Clinical trial NCT05238675: A Study to Test Whether Different Doses of BI 1291583 Help People With Bronchiectasis
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Bronchiectasis
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2022-02-14
Enrollment: 322
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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
  * 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
  * 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

Primary outcomes:
measure: Time to first pulmonary exacerbation up to 48 weeks after first drug administration
timeFrame: Up to week 48
Secondary outcomes:
measure: Key secondary: Rate of pulmonary exacerbations (number of events per person-time) up to week 48 after first drug administration
timeFrame: Up to week 48
measure: Absolute change from baseline in Quality of Life Questionnaire - Bronchiectasis (QOLB) respiratory symptoms domain score at week 24 after first drug administration
timeFrame: At baseline and at week 24
measure: Relative change from baseline in neutrophil elastase (NE) activity in sputum at week 12 after first drug administration
timeFrame: At baseline and at week 12
measure: Absolute change from baseline in St. George's Respiratory Questionnaire (SGRQ) Symptoms score at week 24 after first drug administration
timeFrame: At baseline and at week 24
measure: Absolute change from baseline in percent predicted post-bronchodilator forced expiratory volume in one second (FEV1%pred) at week 24 after first drug administration
timeFrame: At baseline and at week 24
measure: Occurrence of an exacerbation by week 24 after first drug administration
timeFrame: Up to week 24
Other outcomes:
Locations:
city: Peoria
country: United States
facility: Phoenix Medical Group
state: Arizona
city: Newport Beach
country: United States
facility: Newport Native MD, Inc
state: California
city: Sacramento
country: United States
facility: University of California Davis
state: California
city: Altamonte Springs
country: United States
facility: Central Florida Pulmonary Group
state: Florida
city: Gainesville
country: United States
facility: Malcom Randall VA Medical Center
state: Florida
city: Jacksonville
country: United States
facility: University of Florida College of Medicine
state: Florida
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: New York
country: United States
facility: New York University Langone Medical Center
state: New York
city: New York
country: United States
facility: NewYork-Presbyterian/Weill Cornell Medical Center
state: New York
city: Winston-Salem
country: United States
facility: Southeastern Research Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Greenville
country: United States
facility: Institute for Translational Oncology Research
state: South Carolina
city: McKinney
country: United States
facility: Metroplex Pulmonary & Sleep Center
state: Texas
city: San Antonio
country: United States
facility: Diagnostics Research Group
state: Texas
city: Tyler
country: United States
facility: University of Texas Health Science Center at Tyler
state: Texas
city: North Ryde
country: Australia
facility: Macquarie University
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Chermside
country: Australia
facility: Lung Research Queensland
state: Queensland
city: South Brisbane
country: Australia
facility: Mater Research Institute
state: Queensland
city: Nedlands
country: Australia
facility: Institute for Respiratory Health
state: Western Australia
city: Spearwood
country: Australia
facility: Trialswest
state: Western Australia
city: Gent
country: Belgium
facility: UNIV UZ Gent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Kozloduy
country: Bulgaria
facility: Medical Center "Zdrave-1"
city: Montana
country: Bulgaria
facility: Medica Center Hera - Montana Branch
city: Razgrad
country: Bulgaria
facility: Medical Center ReSpiro Ltd
city: Ruse
country: Bulgaria
facility: SHATPFD "Dr. Dimitar Gramatikov"
city: Sofia
country: Bulgaria
facility: Medical Center Hera EOOD
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Migration Data
city: Montreal
country: Canada
facility: Centre Hospitalier de l'Universite de Montreal (CHUM)
state: Quebec
city: Quebec
country: Canada
facility: IUCPQ (Laval University)
city: Kralupy nad Vltavou
country: Czechia
facility: Pulmonary Private Practice Kralupy
city: Prague 9
country: Czechia
facility: The First Pulmonary Private Practice
city: Hvidovre
country: Denmark
facility: Hvidovre Hospital
city: København Ø
country: Denmark
facility: Copenhagen University Hospital, Rigshospitalet
city: Odense
country: Denmark
facility: Odense University Hospital
city: Roskilde
country: Denmark
facility: Sjællands Universitetshospital
city: Vejle
country: Denmark
facility: Vejle University Hospital
city: Ålborg
country: Denmark
facility: Aalborg Sygehus Syd
city: Amiens
country: France
facility: HOP Amiens-Picardie Sud
city: Montpellier
country: France
facility: HOP Arnaud de Villeneuve
city: Paris
country: France
