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

Bronchiectasis Clinical Trial

Official title:

A Randomised, Double-blind, Placebo-controlled, Parallel Group, Dose-finding Study Evaluating Efficacy, Safety and Tolerability of BI 1291583 qd Over at Least 24 Weeks in Patients With Bronchiectasis (AirleafTM)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05238675
• Other study ID #: 1397-0012
• Secondary ID: 2021-003304-41
• Status: Completed
• Phase: Phase 2
• Start date: March 21, 2022
• Est. completion date: May 30, 2024

Study information

• Verified date: June 2024
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 322
• Est. completion date: May 30, 2024
• Est. primary completion date: May 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

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

• a1-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

• Hypothyroidism, myxedema, chronic lymphedema with associated hyperkeratosis of the skin, acrocyanosis. If a subject has hypothyroidism but is treated and compensated, the subject is allowed into the trial

• Psoriasis affecting palms and soles; or body surface area for psoriasis = 10%

• Reactive arthritis (Reiter's syndrome); keratoderma blennorrhagicum

• Pityriasis rubra pilaris

• Atopic dermatitis affecting palms and soles; or body surface area for atopic dermatitis = 10%

• Active extensive verruca vulgaris, as per investigator's discretion

• Active fungal infection of hand and/or feet not adequately treated, or not responsive to antifungal therapy, as per investigator's discretion.

• Any clinically relevant (at the discretion of the investigator) acute respiratory infection within 4 weeks prior Visit 2, or any other acute infection requiring systemic or inhaled anti-infective therapy within 4 weeks prior Visit 2.

• Any evidence of a concomitant disease, such as Papillon-Lefevre Syndrome, relevant pulmonary, gastrointestinal, hepatic, renal, cardiovascular, metabolic, immunological, hormonal disorders, or patients who are immunocompromised with a higher risk of invasive pneumococcal disease or other invasive opportunistic infections (such as histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis), that in the opinion of the investigator, may put the patient at risk by participating in the study.

• Received any live attenuated vaccine within 4 weeks prior to Visit 2.

• Medical conditions associated with periodontal disease (to be evaluated by a periodontist or dentist):

• Any tooth that can potentially cause pain or infection as noted in the oral exam unless they are corrected before the study (e.g. pulp necrosis).

• Severe periodontal disease defined as with pocket depth measurements = 6 mm on 2 or more teeth.

• Class-3 mobility or Class-3 furcation involvement.

• Scheduled tooth extraction during the study period.

• Patients who must or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial.

