Siplizumab in T1DM

Inclusion Criteria: 1. Ability to provide informed consent (parental permission and informed assent of minor, if applicable). 2. Male or female between 8 to 45 years of age. 3. Diagnosis of T1DM within 18 months (550 days) of enrollment (V0). 4. Positive for at least one diabetes-related autoantibody, including: 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), or 4. Zinc transporter-8 (ZnT8). 5. Peak stimulated C-peptide level \> 0.15 nmol/L following a MMTT conducted ≥ 21 days from diagnosis and within 37 days of enrollment (V0). 6. Completion of a SARS-CoV-2 vaccination, according to current CDC recommendations and FDA approval(s) or emergency use authorization(s). If the participant requires administration of vaccine(s) to meet eligibility requirements, they must complete the vaccination series at least 2 weeks prior to enrollment (V0). Exclusion Criteria: 1. 1\. Use of investigational drugs within 24 weeks of participation with the exception of any vaccine for the prevention of SARS-CoV-2 infection and emergency use authorization medications for treating SARS-CoV-2. 2. Severe reaction or anaphylaxis to humanized monoclonal antibodies. 3. Inability to complete a mixed meal tolerance test: 1. History of significant allergy (e.g., anaphylaxis) to milk or soy proteins. 2. Inability to disable hybrid closed loop system. 4. History of recent (within 180 days of V0) or ongoing uncontrolled bacterial, viral, fungal or other opportunistic infections, including: 1. Human immunodeficiency virus (HIV), 2. Current or prior infection with hepatitis B (HBV), as indicated by positive HBsAg or positive HBcAb, 3. Current or prior hepatitis C (HCV), unless treated with anti-viral therapy with achievement of a sustained virologic response (undetectable viral load 12 weeks after cessation of therapy), 4. Positive QuantiFERON-TB Gold or QuantiFERON-TB Gold Plus tests. PPD or T-SPOT®.TB may be substituted for the QuantiFERON-TB Gold or QuantiFERON-TB Gold Plus tests, 5. Active infection with EBV as detected by PCR or serology at the screening visit (V-1), 6. Active infection with cytomegalovirus (CMV) as detected by PCR or serology at the screening visit (V-1), 5. Positive molecular testing of SARS-CoV-2 within 30 days of V-1. 6. Any of the following laboratory abnormalities confirmed by repeat tests at least 1 week apart: 1. White blood count (WBC) \< 3 x 103/μL;, 2. CD 3+ CD4+, T cell count below the lower limit of normal, 3. Platelet count \< 150,000 /μL, 4. Hemoglobin \< 10 g/dL, 5. ALT ≥ 2x upper limit of normal (ULN) or 6. AST ≥ 2x ULN 7. Serum creatinine \>1.5x ULN in adults or \>ULN in pediatrics. 8. Absolute lymphocyte count (ALC) below the LLN. 7. Prior or current treatment that is known to alter the natural history of T1DM or immunologic status, including high dose inhaled, extensive topical or systemic glucocorticoids. 8. Current or prior (within last 14 days of the V-1 MMTT) use of any medication known to influence glucose tolerance (e.g., atypical antipsychotics, diphenylhydantoin, thiazide, or other potassium-depleting diuretics, β-adrenergic blockers, niacin). 9. Current or prior (within the last 30 days of the V-1 MMTT) use of non-insulin medications to treat insulin resistance or elevated glucose levels. 10. Previous or current diagnosis of malignancy. 11. History of bone marrow transplantation, solid organ transplantation, or primary immunodeficiencies. 12. History or diagnoses of other autoimmune diseases with the exception of stable thyroid or celiac disease. 13. History of significant cardiovascular disease. 14. Vaccination with a live attenuated vaccine (e.g., varicella, measles, mumps, rubella, cold-attenuated intranasal influenza vaccine, bacillus Calmette- Guérin, and smallpox) within 30 days of V0. 15. Women of child-bearing potential who are unwilling to use a medically acceptable form of contraception from 14 days prior to V0 until study Week 52. 16. Women who are pregnant, lactating, or planning on pregnancy during the study. 17. Current, diagnosed mental illness (e.g., severe depression), current diagnosed or self-reported drug, or alcohol abuse that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements. 18. Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.