E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
adult subjects with moderate-to-severe plaque psoriasis |
soggetti adulti con psoriasi a placche da moderata a severa |
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E.1.1.1 | Medical condition in easily understood language |
adults with moderate-to-severe psoriasis |
adulti con psoriasi a placche da moderata a severa |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
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 compare the efficacy of brodalumab with guselkumab in adult subjects with moderate-to-severe plaque psoriasis and prior inadequate response to ustekinumab. |
Confrontare l'efficacia di brodalumab rispetto a guselkumab in soggetti adulti con psoriasi a placche da moderata a severa e precedente risposta inadeguata a ustekinumab. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of brodalumab compared with guselkumab while ontreatment for up to 28 weeks in adult subjects with moderate-to-severe plaque psoriasis and prior inadequate response to ustekinumab.
To evaluate the efficacy of brodalumab compared with guselkumab through Week 28 in adult subjects with moderate-to-severe plaque psoriasis and prior inadequate response to ustekinumab.
To evaluate the safety of brodalumab compared with guselkumab throughout the trial (28 weeks) in adult subjects with moderate-to-severe plaque psoriasis and prior inadequate response to ustekinumab. |
Valutare l'efficacia di brodalumab rispetto a guselkumab durante il trattamento per un massimo di 28 settimane in soggetti adulti con psoriasi a placche da moderata a severa e precedente risposta inadeguata a ustekinumab.
Valutare l'efficacia di brodalumab rispetto a guselkumab fino alla Settimana 28 in soggetti adulti con psoriasi a placche da moderata a severa e precedente risposta inadeguata a ustekinumab.
Valutare la sicurezza di brodalumab rispetto a guselkumab durante l'intero studio (28 settimane) in soggetti adulti con psoriasi a placche da moderata a severa e precedente risposta inadeguata a ustekinumab. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Subject is =18 years of age at the time of screening.
- Subject has a diagnosis of plaque psoriasis for at least 6 months before the first administration of investigational medicinal product (IMP) as determined by the investigator.
- Subject has inadequately controlled plaque psoriasis currently treated with ustekinumab, and fulfil ALL of the following criteria: - Ustekinumab administered at least 3 times at or higher than the approved dose or frequency for at least 24 weeks. - IGA =2 at screening and baseline. - Absolute PASI >3 at screening and baseline. - The last administration of ustekinumab was =12 weeks before randomisation.
- Subject has no active tuberculosis at screening (negative QuantiFERON® or purified protein derivative [PPD] test). Subjects with adequately treated latent tuberculosis are eligible. |
-Il soggetto alla data dello screening ha un’età =18 anni - Il soggetto presenta una diagnosi di psoriasi a placche da almeno 6 mesi prima della prima somministrazione del medicinale sperimentale (IMP), come determinato dallo sperimentatore. - Il soggetto presenta un controllo inadeguato della psoriasi a placche, attualmente trattata con ustekinumab, e soddisfa TUTTI i seguenti criteri: o Ustekinumab somministrato almeno 3 volte oppure a una dose o a una frequenza più elevata di quella approvata per almeno 24 settimane. o IGA =2 allo screening e al basale. o PASI assoluto >3 allo screening e al basale. o L'ultima somministrazione di ustekinumab è avvenuta =12 settimane prima della randomizzazione. - Il soggetto non presenta tubercolosi attiva allo screening (QuantiFERON® o test del derivato proteico purificato [PPD] negativo). Sono idonei i soggetti con tubercolosi latente adeguatamente trattata. |
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E.4 | Principal exclusion criteria |
- Subject was diagnosed with erythrodermic psoriasis, pustular psoriasis, guttate psoriasis, medication-induced psoriasis, or other skin conditions (e.g. eczema) that would interfere with evaluations of the effect of IMP on plaque psoriasis.
- Subject has clinically important active infections or infestations, chronic, recurrent, or latent infections or infestations, or is immunocompromised (e.g. human immunodeficiency virus).
- Subject has any systemic disease (e.g. renal failure, heart failure, hypertension, liver disease, diabetes, anaemia) considered by the investigator to be clinically significant and uncontrolled.
- Subject has a known history of Crohn’s disease.
- Subject has any active malignancy, including evidence of cutaneous basal or squamous cell carcinoma or melanoma.
- Subject has a history of malignancy within 5 years, except for treated and considered cured cutaneous squamous or basal cell carcinoma, in situ cervical cancer, or in situ breast ductal carcinoma.
- Subject has a known history of active tuberculosis.
- Subject has a history of suicidal behaviour (i.e. ‘actual suicide attempt’, ‘interrupted attempt’, ‘aborted attempt’, or ‘preparatory acts or behaviour’) based on the Columbia-Suicide Severity Rating Scale (CSSRS) questionnaire at screening or baseline.
- Subject has any suicidal ideation of severity 4 or 5 (‘some intent to act, no plan’ or ‘specific plan and intent’) based on the C-SSRS questionnaire at screening or baseline.
- Subject has a Patient Health Questionnaire-8 (PHQ-8) score of =10, corresponding to moderate-to-severe depression at screening or baseline.
- Subject has previously received more than 1 tumour necrosis factor-a (TNF-a) inhibitor.
