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. - ACT-RAY

Conditions: Rheumatoid Arthritis

Registration Number: EUCTR2008-001847-20-NL

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)
5.Patients currently receiving MTX 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 exceptions. 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 a calculated glomerular filtration rate (or creatinine clearance) < 60 ml/min.
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 (an exception to this criterion may be granted for single-dose exposure upon application to the sponsor on a case by case basis)
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 ULN (If initial sample yields ALT [SGPT] or AST [SGOT] > 1.5 ULN, a second sample may be taken and tested during the screening period)
14.Platelet count < 100 x 109/L (100,000/mm3)
15.Hemoglobin < 85 g/L (8.5 g/dL; 5.3 mmol/L)
16.WBC count < 1.0 x 109/L (1000/mm3), absolute neutrophil count < 0.5 x 109/L (500/mm3)
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 (If initial sample yields bilirubin > ULN, a second sample may be taken and tested during the screening period)
20.Triglycerides > 10 mmol/L (> 900 mg/dL) at screening (non-fasted)

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare the effect of TCZ in combination with MTX versus TCZ alone (i.e. receiving placebo matching MTX) on DAS28 remission at week 24 in MTX inadequate responders with moderate to severe active RA.;Secondary Objective: To compare the effect of TCZ in combination with MTX (with or without an additional DMARD) versus TCZ alone (with or without an additional DMARD) on progression of structural damage at week 52 in MTX inadequate responders with moderate to severe active RA.<br><br>To compare the safety of TCZ in combination with MTX (with or without an additional DMARD) versus TCZ alone (with or without an additional DMARD) with regard to adverse events and laboratory assessments.<br><br>To assess the efficacy after 2 years of treatment with TCZ in combination with MTX (with or without an additional DMARD) versus TCZ alone (with or without an additional DMARD).<br>;Primary end point(s): •DAS28 remission rate (RR) at week 24

Secondary Outcome Measures