A Study to Test Whether Different Doses of BI 1291583 Help People With Bronchiectasis

NCT05238675 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: 1397-00122021-003304-41
• Study Type: interventional
• Target: 322
• Locations: 23 countries
• Sites: 112

Brief Summary

This study is open to adults with bronchiectasis. People can join the study if they produce sputum and have a history of flare-ups (also called exacerbations). The purpose of this study is to find out whether a medicine called BI 1291583 helps people with bronchiectasis. Participants are put into 4 groups randomly, which means by chance. Participants in groups 1, 2, and 3 get different doses of BI 1291583. Participants in group 4 get placebo. Placebo tablets look like BI 1291583 tablets, but do not contain any medicine. Participants take the tablets once a day. Participants are in the study for between 6 months and 1 year. During this time, they visit the study site about 10 times and get about 5 phone calls from the site staff. The doctors document when participants experience flare-ups during the study. The time to the first flare-ups is compared between the treatment groups. Doctors also regularly check participants' health and take note of any unwanted effects.

Conditions

Bronchiectasis

Outcome Measures

Primary Outcomes (1)

• Time to first pulmonary exacerbation up to 48 weeks after first drug administration

  Up to week 48

Secondary Outcomes (6)

• Key secondary: Rate of pulmonary exacerbations (number of events per person-time) up to week 48 after first drug administration

  Up to week 48

• Absolute change from baseline in Quality of Life Questionnaire - Bronchiectasis (QOLB) respiratory symptoms domain score at week 24 after first drug administration

  At baseline and at week 24

• Relative change from baseline in neutrophil elastase (NE) activity in sputum at week 12 after first drug administration

  At baseline and at week 12

• Absolute change from baseline in St. George's Respiratory Questionnaire (SGRQ) Symptoms score at week 24 after first drug administration

  At baseline and at week 24

• Absolute change from baseline in percent predicted post-bronchodilator forced expiratory volume in one second (FEV1%pred) at week 24 after first drug administration

  At baseline and at week 24

Study Arms (4)

BI 1291583: Low dose group

EXPERIMENTAL

Drug: BI 1291583

BI 1291583: Medium dose group

EXPERIMENTAL

Drug: BI 1291583

BI 1291583: High dose group

EXPERIMENTAL

Drug: BI 1291583

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

BI 1291583 DRUG

BI 1291583

Also known as: Verducatib

BI 1291583: High dose group; BI 1291583: Low dose group; BI 1291583: Medium dose group

Placebo DRUG

Placebo

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:

• \- Male or female patients: Women of childbearing potential (WOCBP) must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly, as well as one barrier method. A list of contraception methods meeting these criteria is provided in the patient information.
• Men participating in this clinical trial must use male contraception (condom or sexual abstinence) if their sexual partner is a WOCBP.
• Signed and dated written informed consent prior to admission to the study, in accordance with Good Clinical Practice (GCP) and local legislation.
• Age of patients when signing the informed consent ≥18 (for Korea: ≥19) and ≤85 years.
• Clinical history consistent with bronchiectasis (e.g., cough, chronic sputum production and/or recurrent respiratory infections) and investigator confirmed diagnosis of bronchiectasis by computed tomography (CT) scan. Subjects whose past chest radiographic image records are not available will undergo a chest CT scan during Screening. Historical scans must not be older than 5 years.
• History of pulmonary exacerbations requiring antibiotic treatment. In the 12 months before Visit 1, patients must have had either:
• at least 2 exacerbations, or
• at least 1 exacerbation and a St. George´s Respiratory Questionnaire (SGRQ) Symptoms score of \>40 at screening visit 1.
• For patients on stable oral or inhaled antibiotics as chronic treatment for bronchiectasis, at least one exacerbation must have occurred since initiation of stable antibiotics.
• \- Current sputum producers with a history of chronic expectoration who are able to provide a spontaneous (not induced) sputum sample at Screening Visit 1.

