E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
moderate-to-severe plaque psoriasis and a body weight =120 kg. |
psoriasi a placche da moderata a grave e =120 kg di peso corporeo |
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E.1.1.1 | Medical condition in easily understood language |
moderate-to-severe psoriasis and a body weight =120 kg. |
psoriasi da moderata a grave e =120 kg di peso corporeo |
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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 | 10033899 |
E.1.2 | Term | Parapsoriasis en plaques |
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 compare the effect on psoriasis symptoms of an adjustable brodalumab dosage regimen to standard brodalumab treatment in subjects with moderate-to-severe psoriasis and a body weight =120 kg. |
Confrontare l'effetto sui sintomi della psoriasi di un regime di dosaggio di brodalumab adattabile rispetto al trattamento standard con brodalumab in soggetti con psoriasi da moderata a grave e un peso corporeo =120 kg |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety of an adjustable brodalumab dosage regimen in subjects with moderate-to-severe psoriasis and a body weight > =120 kg.
To evaluate pharmacokinetics (PK) of brodalumab in subjects with moderate to-severe psoriasis and a body weight >=120 kg.
To explore the effect of brodalumab on systemic inflammation in subjects with moderate-to-severe psoriasis and a body weight >=120 kg. |
Valutare la sicurezza di un regime di dosaggio di brodalumab dattabile in soggetti con psoriasi da moderata a grave e un peso corporeo >= 120 kg. Valutare la farmacocinetica (PK) di brodalumab in soggetti con psoriasi da moderata a grave e un peso corporeo > = 120 kg Esplorare l'effetto di brodalumab sull'infiammazione sistemica in soggetti con psoriasi da moderata a grave e un peso corporeo > = 120 kg |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Other types of substudies Specify title, date and version of each substudy with relative objectives: Objective (secondary): To explore the effect of brodalumab on skin and subcutaneous adipose tissue inflammation in subjects with moderate-tosevere psoriasis and a body weight =120 kg. Objective (secondary): To explore the effect of brodalumab on endothelial dysfunction in subjects with moderate-to-severe psoriasis and a body weight =120 kg.
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Altre tipologie di sottostudi specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: Obiettivo (secondario): esplorare l'effetto di brodalumab sulla pelle e sull'infiammazione del tessuto adiposo sottocutaneo in soggetti con psoriasi da moderata a grave e un peso corporeo =120 kg. Obiettivo (secondario): esplorare l'effetto di brodalumab sulla disfunzione endoteliale in soggetti con psoriasi da moderata a grave e un peso corporeo =120 kg.
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E.3 | Principal inclusion criteria |
Signed and dated informed consent has been obtained prior to any
protocol-related procedures.
- Age =18 to <75 years at the time of screening.
- Diagnosed with chronic plaque psoriasis at least 6 months before
randomisation.
- Body weight =120 kg at the time of screening.
- Moderate-to-severe plaque psoriasis as defined by: BSA =10% and
PASI =12 at screening and baseline.
- No current active tuberculosis. |
- Il consenso informato firmato e datato è stato ottenuto prima di qualsiasi procedura relativa al protocollo. - Età compresa tra =18 e <75 anni al momento dello screening. - Diagnosi di psoriasi a placche cronica almeno 6 mesi prima della randomizzazione. -Peso corporeo =120 kg al momento dello screening. -Psoriasi a placche da moderata a grave come definita da: BSA =10% e PASI =12 allo screening e al basale. - Assenza di tubercolosi attiva in corso. |
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E.4 | Principal exclusion criteria |
- 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 the
investigational medicinal product (IMP) on subjects with plaque psoriasis
- Clinically important active infections or infestations, chronic, recurrent or latent infections or infestations, or is immunocompromised (e.g., human immunodeficiency virus, hepatitis B, and hepatitis C).
- Any systemic disease considered by the investigator to be uncontrolled and either immunocompromising the subject and/or placing the subject at undue risk of intercurrent diseases (including, but not limited to, renal failure, heart failure, liver disease, diabetes, and anaemia).
- Known history of Crohn’s disease.
- Myocardial infarction or stroke, or unstable angina pectoris within the past 12 months.
- Any active malignancy.
- 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.
- 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 (C-SSRS) questionnaire at screening or at baseline.
- Any suicidal ideation of category 4 or 5 (‘active suicidal ideation with some intent to act, without specific plan’ or ‘ active suicidal ideation with specific plan and intent’) based on the C-SSRS questionnaire at screening or at baseline.
