Modulation of STAT3 Signaling With Siltuximab in Type 1 Diabetes

This is an open-label (all people know the identity of the intervention), single center,
non-randomized (patients are not assigned by chance to treatment groups), Mechanistic Study
(a study that focuses on the biologic activity of the drug, rather than on disease
treatment). Up to 10 patients with Type 1 diabetes (T1D) will be enrolled in the study.
Participants will receive a single dose of siltuximab and blood samples will be obtained a
total of 6 times until 12 weeks after dosing. Cells will be isolated from the blood samples
and used to measure specific activities of cells in the immune system. Safety evaluations for
adverse events, clinical laboratory tests, vital signs, and physical examination will be
performed throughout the study. The end of study is the date of the last assessment for the
last patient.

Inclusion Criteria:

1. Positive for at least one diabetes-related autoantibody any time since diagnosis,
including by not limited to: Glutamate decarboxylase (GAD-65) Insulin, if obtained
within 10 days of the onset of exogenous insulin therapy; IA-2; ZnT8

2. Peak stimulated C-peptide level ≥ 0.1 pmol/mL following a mixed meal tolerance test
(MMTT) conducted within 60 days of enrollment

3. Females of child-bearing potential must be willing to use effective birth control and
refrain from donating eggs for the purposes of assisted reproduction for duration of
study.

4. A woman of childbearing potential must have a negative serum (β-human chorionic
gonadotropin [β-hCG]) or urine pregnancy test at screening and prior to dosing.

5. During the study, and for 3 months after receiving the study agent, a woman must agree
to not donate eggs (ova, oocytes) for the purposes of assisted reproduction.

6. Willing and able to give informed consent for participation.

Exclusion Criteria:

1. History of severe reaction or anaphylaxis to human, humanized or murine monoclonal
antibodies;

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

3. Any history of recent (within 3 months) serious bacterial, viral, fungal, or other
opportunistic infections;

4. History or serologic evidence of current or past HIV, Hepatitis B, or Hepatitis C;

5. Positive QuantiFERON or PPD TB test, history of tuberculosis, or active TB infection;

6. Active infection with EBV ;

7. Active infection with CMV;

8. Diagnosis of liver disease or elevated hepatic enzymes, confirmed by repeat tests, as
defined by ALT, AST, or both > 1.5 x the upper limit of age-determined normal (ULN) or
total bilirubin > ULN;

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

- White blood count <3,000/μL or >14,000/μL

- Lymphocyte count <500/μL

- Platelet count <150,000 /μL

- Hemoglobin <8.5 g/dL or > or = to 17 g/dL

- Neutrophil count <2,000 cells/μL

10. Females who are pregnant or lactating;

11. 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 treatment;

12. Receipt of non-live vaccine in the 4 weeks before treatment;

13. Any medical or psychological condition that in the opinion of the Sponsor Investigator
would interfere with the safe completion of the trial;

14. Receipt of an investigational drug (including investigational vaccines) or used an
invasive investigational medical device within 3 months or 5 half-lives before
enrollment or is currently enrolled in the treatment stage of an investigational
study;

15. Receipt of any immune-modulating biologic drug within 3 months of enrolling in the
study.