Moderate to severe active rheumatoid arthritis (RA), who are inadequate responders to DMARDs. MedDRA version: 12.0 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis
Conditions
Interventions
Product Name: Tocilizumab
Product Code: Ro487-7533
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: RoActemra
CAS Number: 375823-41-9
Current Sponsor code: Ro487-7533
Co
Sponsors
ROCHE
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Men and women ≥ 18 years of age with a diagnosis of RA of ≥ 6 months duration, who are currently experiencing moderate to severe active RA (DAS28 > 3.2) and an inadequate clinical response to a stable dose of non-biologic DMARD therapy - Inclusion criteria 1.Male or non-pregnant, non-nursing female 2.Age ≥ 18 years 3.Patients with diagnosis of RA of ≥ 6 months duration 4.Patients currently experiencing moderate to severe active RA (DAS28 > 3.2) 5.Patients with: SJ ≥ 6; TJ ≥ 8 6.Patients receiving treatment on an outpatient basis 7.Patients with inadequate clinical response to a stable dose of non-biologic DMARD for at least 2 months 8.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) 9.Subjects 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: Disease-specific criteria: 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), systemic sclerosis, 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 can be included in the study. Patients with secondary Sj?gren?s Syndrome associated with RA can be included in the study 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 criteria: 5.Treatment with any investigational agent within 4 weeks (or 5 half-lives of investigational agent, whichever is longer) before screening 6.Previous inadequate response to treatment with biologic DMARDs Previous biologic treatment allowed if assumed for no more than 1 month and stopped for tolerability reasons at least 6 months before the enrollment in the study. 7.Intraarticular or parenteral corticosteroids within 6 weeks prior to baseline 8.Immunization with a live/attenuated vaccine within 4 weeks prior to baseline 9.Previous treatment with tocilizumab (an exception to this criterion may be granted for single-dose exposure upon application to the sponsor on a case by case basis) 10.Any previous treatment with alkylating agents, such as cyclophosphamide or chlorambucil, or with total lymphoid irradiation Laboratory-specific criteria (at screening): 11.Serum creatinine > 142 μmol/L (1.6 mg/dL) in female patients and > 168 μmol/L (1.9 mg/dL) in male patients 12.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) 13.Platelet count ULN (If initial sample yields bilirubin > ULN, a second sample may be taken and tested during the screening period) 19.Triglycerides > 10 mmol/L (> 900 mg/dL) at screening (non-fasted) General medical: 20.Pregnant women or nursing (breastfeeding) mothers 21.Females of child-bearing potential who are not using a reliable method of contraception 22.History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies 23.History of severe or anaphylactic reactions to gadolinium. 24.Chest X-ray evidence of any clinically significant abnormality. 25.Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus) or GI disease. Et al.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effects of tocilizumab in changes of the synovial membrane enhancement in the wrist joints of RA patients with inadequate clinical response to treatment with traditional DMARDs, defined as a baseline DAS28 > 3.2.;Secondary Objective: The secondary objectives of this study are to assess the effects of tocilizumab on the following parameters: 1.Extent of bone marrow edema, and number and extent of erosions in the wrist and metacarpo-phalangeal joints using dedicated MRI; 2.Radiographic changes in the hands evaluated by the modified Sharp score; 3.Ritchie articular index; 4.HAQ; 5.Pain by using a visual-analogue scale; 6.General health by using a visual-analogue scale; 7.DAS 28-CRP; 8.VEGF concentrations; 9.ESR and hsCRP concentration; 10.Hb and soluble transferrin receptor concentrations; 11.Immunological and inflammatory parameters 12.Tolerability and safety parameters. To assess early effects (Day 2) of tocilizumab on immunological and inflammatory parameters, an additional laboratory assessment will be performed only on patients who will agree to give a supplementary written informed consent.;Primary end point(s): ASSESSMENTS OF: -EFFICACY 1.Changes from baseline of the synovial membrane enhancement, in the wrist joints of RA, as follows: i.Extension and degree of synovitis of the wrist according to the RAMRIS score developed by OMERACT ii.Number of bones with, and extension of bone marrow oedema in the wrist and in the metacarpo-phalangeal area according to the RAMRIS score developed by OMERACT iii.Quantitative assessment of the degree of synovitis by dynamic, gadolinium-enhanced MRI (DCE-MRI) of the wrist 2.Radiographic changes in the hands evaluated by the modified Sharp score; 3.Changes from baseline of the Ritchie articular index 4.Changes from baseline of pain by using a visual-analogue scale (VAS) 5.Changes from baseline of general health by using a VAS 6.Changes from baseline of the DAS 28-CRP 7.Change | — |
Countries
Italy
Outcome results
None listed