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

Study Overview
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Brief Summary
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The study will determine whether the anti-CD3 monoclonal antibody, teplizumab, can help to prevent or delay the onset of type 1 diabetes (T1D) in relatives determined to be at very high risk for developing the disease. Teplizumab has been studied in new onset type 1 diabetes for testing of efficacy and safety in previous studies; other studies are currently in progress. The results of previous studies indicate that teplizumab reduces the loss of insulin production during the first year after diagnosis in individuals with type 1 diabetes. The purpose of this study is to determine if teplizumab can interdict the immune process that causes the destruction of insulin secreting beta cells in the pancreas during the pre-diabetic state and thereby prevent or delay the onset of type 1 diabetes.

Detailed Description
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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.

Official Title
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AntiCD3 Mab (Teplizumab) For Prevention of Diabetes In Relatives At-Risk for Type 1 Diabetes Mellitus

Conditions
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High Risk, Autoantibody Positive, Non-diabetic Relatives at Risk for Type 1 Diabetes, Impaired Glucose Tolerance

Intervention / Treatment
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* Drug: Teplizumab
* Drug: Placebo infusion


Participation Criteria
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Eligibility Criteria
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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, international normalised ratio (INR), positive purified protein derivative (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

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: teplizumab<br>Intravenous infusions of teplizumab given for 14 consecutive days. Each infusion takes about 30 minutes and is followed by a 2 hour observation period. | Drug: Teplizumab<br>* intravenous infusions<br>|
| Placebo Comparator: Placebo infusion<br>Intravenous infusion of placebo (saline) will be given for 14 consecutive days. Infusions will take approximately 30 minutes and will be followed by a two hour observation period. | Drug: Placebo infusion<br>* Placebo for Teplizumab<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of New Diabetes Per Year | Rate at which criteria are met for diabetes onset as defined by the American Diabetes Association (ADA) based on glucose testing or the presence of unequivocal hyperglycemia with acute metabolic decompensation. | During follow-up, median 745 days, range 74 to 2683 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | Adverse events categorized and graded via CTCAE. | Baseline Visit to Diagnosis of Type 1 Diabetes median 745 days, range 74 to 2683 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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type 1 diabetes, pre-diabetic, autoantibody positive, at risk for type 1 diabetes, glucose intolerance, relatives of people with type 1 diabetes