You may not qualify if:

• Laboratory and medical examination
• Aspartate Aminotransferase (AST) and / or Alanine Aminotransferase (ALT) \>3.0 x upper limit of normal (ULN) at Visit 1, or moderate or severe liver disease (defined by Child-Pugh score B or C hepatic impairment).
• Estimated glomerular filtration rate (eGFR) according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula \< 30 mL/min at Visit 1.
• An absolute blood neutrophil count \<1,000/mm\^3 at Visit 1 (equivalent to \<1,000 cells/µL or \<109 cells/L).
• Any findings in the medical examination and/or laboratory value assessed at Screening Visit 1 or during screening period, that in the opinion of the investigator may put the patient at risk by participating in the trial.
• Positive serological tests for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection, or known infection status.
• Concomitant diagnosis and therapy
• A current diagnosis of:
• Cystic Fibrosis
• Hypogammaglobulinemia
• Common variable immunodeficiency
• α1-antitrypsin deficiency being treated with augmentation therapy
• Allergic bronchopulmonary aspergillosis being treated or requiring treatment
• Tuberculosis or non-tuberculous mycobacterial infection being treated or requiring treatment according to local guidelines
• Palmoplantar keratosis; or keratoderma climactericum

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (112)

Phoenix Medical Group

Peoria, Arizona, 85381, United States

Location

Newport Native MD, Inc

Newport Beach, California, 92663, United States

Location

University of California Davis

Sacramento, California, 95817, United States

Location

Central Florida Pulmonary Group

Altamonte Springs, Florida, 32701, United States

Location

Malcom Randall VA Medical Center

Gainesville, Florida, 32608, United States

Location

University of Florida College of Medicine

Jacksonville, Florida, 32209, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

New York University Langone Medical Center

New York, New York, 10016, United States

Location

NewYork-Presbyterian/Weill Cornell Medical Center

New York, New York, 10065, United States

Location

Southeastern Research Center

Winston-Salem, North Carolina, 27103, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Institute for Translational Oncology Research

Greenville, South Carolina, 29605, United States

Location

Metroplex Pulmonary & Sleep Center

McKinney, Texas, 75069, United States

Location

Diagnostics Research Group

San Antonio, Texas, 78229, United States

Location

University of Texas Health Science Center at Tyler

Tyler, Texas, 75708, United States

Location

Macquarie University

North Ryde, New South Wales, 2109, Australia

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Lung Research Queensland

Chermside, Queensland, 4032, Australia

Location

Mater Research Institute

South Brisbane, Queensland, 4101, Australia

Location

Institute for Respiratory Health

Nedlands, Western Australia, 6009, Australia

Location

Trialswest

Spearwood, Western Australia, 6153, Australia

Location

UNIV UZ Gent

Ghent, 9000, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Medical Center "Zdrave-1"

Kozloduy, 3320, Bulgaria

Location

Medica Center Hera - Montana Branch

Montana, 3400, Bulgaria

Location

Medical Center ReSpiro Ltd

Razgrad, 7200, Bulgaria

Location

SHATPFD "Dr. Dimitar Gramatikov"

Rousse, 7002, Bulgaria

Location

Medical Center Hera EOOD

Sofia, 1510, Bulgaria

Location

Jewish General Hospital

Montreal, Migration Data, H3T 1E2, Canada

Location

Centre Hospitalier de l'Universite de Montreal (CHUM)

Montreal, Quebec, H2X 0A9, Canada

Location

IUCPQ (Laval University)

