At-Risk for Type 1 Diabetes Extension Study

Study Overview
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Brief Summary
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This study is an extension of the NIH-sponsored AT-Risk (TN-10) type 1 diabetes study (NCT 01030861). Teplizumab-treated and placebo-treated participants in the NIH trial who develop clinical type 1 diabetes after the conclusion of that trial, are eligible to enroll and receive teplizumab treatment within one year of diagnosis of clinical type 1 diabetes.

Detailed Description
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The study is a single-arm, multicenter, open-label clinical trial. All participants will receive a 12-day course of teplizumab given through daily IV infusion and will be followed for 78 weeks. The purpose of this study is to evaluate the safety and tolerability of teplizumab treatment, administered intravenously (IV) to participants in the NIH-sponsored trial who have developed type 1 diabetes and are able to start teplizumab treatment within 1 year of diagnosis of type 1 diabetes. Whether teplizumab treatment reduces the loss of insulin-producing pancreatic beta cells will also be evaluated.

Official Title
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An Open-Label Study to Evaluate the Safety of Teplizumab (PRV-031) in At-Risk Relatives Who Develop Type 1 Diabetes

Conditions
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Diabetes Mellitus, Type 1

Intervention / Treatment
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* Biological: teplizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Previous participant in the TN-10 study Participant has received a diagnosis of type 1 diabetes after the conclusion of the TN-10 study, according to the criteria from the American Diabetes Association (ADA). Participant is able to initiate teplizumab treatment required in this study within 1 year of type 1 diabetes diagnosis. Participant is willing to forego other forms of experimental treatment during the entire study. Participant and/or guardian has given informed consent and assent as applicable. Exclusion Criteria: Has an active infection and/or fever. Has a history of or serologic evidence at screening of current or past infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). An individual who has a medical, psychological or social condition that, in the opinion of the Principal Investigator, would interfere with safe and proper completion of the trial.
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
Intervention Model: Single Group Assignment
Interventional Model Description: Single-arm, multicenter, open-label clinical trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Teplizumab treated<br>Administration of teplizumab by intravenous infusion | Biological: teplizumab<br>* anti-CD3 humanized monoclonal antibody<br>* Other names: PRV-031;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of teplizumab treatment | Incidence of treatment-emergent adverse events, adverse events of special interest, and serious adverse events | 78 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of Teplizumab | Levels of teplizumab in the serum | 78 weeks | 
| Immunogenicity of Teplizumab | Levels of anti-drug antibodies in the serum | 78 weeks | 
| Loss of C-peptide Produced by Pancreatic Beta Cells in Individuals with Recent Diagnosis of type 1 diabetes | area under the time-versus-concentration curve of C-peptide after a 4-hour mixed meal tolerance test, a measure of endogenous insulin production and beta cell function | 78 weeks | 
| Clinical Parameter 1 of Diabetes Management | HbA1c levels | 78 weeks | 
| Clinical Parameter 2 of Diabetes Management | insulin use | 78 weeks | 
| Clinical Parameter 3 of Diabetes Management | frequency of clinical important hypoglycemic episodes | 78 weeks | 
| Change in T-cell Subpopulations | Change in T-cell subpopulations analyzed by flow cytometry | 78 weeks |