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

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)76 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Autoantibody Positive

Eligibility

Sex: ALLMin age: 8 YearsMax age: 45 Years

Medical Language ↔ Plain English

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

Locations (19)

University of California in San Francisco

San Francisco, California, United States

University of California-San Francisco

San Francisco, California, United States

Stanford University

Stanford, California, United States

Barbara Davis Center for Childhood Diabetes/ University of Colorado

Denver, Colorado, United States

Yale University School of Medicine

New Haven, Connecticut, United States

University of Florida

Gainesville, Florida, United States

University of Miami

Miami, Florida, United States

University of South Florida

Tampa, Florida, United States

Indiana University

Indianapolis, Indiana, United States

University of Minnesota

Minneapolis, Minnesota, United States

...and 9 more locations

Outcomes

Primary Outcomes

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.

Time frame: During follow-up, median 745 days, range 74 to 2683

Secondary Outcomes

Number of Participants With Adverse Events

Adverse events categorized and graded via CTCAE.

Time frame: Baseline Visit to Diagnosis of Type 1 Diabetes median 745 days, range 74 to 2683