E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Atopic Dermatitis |
Dermatitis atópica. |
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E.1.1.1 | Medical condition in easily understood language |
Atopic dermatitis (AD) or eczema is a common inflammatory skin disease characterized by dry skin, red and crusting rash and intense pruritus that may affect people of all age. |
Dermatitis atópica o eczema es un trastorno inflamatorio crónico común de la piel,se caracteriza por xerosis, erupción eritematosa con costras y prurito intenso, afecta a personas de todas las edades. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
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 | 10012438 |
E.1.2 | Term | Dermatitis atopic |
E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue 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 primary objective of this study is to evaluate the efficacy and safety of lebrikizumab used as adjunctive therapy with topical corticosteroid (TCS) compared with TCS alone in patients with persistent moderate to severe atopic dermatitis. |
El objetivo principal de este estudio es evaluar la eficacia y seguridad de lebrikizumab cuando se utiliza como tratamiento adyuvante en combinación con corticosteroides tópicos (CST), comparado con CST solo, en pacientes con DA persistente moderada a grave. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of lebrikizumab adjunctive therapy with TCS compared with TCS alone, as measured by AD symptoms, including pruritis, and AD-specific health-related quality of life. ? To evaluate the pharmacokinetics and immunogenicity of lebrikizumab administered by subcutaneous (SC) injection ? To evaluate AD-related biomarkers and the effect on their expression from lebrikizumab used as adjunctive therapy with TCS compared with TCS |
Evaluar la eficacia de lebrikizumab cuando se utiliza como tratamiento adyuvante en combinación con CST, comparado con CST solo, que se determinará basándose en los síntomas de la DA, incluyendo prurito, y la calidad de vida (CV) relacionada. - Evaluar la farmacocinética e inmunogenicidad de lebrikizumab administrado en inyección subcutánea (SC). - Evaluar biomarcadores relacionados con la DA y el efecto de lebrikizumab cuando se utiliza como tratamiento adyuvante en combinación con CST, comparado con CST solo, sobre la expresión de estos biomarcadores. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age 18 to 75 years, inclusive, at the start of the run-in period - AD diagnosed by the Hanifin/Rajka criteria and that has been present for at least 1 year at screening - Moderate to severe AD as graded by the Rajka/Langeland criteria at screening - History of inadequate response to a >/= 1 month (within the 3 months prior to the screening visit) treatment regimen of at least daily TCS and regular emollient for treatment of AD - EASI score >/= 14 at screening - IGA score >/= 3 - AD involvement of >/= 10% body surface area - Pruritus Visual Analog Scale score >/= 3 |
- Tener entre 18 y 75 años de edad, al inicio del período de introducción. - Presentar DA, diagnosticada de acuerdo con los criterios de Hanifin/Rajka, desde hace al menos 1 año en el momento de la visita de selección. - Presentar DA moderada a grave, clasificada de acuerdo con los criterios de Rajka/Langeland, en el momento de la visita de selección. - Respuesta inadecuada a un tratamiento previo para la DA administrado durante >/=1 mes (en los 3 meses anteriores a la visita de selección) con un CST y un emoliente de uso habitual, aplicados como mínimo una vez al día. - Puntuación EASI >/= 14 en la visita de selección. - Puntuación IGA >/= 3. - DA que afecta a >/= 10% del área de superficie corporal. - Puntuación >/= 3 en la EVA de prurito. |
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E.4 | Principal exclusion criteria |
- Past and/or current use of any anti-IL-13 or anti-IL-4/IL-13 therapy, including lebrikizumab - Use of an investigational agent within 4 weeks prior to screening or within 5 half-lives of the investigational agent, whichever is longer - Evidence of other skin conditions, including, but not limited to, T-cell lymphoma or allergic contact dermatitis - History of a severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of the lebrikizumab injection - Use of any complementary, alternative, or homeopathic medicines including, but not limited to, phytotherapies, traditional or non-traditional herbal medications, essential fatty acids, or acupuncture within 7 days prior to the run-in period or need for such medications during the study - Evidence of other skin conditions; including, but not limited to, T-cell lymphoma or allergic contact dermatitis - Evidence of, or ongoing treatment (including topical antibiotics) for active skin infection at screening - Other recent infections meeting protocol criteria - Active tuberculosis requiring treatment within the 12 months prior to Visit 1 - Evidence of acute or chronic hepatitis or known liver cirrhosis - Known immunodeficiency, including HIV infection - Use of a topical calcineurin inhibitor (TCI) at the time of screening, unless the patient is willing to stop TCI use during the study (including the run-in period) and, in the investigators opinion, it is safe to do so - Clinically significant abnormality on screening ECG or laboratory tests - Known current malignancy or current evaluation for a potential malignancy, including basal or squamous cell carcinoma of the skin or carcinoma in situ - History of malignancy within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer |
