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 (AR) |
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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 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 to csDMARDs. • To compare the safety and tolerability of ABT-494 versus placebo in subjects with moderately to severely active RA who are on a stable dose of csDMARDs and have an inadequate response to csDMARDs. • To evaluate the long-term safety, tolerability, and efficacy of ABT-494 in subjects with RA.
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•Confrontare l’efficacia di ABT-494 rispetto a placebo per il trattamento di segni e sintomi dei soggetti affetti da artrite reumatoide (AR) in fase attiva di grado da moderato a severo in corso di trattamento a dose stabile con farmaci antireumatici sintetici convenzionali modificanti la malattia (csDMARD) a dose stabile e con risposta inadeguata ai csDMARD. •Confrontare la sicurezza e la tollerabilità di ABT-494 rispetto a placebo in soggetti affetti da AR in fase attiva di grado da moderato a severo in corso di trattamento a dose stabile con csDMARD e con risposta inadeguata ai csDMARD. •Valutare la sicurezza, tollerabilità ed efficacia a lungo termine nei soggetti affetti da AR.
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E.2.2 | Secondary objectives of the trial |
Not applicable |
Non applicabile |
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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 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. • Meets the minimum disease activity criteria: ≥ 6 swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits. • Subjects with prior exposure to at most one bDMARD may be enrolled (up to 20% of study population).
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• Soggetti adulti di ambo i sessi di età pari o superiore a 18 anni. • Soggetti con diagnosi di AR da ≥ 3 mesi •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. • Soggetti che soddisfano i criteri minimi di attività della malattia: tumefazione di ≥ 6 articolazioni (su conta totale di 66 articolazioni) e dolorabilità alla palpazione di ≥ 6 articolazioni (su conta totale di 68 articolazioni) alle visite di Screening e Baseline. • Potranno essere arruolati soggetti con pregressa esposizione a non più di un bDMARD (fino al 20% della popolazione della sperimentazione). |
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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. • Subjects who are considered inadequate responders to bDMARD therapy as determined by the Investigator.
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• 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. • Soggetti che a giudizio dello Sperimentatore hanno avuto una risposta inadeguata alla terapia con bDMARD
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the proportion of subjects achieving ACR20 response / the proportion of subjects achieving LDA at Week 12. |
L’endpoint primario è rappresentato dalla percentuale di soggetti che ottengono la risposta ACR20 oppure la percentuale di soggetti che ottengono la risposta LDA 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-reactive protein [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) • Proportion of subjects achieving Clinical remission (CR) based on DAS28 (CRP) • Change from baseline in Functional Assessment of chronic Illness Therapy-Fatigue (FACIT-F) • Change from baseline in Work Stability Scale for Rheumatoid Arthritis (FA-WIS) • Change from baseline in morning stiffness (severity).
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• Variazione rispetto al baseline del punteggio Disease Activity Score (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); • Percentuale di soggetti che ottengono Remissione clinica (RC) in base al punteggio DAS28 (PCR); • Variazione rispetto al baseline del punteggio FACIT-F (Functional Assessment of Chronic Illness Therapy-Fatigue); • Variazione rispetto al baseline del punteggio RA-WIS (Work Instability Scale for Rheumatoid Arthritis); • Variazione rispetto al baseline della rigidità al mattino (gravità).
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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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 81 |
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 |
Barbados |
Bosnia and Herzegovina |
Brazil |
Canada |
Chile |
Colombia |
Egypt |
European Union |
Hong Kong |
Israel |
Japan |
Kazakhstan |
Korea, Democratic People's Republic of |
Korea, Republic of |
Malaysia |
Mexico |
New Zealand |
Puerto Rico |
Russian Federation |
Serbia |
Singapore |
South Africa |
Switzerland |
Taiwan |
Turkey |
Ukraine |
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 |
LVLS o ultimo follow-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 | 5 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |