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 | 17.1 |
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 |
? To evaluate the efficacy of lebrikizumab compared with placebo as measured by the ability of patients to achieve lower daily doses of oral corticosteroids (OCS; prednisolone) while maintaining control of their asthma ? To evaluate periostin as a predictive biomarker to select patients most likely to receive benefit from lebrikizumab therapy ? To evaluate the safety and tolerability of lebrikizumab compared with placebo. |
-Evaluar la eficacia de lebrikizumab frente al placebo, medida mediante la capacidad de los pacientes para reducir las dosis diarias de CEO manteniendo su asma bajo control. -Evaluar la periostina como un biomarcador predictivo para seleccionar a aquellos pacientes que tengan más probabilidad de beneficiarse de la terapia con lebrikizumab -Evaluar la seguridad y la tolerabilidad de lebrikizumab frente al placebo. |
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E.2.2 | Secondary objectives of the trial |
? To assess the efficacy of lebrikizumab compared with placebo as measured by asthma exacerbation rate, lung function, fraction of exhaled nitric oxide (FeNO). |
-Evaluar la eficacia de lebrikizumab frente al placebo, medida mediante la tasa de exacerbaciones del asma, función pulmonar yFeNO. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patients, age 12-75 years at the time of informed consent
- Severe asthma despite intensive follow-up by an asthma specialist for at least 6 months prior to Visit 1
- Baseline forced expiratory volume in 1 second (FEV1) >=40% of predicted prior to randomization
-Receiving high doses of inhaled glucocorticosteroids at a total daily dose of >= 1500 mcg beclomethasone dipropionate daily or equivalent and long-acting beta-adrenoceptor agonist (LABA), with or without an additional controller, for at least 3 months prior to Visit 1
- Chronic treatment with maintenance oral corticosteroids for at least 6 months prior to Visit 1
- Assessment to ensure diagnosis of refractory asthma and oral corticosteroid dependence on minimal effective or maximum tolerated dose with compliance |
-Edad de 12 a 75 en el momento de dar el consentimiento informado. -Asma grave a pesar de un seguimiento intensivo por parte de un especialista en asma durante al menos los 6 meses previos de la Visita 1. -Volumen de expiración forzado en visita basal en 1 segundo (FEV1)>= 40% del previsto antes de la aleatorización. -Estar siendo tratados con altas dosis de glucocorticosteroides inhalados a una dosis diaria total de >= 1500 ?g de dipropionato de beclometasona o equivalente y LABA, con o sin un medicamento de control adicional, durante al menos los 3 meses previos a la Visita 1. -Tratamiento crónico con CEO de mantenimiento durante al menos los 6 meses previos a la Visita 1. -Valoración para garantizar el diagnóstico de asma resistente y de dependencia de CEO en la dosis mínima eficaz o en la dosis máxima tolerada con conformidad. |
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E.4 | Principal exclusion criteria |
- History of a severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of the lebrikizumab injection
- Asthma exacerbation within 28 days prior to Visit 1 or during screening (prior to Visit 3)
- For adults: Active tuberculosis requiring treatment within the 12 months prior to visit 1
- For adolescents: History of active tuberculosis requiring treatment
- Evidence of acute or chronic hepatitis or known liver cirrhosis
- Known current malignancy or current evaluation for a potential malignancy
- History of interstitial lung disease, chronic obstructive pulmonary disease, or other clinically significant lung disease other than asthma
- Infection requiring hospital admission or requiring treatment with IV or IM antibiotics within 4 weeks prior to visit 1 or during screening
- Upper or lower respiratory tract infection within 4 weeks prior to visit 1 or during screening
- Active parasitic infection or Listeria monocytogenes infection within 6 months prior to visit 1 or during screening
- Current smoker or former smoker with a smoking history of >15 pack-years
- Current use of an immunomodulatory/immunosuppressive therapy or past use within 3 months or 5 drug half-lives (whichever is longer) prior to visit 1
- Use of a licensed or investigational monoclonal antibody other than anti IL-13 or anti IL-4/IL-13, including, but not limited to, omalizumab, anti IL-5, or anti IL-17, within 6 months or 5 drug half-lives (whichever is longer) prior to visit 1
- Receipt of a live, attenuated vaccine within the 4 weeks prior to visit 1, during screening or anticipation of receipt of alive, attenuated vaccine throughout the study |
