A Multicenter, Randomized, Double-Blind, Placebo-Controlled,
Parallel Group Study to Evaluate the Efficacy and Safety of
Sirukumab in the Treatment of Patients with Giant Cell Arteritis

1. Diagnosis of GCA defined by the following Revised GCA Diagnosis Criteria:
* Age *50 years.
* History of ESR * 50 mm/hour or CRP * 2.45 mg/dL.
* Presence of at least one of the following:
* Unequivocal cranial symptoms of GCA (new onset localized headache, scalp or temporal artery tenderness, ischemia-related vision loss, or otherwise unexplained mouth or jaw pain upon mastication).
* Unequivocal symptoms of PMR, defined as shoulder and/or hip girdle pain associated with inflammatory stiffness.
* Presence of at least one of the following:
* Temporal artery biopsy revealing features of GCA.
* Evidence of large-vessel vasculitis by angiography or cross-sectional imaging, including but not limited to magnetic resonance angiography (MRA), computed tomography angiography (CTA), ultrasound (UT) or positron emission tomography-computed tomography (PET-CT)
* Evidence of temporal artery vasculitis on US (for US imaging qualified centers only).;2. Active GCA within 6 weeks of Randomization (Baseline) where active disease is defined by an ESR *30 mm/hr or CRP * 1 mg/dL (*10 mg/L) AND the presence of at least one of the following:
* Unequivocal cranial symptoms of GCA (new onset localized headache, scalp or temporal artery tenderness, ischemia-related vision loss [permanent vision loss due to AION, amaurosis fugax, episodic blurry vision], diplopia, or otherwise unexplained mouth or jaw pain upon mastication [i.e., jaw claudication]).
* Unequivocal symptoms of PMR, defined as shoulder and/or hip girdle pain associated with inflammatory stiffness.
* Other features judged by the clinician investigator to be consistent with GCA or PMR flares (i.e., new or worsened extremity claudication, fever of unknown origin).;3. At screening, receiving or able to initiate prednisone treatment with a minimum dose of 20mg/day for the treatment of active GCA. Subjects not currently receiving prednisone treatment must commence dosing (minimum 20 mg/day of prednisone) at the screening visit.;4. Clinically stable GCA disease at baseline such that the subject is able to safely participate in the blinded prednisone taper regimen in the opinion of the investigator.;5. Practicing acceptable methods of birth control as follows:
Males:
Male subjects with female partners of child bearing potential must comply with the following contraception requirements from the time of first dose of study medication until 4 months after the last dose of study medication:
a. Vasectomy with documentation of azoospermia.
b. Male condom plus female partner use of one of the GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of
Childbearing potential.
Male subjects should also not donate sperm from the time of first dose of study medication until 4 months after the last dose of study medication.;Females:
Female subjects of child-bearing potential must use of one of the GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Childbearing potential.;6. No evidence of active or latent infection with Mycobacterium tuberculosis (TB), as defined by all of the following:
a. No history of active or latent TB infection.
b. A negative diagnostic TB test at Screening defined as a negative QuantiFERON Gold test (NB: 2 successive indeterminate QuantiFERON tests
will be considered as a positive result). In cases where an initial indeterminate QuantiFERON test result may be related to sample processing issues, the second QuantiFERON test may be performed at either the local laboratory or the central laboratory at the discretion of the investigator. Re-testing is only permitted for indeterminate results. If the re-test also produces an indeterminate result, further re-testing to determine study eligibility is not
permitted either at the local or central laboratory.
c. Chest radiograph (both posterior-anterior and lateral views unless local guidelines recommend only a single view), taken within 12 weeks prior to
baseline or at Screening, and read locally by a qualified radiologist, with no evidence of current active or previous inactive pulmonary tuberculosis.
NB: If there has been recent close contact with persons who have active TB prior to study enrolment the subject will be referred to a TB physician to undergo additional evaluation.

1. Are pregnant or breastfeeding.
2. Recent (within the past 12 weeks) or planned major surgery that would impact on study procedures or assessments.
3. Organ transplantation recipients (except corneas within 3 months prior to baseline visit).
4. Had prior treatment with any of the following:
* Systemic immunosuppressives, including azathioprine, oral cyclosporine A, tacrolimus, mycophenolate mofetil, leflunomide, oral or parenteral gold, and IL-1ra (anakinra) within 4 weeks of baseline.
