Rheumatoid Arthritis
Conditions
Sponsors
Roche Products Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients must meet the following criteria for study entry: 1. Able and willing to give written informed consent and comply with the requirements of the study protocol. 2. Patients at least 18 years of age. 3. Patients with a diagnosis of active RA according to the revised (1987) ACR criteria or EULAR/ACR (2010) criteria. 4. Oral corticosteroids (=10 mg/day prednisone or equivalent) and nonsteroidal anti- inflammatory drugs (NSAIDs; up to the maximum recommended dose) are permitted if on a stable dose regimen for =4 weeks prior to Baseline. 5. Permitted non-biologic DMARDs are allowed if at a stable dose for at least 4 weeks prior to Baseline. 6. Receiving treatment on an outpatient basis, not including Tocilizumab. 7. Females of childbearing potential and males with female partners of childbearing potential may participate in this study only if using a reliable means of contraception (e.g., physical barrier [patient or partner], contraceptive pill or patch, spermicide and barrier, or intrauterine device) during the study. Females of childbearing potential and males with female partners of childbearing potential must use a reliable means of contraception for at least 3 months following the last dose of TCZ. 8. If female of childbearing potential, the patient must have a negative pregnancy test at Screening and Baseline visits. 9.Patients who have an inadequate response to current non-biologic DMARD therapy or the first anti-TNF agent (in monotherapy or in combination with MTX or other non-biologic DMARDs). Inadequate response to anti-TNF treatment is defined as not achieving an adequate response to treatment at 24 weeks or after a minimum period of 12 weeks therapy if permitted by local guidance (timing of assessment according to local clinical practice and no more than 8 weeks post-Week 24) defined by NICE as a DAS28 score improvement of less than 1.2 or patients achieving a 1.2 reduction in DAS28 but not achieving low disease activity (current DAS28 ESR above 3.2) and have not been previously exposed to treatment with tocilizumab. 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: A patient will be excluded if the answer to any of the following statements is “yes”. General: 1. Major surgery (including joint surgery) within 8 weeks prior to Screening or planned major surgery within 6 months following baseline. 2. Rheumatic autoimmune disease other than RA, including systemic lupus erythematosis, mixed connective tissue disorder, scleroderma, polymyositis, or significant systemic involvement secondary to RA (e.g., vasculitis, pulmonary fibrosis or Felty’s syndrome). Secondary Sjögren’s syndrome with RA is permitted. 3. Functional Class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis (Appendix 2). 4. Diagnosis of juvenile idiopathic arthritis or juvenile RA, and/or RA before the age of 16. 5. Prior history of or current inflammatory joint disease other than RA (e.g., gout, Lyme disease, seronegative spondyloarthropathy including reactive arthritis, psoriatic arthritis, and arthropathy of inflammatory bowel disease). Excluded Previous or Concomitant Therapy: 6. Exposure to Tocilizumab (either IV or SC) at any time prior to Baseline. 7. Treatment with any investigational agent within 4 weeks (or five half-lives of the investigational drug, whichever is longer) of Screening. 8. Previous treatment with any cell-depleting therapies, including investigational agents or approved therapies, some examples are CAMPATH, anti CD4, anti-CD5, anti CD3, anti CD19, and anti CD20. 9. Treatment with IV gamma globulin, plasmapheresis within 6 months of Baseline. 10. Intraarticular (IA) or parenteral corticosteroids within 4 weeks prior to Baseline. 11. Immunization with a live/attenuated vaccine within 4 weeks prior to Baseline. 12. Any previous treatment with alkylating agents such as chlorambucil, or with total lymphoid irradiation. Exclusions for General Safety: 13. History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies. 14. Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus), or GI disease. 15. History of diverticulitis, diverticulosis requiring antibiotic treatment, or chronic ulcerative lower GI disease such as Crohn’s disease, ulcerative colitis, or other symptomatic lower GI conditions that might predispose to perforation. 