Randomized placebo-controlled study to evaluate the safety and efficacy of adding tocilizumab (TCZ) to methotrexate (MTX) versus switching to TCZ (placebo controlled), with possible addition of other disease-modifying anti-rheumatic drugs (DMARDs), in patients with active rheumatoid arthritis who have inadequately responded to prior MTX treatment.

Conditions: Rheumatoid Arthritis

Registration Number: EUCTR2008-001847-20-EE

Lead Sponsor: F Hoffmann-La Roche Ltd.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 470

Inclusion Criteria

1.Male or non-pregnant, non-nursing female
2.= 18 years of age
3.Body weight = 150 kg
4.Patients currently experiencing active moderate to severe RA (DAS28 > 4.4) according to the revised 1987 ACR criteria for the diagnosis of RA at baseline. At screening the DAS28 must be equal or greater than 4.0 (DAS28 =4.0).
5.Patients currently receiving MTX (oral or parenteral) for at least 12 weeks and who have received MTX at a stable dose of at least 15 mg/week for at least 6 weeks prior to treatment (day 1), with the following exception: 10 mg instead of 15 mg is acceptable in patients with a body weight < 50 kg, low grade toxicity to MTX (such as nausea), or calculated glomerular filtration rate (or creatinine clearance) < 60 mL/min.
Patients with a history of parenteral (subcutaneous or intramuscular) MTX prior to baseline are eligible. However, prior to treatment (day 1) these patients must have been on a stable dose of oral MTX of at least 15 mg/week for at least 6 weeks.
6.If patients are receiving an oral corticosteroid, the dose must have been = 10 mg/day prednisone (or equivalent) and stable for at least 25 out of 28 days prior to treatment (day 1)
7.Patients receiving treatment on an outpatient basis
8.Patients able and willing to give written informed consent and comply with the requirements of the 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

Disease
1.Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization
2.Rheumatic autoimmune disease other than RA, including systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), scleroderma, polymyositis, or significant systemic involvement secondary to RA (e.g. vasculitis, pulmonary fibrosis or Felty’s syndrome). Patient with interstitial pulmonary fibrosis and still able to tolerate MTX therapy are permitted. Sjögren’s Syndrome with RA is permitted
3.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)
4.Prior history of or current inflammatory joint disease other than RA (e.g. gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy, Lyme disease)
Drug-specific
5.Treatment with any investigational agent within 4 weeks (or 5 half-lives of investigational agent, whichever is longer) before screening
6.Previous treatment with TCZ
7.Previous treatment with any biologic drug that is used in the treatment of RA
8.Any previous treatment with alkylating agents, such as cyclophosphamide or chlorambucil, or with total lymphoid irradiation
9.Treatment with IV gamma globulin, plasmapheresis or Prosorba® column within 6 months before baseline
10.Intraarticular or parenteral corticosteroids within 6 weeks prior to baseline
11.Immunization with a live/attenuated vaccine within 4 weeks prior to baseline
Laboratory analyses (at screening)
12.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
13.ALT (SGPT) or AST (SGOT) > 1.5 x ULN
14. Platelet count < 100 x 10e9/L (100,000/mm3)
15.Hemoglobin < 85 g/L (8.5 g/dL; 5.3 mmol/L)
16.WBC count < 1.0 x 10e9/L (1000/mm3), absolute neutrophil count < 1.0 x 10e9/L (1000/mm3). Patients enrolled prior to amendment based on a lower ANC threshold may continue to stay in the study, if deemed appropriate by the investigator.
17.Absolute lymphocyte count < 0.5 x 109/L (500/mm3)
18.Positive hepatitis B surface antigen or hepatitis C antibody
19.Total bilirubin > ULN
20.Triglycerides > 10 mmol/L (> 900 mg/dL) at screening (non-fasted or fasting)