E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderately to Severely Active Rheumatoid Arthritis (RA) |
Artritis Reumatoide (AR) activa moderada a grave |
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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 | 19.0 |
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. |
- Comparar la eficacia de ABT-494 con placebo para el tratamiento de los signos y los síntomas de sujetos con AR activa de moderada a grave que reciben una dosis estable de fármacos antirreumáticos modificadores de la enfermedad sintéticos convencionales ( FARMEsc ) y que no han respondido de forma adecuada a los FARMEsc - Comparar la seguridad y la tolerabilidad de ABT-494 con placebo en sujetos con AR activa de moderada a grave que reciben una dosis estable de FARMEsc y que no han respondido de forma adecuada a los FARMEsc. - Para evaluar la seguridad a largo plazo, tolerabilidad, y eficacia del ABT-494 en pacientes 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 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). |
- Adulto de cualquier sexo, mayor de 18 años - Diagnóstico de AR durante ? 3 meses - Haber sido tratados con un FARMEsc durante ? 3 meses y haber recibido una dosis estable durante ? 4 semanas antes de la primera administración del fármaco del estudio.Se permiten los siguientes FARMEsc: MTX, sulfasalazina, hidroxicloroquina, cloroquina, y leflunomida. - Cumplir los siguientes requisitos de actividad de la enfermedad mínima: ? 6 articulaciones inflamadas (de un total de 66) y ? 6 articulaciones dolorosas (de un total de 68) en las visitas de selección y basal - Los sujetos con exposición previa a como máximo un FARMEb pueden incluirse en el estudio (con un máximo del 20% de la población del estudio) |
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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. |
- Exposición previa a cualquier inhibidor de la Janus kinasa (JAK) (como tofacitinib, baricitinib y filgotinib, entre otros). - Antecedentes de artropatía inflamatoria distinta de la AR. Se permiten los antecedentes de síndrome de Sjogren secundario. - Sujetos que se consideren con insuficiente respuesta al tratamiento con FARMEb determinado por el investigador. |
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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. |
La variable principal es la proporción de pacientes que alcazan respuesta ACR20 / proporción de pacientes que alcanzan LDA en 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) ? 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) |
- Variación de l grado de actividad de la enfermedad (DAS) 28 (PCR- proteína reactiva C) con respecto al momento basal - Variación de HAQ-DI con respecto al momento basal - Respuesta ACR50 - Respuesta ACR70 - Variación del formulario abreviado 36 (SF-36) el grado de componente físico (PCS) con respecto al momento basal - Proporción de pacientes que alcazan la Remisión clínica (RC) basada en DAS28( PCR) - Variación de la evaluación funcional de terapaia de fatiga de enfermedad crónica ( FACIT-F) conrespecto al momento basal - Variación de la escala de estabilidad de trabajo de artritis reumatoide (FA-WIS) con respecto al momento basal. - Variación de la rigidez matutina con respecto al momento basal (gravedad) |
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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 | 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 |
Belarus |
Bosnia and Herzegovina |
Brazil |
Canada |
Chile |
Colombia |
Egypt |
European Union |
Hong Kong |
Israel |
Kazakhstan |
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
|
LVLS or last follow up contact whichever is later |
Última visita del último paciente 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 | 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 |