Extension Phase of the Multi-National Open-Label Study to Evaluate the Safety, Tolerability and Efficacy of Tocilizumab in Patients with Active Rheumatoid Arthritis on Background Non-biologic DMARDs who have an Inadequate Response to Current Non-biologic DMARD and/or Anti-TNF Therapy - extension to study MA21573

Conditions: Adult patients with moderate to severe active rheumatoid arthritis (RA) who are inadequate responders to disease-modifying antirheumatic drugs (DMARDs) or anti-TNF therapies.
MedDRA version: 9.1Level: LLTClassification code 10039073Term: Rheumatoid arthritis

Registration Number: EUCTR2008-006924-68-IT

Lead Sponsor: F. Hoffmann-La Roche

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 1200

Inclusion Criteria

1. Completed the 24-week MA21573 core study, had at least a moderate response (EULAR definition criteria) and no AEs, SAEs or conditions that lead to unacceptable risk of continued treatment. Patients should be scheduled to receive the first tocilizumab (TCZ) infusion in MA22460 between 4 and 16 weeks after the last iv infusion in the core study. 2. Willing to give written informed consent for participation in the extension study 3. Able and willing to comply with the requirements of the extension study protocol
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

1. Functional class IV as defined by the ACR Classification of Functional Status in RA (largely or wholly incapacitated with patient bedridden or confined to wheel chair, permitting little or no self-care). If female and of child-bearing potential, the patient must have a negative urine pregnancy test at day 1 2. Serum creatinine > 142 micromol/L (1.6 mg/dL) in female patients and > 168 micromol/L (1.9 mg/dL) in male patients and no active renal disease 3. ALT (SGPT) or AST (SGOT) > 3 ULN (If initial yield ALT or AST >3 ULN, a second sample may be taken and tested) 4. Platelet count < 100 x 109/L (100,000/mm3) 5. Hemoglobin < 85 g/L (8.5 g/dL; 5.3 mmol/L) 6. WBC < 1.0 x 109/L (1000/mm3), ANC < 1 x 109/L (1000/mm3) 7. Absolute lymphocyte count < 0.5 x 109/L (500/mm3) 8. Known positive hepatitis B surface antigen or hepatitis C antibody 9. Total bilirubin > ULN (If initial sample yields bilirubin > ULN, a second sample may be taken and tested) 10. Triglycerides > 10 mmol/L (> 900 mg/dL) at inclusion in extension study General medical 11.Treatment with any investigational agent since the last administration of study drug in the MA21573 study 12. Previous treatment with any cell depleting therapies, including investigational agents (e.g. CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19 and anti-CD20) since the last administration of study drug in the MA21573 study 13. Treatment with iv gamma globulin, plasmapheresis or Prosorba? column since the last administration of study drug in the MA21573 study 14. Treatment with an anti-TNF or anti-IL1 agent, or a T-cell co-stimulation modulator or any biologic or participation in any research study since the last administration of study drug in the MA21573 study 15. Parenteral, intramuscular or intra-articular corticosteroids within 6 weeks since the last administration of study drug in the MA21573 study 16. Immunization with a live/attenuated vaccine since the last administration of study drug in the MA21573 study 17. Any previous treatment with alkylating agents such as cyclophosphamide or chlorambucil, or with total lymphoid irradiation since the last administration of study drug in the MA21573 study 18. Females of child-bearing potential who are not using a reliable means of contraception, e.g. physical barrier (patient and partner), contraceptive pill or patch, spermicide and barrier, or intrauterine device (IUD) 19. Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus) or GI disease 20. Uncontrolled disease states, such as asthma, psoriasis or inflammatory bowel disease where flares are commonly treated with oral or parenteral corticosteroids 21. Current liver disease as determined by the investigator. Patients with prior history of ALT (SGPT) elevation are not excluded 22. Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections (including but not limited to tuberculosis and atypical mycobacterial disease, hepatitis B and C, and herpes zoster, but excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization or treatment with IV antibiotics or oral antibiotics 23. History of or currently active primary or secondary immunodeficiency
Et al.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the long-term safety and tolerability of tocilizumab (TCZ) monotherapy or in combination with non-biologic DMARDs in patients with RA;Secondary Objective: To assess the long-term efficacy of TCZ monotherapy or its combination with non-biologic DMARDs;Primary end point(s): Incidence of AEs and SAEs of TCZ monotherapy or combined treatment with TCZ and one or more of the background non-biologic DMARD approved for RA in patients with moderate to severe active RA.

Secondary Outcome Measures