facility: HOP Cochin
city: Rennes
country: France
facility: HOP Pontchaillou
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Essen
country: Germany
facility: Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH
city: Frankfurt
country: Germany
facility: IKF Pneumologie GmbH & Co. KG
city: Großhansdorf
country: Germany
facility: Velocity Clinical Research Germany GmbH
city: Immenhausen
country: Germany
facility: Lungenfachklinik Immenhausen
city: Konstanz
country: Germany
facility: Klinikum Konstanz
city: Lübeck
country: Germany
facility: Velocity Clinical Research Germany GmbH
city: München
country: Germany
facility: Klinikum der Universität München - Campus Innenstadt
city: Wiesbaden
country: Germany
facility: Velocity Clinical Research Germany GmbH
city: Ioannina
country: Greece
facility: Univ. Gen. Hosp. of Ioannina
city: Budapest
country: Hungary
facility: Semmelweis University
city: Pecs
country: Hungary
facility: Da Vinci Private Clinic
city: Beer Sheva
country: Israel
facility: Soroka Univ. Medical Center
city: Haifa
country: Israel
facility: Lady Davis Carmel Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center, Ein-Karem
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center
city: Palermo
country: Italy
facility: A.O. Univ. Policlinico "Paolo Giaccone"
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico S. Matteo
city: Rozzano (MI)
country: Italy
facility: Istituto Clinico Humanitas
city: Aichi, Nagoya
country: Japan
facility: Nagoya University Hospital
city: Aomori, Hirosaki
country: Japan
facility: Hirosaki University Hospital
city: Chiba, Kamogawa
country: Japan
facility: Kameda Clinic
city: Fukuoka, Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Fukuoka, Fukuoka
country: Japan
facility: Fukuoka University Hospital
city: Ibaraki, Naka-gun
country: Japan
facility: Ibarakihigashi National Hospial
city: Kagoshima, Kagoshima
country: Japan
facility: Kagoshima University Hospital
city: Mie, Matsusaka
country: Japan
facility: Matsusaka City Hospital
city: Niigata, Niigata
country: Japan
facility: Niigata University Medical and Dental Hospital
city: Osaka, Toyonaka
country: Japan
facility: Osaka Toneyama Medical Center
city: Saga, Saga
country: Japan
facility: Saga University Hospital
city: Tokyo, Kiyose
country: Japan
facility: Fukujuji Hospital
city: Tokyo, Minato-ku
country: Japan
facility: Kitasato Institute Hospital
city: Cheongju
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Seoul
country: Korea, Republic of
facility: SMG-SNU Boramae Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Eunpyeong St. Mary's Hospital
city: Daugavpils
country: Latvia
facility: Daugavpils Regional Hospital LTD Centre Outpatient Clinic
city: Daugavpils
country: Latvia
facility: Med.Center OLVI Health Center Assotiation,Private Practice
city: Jurmala
country: Latvia
facility: VCA Dubultu Medical center
city: Riga
country: Latvia
facility: Riga 1st Hospital
city: Riga
country: Latvia
facility: Pauls Stradins Clinical University Hospital
city: Riga
country: Latvia
facility: LUMPII Doctors practice
city: Chihuahua
country: Mexico
facility: Mediadvance Clinical S.A.P.I de C.V.
city: Monterrey, Nuevo León
country: Mexico
facility: Hospital Universitario Nuevo de Nuevo León - CEPREP
city: Monterrey
country: Mexico
facility: Accelerium S de RL de CV
city: Nuevo Leon
country: Mexico
facility: Hospital Universitario Dr Jose Eleuterio Gonzalez
city: Oaxaca
country: Mexico
facility: Oaxaca Site Management Organization, S.C.
city: Tlalnepantla
country: Mexico
facility: Clinical Research Institute S.C.
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, location VUMC
city: Zutphen
country: Netherlands
facility: Gelre Ziekenhuis Zutphen
city: Bialystok
country: Poland
facility: Respiratory Medicine Centre, private prac., Bialystok
city: Piaseczno
country: Poland
facility: Screenmed Sp. z o.o.
city: Swidnik
country: Poland
facility: Alergopneuma Medical Center
city: Warszawa
country: Poland
facility: Altamed Specjalistyczna Praktyka Lekarska Pawel Siwinski
city: Wroclaw
country: Poland
facility: Dr. Piotr Napora, Center of Clinical Research
city: Lisboa
country: Portugal
facility: ULS de Santa Maria, E.P.E
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: L'Hospitalet de Llobregat
country: Spain
facility: Hospital de Bellvitge
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Mérida
country: Spain
facility: Hospital de Mérida
city: Pozuelo de Alarcón
country: Spain
facility: Hospital Quirónsalud Madrid
city: Bursa
country: Turkey
facility: Uludag Universitesi Tip Fakultesi
city: Istanbul
country: Turkey
facility: Marmara University Pendik Training and Research Hospital
city: Istanbul
country: Turkey
facility: Sureyyapasa Egitim ve Arastirma Hastanesi
city: Cambridge
country: United Kingdom
facility: Royal Papworth Hospital
city: Dundee, Scotland
country: United Kingdom
facility: Ninewells Hospital & Medical School
city: Liverpool
country: United Kingdom
facility: Liverpool Heart & Chest Hospital
Study officials:
References: