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. - this is an extension study to MA21573

Conditions: Rheumatoid arthritis
MedDRA version: 9.1Level: LLTClassification code 10039073Term: Rheumatoid arthritis

Registration Number: EUCTR2008-006924-68-CZ

Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 1200

Inclusion Criteria

To be eligible for this trial, patients must meet all of the following criteria:
1. Completed the 24-week MA21573 core study, had at least a moderate response (EULAR definition criteria Appendix 7) 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 6 weeks after the last TCZ 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
4. If female and of child-bearing potential, the patient must have a negative urine pregnancy test at Day 1 before the infusion takes place.

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

Patients with any of the following criteria will not be eligible to participate in the study:
Disease
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)

Laboratory analyses (at transition from core study)

Lab values from the Week 20 visit of the core study are to be used for the determination of the patient’s eligibility for MA22460. If the patient is not eligible based on Week 20 laboratory values, the sample from Week 24 can be used. Therefore a delay of the study infusion will be permitted until the laboratory results are available.
Study drug administration can occur on the week 24 visit which is then Day 1 of this study. In case that the drug administration needs to be delayed for any other reasons, and study drug administration will not occur at the Week 24 visit, it can be delayed by a maximum of 2 weeks. Day 1 is defined as the day of the first study drug administration under MA22460.

2. Serum creatinine > 142 µmol/L (1.6 mg/dL) in female patients and > 168 µmol/L (1.9 mg/dL) in male patients and no active renal disease
3. ALT (SGPT) or AST (SGOT) > 3 ULN
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
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. Immunization with a live/attenuated vaccine since the last administration of study drug in the MA21573 study
16. 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
17. 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) and who do not agree to continue using reliable contraception during the study period and 3 months after treatment.
18. Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus) or GI disease
19. Uncontrolled disease states, such as asthma, psoriasis or inflammatory bowel disease where flares are commonly treated with oral or parenteral corticosteroids
20. Current liver disease as determined by the investigator. Patients with prior history of ALT (SGPT) elevation are not excluded
21. Known active current

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 TCZ monotherapy or in combination with non-biologic DMARDs in patients with RA and at least a moderate response to TCZ after 24 weeks of treatment.;Secondary Objective: To assess the long-term efficacy of TCZ monotherapy or its combination with non-biologic DMARDs in patients with RA and at least a moderate response to TCZ after 24 weeks of treatment.;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 DMARDs approved for RA in patients with moderate to severe active RA.

Secondary Outcome Measures