Tocilizumab for Patients With Giant Cell Arteritis
Condition: Giant Cell Arteritis
MeSH terms: Polymyalgia Rheumatica; Giant Cell Arteritis; Arteritis
Intervention: Tocilizumab + Glucocorticoids (GCs); Placebo + Glucocorticoids (GCs)
Intervention description: Tocilizumab 8mg/kg every 4 weeks until week 52.; Placebo every 4 weeks until week 52.
Intervention MeSH terms: Glucocorticoids
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 30.0
Sex: All
Minimum age: 50 Years
Healthy volunteers: No
Keywords: Giant Cell Arteritis; Tocilizumab; Antibodies, Monoclonal; Glucocorticoids

Summary:

      Giant-cell arteritis (GCA) is an immune-mediated disease that mostly affects people older
      than 50 years of age. Glucocorticoid (GC) treatment dramatically alters the symptoms and
      course of GCA, reducing the likelihood of vascular complications that could lead e.g. to
      blindness. However, relapses usually occur when GC dosages are tapered, resulting in frequent
      re-treatment with high cumulative dosages of GC over time with substantial toxicity and
      morbidity (e.g. diabetes mellitus, infections, enhanced cardiovascular risk, osteoporotic
      fractures, cataracts).

      Therefore, novel therapies are needed that effectively reduce the dose and duration of GC
      treatment and provide more durable remissions of GCA.

      Tocilizumab (TCZ) is a humanized monoclonal antibody directed against the human interleukin-6
      receptor (IL-6R). Elevated tissue and serum levels of IL-6 have been implicated in giant cell
      arteritis. Inhibition of IL-6 and/or its receptor therefore represents a new and novel
      approach for the treatment of RA.

      The primary endpoint is the proportion of patients that have achieved complete remission of
      disease after treatment with TCZ compared to treatment with placebo at week 12. All patients
      will receive glucocorticoids in a standardized form.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with newly onset or relapsed GCA

          -  > 50 years of age

          -  satisfying ACR criteria

          -  elevated sedimentation rate above 40 mm

          -  CRP > 20 mg/L

          -  Patients with histologically proven GCA or with large vessel vasculitis assessed by
             MRI

        Exclusion Criteria

          -  Rheumatic diseases (except for CPPD/chondrocalcinosis) other than GCA/Takayasu disease
             or polymyalgia rheumatica (i.e., RA, autoimmune connectivitides, other systemic
             vasculitides, a.o.)

          -  Evidence of significant and/or uncontrolled concomitant disease

          -  Diagnosis of GCA > 4 weeks before screening visit and beginning of GC treatment > 4
             weeks before screening (only valid for new onset GCA), or when a patient received
             treatment with tocilizumab or with other biological agents (such as TNFα-blockers)
             within 3 months before screening

          -  Any condition or general state of health which, in the Investigator's opinion, would
             preclude participation in the study

          -  Actual or recent myocardial infarction (within the last 3 months before screening
             visit)

          -  Significant cardiac disease (NYHA Class III and IV), known severe chronic obstructive
             pulmonary disease (COPD) (FEV1 < 50% predicted or Functional dyspnoea > Grade 3 on the
             MRC Dyspnoea Scale) or other significant pulmonary disease

          -  Uncontrolled disease (such as asthma, psoriasis or inflammatory bowel disease) where
             flares are commonly treated with oral or injectable corticosteroids

          -  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 prior to baseline

          -  History of deep space/tissue infection (e.g. fasciitis, abscess, osteomyelitis) within
             52 weeks prior to baseline

          -  Any surgical procedure, including bone/joint surgery within 8 weeks prior to baseline
             or planned within the duration of the study

          -  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
             prior to screening)

          -  Lack of peripheral venous access

          -  Body weight > 150 kg or BMI > 35

          -  Previous treatment with tocilizumab or any other biological agent

          -  Treatment with any investigational agent within 28 days of screening or 5 half-lives
             of the investigational drug (whichever is the longer)

          -  History of severe allergic or anaphylactic reaction to any biologic agent or known
             hypersensitivity to any component of tocilizumab (RoActemra)

          -  Receipt of any vaccine within 28 days prior to baseline (a patient's vaccination
             record and need for immunization prior to receiving tocilizumab/placebo must be
             carefully investigated)

          -  Positive tests for hepatitis B surface antigen (HBsAg), Hepatitis B core antibody
             (HbcAb) or hepatitis C serology

          -  Positive Quantiferon-TB® test for latent Tb without subsequent INH prophylaxis

          -  Patients with active Tb which had to be treated for Tb within 2 years before the
             screening visit