Rheumatoid Arthritis MedDRA version: 18.0 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Sponsors
Roche a/s
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 TCZ. 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 and for a least 5 months following the last dose ot TCZ 8. If female of childbearing potential, the patient must have a negative pregnancy test at Screening and Baseline visits. 9. Patient with inadequate response and/or intolerance to MTX or other non-biologic DMARDs and/or where MTX or other non-biologic DMARDs are inappropriate 10. Have moderate to severe RA, DAS-28-ESR>3.2 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 120 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: 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 syndorme). 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 Previous or Concomitant Therapy 6. Exposure to any biologic DMARDs, including 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 weeds prior to Baseline 11. Immunization with a live/attenuated vaccine 4 weeks prior to Baseline 12. Any previous treatment with alkylating agents such as chlorambucil or with total lymphoid irradation 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 gastrointestinal (GI) disease. 15. History of diverticulitis, diverticulosis requiring antibiotic treatment, or chronic ulcerative lower GI diseases such as Crohn’s disease, ulcerative colitis or other symptomatic lower GI condition 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. Patient should be screened for latent TB and, if positive, treated following local practice guidelines prior to initiating TCZ. Patient 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 and 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 h
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Objective: To evaluate early changes in clinical efficacy by measuring mean change in CDAI at 12 weeks after onset of treatment with SC TCZ, either in monotherapy or in combination with MTX or other non-biologic DMARDs, in patient with rheumatoid arthritis receiving their first biologic treatment. ;Secondary Objective: Secondary Objectives: 1. To evaluate the safety and tolerability of subcutaneous (SC) tocilizumab (TCZ) in monotherapy or in combination with MTX or other non-biologic DMARDS, comprising adverse events (AEs), physical examination, vital signs, and clinical laboratory assessments, including immunogenicity, in patients with active rheumatoid arthritis (RA) during 24 weeks. 2. To assess the efficacy of SC TCZ in monotherapy or in combination with MTX or other non-biologic DMARDs, over time using endpoints such as Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR), American College of Rheumatology (ACR) repsonse scores, European League Against Rheumatism (EULAR) response criteria, Simplified DIsease Activity Index (SDAI) or Clinical Disease Activity Index (CDAI), tender joint count (TJC)/swollen joint count (SJC), and patient reported outcome (PROs) at Week 24, including onset of action at Week 2.;Primary end point(s): Mean change in CDAIat week 12;Timepoint(s) of evaluation of this end point: Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy Outcome 1 Change in DAS28-ESR up to Week 24. 2. ACR response scores up to Week 24. 3. EULAR response criteria up to Week 24. 4. Change in SDAI or CDAI up to Week 24. 5. Change in total TJC and total SJC over time. Safety Outcome 1.Incidence and severity of AEs, serious adverse events, and AEs of special interest over time up to Week 24. 2.Rates of AEs leading to dose modification or study withdrawal up to Week 24. 3.Assessment of physical examination and vital signs up to Week 24. 4.Incidence of clinically significant laboratory abnormalities following TCZ SC administration up to Week 24. 5.Assessment of immunogenicity following SC TCZ administration up to Week 24 and 8 weeks after last dose. Patient outcome 1. Patient Global Assessment of disease activity visual analogue scale (VAS) up to Week 24. 2. Patient Pain VAS up to Week 24. 3. Health Assessment Questionnaire-Disability Index up to Week 24. 4. Patient compliance (patient diary cards and return records) up to Week 24. 5. Patient Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F) up to week 24 ;Timepoint(s) of evaluation of this end point: Efficacy outcome 1. Week 24. 2. Week 24. 3. Week 24. 4. Week 24. 5. Over time. Safety outcome 1. Over time up to Week 24. 2. Over time up to Week 24. 3. Over time up to Week 24. 4. Over time up to Week 24. 5. Over time up to Week 24 and 8 weeks after last dose. Patient outcome 1. Over time to Week 24. 2. Over time up to Week 24. 3. Over time up to Week 24. 4. Over time up to Week 24. 5. Over time up to week 24 | — |
Countries
Denmark, Finland, Sweden
Contacts
Public ContactBirte Agular
Roche a/s
Outcome results
None listed