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Citation
Krischer, Jeffrey (2024). Anti-CD3 Mab (Teplizumab) for Prevention of Diabetes in Relatives At-Risk for Type 1 Diabetes Mellitus (TN10) (Version 3) [Dataset] NIDDK Central Repository. https://doi.org/10.58020/vwa2-e568
Data Availability Statement
Data from the Anti-CD3 Mab (Teplizumab) for Prevention of Diabetes in Relatives At-Risk for Type 1 Diabetes Mellitus (TN10) [(Version 3) https://doi.org/10.58020/vwa2-e568] reported here are available for request at the NIDDK Central Repository (NIDDK-CR) website, Resources for Research (R4R), https://repository.niddk.nih.gov/.
Acknowledgment Statement
This research was performed using resources generated by the Type 1 Diabetes TrialNet Study Group, a clinical trials network funded through a cooperative agreement by the National Institutes of Health (NIH) through the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Institute of Allergy and Infectious Diseases (NIAID), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the Juvenile Diabetes Research Foundation (JDRF) and supplied by NIDDK Central Repository (NIDDK-CR). This manuscript was not prepared under the auspices of the TrialNet network and does not necessarily represent the opinions or views of TrialNet, NIDDK-CR, or NIH.
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General Description

Up to ten percent of all diagnosed diabetics have type 1 diabetes. Type 1 diabetes is a condition that develops due to an autoimmune attack against beta cells in the pancreas, which causes the body to stop producing insulin. Occurring most often in children and young adults, this type of diabetes appears suddenly and can lead to lifelong health complications. Relatives of people with type 1 diabetes have a greater risk of developing the disease. Type 1 Diabetes TrialNet is an international clinical trials network that conducts studies to find ways to prevent or delay the development of the disease and to enhance treatment for the newly diagnosed.

Teplizumab (Anti-CD3) is a monoclonal antibody that interferes in the autoimmune attack of pancreatic beta cells. Previous studies have shown that teplizumab reduces the loss of insulin production in type 1 diabetics during the first year after diagnosis. TrialNet 10 (TN10) was a phase 2 prevention trial of TrialNet, studying the effect of teplizumab on insulin production in the relatives of type 1 diabetics who were at high risk of developing the disease. Participants were randomly assigned to either the active or placebo group of the study, and monitored and tested over time until diagnosed with diabetes.

Objectives

The primary objective of TN10 was to determine whether intervention with teplizumab prevents or delays the development of type 1 diabetes (T1D) in high-risk autoantibody positive non-diabetic relatives of individuals with T1D.

Outcome Measure

TN10 compared the elapsed time from random treatment to development of diabetes for participants given teplizumab and those given the placebo. Criteria for diabetes onset were defined by the American Diabetes Association based on glucose testing or the presence of unequivocal hyperglycemia with acute metabolic decompensation. In addition, the association of demographic, genetic, immunologic, metabolic, and lifestyle factors were analyzed over time until the diagnosis of diabetes.

Eligibility Criteria

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 within 7 weeks of the baseline visit
  • Presence of at least two confirmed diabetes autoantibodies
Exclusion criteria:
  • Type 1 diabetes previously diagnosed or detected at screening
  • Abnormalities in blood counts, liver enzymes, or international normalized 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 HIV, hepatitis B, or hepatitis C infection
  • Currently pregnant or lactating
  • Prior treatment with study drug or other monoclonal antibody

Detailed inclusion and exclusion criteria can be found in the study protocol.

Outcome

In this phase 2 trial, a single course of teplizumab significantly slowed progression to clinical type 1 diabetes in high-risk, non-diabetic relatives of participants with diabetes who had at least two autoantibodies and abnormal results of an oral glucose-tolerance test at trial entry. The median delay in the diagnosis of diabetes was 2 years; at the conclusion of the trial, the percentage of diabetes-free persons in the teplizumab group (57%) was double that in the placebo group (28%).

Research Area

Diabetes

Study Type

Interventional

Study Sites

15

Study Start Date

2010-08

Study End Date

2019-06

Condition

Type 1 Diabetes Mellitus

Keywords

Teplizumab, Prediabetic State, Diabetes Mellitus, Type 1, Experimental Anti-CD3

NIDDK Division

DEM

76
Participants

Target Population
Adults, Children
Location statistics is not available for this study

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Specimen
Count
DNA30
PB-PBMC3223
Plasma4040
RNA967
Serum2111
Supernatant213
Whole Blood96