- Uso previo y/o actual de cualquier tratamiento anti-IL-13 o anti-IL-4/IL-13, incluyendo lebrikizumab. - Uso de un agente en investigación en las 4 semanas previas a la visita de selección o durante 5 vidas medias del agente, dependiendo de lo que sea más prolongado. - Antecedentes de reacciones alérgicas graves o anafilácticas a un agente biológico o hipersensibilidad conocida a cualquiera de los excipientes de la inyección de lebrikizumab. - Uso de medicinas complementarias, alternativas u homeopáticas, incluyendo, aunque no exclusivamente, fitoterapia, medicinas herbales tradicionales o no tradicionales, ácidos grasos esenciales o acupuntura, en los 7 días previos al período de introducción o necesidad de utilizar estas medicaciones durante el estudio. - Evidencia de otras patologías cutáneas, incluyendo, aunque no exclusivamente, linfoma de células T o dermatitis alérgica por contacto. -Tratamiento en curso (incluyendo antibióticos tópicos) para una infección cutánea activa, confirmado en la visita de selección. - Otras infecciones que cumplan criterios del protocol. - Tuberculosis activa que haya requerido tratamiento en los 12 meses previos a la visita 1. - Evidencia de hepatitis aguda o crónica o cirrosis hepática documentada. - Inmunodeficiencia documentada, incluyendo infección por VIH. - Uso de ICT en el momento de la visita de selección, a menos que el paciente esté dispuesto a interrumpir su aplicación durante el estudio (incluyendo el período de introducción) y el investigador considere que es seguro hacerlo. - Anomalías clínicamente significativas en el ECG o las pruebas de laboratorio realizadas en la visita de selección. - Pacientes que en la actualidad presenten algún tipo de neoplasia maligna documentada, incluyendo carcinoma de piel basocelular o de células escamosas o carcinoma in situ. - Antecedentes de cáncer en los 5 años previos a la visita de selección, exceptuando carcinoma in situ de cérvix, carcinoma de piel no melanomatoso o cáncer de útero en estadio I. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of patients achieving a 50% reduction in Eczema Area and Severity Index (EASI) score (EASI-50) from baseline to Week 12 |
Porcentaje de pacientes que alcanzan EASI-50 (reducción del 50% de la puntuación EASI respecto al valor basal) en la semana 12. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From Baseline to Week 12 |
Desde basal a semana 12. |
|
E.5.2 | Secondary end point(s) |
1. Outcome Measure: Efficacy (composite outcome measure): Percent and absolute change from baseline in EASI score at Week 12 2. Outcome Measure: Percent of patients achieving an Investigators Global Assessment (IGA) score of 0 or 1 at Week 12 3. Outcome Measure: Efficacy (composite outcome measure): Percent and absolute change from baseline in Severity Scoring of Atopic Dermatitis (SCORAD) at Week 12 4. Outcome Measure: Frequency and severity of treatment-emergent adverse events |
1. Variable valoración: Eficacia (variable valoración compuesta): Cambio porcentual y absoluto, respecto al valor basal, en la puntuación EASI en la semana 12. 2. Variable valoración: Porcentaje de pacientes que alcanzan una puntuación IGA de 0 o 1 en la semana 12. 3. Variable valoración: eficacia (variable valoración compuesta): Cambio absoluto y porcentual, respecto al valor basal, en el SCORAD en la semana 12. 4. Variable valoración: Frecuencia y severidad de los acontecimientos adversos originados por el tratamiento. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 to 3. From Baseline to Week 12 4. Up to Week 20 |
1 a 3. Desde basal a semana 12. 4. Hasta semana 20. |
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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) | 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 |
Periodo de introducción |
Run-in period |
|
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
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 |
Canada |
Czech Republic |
Finland |
France |
Germany |
Korea, Republic of |
Netherlands |
Poland |
Spain |
Switzerland |
Taiwan |
United Kingdom |
United States |
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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
|
LVLS |
Última visita del útimo paciente (UVUP). |
|
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 | 15 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial months | 16 |
E.8.9.2 | In all countries concerned by the trial days | 0 |