Rheumatoid arthritis
Conditions
Interventions
Trade Name: RoActemra
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
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Completion of 24 weeks of treatment with tocilizumab (MRA) in WA17822, and scheduled to receive the first tocilizumab (MRA) infusion in WA18695 between 4 and 12 weeks after the last iv infusion in WA17822. 2) Able and willing to give written informed consent and comply with the requirements of the study protocol. 3) Have received methotrexate at a stable dose of between 10 and 25 mg/week (p.o. or parenteral) since the last administration of study drug in WA17822. 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 WA17822. 5) Must be willing to receive oral folate (at least 5 mg/week). 6) Females of child-bearing potential and males with female partners of childbearing 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 WA17822. 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 WA17822. 4) Treatment with an anti-TNF or anti-IL1 agent, or a T-cell costimulation modulator since the last administration of study drug in WA17822. 5) Parenteral, intramuscular or intra-articular corticosteroids within 6 weeks prior to baseline in WA18695. 6) Immunization with a live/attenuated vaccine since the last administration of study drug in WA17822. 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) Evidence of active malignant disease, malignancies diagnosed within the previous 10 years (including solid tumors and hematologic malignancies, except basal cell carcinoma of the skin that has been excised and cured), or breast cancer diagnosed within the previous 20 years. 12) Patients whose AST or ALT = 3 times ULN, bilirubin > 2 times ULN or > 2.5 mg/dL (43 umol/L), neutrophils < 1000/cubic mm (1 x 103 /uL or 1 GI/L), or who have an infection. Patients with history of inflammatory lower GI disease, such as diverticulitis, colitis, enteritis, as well as symptomatic diverticulosis (with or without history of bleeding) are excluded. Patients already randomized in the study will be re-evaluated for history of lower GI disease at the next scheduled study visit and their risk/benefit assessed to determine if they may continue in the study (details given in Section 7.3.1). If agreed to continue in the study, patients with history of lower GI disease will be required to sign an addendum to the informed consent indicating their willingness to remain in the study and undergo the additional tests required. Patients who have a negative outcome to the risk/benefit assessment or who are not willing to undergo the additional tests will be withdrawn.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the long-term safety of 8 mg/kg tocilizumab (MRA) 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 • To better understand and predict tocilizumab (MRA) efficacy, response, safety, progression of RA and associated diseases with regard to its effect on biomarkers;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 tocilizumab (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 WA18695 baseline to weeks 24, 48, 96 and 264. • The proportion of patients who are categorical DAS responders (EULAR response) at 24, 48, 96 and 264 weeks. • The proportion of patients who remain categorical DAS responders (EULAR response) consecutively for 24, 48, 96 and 264 weeks. | — |
Countries
Bulgaria, Germany, Hungary, Italy, Slovakia
Outcome results
None listed