Rheumatoid Arthritis MedDRA version: 16.0 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Product Name: Tocilizumab SC
Product Code: Ro 487-7533/F10-04
Pharmaceutical Form: Solution for injection
Sponsors
ROCHE HELLAS S.A.
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 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. Females of childbearing potential must use a reliable means of contraception for at least 3 month following the last dose of TCZ. 8. If female of childbearing potential, the patient must have a negative pregnancy test at the Screening and Baseline visits. 9. The target population for this study is adult men or women with active Rheumatoid Arthritis ,DAS28(ESR) >3.2, early RA of less than 6 month duration or established RA of more than 6 month duration , either naïve to MTX and /or other non biologic DMARD’s treatment, or having inadequate response (inefficacy/intolerance) to previous non biologic DMARDs ( MTX-IR, DMARD-IR) and/or having inadequate response (inefficacy/ intolerance) to previous biologic DMARDs (including Tumor necrosis factor-TNFiIR or Abatacept- when this was assigned as first line biologic-Abatacept IR IR). Patients who have experienced inadequate responses (inefficacy/intolerance) to previous biologics DMARDs could participate in this study with or without going through a biologic wash-out period. The time between the last dose of TNF inhibitor or Abatacept and the inclusion in the study could be between 1 and 8 weeks depending on the approved dosing interval as reported in the SmPC and according to the physician’s judgment. 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). 6. Patients with lack of peripheral venous access. Excluded Previous or Concomitant Therapy: 7. Exposure to TCZ (either IV or SC) at any time prior to Baseline. 8. Treatment with any investigational agent within 4 weeks (or five half-lives of the investigational drug, whichever is longer) of Screening. 9. 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. 10. Treatment with IV gamma globulin, plasmapheresis within 6 months of Baseline. 11. Intraarticular (IA) or parenteral corticosteroids within 4 weeks prior to Baseline. 12. Immunization with a live/attenuated vaccine within 4 weeks prior to Baseline. 13. Any previous treatment with alkylating agents such as chlorambucil, or with total lymphoid irradiation. Exclusions for General Safety: 14. History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies. 15. Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus), or GI disease. 16. 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. 17. 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). 18. 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. 19. 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. 20. Current liver disease as determined by the Investigator. 21. Positive hepatitis B surface antigen (HbsAg) or hepatitis C antibody. 22. Primary or secondary immunodeficiency (history of or currently active). 23. Evidence of active malignant disease, malignancies diagnosed within the previous 10 years (i
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of treatment with SC TCZ monotherapy and/or in combination with MTX or other non biologic DMARDs with regard to achievement of clinical remission as measured by Disease Activity Score 28 (DAS28) <2.6 at the end of 24 weeks of treatment in patients with active rheumatoid arthritis (RA) ;Secondary Objective: To assess the efficacy of treatment with SC TCZ monotherapy and/or in combination with MTX or other non-biol. DMARDs over time at wk 24 & 52, includ. onset of action at wk 2.To evaluate the ability to maintain the optimal therapeutic target (Remission or LDA) of SC TCZ monotherapy, following MTX/other non-biol.(nb) DMARDs discontinuation from SC TCZ in combination with MTX/other nb DMARDs from wk 24 to 52.To evaluate the proportions of patients who will flare while on SC TCZ monotherapy and will necessitate add-on of MTX/other NB DMARDs to maintain the optimal therapeutic target (Remission or LDA), achieved between wk 24 – 52.To evaluate the safety and tolerability of SC TCZ as monotherapy and/or in combination with MTX or other NB DMARDs comprising AEs, physical examination, vital signs, and clinical lab.assessments, includ. immunogenicity, in patients with active RA at wk 24 & 52.Proportion of patients and reasons for corticosteroid dose reductions and/or discontinuation over time;Primary end point(s): The primary endpoint is to estimate the proportion of patients who will achieve DAS28 remission at Week 24. ;Timepoint(s) of evaluation of this end point: Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy Outcome Measures · Proportions of patients that achieve DAS28 Remission up to Week 24 · Proportions of patients that maintain DAS28 Remission/LDA from Week 24 up to week 52, for the patients on SC TCZ monotherapy since Week 24 · Proportions of patients that achieve DAS28 Remission/LDA up to week 52 for the patients with intensification of MTX/non biologic DMARD treatment in combination with SC TCZ since Week 24. · Change in DAS28-ESR over time up to Week 52 · ACR response scores over time up to Week 52 · EULAR response criteria over time up to Week 52 · Change in SDAI or CDAI over time up to Week 52 · Change in total TJC and total SJC over time up to Week 52 · Proportion of patients and reasons for corticosteroid dose reductions and/or discontinuation over time. Safety Outcome Measures 1. Incidence and severity of AEs, SAEs, and AEs of special interest over time up to Week 52. 2. Rates of AEs leading to dose modification or study withdrawal up to Week 52 3. Assessment of physical examination and vital signs up to Week 52. 4. Incidence of clinically significant laboratory abnormalities following TCZ SC administration up to Week 52 . 5. Assessment of immunogenicity following SC TCZ administration up to Week 52 and 8 weeks after the last dose.;Timepoint(s) of evaluation of this end point: Week 52 | — |
Countries
Greece
Contacts
Public ContactANNA MARIA KOURKOUTA
ROCHE HELLAS S.A.
Outcome results
None listed