Rheumatoid Arthritis MedDRA version: 14.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Sponsors
Roche S.p.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Able and willing to give written informed consent and comply with the requirements of the study protocol. Patients at least 18 years of age. Patients with a diagnosis of active RA according to the revised (1987) ACR criteria or EULAR/ACR (2010) criteria. Oral corticosteroids (=10 mg/day prednisone or equivalent) and non-steroidal anti-inflammatory drugs (NSAIDs; up to the maximum recommended dose) are permitted if on a stable dose regimen for =4 weeks prior to baseline. Permitted non-biologic DMARDs are allowed if at a stable dose for at least 4 weeks prior to baseline. Receiving treatment on an outpatient basis, not including TCZ. 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, contraceptive pill or patch, spermicide and barrier, or intrauterine device) during the study. Females of childbearing potential must use a reliable means of contraception for at least 3 months following the last dose of TCZ. If female of childbearing potential, the patient must have a negative pregnancy test at Screening and baseline visits. Patients with moderate to severe RA (CDAI = 10 and DAS28 = 3.2) at screening. Patients who are Tumor Necrosis Factor (TNF)-Inadequate Responder (IR), MTX-IR, DMARD-IR. The time between the last dose of TNF inhibitor and the randomization in the study should depend on the approved dosing interval as reported in the SmPC and Prescribing Information (PI). 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 191 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 34
Exclusion criteria
Exclusion criteria: Major surgery (including joint surgery) within 8 weeks prior to Screening or planned major surgery within 12 months following baseline. 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 gastrointestinal (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 TCZ. 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 or hepatitis C antibody. 21. Primary or secondary immunodeficiency (history of or currently active). 22. Evidence of active malignant disease, malignancies diagnosed within the previous 10 years (including hematological malignancies and solid tumors, except basal and squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that has been excised and cured), or breast cancer diagnosed within the previous 20 years. 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. 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 TCZ (either intravenous [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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of subcutaneous (SC) tocilizumab (TCZ) administered in monotherapy or in combination with methotrexate (MTX) and/or other non-biological disease modifying antirheumatic drugs (DMARDs) using Clinical Disease Activity Index (CDAI) over time up to 24, including onset of action at Week 2.;Secondary Objective: To assess the efficacy of SC TCZ monotherapy or in combination with MTX and/or other non-biological DMARDs in CDAI remission (defined as a CDAI =2.8 during any two consecutive visits, not including the baseline visit), up to Week 52. To evaluate the safety and tolerability of SC TCZ monotherapy or in combination with MTX and/or other non-biological DMARDs comprising adverse events (AEs), physical examination, vital signs and clinical laboratory assessments, including immunogenicity, in patients with active rheumatoid arthritis (RA) at week 24 and 52. [...] The complete list of secondary Objectives can be found in the protocol.;Primary end point(s): To assess the efficacy of subcutaneous (SC) tocilizumab (TCZ) administered in monotherapy or in combination with methotrexate (MTX) and/or other non-biological disease modifying antirheumatic drugs (DMARDs) using Clinical Disease Activity Index (CDAI) over time up to 24, including onset of action at Week 2.;Timepoint(s) of evaluation of this end point: week 24, including onset of action at Week 2. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To assess the efficacy of SC TCZ monotherapy or in combination with MTX and/or other non-biological DMARDs in CDAI remission (defined as a CDAI =2.8 during any two consecutive visits, not including the baseline visit), up to Week 52.;Timepoint(s) of evaluation of this end point: week 52 | — |
Countries
Italy
Contacts
Public ContactCLINICAL OPERATIONS
Roche S.p.A.
Outcome results
None listed