Clairleafᵀᴹ: A Study to Test Long-term Treatment With BI 1291583 in People With Bronchiectasis Who Took Part in a Previous Study With This Medicine

Study Overview
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Brief Summary
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This study is open to adults aged 18 years and older with bronchiectasis. People can join the study if they were previously enrolled in another study with BI 1291583 (1397-0012: Airleafᵀᴹ). The purpose of this study is to find out whether a medicine called BI 1291583 helps people with bronchiectasis, an inflammatory lung condition. The investigators also want to know how well people with this condition can tolerate BI 1291583 in the long term. Participants take a low, medium, or high dose of BI 1291583 as a tablet once a day for up to 1 year. Participants who were taking placebo in the Airleafᵀᴹ study are put into the BI 1291583 dosage groups randomly, which means by chance. Placebo tablets look like BI 1291583 but do not contain any medicine. Participants who were taking BI 1291583 in the Airleafᵀᴹ study continue to take the same dose. Participants visit the study site 9 times and get 4 phone calls from the site staff. During the visits, the doctors collect information on any health problems of the participants. The doctors also check whether BI 1291583 helps reduce the symptoms of bronchiectasis.

Official Title
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A Randomised, Double-blind, Parallel Group, Roll-over Study Evaluating Long-term Safety and Efficacy of Oral Doses of BI 1291583 q.d. in Patients With Bronchiectasis ((Clairleafᵀᴹ)

Conditions
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Bronchiectasis

Intervention / Treatment
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* Drug: BI 1291583
* Drug: Placebo matching BI 1291583


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who completed the treatment period in Phase II trials (1397-0012) as planned per protocol. 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 trial, in accordance with Good Clinical Practice (GCP) and local legislation. Exclusion Criteria: Laboratory and medical examination Moderate or severe liver disease (defined by Child-Pugh score B or C hepatic impairment) or aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >3.0x Upper limit of normal (ULN) at Visit 1 (or at the last safety assessment in the parent trial, if no more than 6 weeks passed since then). Estimated glomerular filtration rate (eGFR) according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula <30 mL/min at Visit 1 (or at the last safety assessment in the parent trial, if no more than 6 weeks passed since then). An absolute blood neutrophil count <1,000/mm^3 (equivalent to <1,000 cells/μL or <10^9 cells/L) at Visit 1 (or at the last safety assessment in the parent trial, if no more than 6 weeks passed since then). Any findings in the medical examination and/or laboratory value assessed at Visit 1 (or at the last safety assessment in the parent trial, concerning the lab tests, if no more than 6 weeks passed since then), that in the opinion of the investigator may put the patient at risk by participating in the trial. New concomitant diagnosis and therapy A new diagnosis of Hypogammaglobulinemia Common variable immunodeficiency α1-antitrypsin deficiency being treated 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 and responsive to antifungal therapy, as per investigator's discretion. Any clinically relevant respiratory infection within 4 weeks prior Visit 2. Any acute infection requiring systemic or inhaled anti-infective therapy within 4 weeks prior Visit 2. Positive serological tests for hepatitis B, hepatitis C (also confirmed with ( Hepatitis C Virus ribonucleic acid test (HCV RNA))), or human immunodeficiency virus (HIV) infection, or known infection status at Visit 2. (The test results will be available after randomisation. In case the results no longer satisfy the entry criteria, these patients will be discontinued.) Any new evidence of a concomitant disease, such as Papillon-Lefèvre Syndrome (PLS), 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 trial. Received any live attenuated vaccine within 4 weeks prior to Visit 1. Further exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 1291583 low dose arm<br> | Drug: BI 1291583<br>* Tablet<br>Drug: Placebo matching BI 1291583<br>* Tablet<br>|
| Experimental: BI 1291583 medium dose arm<br> | Drug: BI 1291583<br>* Tablet<br>Drug: Placebo matching BI 1291583<br>* Tablet<br>|
| Experimental: BI 1291583 high dose arm<br> | Drug: BI 1291583<br>* Tablet<br>Drug: Placebo matching BI 1291583<br>* Tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of treatment-emergent adverse events (TEAEs) |  | up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first pulmonary exacerbation from first drug administration in this trial to the end of the trial | A pulmonary exacerbation in this trial is defined as having three or more of the following symptoms for at least 48 hours resulting in a physician's decision to prescribe antibiotics (oral or intravenous): Increased cough Increased sputum volume or change in sputum consistency Increased sputum purulence Increased breathlessness and/or decreased exercise tolerance Fatigue and/or malaise Hemoptysis | up to 12 months | 
| Rate of pulmonary exacerbations (number of events per person-time) over the course of this trial |  | up to 12 months |