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 |
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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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003639 |
E.1.2 | Term | Atopic dermatitis |
E.1.2 | System Organ Class | 100000004858 |
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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 tralokinumab in combination with topical corticosteroids (TCS) is superior to placebo in combination with TCS in treating severe Atopic Dermatitis (AD) in subjects who are not adequately controlled with or have contraindications to oral cyclosporine A (CSA). |
Demostrar que tralokinumab en combinación con corticosteroides tópicos (CST) es superior al placebo en combinación con CST en el tratamiento de la DA grave en pacientes que no están suficientemente controlados con ciclosporina A oral (CSA) o para los que este fármaco está contraindicado. |
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E.2.2 | Secondary objectives of the trial |
* To evaluate the efficacy of tralokinumab in combination with TCS on severity and extent of AD, itch, and health-related quality of life compared to placebo in combination with TCS. * To evaluate the safety of tralokinumab in combination with TCS when treating severe AD in subjects who are not adequately controlled with or have contraindications to oral CSA compared to placebo in combination with TCS. |
* Evaluar la eficacia de tralokinumab en combinación con CST comparada con la del placebo en combinación con CST para reducir la gravedad, la extensión y el prurito de la DA y para mejorar la calidad de vida relacionada con la salud. * Evaluar la seguridad de tralokinumab en combinación con CST comparada con la del placebo en combinación con CST para tratar la DA grave en pacientes que no están suficientemente controlados con CSA oral o para los que este fármaco está contraindicado. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
* Age 18 and above. * Diagnosis of AD as defined by the Hanifin and Rajka (1980) criteria for AD. * History of AD for ≥1 year. * AD involvement of ≥10% body surface area at screening and baseline according to component A of SCORAD. * Subjects who have a recent history (within 1 year before the screening visit) of inadequate response to treatment with topical medications. *Documented history of either no previous CSA exposure and not currently a candidate for CSA treatment OR previous exposure to CSA in which case CSA treatment should not be continued or restarted. *Subjects must have applied a stable dose of emollient twice daily (or more, as needed) for at least 14 days before randomisation. |
•Edad mínima de 18 años. •Diagnóstico de DA definido por los criterios de Hanifin y Rajka (1980) para la DA.•Antecedentes de DA durante ≥1 año. •DA que afecte a ≥10 % del área de superficie corporal en la selección y en el inicio según el componente A de SCORAD. •Antecedentes recientes (menos de 1 año antes de la visita de selección) de respuesta insuficiente al tratamiento con medicación tópica. •Historial documentado de no exposición previa a CSA y que actualmente no sea candidato para el tratamiento con CSA ó exposición previa a CSA, en cuyo caso el tratamiento con CSA no se debe continuar ni reiniciar. •A los pacientes se les debe aplicar una dosis estable de emoliente dos veces al día (o más, si es necesario) durante al menos 14 días antes de la aleatorización. |
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E.4 | Principal exclusion criteria |
* Subjects for whom TCSs are medically inadvisable e.g., due to important side effects or safety risks * Use of tanning beds or phototherapy within 6 weeks prior to randomisation. * Treatment with systemic immunosuppressive/immunomodulating drugs and/or systemic corticosteroid within 4 weeks prior to randomisation. * Treatment with topical phosphodiesterase-4 (PDE-4) inhibitor within 2 weeks prior to randomisation. *Receipt of any marketed biological therapy (i.e. immunoglobulin, anti immunoglobulin E) including dupilumab or investigational biologic agents. * Active skin infection within 1 week prior to randomisation. * Clinically significant infection within 4 weeks prior to randomisation. * A helminth parasitic infection within 6 months prior to the date informed consent is obtained. * Tuberculosis requiring treatment within the 12 months prior to screening. * Known primary immunodeficiency disorder. |
•Pacientes para quienes los CST resulten desaconsejables por razones médicas, como efectos secundarios importantes o riesgos para la seguridad. •Uso de camas bronceadoras o fototerapia en las 6 semanas previas a la aleatorización. •Tratamiento con fármacos inmunosupresores/inmunomoduladores sistémicos o con corticoides sistémicos en las 4 semanas previas a la aleatorización. •Tratamiento con inhibidor de fosfodiesterasa 4 (FDE-4) por vía tópica en las 2 semanas previas a la aleatorización. •Recepción de cualquier tratamiento biológico comercializado (p. ej.,inmunoglobulina, anti-inmunoglobulina E), incluidos dupilumab o biofármacos en fase de investigación. •Infección cutánea activa en la semana previa a la aleatorización. •Infección clínicamente significativa en las 4 semanas previas a la aleatorización. •Infección por parásito helminto en los 6 meses previos a la fecha de obtención del consentimiento informado. •Tuberculosis que haya requerido tratamiento en los 12 meses previos ala selección. •Inmunodeficiencia primaria conocida. |
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E.5 End points |
E.5.1 | Primary end point(s) |
At least 75 percent reduction in EASI score (EASI75) |
Reducción de al menos 75 en la puntuación EASI (EASI75) |
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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) |
Severity and extent of AD * IGA score of 0 (clear) or 1 (almost clear) * Change in SCORAD from baseline * EASI75 Itch Reduction of Worst Daily Pruritus NRS4 (weekly average) of at least 4 Health-related quality of life * Change in DLQI score from baseline to Week 16 Number of adverse events Presence of anti-drug antibodies |
Gravedad y extensión de la DA •Puntuación EGI2 de 0 (ausente) o1 (casi ausente) en la semana 16 •Puntuación EGI de 0 (ausente) o 1(casi ausente) en la semana 26 •Cambio en SCORAD3 desde el inicio hasta la semana 16 •Cambio en SCORAD desde el inicio hasta la semana 26 •EASI75 en la semana 26 Prurito •Disminución de la ENC del peor prurito diario4 (promedio semanal)de al menos 4 desde el inicio hasta la semana 16 •Disminución de la ENC del peor prurito diario (promedio semanal) de al menos 4 desde el inicio hasta la semana 26 Calidad de vida relacionada con la salud •Cambio en la puntuación DLQI5desde el inicio hasta la semana 16 •Cambio en la puntuación DLQI desde el inicio hasta la semana 26 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 16 and Week 26, respectively |
Semana 16 y semana 26, respectivamente |
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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 | 2 |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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LVLS |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |