Estudio fase III, multicéntrico, randomizado, controlado, doble ciego, con grupos de tratamiento paralelos, para evaluar la seguridad y eficacia de Rituximab en combinación con metotrexato (MTX), en comparación con metotrexato sólo en pacientes con artritis reumatoide activa no tratados previamente con metotrexato”

Conditions: Artritis reumatoide / Rheumatoid arthritis

Registration Number: EUCTR2005-002395-15-ES

Lead Sponsor: F. Hoffmann-La Roche Ltd.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 853

Inclusion Criteria

1.Capacidad y voluntad de otorgar el consentimiento informado por escrito y de cumplir los requisitos del protocolo del estudio.
2.Pacientes con artritis reumatoide de 8 semanas de duración como mínimo y de 4 años como máximo, diagnosticada de acuerdo con los criterios del American College of Rheumatology (ACR) revisados en 1987, para la clasificación de la artritis reumatoide.
3.Pacientes que no han sido tratados previamente con metotrexato y que se consideren candidatos a recibir este tratamiento.
4.Presentar un recuento de articulaciones inflamadas (SJC) ? 8 (recuento de 66 articulaciones) y de articulaciones dolorosas (TJC) ? 8 (recuento de 68 articulaciones) en las evaluaciones de selección y basal.
5.Concentración de PCR ? 1,2 mg/dl (12 mg/l) en la evaluación de selección
6.Edad 18-80 años.
7.Se permite el tratamiento con glucocorticoides (? 10 mg de prednisolona al día o equivalente) si la dosis se ha mantenido estable como mínimo durante las 4 semanas previas a la evaluación basal.
8.Se permite el uso de AINEs si la dosis se ha mantenido estable como mínimo durante las 2 semanas previas a la evaluación basal.
9.Los pacientes en edad fértil (tanto varones como mujeres) deben utilizar un método anticonceptivo eficaz (p. ej. anticonceptivos hormonales, parche anticonceptivo, dispositivo intrauterino, métodos de barrera) durante su participación en el estudio.
10.Los pacientes deben estar dispuestos a recibir folato por vía oral.
11.(Sólo para los pacientes con FR negativo). Los pacientes deben presentar indicios radiográficos de erosión definida, como mínimo, en una articulación, que sea atribuible a AR.
12. Pacientes que van a recibir o que están recibiendo actualmente tratamiento en régimen ambulatorio.

Are the trial subjects under 18?
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Rheumatic autoimmune disease other than RA, or significant systemic involvement secondary to RA (including but not limited to vasculitis, pulmonary fibrosis or Felty’s syndrome). Secondary Sjögren’s syndrome or secondary limited cutaneous vasculitis with RA is permitted.
2. Functional class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis.
3. History of, or current, inflammatory joint disease other than RA (including, but not limited to, gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy, Lyme disease) or other systemic autoimmune disorder (including, but not limited to, systemic lupus erythematosus, inflammatory bowel disease, scleroderma, inflammatory myopathy, mixed connective tissue disease or any overlap syndrome).
4. Diagnosis of juvenile idiopathic arthritis (JIA) or juvenile rheumatoid arthritis (JRA) and/or RA before age 16.
5. Any surgical procedure, including bone/joint surgery/synovectomy (including joint fusion or replacement) within 12 weeks prior to baseline or planned during the study.
6. Lack of peripheral venous access.
7. Pregnancy or breast feeding.
8. Significant and/or uncontrolled cardiac or pulmonary disease (including obstructive pulmonary disease).
9. Evidence of significant concomitant disease, including but not limited to, nervous system, renal, hepatic, endocrine or gastrointestinal disorders which, in the investigator’s opinion, would preclude patient participation.
10. Primary or secondary immunodeficiency (history of, or currently active), including known history of HIV infection.
11. Known active infection of any kind (excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization or treatment with i.v. anti-infectives within 4 weeks of baseline or completion of oral antiinfectives within 2 weeks prior to baseline.
12. History of deep space/tissue infection (e.g. fasciitis, abscess, osteomyelitis) within 52 weeks prior to baseline.
13. History of serious recurrent or chronic infection (for screening for a chest infection a chest radiograph will be performed at screening if not performed within 12 weeks prior to screening).
14. History of cancer, including solid tumors, hematologic malignancies and carcinoma in situ (except basal cell and squamous cell carcinoma of the skin that have been excised and cured).
15. Any neurological (congenital or acquired), vascular or systemic disorder which could affect any of the efficacy assessments, in particular, joint pain and swelling (e.g. Parkinsons disease, cerebral palsy, diabetic neuropathy).
16. Currently active alcohol or drug abuse or history of alcohol or drug abuse within 24 weeks prior to baseline.
17.History of a severe allergic or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of rituximab or to murine proteins.
18. Previous treatment with any approved or investigational biologic agent for RA.
19. Previous treatment with an anti-alpha 4 integrin antibody or co-stimulation modulator.
20. Concurrent treatment with any biologic agent or DMARD other than MTX. Treatment must be discontinued 14 days prior to baseline, except for the following: azathioprine for = 28 days; leflunomide for = 8 weeks (or = 14 days after 11 days of standard cholestyramine or activated charcoal washout).
21. Previous treatment with any cell depleting therapies, including investigational agents (e.g. CAMPATH, anti-CD4, anti-CD5, anti-CD3,