E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10006445 |
E.1.2 | Term | Bronchiectasis |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- 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
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E.4 | Principal exclusion criteria |
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 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 -- α1-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 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. - 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1) Time to first pulmonary exacerbation up to 48 weeks after first drug adminstration |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | 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. Secondary endpoints: 1) Absolute change from baseline in Quality of Life Questionnaire – Bronchiectasis (QOL-B) respiratory symptoms domain score at week 24 after first drug administration 2) Relative change from baseline in neutrophil elastase (NE) activity in sputum at week 12 after first drug administration 3) Absolute change from baseline in St. George's Respiratory Questionnaire (SGRQ) Symptoms score at week 24 after first drug administration 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 5) Occurrence of an exacerbation by week 24
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) week 12 2) up to week 48 3) week 24 4) week 24 5) week 24 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 65 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Canada |
Israel |
Japan |
Korea, Republic of |
Mexico |
United Kingdom |
United States |
Belgium |
Bulgaria |
Czechia |
Denmark |
France |
Germany |
Greece |
Hungary |
Ireland |
Italy |
Latvia |
Netherlands |
Poland |
Portugal |
Spain |
Türkiye |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 13 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |