Health Condition 1: null- Active Rheumatoid Arthritis
Conditions
Interventions
Intervention1: Tocilizumab: 8 mg/kg of body weight every 4 weeks for a total of 6 infusions
Control Intervention1: NIL: NIL
Sponsors
Roche Products India Pvt Ltd
Eligibility
Inclusion criteria
Inclusion criteria: 1. Male or non-pregnant, non-nursing female 2. Greater or equal to 18 years of age 3. Diagnosis of RA of Greater or equal to 6 months duration and moderate to severe disease activity defined as a DAS28 greater 3.2 at screening 4. Receiving treatment on an outpatient basis 5. Patients on greater or equal to 1 non-biologic DMARDs and/or anti-TNF therapy (see section 6.1) at a stable dose for a period greater or equal to 8 weeks at any time prior to treatment (baseline) 6. Patients with inadequate clinical response to a stable dose of non-biologic DMARD or anti-TNF therapy 7. 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) 8. Able and willing to give written informed consent and comply with the requirements of the study protocol
Exclusion criteria
Exclusion criteria: Disease 1. Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following enrollment 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 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 6. Previous treatment with any cell-depleting therapies, including investigational agents (e.g. CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19 and anti-CD20) 7. Previous treatment with abatacept 8. Treatment with leflunomide in combination with MTX 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 12. 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) 13. Any previous treatment with alkylating agents, such as cyclophosphamide or chlorambucil, or with total lymphoid irradiation Laboratory analyses (at screening) 14. Serum creatinine > 142 &#956;mol/L (1.6 mg/dL) in female patients and > 168 &#956;mol/L (1.9 mg/dL) in male patients and no active renal disease. 15. 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) 16. Platelet count < 100 x 109/L (100,000/mm3) 17. Hemoglobin < 85 g/L (8.5 g/dL; 5.3 mmol/L) 18. WBC count < 1.0 x 109/L (1000/mm3), ANC < 1 x 109/L (1000/mm3) 19. ALC < 0.5 x 109/L (500/mm3) 20. Positive hepatitis B surface antigen (HBsAg) or hepatitis C antibody 21. Total bilirubin > ULN (If initial sample yields bilirubin > ULN, a second sample may be taken and tested during the screening period) 22. Triglycerides > 10 mmol/L (> 900 mg/dL) at screening (non-fasted) General medical 23. Pregnant women or nursing (breastfeeding) mothers 24. Females of child-bearing potential who are not using a reliable means of contraception, e.g. physical barrier (patient and partner), contraceptive pill or patch, spermicide and barrier, or IUD 25. History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies 26. CXR evidence of any clinically significant abnormality 27. Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocri
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To assess the safety and tolerability of tocilizumab (TCZ) monotherapy or in combination with non-biologic diseasemodifying antirheumatic drugs (DMARDs) in patients with moderate to severe active RATimepoint: Incidence of adverse events and serious adverse events during 24 weeks of TCZ monotherapy or combined treatment with TCZ and one or more of the background nonbiologic disease modifying anti-rheumatic drugs (DMARDs) approved for rheumatoid arthritis (RA) in patients with moderate to severe active RA | — |
Secondary
| Measure | Time frame |
|---|---|
| To assess the efficacy of TCZ monotherapy or in combination with non-biologic DMARDsTimepoint: ? Number and percentage of patients with AE- and SAErelated discontinuation of TCZ at every visit ? Number and percentage of patients with all-cause discontinuation of TCZ at every visit ? Incidence of AEs, SAEs and discontinuations in current and prior users of TNF antagonists at every visit ? Number and percentage of patients with ALT (SGPT) or AST (SGOT) elevations > 1.5 ULN, > 3 ULN and > 5 ULN at every visit ? Number and percentage of serious infections at each visit ? Change from baseline to highest values for ALT (SGPT) or AST (SGOT), LDL and total cholesterol and to lowest value for ANC ? Number and percentage of patients with elevations in lipids according to the ATPIII guidelines at every visit ? Number and percentage of patients achieving a clinically meaningful improvement in Disease Activity Score 28 (DAS28) (reduction of at least 1.2 units) at every visit and time to clinically meaningful improvement in DAS28 ? Number and percentage of patients achieving low disease activity (DAS28 < 3.2) at every visit and time to low disease activity ? Number and percentage of patients achieving remission (DAS28 < 2.6) at every visit and time to DAS28 remission ? Disease activity as measured by DAS28 at every visit ? Number and percentage of patients achieving ACR20, ACR50, ACR70 and ACR90 response at every visit ? CRP and ESR at every visit ? Mean change from baseline in individual parameters of ACR core data set at every visit | — |
Countries
Belgium, Denmark, Germany, Ireland, Luxembourg, Netherlands, Poland, Portugal, Romania, Saudi Arabia, Spain, Sweden, Switzerland, Turkey, United Kingdom
Contacts
Public ContactDr Aditi Parekh
Roche Products (India) Pvt. Ltd.
Outcome results
None listed