E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to Severe Atopic Dermatitis |
Dermatitis atópica de moderada a grave |
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E.1.1.1 | Medical condition in easily understood language |
Moderate to Severe Atopic Dermatitis (eczema) |
Dermatitis atópica de moderada a grave (Eczema) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
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 study objective, related to Study Period 1, is to assess the efficacy and safety of upadacitinib, initiated at 15 mg once daily (QD) and dose adjusted based on clinical response, compared with dupilumab as per its label. An additional objective, related to Study Period 2, is to assess the efficacy and safety of upadacitinib, initiated at 15 mg QD, in subjects with inadequate response to dupilumab. The primary efficacy objective is based on the achievement of an at least 90% reduction in Eczema Area and Severity Index (EASI 90) from baseline and a Worst Pruritus Numerical Rating Scale (NRS) of 0 or 1 at Week 16 with the treatment of upadacitinib compared with dupilumab in the Intent-to-Treat (ITT) Population. |
El objetivo principal del estudio, relacionado con el período de estudio 1, es evaluar la eficacia y la seguridad de upadacitinib, administrado inicialmente en dosis de 15 mg una vez al día y ajustado en función de la respuesta clínica, en comparación con dupilumab administrado de acuerdo con la ficha técnica. Otro objetivo, relacionado con el período de estudio 2, es evaluar la eficacia y la seguridad de upadacitinib, administrado inicialmente en dosis de 15 mg una vez al día, en pacientes con una respuesta insuficiente a dupilumab. El objetivo principal de eficacia se basa en la consecución de una reducción de al menos el 90 % con respecto al momento basal en la puntuación del índice de superficie y gravedad del eccema (respuesta EASI 90) y de una puntuación de 0 o 1 en la escala de valoración numérica del peor prurito (respuesta WP-NRS 0/1) a las 16 semanas d tratamiento con upadacitinib en comparación con dupilumab en la población por intención de tratar (IT). |
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E.2.2 | Secondary objectives of the trial |
Ranked Secondary Endpoints: 1. Achievement of EASI 90 at Week 16. 2. Achievement of WP-NRS 0/1 at Week 16 among subjects with Baseline Worst Pruritus NRS > 1. 3. Achievement of an improvement (reduction) in Worst Pruritus NRS ≥ 4 at Week 16 among subjects with Baseline Worst Pruritus NRS ≥ 4. 4. Achievement of WP-NRS 0/1 at Week 4 among subjects with Baseline Worst Pruritus NRS > 1. 5. Achievement of WP-NRS 0/1 at Week 2 among subjects with Baseline Worst Pruritus NRS > 1. 6. Achievement of EASI 90 at Week 4. 7. Achievement of EASI 75 at Week 2. 8. Achievement of EASI 100 at Week 16 |
Los criterios de valoración secundarios ordenados son: 1. Consecución de la respuesta EASI 90 en la semana 16. 2. Consecución de la respuesta WP-NRS 0/1 en la semana 16 entre los pacientes con una puntuación WP-NRS basal >1. 3. Consecución de una mejoría (reducción) de la puntuación WP NRS ≥4 en la semana 16 entre los pacientes con una puntuación WP-NRS basal ≥4. 4. Consecución de la respuesta WP-NRS 0/1 en la semana 4 entre los pacientes con una puntuación WP-NRS basal >1. 5. Consecución de la respuesta WP-NRS 0/1 en la semana 2 entre los pacientes con una puntuación WP-NRS basal >1. 6. Consecución de la respuesta EASI 90 en la semana 4. 7. Consecución de la respuesta EASI 75 en la semana 2. 8. Consecución de la respuesta EASI 100 en la semana 16 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
o Subjects must be at least ≥ 12 years old and < 65 years old at Screening Visit. Adolescent subjects (between ≥ 12 and < 18 years of age) may be enrolled only if there is local approval for dupilumab in this age group. o Body weight must be ≥ 40 kg at the Baseline Visit for subjects between ≥ 12 and < 18 years of age, unless there are higher weight requirements per the local approved label for dupilumab, in which case the more restricted requirement must be followed. o Chronic AD with onset of symptoms at least 3 years prior to baseline and subject meets Hanifin and Rajka criteria o EASI score ≥ 16; vIGA-AD score ≥ 3 and ≥ 10% BSA of AD involvement at the Baseline Visit; o Baseline weekly average of daily Worst Pruritus NRS ≥ 4. o Documented history of inadequate response to previous systemic treatment defined as documented history of previous inadequate response to at least one prior systemic treatment for AD OR for whom other systemic treatments are otherwise medically inadvisable (e.g., because of important side effects or safety risks). |
