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 | 18.1 |
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 |
In patients with severe asthma and high eosinophil counts (?250 cells/?l) receiving SoC asthma therapy, to demonstrate the efficacy (as measured by rate of moderate-to-severe asthma exacerbations) of at least one dose level of QAW039 (150 mg or 450 mg once daily), compared with placebo, at the end of the 52-week active-treatment epoch. In patients with severe asthma receiving SoC asthma therapy, to demonstrate the efficacy (as measured by rate of moderate-to-severe asthma exacerbations) of at least one dose level of QAW039 (150 mg or 450 mg once daily), compared with placebo, at the end of the 52-week active-treatment epoch. |
En pacientes con asma grave y recuentos de eosinófilos altos (? 250 células/µl) que reciben tratamiento estándar (SOC) para el asma, demostrar la eficacia (medida según la tasa de exacerbaciones asmáticas de moderadas a graves) de al menos un nivel de dosis de QAW039 (150 o 450 mg una vez al día), en comparación con placebo, al final de la fase de tratamiento activo de 52 semanas. En pacientes con asma grave que reciben tratamiento estándar (SOC) para el asma, demostrar la eficacia (medida según la tasa de exacerbaciones asmáticas de moderadas a graves) de al menos un nivel de dosis de QAW039 (150 o 450 mg una vez al día), en comparación con placebo, al final de la fase de tratamiento activo de 52 semanas. |
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E.2.2 | Secondary objectives of the trial |
In patients with severe asthma and high eosinophil counts (?250 ells/?l) receiving SoC asthma therapy to demonstrate the efficacy of at least one dose level of QAW039 (150 mg or 450 mg once daily), compared with placebo, with respect to change from baseline, at the end of the 52-week active-treatment epoch, in AQLQ+12 scores, ACQ-5 score and pre-dose FEV1.
In all patients with severe asthma receiving SoC asthma therapy to demonstrate the efficacy of at least one dose level of QAW039 (150 mg or 450 mg once daily), compared with placebo, with respect to change from baseline, at the end of the 52-week active-treatment epoch, in : AQLQ+12 scores , ACQ-5 score and pre-dose FEV1.
To assess the safety of QAW039 (150 mg and 450 mg once daily), compared with placebo, with respect to adverse events, ECGs, vitals sign, laboratory tests and hypersensitivity reactions. |
En pacientes con asma grave y recuentos de eosinófilos altos (? 250 células/µl) que reciben tratamiento estándar para el asma demostrar la eficacia de al menos un nivel de dosis de QAW039 (150 o 450 mg una vez al día), en comparación con placebo, en relación con el cambio respecto a la basal en la puntuación del AQLQ+12, ACQ-5 y valor FEV1 pre-dosis al final de la fase de tratamiento activo de 52 semanas. En todos los pacientes con asma grave que reciben tratamiento estándar para el asma demostrar la eficacia de al menos un nivel de dosis de QAW039 (150 o 450 mg una vez al día), en comparación con placebo, en relación con el cambio respecto a la basal en la puntuación del AQLQ+12, ACQ-5 y valor FEV1 pre-dosis al final de la fase de tratamiento activo de 52 semanas. Evaluar la seguridad de QAW039, en comparación con placebo, respecto a los acontecimientos adversos, electrocardiogramas (ECG), constantes vitales, pruebas analíticas y reacciones de hipersensibilidad. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Written informed consent. -Male and female patients aged ?12 years. -A diagnosis of severe asthma, uncontrolled on GINA 4/5 asthma medication. -Evidence of airway reversibility or airway hyper-reactivity. -FEV1 of ?40% and ?80% of the predicted normal value. -An ACQ score ?1.5. -A history of 2 or more asthma exacerbations within the 12 months prior to entering the study.
Other inclusion criteria apply. See protocol for full details |
?Consentimiento informado por escrito ?Pacientes adultos de ambos sexos ? 12 años de edad. ?Diagnostico de asma grave, no controlada en tratamiento segun los pasos 4/5 GINA 2015 ?Evidencia de reversibilidad o hiperreactividad de las vías respiratorias ?FEV1 ? 40 % y ? 80 % del valor teórico normal ?ACQ ? 1,5 ?Antecedentes de 2 o más exacerbaciones asmáticas durante los 12 meses anteriores a la visita 1 Para el resto de criterios de inclusion, refierase al protocolo. |
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E.4 | Principal exclusion criteria |
-Use of other investigational drugs within 5 half-lives of study entry, or within 30 days, whichever is longer. -Subjects who have participated in another trial of QAW039. -A QTcF (Fridericia) ?450 msec (male) or ?460 msec (female). -History of malignancy with the exception of local basal cell carcinoma of the skin. -Pregnant or nursing (lactating) women. -Serious co-morbidities. -Patients on >20 mg of simvastatin, > 40 mg of atorvastatin, >40 mg of pravastatin, and >2 mg of pitavastatin
Other exclusion criteria apply. See protocol for full details |
?Uso de cualquier otro fármaco en investigación dentro de un tiempo de 5 vidas medias de la inclusión o 30 días hasta que el efecto farmacodinámico previsto vuelva a los valores basales (aquel periodo que sea más largo). ?Sujetos que hayan participado en otro ensayo de QAW039 ?QTcF (Fridericia) ? 450 ms (hombres) o ? 460 ms (mujeres) ?Pacientes con antecedentes de tumores malignos en cualquier órgano, a excepción de carcinoma cutáneo de células basales localizado. ?Mujeres embarazadas o en periodo de lactancia ?Pacientes con comorbilidades graves ?Pacientes que reciban >20 mg de simvastatina, > 40 mg de atorvastatina, >40 mg de pravastatina o >2 mg de pitavastatina Para el resto de criterios de exclusión, refierase al protocolo. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Reduction in the rate of moderate-to-severe asthma exacerbations. A severe asthma exacerbation is defined as treatment with ?rescue? systemic corticosteroids for greater than or equal to 3 days and hospitalization; or treatment with ?rescue? systemic corticosteroids for greater than or equal to 3 days and emergency department visit (greater than 24 hours); or death due to asthma. A moderate asthma exacerbation is defined as treatment with ?rescue? systemic corticosteroids for greater than or equal to 3 days either as an outpatient or in emergency department visits (Emergency department visit less than or equal to 24 hours). |
Reducción en la tasa de exacerbaciones de asma de moderadas a graves. Una exacerbación asmática grave se define como el ratamiento con corticosteroides sistémicos «de rescate» durante al menos 3 días y hospitalización; o el tratamiento con corticosteroides sistémicos «de rescate» durante al menos 3 días y visita a urgencias (más de 24 horas); o muerte debida al asma. Una exacerbación asmática moderada se define como tratamiento con corticosteroides sistémicos «de rescate» durante al menos 3 días con visita ambulatoria o visita a urgencias (de un máximo de 24 horas). |
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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 AQLQ+12 score. AQLQ+12 consists of 32 questions each scaled from 1 to 7, where 1 indicates maximal impairment and 7 indicates no impairment. - Change from baseline in ACQ-5 score. The ACQ- 5 consists of 5 questions on a 7-point scale (0=no impairment, 6=maximum impairment). - Change from baseline in pre-dose FEV1 (liters). - Adverse event monitoring. |
- Cambio respecto a la basal en la puntuación del AQLQ+12. El AQLQ+12 comprende un total de 32 preguntas individuales y cada ítem puntúa en una escala de 1 a 7 (7 = ningún deterioro; 1 = grave deterioro). - Cambio respecto a la basal en la puntuación delACQ-5. El ACQ-5 consiste en 5 preguntas con una escala de 7 puntos (0 = ninguna afectación, 6 = afectación máxima). - Cambio respecto a la basal en el valor FEV1 pre-dosis (litros) - seguimiento efectos adversos |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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 | 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 | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 69 |
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 |
Canada |
Czech Republic |
Greece |
India |
Israel |
Japan |
Korea, Democratic People's Republic of |
Malaysia |
Mexico |
Netherlands |
Russian Federation |
Serbia |
Slovakia |
South Africa |
Spain |
Taiwan |
United States |
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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: 15-November-2018 |
Ultima visita del ultimo paciente: 15-Nov-2018 |
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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 | 9 |
E.8.9.1 | In the Member State concerned days | |
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 | 11 |