Rheumatoid arthritis
Conditions
Interventions
Trade Name: Mabthera
Product Name: Mabthera
Product Code: Rituximab
Pharmaceutical Form: Concentrate for solution for infusion
Pharmaceu
Sponsors
University of Leeds
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients with rheumatoid arthritis for at least 6 months, diagnosed according to the revised 1987 ACR criteria for the classification of rheumatoid arthritis 2. Patients who have experienced an inadequate response to previous or current treatment with etanercept, infliximab or adalimumab because of toxicity or inadequate efficiency or be unsuitable for treatment with anti-TNF therapy because of contra-indication 3. Patients must have received methotrexate at a dose of 10-25mg/week (po or parenteral) at a stable dose for 4 weeks prior to screening 4. DAS28 >5.1 5. Age 18-80 years 6. Corticosteroids (=10mg/day prednisolone or equivalent) permitted if stable for at least 4 weeks prior to screening and NSAIDs permitted if stable for at least 2 weeks prior to screening. 7. Patients of reproductive potential (males and females) using a reliable means of contraception (eg contraceptive pill, IUD, physical barrier) 8. Presence of erosive joint disease of at least 1 joint on x-ray ( except if DIP joint of the hand) 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) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Bone/joint surgery within 8 weeks prior to therapy or joint surgery planned within 24 weeks of therapy 2. Rheumatic autoimmune disease other than RA or significant systemic involvement secondary to RA 3. History of, or current, inflammatory joint disease other than RA or other systemic rheumatic disorder 4. Concurrent treatment with any DMARD (apart from methotrexate) or any anti-TNF therapy or other biologic agent 5. Treatment with any investigational agent within 4 weeks of screening or 5 half lives of the investigational drug 6. Previous treatment with any cell depleting therapy therapies. 7. Intra-articular or parenteral steroids within 4 weeks prior to therapy (except for joints undergoing ultrasound or MRI where IA steroids are not permitted within 12 weeks prior to therapy or assessment) 8. Previous treatment with Rituximab 9. History of severe allergic or anaphylactic reactions to humanised or murine monoclonal antibodies. 10. Evidence of significant uncontrolled concomitant diseases. 11. Known active bacterial, viral, fungal mycobacterial infection or any episode of infection requiring hospitalisation or treatment with iv antibiotics within 4 weeks of therapy or oral antibiotics within 2 weeks of therapy 12. History of, or currently active, primary or secondary immunodeficiency 13. History of solid organ malignancy in the past 5 years (excluding basal cell or squamous cell carcinomas of the skin which have been excised and cured) 14. Pregnant women or breastfeeding mothers 15. History of alcohol, drug or chemical abuse within 6 months prior to screening 16. Neuropathies or neurovasculopathies which might interfere with pain evaluation 17. Significant laboratory abnormalities.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess efficacy of extra dose of rituximab in patients selected on the basis of B cell analysis with resistant RA compared with placebo dose, following standard rituximab therapy. ; Secondary Objective: i) to study the efficacy and safety of an extended course of rituximab in patients with resistant RA who have B CELLS following rituximab therapy ii) to study the utility of B CELLS as a marker to indicate whether patients will benefit from extended treatment with rituximab iii) to study the effects of rituximab on underlying structural joint disease and B cell profiles in the peripheral circulation ; Primary end point(s): Proportion of patients with B CELLS receiving three doses of rituximab (Group A) vs proportion of patients with B CELLS who receive standard dose (two doses) rituximab (Group B) achieving ACR20 response at Week 28. | — |
Countries
United Kingdom
Outcome results
None listed