Québec, G1V 4G5, Canada

Location

Pulmonary Private Practice Kralupy

Kralupy nad Vltavou, 27801, Czechia

Location

The First Pulmonary Private Practice

Prague, 19000, Czechia

Location

Aalborg Sygehus Syd

Aalborg, 9000, Denmark

Location

Hvidovre Hospital

Hvidovre, 2650, Denmark

Location

Copenhagen University Hospital, Rigshospitalet

København Ø, 2100, Denmark

Location

Odense University Hospital

Odense, 5000 C, Denmark

Location

Sjællands Universitetshospital

Roskilde, 4000, Denmark

Location

Vejle University Hospital

Vejle, 7100, Denmark

Location

HOP Amiens-Picardie Sud

Amiens, 80054, France

Location

HOP Arnaud de Villeneuve

Montpellier, 34295, France

Location

HOP Cochin

Paris, 75679, France

Location

HOP Pontchaillou

Rennes, 35033, France

Location

Charité - Universitätsmedizin Berlin

Berlin, 10117, Germany

Location

Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH

Essen, 45239, Germany

Location

IKF Pneumologie GmbH & Co. KG

Frankfurt, 60596, Germany

Location

Velocity Clinical Research Germany GmbH

Großhansdorf, 22927, Germany

Location

Lungenfachklinik Immenhausen

Immenhausen, 34376, Germany

Location

Klinikum Konstanz

Konstanz, 78464, Germany

Location

Velocity Clinical Research Germany GmbH

Lübeck, 23552, Germany

Location

Klinikum der Universität München - Campus Innenstadt

München, 80336, Germany

Location

Velocity Clinical Research Germany GmbH

Wiesbaden, 65189, Germany

Location

Univ. Gen. Hosp. of Ioannina

Ioannina, 45 500, Greece

Location

Semmelweis University

Budapest, 1083, Hungary

Location

Da Vinci Private Clinic

Pécs, 7635, Hungary

Location

Soroka Univ. Medical Center

Beersheba, 8410101, Israel

Location

Lady Davis Carmel Medical Center

Haifa, 3436212, Israel

Location

Hadassah Medical Center, Ein-Karem

Jerusalem, 9112001, Israel

Location

Sourasky Medical Center

Tel Aviv, 6093246, Israel

Location

A.O. Univ. Policlinico "Paolo Giaccone"

Palermo, 90127, Italy

Location

Fondazione IRCCS Policlinico S. Matteo

Pavia, 27100, Italy

Location

Istituto Clinico Humanitas

Rozzano (MI), 20089, Italy

Location

Nagoya University Hospital

Aichi, Nagoya, 466-8560, Japan

Location

Hirosaki University Hospital

Aomori, Hirosaki, 036-8563, Japan

Location

Kameda Clinic

Chiba, Kamogawa, 296-0041, Japan

Location

Kyushu University Hospital

Fukuoka, Fukuoka, 812-8582, Japan

Location

Fukuoka University Hospital

Fukuoka, Fukuoka, 814-0180, Japan

Location

Ibarakihigashi National Hospial

Ibaraki, Naka-gun, 319-1113, Japan

Location

Kagoshima University Hospital

Kagoshima, Kagoshima, 890-8520, Japan

Location

Matsusaka City Hospital

Mie, Matsusaka, 515-8544, Japan

Location

Niigata University Medical and Dental Hospital

Niigata, Niigata, 951-8520, Japan

Location

Osaka Toneyama Medical Center

Osaka, Toyonaka, 560-8552, Japan

Location

Saga University Hospital

Saga, Saga, 849-8501, Japan

Location

Fukujuji Hospital

Tokyo, Kiyose, 204-8522, Japan

Location

Kitasato Institute Hospital

Tokyo, Minato-ku, 108-8642, Japan

Location

Daugavpils Regional Hospital LTD Centre Outpatient Clinic

Daugavpils, 5401, Latvia

Location

Med.Center OLVI Health Center Assotiation,Private Practice

Daugavpils, 5410, Latvia

Location

VCA Dubultu Medical center

Jūrmala, 2015, Latvia

Location

Riga 1st Hospital

Riga, 1001, Latvia

Location

Pauls Stradins Clinical University Hospital

Riga, 1002, Latvia

Location

LUMPII Doctors practice

Riga, 1011, Latvia

Location

Mediadvance Clinical S.A.P.I de C.V.

