E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
bronchiectasis |
bronquiectasia |
|
E.1.1.1 | Medical condition in easily understood language |
bronchiectasis |
bronquiectasia |
|
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 |
|
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. |
El objetivo principal del ensayo es demostrar una curva dosis-respuesta no plana y evaluar la relación dosis-respuesta de 3 pautas posológicas orales de BI 1291583 frente a placebo, en el criterio principal de valoración, el tiempo hasta la primera reagudización pulmonar hasta las semana 48. |
|
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. |
El objetivo secundario es demostrar la superioridad de 5 mg de BI 1291583 frente a placebo en el criterio principal de valoración, el tiempo transcurrido hasta la primera reagudización pulmonar hasta la semana 48, así como en el criterio secundario de valoración, la tasa de reagudizaciones pulmonares hasta la semana 48. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female (not of childbearing potential) 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 |
- Pacientes hombres o mujeres (sin capacidad de gestación) - Edad de los pacientes al firmar el consentimiento informado ≥18 y ≤85 años. - Antecedentes clínicos compatibles con bronquiectasia (tos, producción crónica de esputo y/o infecciones respiratorias recurrentes) y diagnóstico confirmado por el investigador de bronquiectasia por tomografía computarizada (TAC). - Historia de reagudizaciones pulmonares que requieren tratamiento antibiótico. En los 12 meses anteriores a la visita 1, los pacientes deben haber tenido: — al menos 2 reagudizaciones, o — al menos 1 reagudización y una puntuación >40 de síntomas SGRQ en la visita 1 de cribado. En pacientes en mantenimiento con antibióticos orales o inhalados como tratamiento crónico de la bronquiectasia, debe haberse producido al menos una reagudización desde el inicio de la administración estable de antibióticos. - Productores actuales de esputo con antecedentes de expectoración crónica |
|
E.4 | Principal exclusion criteria |
- AST and / or ALT >3.0 x ULN at Visit 1 - 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 clinically relevant finding in the medical examination (including BP, PR, or ECG) and/or laboratory value assessed by the Investigator at Screening Visit 1 or during screening period. - 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 -- α1-antitrypsin deficiency -- Allergic bronchopulmonary aspergillosis 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 acute infections (including respiratory infections) defined as infections requiring systemic or inhaled antibiotic therapy within 4 weeks prior Visit 1 and throughout screening. - Any evidence of a concomitant disease, such as Papillon-Lefevre Syndrome, relevant pulmonary, gastrointestinal, hepatic, renal, cardiovascular, metabolic, immunological, or hormonal disorders. - 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. |
- AST y/o ALT >3,0 x ULN en la visita 1 - Tasa estimada de filtración glomerular (eGFR) según la fórmula CKD-EPI < 30 mL/min en la visita 1. - Recuento absoluto de neutrófilos en sangre <1.000/mm3 en la visita 1. - Cualquier hallazgo clínicamente relevante en el examen médico (incluyendo PA, RP o ECG) y/o valor de laboratorio evaluado por el investigador en la visita de detección 1 o durante el periodo de cribado. - Pruebas serológicas positivas para hepatitis B, hepatitis C o infección por el virus de la inmunodeficiencia humana (VIH), o estado de infección conocido - Un diagnóstico actual de: — Fibrosis quística — Hipogammaglobulinemia — Inmunodeficiencia variable común — Deficiencia de alfa1-antitripsina — Aspergilosis broncopulmonar alérgica actual que requiere tratamiento — Tuberculosis o infección micobacteriana no tuberculosa tratada o que requiera tratamiento de acuerdo con las directrices locales — Queratosis palmoplantar; o queratoderma climactericum — Hipotiroidismo, mixoedema, linfoedema crónico con hiperqueratosis cutánea asociada, acrocianosis. Si un sujeto tiene hipotiroidismo pero es tratado y compensado, el sujeto es admitido en el ensayo — Psoriasis que afecta a las palmas y a las plantas; o superficie corporal para psoriasis ≥ 10% — Artritis reactiva (síndrome de Reiter); queratoderma blennorrhagicum — Pityriasis rubra pilaris — Dermatitis atópica que afecta a las palmas y a las plantas; o superficie corporal para dermatitis atópica ≥ 10%. — Verruca vulgaris extensiva activa, a discreción del investigador — Infección fúngica activa de manos y/o pies no tratada adecuadamente y que no responde a la terapia antifúngica, a discreción del investigador - Cualquier infección aguda (incluyendo infecciones respiratorias) definida como infecciones que requieren tratamiento con antibióticos sistémicos o inhalados en las 4 semanas previas a la Visita 1 y durante el cribado. - Cualquier evidencia de una enfermedad concomitante, como el Síndrome de Papillon-Lefevre, trastornos pulmonares, gastrointestinales, hepáticos, renales, cardiovasculares, - Recibida cualquier vacuna viva atenuada en las 4 semanas previas a la visita 2. - Afecciones médicas asociadas a enfermedad periodontal (a evaluar por un periodoncista o dentista). - Pacientes que deben o desean continuar la ingesta de medicamentos restringidos o de cualquier medicamento que se considere que pueda interferir con la seguridad del ensayo.
Se aplican otros criterios. |
|
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 |
1) Tiempo transcurrido hasta la primera reagudización pulmonar hasta 48 semanas después de la primera administración del fármaco |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1) Relative change from baseline in neutrophil elastase (NE) activity in sputum at week 12 after first drug administration 2) Rate of pulmonary exacerbations (number of events per person-time) up to week 48 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 after first drug administration |
1) Variación relativa respecto al inicio en la actividad de la neutrófilo elastasa (NE) en el esputo en la semana 12 tras la primera administración del fármaco 2) Tasa de reagudizaciones pulmonares (número de acontecimientos por persona-tiempo) hasta la semana 48 tras la primera administración del fármaco 3) Variación absoluta respecto al valor basal en la puntuación de síntomas del St. George’s Respiratory Questionnaire (SGRQ) en la semana 24 tras la primera administración del fármaco 4) Variación absoluta con respecto al inicio en el porcentaje teórico después del broncodilatador del volumen espiratorio forzado en un segundo (FEV1%teór) en la semana 24 tras la primera administración del fármaco 5) Aparición de una reagudización en la semana 24 tras la primera administración del fármaco |
|
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 |
1) Semana 12 2) hasta la semana 48 3) Semana 24 4) Semana 24 5) Semana 24 |
|
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 | 3 |
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 |
Mexico |
Turkey |
Belgium |
Bulgaria |
Canada |
Czechia |
Denmark |
Germany |
Greece |
Hungary |
Ireland |
Israel |
Italy |
Japan |
Korea, Republic of |
Latvia |
Netherlands |
New Zealand |
Poland |
Portugal |
Russian Federation |
Spain |
Ukraine |
United Kingdom |
United States |
France |
|
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
|
LVLS |
Última visita del último paciente |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | |
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 |