-Historial de reacción alérgica grave o reacción anafiláctica a un agente biológico o conocida hipersensibilidad a cualquier componente de la inyección de lebrikizumab. -Exacerbación del asma en los 28 días previos a la Visita 1 o durante la selección (antes de la Visita 3). -Para adultos: Tuberculosos activa que haya requerido tratamiento en los 12 meses previos a la Visita 1. -Para adolescentes: Historial de tuberculosis activa que requiera tratamiento. -Evidencia de hepatitis aguda o crónica o de cirrosis hepática conocida. -Malignidad actual conocida o evaluación actual de una posible malignidad. -Historial de enfermedad pulmonar intersticial, enfermedad pulmonar obstructiva crónica u otra enfermedad pulmonar clínicamente significativa aparte del asma. -Cualquier infección que haya provocado un ingreso hospitalario o que haya requerido tratamiento con antibióticos IM o IV en las 4 semanas previas a la Visita 1 o durante la selección. -Infección en las vías altas o bajas del tracto respiratorio en las 4 semanas previas a la Visita 1 o durante la selección. -Infección parasitaria activa o infección por Listeria monocytogenes en los 6 meses previos a la Visita 1 o durante la selección. -Fumador o exfumador con un historial de tabaquismo de 15 paquetes-año. -Uso de una terapia con inmunomoduladores/inmunodepresores en la actualidad o en los 3 meses o 5 vidas medias del fármaco (aquello que sea mayor) anteriores a la Visita 1. -Uso de un anticuerpo monoclonal autorizado o en fase de investigación distinto a anti?IL-13 o anti?IL-4/IL-13, incluyendo pero sin limitarse a omalizumab, anti?IL-5 o anti?IL-17, en los 6 meses o 5 vidas medias del fármaco previos a la Visita 1 (aquello que sea mayor). -Recepción con una vacuna viva debilitada en las 4 semanas previas a la Visita 1 durante la selección o previsión de recibir una vacuna viva debilitada durante el transcurso del estudio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Relative change in daily oral corticosteroids dose |
Variación relativa de la dosis diaria de CEO |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
from baseline to week 44 |
Desde nivel basal hasta la Semana 44 |
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E.5.2 | Secondary end point(s) |
1. Percentage of patients achieving at least a 50% reduction in their daily oral corticosteroid dose relative to baseline
2. Percentage of patients discontinuing oral corticosteroid therapy or having achieved an adrenal maintenance dose
3.Relative change in average oral corticosteroids dose during the oral corticosteroids reduction phase
4. Incidence and frequency of adverse events during the stable treatment phase and oral corticosteroids reduction phase
5. Severity of adverse events during the stable treatment phase and oral corticosteroids reduction phase
6. Frequency and severity of adverse events during the open label treatment extension period and safety follow-up period
7. Absolute change in daily oral corticosteriods dose
8. Rate of asthma exacerbations during the stable treatment phase and oral corticosteroids reduction phase |
1-Porcentaje de pacientes que consiguen una reducción de al menos un 50% en la dosis diaria de CEO que toman. 2-Porcentaje de pacientes que interrumpen la terapia con CEO o que han conseguido una dosis de mantenimiento adrenal. 3-Variación relativa de la dosis media de CEO durante la fase de reducción de CEO. 4-Incidencia y frecuencia de acontecimientos adversos durante la fase de tratamiento estable y durante la fase de reducción de CEO. 5-Gravedad de los acontecimientos adversos durante la fase de tratamiento estable y durante la fase de reducción de CEO. 6-Frecuencia y gravedad de los acontecimientos adversos durante el periodo ATA y el periodo de seguimiento de seguridad. 7-Variación absoluta de la dosis diaria de CEO. 8-Tasa de exacerbaciones del asma durante la fase de tratamiento estable y durante la fase de reducción de corticosteroides. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. week 44
2. from baseline to Week 44
3. from week 12 to week 44
4. 44 weeks
5. 44 weeks
6. from week 44 to week 96
7. from baseline to week 44
8. 44 weeks |
1. Semana 44
2. Desde nivel basal a semana 44
3. De semana 12 a semana 44
4. 44 semanas
5. 44 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 | No |
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 | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability |
Tolerabilidad |
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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 | Yes |
E.8.1.7.1 | Other trial design description |
Ampliacion del tratamiento activo |
Active treatment extension (ATE) |
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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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 47 |
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 |
Belgium |
Bulgaria |
Czech Republic |
France |
Netherlands |
New Zealand |
Poland |
Slovakia |
Slovenia |
Spain |
United Kingdom |
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' |
Ultimo paciente realiza la última visita (LPLV) |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |