E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderately to Severely Active Rheumatoid Arthritis (RA) |
Artrite Reumatoide (AR) in Fase Attiva e di Grado da Moderato a Severo. |
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E.1.1.1 | Medical condition in easily understood language |
Rheumatoid Arthritis (RA) |
Artrite Reumatoide (RA) |
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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 | 20.0 |
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 |
• To compare the safety and efficacy of ABT-494 versus placebo for the treatment of signs and symptoms of subjects with moderately to severely active rheumatoid arthritis (RA) who are on a stable dose of conventional synthetic disease- modifying anti-rheumatic drugs (csDMARDs) and have an inadequate response or intolerance to biologic disease-modifying anti-rheumatic drugs (bDMARDs). • To evaluate the long-term safety, tolerability, and efficacy of ABT-494 in subjects with RA. |
• Confrontare la sicurezza e l’efficacia di ABT-494 rispetto a placebo per il trattamento di segni e sintomi di soggetti con artrite reumatoide (AR) in fase attiva e di grado da moderato a severo che sono in Trattamento Stabile con Farmaci Antireumatici Sintetici Convenzionali Modificanti la Malattia (csDMARD) ed hanno una risposta inadeguata o intolleranza ai Farmaci Antireumatici Biologici Modificanti la Malattia (bDMARDs). • Valutare la sicurezza, tollerabilità ed efficacia a lungo termine di ABT-494 nei soggetti con AR.
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Adult male or female, at least 18 years old. • Diagnosis of RA for ≥ 3 months. • Subjects have been treated for ≥ 3 months with ≥ 1 bDMARD therapy, but continue to exhibit active RA or had to discontinue due to intolerability or toxicity, irrespective of treatment duration prior to the first dose of study drug. • Subjects have been receiving csDMARD therapy ≥ 3 months and on a stable dose for ≥ 4 weeks prior to the first dose of study drug. The following csDMARDs are allowed: MTX, sulfasalazine, hydroxychloroquine, chloroquine, and leflunomide. A combination of up to two background csDMARDs is allowed except the combination of MTX and leflunomide. • Meets the following criteria: ≥ 6 swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits. |
• Soggetti adulti di ambo i sessi di età pari o superiore a 18 anni. • Soggetti con diagnosi di AR da ≥ 3 mesi • Soggetti che hanno ricevuto trattamento per ≥ 3 mesi con ≥ 1 bDMARD ma che continuano a manifestare AR attiva oppure hanno dovuto interrompere il trattamento a causa di intolleranza o tossicità, a prescindere dalla durata del trattamento prima della prima dose del medicinale sperimentale. • Soggetti che ricevono csDMARD da ≥ 3 mesi, sono in trattamento a dose stabile da ≥ 4 settimane prima della prima dose del medicinale sperimentale. Sono permessi i seguenti csDMARD: MTX, sulfasalazina, idrossiclorochina, clorochina e leflunomide. È permessa la combinazione di un massimo di due csDMARD di background Con l’eccezione della combinazione di MTX e leflunomide. • Soggetti che soddisfano i seguenti criteri: tumefazione di ≥ 6 articolazioni (basata sulla conta di 66 articolazioni) e dolorabilità alla palpazione di ≥ 6 articolazioni (basata sulla conta totale di 68 articolazioni) alle visite di Screening e Baseline.
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E.4 | Principal exclusion criteria |
• Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, and filgotinib).
• History of inflammatory joint disease other than RA. History of secondary Sjogren's Syndrome is permitted. |
• Pregressa esposizione a qualsiasi inibitore delle proteine Janus chinasi (JAK) (compresi, a titolo esemplificativo ma non esaustivo, tofacitinib, baricitinib e filgotinib). • Storia di artropatia infiammatoria diversa da AR. Possono essere arruolati i soggetti con storia di Sindrome di Sjogren secondaria.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the proportion of subjects achieving ACR 20response / the proportion of subjects achieving low disease activity (LDA) at Week 12. |
L’endpoint primario è rappresentato dalla percentuale di soggetti che ottengono la risposta ACR20 / la percentuale di soggetti che ottengono la risposta LDA(Low Disease Activity) alla Settimana 12. |
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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) |
• Change from baseline in Disease Activity Score (DAS) 28 (C-reactiveprotein [CRP]) • Change from baseline in HAQ-DI • ACR 50 response rate • ACR 70 response rate • Change from baseline in Short Form-36 (SF-36) Physical Component Score (PCS) • ACR 20 response rate at week 1 |
• Variazione rispetto al baseline del punteggio di Attività della Patologia (DAS) 28 (Proteina C Reattiva [PCR]); • Variazione rispetto al baseline del punteggio HAQ-DI; • Tasso di risposta ACR50 • Tasso di risposta ACR70; • Variazione rispetto al baseline del punteggio del Dominio Fisico (Physical Component Score, PCS) del questionario SF-36 (Short- Form-36); • Tasso di risposta ACR20 alla Settimana 1.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | 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 | 4 |
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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 127 |
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 |
Argentina |
Australia |
Brazil |
Canada |
Chile |
Colombia |
European Union |
Hong Kong |
Israel |
Korea, Republic of |
Mexico |
New Zealand |
Norway |
Puerto Rico |
Russian Federation |
Switzerland |
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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LVLS or last follow up contact whichever is later. |
LSLV o ultimo follw-up in funzione di quale avvenga dopo. |
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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 | 6 |
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 | 6 |
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 |