A study to test whether different doses of BI 1291583 help people with bronchiectasis
- Conditions
- bronchiectasisMedDRA version: 21.0Level: PTClassification code 10006445Term: BronchiectasisSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disordersTherapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2021-003304-41-DK
- Lead Sponsor
- Boehringer Ingelheim B.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 240
- Male or female patients
- Age of patients when signing the informed consent =18 and =85 years.
- Clinical history consistent with bronchiectasis (cough, chronic sputum production and/or recurrent respiratory infections) and investigator confirmed diagnosis of bronchiectasis by computed tomography (CT) scan.
- 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 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 140
1) AST and / or ALT >3.0 x ULN at Visit 1, or moderate or severe liver disease (defined by Child-Pugh score B or C hepatic impairment).
2) Estimated glomerular filtration rate (eGFR) according to CKD-EPI formula < 30 mL/min at Visit 1.
3) An absolute blood neutrophil count <1,000/mm3 (equivalent to <1,000 cells/µL or <109 cells/L) at Visit 1.
4) 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.
5) Positive serological tests for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection, or known infection status.
6) A current diagnosis of
-- Cystic Fibrosis
-- Hypogammaglobulinemia
-- Common variable immunodeficiency
-- a1-antitrypsin deficiency 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 [Laboratory tests (e.g. Quantiferon Gold test) may be performed at the discretion of the investigator]
-- 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
7) 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.
8) Any evidence of a concomitant disease, such as Papillon-Lefevre Syndrome, relevant pulmonary, gastrointestinal, hepatic, renal, cardiovascular, metabolic, immunological, or 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.
9) Received any live attenuated vaccine within 4 weeks prior to Visit 2.
10) Medical conditions associated with periodontal disease (to be evaluated by a periodontist or dentist).
11) 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 criteria apply.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of the trial is to assess a non-flat dose-response curve and to evaluate the dose-response relationship for 3 oral dose regimens of BI 1291583 versus placebo, on the primary endpoint, time to first pulmonary exacerbation up to 48 weeks.;Secondary Objective: The secondary objective is to assess superiority of BI 1291583 5 mg versus placebo on the primary endpoint, the time to first pulmonary exacerbation up to week 48, as well as on the secondary endpoint, the rate of pulmonary exacerbations up to week 48.;Primary end point(s): 1) Time to first pulmonary exacerbation up to 48 weeks after first drug administration;Timepoint(s) of evaluation of this end point: 1) week 48
- Secondary Outcome Measures
Name Time Method Secondary end point(s): The key secondary endpoint is the rate of pulmonary exacerbations (number of events per person-time) up to week 48 after first drug administration.<br>secondary endpoints:<br>1) Absolute change from baseline in Quality of Life Questionnaire – Bronchiectasis (QOL-B) respiratory symptoms domain score at week 24 after first drug administration <br>2) Relative change from baseline in neutrophil elastase (NE) activity in sputum at week 12 after first drug administration<br>3) Absolute change from baseline in St. George’s Respiratory Questionnaire (SGRQ) Symptoms score at week 24 after first drug administration<br>4) Absolute change from baseline in percent predicted post-bronchodilator forced expiratory volume in one second (FEV1%pred) at week 24 after first drug administration<br>5) Occurrence of an exacerbation by week 24;Timepoint(s) of evaluation of this end point: 1) week 12<br>2) up to week 48<br>3) week 24<br>4) week 24<br>5) week 24