- Subject has previously been treated with any anti-interleukin (IL)-17A, anti-IL-17 receptor subunit A, or anti-IL-23 besides ustekinumab.
- Subject has known or suspected hypersensitivity to any component(s) of the IMPs. |
- Al soggetto sono state diagnosticate psoriasi eritrodermica, psoriasi pustolosa, psoriasi guttata, psoriasi indotta da farmaci o altre patologie dermatologiche (ad es. eczema) che interferirebbero con le valutazioni dell'effetto dell'IMP sulla psoriasi a placche. - Il soggetto presenta infezioni o infestazioni attive clinicamente importanti, infezioni o infestazioni croniche, ricorrenti o latenti oppure è immunocompromesso (ad esempio, virus dell'immunodeficienza umana). - Il soggetto presenta qualsiasi malattia sistemica (ad es. insufficienza renale, insufficienza cardiaca, ipertensione, epatopatia, diabete, anemia) considerata dallo sperimentatore come clinicamente significativa e non controllata. - Il soggetto presenta una storia nota di malattia di Crohn. - Il soggetto presenta qualsiasi tumore maligno attivo, inclusa evidenza di carcinoma cutaneo squamoso o basocellulare o melanoma. - Il soggetto presenta una storia di tumore maligno negli ultimi 5 anni, ad eccezione di carcinoma cutaneo squamoso o basocellulare, cancro della cervice in situ o carcinoma duttale della mammella in situ trattati e considerati curati. - Il soggetto presenta una storia nota di tubercolosi attiva. - Il soggetto presenta una storia di comportamento suicidario (ovvero "tentato suicidio effettivo", "tentativo interrotto", "tentativo fallito" o "atti o comportamenti preparatori") in base al questionario Columbia-Suicide Severity Rating Scale (C-SSRS, scala di valutazione Columbia della gravità del suicidio) allo screening o al basale. - Il soggetto presenta ideazione suicidaria di gravità 4 o 5 ("certa intenzione di passare all'azione, nessun piano" o "piano e intenzioni specifiche") in base al questionario C-SSRS allo screening o al basale. - Il soggetto presenta un punteggio del questionario Patient Health Questionnaire-8 (PHQ-8, questionario sulla salute del paziente) =10 corrispondente a depressione da moderata a severa allo screening o al basale. - Il soggetto è stato trattato precedentemente con più di 1 inibitore del fattore di necrosi tumorale a (TNF-a). - Il soggetto è stato trattato precedentemente con qualsiasi anti-interleuchina (IL)-17A, anti subunità A del recettore per l’ IL-17 o anti-IL-23 oltre a ustekinumab. - Il soggetto presenta ipersensibilità nota o sospetta a qualsiasi componente degli IMP. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint:
Having PASI 100 response at Week 16.
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Endpoint primario • Risposta PASI1 100 alla Settimana 16 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At week 16 |
Alla settimana 16 |
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E.5.2 | Secondary end point(s) |
Key secondary endpoint:
Time to PASI 100 response
Secondary endpoints:
Time to PASI 90 response
Having PASI 100 response, assessed separately at Weeks 4, 8, and 28.
Having PASI 90 response, assessed separately at Weeks 4, 8, 16, and 28.
Having IGA of 0, assessed separately at Week 16 and Week 28.
Having IGA of 0 or 1, assessed separately at Week 16 and Week 28.
Having DLQI total score of 0 or 1, assessed separately at Weeks 4, 8, 12, 16, 20, 24, and 28.
Change in SF-36v24 score from baseline, assessed separately at Weeks 4, 8, 16, and 28.
Occurrence of TEAEs from baseline to Week 28.; Endpoint chiave secondario - Tempo alla risposta PASI 100.
Endpoint secondario - Tempo alla risposta PASI 90.
Endpoint secondari • Risposta PASI 100, valutata separatamente alle Settimane 4, 8 e 28. • Risposta PASI 90, valutata separatamente alle Settimane 4, 8, 16 e 28. • Punteggio IGA2 di 0, valutato separatamente alla Settimana 16 e alla Settimana 28. • Punteggio IGA di 0 di 1, valutato separatamente alla Settimana 16 e alla Settimana 28. • Punteggio totale DLQI3 di 0 o 1, valutato separatamente alle Settimane 4, 8, 12, 16, 20, 24 e 28. • Variazione del punteggio SF-36v24 dal basale, valutato separatamente alle Settimane 4, 8, 16 e 28. • Comparsa di AE emergenti dal trattamento dal basale alla Settimana 28. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Between week 0 and 28, as specified for each endpoint. |
Tra la settimana 0 e 28, come specificato per ciascun endpoint. |
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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) | No |
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 | Yes |
E.8.1.4 | Double blind | No |
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 |
subject- and assessor-blinded |
subject- and assessor-blinded |
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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 | 69 |
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 |
Austria |
Belgium |
Denmark |
France |
Germany |
Greece |
Italy |
Netherlands |
Spain |
Sweden |
Switzerland |
United Kingdom |
Czechia |
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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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Last visit of the last subject at global level. |
Last visit of the last subject at global level. |
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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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |