E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderately to Severely Active Psoriatic Arthritis |
Artritis psoriásica de moderada a intensamente activa |
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E.1.1.1 | Medical condition in easily understood language |
Psoriatic Arthritis |
Artritis Psoriásica |
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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 | LLT |
E.1.2 | Classification code | 10037160 |
E.1.2 | Term | Psoriatic arthritis |
E.1.2 | System Organ Class | 100000018188 |
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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 |
Primary Objective 1. To compare the efficacy of ABT-494 15 mg QD and 30 mg QD versus placebo and versus adalimumab (ADA) for the treatment of signs and symptoms of PsA in subjects with moderately to severely active PsA who have an inadequate response or intolerance to 1 or more non-biologic DMARD (DMARD-IR). Secondary Objective 2. To compare the efficacy of ABT-494 15 mg QD and 30 mg QD versus placebo for the prevention of structural progression in subjects with moderately to severely active PsA who have an inadequate response or intolerance to 1 or more non-biologic DMARD (DMARD-IR). 3. To compare the safety and tolerability of ABT-494 15 mg QD and 30 mg QD versus placebo and versus adalimumab in subjects with moderately to severely active PsA who have an inadequate response or intolerance to 1 or more non-biologic DMARD (DMARD-IR). |
Objetivo Primario 1. Comparar la eficacia de ABT-494 15 mg una vez al día y 30 mg una vez al día frente a placebo y frente a adalimumab (ADA) para el tratamiento de los signos y síntomas de APs en pacientes con APs de moderada a intensamente activa con una historia previa de respuesta inadecuada o intolerancia a al menos un FAME no biológico (RI-FAME). Objetivo Secundario 2. Comparar la eficacia de ABT-494 15 mg una vez al día y 30 mg una vez al día frente a placebo para la prevención de la progresión estructural en pacientes con APs de moderada a intensamente activa con una historia previa de respuesta inadecuada o intolerancia a al menos un FAME no biológico (RI-FAME). 3. Comparar la seguridad y tolerabilidad de ABT-494 15 mg una vez al día y 30 mg una vez al día frente a placebo y frente a adalimumab en pacientes con APs de moderada a intensamente activa con una historia previa de respuesta inadecuada o intolerancia a al menos un FAME no biológico (RI-FAME) |
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E.2.2 | Secondary objectives of the trial |
To evaluate the long-term safety, tolerability and efficacy of ABT-494 15 mg QD and 30 mg QD in subjects with PsA who have completed Period 1. |
Evaluar la seguridad, tolerabilidad y eficacia a largo plazo de ABT-494 15 mg una vez al día y 30 mg una vez al día en pacientes con APs que finalicen el Período 1. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female, at least 18 years of age 2. Diagnosed with psoriatic arthritis with symptom onset at least 6 months prior to the Screening Visit and fulfillment of the Classification Criteria for PsA (CASPAR) 3. Subject has active disease at Baseline defined as ≥ 3 tender joints (based on 68 joint counts) and ≥ 3 swollen joints (based on 66 joint counts) at Screening and Baseline Visits 4. Diagnosis of active plaque psoriasis or documented history of plaque psoriasis 5. Subject is on current treatment with ≤ 2 nonbiologic DMARDs 6. Subject has had an inadequate response to previous or current treatment with at least 1 non-biologic DMARD (MTX, SSZ, LEF, apremilast, bucillamine, or iguratimod), or subject has an intolerance to or contraindication for DMARDs 7. Presence of either at Screening: • ≥ 1 erosion on x-ray • hs-CRP > laboratory-defined upper limit of normal (ULN) |
1. Varones o mujeres adultos, que hayan cumplido 18 años de edad 2.Diagnóstico clínico de APs con inicio de los síntomas al menos 6 meses antes de la visita de Selección, y que cumplan los criterios de clasificación de la APs (CASPAR). 3. Enfermedad activa en el momento basal, definida como presencia de 3 o más articulaciones doloridas (sobre recuentos de 68 articulaciones) y 3 o más articulaciones con tumefacción (sobre recuentos de 66 articulaciones) en las visitas de Selección y Basal. 4. Diagnóstico de psoriasis en placas activa o historia documentada de psoriasis en placas. 5. El paciente está recibiendo tratamiento concomitante ≤ 2 FAMEs no biológicos 6. Los pacientes deben haber tenido una respuesta inadecuada al tratamiento previo o concomitante con al menos un FAME no biológico (MTX, SSZ, LEF, apremilast, bucillamina o iguratimod) o presentar intolerancia o contraindicación para el uso de FAME 7. Observación en la Selección de alguno de los elementos siguientes: • Una o más erosiones detectables radiográficamente • hs-CRP > límite superior de la normalidad (LSN) |
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E.4 | Principal exclusion criteria |
1. Prior exposure to any Janus Kinase (JAK) inhibitor 2. Current treatment with > 2 non-biologic DMARDs; or use of DMARDs other than MTX, SSZ, LEF, apremilast, HCQ, bucillamine, or iguratimod; or use of MTX in combination with LEF. |
1. Exposición anterior a cualquier inhibidor de las janocinasas (JAK) 2. Tratamiento actual con más de 2 FAME no biológicos o uso de otros FAME distintos de MTX, SSZ, LEF, aprernilast, HCQ, bucillamina o iguratimod, o uso de MTX en combinación con LEF |
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E.5 End points |
E.5.1 | Primary end point(s) |
The proportion of subjects achieving ACR20 response |
The proportion of subjects achieving ACR20 response |
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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. Change from baseline in HAQ-DI 2. Proportion of subjects achieving a static Investigator Global Assessment (sIGA) of Psoriasis of 0 or 1 and at least a 2-point improvement from baseline 3. Psoriasis Area Severity Index (PASI) 75 response (for subjects with ≥ 3% BSA psoriasis at baseline) 4. Change from baseline in modified PsA Sharp/van der Heijde Score (SHS) 5. Proportion of subjects achieving Minimal Disease Activity (MDA) 6. Change from baseline in Leeds Enthesitis Index (LEI) 7. Change from baseline in Leeds Dactylitis Index (LDI) 8. ACR 20 response rate (non-inferiority of ABT-494 vs adalimumab); 9. Change from baseline in SF-36 PCS 10. ACR 20 response rate (superiority of ABT-494 vs adalimumab); 11. Change from baseline in Patient's Assessment of Pain NRS (superiority of ABT-494 vs. adalimumab); 12. Change from baseline in HAQ-DI (superiority of ABT-494 vs. adalimumab); 13. Change from baseline in FACIT-Fatigue Questionnaire; and Change from baseline in Self-Assessment of Psoriasis Symptoms (SAPS) Questionnaire 14. ACR 50/70 response rate 15. ACR 20 response rate |
1. Variación del HAQ-DI desde el momento basal 2. Proporción de pacientes que obtienen una evaluación global del investigador estable (EGis) de la psoriasis de 0 o 1 y una mejoría de al menos 2 puntos desde el momento basal 3. Respuesta de 75 en el índice de intensidad y área de la psoriasis (PASI) (para los pacientes con psoriasis que afecta a ≥ 3% SC en la valoración basal) 4. Variación de la SHS desde el momento basal 5. Porcentaje de pacientes que alcanzan MDA 6. Variación de la LEI desde el momento basal 7. Variación de la LDI desde el momento basal 8. Tasa de respuesta ACR 20 (no inferioridad de ABT-494 frente a adalimumab); 9. Variación desde el momento basal de la puntuación SF-36 PCS 10. Tasa de respuesta ACR 20 (superioridad de ABT-494 frente a adalimumab). 11. Variación respecto al valor basal de la evaluación que hace el paciente del dolor NRS (superioridad de ABT-494 frente a adalimumab). 12. Variación respecto al valor basal del HAQ-DI (superioridad de ABT-494 frente a adalimumab). 13. Variación respecto al valor basal del Cuestionario FACIT-Cansancio; y variación respecto al valor basal del Cuestionario de autoevaluación de los síntomas de psoriasis (SAPS) 14. Respuesta ACR 50/70 15. Respuesta ACR20 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Week 12 2. Week 16 3. Week 16 4. Week 24 5. Week 24 6. Week 24 7. Week 24 8. Week 12 9. Week 12 10. Week 12 11. Week 12 12. Week 12 13. Week 12; 16 14. Week 12 15. Week 2 |
1. Semana 12 2. Semana 16 3. Semana 16 4. Semana 24 5. Semana 24 6. Semana 24 7. Semana 24 8. Semana 12 9. Semana 12 10. Semana 12 11. Semana 12 12. Semana 12 13. Semana 12; 16 14. Semana 12 15. Semana 2 |
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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 | Yes |
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) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 5 |
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 | 115 |
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 |
China |
Colombia |
Egypt |
Hong Kong |
Israel |
Japan |
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
|
Last subjects' last visit or the actual date of follow-up contact, whichever is later. |
Último paciente, última visita o la fecha del último contacto de seguimiento, lo que ocurra mas 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 | |
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 |