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

* Hospitalized
* COVID-19 pneumonia confirmed by a positive polymerase chain reaction (PCR) of any specimen and radiographic imaging
* SpO2 \< 94% while on ambient air

Inclusion Criteria Specific to Long-Term Extension

* Participated in Study ML42528 (EMPACTA) (includes participants who completed or discontinued early from the main study)

Exclusion Criteria

* Known severe allergic reactions to TCZ or other monoclonal antibodies
* Require continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), or invasive mechanical ventilation
* Suspected active bacterial, fungal, viral, or other infection (besides COVID-19)
* In the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments
* Immunocompromised (besides well-controlled HIV) or on immunosuppressive therapy (except for steroids for COVID), advanced cancer
* Have received oral anti-rejection or immunomodulatory drugs (including TCZ) within the past 3 months
* Participating in another interleukin (IL)-6 antagonist clinical trial or other drug clinical trials (participation in COVID-19 anti-viral trials may be permitted if approved by Medical Monitor)
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 10 x upper limit of normal (ULN) detected within 24 hours at screening (according to local laboratory reference ranges)
* Absolute neutrophil count (ANC) \< 1000/uL at screening (according to local laboratory reference ranges)
* Platelet count \< 50,000/uL at screening (according to local laboratory reference ranges)
* Pregnant or breastfeeding, or positive pregnancy test in a pre-dose examination
* Treatment with an investigational drug within 5 half lives or 30 days (whichever is longer) of randomization (investigational COVID-19 antivirals may be permitted if approved by Medical Monitor)
* Any serious medical condition or abnormality of clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study
* Any history of Diverticulitis or GI perforation
* Use of systemic corticosteroids unless on a stable chronic dose
B: Key Inclusion Criteria:

* Laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction (PCR), result from any specimen (or other commercial or public health assay) within 2 weeks prior to randomization and no alternative explanation for current clinical condition
* Hospitalized with illness of any duration with evidence of pneumonia, requires supplemental oxygen and/or assisted ventilation and meets one of the following:
* Phase 2 and Phase 3 Cohort 1:

Meets 1 of the following criteria at baseline:

* Severe disease OR
* Critical disease OR
* Multi-system organ dysfunction OR
* Immunocompromised
* Phase 3 Cohort 2:

Patients must be receiving mechanical ventilation to treat respiratory failure due to COVID-19

* Phase 3 Cohort 3:

Patients must be receiving supplemental oxygen to treat hypoxemia delivered by one of the following devices:

* Non-rebreather mask, OR
* High-flow device with at least 50% FiO2, OR
* Non-invasive positive pressure ventilator
* Ability to provide informed consent signed by study patient or legally acceptable representative
* Willingness and ability to comply with study-related procedures/assessments

Key Exclusion Criteria:

* In the opinion of the investigator, not expected to survive for more than 48 hours from screening
* Presence of any of the following abnormal laboratory values at screening: absolute neutrophil count (ANC) less than 2000 mm3, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 5 x upper limit of normal (ULN), platelets \<50,000 per mm3
* Treatment with anti-IL 6, anti-IL-6R antagonists, or with Janus kinase inhibitors (JAKi) in the past 30 days or plans to receive during the study period
* Current treatment with the simultaneous combination of leflunomide and methotrexate
* Known active tuberculosis (TB), history of incompletely treated TB, suspected or known extrapulmonary TB, suspected or known systemic bacterial or fungal infections
* Participation in a double-blind clinical research study evaluating an investigational product (IP) or therapy within 3 months and less than 5 half-lives of IP prior to the screening visit (The use of remdesivir, hydroxychloroquine, or other treatments being used for COVID-19 treatments in the context of an open-label study, Emergency Use Authorization (EUA), compassionate use protocol or open-label use is permitted)
* Any physical examination findings, and/or history of any illness, concomitant medications or recent live vaccines that, in the opinion of the study investigator, might confound the results of the study or pose an additional risk to the patient by their participation in the study
* Known systemic hypersensitivity to sarilumab or the excipients of the drug product
* Phase 3 Cohort 2 and Cohort 3 only:
* Known or suspected history of immunosuppression or immunodeficiency disorder
* Patients who require renal replacement therapy for acute kidney injury at randomization or who required renal replacement therapy within 72 hours prior to randomization
* Patients who have circulatory shock requiring vasopressors at randomization or within 24 hours prior to randomization
* Use of extracorporeal life support (eg, ECMO) or, in the opinion of the investigator, there is a high likelihood that extracorporeal life support will be initiated within 48 hours after randomization

NOTE: Other protocol defined inclusion / exclusion criteria may apply
C: Inclusion Criteria:

* Adults aged 18-90
* Confirmed laboratory COVID-19 infection by RT-PCR
* Meeting severe or critical criteria of COVID-19 infection as defined at treating hospital
* Confirmed pneumonia by chest radiograph or computed tomography
* Fever defined as temperature ≥ 36.6 °C armpit, ≥ 37.2 °C oral, or ≥ 37.8 °C rectal
* Oxygen saturation less than 92%

Exclusion Criteria:

* Recent use of illicit drugs or alcohol abuse
* Known allergy to tradipitant or other neurokinin-1 antagonists
* Pregnancy
* Known HIV, HBV, or HCV infection
* Malignant tumor, other serious systemic diseases
* Inability to provide informed consent or to have an authorized relative or designated person provide informed consent, or to comply with the protocol requirements
D: 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

Answer: D