E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Rheumatoid arthritis |
Artrite reumatoide |
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E.1.1.1 | Medical condition in easily understood language |
Rheumatoid arthritis |
Artrite reumatoide |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
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 | 10039073 |
E.1.2 | Term | Rheumatoid arthritis |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective 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 |
Demonstrate the efficacy of secukinumab (75mg or 150mg) versus placebo (measured with ACR 20) after 24 weeks of treatment |
Dimostrare, sulla base della proporzione di pazienti che raggiunge una risposta ACR20 alla settimana 24, che l’efficacia di secukinumab 75 mg o 150 mg è superiore a placebo in pazienti con AR attiva |
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E.2.2 | Secondary objectives of the trial |
• Change of the HAQ-DI from baseline on secukinumab 75 mg or 150 mg compared to placebo after 24 weeks of treatment; • Change of the van der Heijde total modified Sharp score from baseline on secukinumab compared to placebo; • Proportion of patients achieving major clinical response on secukinumab 75 mg or 150 mg compared to placebo after 1 year of treatment. |
• dimostrare che a 24 settimane di trattamento, secukinumab 75 o 150 mg è in grado di apportare un miglioramento superiore a placebo rispetto al basale sulla base del questionario di valutazione della malattia (HAQ-DI) •dimostrare che il cambiamento rispetto al basale indotto da secukinumab (75 mg e 150 mg, a dosi singole o combinate) a 24 settimane è superiore al placebo sulla scala van der Heijde total modified Sharp score (TSS) •dimostrare che secukinumab 75 o 150 mg è superiore a placebo (seguendo la randomizzazione iniziale) nei confronti della popolazione percentuale che raggiunge una risposta clinica rilevante (risposta ACR70 mantenuta per 6 mesi) ad un anno di trattamento |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male or non-pregnant, non-lactating female patients; • Presence of Rheumatoid Arthritis classified by ACR 2010 revised criteria for at least 3 months before screening; • At Baseline: Disease activity criteria defined by ≥ 6 tender joints out of 68 and ≥ 6 swollen joints out of 66 WITH at least 1 of the following at screening: Anti-CCP antibodies positive OR Rheumatoid Factor positive AND WITH at least 1 of the following at screening: hsCRP ≥ 10 mg/L OR ESR ≥ 28 mm/1st hr; • Patients must have been taking at least one anti-TNF-α agent given at an approved dose for at least 3 months before randomization and have experienced an inadequate response to treatment or have been intolerant to at least one administration of an anti-TNF-α agent; • Patients must be taking MTX for at least 3 months before randomization and have to be on a stable dose at least 4 weeks before randomization (7.5 to 25 mg/week (For Japan only: 6 to 25 mg/week)). Other protocol-defined inclusion criteria may apply. |
•Maschi, o femmine non gravide nè in allattamento, di almeno 18 anni di età •Diagnosi di artrite reumatoide da almeno 3 mesi prima della visita di screening, classificata in accordo ai criteri revisionati ACR 2010 •Al basale: attività di malattia definita da ≥ 6 articolazioni doloranti (su 68) e ≥ 6 articolazioni gonfie (su 66) con almeno uno dei seguenti parametri allo screening o Anticorpi anti-CCP positivi oppure o Fattore reumatoide positivo e con almeno uno dei seguenti parametri allo screening o hsPCR ≥ 10 mg/L oppure o VES ≥ 28 mm/1^ ora • Trattamento con almeno un agente anti-TNF-alfa(quale etanercept, adalimumab, infliximab, certolizumab o golimumab) a dose appropriata per almeno 3 mesi prima della randomizzazione, con una risposta terapeutica inadeguata o un’intolleranza ad almeno una somministrazione. •Trattamento con MTX per almeno 3 mesi prima della randomizzazione, con una dose stabile mantenuta per almeno 4 settimane prima della randomizzazione (MTX range da 7.5 a 25 mg/settimana) |
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E.4 | Principal exclusion criteria |
• Chest x-ray with evidence of ongoing infectious or malignant process, obtained within 3 months prior to screening and evaluated by a qualified physician; • Rheumatoid arthritis patients functional status class IV according to the ACR 1991 revised criteria; • Patients who have ever received biologic immunomodulating agents except for those targeting TNFα; • Previous treatment with any cell-depleting therapies. Other protocol-defined exclusion criteria may apply. |
•Evidenza all’indagine radiografica del torace effettuata entro 3 mesi dallo screening, e validata da personale qualificato, di infezioni attive o processi neoplastici •Diagnosi di AR con status funzionale di classe IV in accordo con i criteri revisionati ACR 1991 •Trattamento pregresso con agenti biologici immunomodulanti ad eccezione dei tarmaci mirati all’inibizione del TNF •Trattamento pregresso con terapie di deplezione cellulare quali, ma non solo, anti CD20, o farmaci in sperimentazione (CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19) |
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E.5 End points |
E.5.1 | Primary end point(s) |
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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) |
HAQ-DI,van der Heijde total modified Sharp score and Major clinical response |
HAQ-DI van der Heijde alla settimana 24, obiettivo strutturale alla settimana 24, e risposta clinica maggiore alla settimana 52. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 24 and 1 year |
Alla settimana 24 e a 1 anno |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity, Biomarkers analysis |
Immunogenicità, Analisi biomarcatori |
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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 | 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 | 3 |
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 | 29 |
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 |
Canada |
Colombia |
Guatemala |
India |
Japan |
Mexico |
Panama |
Peru |
Thailand |
Turkey |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 33 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 38 |
E.8.9.2 | In all countries concerned by the trial days | 0 |