An Efficacy and Safety Study of Tocilizumab (RoActemra/Actemra) in Participants With Giant Cell Arteritis (GCA)
Condition: Giant Cell Arteritis
MeSH terms: Polymyalgia Rheumatica; Giant Cell Arteritis; Arteritis
Intervention: Tocilizumab; Prednisone; Tocilizumab Placebo; Prednisone Placebo; Corticosteroids; Methotrexate
Intervention description: Tocilizumab will be administered at a dose of 162 mg as SC injection qw or q2w for 52 weeks in Part 1 of the study and at a dose 162 mg as SC injection qw for 104 week at the discretion of the investigator in Part 2 of the study.; Prednisone will be administered at tapering oral doses as tablets daily for 26 or 52 weeks according to the protocol-defined schedule in Part 1 of the study. Prednisone will also be administered as escape therapy to treat disease flares in an open-label manner during Part 1 at a dose and duration selected by the investigator.; Tocilizumab placebo will be administered as SC injection qw or q2w for 52 weeks in Part 1 of the study.; Prednisone placebo will be administered as tablets orally daily according to the protocol-defined schedule (from Week 26 to Week 52) in Part 1 of the study.; Participants without sustained remission at Week 52 will receive corticosteroids at a dose and schedule at the discretion of the investigator for a maximum of 104 weeks.; Participants without sustained remission at Week 52 will receive methotrexate at a dose and schedule at the discretion of the investigator for a maximum of 104 weeks.
Intervention MeSH terms: Prednisone; Methotrexate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 251.0
Sex: All
Minimum age: 50 Years
Healthy volunteers: No

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