E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to Severe Atopic Dermatitis |
Dermatite atipica da moderata a severa |
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E.1.1.1 | Medical condition in easily understood language |
Moderate to Severe Atopic Dermatitis |
Dermatite atipica da moderata a severa |
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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 objectives are: 1) To generate descriptive data on the efficacy and safety of dose escalation to upadacitinib 30 mg QD and dose reduction to upadacitinib 15 mg QD based on a clinical response after 12 weeks of treatment. This data will inform the clinical management for subjects with moderate to severe AD treated with both approved doses of upadacitinib. 2) To generate evidence on the subject impact of upadacitinib treatment decision-making based on targeting at least a 90% reduction in Eczema Area and Severity Index (EASI 90) skin clearance (Treat to Target). |
Gli obiettivi primari dello studio sono: 1) Generare dati descrittivi relativi all’efficacia e alla sicurezza dell’incremento della dose a upadacitinib 30 mg QD e alla riduzione della dose a upadacitinib 15 mg QD, sulla base della risposta clinica dopo 12 settimane di trattamento. Questi dati orienteranno la gestione clinica dei soggetti affetti da DA di grado da moderato a grave trattati con entrambe le dosi approvate di upadacitinib. 2) Generare evidenza relativa all’impatto sui soggetti del processo decisionale relativo al trattamento con upadacitinib che si basa sul target rappresentato da una riduzione pari ad almeno il 90% nel punteggio EASI (Eczema Area and Severity Index) (EASI 90) relativo alla completa risoluzione delle lesioni cutanee (skin clearance) (Treat to Target). |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male or female subjects = 18 and < 65 years of age • Chronic AD with onset of symptoms at least 3 years prior to Baseline and subject meets Hanifin and Rajka criteria • Candidate for systemic treatment defined as prior use of systemic treatment for AD
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• Soggetti adulti di età compresa fra = 18 e < 65 anni. • DA cronica con insorgenza dei sintomi almeno 3 anni prima del Baseline, e soddisfacimento da parte del soggetto dei criteri Hanifin e Rajka. • Candidato al trattamento sistemico definito quale uso pregresso di trattamento sistemico per DA |
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E.4 | Principal exclusion criteria |
• Prior exposure to any JAK inhibitor • Unable or unwilling to discontinue current AD treatments prior to the study • Requirement of prohibited medications during the study treatment • Female subject who is pregnant, breastfeeding, or considering pregnancy during the study |
• Esposizione pregressa a qualsiasi inibitore di JAK • Non in grado o non disposto a interrompere i trattamenti in atto per la DA prima dello studio • Necessità di medicinali proibiti nel corso del trattamento sperimentale • Soggetto femminile che è in stato di gravidanza, sta allattando o intende iniziare una gravidanza nel corso dello studio |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoints are: 1. Achievement of EASI 75 at Week 24. 2. Achievement of EASI 90 at Week 24. 3. Achievement of EASI 90 and Worst Pruritus NRS of 0 or 1 for subjects with Worst Pruritus NRS > 1 at Baseline at Week 24. |
Gli endpoint primari sono: • Ottenimento di EASI 75 alla Settimana 24. • Ottenimento di EASI 90 alla Settimana 24. • Ottenimento di EASI 90 e di punteggio relativo al Peggior Prurito alla scala NRS pari a 0 o 1 alla Settimana 24 per i soggetti con punteggio NRS relativo al Peggior Prurito > 1 al Baseline. |
