Rheumatoid Arthritis
Conditions
Interventions
Trade Name: RoActemra®EV Product Code: PRD82321
Product Name: Tocilizumab
Product Code: RO4877533
Pharmaceutical Form: Concentrate for solution for infu
Sponsors
University of Leeds
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Diagnosis of rheumatoid arthritis (1987 revised ACR criteria) confirmed at least 6 months prior to screening. 2.Persistent RA disease activity not responsive (ACR 0 and / or EULAR None-response) whilst being treated with an anti-TNF agent for at least 12 weeks. 3.Patients who have previously discontinued anti-TNF due to toxicity. 4.Patients have previously qualified for anti-TNF (NICE / BSR criteria) but therapy is contra-indicated. 5.Methotrexate dose stable for 12 weeks prior to screening and to be continued for the duration of the study. 6.Subjects with active RA at baseline are defined as: DAS28 > 5.1 7.Female patients will only be enrolled into the study if they are of non child bearing potential (surgically sterile or at least 2 years postmenopausal) or have satisfied the investigator as having an adequate form of contraception. Male patients must consent to practice contraception during the study. 8.Patients on NSAIDs and / or corticosteroids must have remained on an unchanged regimen for at least 28 days prior to study drug administration. 9. Discontinuation of a prohibited DMARD (e.g. oral or injectable gold, chloroquine, hydroxychloroquine, cyclosporine, azathioprine, leflunomide, sulphasalazine) or TNF-blocker (infliximab, etanercept or adalimumab) must occur at least 28 days prior to study drug administration (week 0). 10. Patients must be able and willing to comply with the terms of this protocol including attending for arthroscopy and imaging assessments. 11. Informed consent must be obtained in writing for all subjects at enrolment into the study. 4.3 EXCLUSION CRITERIA 1. Patients unwilling or unable to receive MTX for the duration of the study. 2. Patients with inflammatory joint disease of different origin, mixed connective tissue disease, Reiter’s syndrome, psoriatic arthritis, systemic lupus erythematosus, or any arthritis with onset prior to 16 years of age. 3. Suspicion of diagnosis of tuberculosis (positive tuberculosis test (>5mm induration if previous BCG or >10mm if no previous BCG) or abnormal chest x-ray)… Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 0 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. Patients unwilling or unable to receive MTX for the duration of the study. 2. Patients with inflammatory joint disease of different origin, mixed connective tissue disease, Reiter’s syndrome, psoriatic arthritis, systemic lupus erythematosus, or any arthritis with onset prior to 16 years of age. 3. Suspicion of diagnosis of tuberculosis (positive tuberculosis test (>5mm induration if previous BCG or >10mm if no previous BCG) or abnormal chest x-ray). 4. Patients with concomitant medical condition which would in the investigator’s opinion compromise the patient’s ability to tolerate, absorb, metabolise or excrete the study medication. 5. Patients with serious infections within 3 month of enrolment (screening) or persistent infections. 6. Patients at significant risk of infection (e.g. leg ulceration, indwelling urinary catheter, septic joint within 1 year (or ever if prosthetic joint still in situ)). 7. Patients with malignancy (other than excised basal cell carcinoma) within the last 5 years before study entry (screening). 8. Patients with history of Felty’s syndrome, uncontrolled diabetes, uncontrolled hypertension, unstable ischaemic heart disease, active bowel disease, active peptic ulcer disease, recent stroke (within three month before study entry (screening)), or other condition which, in the opinion of the investigator, would put the patient at risk to participate in the study. 9. Known positive serology for hepatitis B or C, or HIV 10. Patients with acute major trauma. 11. Patients with body weight 150 umol / L • Creatinine Clearance ? 50 ml/min 16. Therapy within the previous 28 days before study drug administration with: • Other biological agents, e.g. anti-TNF, interferon, monoclonal antibodies, growth factor, cytokines. • Other DMARDs (e.g. oral or injectable gold, chloroquine, hydroxychloroquine, cyclosporine, azathioprine, leflunomide, sulfasalazine, D-penicillamine, alkylating agents, e.g. cyclophosphamide, chlorambucil) 17. Doses of prednisolone > 10mg/d within the previous 28 days before study drug administration (week 0). 18. Intra-articular or intra-muscular steroid administration within 28 days before screening. Intra-articular steroid into joint to be scanned / biopsied within 12 weeks of baseline assessments. 19. Previous treatment with total lymphoid irradiation or anti - CD4 or CAMPATH 1-H monoclonal antibodies, resulting in CD4-Lymphopenia and possible immunosuppression (CD4 lymphocytes < 500/mm3). 20. Pregnant women or women of childbearing potential. Pregnancy must be excluded before start of treatment with the study drug. 21. Women who are Breast-fe
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess changes in synovial tissue to identify onset of action and potential predictors of response to tocilizumab based on changes in: • synovial volume, bone oedema on knee MRI at 4 weeks • synovial tissue histology and immunohistochemistry;Primary end point(s): To assess changes in synovial tissue to identify onset and mechanism of action and potential predictors of response to tocilizumab based on changes in: • synovial volume, bone oedema on knee MRI at 4 weeks • synovial tissue histology and immunohistochemistry;Secondary Objective: o To evaluate the safety of tocilizumab and MTX combination for the treatment of rheumatoid arthritis by assessment of: Incidence of adverse events, Vital signs and urinalysis, Blood haematology and chemistry, and ECG o To evaluate efficacy of tocilizumab and MTX/DMARD combination by: Clinical assessment (Composite scores: ACR and DAS28/EULAR response, 28 joint counts, Patient pain and general health VAS, Duration of morning stiffness, HAQ and RAQol, Physician Global VAS, and hsCRP and ESR), Radiological Assessment (MRI and ultrasonographical features, Plain radiology, and Bone densitometry, and Synovial Assessment (Macroscopic synovitis and vascularity scores, Change in histological score and pro-inflammatory cytokine expression in biopsies). | — |
Countries
United Kingdom
Outcome results
None listed