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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003553 |
E.1.2 | Term | Asthma |
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 |
To demonstrate that the efficacy of two treatment arms of the fixed-dose combination product QVM149 is non-inferior to the efficacy of the free combination arm of salmeterol/fluticasone + tiotropium in uncontrolled asthmatics. |
Demostrar que la eficacia de las dos concentraciones del producto de combinación a dosis fija QVM149 no es inferior a la eficacia de la combinación libre de salmeterol/propionato de fluticasona + tiotropio en asmáticos no controlados. |
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E.2.2 | Secondary objectives of the trial |
- To evaluate efficacy of QVM149 high-dose and QVM149 medium-dose compared to salmeterol/ fluticasone + tiotropium in terms of Trough FEV1 after 24 weeks of treatment. - To evaluate efficacy of QVM149 high-dose and QVM149 medium-dose compared to salmeterol/ fluticasone + tiotropium in terms of Asthma Quality of Life Questionnaire over 24 weeks of treatment. - To evaluate efficacy of QVM149 high-dose and QVM149 medium-dose compared to salmeterol/ fluticasone + tiotropium in terms of Asthma Control Questionnaire over 24 weeks of treatment. - To evaluate efficacy of QVM149 high-dose and QVM149 medium-dose compared to salmeterol/ fluticasone + tiotropium in terms of lung function over 24 weeks of treatment. |
- Evaluar la eficacia de una dosis alta de QVM149 y una dosis media de QVM149 en comparación con salmeterol/fluticasona + tiotropio en cuanto al FEV1 valle después de 24 semanas de tratamiento. - Evaluar la eficacia de una dosis alta de QVM149 o una dosis media de QVM149 en comparación con salmeterol/fluticasona + tiotropio después de 24 semanas de tratamiento en cuanto al Asthma Quality of Life Questionnaire. - Evaluar la eficacia de una dosis alta de QVM149 y una dosis media de QVM149 en comparación con salmeterol/fluticasona + tiotropio en cuanto al Asthma Control Questionnaire durante 24 semanas de tratamiento. - Evaluar la eficacia de una dosis alta de QVM149 y una dosis media de QVM149 en comparación con salmeterol/fluticasona + tiotropio en cuanto a la función pulmonar durante 24 semanas de tratamiento. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patients with a diagnosis of asthma for a period of at least 6 months prior to Visit 1 with current asthma severity ≥ step 4 (GINA 2017). - Patients who have used ICS/LABA combinations for asthma for at least 3 months and at stable medium or high dose of ICS/LABA for at least 1 month prior to Visit 1. - Patients must be symptomatic at screening despite treatment with medium or high stable doses of ICS/LABA as defined by ACQ-7 score ≥ 1.5 at visits 101 and 201 (randomization visit). - Patients with history of at least one severe asthma exacerbation which required medical care from a physician, ER visit (or local equivalent structure) or hospitalization in the 12 months prior to Visit 1 and required systemic corticosteroid treatment for at least 3 days including physician guided self-management treatment with oral corticosteroids as part of written asthma action plan. - Pre-bronchodilator FEV1 of < 85 % of the predicted normal value for the patient after withholding bronchodilators prior to spirometry at both Visit 101 and Visit 201. - Patients who demonstrate an increase in FEV1 of ≥ 12% and 200 mL. |
- Pacientes con un diagnóstico de asma durante al menos los 6 meses anteriores a la visita 1 con un escalón de gravedad del asma actual ≥ 4 (GINA 2017). - Pacientes que hayan utilizado combinaciones de CI/LABA para el asma durante al menos 3 meses y con una dosis media o alta estable de CI/LABA durante al menos el mes anterior a la visita 1. - Los pacientes deben continuar sintomáticos en la fase de selección a pesar del tratamiento con dosis medias o altas estables de CI/LABA según la definición de la puntuación del ACQ-7 ≥ 1,5 en las visitas 101 y 201 (visita de aleatorización). - Pacientes con antecedentes de al menos una exacerbación asmática que requiriese asistencia médica, visita a urgencias (URG.) (o estructura local equivalente) u hospitalización en los 12 meses anteriores a la visita 1 y que requiriese tratamiento con corticosteroides sistémicos (CS) durante al menos 3 días, incluido un tratamiento administrado por el propio paciente y guiado por el médico con corticosteroides orales (CO) como parte de un plan de acción escrito para el asma. - FEV1 prebroncodilatador < 85 % del valor teórico normal para el paciente, después de suspender el tratamiento con broncodilatadores antes de la espirometría en las visitas 101 y 201. - Pacientes que demuestren un incremento del FEV1 ≥ 12 % y 200 ml. |
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E.4 | Principal exclusion criteria |
- Patients who have a smoking history of greater than 20 pack years. - Patients diagnosed with Chronic Obstructive Pulmonary Disease (COPD). - Patients who have had an asthma attack/exacerbation requiring systemic steroids or hospitalization or emergency room visit within 6 weeks of Visit 1 (Screening). - Patients treated with a LAMA for asthma within 3 months prior to Visit 1. - Patients who have had a respiratory tract infection or clinical significant asthma worsening as defined by Investigator within 4 weeks prior to Visit 1 or between Visit 1 and Visit 201. |
- Pacientes que tengan antecedentes de consumo de tabaco > 20 paquetes año. - Pacientes con diagnóstico de enfermedad pulmonar obstructiva crónica (EPOC). - Pacientes que hayan tenido un ataque/exacerbación de asma que hayan requerido esteroides sistémicos, hospitalización o visita a urgencias durante las 6 semanas anteriores a la visita 1 (selección). - Pacientes tratados con un LAMA para el asma durante los 3 meses anteriores a la visita 1. - Pacientes que hayan tenido una infección del tracto respiratorio o empeoramiento del asma clínicamente significativo según la definición del investigador durante las 4 semanas anteriores a la visita 1 o entre la visita 1 y la visita 201. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in Asthma Quality of Life Questionnaire (AQLQ) total score |
Cambio respecto a la basal en la puntuación total del Asthma Quality of Life Questionnaire (AQLQ) |
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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) |
- Change from baseline in Trough FEV1 - Change from baseline in Asthma Control Questionnaire (ACQ-7) total score - Change from baseline in Asthma Quality of Life Questionnaire (AQLQ) total score - Percentage of patients achieving the minimal important difference (MCID) change from baseline ACQ-7 ≥ 0.5 decrease - Percentage of patients achieving the minimal important difference (MCID) change from baseline AQLQ ≥ 0.5 increase - Change from baseline in Forced Vital Capacity (FVC) - Change from baseline in Forced Expiratory Flow between 25% and 75% of Forced Vital Capacity (FEF25-75) |
- Cambio respecto a la basal en el FEV1. - Cambio respecto a la basal en la puntuación total del Asthma Control Questionnaire (ACQ-7). - Cambio respecto a la basal en la puntuación total del Asthma Quality of Life Questionnaire (AQLQ). - Porcentaje de pacientes que alcanzan una disminución en la diferencia mínimamente significativa (MCID) respecto al ACQ-7 basal ≥ 0,5 - Porcentaje de pacientes que alcanzan un cambio en la diferencia mínimamente significativa (MCID) respecto al AQLQ basal ≥ 0,5. - Cambio respecto a la basal en la FVC - Cambio respecto a la basal en el flujo espiratorio forzado entre el 25 % y el 75 % de la capacidad vital forzada (FEF25-75). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- 8 weeks, 16 weeks, 24 weeks - 16 weeks, 24 weeks - 16 weeks - 16 weeks, 24 weeks - 16 weeks, 24 weeks - 8 weeks, 16 weeks, 24 weeks - 8 weeks, 16 weeks, 24 weeks |
- 8 semanas, 16 semanas, 24 semanas - 16 semanas, 24 semanas - 16 semanas - 16 semanas, 24 semanas - 16 semanas, 24 semanas - 8 semanas, 16 semanas, 24 semanas - 8 semanas, 16 semanas, 24 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 | No |
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 | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Partially blind with double blind for QVM149 arms and open-label for comparator arm. |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 135 |
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 |
Brazil |
Chile |
China |
Colombia |
Czech Republic |
Egypt |
Germany |
Greece |
Hungary |
India |
Israel |
Italy |
Mexico |
Peru |
Poland |
Romania |
Russian Federation |
Serbia |
Singapore |
South Africa |
Taiwan |
Turkey |
United Kingdom |
Vietnam |
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E.8.7 | Trial has a data monitoring committee | No |
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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LPLV |
Ultima Visita del ultimo 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 | |
E.8.9.1 | In the Member State concerned months | 16 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 18 |