E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to severe psoriasis. |
Psoriasi 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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10037153 |
E.1.2 | Term | Psoriasis |
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 objective is to assess the efficacy (PASI 75) of IFX (5 mg/kg) in adult subjects (aged 18 to 75 years) with moderate to severe chronic psoriasis not responding and/or intollerant to systemic standard or biologic therapies. |
Obiettivo primario e' valutare l'efficacia di Infliximab 5 mg/kg espressa in termini di PASI 75 in soggetti adulti (18-75 anni) affetti da psoriasi da moderata a severa resistenti e/o intolleranti a terapie sistemiche convenzionali o biologiche. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety, efficacy (PASI 50, 90, BSA, SAPASI) and the impact on QOL (SF-36, EQ-5D, SKINDEX 29, Itch Measure VAS) of IFX. |
Valutare la tollerabilita',l'efficacia (PASI 50,90,BSA,SAPAS)e l'impatto di Infliximab sulla qualita' di vita (SF-36,EQ-5D,SKINDEX 29,Itch Measure VAS). |
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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 |
ALTRI SOTTOSTUDI: Studio biochimico per valutare con tecniche immunoistochimiche la variazione nel numero e grado di attivazione dei diversi tipi di cellule dendritiche presenti nella cute psoriasica.
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E.3 | Principal inclusion criteria |
- Patients must be <=18 to 75 years of age, of eigher gender and of any race. - Patients must have psoriasis covering at least 10% of total BSA and PASI score of 12 or greater at screening and baseline. - Patients must have had a diagnosis of moderate to severe psoriasis at least 24 months prior to screening (patients with concurrent psoriatic arthritis may be enrolled). - Patients eligible to Infliximab treatment who have failed at least on of the following psoriasis treatments: Corticosteroids, MTX, systemic retinoids, Cyclosporine, PUVA, UVB phototherapy and/or biologics (etanercept or efalizumab). - Patients are considered eligible according to the tubercolosis (TB) eligibility assessment, screening and early detection of reactivation rules (specific section in the protocol). - Patients must have had a chest X-ray (posterior-anterior and lateral) within 3 months prior the screening with no evidence of malignancy, infections, or fibrosis. - Patients' screening and baseline test (CBC, blood chemistry, and urianalysis)must be within the following parameters: Hemoglobin: <= 10 g/dL White blood cells: <=3.5x109L Neutrophils: <=1.5x109L Platelets: <=100x109L Serum creatinine: >1.5 mg/dL AST, ALT, alkaline phosphatase and gamma-glutamyltransferase >= x upper normal limit of normal range for the laboratory conducting the test. Patients must be free of any clinically significant disease (other than psoriasis or psoriatic arthritis) that could interfere with the study evaluation. Patients must be willing to give written informed consent and be able to adhere to protocol visit and procedures. |
- Pazienti adulti (eta': 18-75 anni) di sesso femminile e maschile, di qualsiasi gruppo etnico. - Pazienti con psoriasi a placche con interessamento di almeno il 10% della superficie corporea totale (BSA:<=10%) e con valore del PASI di almeno 12 alla visita 1 (screening) e alla visita 2 (basale). - Pazienti con diagnosi di psoriasi a placche da moderata a severa formulata almeno 6 mesi prima della visita di screening (possono essere arruolati pazienti con concomitante artrite psoriasica). - Pazienti eleggibili al trattamento con infliximab che siano resistenti ad almeno una delle terapie sistemiche convenzionali (metotressato, retinoidi, ciclosporina, PUVA-terapia, fototerapia con UVB) e/o con farmaci biologici (etanercept, efalizumab) e/o in cui le suddette terapie non possono essere utilizzate per problemi di tollerabilita', compliance e/o controindicazioni. - Pazienti che presentino i requisiti di idoneita' ai test di screening e di diagnosi di tubercolosi (secondo procedure descritte nel paragrafo 8.11 del protocollo). - Pazienti in cui la radiografia del torace in 2 proiezioni effettuata nei 3 mesi precedenti la visita di screening non abbia evidenziato segni di neoplasia, infezione o fibrosi. - Pazienti in cui gli esami di laboratorio eseguiti alla visita 1 (o nel periodo compreso tra visita 1 e visita 2) abbiano mostrato parametri inclusi nei seguenti valori: Emoglobina: <=10 g/dL Globuli bianchi: <=3,5x10MLD Neutrofili: <=1,5x10MLD Piastrine: <=100x10MLD Creatininemia: >1,5 mg/dL Transaminasi (AST, ALT), fosfatasi alcalina, bilirubina totale e gamma-glutamiltransferasi >=1,5 volte il limite superiore del range di normalita'. - Pazienti che non siano affetti da malattie clinicamente rilevanti (eccezion fatta per psoriasi o artrite psoriasica) che possano interferire con le valutazioni previste nello studio. - Pazienti che abbiano manifestato la loro volonta' a partecipare allo studio, rilasciando il proprio consenso informato, e che siano in grado di sottoporsi alle visite e procedure dello studio. |
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E.4 | Principal exclusion criteria |
- Standard concomitant psoriasis therapies. - Active or latent TB. - History of chronic infectious disease, opportunistic infection or serious infection within 2 months of enrollment. - History of lymphoproliferative disease. - Malignancy in past 5 years (except treated BCC). - Treatment with TNF antagonist within previous 12 weeks or other experimental drugs within previous 4 weeks. - Patients who have current-drug induced psoriasis. - Female patients who are pregnant or nursing. Patients previously treated with Infliximab. - Patients who have a concomitant diagnosis of CHF. |
- Terapie concomitanti con la psoriasi. - TB attiva o latente. - Storia di malattie infettive croniche, infezioni opportunistiche o infezioni serie entro due mesi dall'arruolamento. - Storia di malattia linfoproliferativa. - Neoplasie negli ultimi 5 anni (eccettuati epiteliomi basocellulari trattati senza recidiva). - Trattamento con antagonisti del TNF-alfa nelle precedenti 12 settimane o con farmaci sperimentali nelle 4 settimane precedenti l'arruolamento. - Pazienti in trattamento con farmaci che inducano psoriasi. - Pazienti di sesso femminile che siano in gravidanza o allattamento. - Pazienti precedentemente trattati con Infliximab. - Pazienti con concomitante diagnosi di insufficienza cardiaca congestizia. |
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E.5 End points |
E.5.1 | Primary end point(s) |
PASI 75 response rate at week 10 will be evaluated. PASI 75 will be summarized by counts and percentages. The PASI 75 response rate will be estimated and its 95% Confidence Interval will be calculated. |
Sara' valutata la frequenza di risposta in termini di PASI 75 alla settimana 10, in numero assoluto ed in percentuale di pazienti. Sara' fatta una stima della frequenza e sara' calcolato l'intervallo di confidenza al 95%. |
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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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 38 |
E.8.5 | The trial involves multiple Member States | No |
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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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 |