An Efficacy and Safety Study of Tocilizumab (RoActemra/Actemra) in Participants With Giant Cell Arteritis (GCA)

Roche

Status and phase: Completed; Phase 3

Conditions: Giant Cell Arteritis

Treatments: Drug: Prednisone; Drug: Corticosteroids; Drug: Methotrexate; Drug: Prednisone Placebo; Drug: Tocilizumab Placebo; Drug: Tocilizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT01791153

WA28119

2011-006022-25 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 251 patients

Sex: All

Ages: 50+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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251 participants in 5 patient groups, including a placebo group

Part 1: Tocilizumab qw + 26 weeks prednisone taper

Experimental group

Description:

Participants will receive tocilizumab at a dose of 162 milligrams (mg) as subcutaneous (SC) injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants will receive prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.

Treatment:

Drug: Prednisone Placebo

Drug: Tocilizumab

Drug: Prednisone

Part 1: Tocilizumab q2w + 26 weeks prednisone taper

Experimental group

Description:

Participants will receive tocilizumab at a dose of 162 mg as SC injection q2w (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants will receive prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.

Treatment:

Drug: Prednisone Placebo

Drug: Tocilizumab

Drug: Tocilizumab Placebo

Drug: Prednisone

Part 1: Placebo + 26 weeks prednisone taper

Placebo Comparator group

Description:

Participants will receive tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants will receive prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.

Treatment:

Drug: Prednisone Placebo

Drug: Tocilizumab Placebo

Drug: Prednisone

Part 1: Placebo + 52 weeks prednisone taper

Placebo Comparator group

Description:

Participants will receive tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to a protocol-defined schedule. Participants will receive prednisone tapering oral daily doses for 52 weeks.

Treatment:

Drug: Prednisone Placebo

Drug: Tocilizumab Placebo

Drug: Prednisone

Part 2: Open-Label Tocilizumab qw

Experimental group

Description:

Participants without sustained remission at Week 52 will receive open-label tocilizumab at a dose of 162 mg as SC injection qw and/or corticosteroids and/or methotrexate at the discretion of the investigator for a maximum of 104 weeks.

Treatment:

Drug: Methotrexate

Drug: Tocilizumab

Drug: Corticosteroids