| Eligibility |
Inclusion Criteria
1. Patients aged older than 50 years with large vessel giant cell arteritis (LV-GCA)
2. PET/CT showing vascular FDG uptake =2 in at least one vascular district
3. ESR >40 mm/h or CRP >10 mg/l OR Cranial or systemic symptoms of GCA or symptoms of
polymyalgia rheumatica (PMR)
4. Patient's written informed consent.
Exclusion Criteria
1. Use of more than 10 mg/day of prednisone (or equivalent) for more than 10 consecutive
days in the previous three months
2. Rheumatic diseases (except for CPPD/chondrocalcinosis) other than GCA or polymyalgia
rheumatica (i.e., RA, autoimmune connectivitides, other systemic vasculitides, a.o.)
3. Chronic use of systemic CS with inability, in the opinion of the investigator, to
withdraw CS treatment at day 4 according to protocol
4. Evidence of significant and/or uncontrolled concomitant disease such as, but not
limited to, cardiovascular disease, nervous system, pulmonary, renal, hepatic,
endocrine (in particular diabetes mellitus) or gastrointestinal disorders (including
previous complicated diverticulitis) which, in the investigator's opinion, would
preclude patient participation or impact the benefit-risk ratio
5. History of amaurosis fugax,visual loss or diplopia
6. Any condition or general state of health which, in the Investigator's opinion, would
preclude participation in the study
7. Actual or recent myocardial infarction (within the last 3 months before screening
visit)
8. Significant cardiac disease (NYHA Class III and IV), known severe chronic obstructive
pulmonary disease (COPD) (FEV1 < 50% predicted or Functional dyspnea > Grade 3 on the
MRC Dyspnea Scale) or other significant pulmonary disease
9. Uncontrolled disease (such as asthma, psoriasis or inflammatory bowel disease) where
flares are commonly treated with oral or injectable corticosteroids
10. Known active infection of any kind, or any major episode of infection requiring
hospitalization or treatment with i.v. anti-infectives within 4 weeks of baseline or
completion of oral anti-infectives within 2 weeks before screening visit
11. History of deep space/tissue infection (e.g. fasciitis, abscess, osteomyelitis) within
52 weeks before screening visit
12. Any surgical procedure, including bone/joint surgery within 8 weeks prior before
screening visit or planned within the duration of the study
13. History of serious recurrent or chronic infection (for screening for a chest infection
a chest radiograph will be performed at screening if not performed within 12 weeks
before screening visit
14. Lack of peripheral venous access
15. Body weight > 150 kg or BMI > 35
16. Previous treatment with tocilizumab or any other biological agent within last 6 months
before screening visit; Rituximab within 12 months before screening visit
17. Treatment with any investigational agent within 28 days of screening visit or 5
half-lives of the investigational drug (whichever is the longer)
18. History of severe allergic or anaphylactic reaction to any biologic agent or known
hypersensitivity to any component of tocilizumab
19. Receipt of any vaccine within 28 days prior to screening visit (a patient's
vaccination record and need for immunization prior to receiving tocilizumab/placebo
must be carefully investigated)
20. Positive tests for hepatitis B surface antigen (HBsAg) or hepatitis C serology
21. Positive Quantiferon-TB® test for latent Tb without subsequent INH prophylaxis
22. Patients with active Tb which had to be treated for Tb within 2 years before the
screening visit
23. Absolute neutrophil count (ANC) < 2.0 x 103/µL, white blood cells < 2.5 x 103/µL,
platelet count < 100,000/ µL
24. Hemoglobin < 8.0 g/dL
25. Concentrations of serum IgG and/or IgM below 5.0 mg/mL and 0.40 mg/mL, respectively
26. Serum creatinine > 2.0 mg/dL (200 µmol/L)
27. Alanine aminotransferase (ALT) or aspartate amino-transferase (AST) > 1.5 times the
upper limit of normal (ULN)
28. Total bilirubin > 1.5 times the upper limit of normal (ULN)
29. Triglycerides > 400 mmol/dL (non-fasted) or > 250 mmol/dL (fasted) at screening
30. Premenopausal status and nursing (definition of postmenopausal status: Female
participants who are surgically sterilised / hysterectomised or post-menopausal for
longer than 2 years are not considered as being of child-bearing potential)
31. Technical implants such as cardiac pacemakers (for MR-angiogram)
32. Claustrophobia (for MR-angiogram)
33. Known allergy against the contrast media (Multihance® or Dotarem® as alternative)
34. Evidence of malignant disease or malignancies diagnosed within the 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)
|
