E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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. |
|
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 |
|
E.2.2 | Secondary objectives of the trial |
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.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
|
|
E.4 | Principal 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
|
|
E.5 End points |
E.5.1 | 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 |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
|
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 11 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
Date of last visit of the last patient (LPLV; week 24) |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |