Men and women > 18 years of age with RA who are currently experiencing an inadequate clinical response to a stable dose of non-biologic DMARDs (at least 12 weeks) and with MRI documented synovitis of dominant hand.
Conditions
Interventions
Trade Name: RoActemra
Pharmaceutical Form: Concentrate for solution for infusion
Sponsors
Roche Farmacêutica Química, Lda.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Male or non-pregnant, non-nursing female • = 18 years of age • Diagnosis of RA of =6 months duration and moderate to severe disease activity defined as a DAS28 > 3.2 at screening • Synovitis in the wrist of the dominant hand (defined as the presence of swollen and tender wrist joint and confirmed by MRI screening) • Receiving treatment on an outpatient basis • Patients on = 1 non-biologic DMARDs at a stable dose for a period = 12 weeks prior to treatment (baseline) • If patients are receiving an oral corticosteroid, the dose must have been stable for at least 25 out of 28 days prior to treatment (baseline) • 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
Exclusion criteria: • Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following enrollment • 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) • 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) • Prior history of or current inflammatory joint disease other than RA (e.g. gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy, Lyme disease) • Patient with interstitial pulmonary fibrosis and still able to tolerate MTX therapy are allowed • Sjögren’s Syndrome with RA is allowed • Treatment with any investigational agent or with anakinra, calcineurin inhibitors (e.g. tacrolimus or cyclosporine), mycophenolate mofetil or mycophenolic acid sodium within 4 weeks (or 5 half-lives of investigational agent, whichever is longer) before screening • Previous treatment with any cell-depleting therapies, including investigational agents (e.g. CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19 and anti-CD20) • Previous treatment with abatacept • Previous treatment with anti-TNF • Treatment with leflunomide in combination with MTX • Treatment with IV gammaglobulin, plasmapheresis or Prosorba® column within 6 months before baseline • Intraarticular or parenteral corticosteroids within 6 weeks prior to baseline • Intraarticular corticosteroids on dominant hand to be imaged within 6 months prior to baseline • Immunization with a live/attenuated vaccine within 4 weeks prior to baseline • 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) • Any previous treatment with alkylating agents, such as cyclophosphamide or chlorambucil, or with total lymphoid irradiation • Any previous treatment with a biologic agent for RA
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of TCZ on synovitis as measured by MRI compared to placebo at 12 weeks after initiation of therapy in patients with RA;Secondary Objective: Evaluate the changes in individual components and in global OMERACT-RAMRIS score as well as in DCE-MRI EER at 12 and 24 weeks after initiation of TCZ compared to placebo Evaluate the positive and negative predictive value of MRI response at 12 weeks, as an estimator of clinical response, assessed by DAS28, at 24 weeks of treatment with TCZ Evaluate the positive and negative predictive value of MRI response at 12 weeks, as an estimator of MRI changes at 24 weeks of treatment with TCZ Evaluate the effect of TCZ on global DAS28 score and its individual components (swollen and tender joint count, VAS and ESR) and CRP at 24 weeks Evaluate the effect of TCZ on disability measured by HAQ-DI at 24 weeks Assess the safety and tolerability of tocilizumab in combination with non-biologic DMARDs Investigate the potential of steroid hormone status to predict clinical response to tocilizumab Assess the impact of IL-6 blockade upon endogenous steroid hormone secretion and neuropeptide Y. ;Primary end point(s): • Change in MRI-assessed synovial volume in the wrist and/or 2nd to 5th MCP joints of the dominant hand at 12 weeks after treatment initiation | — |
Countries
Portugal
Outcome results
None listed