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

• Status: Active, not recruiting
• Trial end date: 2021-11-01
• Target enrollment: 0
• Participant gender: All

Summary

The study is a 2-arm, multicenter, 1:1 randomized, placebo controlled clinical trial.

All subjects will receive close monitoring for development of AGT or T1DM. Subjects will receive Abatacept or placebo and close monitoring for development of AGT or T1DM. To assess the safety, efficacy, and mode of action of Abatacept to prevent AGT and T1DM.

The primary objective is to determine whether intervention with Abatacept will prevent or delay the development of AGT in at-risk autoantibody positive non-diabetic relatives of patients with T1DM.

Secondary outcomes include: the effect of Abatacept on the incidence of T1DM; analyses of C-peptide and other measures from the OGTT; safety and tolerability; and mechanistic outcomes.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Collaborators: American Diabetes Association; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Juvenile Diabetes Research Foundation; National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Abatacept

Criteria

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).