Artritis reumatoide Rheumatoid Arthritis MedDRA version: 9.1 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis
Conditions
Interventions
Trade Name: MABTHERA 500 mg concentrado para solución para perfusión
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: RITUXIMAB
CAS Number: 174722-31-7
Current Sponsor c
Sponsors
F Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Able and willing to give written informed consent and comply with the requirements of the study protocol 2. Age 18 - 65 years 3. Rheumatoid arthritis diagnosed according to the American Rheumatism Association 1987 revised criteria for the classification of RA 4. Functional Status I-III according to the 1991 ACR revised criteria for the classification of global functional status in RA 5. Swollen joint count (SJC) ? 4 (28 joint count) and tender joint count (TJC) ? 4 (28 joint count) at screening and baseline 6. DAS28-ESR > 3.2 at screening 7. CRP ? 0.6 mg/dL using a high-sensitivity assay and/or ESR ? 30 mm/h at screening 8. RF positive and/or anti-CCP positive 9. Must have an inadequate response to MTX and have been receiving and tolerating this at a dose of 7.5 - 25 mg weekly (p.o. or parenterally) for at least 12 weeks, with the last 4 weeks prior to screening at a stable dose 10. Patients may have failed (through lack of efficacy or tolerability) up to 1 approved anti-TNF agent (infliximab, etanercept or adalimumab), and up to 6 non-biologic disease-modifying antirheumatic drugs (DMARDs), including MTX. The following non-biologic DMARDS are considered as a single agent for this count: - All forms of gold - Leflunomide - Chloroquine and hydroxychloroquine - Dapsone or azathioprine - Sulfasalazine and mesalazine - Cyclosporine A 11. All DMARDs other than methotrexate must be withdrawn at least 4 weeks prior to randomization except as follows: 2 weeks for etanercept, 8 weeks for infliximab, and 12 weeks for leflunomide (8 weeks if cholestyramine or activated charcoal is used to accelerate leflunomide withdrawal) 12. Oral corticosteroids (? 10 mg/day prednisolone or equivalent) and NSAIDs (up to the maximum recommended dose, including COX-2 inhibitors) are permitted if the dose has been stable for at least 4 weeks prior to baseline. No patient may be using more than one NSAID simultaneously (with the exception of low-dose aspirin for cardioprotection) 13. Patients must be willing to receive oral folic acid at a stable dose of at least 5 mg/week 14. Current treatment for RA on an outpatient basis 15. Female patients of child bearing potential may participate in this study if using reliable means of contraception for the duration of the study, and for up to 3 months after their last dose of tocilizumab, and up to 1 year after their last dose of rituximab, or until their peripheral CD20+ B cells have repleted 16. Female patients of childbearing age must have a negative serum pregnancy test at screening 17. Male patients with female partners of child bearing potential may participate in this study only if the patient or the partner are using reliable means of contraception for the duration of the study, and for up to 3 months after their last dose of tocilizumab, and up to 1 year after their last dose of rituximab, or until their peripheral CD20+ B cells have repleted. Are the trial subjects under 18? no 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) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Functional Status IV - 1991 ACR criteria 2. Rheumatic AI disease other than RA (e.g SLE, Mixed Connective Tissue Disease, scleroderma/variants, polymyositis) or significant systemic involvement secondary to RA (e.g. vasculitis, pulmonary fibrosis, Felty?s syndrome); Secondary Sjögren?s and limited cutaneous vasculitis or nodulosis with RA allowed 3. History of/current inflammatory joint disease other than RA (e.g: gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy, Lyme disease, pseudogout, arthropathy of inflammatory bowel disease) 4. Diagnosis of JIA/JRA and/or RA before age 16 5. Significant +/or uncontrolled concomitant disease e.g cardiovascular disease, nervous system, pulmonary, renal, hepatic, endocrine or GI disorders (including previous complicated diverticulitis) which, in Investigator?s opinion, would preclude participation or impact benefit-risk 6. Any condition or general state of health which, in Investigator?s opinion, would preclude participation 7. Significant cardiac disease (NYHA Class III/IV), known severe COPD (FEV1 150 kg or BMI > 35 22. Previous treatment with any biological agent for RA other than infliximab, etanercept or adalimumab 23. Previous treatment with tocilizumab or rituximab 24. Previous/concurrent treatment with anti-alpha 4 integrin inhibitors (e.g. natalizumab) 25. Previous/concurrent treatment with any cell depleting therapies, including investigational agents (e.g. CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19, anti-CD11a, anti-CD22, anti-BLys/BAFF, anti-CD20) 26. Treatment with intravenous gamma globulin, plasmapheresis or Prosorba® column within 6 months of baseline 27. Any prev
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the safety, tolerability and efficacy of rituximab in combination with tocilizumab in patients with active RA despite a stable dose of methotrexate.;Secondary Objective: To investigate the pharmacokinetics of rituximab and tocilizumab when given in combination to rheumatoid arthritis patients. To explore the effect of the combination of rituxmab and tocilizumab upon exploratory pharmacodynamic endpoints in rheumatoid arthritis.;Primary end point(s): Proportion of patients with a low DAS (DAS </= 3.2) at week 16 using DAS-ESR. | — |
Countries
France, Germany, Greece, Netherlands, Spain, United Kingdom
Outcome results
None listed