Modulation of STAT3 Signaling With Siltuximab in Type 1 Diabetes

Inclusion Criteria

• 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
• Peak stimulated C-peptide level ≥ 0.1 pmol/mL following a mixed meal tolerance test (MMTT) conducted within 60 days of enrollment
• 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.
• 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.
• 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.
• Willing and able to give informed consent for participation.

Exclusion Criteria

• History of severe reaction or anaphylaxis to human, humanized or murine monoclonal antibodies;
• History of malignancy or serious uncontrolled cardiovascular disease or hypertension, nervous system, pulmonary, renal, or gastrointestinal disease, or significant dyslipidemia despite therapy;
• Any history of recent (within 3 months) serious bacterial, viral, fungal, or other opportunistic infections;
• History or serologic evidence of current or past HIV, Hepatitis B, or Hepatitis C;
• Positive QuantiFERON or PPD TB test, history of tuberculosis, or active TB infection;
• Active infection with EBV ;
• Active infection with CMV;
• 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;
• Any of the following hematologic abnormalities, confirmed by repeat tests:
• White blood count 14,000/μL
• Lymphocyte count or = to 17 g/dL
• Neutrophil count <2,000 cells/μL
• Females who are pregnant or lactating;
• 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;
• Receipt of non-live vaccine in the 4 weeks before treatment;
• Any medical or psychological condition that in the opinion of the Sponsor Investigator would interfere with the safe completion of the trial;
• 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;
• Receipt of any immune-modulating biologic drug within 3 months of enrolling in the study.