E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderately to Severely Active Rheumatoid Arthritis (RA) |
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E.1.1.1 | Medical condition in easily understood language |
Rheumatoid Arthritis (RA) |
Artritis 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 | 18.1 |
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 |
? 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. |
?Comparar la seguridad y la eficacia de ABT-494 versus placebo para el tratamiento de signos y síntomas en sujetos con artritis reumatoide de actividad moderada a grave que están tratamiento estable con fármacos antirreumáticos modificadores de la enfermedad sintéticos convencionales (FARMEsc) y tienen una respuesta insuficiente o intolerancia a los FARME biológicos (FARMEb) ?Evaluar la seguridad a largo plazo, la tolerancia y la eficacia de ABT-494 en sujetos 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. |
? Adultos, hombre o mujeres, con edad mínima de 18 años ? Diagnóstico de AR desde hace ? 3meses ? Sujetos que hayan recibido tratamiento durante ?3meses con ? 1 FARMEb, pero que continúen mostrando AR activa o hayan interrumpido el tratamiento debido a intolerancia o toxicidad, independientemente de la duración del tratamiento, antes de la primera dosis del fármaco de estudio. ? Sujetos que hayan recibido tratamiento con FARMEsc durante ? 3meses y una dosis estable durante ? 4 semanas antes de la primera dosis del fármaco. Se permiten los siguientes FARMEsc: MTX, sulfasalazina, hidroxicloroquina, cloroquina y leflunomida. Se permite una combinación de hasta dos FARMEsc como tratamiento base, excepto la combinación de MTX y leflunomida. ? Que cumplan los siguientes criterios: ? 6 articulaciones hinchadas (partiendo de 66 articulaciones) y ? 6 articulaciones dolorosas (partiendo de 68 articulaciones) en las visitas de selección y basal. |
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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. |
?Exposición previa a cualquier inhibidor de las Janus kinasa (JAK) (incluyendo tofacitinib, baricitinib y filgotinib). ?Antecendentes de enfermedad articular inflamatoria que no sea AR. Se permiten antecedentes de síndrome de Sjogren. |
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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 20 response / the proportion of subjects achieving low disease activity (LDA) at Week 12. |
El criterio de valoración principal es la proporción de sujetos que logren una respuesta ACR20 / la proporción de sujetos que alcancen una baja actividad de la enfermedad (LDA) en la semana 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) ? ACR 20 response rate at week 1 |
?Variación de la puntuación DAS28 (PCR) con respect al valor basal. ?Variación del HAQ-DI con respect al valor basal. ?Tasa de respuesta ACR 50 ?Tasa de respuesta ACR 70 ?Variación de la puntuación del componente físico (PCS) del cuestionario de salud abreviado 36 (SF-36) con respecto al valor basal. ?Tasa de respuesta ACR 20 en la semana 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 | 9 |
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 | 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 |
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 |
Última visita del último sujeto o último contacto de seguimiento, lo que ocurra más tarde. |
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |