Clinical trial: Tocilizumab Plus a Short Prednisone Taper for GCA (NCT03726749)

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)
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 50 Years old.


Patient description (medical language): A 61-year-old man comes to the emergency department complaining of an acute vision disturbance. He had an episode of vision disturbance in the right eye that occurred suddenly and resolved spontaneously in 15 minutes. He also has right jaw pain while chewing.  He also complains of fatigue and hip muscle aches over the last several months.  The patient has a history of mild hyperlipidemia that has been controlled by diet and lifestyle modifications.  On examination, his blood pressure is 130/70 mm Hg and pulse is 66/min.  Neurological examination is unremarkable.  Visual examination is also normal. ESR is 103 mm/h. Temporal artery biopsy shows multinuclear giant cells and internal elastic membrane fragmentation.

Patient description (patient's own words): I’m a 61-year-old man and I came to the ER because I had a sudden episode where I couldn’t see out of my right eye. It only lasted about 15 minutes and went away on its own but it really scared me. I’ve also been having pain in my right jaw when I chew. For the past few months I’ve felt really tired and noticed my hips ache a lot. I have a history of mild cholesterol issues but I’ve been managing that with my diet and lifestyle. When the doctors checked me my blood pressure and pulse were normal and my vision and neurological exams didn’t show anything wrong. However they ran some tests and said my ESR levels were very high and a biopsy of my temporal artery showed some inflammation and damage.

Does the patient match the trial criteria? Entailment