P3 Research	Tauranga	BOP
Poland	Grazyna Jasieniak Pinis Niepubliczny Zaklad Opieki Zdrowotnej Atopia	Kraków
Poland	NZOZ Krak-Medyk Sp. z o.o	Kraków
Poland	Medical University of Lodz Poland	Lódz
Poland	Gabinet Lekarski Pediatryczno-Alergologiczny Zenon Bukowczan	Sucha Beskidzka
Poland	Centrum Badan Klinicznych, Piotr Napora Lekarze i Spolka Partnerska, Osrodek Badan Wczesnej Fazy	Wroclaw	Dolnoslaskie
Singapore	Changi General Hospital	Singapore
Singapore	Singapore General Hospital	Singapore
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitari de Bellvitge	Barcelona
Spain	Hospital Universitari de Girona Dr. Josep Trueta	Girona
Spain	Hospital Universiatrio y politecnico La Fe	Valencia
United Kingdom	Blackpool Teaching Hospitals NHS Foundation Trust	Blackpool	Lancashire
United Kingdom	Papworth Hospital NHS Foundation Trust	Cambridge	Cambridgeshire
United Kingdom	Ashford and St Peter's Hospitals NHS Foundation Trust	Chertsey	Surrey
United Kingdom	NHS Tayside	Dundee	Angus
United Kingdom	NHS Lothian	Edinburgh	Scotland
United Kingdom	Liverpool Heart and Chest Hospital NHS Foundation Trust	Liverpool	Merseyside
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	The Royal Wolverhampton NHS Trust	Wolverhampton	West Midlands
United States	Michigan Medicine	Ann Arbor	Michigan
United States	The Emory Clinic, Pulmonology	Atlanta	Georgia
United States	Johns Hopkins University, Division of Pulmonary and Critical Care Medicine	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Clinical Research Specialists, LLC	Celebration	Florida
United States	The University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Novant Health Pulmonary Medicine South	Charlotte	North Carolina
United States	University of Chicago	Chicago	Illinois
United States	St. Francis Medical Institute	Clearwater	Florida
United States	Cleveland Clinic	Cleveland	Ohio
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	National Jewish Heath	Denver	Colorado
United States	UConn Health Center	Farmington	Connecticut
United States	University of Florida	Gainesville	Florida
United States	University of Iowa	Iowa City	Iowa
United States	SMS Clinical Research, LLC	Mesquite	Texas
United States	University of Miami Miller School of Medicine	Miami	Florida
United States	San Marcus Research Clinic, Inc.	Miami Lakes	Florida
United States	LSU Health Sciences Center	New Orleans	Louisiana
United States	Columbia University Medical Center/ New York Presbyterian Hospital	New York	New York
United States	NYU Pulmonary & Critical Care Associates	New York	New York
United States	NewportNativeMD	Newport Beach	California
United States	Palmtree Clinical Research	Palm Springs	California
United States	Phoenix Medical Group	Peoria	Arizona
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	UC Davis Medical Center	Sacramento	California
United States	Sarasota Memorial Hospital Clinical Research Center	Sarasota	Florida
United States	Stanford University Medical Center	Stanford	California
United States	MultiCare Institute for Research & Innovation	Tacoma	Washington
United States	Pulmonary and Critical Care Associates of Baltimore	Towson	Maryland
United States	The University of Texas Health Science at Tyler	Tyler	Texas
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	Mid Atlantic Pulmonary & Research Center	Westminster	Maryland
United States	Southeastern Research Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Insmed Incorporated

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Bulgaria,  Denmark,  Germany,  Italy,  Korea, Republic of,  Netherlands,  New Zealand,  Poland,  Singapore,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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