Teplizumab for Prevention of Type 1 Diabetes In Relatives "At-Risk"

The study plans to enroll approximately 71 subjects between the ages of 8-45 years, over 2-3
years. The study is projected to last between 4-6 years, depending upon rate of enrollment
and number of subjects who develop diabetes.

The main study objective is to determine whether intervention with teplizumab will prevent or
delay the development of type 1 diabetes in high risk autoantibody positive non-diabetic
relatives of individuals with T1D. Secondary outcomes are to include analyses of C-peptide
and other measures from Oral Glucose Tolerance Testing (OGTT), safety, tolerability, and
other mechanistic outcomes will be assessed during the study.

Inclusion Criteria:

- Between ages of 8-45 years

- Have a relative with type 1 diabetes

- If first degree relative must be 8-45 years old (brother, sister, parent, offspring)

- If second degree relative must be between 8-20 years old (niece, nephew, aunt, uncle,
grandchild, cousin)

- Abnormal glucose tolerance by OGTT confirmed with 7 weeks of baseline visit [fasting
blood glucose greater than 110mg/dL or and less than 126 mg/dL OR 2 hour glucose
greater or equal to 140 mg/dL and less than 200 mg/dL OR 30, 60, or 90 minute value on
OGTT greater than or equal to 200 mg/dL]

- Presence of at least two confirmed diabetes autoantibodies

Exclusion Criteria:

- type 1 diabetes previously diagnosed or detected at screening [fasting glucose greater
or equal to 126 mg/dL or 2 hour glucose greater or equal to 200 mg/dL]

- abnormalities in blood counts, liver enzymes, INR,

- positive PPD test

- vaccination with live virus within 6 weeks of randomization

- evidence of acute infection based on laboratory testing or clinical evidence

- serological evidence of past current or past HIV , hepatitis B, or hepatitis C
infection

- Be currently pregnant or lactating

- Prior treatment with study drug

- Prior treatment with other monoclonal antibody in past one year