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 (Airleaf*)
- Conditions
- bronchiectasisdilatation and inflammation of the bronchi10006436
- Registration Number
- NL-OMON53709
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 7
- 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
- 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).
- Estimated glomerular filtration rate (eGFR) according to CKD-EPI formula <30
mL/min at Visit 1.
- An absolute blood neutrophil count <1,000/mm3 at Visit 1.
- 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.
- 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 and
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, 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.
- 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).
- 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
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary endpoint is the time to first pulmonary exacerbation up to 48 weeks<br /><br>after first drug adminstration.</p><br>
- Secondary Outcome Measures
Name Time Method <p>The key secondary endpoint is the rate of pulmonary exacerbations (number of<br /><br>events per person-time) up to week 48 after first drug administration.<br /><br><br /><br>secondary endpoints:<br /><br>1) Absolute change from baseline in Quality of Life Questionnaire -<br /><br>Bronchiectasis (QOL-B) respiratory symptoms domain score at week 24 after first<br /><br>drug administration<br /><br>2) Relative change from baseline in neutrophil elastase (NE) activity in sputum<br /><br>at week 12 after first drug administration<br /><br>3) Absolute change from baseline in St. George's Respiratory Questionnaire<br /><br>(SGRQ) Symptoms score at week 24 after first drug administration<br /><br>4) Absolute change from baseline in percent predicted postbronchodilator forced<br /><br>expiratory volume in one second (FEV1%pred) at week 24 after first drug<br /><br>administration<br /><br>5) Occurrence of an exacerbation by week 24</p><br>