Tocilizumab Plus a Short Prednisone Taper for GCA
Condition: Giant Cell Arteritis
MeSH terms: Polymyalgia Rheumatica; Giant Cell Arteritis; Arteritis
Intervention: Tocilizumab; Prednisone
Intervention description: Tocilizumab is an interleukin-6 (IL-6) receptor inhibitor; Prednisone is an anti-inflammatory medication
Intervention MeSH terms: Prednisone; Glucocorticoids
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 50 Years
Healthy volunteers: No
Keywords: GCA; Tocilizumab; Prednisone

Summary:

      This is an open-label pilot study of tocilizumab (TCZ) 162 mg weekly administered
      subcutaneously for 52 weeks in combination with 8 weeks of oral prednisone.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Ability and willingness to provide written informed consent and to comply with the
             study protocol

          2. Diagnosis of GCA classified per the following criteria:

             • Age 50 years or older

             AND at least one of the following:

               -  Unequivocal cranial symptoms of GCA (new-onset localized headache, scalp
                  tenderness, temporal artery tenderness or decreased pulsation, ischemia-related
                  vision loss, or otherwise unexplained mouth or jaw pain upon mastication)

               -  Symptoms of polymyalgia rheumatica (PMR), defined as shoulder and / or hip girdle
                  pain associated with inflammatory morning stiffness

             AND at least one of the following:

               -  Cranial artery biopsy revealing features of GCA (e.g., mononuclear cell
                  infiltration or granulomatous inflammation).

               -  Evidence of large-vessel vasculitis by angiography or cross-sectional imaging
                  study such as Image result for magnetic resonance angiogram (MRA), Computed
                  tomography angiography (CTA) , or Image result for positron emission tomography
                  (PET) and computed tomography (CT) (PET-CT)

               -  Ultrasound demonstration of features of GCA in a cranial artery.

          3. New-onset or relapsing/refractory active disease defined as follows:

               -  New onset: diagnosis of GCA within 6 weeks of baseline visit

               -  Relapsing/refractory: diagnosis of GCA > 6 weeks before baseline visit

        AND

        • Active GCA within 6 weeks of baseline visit defined as the presence of clinical signs and
        symptoms [cranial or PMR] and erythrocyte sedimentation rate (ESR) ≥ 30 mm/hour or
        C-reactive protein (CRP) ≥ 10 mg/L)

        Exclusion Criteria:

          1. General exclusion criteria

               -  Major surgery within 8 weeks prior to screening or planned major surgery within
                  12 months after randomization

               -  Transplanted organs (except corneal transplant performed more than 3 months prior
                  to screening)

               -  Major ischemic event, unrelated to GCA, within 12 weeks of screening

          2. Exclusions related to prior or concomitant therapy*

               -  Treatment with any investigational agent within 12 weeks (or 5 half-lives of the
                  investigational drug, whichever is longer) of screening

               -  Previous treatment with cell-depleting therapies, including investigational
                  agents, including but not limited to Campath (alemtuzumab), anti-CD4 (cluster of
                  differentiation 4), anti-CD5, anti-CD3, anti-CD19, and anti-CD20

               -  Previous treatment with alkylating agents, such as chlorambucil, or with total
                  lymphoid irradiation

               -  Immunization with a live/attenuated vaccine within ≤ 4 weeks prior to baseline

               -  Treatment with cyclosporine A, azathioprine, cyclophosphamide or Mycophenolate
                  mofetil (MMF) within 4 weeks of baseline. Patients on methotrexate at screening
                  will require discontinuation of this agent prior to baseline visit.

               -  Treatment with etanercept within 2 weeks; infliximab, certolizumab, golimumab,
                  abatacept, or adalimumab within 8 weeks; or anakinra within 1 week of baseline

               -  Patients requiring systemic glucocorticoid therapy 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 TCZ

               -  Inability, in the opinion of the investigator, to withdraw GC treatment through
                  protocol-defined taper regimen due to suspected or established adrenal
                  insufficiency

                    -  Patients treated with TCZ before will be permitted to participate in the
                       trial if they demonstrated treatment efficacy and they did not discontinue
                       TCZ because of an adverse effect.

          3. Exclusions related to general safety

               -  History of severe allergic or anaphylactic reactions to human, humanized, or
                  murine monoclonal antibodies or to prednisone

               -  Evidence of serious uncontrolled concomitant cardiovascular, nervous system,
                  pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine
                  (including uncontrolled diabetes mellitus), psychiatric,
                  osteoporosis/osteomalacia, glaucoma, corneal ulcers/injuries, or gastrointestinal
                  (GI) disease

               -  Current liver disease, as determined by the investigator

               -  History of diverticulitis or active chronic ulcerative lower GI disease such as
                  Crohn's disease, ulcerative colitis, or other symptomatic lower GI conditions
                  that might predispose a patient to perforations

               -  Known active current or history of recurrent bacterial, viral, fungal,
                  mycobacterial, or other infections (including but not limited to tuberculosis
                  [TB] and atypical mycobacterial disease, hepatitis B and C, and herpes zoster,
                  but excluding fungal infections of the nail beds)

               -  Any major episode of infection requiring hospitalization or treatment with IV
                  antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks of
                  screening

               -  Active TB requiring treatment within the previous 3 years. Patients treated for
                  TB with no recurrence within 3 years are eligible

               -  Untreated latent TB infection (LTBI). Patients should be screened for latent TB
                  and, if positive, treated according to local practice guidelines prior to
                  initiating TCZ treatment. Patients treated for LTBI within 3 years are eligible.
                  Patients with current LTBI are eligible for enrollment one month after initiating
                  treatment for LTBI.

               -  Primary or secondary immunodeficiency (history of or currently active)

               -  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)

               -  Females of childbearing potential and females who are breastfeeding

               -  Males of reproductive potential who are not willing to use an effective method of
                  contraception, such as condom, sterilization, or true abstinence throughout study
                  and for a minimum of 6 months after study drug therapy

               -  History of alcohol, drug, or chemical abuse within 1 year prior to screening

          4. Laboratory exclusions

               -  ALT or AST > 1.5 × upper limit of normal (ULN)

               -  Total bilirubin > ULN

               -  Platelet count < 100× 109/L (100,000/mm3)

               -  Hemoglobin < 85 g/L (8.5 g/dL; 5.3 mmol/L)

               -  White blood cells < 3.0 × 109/L (3000/mm3)

               -  Absolute neutrophil count < 1.0 × 109/L (1000/mm3)

               -  Absolute lymphocyte count < 0.5 × 109/L (500/mm3)