CTLA4-Ig (Abatacept)for Prevention of Abnormal Glucose Tolerance and Diabetes in Relatives At -Risk for Type 1

Inclusion Criteria:

• Participant in TrialNet Natural History/Pathway to Prevention Study and thus, a relative of a proband with T1DM.
• Between the ages of 1-45 years at the time of enrollment in TN01 and age ≥ 6 at time of randomization in this trial.
• Willing to provide Informed Consent or have a parent or legal guardian provide informed consent if the subject is <18 years of age.

• Normal glucose tolerance by OGTT confirmed within 7 weeks (no more than 52 days) of baseline (visit 0). If previous abnormal glucose tolerance, has had two consecutive OGTTs with normal glucose tolerance.

  1. Fasting plasma glucose < 110 mg/dL (6.1 mmol/L), and
  2. 2 hour plasma glucose <140 mg/dL (7.8 mmol/L), and
  3. 30, 60, or 90 minute value on OGTT< 200mg/dL (11.1 mmol/L)
• At least two diabetes-related autoantibodies confirmed to be present on two occasions, not including mIAA. Confirmation of 2 positive autoantibodies must occur within the six months prior to randomization, but the confirmation does not have to involve the same 2 autoantibodies.
• Weight ≥ 20 kg at Baseline Visit.
• If a female participant with reproductive potential, willing to avoid pregnancy and undergo pregnancy testing prior to each infusion.
• At least three months from date of last live immunization.
• Willing to forgo live vaccines while receiving treatment on study and for three months following last study drug administration.

Exclusion Criteria:

• Abnormal Glucose Tolerance or Diabetes

  1. Fasting plasma glucose ≥ 110 mg/dL (6.1 mmol/L), or
  2. 2 hour plasma glucose ≥ 140 mg/dL (7.8 mmol/L), or
  3. 30, 60, 90 minute plasma glucose during OGTT ≥ 200 mg/dL (11.1 mmol/L)
• Insulin autoantibodies (mIAA).
• Are immunodeficient or have clinically significant chronic lymphopenia.
• Have an active infection at time of randomization.
• Have a positive PPD test result or history of previously treated TB, or positive interferon-gamma release assay (IGRA) test.
• Be currently pregnant or lactating, or anticipate getting pregnant within 3 months of the last study drug administration.
• Use of medications known to influence glucose tolerance.
• Require use of other immunosuppressive agents.
• Have serologic evidence of current or past HIV, Hepatitis B (positive for Hepatitis B core antibody or surface antigen), or Hepatitis C infection.
• Have serological evidence of current CMV infection.
• Have evidence of active EBV infection.
• Have any complicating medical issues or abnormal clinical laboratory results that interfere with study conduct or cause increased risk. These include pre-existing cardiac disease, COPD, neurological, or blood count abnormalities (such as lymphopenia, leukopenia, or thrombocytopenia).