Further exclusion criteria apply

Related Conditions & MeSH terms

• Bronchiectasis

Intervention

Drug:
• BI 1291583
BI 1291583
• Placebo
Placebo

Locations

Country	Name	City	State
Australia	Lung Research Queensland	Chermside	Queensland
Australia	Institute for Respiratory Health	Nedlands	Western Australia
Australia	Macquarie University	North Ryde	New South Wales
Australia	Mater Research Institute	South Brisbane	Queensland
Australia	Trialswest	Spearwood	Western Australia
Australia	Westmead Hospital	Westmead	New South Wales
Belgium	UNIV UZ Gent	Gent
Belgium	UZ Leuven	Leuven
Bulgaria	Medical Center "Zdrave-1"	Kozloduy
Bulgaria	Medica Center Hera - Montana Branch	Montana
Bulgaria	Medical Center ReSpiro Ltd	Razgrad
Bulgaria	SHATPFD "Dr. Dimitar Gramatikov"	Ruse
Bulgaria	Medical Center Hera EOOD	Sofia
Canada	Centre Hospitalier de l'Universite de Montreal (CHUM)	Montreal	Quebec
Canada	Jewish General Hospital	Montreal	Migration Data
Canada	IUCPQ (Laval University)	Quebec
Czechia	Pulmonary Private Practice Kralupy	Kralupy nad Vltavou
Czechia	The First Pulmonary Private Practice	Prague 9
Denmark	Aalborg Sygehus Syd	Ålborg
Denmark	Hvidovre Hospital	Hvidovre
Denmark	Copenhagen University Hospital, Rigshospitalet	København Ø
Denmark	Odense University Hospital	Odense
Denmark	Sjællands Universitetshospital	Roskilde
Denmark	Vejle University Hospital	Vejle
France	HOP Amiens-Picardie Sud	Amiens
France	HOP Arnaud de Villeneuve	Montpellier
France	HOP Cochin	Paris
France	HOP Pontchaillou	Rennes
Germany	Charité - Universitätsmedizin Berlin	Berlin
Germany	Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH	Essen
Germany	IKF Pneumologie GmbH & Co. KG	Frankfurt
Germany	Velocity Clinical Research Germany GmbH	Großhansdorf
Germany	Lungenfachklinik Immenhausen	Immenhausen
Germany	Klinikum Konstanz	Konstanz
Germany	Velocity Clinical Research Germany GmbH	Lübeck
Germany	Klinikum der Universität München - Campus Innenstadt	München
Germany	Velocity Clinical Research Germany GmbH	Wiesbaden
Greece	Univ. Gen. Hosp. of Ioannina	Ioannina
Hungary	Semmelweis University	Budapest
Hungary	Da Vinci Private Clinic	Pecs
Israel	Soroka Univ. Medical Center	Beer Sheva
Israel	Lady Davis Carmel Medical Center	Haifa
Israel	Hadassah Medical Center, Ein-Karem	Jerusalem
Israel	Sourasky Medical Center	Tel Aviv
Italy	A.O. Univ. Policlinico "Paolo Giaccone"	Palermo
Italy	Fondazione IRCCS Policlinico S. Matteo	Pavia
Italy	Istituto Clinico Humanitas	Rozzano (MI)
Japan	Nagoya University Hospital	Aichi, Nagoya
Japan	Hirosaki University Hospital	Aomori, Hirosaki
Japan	Kameda Clinic	Chiba, Kamogawa
Japan	Fukuoka University Hospital	Fukuoka, Fukuoka
Japan	Kyushu University Hospital	Fukuoka, Fukuoka
Japan	Ibarakihigashi National Hospial	Ibaraki, Naka-gun
Japan	Kagoshima University Hospital	Kagoshima, Kagoshima
Japan	Matsusaka City Hospital	Mie, Matsusaka
Japan	Niigata University Medical and Dental Hospital	Niigata, Niigata
Japan	Osaka Toneyama Medical Center	Osaka, Toyonaka
Japan	Saga University Hospital	Saga, Saga
Japan	Fukujuji Hospital	Tokyo, Kiyose
Japan	Kitasato Institute Hospital	Tokyo, Minato-ku
Korea, Republic of	Chungbuk National University Hospital	Cheongju
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	SMG-SNU Boramae Medical Center	Seoul
Korea, Republic of	The Catholic University of Korea, Eunpyeong St. Mary's Hospital	Seoul
Latvia	Daugavpils Regional Hospital LTD Centre Outpatient Clinic	Daugavpils
Latvia	Med.Center OLVI Health Center Assotiation,Private Practice	Daugavpils
Latvia	VCA Dubultu Medical center	Jurmala
Latvia	LUMPII Doctors practice	Riga
Latvia	Pauls Stradins Clinical University Hospital	Riga
Latvia	Riga 1st Hospital	Riga
Mexico	Mediadvance Clinical S.A.P.I de C.V.	Chihuahua
Mexico	Accelerium S de RL de CV	Monterrey
Mexico	Hospital Universitario Nuevo de Nuevo León - CEPREP	Monterrey, Nuevo León
Mexico	Hospital Universitario Dr Jose Eleuterio Gonzalez	Nuevo Leon
Mexico	Oaxaca Site Management Organization, S.C.	Oaxaca
Mexico	Clinical Research Institute S.C.	Tlalnepantla
Netherlands	Amsterdam UMC, Locatie AMC	Amsterdam
Netherlands	Gelre Ziekenhuis Zutphen	Zutphen
Poland	Respiratory Medicine Centre, private prac., Bialystok	Bialystok
Poland	Screenmed Sp. z o.o.	Piaseczno
Poland	Alergopneuma Medical Center	Swidnik
Poland	Altamed Specjalistyczna Praktyka Lekarska Pawel Siwinski	Warszawa
Poland	Dr. Piotr Napora, Center of Clinical Research	Wroclaw
Portugal	ULS de Santa Maria, E.P.E	Lisboa
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Hospital de Bellvitge	L'Hospitalet de Llobregat
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	Hospital de Mérida	Mérida
Spain	Hospital Quirónsalud Madrid	Pozuelo de Alarcón
Turkey	Uludag Universitesi Tip Fakultesi	Bursa
Turkey	Marmara University Pendik Training and Research Hospital	Istanbul
Turkey	Sureyyapasa Egitim ve Arastirma Hastanesi	Istanbul
United Kingdom	Royal Papworth Hospital	Cambridge
United Kingdom	Ninewells Hospital & Medical School	Dundee, Scotland
United Kingdom	Liverpool Heart & Chest Hospital	Liverpool
United States	Central Florida Pulmonary Group	Altamonte Springs	Florida
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Cincinnati	Cincinnati	Ohio
United States	Malcom Randall VA Medical Center	Gainesville	Florida
United States	Institute for Translational Oncology Research	Greenville	South Carolina
United States	University of Florida College of Medicine	Jacksonville	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Metroplex Pulmonary & Sleep Center	McKinney	Texas
United States	New York University Langone Medical Center	New York	New York
United States	NewYork-Presbyterian/Weill Cornell Medical Center	New York	New York
United States	Newport Native MD, Inc	Newport Beach	California
United States	Phoenix Medical Group	Peoria	Arizona
United States	University of California Davis	Sacramento	California
United States	Diagnostics Research Group	San Antonio	Texas
United States	University of Texas Health Science Center at Tyler	Tyler	Texas
United States	Southeastern Research Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Bulgaria,  Canada,  Czechia,  Denmark,  France,  Germany,  Greece,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Latvia,  Mexico,  Netherlands,  Poland,  Portugal,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to first pulmonary exacerbation up to 48 weeks after first drug administration		Up to week 48
Secondary	Key secondary: Rate of pulmonary exacerbations (number of events per person-time) up to week 48 after first drug administration		Up to week 48
Secondary	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
Secondary	Relative change from baseline in neutrophil elastase (NE) activity in sputum at week 12 after first drug administration		At baseline and at week 12
Secondary	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
Secondary	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
Secondary	Occurrence of an exacerbation by week 24 after first drug administration		Up to week 24

External Links

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