Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III, Multicenter, Randomized, Double-Blind Placebo-Controlled Study to Assess the Efficacy and Safety of Tocilizumab in Subjects With Giant Cell Arteritis
Brief Summary: This multicenter, randomized, double-blind, placebo-controlled, parallel-group study will evaluate the efficacy and safety of tocilizumab in participants with GCA. The study will consist of 2 parts: a 52-week double-blind treatment period (Part 1) followed by a 104-week open label long-term follow-up period (Part 2). In Part 1 of the study eligible participants will be randomized to receive either tocilizumab every week (qw) or every 2 weeks (q2w) or placebo for 52 weeks, with tapering oral daily doses of prednisone. After Week 52, participants in remission will stop study treatment and enter long-term follow-up, whereas participants with disease activity or flares will receive open-label tocilizumab or other treatment at the discretion of the investigator for a maximum period of 104 weeks.


Options:
A: Inclusion Criteria:

* Male and females with 18 years and older
* Confirmed diagnosis of SARS-CoV 2 infection
* More than 3 days of symptoms related to COVID-19
* Computed tomography (or Chest X-Ray) with COVID-19 alterations
* Both of the criteria

  1. Need for oxygen supplementation to keep SPO2 \> 93% OR need for mechanical ventilation for less than 24 hours before the randomization
  2. At least two of the following inflammatory tests above the cutoff :

     1. D-dimer \> 1,000 ng/mL
     2. Reactive C protein \> 5 mg/dL
     3. Ferritin \> 300 mg/dL
     4. Lactate dehydrogenase \> upper level limit

Exclusion Criteria:

* Need for mechanical ventilation for 24 hours or more before the randomization
* Hypersensitivity to tocilizumab
* Patients without therapeutic perspective or in palliative care
* Active non controlled infections
* Other clinical conditions that contraindicate tocilizumab, according to the assistant physician
* Low neutrophils count (\< 0.5 x 109/L)
* Low platelets count (\< 50 x 109/L)
* Liver disease, cirrhosis or elevated AST or ALT above 5 times the upper level limit
* Renal disease with estimate glomerular filtration below 30 mL/min/1.72 m2 (MDRD or CKD-EPI scores)
* Active diverticulitis
* Breastfeeding women
* Pregnancy
B: Inclusion Criteria:

* Diagnosis of GCA classified according to age \>/=50 years; history of ESR \>/=50 mm/hr or history of CRP \>/=2.45 mg/dL; and at least one of the following: unequivocal cranial symptoms of GCA or symptoms of polymyalgia rheumatica \[PMR\]; and at least one of the following: temporal artery biopsy revealing features of GCA or evidence of large-vessel vasculitis by angiography or cross-sectional imaging
* New onset (diagnosis within 6 weeks of baseline) or refractory (diagnosis greater than \[\>\] 6 weeks before baseline and previous treatment with \>/= 40 milligrams per day prednisone \[or equivalent\] for at least 2 consecutive weeks at any time) GCA
* Active disease (presence of clinical signs and symptoms \[cranial or PMR\] and ESR \>/=30 mm/hour or CRP \>/=1 mg/dL) within 6 weeks of baseline visit

Exclusion Criteria:

* Major surgery within 8 weeks prior to screening or planned within 12 months after randomization
* Transplanted organs (except corneas with transplant performed \>3 months prior to screening)
* Major ischemic event, unrelated to GCA, within 12 weeks of screening
* Prior treatment with any of the following: investigational agent within 12 weeks (or 5 half-lives of the investigational drug, whichever is longer) of screening; cell-depleting therapies including investigational agent; intravenous (IV) gamma globulin or plasmapheresis within 6 months of baseline; alkylating agents or with total lymphoid irradiation; tocilizumab; hydroxychloroquine, cyclosporine A, azathioprine, or mycophenolate mofetil within 4 weeks of baseline; etanercept within 2 weeks of baseline; infliximab, certolizumab, golimumab, abatacept, or adalimumab within 8 weeks of baseline; anakinra within 1 week of baseline; tofacitinib; cyclophosphamide within 6 months of baseline; \>100 milligrams of daily IV methylprednisolone within 6 weeks of baseline
* Participants requiring systemic glucocorticoids 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 the test article
* History of severe allergic reactions to monoclonal antibodies or to prednisone
* Evidence of serious uncontrolled concomitant disease (for example, cardiovascular, respiratory, renal, endocrine, psychiatric, corneal ulcers/injuries, or gastrointestinal \[GI\] disease)
* Current liver disease, as determined by the investigator
* History of diverticulitis, inflammatory bowel disease, or other symptomatic GI tract condition that might predispose to bowel perforation
* Known active or history of recurrent bacterial, viral fungal, mycobacterial, or other infection
* Primary or secondary immunodeficiency
* Evidence of malignancies diagnosed within 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)
* Inadequate hematologic, renal or liver function
* Positive for hepatitis B or hepatitis C infection
C: Inclusion criteria:

Subjects who meet all of the following criteria will be eligible to participate in the study:

1. Must have provided informed consent in a manner approved by the Investigator's Institutional Review Board (IRB) or Independent Ethics Committee (IEC) prior to any assessments. If a patient is unable to provide informed consent due to their medical condition, the patient's legally authorized representative may consent on behalf of the study patient, as permitted by local law and institutional Standard Operating Procedures;
2. Age Range: 19-85 years old
3. Male or female gender
4. Confirmed SARS-CoV-2 infection by nasopharyngeal swab PCR or serum assay for IgM antibody
5. Requiring hospital but not mechanical ventilation
6. Oxygen supplementation not greater than 10L delivered by any device
7. WITH evidence of severe COVID-19 (at least 2 of the following):

   1. Fever \> 38C within 72 hours
   2. Pulmonary infiltrate on CXR
   3. Need for supplemental O2 to maintain saturation \> 92%
8. AND at least 1 of the following:

   1. Ferritin \> 500 ng/ml
   2. CRP \> 50 mg/L
   3. LDH \>250 U/L
   4. D-dimer \> 1000 ng/mL
9. Women of childbearing potential (ie, not post-menopausal or surgically sterilized) must have a negative highly sensitive urine or serum pregnancy test before randomization. Participating women of childbearing potential must be willing to consistently use effective methods of contraception (ie, condom, combined oral contraceptive, implant, injectable, indwelling intrauterine device, or a vasectomized partner) from screening until at least 90 days after administration of the last dose of study drug;
10. The subject must be willing and able to provide informed consent and abide all study requirements and restrictions.

Exclusion criteria:

Subjects who meet any of the following criteria will be excluded from participation in the study:

1. Unable to provide verbal informed consent or have verbal agreement to participate through attestation and signature of a Witness required, as outlined in the Partners IRB's Table for Consenting in COVID Research that is More than Minimal Risk.
2. Subjects between the ages of 79 and 86 will be excluded if they have NYHA Class III/IV heart failure, insulin-dependent diabetes mellitus, angina, or treatment of a malignancy (excluding non-melanoma skin cancer) within six months
3. Uncontrolled bacterial, fungal, or non-COVID viral infection
4. Active TB
5. Any prior investigational immunosuppressive therapy within 28-days or 3 half-lives of the agent (for instance with biologic or JAK inhibitor)
6. Any concurrent immunosuppressive medication that the PI believes would put the patient at higher risk
7. Receipt of intravenous tocilizumab for the treatment of a non-COVID condition within three weeks of the first COVID symptom
8. History of hypersensitivity to tocilizumab
9. Any concurrent immunosuppressive medication that the PI believes would put the patient at higher risk
10. Treatment with other biologic or small-molecule immunosuppressive therapy such as IL1R-antagonism, JAK inhibition, or other agents
11. Treatment with convalescent plasma
12. History of diverticulitis or bowel perforation
13. ANC \<500, Platelets \<50,000\*
14. AST/ALT \> 5X ULN
15. Women who are pregnant or planning to get pregnant in the next 90 days;
16. Any condition that could interfere with, or for Known allergy to the study drug or any of its ingredients or known allergy to any other anti IL 6 agents;
17. Any condition that could interfere with or for which the treatment might interfere with, the conduct of the study or interpretation of the study results, or that would, in the opinion of the Investigator, increase the risk of the subject by participating in the study.

We note that anti-viral therapies may be administered to subjects if given in the context of a clinical trial. Nitric oxide treatment is also permitted at the discretion of the care team, ideally in the context of a clinical trial. Co-treatment chloroquine, hydroxychloroquine, and/or azithromycin is permitted for subjects in this protocol.
D: Inclusion Criteria:

1. Patients included in the CORIMUNO-19 cohort
2. Patients belonging to one of the 2 following groups:

   * Group 1: Cases meeting all of the following criteria

     * Requiring more than 3L/min of oxygen
     * OMS/WHO progression scale = 5
     * No NIV or High flow
   * Group 2: Cases meeting all of the following criteria

     * Respiratory failure AND (requiring mechanical ventilation OR NIV OR High flow)
     * WHO progression scale \>=6
     * No do-not-resuscitate order (DNR order)

Exclusion Criteria:

* Patients with exclusion criteria to the CORIMUNO-19 cohort.
* Known hypersensitivity to Tocilizumab or to any of their excipients.
* Pregnancy
* Current documented bacterial infection
* Patient with any of following laboratory results out of the ranges detailed below at screening should be discussed depending of the medication:
* Absolute neutrophil count (ANC) ≤ 1.0 x 109/L
* Haemoglobin level: no limitation
* Platelets (PLT) \< 50 G /L
* SGOT or SGPT \> 5N

Answer: B