Rheumatoid arthritis
Conditions
Interventions
Product Name: MRA
Product Code: RO4877533
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: tocilizumab
CAS Number: 375823-41-9
Current Sponsor code: RO4877533
Concentrat
Sponsors
F Hoffmann La-Roche AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Completion of treatment as specified in the core studies, and scheduled to receive the first tocilizumab (MRA) infusion in WA18696 between 4 and 12 weeks after the last iv infusion in the core studies. 2) Able and willing to give written informed consent and comply with the requirements of the study protocol. 3) Have received MTX or other allowable DMARD at a stable dose and route of administration since the last administration of study drug in the core studies. Patients enrolled from study WA17824, will receive tocilizumab (MRA) 8 mg/kg monotherapy or combination therapy at the discretion of the investigator. 4) Oral corticosteroids (=10 mg/day prednisone or equivalent) and NSAIDS (up to the maximum recommended dose) are permitted if dose stable since the last administration of study drug in the core studies. 5) If taking MTX, must be willing to receive oral folate (at least 5 mg/week). 6) Females of child-bearing potential and males with female partners of child-bearing potential may participate in this trial only if using a reliable means of contraception (e.g. physical barrier (patient and partner), contraceptive pill or patch, spermicide and barrier, or IUD). 7) If female and of child-bearing potential, the patient must have a negative urine pregnancy test at baseline. 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: 1) Treatment with any investigational agent since the last administration of study drug in the core studies. 2) Previous treatment with any cell depleting therapies, including investigational agents (e.g. CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19 and anti-CD20) 3) Treatment with iv gamma globulin, plasmapheresis or Prosorba™ column since the last administration of study drug in the core studies. 4) Treatment with an anti-TNF or anti-IL1 agent, or a T-cell costimulation modulator or any biologic or participation in any research study since the last administration of study drug in the core studies. 5) Parenteral, intramuscular or intra-articular corticosteroids within 6 weeks prior to baseline in WA18696. 6) Immunization with a live/attenuated vaccine since the last administration of study drug in the core studies. 7) Any previous treatment with alkylating agents such as cyclophosphamide or chlorambucil, or with total lymphoid irradiation. 8) History of severe allergic or anaphylactic reaction to human, humanized or murine monoclonal antibodies. 9) Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (incl. obstructive pulmonary disease), renal, hepatic, endocrine (incl. uncontrolled diabetes mellitus), immunologic or gastrointestinal disease. 10) Known active or history of recurrent bacterial, viral, fungal, mycobacterial or other infections (including but not limited to tuberculosis and atypical mycobacterial disease, clinically significant abnormalities on chest X-ray as determined by the investigator, HIV, hepatitis B and C, and Herpes zoster, but excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization or treatment with iv antibiotics within four weeks prior to baseline or oral antibiotics within two weeks prior to baseline. 11) History of malignancy, including solid tumors and hematologic malignancies (except basal cell carcinoma of the skin that has been excised and cured). 12) Patients whose AST or ALT = 3 times ULN, bilirubin > 2 times ULN and > 2.5 mg/dL (43 umol/L), neutrophils < 1000/mm3 (1 x 103 /uL or 1 GI/L), or who have an infection.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the long-term safety of 8 mg/kg tocilizumab (MRA) as monotherapy or in combination with background DMARD therapy(ies) with regard to adverse events and laboratory result abnormalities.;Secondary Objective: •To explore the possibility of reducing concomitant steroid treatment •To determine the long-term efficacy of 8 mg/kg tocilizumab (MRA) with regard to reduction in signs and symptoms ;Primary end point(s): The primary parameters of interest are safety and long-term efficacy. The following endpoints will be summarized descriptively: • The safety of MRA with regard to adverse events and laboratory result abnormalities. • Concomitant steroid treatment will be summarized by visit. • Number of patients who withdraw from treatment. • The proportion of patients achieving an ACR20, ACR50 and ACR70 response by visit. • The proportion of patients who maintain an ACR20, ACR50 or ACR70 response consecutively for 24, 48, 96 and 264 weeks. • The individual components of the ACR core set will be summarized by visit. • Change in Disease Activity Score (DAS28) from first dose of 8 mg/kg tocilizumab (MRA) to weeks 24, 48, 96 and 264. • Change in Disease Activity Score (DAS28) from WA18696 baseline to weeks 24, 48, 96 and 264. • The proportion of patients who are categorical DAS responders (EULAR response) by visit. • The proportion of patients who remain categorical DAS responders (EULAR response) consecutively for 24, 48, 96 and 264 weeks. • The proportion of patients who change from monotherapy to combination treatment by visit. | — |
Countries
Czech Republic, Denmark, Finland, Germany, Iceland, Italy, Portugal, Slovenia, Spain, Sweden, United Kingdom
Outcome results
None listed