* Biologic agents targeted at reducing TNF (including but not limited to infliximab, golimumab, certolizumab pegol, etanercept, yisaipu, and adalimumab) within 2-8 weeks of baseline, depending on the agent *.
* Anti-IL-6 (tocilizumab or any other anti-IL-6 agent) if:
* Used within 8 weeks of randomization
* Associated with a history of intolerance that precluded further treat
* Associated with an inadequate response to 3 months of therapy
* B-cell depleting agents (eg, rituximab) within 12 months prior to baseline or longer if B cell counts have not returned to normal range or baseline levels.
* Cytotoxic drugs such as cyclophosphamide, chlorambucil, nitrogen mustard, or other alkylating agents within 4 weeks of baseline.
* Abatacept within 8 weeks of baseline.
* Tofacitinib within 4 weeks of baseline.
* Methotrexate use within 2 weeks of baseline.
* Methylprednisolone > 100 mg/day IV (or equivalent) within 8 weeks of baseline.
5. History of severe allergic reactions to monoclonal antibodies, human proteins, or excipients.
6. Evidence of serious concomitant disease, which in the opinion of the investigator makes them unsuitable for participation in the study.
7. Major ischemic event, unrelated to giant cell arteritis, within 12 weeks of screening.
8. Marked baseline prolongation of QTc interval * 480 msec (QTcB or QTcF) or QTc > 500 msec in subjects with Bundle Branch Block **, history of Torsade de Pointes, family history of long QT syndrome, history of second or third degree heart block.
**The QTc should be based on averaged QTc values of triplicate ECGs obtained over a brief (e.g., 5-10 minute) recording period.
9. Current liver disease that could interfere with the trial as determined by the physician investigator.
10. History of or current active diverticulitis, inflammatory bowel disease, or other symptomatic GI tract condition that might predispose to bowel perforation.
11. History of known demyelinating diseases such as multiple sclerosis or optic neuritis.
12. Active infections, or history of recurrent infections or have required management of acute or chronic infections, as follows:
* Currently on any suppressive therapy for a chronic infection (such as tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster and atypical mycobacteria,
* History or suspicion of chronic infection (e.g joint infection).
OR
* Hospitalization for treatment of infection within 60 days of the baseline visit.
OR
* Use of parenteral (IV or IM) antimicrobials (antibacterials, antivirals, antifungals, or antiparasitic agents) within 60 days of baseline or oral antimicrobials within 30 days of baseline.
13. Primary or secondary immunodeficiency.
14. HIV infection (positive serology for HIV antibody), hepatitis C (positive serology for hepatitis C antibody confirmed positive by hepatitis C RNA PCR which is reflexively performed).
15. Hepatitis B infection (positive test results for hepatitis B surface antigen or hepatitis B core antibody).
16. Active malignancy or history of malignancy within previous 5 years (except basal and squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that has been excised and cured).
17. Laboratory abnormalities:
* AST or ALT >2.0 × upper limit of normal (ULN).
* Total bilirubin >ULN with the exception of Gilbert*s disease.
* Platelet count <140 × 109/L.
* Hemoglobin <8.5 g/dL.
* WBC count <3.5 × 109/L.
* ANC <2 × 109/L.
* ALC <0.5 × 109/L.
* Serum creatinine * 2.0 mg/dL (SI: positive * 177 µmol/L).
18. Has received, or is expected to receive, any live virus or bacterial vaccination within 3 months before the first administration of study drug, during the study, or within 4 months after the last administration of study drug.
19. Any other autoimmune disease (such as SLE, RA, inflammatory arthritis, other vasculitides, scleroderma, polymyositis, dermatomyositis or other similar systemic connective tissue diseases).
20. Uncontrolled psychiatric or emotional disorder, drug abuse, alcohol abuse within past 3 years.
*Please refer to the Study Procedures Manual (SPM) for guidance.
** If seropositive, consultation with a physician with expertise in the treatment of HIV or hepatitis B or C virus infection is recommended.