- A Patient Health Questionnaire (PHQ)-8 score of =10 corresponding to moderate-to-severe depression at screening or at baseline. |
-Diagnosi di psoriasi eritrodermica, psoriasi pustolosa, psoriasi guttata, psoriasi indotta da farmaci o altre patologie della pelle (ad es. eczema) che interferirebbero con le valutazioni dell'effetto del medicinale sperimentale (IMP) su soggetti con psoriasi a placche. - Infezioni o infestazioni clinicamente importanti, infezioni o infestazioni croniche, ricorrenti o latenti, oppure soggetti immunocompromessi (ad esempio, virus dell'immunodeficienza umana, epatite B ed epatite C). - Qualsiasi malattia sistemica considerata dallo sperimentatore incontrollata e che possa immunocompromettere il soggetto e/o esporlo a rischio indebito di malattie intercorrenti (tra cui, a titolo esemplificativo, insufficienza renale, insufficienza cardiaca, insufficienza epatica, diabete e anemia). - Storia nota di morbo di Crohn. - Infarto miocardico o ictus, oppure angina pectoris instabile negli ultimi 12 mesi. - Qualsiasi neoplasia attiva. - Storia di neoplasia negli ultimi 5 anni, ad eccezione del carcinoma cutaneo squamoso o basocellulare trattato e considerato curato, carcinoma cervicale in situ o carcinoma duttale della mammella in situ. - Storia di comportamento suicidario (ovvero "tentato suicidio effettivo", "tentativo interrotto", "tentativo fallito" o "atti o comportamenti preparatori") basato sul questionario Columbia-Suicide Severity Rating Scale (C-SSRS) allo screening o al basale. -Qualsiasi idea suicida di categoria 4 o 5 ("idea suicida attiva con un certo intento di agire, senza piano specifico" o "idea suicida attiva con piano e intento specifici") basata sul questionario C-SSRS allo screening o al basale. -Uno score relativo al questionario sulla salute del paziente (PHQ, Patient Health Questionnaire) -8 di =10 corrispondente alla depressione da moderata a grave allo screening o al basale. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint:
Having at least 90% lower Psoriasis Area and Severity Index (PASI) score relative to baseline (PASI 90 response) at Week 40. |
Presentare uno score Psoriasis area severity index (PASI) diminuito di almeno il 90% rispetto al basale (risposta PASI 90) alla Settimana 40. |
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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) |
Key secondary endpoint: - Having static Physician’s Global Assessment (sPGA) score of 0 or 1 at Week 40. Secondary endpoints: - Having PASI 90 response at Week 52. - Having sPGA score of 0 or 1 at Week 52. - Having sPGA of genitalia (sPGA-G) of 0 or 1 at both Weeks 40 and 52. - Having sPGA-G score of 0 or 1 at Week 40. - Having sPGA-G score of 0 or 1 at Week 52. - Having PASI 100 response at Week 40. - Having PASI 100 response at Week 52. - Change from baseline at Weeks 40 and 52 in PASI score. - Change from baseline at Weeks 40 and 52 in affected body surface area (BSA). - Having Dermatology Life Quality Index (DLQI) total score of 0 or 1 at Week 40. - Having DLQI total score of 0 or 1 at Week 52. - Change from baseline at Weeks 40 and 52 in DLQI total score. |
- Presentare la risposta PASI 90 alla Settimana 52. • Presentare uno score sPGA di 0 o 1 alla Settimana 52. • Presentare uno score di valutazione globale degli organi genitali del medico (static Physician's Global Assessment of Genitalia - sPGA-G) di 0 o 1 alle Settimane 40 e 52. • Presentare uno score sPGA-G di 0 o 1 alla Settimana 40. • Presentare uno score sPGA-G di 0 o 1 alla Settimana 52. • Presentare la risposta PASI 100 alla Settimana 40. • Presentare la risposta PASI 100 alla Settimana 52. • Variazione dello score PASI rispetto al basale alle Settimane 40 e 52. • Variazione rispetto al basale alle Settimane 40 e 52 nell'area della superficie corporea (BSA, Body Surface Area) interessata. • Presentare uno score totale Dermatology Life Quality Index (DLQI) di 0 o 1 alla Settimana 40. • Presentare uno score DLQI di 0 o 1 alla Settimana 52. • Variazione dello score totale DLQI rispetto al basale alle Settimane 40 e 52. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 40/Week 52 |
Settimana 40/ Settimana 52 |
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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 | 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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 56 |
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 |
Russian Federation |
Belgium |
Czechia |
Denmark |
France |
Germany |
Greece |
Italy |
Netherlands |
Spain |
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 the trial is defined as the date of the last visit of the last subject in the trial globally. |
La fine della sperimentazione è definita come l'ultima visita delll'ultimo paziente nella sperimentazione globale. |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |