E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Progressive Fibrosing Interstitial Lung Diseases (PF-ILDs) |
Enfermedades Pulmonares Intersticiales Fibrosantes Progresivas (EPI-FP) |
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E.1.1.1 | Medical condition in easily understood language |
Progressive Fibrosing Interstitial Lung Disease |
Enfermedad Pulmonar Intersticial Fibrosante Progresiva |
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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 | 23.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10084309 |
E.1.2 | Term | Progressive fibrosing interstitial lung disease |
E.1.2 | System Organ Class | 100000004855 |
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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 trial will evaluate efficacy and safety of BI 1015550. The primary objective is to assess a reduction in lung function decline as measured by the change from baseline in FVC for BI 1015550 when compared to placebo in patients with progressive fibrosing ILDs. |
El ensayo evaluará la eficacia y seguridad de BI 1015550. El objetivo principal es evaluar una reducción en la disminución de la función pulmonar medida por el cambio en la CVF desde el inicio para BI 1015550 en comparación con placebo en pacientes con EPI fibrosante progresiva. |
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E.2.2 | Secondary objectives of the trial |
The main secondary objective of the trial is to assess BI 1015550’s ability in reducing the occurrence of clinically meaningful events such as acute ILD exacerbations, hospitalization for respiratory cause or death over the duration of the trial when compared to placebo in patients with progressive fibrosing ILDs. An additional secondary objective of the trial is to show an effect of BI 1015550 on symptoms and lung function. |
El objetivo secundario principal del ensayo es evaluar la capacidad de BI 1015550 de reducir la aparición de acontecimientos clínicamente significativos, como exacerbaciones agudas de la EPI, hospitalización por causa respiratoria o muerte durante la duración del ensayo, en comparación con placebo en pacientes con EPI fibrosantes progresivas. Un objetivo secundario adicional del ensayo es mostrar un efecto del BI 1015550 sobre los síntomas y la función pulmonar. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients ≥18 years old at the time of signed informed consent. 2. Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial. 3. Diagnosis of progressive fibrosing ILD other than IPF (physician confirmed; Section 3.3.1) 4. Patients may be either: -- on a stable therapy* with nintedanib for at least 12 weeks prior to Visit 1 and during screening and are planning to stay on this background treatment after randomization. *stable therapy is defined as a tolerated regimen of nintedanib (with no dose changes) for at least 12 weeks. -- not on treatment with nintedanib for at least 8 weeks prior to Visit 1 and during the screening period (e.g. either AF-treatment naïve or previously discontinued) and do not plan to start or re-start antifibrotic treatment. 5. Forced Vital Capacity (FVC) ≥45% of predicted normal at Visit 1. 6. DLCO corrected for Hemoglobin (Hb) [Visit 1] ≥25% and <90% predicted of normal at Visit 1. 7. Women of childbearing potential (WOCBP)1 must be ready and able to use highly effective methods of birth control. Of note, oral hormonal contraceptives are not considered a highly effective method due to potential drug-drug interactions. 8. Patients treated with permitted immunosuppressive agents for an underlying systemic disease (e.g. MTX, AZA) need to be on a stable treatment for at least 12 weeks prior to Visit 1 and during the screening period. |
1. Pacientes ≥18 años en el momento de la firma del consentimiento informado. 2. Consentimiento informado firmado y fechado por escrito de conformidad con ICH-GCP y la legislación local antes de la admisión en el ensayo. 3. Diagnóstico de EPI fibrosante progresiva distinta de la FPI (confirmado por el médico; sección 3.3.1) 4. Los pacientes pueden: — estar en tratamiento estable* con nintedanib durante al menos 12 semanas antes de la visita 1 y durante la selección y tienen previsto permanecer con este tratamiento de base después de la aleatorización. *la terapia estable se define como un régimen tolerado de nintedanib (sin cambios de dosis) durante al menos 12 semanas. — no estar en tratamiento con nintedanib durante al menos 8 semanas antes de la visita 1 y durante el periodo de selección (por ejemplo, sin tratamiento previo con AF o previamente interrumpido) y no planear iniciar o reiniciar el tratamiento antifibrótico. 5. Capacidad vital forzada (CVF) ≥45 % de la normal prevista en la visita 1. 6. DLCO corregido para Hemoglobina (Hb) [Visita 1] ≥25% y < 90 % del valor normal en la Visita 1. 7. Las mujeres en edad fértil (WOCBP) deben estar preparadas y ser capaces de utilizar métodos anticonceptivos altamente eficaces. Cabe destacar que los anticonceptivos hormonales orales no se consideran un método muy eficaz debido a las posibles interacciones entre medicamentos. 8. Los pacientes tratados con agentes inmunosupresores permitidos para una enfermedad sistémica subyacente (p. ej., MTX, AZA) deben estar en tratamiento estable durante al menos 12 semanas antes de la visita 1 y durante el periodo de selección. |
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E.4 | Principal exclusion criteria |
1. Relevant airways obstruction (prebronchodilator FEV1/FVC <0.7) at Visit 1 2. In the opinion of the Investigator, other clinically significant pulmonary abnormalities. 3. Acute ILD exacerbation within 3 months prior to Visit 1 and/or during the screening period (investigator-determined). 4. Relevant chronic or acute infections including human immunodeficiency virus (HIV) and viral hepatitis. 5. Patients having developed ILD due to SARS-CoV-2 infection/COVID-19 within 12 months of screening (based on investigators judgement). 6. Major surgery (major according to the investigator’s assessment) performed within 6 weeks prior to Visit 2 or planned during the trial period, e.g. hip replacement. Registration on lung transplantation list would not be considered as planned major surgery. 7. Any documented active or suspected malignancy or history of malignancy within 5 years prior to Visit 1, except appropriately treated basal cell carcinoma of the skin, in situ squamous cell carcinoma of the skin or in situ carcinoma of uterine cervix. 8. AST or ALT >2.5 x ULN or total Bilirubin >1.5 x ULN at Visit 1. 9. eGFR ≤30 mL/min/1.73 m2 at Visit 1. (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula or Japanese version of CKD-EPI for Japanese patients) 10. Patients with underlying chronic liver disease (Child Pugh A, B, or C hepatic impairment). 11. Cardiovascular diseases, any of the following: a. Severe hypertension (uncontrolled under treatment ≥160/100 mmHg at multiple occasions) within 3 months of Visit 1 b. Myocardial infarction, stroke or transient ischemic attack within 6 months of Visit 1 c. Unstable cardiac angina within 6 months of Visit 1 12. Use of any of the following medications: prednisone >15mg/day or equivalent within 4 weeks of Visit 1; cyclophosphamide, tocilizumab, mycophenolate, pirfenidone within 8 weeks of Visit 1; rituximab within 6 months of Visit 1.
Further criteria apply. |
1. Obstrucción importante de las vías aéreas (VEF1/CVF < 0,7 antes de la broncodilatación) en la visita 1 2. En opinión del investigador, otras anomalías pulmonares clínicamente significativas. 3. Exacerbación aguda de la EPI en los 3 meses anteriores a la visita 1 y/o durante el período de selección (determinado por el investigador). 4. Infecciones crónicas o agudas pertinentes, incluidos el virus de la inmunodeficiencia humana (VIH) y la hepatitis vírica. 5. Pacientes que han desarrollado EPI debido a infección por SARS-CoV-2/COVID-19 dentro de los 12 meses de la selección (basado en el criterio de los investigadores). 6. Cirugía mayor (mayor según la evaluación del investigador) realizada en las 6 semanas previas a la visita 2 o planificada durante el período del ensayo, por ejemplo, reemplazo de cadera. El registro en la lista de trasplante de pulmón no se consideraría una cirugía mayor planificada. 7. Cualquier neoplasia maligna activa o sospechada documentada o antecedentes de neoplasia maligna en los 5 años anteriores a la visita 1, excepto el carcinoma basocelular de la piel tratado adecuadamente, el carcinoma de células escamosas in situ de la piel o el carcinoma in situ de cérvix uterino. 8. AST o ALT > 2,5 x LSN o bilirrubina total > 1,5 x LSN en la visita 1. 9. TFGe ≤30 ml/min/1,73 m2 en la visita 1. (fórmula de Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] o versión japonesa de CKD-EPI para pacientes japoneses) 10. Pacientes con enfermedad hepática crónica subyacente (insuficiencia hepática Child Pugh A, B o C). 11. Enfermedades cardiovasculares, cualquiera de las siguientes: a. Hipertensión grave (no controlada con un tratamiento ≥ 160/100 mmHg en múltiples ocasiones) dentro de los 3 meses de la visita 1 b. Infarto de miocardio, ictus o ataque isquémico transitorio en los 6 meses siguientes a la visita 1 c. Angina cardiaca inestable dentro de los 6 meses de la visita 1 12. Uso de cualquiera de los siguientes medicamentos: prednisona >15 mg/día o equivalente en las 4 semanas anteriores a la Visita 1; ciclofosfamida, tocilizumab, micofenolato, pirfenidona en las 8 semanas anteriores a la Visita 1; rituximab en los 6 meses anteriores a la Visita 1.
Se aplican otros criterios. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1) absolute change from baseline in Forced Vital Capacity (FVC) [mL] at Week 52 |
1) Cambio absoluto respecto al inicio en la Capacidad Vital Forzada (CVF) [ml] en la semana 52 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1) 52 weeks |
1) 52 semanas |
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E.5.2 | Secondary end point(s) |
1) key secondary endpoint: time to the first occurrence of any of the components of the composite endpoint: time to first acute ILD exacerbation, first hospitalization for respiratory cause, or death (whichever occurs first) over the duration of the trial 2) Time to first acute ILD exacerbation or death over the duration of the trial 3) Time to hospitalization for respiratory cause or death over the duration of the trial 4) Time to absolute decline in FVC % predicted of >10% from baseline or death over the duration of the trial 5) Time to absolute decline in (DLCO) % predicted of >15% from baseline or death over the duration of the trial 6) Time to death over the duration of the trial 7) Absolute change from baseline in Living with Pulmonary Fibrosis (L-PF) Symptoms Dyspnea domain score at Week 52 8) Absolute change from baseline in Living with Pulmonary Fibrosis (L-PF) Symptoms Cough domain score at Week 52 9) Absolute change from baseline in Living with Pulmonary Fibrosis (L-PF) Symptoms Fatigue domain score at Week 52 10) Absolute change from baseline in FVC % predicted at Week 52 11) Absolute change from baseline in DLCO % predicted at Week 52 |
1) Variable secundaria clave: tiempo hasta la primera aparición de cualquiera de los componentes del criterio de valoración compuesto: tiempo transcurrido hasta la primera exacerbación aguda de la EPI, primera hospitalización por causa respiratoria o muerte (lo que ocurra primero) durante la duración del ensayo 2) Tiempo hasta la primera exacerbación aguda de la EPI o hasta la muerte durante el ensayo 3) Tiempo hasta la hospitalización por causa respiratoria o muerte durante la duración del ensayo 4) Tiempo hasta la disminución absoluta del % de CVF prevista > 10 % respecto al valor basal o muerte durante la duración del ensayo 5) Tiempo hasta la disminución absoluta del % previsto de (DLCO) > 15 % desde el inicio o la muerte durante la duración del ensayo 6) Tiempo hasta la muerte durante el ensayo 7) Cambio absoluto respecto al valor inicial en la escala Living with Pulmonary Fibrosis (L-PF) Symptoms del dominio de disnea en la semana 52. 8) Cambio absoluto respecto al valor inicial en la escala Living with Pulmonary Fibrosis (L-PF) Symptoms del dominio de tos en la semana 52. 9) Cambio absoluto respecto al valor inicial en la escala Living with Pulmonary Fibrosis (L-PF) Symptoms del dominio de fatiga en la semana 52. 10) Cambio absoluto respecto al valor inicial en el % de CVF previsto en la semana 52 11) Cambio absoluto con respecto al valor inicial en el % de DLCO previsto en la semana 52 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) 30 months 2) 30 months 3) 30 months 4) 30 months 5) 30 months 6) 30 months 7) 52 weeks 8) 52 weeks 9) 52 weeks 10) 52 weeks 11) 52 weeks |
1) 30 meses 2) 30 meses 3) 30 meses 4) 30 meses 5) 30 meses 6) 30 meses 7) 52 semanas 8) 52 semanas 9) 52 semanas 10) 52 semanas 11) 52 semanas |
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | 3 |
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 | 25 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 179 |
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 |
Argentina |
Australia |
Brazil |
Canada |
Chile |
China |
Egypt |
India |
Israel |
Japan |
Korea, Republic of |
Malaysia |
Mexico |
New Zealand |
Saudi Arabia |
Singapore |
South Africa |
Taiwan |
Thailand |
United States |
Austria |
Estonia |
Finland |
France |
Poland |
Sweden |
Netherlands |
Spain |
Switzerland |
Czechia |
Germany |
Greece |
Italy |
Belgium |
Croatia |
Denmark |
Georgia |
Hungary |
Ireland |
Norway |
Portugal |
Russian Federation |
Serbia |
Slovenia |
Turkey |
Ukraine |
United Kingdom |
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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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LVLS |
Última visita del último paciente |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 4 |