Los criterios de elegibilidad fundamentales del estudio son: 1. Pacientes ≥12 años (y ≥40 kg en el momento basal) y <65 años. 2. Sujetos con DA crónica cuyos síntomas aparecieran al menos 3 años antes del momento basal y que cumplan los criterios de Hanifin y Rajka. 3. Puntuación EASI ≥16, puntuación vIGA-AD ≥3 y superficie corporal (SC) afectada por la DA ≥10 % en la visita basal. 4. Promedio semanal basal de la puntuación diaria en la WP-NRS ≥4. 5. Antecedentes documentados de respuesta insuficiente al tratamiento sistémico previo, definidos como antecedentes documentados de respuesta insuficiente previa a al menos un tratamiento sistémico previo para la DA, O BIEN documentación de que se desaconsejan médicamente otros tratamientos sistémicos por cualquier otro motivo. |
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E.4 | Principal exclusion criteria |
o Prior exposure to any oral or topical JAK inhibitor (including but not limited to upadacitinib [Rinvoq®], tofacitinib [Xeljanz®], ruxolitinib [Jakafi® or Opzelura®], baricitinib [Olumiant®], peficitinib [Smyraf®], abrocitinib [Cibinqo®], and filgotinib [Jyseleca®]) o Prior exposure to dupilumab, tralokinumab, or lebrikizumab |
- Exposición previa a cualquier inhibidor de JAK oral o tópico (incluidos, entre otros, upadacitinib [Rinvoq®], tofacitinib [Xeljanz®], ruxolitinib [Jakafi® u Opzelura®], baricitinib [Olumiant®], peficitinib [Smyraf®], abrocitinib [Cibinqo®] y filgotinib [Jyseleca®])
- Exposición previa a dupilumab, tralokinumab o lebrikizumab |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the achievement of EASI 90 and a Worst Pruritus NRS of 0 or 1 for subjects at Week 16. |
El criterio de valoración principal es la consecución de las respuestas EASI 90 y WP-NRS 0/1 en la semana 16. |
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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) |
The ranked secondary endpoints are: 1. Achievement of EASI 90 at Week 16 2. Achievement of Worst Pruritus NRS of 0 or 1 for subjects with Baseline Worst Pruritus NRS > 1, at Week 16 3. Achievement of an improvement (reduction) in Worst Pruritus NRS ≥ 4 for subjects with Baseline Worst Pruritus NRS ≥ 4, at Week 16 4. Achievement of Worst Pruritus NRS of 0 or 1 for subjects with Baseline Worst Pruritus NRS > 1, at Week 4 5. Achievement of Worst Pruritus NRS of 0 or 1 for subjects with Baseline Worst Pruritus NRS > 1, at Week 2 6. Achievement of EASI 90 at Week 4 7. Achievement of EASI 75 at Week 2 8. Achievement of EASI 100 at Week 16 |
Los criterios de valoración secundarios ordenados son: 1. Consecución de la respuesta EASI 90 en la semana 16. 2. Consecución de la respuesta WP-NRS 0/1 en la semana 16 entre los pacientes con una puntuación WP-NRS basal >1. 3. Consecución de una mejoría (reducción) de la puntuación WP NRS ≥4 en la semana 16 entre los pacientes con una puntuación WP-NRS basal ≥4. 4. Consecución de la respuesta WP-NRS 0/1 en la semana 4 entre los pacientes con una puntuación WP-NRS basal >1. 5. Consecución de la respuesta WP-NRS 0/1 en la semana 2 entre los pacientes con una puntuación WP-NRS basal >1. 6. Consecución de la respuesta EASI 90 en la semana 4. 7. Consecución de la respuesta EASI 75 en la semana 2. 8. Consecución de la respuesta EASI 100 en la semana 16. |
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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) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Efficacy Assessor blinded Study |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 90 |
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 |
Canada |
Chile |
China |
Colombia |
Korea, Republic of |
Mexico |
South Africa |
Taiwan |
United States |
Poland |
Sweden |
Romania |
Spain |
Czechia |
Germany |
Italy |
Croatia |
Portugal |
Slovakia |
United Kingdom |
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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
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The end-of-study is defined as the date of the last subject's last visit or the actual date of follow-up contact, whichever is later; and in the last country where the study was conducted. |
El final del estudio se define como la fecha de la última visita del sujeto o la fecha real de contacto de seguimiento, la que sea posterior; y en el último país donde se realizó el estudio. |
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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 | |
E.8.9.1 | In the Member State concerned months | 30 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 30 |