16. Known active current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections (including but not limited to tuberculosis [TB] and atypical mycobacterial disease, hepatitis B and C, and herpes zoster, but excluding fungal infections of nail beds). 17. Any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of Screening or oral antibiotics within 2 weeks of Screening. 18. Active TB requiring treatment within the previous 3 years. Patients should be screened for latent TB and, if positive, treated following local practice guidelines prior to initiating Tocilizumab. However, if local practice or guidelines allow reference to test results that were obtained prior to the screening period as part of routine clinical practice, this is allowed. Patients treated for TB with no recurrence in 3 years are permitted. 19. Current liver disease as determined by the investigator. 20. Positive hepatitis B surface antigen (HbsAg) or hepatitis C antibody. 21. Primary or secondary immunodef
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective for this study is to assess the efficacy of switching to subcutaneous (SC) Tocilizumab (as monotherapy or in combination with MTX or other non-biologic DMARDs) in patients who are currently being treated with have an inadequate response to current non-biologic DMARD therapy or the first anti-TNF biologic agent (as monotherapy or in combination with MTX or other non-biologic DMARDs). Inadequate response to anti-TNF treatment is assessed at Week 24 or after a minimum period of 12 weeks of therapy if permitted by local guidance (either defined by the National Institute for Health and Clinical Excellence (NICE) as a Disease Activity Score 28 (DAS28) improvement of less than 1.2, or patients not achieving a DAS28 of = 3.2 according to a treat-to-target strategy). Efficacy will be measured by DAS28-ESR and Clinical Disease Activity Index (CDAI) at every visit up to Week 52. ;Secondary Objective: o To evaluate safety & tolerability of SC Tocilizumab over time (as monotherapy or in combination with MTX or other non-biologic DMARDs) comprising AEs, physical examination, vital signs, clinical laboratory assessments, including immunogenicity, in patients with active RA up to wk 52. o To assess efficacy of SC TCZ (monotherapy or in combination with MTX or other non-biologic DMARDs) over time using endpoints such as DAS28 ESR, ACR response scores, EULAR response criteria, SDAI or CDAI, TJC/SJC, and patient reported outcomes (PROs) up to wk 52, including onset of action at wk 2. o Evaluate proportion of patients who achieve low disease activity, defined by DAS28-ESR = 3.2 with SC Tocilizumab (monotherapy or in combination with MTX or other non-biologic DMARDs) at every visit up to wk 52. o Evaluate the proportion of patients who achieve remission defined by DAS28-ESR < 2.6 with SC TCZ (monotherapy or in combination with DMARDs) at every visit up to wk 52. ;Primary end point(s): • Change in DAS28-ESR at every visit up to Week 52 ;Timepoint | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): · ACR response scores at every visit up to Week 52. · EULAR response criteria at every visit up to Week 52. · Change in SDAI or CDAI at every visit up to Week 52. · Change in total TJC and total SJC over time. · Proportion of patients and reasons for non-biologic DMARD/ corticosteroid dose reductions and/or discontinuation over time. MTX adherence in patients being prescribed the biologic DMARD (bDMARD) in combination with a non-biologic DMARD, by using a special designed “Methotrexate adherence questionnaire” at Baseline, W12, W24, W36 and W52.;Timepoint(s) of evaluation of this end point: · ACR response scores at every visit up to Week 52. · EULAR response criteria at every visit up to Week 52. · Change in SDAI or CDAI at every visit up to Week 52. · Change in total TJC and total SJC over time. · Proportion of patients and reasons for non-biologic DMARD/ corticosteroid dose reductions and/or discontinuation over time. MTX adherence in patients being prescribed the biologic DMARD (bDMARD) in combination with a non-biologic DMARD, by using a “Methotrexate adherence questionnaire” at baseline (week 0), week 12, week 24, week 36 and week 52 | — |
Countries
United Kingdom
Contacts
Public ContactClinical Projects Group
Roche Products Limited
Outcome results
None listed