E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Uncontrolled asthma despite the use of an inhaled corticosteroid and a second controller medication. |
Asma no controlada a pesar del uso de un corticosteroide inhalado y un segundo medicamento de control |
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E.1.1.1 | Medical condition in easily understood language |
Uncontrolled asthma despite daily therapy. |
Asma no controlada a pesar de una terapia diaria |
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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 | 14.1 |
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 |
? The efficacy of lebrikizumab compared with placebo as measured by the rate of exacerbations ? The safety of lebrikizumab compared with placebo ? Periostin as a predictive biomarker (diagnostic) ? The efficacy and safety of different dose levels of lebrikizumab compared to placebo. |
-La eficacia de lebrikizumab en comparación con el placebo, valorado mediante la tasa de reagudizaciones -La seguridad de lebrikizumab en comparación con el placebo -El uso de periostina como biomarcador predictivo (diagnóstico) -La seguridad y la eficacia de diferentes dosis de lebrikizumab en comparación con el placebo |
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E.2.2 | Secondary objectives of the trial |
The efficacy of lebrikizumab compared with placebo with respect to lung function, time to first exacerbation, fractional exhaled nitric oxide (FeNO), asthma-specific health-related quality of life, rescue medication use (i.e. short-acting ?-agonists [SABA]), and health care utilization. |
La eficacia de lebrikizumab frente a placebo con respecto a la función pulmonar, tiempo transcurrido hasta la primera reagudización, FeNO, calidad de vida relacionada con la salud específica del asma, uso de medicamentos de rescate (es decir agonistas de acción corta [SABA]) y utilización de recursos sanitarios |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Ability and willingness to provide written informed consent and to comply with the study protocol - 18?75 years old at screening - Asthma diagnosis for ? 12 months prior to the start of screening - Bronchodilator response (defined as a minimum 12% relative improvement in the volume of FEV1 after bronchodilator administration) during the screening period - Pre-bronchodilator FEV1 40%?80% of predicted - On ICS (500-2000 µg/day of fluticasone propionate DPI or equivalent, total daily dose) for ? 6 months prior to the start of screening - On an eligible second controller medication for 6 months prior to the start of screening - Uncontrolled asthma demonstrated during the screening period - Chest X-ray or computed tomography (CT) scan obtained within 12 months prior to screening or chest X-ray during the screening period confirming the absence of other lung disease - Demonstrated adherence with controller medication during the screening period. |
Disposición y capacidad para otorgar el consentimiento informado por escrito y para cumplir los procedimientos del estudio - 18-75 años de edad en la visita 1 -Antecedentes de asma durante ?12 meses antes de la visita de selección - Respuesta al broncodilatador La respuesta a un broncodilatador requiere una mejoría mínima relativa del 12 % del FEV1 después de la administración del broncodilatador - Un FEV1 antes del broncodilatador del 40-80 % del valor previsto - Tratamiento con CI en dosis de 500-2000 ?g/día de propionato de fluticasona DPI o equivalente durante ? 6 meses antes del inicio de la selección - Tratamiento con una segunda medicación de control apto (LABA, AMAP, ARLT o teofilina, en el intervalo posológico prescrito) durante 6 meses antes del inicio de la selección - Asma no controlada, demostrada durante el período de selección -Radiografía de tórax o tomografía computerizada (TC) obtenida en los 12 meses previos a la visita 1, o radiografía de tórax obtenida durante el período de selección. -Cumplimiento demostrado de la medicación de control |
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E.4 | Principal exclusion criteria |
- History of a severe allergic reaction or anaphylactic reaction to a biologic agent - Daily or alternate day oral corticosteroid maintenance therapy within the 3 months prior to screening - Treatment with systemic corticosteroids within the 4 weeks prior to, or at anytime during the screening period - Recent major episode of infection - Active parasitic infection or lysteria monocitogenes infection within the 6 months prior to screening - Active tuberculosis requiring treatment within the 12 months prior to screening - Known immunodeficiency, including, but not limited to, HIV infection - Evidence of acute or chronic hepatitis or known liver cirrhosis - History of cystic fibrosis, chronic obstructive pulmonary disease, and/or other clinically significant lung disease other than asthma - Known current malignancy or current evaluation for a potential malignancy - Other clinically significant medical disease that is uncontrolled despite treatment or that is likely, in the opinion of the investigator, to require a change in therapy or impact the ability to participate in the study - History of alcohol, drug, or chemical abuse - Current smoker (cigarettes, pipe, cigar, or marijuana) or former smoker with a smoking history of > 10 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 screening - Use of a biologic therapy including omalizumab (Xolair) at any time during the 6 months prior to screening - Use of zileuton (ZYFLO) or roflumilast (Daxas, Daliresp) at any time during the 6 months prior to screening - Treatment with an investigational agent within 30 days of screening (or 5 half lives of the investigational agent, whichever is longer) - Receipt of a live/attenuated vaccine within the 4 weeks prior to sreening - Female patients who are pregnant or lactating or unwilling to use a highly effective method of contraception - Body mass index > 38 kg/m2 - Body weight < 40 kg. |
