Tocilizumab (TCZ) in New-onset Type 1 Diabetes

Inclusion Criteria

• Male or female aged 6-45 years*

-*Current Institutional Review Board (IRB)-approved age eligibility criteria is restricted to subjects 6 to 17 years of age at time of study enrollment

• Diagnosis of type 1 diabetes mellitus (T1DM), using the American Diabetes Association T1DM criteria, within 100 days of study enrollment
• Positive for at least one diabetes-related autoantibody, including but not limited to:
• Glutamate decarboxylase (GAD-65)
• Insulin, if obtained within 10 days of the onset of exogenous insulin therapy
• Insulinoma antigen-2 (IA-2)
• Zinc transporter-8 (ZnT8)
• Peak stimulated C-peptide level ≥ 0.2 pmol/mL following a mixed-meal tolerance test (MMTT) conducted at least 21 days from diagnosis and within 37 days of randomization (V0)
• Signed informed consent (and informed assent of minor, if applicable).

Exclusion Criteria

• Severe reaction or anaphylaxis to human, humanized or murine monoclonal antibodies
• History of malignancy or serious uncontrolled cardiovascular, nervous system, pulmonary, renal, or gastrointestinal disease, or significant dyslipidemia
• Any history of recent serious bacterial, viral, fungal, or other opportunistic infections
• Have serologic evidence of current or past HIV (Human immunodeficiency virus), Hepatitis B, or Hepatitis C
• Positive QuantiFERON Tuberculosis (TB) test, history of TB, or active TB infection
• Active infection with Epstein-Barr virus (EBV) as defined by EBV viral load ≥10,000 copies per mL of whole blood
• Active infection with Cytomegalovirus (CMV) as defined by CMV viral load ≥10,000 copies per mL of whole blood
• Diagnosis of liver disease or elevated hepatic enzymes, as defined by Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), or both > 1.5 x the upper limit of age-determined normal (ULN) or total bilirubin > ULN
• Current or prior treatment that is known to cause a significant, ongoing change in the course of T1D or immunologic status
• Current or prior (within last 30 days) use of drugs other than insulin to treat hyperglycemia (e.g. metformin, sulfonylureas, glinides, thiazolidinediones, exenatide, liraglutide, Dipeptidyl peptidase-4 Intravenous (DPP-IV) inhibitors, or amylin)
• Current use of any medication known to significantly influence glucose tolerance (e.g., atypical antipsychotics, diphenylhydantoin, niacin)
• Any of the following hematologic abnormalities, confirmed by repeat tests:
• White blood count 14,000/microL
• Lymphocyte count <500/microL
• Platelet count <150,000 /microL
• Hemoglobin <8.5 g/dL
• . Neutrophil count <2,000 cells/microL.
• Females who are pregnant, lactating, or planning on pregnancy during the 2- year study period
• History or diagnoses of other autoimmune diseases with the exception of stable thyroid or celiac disease
• History of alcohol, drug or chemical abuse within 1 year prior to study eligibility screening evaluation
• Any medical or psychological condition that in the opinion of the principal investigator would interfere with safe completion of the trial
• Prior participation in a clinical trial that could increase risks associated with this clinical trial
• Receipt of live vaccine (e.g. varicella, measles, mumps, rubella, cold-attenuated intranasal influenza vaccine, bacillus Calmette-Guérin, and small pox) in the 6 weeks before randomization
• High lipid levels (fasting Low-density lipoprotein (LDL) cholesterol ≥160 mg/dL)
• History of significant allergy (e.g. anaphylaxis) to milk or soy proteins.