ong-term extension study of safety during treatment with tocilizumab (MRA) in patients completing treatment in WA17822

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 630

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. Patients that are prevented from enrollment prior to 12 weeks after the last iv infusion in WA17822 due to administrative delays outside of the control of the investigator and upon discussion with Roche may be included if they meet all other inclusion criteria, but will undergo a separate analysis of the study results.
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

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; 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 perforations for whom a favourable benefit/risk assessment for study continuation cannot be documented (see section 7.5.).
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.
13) 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 7.5). 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.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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