Tocilizumab (TCZ) in New-onset Type 1 Diabetes

Staggered enrollment is planned for this trial.

Prior to initiating the study in the pediatric age group (6-17 years old), 30-99 eligible
adults (ages 18-45 years) will be randomized 2:1 to tocilizumab or placebo, respectively.
Once the first thirty adult participants have completed 12 weeks of treatment, the FDA and
Data and Safety Monitoring Board (DSMB) will review available data (e.g., interim analysis)
to weigh potential risks and benefits before opening the trial to pediatric participants.

As of ≥ May 15, 2017: Study enrollment is limited to participants ages 6 to 17 years
inclusive.

Inclusion Criteria:

1. 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

2. Diagnosis of type 1 diabetes mellitus (T1DM), using the American Diabetes Association
T1DM criteria, within 100 days of study enrollment

3. Positive for at least one diabetes-related autoantibody, including but not limited to:

1. Glutamate decarboxylase (GAD-65)

2. Insulin, if obtained within 10 days of the onset of exogenous insulin therapy

3. Insulinoma antigen-2 (IA-2)

4. Zinc transporter-8 (ZnT8)

4. 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)

5. Signed informed consent (and informed assent of minor, if applicable).

Exclusion Criteria:

1. Severe reaction or anaphylaxis to human, humanized or murine monoclonal antibodies

2. History of malignancy or serious uncontrolled cardiovascular, nervous system,
pulmonary, renal, or gastrointestinal disease, or significant dyslipidemia

3. Any history of recent serious bacterial, viral, fungal, or other opportunistic
infections

4. Have serologic evidence of current or past HIV (Human immunodeficiency virus),
Hepatitis B, or Hepatitis C

5. Positive QuantiFERON Tuberculosis (TB) test, history of TB, or active TB infection

6. Active infection with Epstein-Barr virus (EBV) as defined by EBV viral load ≥10,000
copies per mL of whole blood

7. Active infection with Cytomegalovirus (CMV) as defined by CMV viral load ≥10,000
copies per mL of whole blood

8. 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

9. Current or prior treatment that is known to cause a significant, ongoing change in the
course of T1D or immunologic status

10. 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)

11. Current use of any medication known to significantly influence glucose tolerance
(e.g., atypical antipsychotics, diphenylhydantoin, niacin)

12. Any of the following hematologic abnormalities, confirmed by repeat tests:

1. White blood count <3,000/microL or >14,000/microL

2. Lymphocyte count <500/microL

3. Platelet count <150,000 /microL

4. Hemoglobin <8.5 g/dL

5. . Neutrophil count <2,000 cells/microL.

13. Females who are pregnant, lactating, or planning on pregnancy during the 2- year study
period

14. History or diagnoses of other autoimmune diseases with the exception of stable thyroid
or celiac disease

15. History of alcohol, drug or chemical abuse within 1 year prior to study eligibility
screening evaluation

16. Any medical or psychological condition that in the opinion of the principal
investigator would interfere with safe completion of the trial

17. Prior participation in a clinical trial that could increase risks associated with this
clinical trial

18. 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

19. High lipid levels (fasting Low-density lipoprotein (LDL) cholesterol ≥160 mg/dL)

20. History of significant allergy (e.g. anaphylaxis) to milk or soy proteins.