Chihuahua City, 31203, Mexico

Location

Accelerium S de RL de CV

Monterrey, 64000, Mexico

Location

Hospital Universitario Nuevo de Nuevo León - CEPREP

Monterrey, Nuevo León, C.P. 64460, Mexico

Location

Hospital Universitario Dr Jose Eleuterio Gonzalez

Nuevo León, 64460, Mexico

Location

Oaxaca Site Management Organization, S.C.

Oaxaca City, 68000, Mexico

Location

Clinical Research Institute S.C.

Tlalnepantla, 54055, Mexico

Location

Amsterdam UMC, location VUMC

Amsterdam, 1081 HV, Netherlands

Location

Gelre Ziekenhuis Zutphen

Zutphen, 7207 AE, Netherlands

Location

Respiratory Medicine Centre, private prac., Bialystok

Bialystok, 15044, Poland

Location

Screenmed Sp. z o.o.

Piaseczno, 05500, Poland

Location

Alergopneuma Medical Center

Świdnik, 21040, Poland

Location

Altamed Specjalistyczna Praktyka Lekarska Pawel Siwinski

Warsaw, 01-456, Poland

Location

Dr. Piotr Napora, Center of Clinical Research

Wroclaw, 51162, Poland

Location

ULS de Santa Maria, E.P.E

Lisbon, 1064-035, Portugal

Location

Chungbuk National University Hospital

Cheongju-si, 28644, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Korea University Guro Hospital

Seoul, 08308, South Korea

Location

SMG-SNU Boramae Medical Center

Seoul, 156-707, South Korea

Location

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

Seoul, 22711, South Korea

Location

Hospital Clínic de Barcelona

Barcelona, 08036, Spain

Location

Hospital de Bellvitge

L'Hospitalet de Llobregat, 08907, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, 28007, Spain

Location

Hospital de Mérida

Mérida, 06800, Spain

Location

Hospital Quirónsalud Madrid

Pozuelo de Alarcón, 28223, Spain

Location

Uludag Universitesi Tip Fakultesi

Bursa, 16120, Turkey (Türkiye)

Location

Marmara University Pendik Training and Research Hospital

Istanbul, 34890, Turkey (Türkiye)

Location

Sureyyapasa Egitim ve Arastirma Hastanesi

Istanbul, 34890, Turkey (Türkiye)

Location

Royal Papworth Hospital

Cambridge, CB2 0AY, United Kingdom

Location

Ninewells Hospital & Medical School

Dundee, Scotland, DD1 9SY, United Kingdom

Location

Liverpool Heart & Chest Hospital

Liverpool, L14 3PE, United Kingdom

Location

Related Publications (1)

• Chalmers JD, Shteinberg M, Mall MA, O'Donnell AE, Watz H, Gupta A, Frahm E, Eleftheraki A, Rauch J, Chotirmall SH, Armstrong AW, Eickholz P, Hasegawa N, Sauter W, McShane PJ. Cathepsin C (dipeptidyl peptidase 1) inhibition in adults with bronchiectasis: AIRLEAF, a phase II randomised, double-blind, placebo-controlled, dose-finding study. Eur Respir J. 2025 Jan 2;65(1):2401551. doi: 10.1183/13993003.01551-2024. Print 2025 Jan.

  PMID: 39255990 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Bronchiectasis

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases

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: February 3, 2022
• First Posted: February 14, 2022
• Study Start: April 28, 2022
• Primary Completion: May 1, 2024
• Study Completion: May 30, 2024
• Last Updated: August 14, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
• Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a 'Data Sharing Agreement'.

Locations

CZ (2); US (16); GR (1); BU (5); LA (6); BE (2); DE (9); NL (2); FR (4); KR (5); GB (3); DK (6); ES (5); IT (3); TU (3); ME (6); PT (1); HU (2); AU (6); CA (3); IL (4); JP (13); PL (5)