E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Rheumatoid arthritis |
Artrite reumatoide |
|
E.1.1.1 | Medical condition in easily understood language |
Rheumatoid arthritis |
Artrite reumatoide |
|
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 | 23.1 |
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 |
|
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 evaluate the efficacy of etanercept monotherapy compared to methotrexate monotherapy on maintenance of remission in subjects with rheumatoid arthritis who were on etanercept plus methotrexate combination therapy. |
Valutare l’efficacia di etanercept in monoterapia rispetto a metotrexato in monoterapia nel mantenimento della remissione dei soggetti con AR precedentemente in terapia con etanercept più metotrexato. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of etanercept plus methotrexate therapy compared to methotrexate monotherapy on maintenance of remission. |
Valutare l’efficacia della terapia con etanercept più metotrexato rispetto a metotrexato in monoterapia nel mantenimento della remissione. |
|
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 |
Pharmacogenetics Version: Prot. Em. 2 Date: 30/10/2015 Title: Optional pharmacogenetic sub-study to evaluate the correlation of inherited genetic variations to rheumatoid arthritis and/or responsiveness to etanercept and methotrexate. Objectives: To evaluate the correlation of inherited genetic variations to rheumatoid arthritis and/or responsiveness to etanercept and methotrexate
|
Farmacogenetica Versione: Prot. Em. 2 Data: 30/10/2015 Titolo: Sottstudio opzionale di farmacogenetica per valutare la correlazione genetiche della artrite reumatoide e/o la risposta all'etanercept e metotrexato Obiettivi: Valutare la correlazione genetiche della artrite reumatoide e/o la risposta all'etanercept e metotrexato
|
|
E.3 | Principal inclusion criteria |
In very good RA disease control for = 6 months in the opinion of the investigator Receiving treatment with etanercept for RA for = 6 months prior to run-in visit 1 Receiving treatment with methotrexate of 10 mg to 25 mg weekly for = 6 months AND on a stable dose of oral methotrexate for = 8 weeks prior to run-in visit 1 = 18 years of age at screening |
I soggetti devono essere adulti con anamnesi di AR da moderata a grave. I soggetti devono presentare un ottimo controllo della malattia per =6 mesi ed essere in remissione, definita come SDAI =3,3 allo screening e alla fine del periodo di run-in. I soggetti devono essere in terapia con etanercept 50 mg a settimana più metotrexato da =6 mesi prima dell’inizio del periodo di run-in. La dose di metotrexato deve essere tra 10 a 25 mg a settimana per =6 mesi prima dell’inizio del periodo di run-in e la dose deve essere stabile per =8 settimane prima dell’inizio del periodo di run-in. Se un soggetto sta assumendo metotrexato per via sottocutanea, deve passare a una dose di metotrexato orale equivalente, pari a 10-25 mg a settimana, e mantenere un dosaggio orale stabile per un periodo =8 settimane prima della visita di run-in. |
|
E.4 | Principal exclusion criteria |
Subject has known history of alcoholic hepatitis, nonalcoholic steatohepatitis or immunodeficiency syndromes, including Human Immunodeficiency Virus infection. Subject has any active infection (including chronic or localized infections) for which anti-infectives were indicated within 4 weeks prior to run-in visit 1. Subject has a serious infection, defined as requiring hospitalization or intravenous anti-infectives within 8 weeks prior to run-in visit 1. Subject has used biologic DMARD other than etanercept OR has used an oral janus kinase inhibitor = 6 months prior to run-in visit 1 Subject has known alcohol addiction or dependency or uses alcohol daily. Subject has one or more significant concurrent medical conditions per investigator judgment
|
Soggetto con storia nota di epatite alcolica, steatoepatite non alcolica o sindromi da immunodeficienza, tra cui l'infezione HIV. Il soggetto presenta qualsiasi infezione attiva (tra cui infezioni croniche o localizzate) per le quali anti-infettivi sono stati indicati nelle 4 settimane precedenti a visita 1 -a run-in. Il soggetto ha una grave infezione, definita come richiedente l’ospedalizzazione o somministrazione per via endovenosa di antinfettivi utilizzati entro 8 settimane prima della visita 1-run-in -. Il soggetto ha utilizzato DMARD biologico oltre a etanercept O ha utilizzato un inibitore orale della Janus chinasi = 6 mesi prima della visita-1- run-in visita Il soggetto ha una nota dipendenza da alcol o usa alcol giornalmente. Il soggetto presenta una o più significative condizioni mediche concorrenti secondo il giudizio dello sperimentatore |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Simplified Disease Activity Index (SDAI) remission (= 3.3) |
SDAI (Simplified Disease Activity Index) (=3,3) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1. SDAI score and change from baseline at all measured timepoints 2. Disease activity score (28 joint) calculated using the erythrocyte sedimentation rate formula (DAS-28-ESR) and change from baseline at all measured timepoints 3. Disease activity score (28 joint) using the C-reactive protein formula (DAS-28-CRP) and change from baseline at all measured timepoints 4. Clinical Disease Activity Index (CDAI) and change from baseline at all measured timepoints 5. SDAI remission (= 3.3) at all measured timepoints 6. Boolean remission at all measured timepoints 7. Disease worsening defined as an SDAI > 3.3 and = 11 during two consecutive visits at least 2 weeks apart or SDAI > 3.3 and = 11 on three or more separate visits or SDAI > 11 after randomization 8. Time to disease worsening defined as an SDAI > 3.3 and = 11 during two consecutive visits at least 2 weeks apart or SDAI > 3.3 and = 11 on three or more separate visits or SDAI > 11 after randomization 9. In subjects that receive rescue treatment: • Time to recapture SDAI remission after starting rescue treatment • SDAI remission at week 48 |
• Punteggio SDAI e variazione rispetto al basale in tutte le visite che richiedono la misurazione • Punteggio sul grado di attività della malattia (giunture articolari) calcolato tramite la formula per la misurazione della velocità di eritrosedimentazione (DAS-28-ESR) e variazione rispetto al basale in tutte le visite che richiedono la misurazione, • Punteggio sul grado di attività della malattia (28 giunture articolari) calcolato tramite la formula per la misurazione della proteina C reattiva (DAS-28-CRP) e variazione rispetto al basale in tutte le visite che richiedono la misurazione, • Indice CDAI (Clinical Disease Activity Index) e variazione rispetto al basale in tutte le visite che richiedono la misurazione Remissione secondo l’indice SDAI (=3,3) in tutte le visite che richiedono la misurazione • Remissione secondo i criteri di Boolean in tutte le visite che richiedono la misurazione • Peggioramento della malattia definito come SDAI >3,3 e =11 durante due visite consecutive ad almeno 2 settimane di distanza o SDAI >3,3 e =11 a tre o più visite separate o SDAI >11 dopo randomizzazione • Tempo di peggioramento della malattia definito come SDAI >3,3 e =11 durante due visite consecutive ad almeno 2 settimane di distanza o SDAI >3,3 e =11 a tre o più visite separate o SDAI >11 dopo randomizzazione Nei soggetti che ricevono la terapia di salvataggio: • Tempo di recupero della remissione secondo l’indice SDAI dopo l’inizio della terapia di salvataggio • Remissione SDAI alla settimana 48 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
•SDAI score, Disease activity score [DAS-28-ESR and DAS-28-CRP], Clinical Disease Activity Index, SDAI remission and Boolean remission evaluated Day 1, week 12, 24, 36 and 48 weeks. •Disease worsening defined as an SDAI > 3.3 and = 11 during two consecutive visits at least 2 weeks apart or SDAI > 3.3 and = 11 on three or more separate visits or SDAI > 11 after randomization. •Time to disease worsening defined as an SDAI > 3.3 and = 11 during two consecutive visits at least 2 weeks apart or SDAI > 3.3 and = 11 on three or more separate visits or SDAI > 11 after randomization. In subjects that receive rescue treatment during the double-blind treatment period: •Time to recapture SDAI remission after starting rescue treatment •SDAI remission at week 48 |
Tutti i soggetti: •SDAI score, Disease activity score [DAS-28-ESR and DAS-28-CRP], Clinical Disease Activity Index, SDAI remission and Boolean remission al giorno 1, settimana 12, 24, 36 e 48. •Disease worsening definite come un punteggio SDAI > 3.3 e = 11 durante due visite consecutive o SDAI > 3.3 e = 11 per tre o più visite separate o SDAI > 11 dopo la randomizzazione. •Time to disease worsening definite come un punteggio SDAI > 3.3 e = 11 durante due visite consecutive o SDAI > 3.3 e = 11 per tre o più visite separate o SDAI > 11 dopo la randomizzazione. In soggetti che ricevono il trattamento di salvataggio durante il period in doppio cieco: •Time to recapture SDAI remission dopo l’inizio della terapia di salvataggio •SDAI remission all settimana 48
|
|
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 | Yes |
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 | 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 | 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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 47 |
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 |
Italy |
Spain |
United Kingdom |
|
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
|
End of Study will be the time when the last subject is assessed or receives an intervention for evaluation in the study. |
End of Study sarà il momento in cui l'ultimo soggetto è valutato o riceve un intervento per la valutazione nello studio. |
|
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 | 9 |
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 | 9 |
E.8.9.2 | In all countries concerned by the trial days | 20 |