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) con actividad de moderada a grave |
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E.1.1.1 | Medical condition in easily understood language |
Rheumatoid Arthritis |
Artritis Reumatoide |
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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 |
1. To compare the safety and efficacy of ABT-494 versus abatacept intravenous (IV) for the treatment of signs and symptoms of rheumatoid arthritis (RA) in bDMARD-inadequate response (bDMARD-IR) or bDMARD-intolerant subjects with moderately to severely active RA. 2. To evaluate the long-term safety, tolerability, and efficacy of ABT-494 in subjects with RA. |
1. Comparar la seguridad y eficacia de ABT-494 frente a abatacept intravenoso (IV) para el tratamiento de los signos y síntomas de la artritis reumatoide (AR) en sujetos con artritis reumatoide de moderada a severa que son respondedores inadecuados a FARMEb (FARMEb-RI) o presentan intolerancia a FARMEb. 2. Evaluar la seguridad, tolerabilidad y eficacia a largo plazo de ABT-494 en sujetos con A |
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E.2.2 | Secondary objectives of the trial |
1. ACR20 response rate at Week 12 (non-inferiority); 2. Change from baseline in DAS28 (CRP) at Week 12 (non-inferiority); 3. Change from baseline in DAS28 (CRP) at Week 12 (superiority). |
1. Ratio de respuesta ACR20 en la Semana 12 (no inferioridad); 2. Cambio desde basal en DAS28 (PCR) en Semana 12 (no inferioridad); 3. Cambio desde basal en DAS28 (PCR) en Semana 12 (superioridad) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Adult male or female, at least 18 years old. 2. Diagnosis of RA for ≥ 3 months. 3. 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 and have never received abatacept prior to the first dose of study drug. 4. 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. 5. 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 and hsCRP ≥ 3 mg/L at Screening. |
1. Hombre o mujer adulto, de al menos 18 años. 2. Diagnóstico de AR desde hace ≥ 3 meses 3. Pacientes que han sido tratados durante ≥ 3 meses con ≥ 1 FARMEb, pero continúan mostrando AR activa o han discontinuado por intolerancia o toxicidad, independientemente de la duración del tratamiento y nunca han recibido abatacept antes de la primera dosis del fármaco del estudio. 4. Sujetos que han estado recibiendo una terapia de FARMEsc durante ≥ 3 meses y en una dosis estable durante ≥ 4 semanas, antes de la primera dosis del fármaco del estudio. Se permiten los siguientes FARMEsc: MTX, sufasalazina, hidroxicloroquina, cloroquina y leflunomida. Se permite una combinación de hasta 2 FARMEsc de fondo excepto la combinación MTX y leflunomida. 5. Cumplen el siguiente criterio: ≥ 6 articulaciones inflamadas (basado en el recuento de 66 articulaciones) y 6 articulaciones sensibles (basado en el recuento de 68 articulaciones) en las visitas de selección y basal, y PCR-hs ≥ 3 mg/L en selección. |
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E.4 | Principal exclusion criteria |
1. Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, and filgotinib). 2. Prior exposure to abatacept 3. History of inflammatory joint disease other than RA. History of secondary Sjogren's Syndrome is permitted. |
1. Exposición previa a cualquier inhibidor de janus quinasas (JAK) (incluyendo, pero no limitado a tofacitinib, baricitinib y filgotinib). 2. Exposición previa a abatacept 3. Historial de enfermedad inflamatoria de las articulaciones distinta a la AR. Se permite historial de Síndrome de Sjogren secundario. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the proportion of subjects achieving low disease activity (LDA) at Week 12. LDA is defined as Disease Activity Score (DAS)28 (C-reactive protein [CRP]) ≤ 3.2 (non-inferiority). |
El resultado primario es la proporción de sujetos que consiguen una baja actividad de la enfermedad (LDA) en la semana 12. El LDA se define como la puntuación de actividad de la enfermedad DAS28 (proteína C reactiva [PRC]) ≤ 3.2 (no inferioridad). |
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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) |
1. ACR20 response rate at Week 12 (non-inferiority); 2. Change from baseline in DAS28 (CRP) at Week 12 (non-inferiority); 3. Change from baseline in DAS28 (CRP) at Week 12 (superiority). |
1. Ratio de respuesta ACR20 en Semana 12 (no inferioridad); 2. Cambio desde basal en DAS28 (PCR) en Semana 12 (no inferioridad); 3. Cambio desde basal en DAS28 (PCR) en Semana 12 (superioridad). |
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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 | 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 | 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) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 76 |
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 |
Brazil |
Canada |
Chile |
Colombia |
European Union |
Israel |
Korea, Democratic People's 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 |
LVLS o el ultimo seguimiento telefónico, 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 | 2 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 7 |