RHEUMATOID ARTHRITIS
Conditions
Interventions
Trade Name: RoActemra 20 mg/ml concentrado para solución para perfusión
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: TOCILIZUMAB
CAS Number: 375823-41-9
Current Sponsor code: RO4877
Sponsors
FUNDACIÓN ESPAÑOLA DE REUMATOLOGIA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Able and willing to give written informed consent and comply with the requirements of the study protocol. 2. Patients with moderate or severe RA diagnosed at least 6 months before inclusion. 3. Patients at least 18 years of age. 4. DAS28 >3.2 at baseline. 5. Oral corticosteroids dose in patients under such treatment should be ?10 mg prednisone [or equivalent] and stable at least within the month prior to [TCZ] treatment initiation (day 1). Patients may have been treated with stable doses of NSAIDs during the month prior to inclusion. 6. Receiving treatment on an outpatient basis. 7. Females of childbearing potential and males with female partners of childbearing potential may participate in this study only if using reliable means of contraception (e.g., physical barrier [patient or partner], contraceptive pill or patch, spermicide and barrier, or intra uterine device) during the study and 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 on MTX as a single treatment or in combination with a biological agent, or patients treated with a biological agent as monotherapy, who present or have presented intolerance or lack of adherence or safety problems to MTX. 10. MTX treatment should have been discontinued 4 weeks before baseline visit. 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 60 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 62
Exclusion criteria
Exclusion criteria: General: 1. Patients with lack of peripheral venous access. 2. Patients who have previously failed to more than two biologics. 3. Exposure to TCZ at any time prior to Baseline. 4. Treatment with any investigational agent within 4 weeks (or five half-lives of the investigational drug, whichever is longer) of Screening. 5. Previous treatment with any cell-depleting therapies, including investigational agents or approved therapies, some examples: CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti CD19, and anti-CD20. 6. Treatment with IV gamma globulin, plasmapheresis within 6 months of Baseline. 7. Intra-articular or parenteral corticosteroids within 4 weeks prior to Baseline. 8. Immunization with a live/attenuated vaccine within 4 weeks prior to Baseline. 9. Any previous treatment with alkylating agents such as chlorambucil, or with total lymphoid irradiation. 10. History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies. 11. Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including chronic obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus), or gastrointestinal (GI) disease. 12. 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. 13. 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). 14. 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. 15. Active TB requiring treatment within the previous year. All Patients will be screened for latent TB in accordance to the SER/AEMS guidelines24. Patients treated for TB with no recurrence in 3 years are permitted. 16. Current liver disease as determined by the Investigator. 17. 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. 18. Pregnant women or nursing (breast feeding) mothers. 19. Patients with reproductive potential not willing to use an effective method of contraception. 20. History of alcohol, drug, or chemical abuse within 1 year prior to Screening. 21. Neuropathies or other conditions that might interfere with pain evaluation. 22. Serum creatinine >1.4 mg/dL (124 ?mol/L) in female patients and >1.6 mg/dL (141 ?mol/L) in male patients. 23. Alanine aminotransferase or aspartate aminotransferase >1.5 times upper limit of normal (ULN) 24. Total bilirubin >ULN. 25. Platelet count <100 x 109/L (100,000/mm3). 26. Hemoglobin <85 g/L (8.5 g/dL; 5.3 mmol/L). 27. White blood cells <3.0 x 109/L (3000/mm3). 28. Absolute neutrophil count <2.0 x 109/L (2000/mm3) 29. Absolute lymphocyte count <0.5 x 109/L (500/mm3).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of TCZ given as monotherapy in RA patients with active disease, in terms of rate of patients reaching good or moderate EULAR response, at week 24.;Secondary Objective: To evaluate the efficacy, of TCZ given as monotherapy in RA patients with active disease, by change in disease activity score DAS28 of EULAR response, from baseline to week 24, To assess, in patients treated with TCZ in monotherapy RA activity as DAS28, SDAI and CDAI. To assess efficacy, in patients treated with TCZ in monotherapy, as per ACR criteria. To evaluate the efficacy, of TCZ given as monotherapy in RA patients with active disease, by change in disease activity score DAS28 of EULAR response, from baseline to week 24, in the subgroups. To determine the percentage of RA patients that, after a six months treatment with TCZ given as monotherapy, achieve LDA by the score ?DAS28?.To assess safety of TCZ as monotherapy during the study period. To assess HRQL of patients treated with TCZ as monotherapy in the subgroups To describe reasons why study RA patients are considered candidates to be treated with a biological compound as monotherapy following protocol recommendations.;Primary end point(s): Rate of patients reaching good or moderate EULAR response, at week 24;Timepoint(s) of evaluation of this end point: 24 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - DAS 28 (Disease Activity Score): It includes 4 variables: TJC (tender joint count), SJC (swollen joint count), ESR/PCR (erythrocyte sedimentation rate or C-reactive protein) and VAS (visual analogue scale for pain assessment). Cut-off points for DAS28 are: DAS2822. - SDAI (Simplified Disease Activity Index): It is calculated by adding TJC, SJC, , patient?s VAS, physician?s VAS and C-reactive protein result (mg/l). Index categories are: remission (<3.3), low activity (<11), moderate activity (11<SDAI<26) and high activity (?26). - ACR response criteria: 20%/50%/70% improvement in swollen joints count, tender joints count, and in at least three of the following: patient?s global assessment, physician?s global assessment, patient?s VAS, physical function questionnaire (HAQ), ESR or C-reactive protein. Safety Variables - The safety of treatment will be assessed by adverse events (AE) reported by patients or diagnosed by the investigator. All AEs will be described, and graded. Relationship of the AE to the administration of tocilizumab will be determined by the investigator. All serious adverse events (SAEs) will be reported to Roche within 24 hours. - Any adverse event occurring during the study will be documented in the clinical chart.;Timepoint(s) of evaluation of this end point: 32 weeks | — |
Countries
Spain
Contacts
Public ContactMARIA AUXILIADORA MARTIN MARTINEZ
FUNDACIÓN ESPAÑOLA DE REUMATOLOGÍA
Outcome results
None listed