Antecedentes de reacción alérgica o reacción anafiláctica graves a un agente biológico, - Mantenimiento con corticoesteroides orales, definido como tratamiento de mantenimiento diario o en días alternos con corticoesteroides orales en los 3 meses anteriores - Tratamiento con corticoesteroides sistémicos (orales, i.v. o i.m.) en las 4 semanas anteriores a la visita 1 o en algún momento durante el período de selección - Un episodio reciente de infección - Infección parasitaria activa o por lysteria monocitogenes en los 6 meses anteriores a la visita 1 - Tuberculosis activa que requiera tratamiento en los 12 meses anteriores a la visita 1 - Inmunodeficiencia conocida, incluida, entre otras, la infección por el VIH - Indicios de hepatitis aguda o crónica, o diagnóstico de cirrosis hepática - Antecedentes de fibrosis quística, EPOC u otra neumopatía de trascendencia clínica distinta del asma - Proceso maligno actual diagnosticado o posible en proceso de evaluación - Otra afección médica significativa que no se controle a pesar del tratamiento, o que es probable que, en opinión del investigador, requiera modificaciones del tratamiento o afecte a la capacidad de participar en el estudio - Antecedentes de alcoholismo, abuso de fármacos o toxicomanía. - Pacientes fumadores o exfumadores, con antecedentes de tabaquismo de > 10 paquetes-año -Tratamiento actual con algún agente inmunomodulador/inmunodepresor, o tratamiento anterior en los 3 meses o 5 semividas (el período que sea más prolongado) antes de la visita 1 - Uso de un tratamiento biológico, incluido omalizumab, en cualquier momento durante los 6 meses anteriores a la visita 1 - Uso de zileuton o roflumilast en algún momento durante los 6 meses anteriores a la visita 1 - Tratamiento con algún fármaco en investigación en los 30 días anteriores a la visita 1 (o 5 semividas del fármaco en investigación, el período que sea más prolongado). - Vacunación con vacunas de virus vivos/atenuados en las cuatro semanas anteriores a la visita 1 - Mujeres en edad fértil que no estén dispuestas a utilizar un método - Índice de masa corporal >38 kg/m2 - Peso corporal < 40 kg |
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E.5 End points |
E.5.1 | Primary end point(s) |
Rate of asthma exacerbations. |
Tasa de reagudizaciones de asma |
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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) |
? Frequency of adverse events during the 52-week placebo-controlled period ? Severity of adverse events during the 52-week placebo-controlled period ? Incidence of anti-therapeutic antibodies during the study relative to the incidence at baseline ? Frequency and severity of adverse events during the 52-week active-treatment extension and during the 24-week safety follow-up period. |
-Frecuencia de acontecimientos adversos durante el período de 52 semanas controlado con placebo -Intensidad de los acontecimientos adversos durante el período de 52 semanas controlado con placebo -Incidencia de anticuerpos contra el tratamiento durante el estudio en relación con la incidencia en el período inicial Frecuencia e intensidad de los acontecimientos adversos durante el período de extensión de 52 semanas con tratamiento activo y durante el período de seguimiento para seguridad de 24 semanas |
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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 | 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 | 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 | 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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 62 |
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 |
Bulgaria |
Canada |
Chile |
China |
Colombia |
Czech Republic |
France |
Germany |
Hungary |
India |
Israel |
Italy |
Japan |
Korea, Republic of |
Mexico |
Peru |
Poland |
Russian Federation |
Slovakia |
South Africa |
Spain |
Turkey |
Ukraine |
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
|
The end of the study is defined as the date when the last patient, last visit (LPLV) occurs. The LPLV is expected to occur a maximum of 124 weeks after the last patient is enrolled and randomized into the study. This timeframe includes the 52-week placebo-controlled period and a maximum of an additional 52-week active-treatment extension followed by the safety follow-up period. All patients will be followed for safety for 24 weeks after the last dose of study treatment. |
El final se define como la fecha en que el último paciente completa la última visita (UVUP). Se espera tenga lugar como máximo 124 semanas después de la aleatorización del último paciente en el estudio. Este tiempo incluye el período de 52 semanas controlado con placebo y un máximo de otras 52 semanas de extensión con tratamiento activo, seguidos por un período de seguimiento de seguridad. Se evaluará a todos los pacientes por seguridad hasta 24 semanas después de la última dosis |
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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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |