Please select the eligibility criteria that correspond to the clinical trial below.
Title: Clinical Trial Phase III, Parallel Group, Randomized, Placebo-controlled, Double-blind, Multicenter Study to Evaluate the Efficacy and Safety of Tocilizumab Administration in Patients With Moderate-to-severe or Sight-threatening Graves' Ophthalmopathy (GO), That Had Not Responded Adequately to Treatment With Intravenous Corticoid Pulses.
Brief Summary: The purpose is to investigate tocilizumab administration in patients with moderately to severely or sight-threatening GO (Graves' ophthalmopathy) without response to treatment with corticoid intravenous pulses. Currently, these patients only have surgery as therapeutic alternative.

The principal aim of this study is to evaluate efficacy and safety of tocilizumab treatment in order to provide a better alternative to surgery for this patients.


Options:
A: Inclusion Criteria:

* Between the ages of 8 and 45 years
* Within 3 months of diagnosis of type 1 diabetes
* Have presence of at least one diabetes-related autoantibody
* Must have stimulated C-peptide levels of at least 0.2 pmol/ml measured during a mixed meal tolerance test (MMTT) within one month of randomization
* If female with reproductive potential, willing to avoid pregnancy and undergo pregnancy testing while participating in the study
* Have not received an immunization for at least one month
* Must be willing to comply with intensive diabetes management
* Must weigh at least 25 kg at study entry

Exclusion Criteria:

* Are immunodeficient or have clinically significant chronic lymphopenia
* Have an active infection or positive purified protein derivative (PPD) test result
* Currently pregnant or lactating; or anticipate becoming pregnant.
* Require chronic use of steroids
* Have current or past HIV, hepatitis B, or hepatitis C infection
* Have any complicating medical issues that interfere with study conduct or cause increased risk
* Have a history of malignancies
* Currently using non-insulin pharmaceuticals that effect glycemic control
* Currently participating in another type 1 diabetes treatment study
B: Inclusion Criteria:

* Patients with clinical activity score (CAS) of ≥4 and moderate to severe disease severity, as defined by thyroid eye disease severity scale based on the first letter of the defining characteristic of each class, the classification is known as: 'no signs or symptoms; only signs; soft tissue; proptosis; extraocular muscle; cornea; sight loss' (NOSPECS) score
* Euthyroid for at least 6-8 weeks
* No immediate need for decompression surgery
* With disease progression over the previous 1-2 months or without evident improvement in the prior 6 months.

Exclusion Criteria:

* Corticosteroid use in the preceding 4 weeks
* HIV, hepatitis C or hepatitis B infections
* Denied consent for HIV or hepatitis testing
* Mild or inactive Graves' ophthalmopathy
* Orbital radiotherapy within 18 months or orbital surgery within the past year
* Absolute neutrophil count \< 1,500/mm\^3
* Pregnant or nursing patients
* Coronary artery disease, congestive heart failure, significant arrhythmias, significant infection or immunodeficiency, other serious illnesses
C: Principal Inclusion Criteria:

Patients diagnosed GO with CAS ≥ 4 and an index of severity, according EUGOGO guidelines, 1. moderately to severely or 2. sight-threatening GO, after receiving corticosteroid pulse treatment due to:

* Poor response to intravenous corticosteroid pulses Or
* Recurrence of the GO, after treatment with intravenous corticosteroids

Exclusion Criteria:

* Orbital decompression surgery needed immediately
* Active smoker
* Patients who could need treatment with radioactive iodine or thyroidectomy during the study
* Pregnant patient or patient who is planning to become pregnant during the study
* History of chronic recurrent or active infection
* History of intestinal ulceration or diverticulitis
* Patients with a history of chronic liver disease or liver disorders: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) above 5 times upper limit of normal (ULN)
* History of HIV, hepatitis C or hepatitis B Positive
* Neutrophil count \< 0.5 × 109/L or a platelet count \< 50×103/μL
* Simultaneous use or contraindications to the use of immunosuppressive agents
* A treatment with another investigational drug within four weeks of selection or five half-lives of study drug
* Cardiovascular or cerebrovascular disease clinically significant
* Uncontrolled diabetes mellitus
* Use of corticosteroids during four weeks before to inclusion period
* History of reactions or anaphylactic allergic severe human monoclonal antibodies, humanized or murine
* Uncontrolled pathologies, whose exacerbations are treated with corticosteroids
D: Inclusion Criteria:

* Clinical diagnosis of Graves' disease associated with active TED and a clinical activity score of ≥ 4
* Fewer than 9 months from onset of TED
* No previous medical or surgical treatment, excluding local supportive measures and oral steroids if the maximum cumulative dose is less than 1000 mg methylprednisolone or equivalent with at least 6 weeks between last administration of oral steroids and randomization
* Euthyroid or with mild hypo or hyperthyroidism defined as free thyroxine (FT4) and free triiodothyronine (FT3) levels less than 50% above or below the normal limits (every effort should be made to correct the mild hypo- or hyperthyroidism promptly)

Exclusion Criteria:

* Optic neuropathy
* Corneal decompensation unresponsive to medical management
* Oral or IV steroid treatment for any non-TED reason in the preceding 3 months
* Poorly controlled diabetes
* Platelets \< 100 x 10\^9/L
* Hemoglobin concentration \> 2 g/dL below the lower limit of normal

Answer: C