an efficacy and safety study of tocilizumab (roactemra/actemra) in participants with giant cell arteritis (gca)

Conditions: Giant Cell Arteritis

Summary: this multicenter, randomized, double-blind, placebo-controlled, parallel-group study will evaluate the efficacy and safety of tocilizumab in participants with gca. the study will consist of 2 parts: a 52-week double-blind treatment period (part 1) followed by a 104-week open label long-term follow-up period (part 2). in part 1 of the study eligible participants will be randomized to receive either tocilizumab every week (qw) or every 2 weeks (q2w) or placebo for 52 weeks, with tapering oral daily doses of prednisone. after week 52, participants in remission will stop study treatment and enter long-term follow-up, whereas participants with disease activity or flares will receive open-label tocilizumab or other treatment at the discretion of the investigator for a maximum period of 104 weeks.


Eligibility criteria:
inclusion criteria: * diagnosis of gca classified according to age \>/=50 years; history of esr \>/=50 mm/hr or history of crp \>/=2.45 mg/dl; and at least one of the following: unequivocal cranial symptoms of gca or symptoms of polymyalgia rheumatica \[pmr\]; and at least one of the following: temporal artery biopsy revealing features of gca or evidence of large-vessel vasculitis by angiography or cross-sectional imaging * new onset (diagnosis within 6 weeks of baseline) or refractory (diagnosis greater than \[\>\] 6 weeks before baseline and previous treatment with \>/= 40 milligrams per day prednisone \[or equivalent\] for at least 2 consecutive weeks at any time) gca * active disease (presence of clinical signs and symptoms \[cranial or pmr\] and esr \>/=30 mm/hour or crp \>/=1 mg/dl) within 6 weeks of baseline visit exclusion criteria: * major surgery within 8 weeks prior to screening or planned within 12 months after randomization * transplanted organs (except corneas with transplant performed \>3 months prior to screening) * major ischemic event, unrelated to gca, within 12 weeks of screening * prior treatment with any of the following: investigational agent within 12 weeks (or 5 half-lives of the investigational drug, whichever is longer) of screening; cell-depleting therapies including investigational agent; intravenous (iv) gamma globulin or plasmapheresis within 6 months of baseline; alkylating agents or with total lymphoid irradiation; tocilizumab; hydroxychloroquine, cyclosporine a, azathioprine, or mycophenolate mofetil within 4 weeks of baseline; etanercept within 2 weeks of baseline; infliximab, certolizumab, golimumab, abatacept, or adalimumab within 8 weeks of baseline; anakinra within 1 week of baseline; tofacitinib; cyclophosphamide within 6 months of baseline; \>100 milligrams of daily iv methylprednisolone within 6 weeks of baseline * participants requiring systemic glucocorticoids for conditions other than gca, which, in the opinion of the investigator, would interfere with adherence to the fixed glucocorticoid taper regimen and/or to assessment of efficacy in response to the test article * history of severe allergic reactions to monoclonal antibodies or to prednisone * evidence of serious uncontrolled concomitant disease (for example, cardiovascular, respiratory, renal, endocrine, psychiatric, corneal ulcers/injuries, or gastrointestinal \[gi\] disease) * current liver disease, as determined by the investigator * history of diverticulitis, inflammatory bowel disease, or other symptomatic gi tract condition that might predispose to bowel perforation * known active or history of recurrent bacterial, viral fungal, mycobacterial, or other infection * primary or secondary immunodeficiency * evidence of malignancies diagnosed within previous 5 years (except basal and squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that have been excised and cured) * inadequate hematologic, renal or liver function * positive for hepatitis b or hepatitis c infection