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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 secondary endpoints are: 1. Achievement of EASI 75 / 90 /100 at Week 12. 2. Achievement of EASI 100 at Week 24. 3. Achievement of EASI 90 and Worst Pruritus NRS of 0 or 1 for subjects with Worst Pruritus NRS > 1 at Baseline at Week 12. 4. Achievement of validated Investigator´s Global Assessment for AD (vIGA-AD) of 0 or 1 at Week 12. 5. Achievement of vIGA-AD of 0 or 1 at Week 24. 6. Achievement of an improvement (reduction) in Worst Pruritus (NRS = 4 for subjects with Worst Pruritus NRS = 4 at Baseline at Week 12. 7. Achievement of an improvement (reduction) in Worst Pruritus NRS = 4 for subjects with Worst Pruritus NRS = 4 at Baseline at Week 24. 8. Achievement of Worst Pruritus NRS of 0 or 1 for subjects with Worst Pruritus NRS > 1 at Baseline at Week 12.' 9. Achievement of Worst Pruritus NRS of 0 or 1 for subjects with Worst Pruritus NRS > 1 at Baseline at Week 24. 10. Achievement of an improvement (reduction) from Baseline in Dermatology Life Quality Index (DLQI) = 4 for subjects with DLQI = 4 at Baseline at Week 12. 11. Achievement of an improvement (reduction) from Baseline in DLQI = 4 for subjects with DLQI = 4 at Baseline at Week 24. 12. Achievement of DLQI 0/1 for subjects with DLQI > 1 at Baseline at Week 12. 13. Achievement of DLQI 0/1 for subjects with DLQI > 1 at Baseline at Week 24. |
Gli endpoint secondari sono: 1. Ottenimento di EASI 75 / 90 /100 alla Settimana 12. 2. Ottenimento di EASI 100 alla Settimana 24. 3. Ottenimento alla Settimana 12 di EASI 90 e di punteggio NRS relativo al Peggior Prurito pari a 0 o 1 per i soggetti con punteggio NRS relativo al Peggior Prurito > 1 al Baseline. 4. Ottenimento di punteggio validato vIGA-AD (validated Investigator´s Global Assessment for AD) pari a 0 o 1 alla Settimana 12. 5. Ottenimento di punteggio vIGA-AD pari a 0 o 1 alla Settimana 24. 6. Ottenimento alla Settimana 12 di miglioramento (riduzione) del punteggio NRS relativo al Peggior Prurito = 4 per i soggetti con punteggio NRS relativo al Peggior Prurito = 4 al Baseline 7. Ottenimento alla Settimana 24 di miglioramento (riduzione) del punteggio NRS relativo al Peggior Prurito = 4 per i soggetti con punteggio NRS relativo al Peggior Prurito = 4 al Baseline. 8. Ottenimento alla Settimana 12 di punteggio NRS relativo al Peggior Prurito pari a 0 o 1 per i soggetti con punteggio NRS relativo al Peggior Prurito > 1 al Baseline. 9. Ottenimento alla Settimana 24 di punteggio NRS relativo al Peggior Prurito pari a 0 o 1 per i soggetti con punteggio NRS relativo al Peggior Prurito > 1 al Baseline. 10. Ottenimento alla Settimana 12 di miglioramento (riduzione) rispetto al Baseline del punteggio DLQI (Dermatology Life Quality Index) = 4 per i soggetti con DLQI = 4 al Baseline. 11. Ottenimento alla Settimana 24 di miglioramento (riduzione) rispetto al Baseline del punteggio DLQI = 4 per i soggetti con DLQI = 4 al Baseline 12. Ottenimento alla Settimana 12 di punteggio DLQI 0/1 per I soggetti con punteggio DLQI > 1 al Baseline. 13. Ottenimento alla Settimana 24 di punteggio DLQI 0/1 per I soggetti con punteggio DLQI > 1 al Baseline. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 12/24 |
Settimana 12/24 |
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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 | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
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) | 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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 107 |
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 | Information not present in EudraCT |
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 |
China |
Israel |
Korea, Republic of |
New Zealand |
Taiwan |
Austria |
France |
Poland |
Bulgaria |
Netherlands |
Spain |
Czechia |
Germany |
Italy |
Belgium |
Hungary |
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 end of study participation by the last subject in the last country where the study was conducted. |
Per fine dello studio si intende la data della fine della partecipazione allo studio da parte dell’ultimo soggetto nell’ultima nazione dove lo studio è stato condotto |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |